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Q: add custom legend in ggplot2 I'm working with ggplot2 to generate some geom_line plots which i've already generated from another data.frame which is not important to mention here. but it also contains the same id value as the following dataframe. I have this data frame called df: id X Y total 1 3214 6786 10000 2 4530 5470 10000 3 2567 7433 10000 4 1267 8733 10000 5 2456 7544 10000 6 6532 6532 10000 7 5642 4358 10000 What i want to do is create custom legend which present for a specific id the percentage of X and Y on each of the geom_line for when the id variable is the same. So basically for each geom_line of e.g(id=1, draw the percentage for that id in the geom_line plot) I've tried to use geom_text, but the problem is that it's printing everything in one line which i cannot see anything of it. how this can be done ?? EDIT olddf dataframe is something like that: id pos X Y Z 1 1..... 1 2 3 4 3 ...... . . that's the code that i've tried for(i in df$id) { test = subset(olddf, id==i) mdata <- melt(test, id=c("pos","id")) pl = ggplot() + geom_line(data=mdata, aes(x=pos, y=value, color=variable)) + geom_text(data=df, aes(x=6000, y=0.1, label=(X*total)/100), size=5) } A: The answer (as discussed in chat) is quite straightforward: Change geom_text(data = df, ...) to geom_text(data = df[df$id == i, ], ...)
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How much louder can the “ban cash” calls get? Recall it was just last year when we catalogued the growing cacophony of crazies for whom banning physical currency is the only way to ensure that depositors can’t simply reassert their economic autonomy under a low or zero rate regime.. Put simply, if interest rates get too low, depositors will simply take their money out the bank and put it in the mattress or the safe where, to quote WSJ from last week, “interest rates are always low no matter what central bankers do. Most recently, Larry Summers called for the abolition of the $100 bill in the US and in Europe the €500 note is to go the way of the dinosaurs. Perhaps the most telling sign that citizens are starting to panic is that in Japan, they’re selling out of safes. Literally. “It shows a vague sense of unease,” one Japanese lawmaker who brought up the soaring safe sales in parliament on Monday remarked. Now, the excuse given for banning big bills is that it combats crime. And maybe it does. But in the end the rationale is simple: if there are no more physical banknotes, people have no economic autonomy. Let’s say consumer spending is stagnating. No problem, take rates to -20%. We bet they’ll start spending then - either that or see their deposits haircut by 20%. In short, no cash means no effective lower bound and with no lower bound, the economy can be completely centrally planned - for all intents and purposes. Consumers not spending? No problem. Just tax their excess account balance. Economy overheating? Again, no problem. Raise the interest paid on account holdings to encourage people to stop spending. So with Citi, Harvard, Denmark and Peter Bofinger, member of the German Council Of Economic Experts, all onboard, we’re surprised to hear that Sweden (already one of the leaders in the cashless society movement) is looking to phase out a series of new bank notes it just introduced last year and moved ever closer to the cashless utopia. “Last year Sweden introduced a series of new banknotes replacing its old kronor notes. But figures suggest these too could be gone from circulation in half a decade if the development towards a cashless society continues,” The Local reports,” continuing that “cash transactions today represent no more than two percent of the value of all payments made in Sweden, [and that estimate] will drop to below 0.5 percent within the next five years. Some welcome the trend - credit card providers, for instances - others have reservations. “It is happening at a furious rate. And it's important to many older people to be able to use cash. I mean, today it is legal tender and you have to be able to use it until parliament decides otherwise,” Christina Tallberg, chairwoman of Swedish pensioners' organization PRO, told Swedish Radio on Friday. Well, until parliament or perhaps more appropriately, until The Riksbank and Stefan Ingves decides it. Because at -0.55, it’s a “how much lower can you go type scenario.” Well, if you go kronor-less, that question ceases to make sense. The "problem" simply goes away. “Sometimes you have to learn new things. It's a little awkward for a transitional period, but I think it's going to be so simple that you pretty soon realize that this is a lot easier and better than having cash,” said working environment ombudsman Krister Colde of the Commercial Employees' Union (Handels). Famous last words Krister.
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Jews in the Olympics July 11, 1984 LOS ANGELES (Jul. 10) The name and Olympic fame (Munich, 1972) of Jewish American swimmer Mark Spitz is well known, but who was the first American Jewish Olympic gold medal winner? He was jumper Myer Prinstein according to “Jews in the Olympics” exhibition running through September in the Jewish Community Building, 6505 Wilshire Blvd. Prinstein won a gold medal in the triple jump and a silver in the running broad jump in Paris in 1900. He also took top step honors in 1904 in St. Louis, winning both events and again in 1906 in Athens, with his golden running broad marks. The international exhibition documenting the achievements of Jews in sports is a project of the Southern California Jewish Historical Society. A commemorative poster and medal are available. Call 213-852-1234.
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Manteo Mitchell is an American hero and a man's man. Running the opening leg of today's 4x400 qualifying heat, Mitchell felt something go in his leg. Pain? You bet. Enough pain to let down his teammates and his country? Fuck and no. "I figured it's what almost any person would've done in that situation," Mitchell said, being far too modest for a nigh-invincible superman. The relay team has been hard-hit by injuries, losing LaShawn Merritt and Jeremy Wariner to hamstring injuries over the last week, and now Mitchell. That leaves the unheralded foursome of Angelo Taylor, Joshua Mance, Tony McQuay, and Bryshon Nellum to run tonight's final. If you're looking for a true American underdog story at these Olympics, you could do a lot worse than the tough, tough-luck 4x400 relay team.
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Tuesday, May 27, 2008 So, one week before we were to set out on our first trail-riding trip of the season, I lost the use of the Riding School's horse trailer and our horse Clifford injured himself in a spectacular way. Amazingly enough, with a large thanks to my wonderful hubby Nick, we managed to secure both a horse trailer and a second (or third??) horse. Nick found this horse trailer on Craigslist and sent me out to the Dalles to look at it. We are now the proud owners of a three-horse slant load: Then, my best friend's mother-in-law (who is also injured in a spectacular fashion) offered to let me take her four year baby for the summer. So I'm putting miles on "Kate", who is quiet and sensible but hasn't had much riding experience under her belt. Nick has agreed to let me board Kate near our house, so for the next three months I have a project horse to work with. I like bringing along babies and Kate is very fancy, so I am thrilled. Monday, May 12, 2008 My first Mother's Day was awesome!! I slept in, had breakfast in bed, went riding, took a long bubble-bath, talked on the phone with friends, toured a new WA state park with the family, and ate whatever I wanted for dinner. Nick got me a sapphire necklace -- it's Lilah's birthstone! And, best of all, I didn't have to change any diapers yesterday. SWEET. Can't every day be Mother's Day?? Wednesday, May 7, 2008 It has been an unusually long time for me not to have posted a blog. I try to post something new at least once a week, but lately I have had my hands full with a sick baby. As timing would have it, Lilah developed her first ear infection while Nick was out-of-town for business. In addition to her ears hurting, she is also teething and has a cold that set her up for red eyes with yellow discharge. Yummy. This led to a very cranky baby -- she has been alternately crying and fussy for the last 48 hours, and has been VERY CLINGY. I can hardly go to the bathroom! I took her to the doctor yesterday and got her started on medicine. Thank god for our modern age with our modern medicine! It has sure made a difference! Nick's appearance at home again helped too. She was so happy to see her Daddy (believe me, I was too!) that Lilah managed to play happily for 30 minutes. She even went to bed fairly easily in her own crib tonight! Thursday, May 1, 2008 The first trail ride of the season! Finally -- this weather has been too crazy to hit the trails. Jessica and I hit the Molalla River Trail system -- a bunch of trails that intersect each other on BLM land. The horses were absolute rock stars -- both led without a fuss and Sweet P was our fearless leader when it came to the numerous bridge crossings. Jess and I determined Clifford had probably never been out on a trail ride where he has to put himself in four-wheel drive, but for the most part he did great. He even neck-reins, which my father-in-law will love.
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Q: Replacing single quotes with double quotes in JS We are currently in the process of translating our VBScript to javascript and one of the steps is to remove single quotes ' and use double quotes instead ". I have the following line of code in the HTML header: document.write("<div style='position:absolute;padding-left:10px;padding-top:50px;color:red;font-size:13pt' id='divtest'><%=resxPleaseWait%><marquee style='border-top:solid 1px black' DIRECTION=RIGHT BEHAVIOR=SCROLL SCROLLAMOUNT=10 SCROLLDELAY=200>.</marquee> </div>") This used to be VB script but is now being written as JS. Further down the page the ID divtest is called. In replacing the single quotes this functionality breaks and I cannot think of an alternative. Any ideas? A: You can use DoubleQuotes " in your javascript by escaping them like this \". document.write("<div style=\"position:absolute;padding-left:10px;padding-top:50px;color:red;font-size:13pt\" id=\"divtest\"><%=resxPleaseWait%> <marquee style=\"border-top:solid 1px black\" DIRECTION=\"RIGHT\" BEHAVIOR=\"SCROLL\" SCROLLAMOUNT=\"10\" SCROLLDELAY=\"200\">.</marquee> </div>") The errors you are experiencing may have been caused by not placing quotes around the marquee properties. I corrected this too in the above code.
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--- abstract: 'Neutrinoless double-beta ($0\nu\beta\beta$) decay is a hypothesized lepton-number-violating process that offers the only known means of asserting the possible Majorana nature of neutrino mass. The Cryogenic Underground Observatory for Rare Events (CUORE) is an upcoming experiment designed to search for $0\nu\beta\beta$ decay of $^{130}$Te using an array of 988 TeO$_2$ crystal bolometers operated at 10 mK. The detector will contain 206 kg of $^{130}$Te and have an average energy resolution of 5 keV; the projected $0\nu\beta\beta$ decay half-life sensitivity after five years of live time is $1.6\times 10^{26}$ y at $1\sigma$ ($9.5\times10^{25}$ y at the 90% confidence level), which corresponds to an upper limit on the effective Majorana mass in the range 40–100 meV (50–130 meV). In this paper we review the experimental techniques used in CUORE as well as its current status and anticipated physics reach.' bibliography: - 'cuore\_review.bib' title: 'Searching for neutrinoless double-beta decay of $^{130}$Te with CUORE' --- Neutrinoless double-beta decay ,Majorana ,Neutrino mass ,Bolometers ,TeO$_{2}$ 23.40.-s ,14.60.Pq ,14.60St ,07.20.Mc ,07.57.Kp Acknowledgments {#acknowledgments .unnumbered} =============== The CUORE Collaboration thanks the directors and staff of the Laboratori Nazionali del Gran Sasso and the technical staff of our laboratories. This work was supported by the Istituto Nazionale di Fisica Nucleare (INFN); the National Science Foundation under Grant Nos. NSF-PHY-0605119, NSF-PHY-0500337, NSF-PHY-0855314, NSF-PHY-0902171, and NSF-PHY-0969852; the Alfred P. Sloan Foundation; the University of Wisconsin Foundation; and Yale University. This material is also based upon work supported by the US Department of Energy (DOE) Office of Science under Contract Nos. DE-AC02-05CH11231 and DE-AC52-07NA27344; and by the DOE Office of Science, Office of Nuclear Physics, under Contract Nos. DE-FG02-08ER41551 and DEFG03-00ER41138. This research used resources of the National Energy Research Scientific Computing Center (NERSC).
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While I could have sworn the culprit would have been Natty Ice, beverage of choice for Welcome Week frat house parties everywhere, a study by the UK's Illicit Encounters (via HuffPo) looked into which brewskis were most favored by unfaithful men. As it turns out, Guinness and Corona were the top two beers of choice for dirty cheating scrubs followed by Peroni San Miguel and Budweiser. Oddly enough, the study claims that men who cheat actually drink less than men in monogamous relationships (you'd think only having sex with one person would actually lead to more boozing) mostly because they're watching their weight and have to stay sharp to pick up Mad Chixx. Some other helpful hints based on our unscientific Cosmo research: If a dude orders a Six Point Sweet Action, he is pretentious. If a dude orders a Flirtini he is probably gay. But it's not only dudes who give themselves away to be cheaters by their personal preferences: The same UK research group found that women who cheat prefer to shop at Banana Republic. I guess nothing says "I'm a mom on my way to a cheap hotel in Midtown to have dirty sex with a guy I knew in college" like "sensible workwear for women at a mid-range price point"
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Noticeboard Call 111 when it's less urgent than 999 If you need medical help fast, but it isn't a 999 emergency, you can now call NHS 111. NHS 111 will assess you, provide advice and direct you straight away to the local service that can help you best. NHS 111 is available 24 hours a day, 7 days a week and calls are free, including from mobiles. For more information visit www.nhs.uk/111 Phone calls Please note that phone calls to the surgery are recorded for training and monitoring purposes Cancelling your Appointment If you are unable to attend an appointment with one of the doctors or nurse, please telephone or use the link at the bottom of this page to cancel your appointment. You can also text a message to us on 07554 071577. Don’t forget to add your surname Registering with the practice Please check that you live within our practice area - see below for details. Please complete the registration form and new patient health form and return them to us. If you are unable to print off these forms then they are all available at reception. If you can please fill out the registration form and new patient health form and return them to the surgery. We do provide a comprehensive new patient information pack which can be obtained from our reception team. Alternatively the details can be found below. Non-English Speakers These fact sheets have been written to explain the role of UK health services, the National Health Service (NHS), to newly-arrived individuals seeking asylum. It covers issues such as the role of GPs, their function as gatekeepers to the health services, how to register and how to access emergency services. Special care has been taken to ensure that information is given in clear language, and the content and style has been tested with user groups.
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The Turkish Ministry of Foreign Affairs condemned the tram attack in Utrecht and expressed condolences for the victims. Why this matters: The suspect in the shooting, 37-year-old Gokmen Tanis, was born in Turkey. He had previous run-ins with law enforcement and was arrested on Monday night, police said. Here's the full statement from the Turkish Ministry of Foreign Affairs:
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Q: how to compile / test TFS Java projects in Eclipse? When I pull from the TFS repo, the projects don't behave like normal Java projects. There is no "Run As" option, and no red marks to show compile errors, etc. How do I make this behave just like a normal Java project so I can build / edit / test ? Thanks A: Importing existing projects You can use the Import Wizard to command link import an existing project into workspace. From the main menu bar, select command link File > Import.... The Import wizard opens. Select General > Existing Project into Workspace and click Next. Choose either Select root directory or Select archive file and click the associated Browse to locate the directory or file containing the projects. Under Projects select the project or projects which you would like to import. Click Finish to start the import. Read more about Importing existing projects Find it here visually step by step about Importing and Exporting Java Projects in Eclipse Note: If the problem is still there then restarting the Eclipse might solve the issue. Look at the Project Facets as well.
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The Ontology team is excited to announce the release of Punica Suite, an Ontology blockchain dApp development framework. Punica provides developers with a complete set of open-source development tools for dApps, including: Punica CLI Solo Chain Punica-Box dApp Tutorial How to utilize Punica? Command line tool Supports intelligent contract compilation, deployment, invocation, and testing. Each item can be completed simply and efficiently through a single line of commands and testing through a configuration file. Supports both Python and TypeScript programming languages; dApp templates and Punica-Box; Smart contract packaging management tools; Supports wallet file management. Test node with UI View block, transaction, contract, push event, log, and other information in real time in the test node software; Create multiple accounts automatically for users to work with SmartX and Cyano wallet. dApp templates and examples Provides a variety of multi-language dApp examples, such as ONT ID, OEP-4, OEP-5, etc.; More development aids will be available for user reference or dApp development. Development tutorials Provides detailed textbook documentation and videos; Provides rich Punica-Box case references; Provides a variety of contract templates for developers to experience. Smart contract templates: Punica being introduce for the first time offline at our tech workshop in Seoul November 6th: At the same time, the Ontology bounty program remains open, and even has a couple of Punica-related tasks! Punica website: https://punica.ont.io/ Punica GitHub: https://github.com/punicasuite Happy dApp building!
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Although otherwise an inoffensive puff piece, CBS’s description of their virtual goddess as “fake” immediately outraged scores of Miku fans: Spoiler Alert! Click to show or hide ‘Congrats to the author for doing absolutely no research into the matter other than reading the summary on Wikipedia. First of all, is Mozart’s music fake because it didn’t feature singing? Miku, and the rest of the voice banks for Vocaloid, are instruments. Sure, anyone can use Vocaloid, but just like any other instrument, it takes an artist to master it. Also, “fake” implies that it’s a scam or doesn’t exist. I don’t see anything fake about Vocaloid; it’s simply an instrument. There’s a guitar sitting five feet to my right; are you telling me it’s not there because it has the same implications as Vocaloid? Finally, every other popstar who’s conditioned for their image rather than voice or talent are just as fake if Miku is fake. Have fun with your content-free articles and questionable reporters, CBS.’ ‘The world is filled with fake celebrities, pretending to be something they are not, remade by image consultants, keeping up appearances with a polished veneer. Hatsune Miku is none of these things. She is exactly what she appears to be, with no pretence or deception. She is the sum total of the hopes and dreams and creative energy of her legions of adoring fans, and can be nothing else. She is quite possibly the most genuine celebrity to ever grace the earth.’ ‘I respectfully ask that you retract that HORRIBLE and MISLEADING title. Hatsune Miku is by no mean FAKE. Calling Hatsune Miku fake is the equivalent of calling ALL of the fan, artists, composers, singers, animators, that celebrate this movement FAKE. It’s an insult.’ ‘If anything, it’s more insulting that you didn’t do much research than it is that you said “fake.”‘ ‘Well, Great job on doing no research! For one thing, you looked at Wikipedia, and everyone knows that they aren’t completely right. Due to the fact that anyone can edit Wikipedia, it comes up with weird BS. On top of that, this is just a stupid article! Miku isn’t “fake”! On the contrary, she is most very real, and extremely loved. She was voiced by a REAL woman named Saki Fujita! I do realize that Vocaloids are just programs, and I would be stupid to not know that. She has a character that the fanbase has given her, but now Crypton has taken it on. Hatsune Miku and every other vocaloid, are amazing creations. [...] Miku is more real of an idol, then most of us will ever be.’ ‘Whoever wrote the article, I would like to politely ask to change the title into something that WOULD NOT annoy/**** off Miku’s fans. Well, I got pissed off when I saw the title. FAKE is not the word, okay? It’s like you’re breaking her image >:/ Please change the title and everything will be okay.’ ‘Note for journalist: There are a few hot button words and phrases with Miku fandom. One, as you might have guessed, is the word “fake”, or the related phrase “she’s not real.” Almost as touchy is the phrase “what anime is she from?” or “she’s an anime character.” Just a suggestion, maybe replace “fakest” (omg that even sounds awkward) with “most unreal.” Unreal is normally used when something is so awesome, reality is incapable of inventing it alone.’ ‘When one uses the word “fakest” when reporting in a news article, it leads me to believe their background research goes only as far as it takes to roll an office chair over to a thesaurus. To address the use of fake in a general sense, we can establish that the adjective form of fake means something which is counterfeit or a sham. To my knowledge, there is nothing counterfeit about a digital pop star whose image is derived from a vast fan-base.’ ‘Hey BAILEY JOHNSON fyi she is CREATED so she is not FAKE and she is way to better than Gaga and Justin Bieber. Your article really sucks. Why this been released through this site? This article is worthless!’ ‘This post is very derogatory and unprofessional. What can we expect from Americans. Please inquire more information about this topic even more. Hatsune Miku is a tool to create music, “She” is like every other item is able to create good music and express the creators feelings and music. Therefore its not considered “fake”.’ ‘The numerous problems with this article astound me. First of all, “fakest” is not a word. Dictionaries are fabulous tools that someone needs to introduce this writer to. Also, using “fake” to describe Miku really gives readers the wrong impression. Is it fake when a person devotes their time and effort into putting their feelings into a song? [...] Now I am going to assume that CBS was joking when they hired this…sham of a writer. Using Wikipedia as a source? You do realize that students are not even allowed to use Wikipedia in high school because of the unreliability, correct? [...] Well, I could go on and on, but I would just be wasting my time. Goodbye CBS, have fun with your shoddy articles and reporters.’ Spoiler Alert! Click to show or hide Personally, I recognize Hatsune Miku as an instrument or a program synthesizer. Since vocaloid is a program that creates or imitate a barely human-like voice like Miku's then she is considered a pop star and not fake. The only difference is that she is virtual but not fake. For the logic: domain of x: Hatsune Miku Let p: x is a program let s: x imitates a barely human-like voice let q: x is considered a popstar let r: x is not fake. I saw nothing disrespectful in the article. In fact it seemed the guy behind it was rather impressed by Miku. He used the word 'fake' because he was, in my opinion, genuinely impressed by the fact that a fabricated character could perform so well. Also he used a sampling of her music in the article which is a lovely performance of Miku's rather than something awkward and weird such as the Vegetable Juice Dance which CNN used in their own article. Yet to hear a song by "Hatsune Miku" that I enjoyed. Most of it is garbage. Fakest sounds about right to me, seeing as she only conveys the songs that others makes and isn't real to begin with. I don't see why people are getting so upset. Maybe it is time to realise that she isn't a real human being who will be your little sister/girlfriend. I find it fascsinating that she has 'live' shows that are well attended. I think she is a cute video game character and has inspired some great cosplay but live shows surprised me. I suppose she isn't much less live than a lip synched Britney Spears concert... Yet to hear a song by "Hatsune Miku" that I enjoyed. Most of it is garbage. Fakest sounds about right to me, seeing as she only conveys the songs that others makes and isn't real to begin with. I don't see why people are getting so upset. Maybe it is time to realise that she isn't a real human being who will be your little sister/girlfriend. The character itself is not the pop star, but the voice that goes with it, however, is based on someone's voice, so you can't entirely dismiss it. The problem with Vocaloid, like any other singer, you're not going to like certain vocaloids or all of the songs they are in. Now, as to why they created characters for these voices is somewhat perplexing, but regardless they still give you a visual. Fans associate the vocaloid with their desginated character design and basing all their fandom on that rather than the original voice sampler. But you can look at it this way, the vocaloid may be a sample of someone's voice, but that person is not doing the performance. You don't credit the creator of an instrument, you credit the performer. The performer in this case is the fictional Miku performing the song writer's lyrics. Either way it's not like I care. I like what I listen to, I don't care what anyone else says, and I'm definitely not hurt over comment on a fictional character. Don't care that its just animation on a stage, its great:) I really don't care about the people who sing the song, if its good I will get it (sure its helpful to know the artist's name, but there should be no problem with that -.- "Hatsune Miku") Anyway they are good, and the animation is good enough xD So.. what's the problem:)
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Home I kept thinking if I waited a little longer, I might have more words. But I’ve learned over the years, that most of the time, words don’t come (at least the right ones) until my fingers hit these keys. One of our pastors said on Sunday, “Vulnerability always comes with a risk.” It’s true. For the last six years, I have met you here, pouring out my heart in the hopes that my vulnerability would lead to your transformation. Because vulnerability without transformation is only transparency. And there is enough of that in our world these days, we do not need any more useless opinions. It’s never been my heart to share our story for the simple fact of sharing our story. My heart over these years has been to share our story so that you can see what we’ve found in Papa God, you can find too. That your family, like mine, can experience His goodness and walk into deeper places in His heart. That you can be His intimate friends, too. The risk involved in sharing our story is that not only have I invited you into the miraculous places in our lives where we’ve found the beauty and victory of the Lord, but it’s only fair for me to share with you the sorrow too. In all actuality, the miracles aren’t really miracles if you don’t know the degree of the impossibility before. It’s only happened twice in my life. The other time was three years ago. The week before our foster son came home. I woke up every morning, believing the “in due time” had finally come. That after all of these years, it was our turn. I was certainly going to see my belly start swelling in the next few weeks. I had calculated the due date and thought through every way I would tell my husband, family, and dear friends. I had imagined the look on their faces, like the ones standing around Lazarus's grave. Even after all the hoping and all the disappointment, I knew this new season our family has stepped in, has looked so different from the old ones. He’s doing a new thing in us, something He’s never done before. And hope never puts us to shame (Romans 5:5), so I wasn’t afraid to hope. Because my hope isn’t in a miracle, it’s a person, my Jesus. This was the third test I took that week. All the other ones said the same results. But I wasn’t going to believe it wasn’t true, until I knew. And I knew on day eight. Right before we looked at the test, Brandon said to me, “You know this doesn’t change a word out of God’s mouth about this.” And I knew that. Still do. It’s not because I don’t have any words, I do. A lot of them really. It’s just that they haven’t found their way out of my heart yet. Also, it’s been a really hard few weeks. I still haven’t learned exactly how to share the hard without sharing my children’s stories. In the very beginning of our journey, I shared a lot. Probably too much. As I grew as their mama and learned more and more about adoption along the way, I realized their story wasn’t mine to share. Grace While We Wait Hey there! I'm so glad you're here. This is one of my absolute favorite spaces. I'm Jessica, wife to my life-crush and mama to two through the miracle of adoption. I'm learning how to walk in my identity as the Father's daughter and finding Him in the hidden, secret places. Go grab a cup of coffee and come join me!
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Q: Regex to get each section Below is the content: router eigrp 1 redistribute ospf 14 route-map test2 redistribute static vrf Automation autonomous-system 52 exec-timeout 5 default router ospf 14 router-id 1.1.1.1 area 0.0.0.25 nssa redistribute static route-map test1 redistribute eigrp 10 route-map test2 area 0.0.0.0 range 10.10.10.0/24 area 0.0.0.0 authentication message-digest area 0.0.0.25 authentication message-digest log-adjacency-changes maximum-paths 8 auto-cost reference-bandwidth 10 Gbps Need help with regex to capture first section of eigrp starting with router eigrp and capturing anything indented by either 2 space or 4 spaces. Same thing for second section starting with router ospf. greedy=yes. Thank you! A: You could use the following regex combined with the multiline flag: ^router (?:.*)(?:\n .*)*
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Giordano, a senior designated hitter, broke the scoreless ballgame in the bottom of the third with a two run bomb off the left field scoreboard. Eric Nieto added the second run of the inning courtesy of a Mark Onorati double down the left field line. The Jaspers added a couple more in the fourth complements of Perez’s two run blast over the left field wall. The homer marked his first of the season and seventh of his career. Perez drove in three RBIs on the afternoon. Senior Dom Lombardi came around to score after leading off the inning with a double to right. Manhattan added three runs to the grand total in the fifth, and chased Saints’ starting lefty Craig Marcellus out of the ballgame after just 4.1 innings of work. Sophomore reliever Mike Gazzola preserved the Jaspers’ seven run advantage shutting down the Saints in the final two innings. Gazzola notched two strikeouts in the shutout effort. Forman was also dominant on the hill, allowing just two hits and striking out seven leading to his third victory of the season. With the win, Manhattan takes its three game series with the Saints. The Jaspers travel West Point on Wednesday for its non-conference match with Army. Game time is slated for 3:30 p.m.
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Use of reverse micelles in membrane protein structural biology. Membrane protein structural biology is a rapidly developing field with fundamental importance for elucidating key biological and biophysical processes including signal transduction, intercellular communication, and cellular transport. In addition to the intrinsic interest in this area of research, structural studies of membrane proteins have direct significance on the development of therapeutics that impact human health in diverse and important ways. In this article we demonstrate the potential of investigating the structure of membrane proteins using the reverse micelle forming surfactant dioctyl sulfosuccinate (AOT) in application to the prototypical model ion channel gramicidin A. Reverse micelles are surfactant based nanoparticles which have been employed to investigate fundamental physical properties of biomolecules. The results of this solution NMR based study indicate that the AOT reverse micelle system is capable of refolding and stabilizing relatively high concentrations of the native conformation of gramicidin A. Importantly, pulsed-field-gradient NMR diffusion and NOESY experiments reveal stable gramicidin A homodimer interactions that bridge reverse micelle particles. The spectroscopic benefit of reverse micelle-membrane protein solubilization is also explored, and significant enhancement over commonly used micelle based mimetic systems is demonstrated. These results establish the effectiveness of reverse micelle based studies of membrane proteins, and illustrate that membrane proteins solubilized by reverse micelles are compatible with high resolution solution NMR techniques.
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This invention relates to methods and compositions for bonding a fluoropolymer to a substrate. Fluorine-containing polymers (also known as xe2x80x9cfluoropolymersxe2x80x9d) are a commercially useful class of materials. Fluoropolymers include, for example, crosslinked fluoroelastomers and semi-crystalline or glassy fluoropolymers. Fluoropolymers are generally of high thermal stability and are particularly useful at high temperatures. They may also exhibit extreme toughness and flexibility at very low temperatures. Many of these fluoropolymers are almost totally insoluble in a wide variety of solvents and are generally chemically resistant. Some have extremely low dielectric loss and high dielectric strength, and may have unique non-adhesive and low friction properties. Fluoroelastomers, particularly the copolymers of vinylidene fluoride with other ethylenically unsaturated halogenated monomers such as hexafluoropropylene, have particular utility in high temperature applications such as seals, gaskets, and linings. Multi-layer constructions containing a fluoropolymer enjoy wide industrial application. Such constructions find utility, for example, in fuel line hoses and related containers and hoses or gaskets in the chemical processing field. Adhesion between the layers of a multi-layered article may need to meet various performance standards depending on the use of the finished article. However, it is often difficult to establish high bond strengths when one of the layers is a fluoropolymer, in part, because of the non-adhesive qualities of fluoropolymers. Various methods have been proposed to address this problem. One approach is to use an adhesive layer or tie layer between the fluoropolymer layer and the second polymer layer. Surface treatments for the fluoropolymer layer, including the use of powerful reducing agents (e,g., sodium naphthalide) and corona discharge, have also been employed to enhance adhesion. In the case of fluoropolymers containing interpolymerized units derived from vinylidene fluoride, exposure of the fluoropolymer to a dehydrofluorinating agent such as a base has been used, as well as polyamine reagents applied to the fluoropolymer surface or incorporated within the fluoropolymer itself. A multi-layer structure includes a fluoropolymer bonded to a substrate. The structure is prepared by exposing a bonding composition to actinic radiation, such as ultraviolet radiation, with optional heating, pressure, or combination thereof, to form the bond. The bonding composition includes a light-absorbing compound and an electron donor. The bonding composition may be free of adhesive materials. In one aspect, a method of bonding a fluoropolymer to a substrate includes providing a bonding composition between a fluoropolymer and a substrate, and exposing the bonding composition to actinic radiation. In another aspect, a method of bonding a fluoropolymer to a substrate includes providing a first substrate including a bonding composition, contacting the treated surface of the first substrate with a surface of a second substrate, and exposing the bonding composition to actinic radiation. The method may include applying heat, pressure, or a combination thereof, to form the bond. Each of the first substrate and the second substrate, independently, includes a matrix material. The matrix material can be a metal, a glass, an organic-inorganic composite, a fluoropolymer, and a non-fluorinated polymer with the proviso that at least one of the first substrate and the second substrate is a fluoropolymer. The bonding composition may be provided between the fluoropolymer and the substrate in different ways. For example, a surface of the fluoropolymer may be treated with the bonding composition and the treated surface of the fluoropolymer may be contacted with a surface of the substrate, or a surface of the substrate may be treated with the bonding composition and the treated surface of the substrate may be contacted with a surface of the fluoropolymer. In certain embodiments, a mixture of the fluoropolymer and the bonding composition may be extruded and a surface of the extruded mixture may be contacted with a surface of the substrate. In other embodiments, the substrate or the fluoropolymer may be cast from solution or polymerized from a monomer. The bonding composition may be exposed to actinic radiation before contacting. In another aspect, a composite article includes a fluoropolymer having a surface, a substrate having a surface, and a bonding composition interposed between the surface of the fluoropolymer and the surface of the substrate. In yet another aspect, a treated fluoropolymer substrate suitable for bonding to a polymeric substrate includes a surface exposed to a combination of a light-absorbing compound and an electron donor and actinic radiation. In still another aspect, a laminated article including a fluoropolymer is bonded to a substrate by a bonding composition including a light-absorbing compound and an electron donor exposed to actinic radiation. In another aspect, a composition includes a fluoroalkylamine, such as a 2,2,2-trifluoroethylamine. The bonding composition includes a light-absorbing compound and an electron donor. The light-absorbing compound may be an ammonium compound, a phosphonium compound, a sulfonium compound, a sulfoxonium compound, an iodonium compound, an arsonium compound, or combinations thereof. The ammonium compound or phosphonium compound may include a benzyl moiety. The electron donor may be an amine, a phosphine, a thioether, or combinations thereof. The amine may be a primary amine, an amino-substituted organosilane, or combinations thereof. The amine may be a mono-, di- or tri-alkylamine. The alkylamine can be a fluoroalkylamine. The amino-substituted organosilane may have a hydrolyzable substituent. The bonding composition may include a vinylsilane. The bonding composition may be exposed to actinic radiation through the fluoropolymer or the substrate. The fluoropolymer may be a perfluorinated polymer or a partially fluorinated polymer. The substrate may include an inorganic substrate, such as a metal and a glass, or an organic substrate, such as a non-fluorinated polymer or fluoropolymer, or an organic-inorganic composite. Bonded multi-layer materials may have combined physical and chemical properties possessed by both fluoropolymers and non-fluorinated polymers, resulting in less expensive, well-performing articles. For example, the fluoropolymer component may be used in automotive hose and container constructions, anti-soiling films, low energy surface PSA tapes and coatings for aircraft. The bonding process is a mild photochemical lamination that may promote adhesion between a fluoropolymer and a substrate. The bonding composition may be used to form a composite article having a fluoropolymer cladding on a conductive and lustrous metal to protect it from corrosion, a fluoropolymer cladding on glass fibers to enhance their physical strength and chemical resistance for telecommunication, or a fluoropolymer layer bonded to a hydrocarbon substrate in a multi-layer materials. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.
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Tox Tuesday: Suvorexant If you have trouble falling asleep at night or staying asleep long enough to get a good night’s rest, you’re not alone. According to recent statistics, approximately 50 million Americans are afflicted with sleep-related problems or disorders such as insomnia. Essential to physical and emotional health, adequate sleep plays a role in helping the body recover from illness and injury and impacts quality of life. That’s why it’s no surprise that prescription drugs to treat sleep disorders like insomnia, are estimated to reach $1.8 billion by 2023. This figure is up from $1.4 billion in 2016, and according to reports will be aided in part by a relatively new drug known as suvorexant — the first of its class of orexin receptor antagonists. Orexin receptor antagonists work by binding to the orexin-1 and −2 receptors in the brain and decreasing the neurotransmitter orexin, which promotes wakefulness. This is different than most traditional prescription sleeping pills, which do the opposite and work by increasing levels of GABA, a neurotransmitter that slows down brain activity. First introduced in 2015, suvorexant is prescribed in doses of 10 mg before bedtime, with the intention of producing rapid onset sleep. It has been classified by the Drug Enforcement Administration (DEA) as a scheduled IV drug meaning it has a currently accepted medical use and a low potential for abuse relative to the drugs in the schedule III class. According to the classification, abuse of the drug may lead to limited physical or psychological dependence. However, some medical professionals believe suvorexant should be seen as a more dangerous substance and questions of its usefulness, potential for misuse, and dangerous side effects have come into play. In addition, there have been reports of people performing complex tasks after taking the drug (such as driving) with little recollection of the events. According to an analysis from two drug safety experts—Steven Woloshin, M.D., and Lisa M. Schwartz, M.D., both at the Geisel School of Medicine at Dartmouth, people who took a 15 mg or 20 mg dose of suvorexant every night for three months fell asleep just six minutes faster on average than those who got a placebo pill. And the suvorexant group slept only 16 minutes longer—6 hours and 12 minutes total versus 5 hours and 56 minutes for the placebo group. Those small improvements in sleep didn’t translate to people feeling more refreshed. Instead, more people who took suvorexant reported feeling drowsy the next day compared with those who took a placebo. In fact, the review states that two people who took the 20 mg dose the night before were so drowsy the next day they had to stop a driving test. Slightly more people in the suvorexant group were involved in driving accidents or got traffic tickets and reported hallucinations or sleep paralysis—a feeling that you can’t move or talk while falling asleep or awakening. Furthermore, others are concerned that suvorexant has the potential to be abused in the form of a “date rape drug” and because it can take up to 72 hours to metabolize a single dose, the feeling of next-day prolonged drowsiness is a real concern. Other experts, however, are less worried. “Nothing happened in the trials that made [suvorexant] look safer or more dangerous than other sleeping pills,” Dr. Thomas Roth, a sleep medicine expert, said in the article also noting that suvorexant’s safety profile “maintains the same precautions and warnings as other sleep medications on the market.” Because of the new nature of the drug, the question of how it can be detected in a forensic setting has also come into play. Currently there are no commercially available metabolites and therefore no available immunoassays to pre-screen samples for this drug. However, in the recent article: “Identification of Suvorexant in Urine using LC-Q/TOF-MS,” published in the Journal of Analytical Toxicology, an instrumental method is outlined for detection of that could meet validation standards required for forensic toxicology for the parent drug. The article explains that due to its high boiling point (669°C), suvorexant is highly retained using gas chromatography, potentially eluting after data acquisition may have concluded using conditions that are commonly used for gas chromatographic screening (potentially greater than 30 minutes). If your lab is interested in an ELISA test kit capable of screening for suvexorant, please contact Neogen’s product manager, Dan Grubb to discuss in more detail.
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In search of the right abstraction: The synergy between art, science, and information technology in the modeling of natural phenomena Abstract The creation of models of nature is the main objective of natural sciences. Without abstraction, however, models would be as complicated as reality itself; they would mimic nature without helping us to understand it. Identifying the essential features of the phenomena being described is therefore a crucial element of model construction. Unfortunately, an emphasis on objective, measurable characteristics, as promoted by current scientific practices, may lead in the wrong direction. An easily measurable characteristic may turn out to be irrelevant; on the other hand, a feature that eludes precise definition or measurement may be of central importance. The paper illustrates this thesis by referring to the modeling of natural forms and patterns (in particular, plants) using the formalism of Lindenmayer systems combined with computer graphics visualizations. In this domain both precise botanical data and artistic observations play an important role. This synergy gives a new perspective to the centuries-old question of the relationship between science and art in describing the world around us.
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Q: Why can't I find ubuntu-restricted-extras in the menu? So I installed the restricted extras but I can't open them nor find them anywhere. I've typed it in the search bar..still nothing. It says its installed but I can't find it anywhere. A: The ubuntu-restricted-extras package doesn't install any applications at all. What the package does do is install media codecs which can be used to play patent or copyright encumbered media formats. These cannot be included in the default Ubuntu installation because of patent and copyright restrictions. Codecs provided by this package include MP3, MPEG, Quicktime, Windows Media Format, and many others. If you're looking for more information, please refer to this page in the Ubuntu wiki.
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#41 Ferris Bueller’s Day Off “The question isn’t what are we going to do, the question is what aren’t we going to do?” I think everyone’s always tried to get themselves a free day off school as a teenager. Hell, even as adults, we all usually want days off work. Ferris Bueller’s Day Off is basically every teenager’s fantasy, the ability to sneak a day off school and enjoying yourself as much as possible without any major consequences. Matthew Broderick plays the titular character, a charming, devious 17-year old with a plan to having the best day of his life, and to do so, he needs to take some time off school. Tricking his parents into believing he’s sick, he grabs his genuinely sick friend Cameron (Alan Ruck) and finds a way to pull his girlfriend Sloane (Mia Sara) out of class, and together they go off and live it up. Meanwhile, uptight principal Mr Rooney (Jeffrey Jones) is determined to stop his plans by any means necessary. The movie doesn’t have the most realistic premise in the world, as Ferris manages to get away with murder far too easily, and some of the characters’ actions are just plain silly. But that’s the whole point. The movie is fulfilling the fantasy I mentioned in the first paragraph. As viewers, we live vicariously through Bueller and just forget about the ramifications of it all. Yet, while the actions themselves aren’t too realistic, the themes behind them certainly are. Initially Bueller seems self-centred and arrogant, as he selfishly drags his friends into his own personal escapade, but underneath all this there’s a theme of close friendship and the transition from adolescence to adulthood. At a few points there are hints that this may be Bueller’s last chance to have as much fun as possible with those he cares about before reality takes hold – which, in a way, makes the silly fantasy nature of the whole thing all the more effective. He even talks about the way his friendship with Cameron may not last as they move into college and jobs later in life, and Sloane picks up on there being ulterior motives to his plotting. Of course, even without this underlying interpretation to give the film depth, the movie is highly entertaining. John Hughes gained a reputation for producing some seriously great 80s and early 90s comedy romps, and it’s clear from this exactly why, as it’s a stellar example of what he was capable of. The jokes are clever, and even when you expect what’s coming (Bueller hands the keys to Cameron’s father’s car to a shady looking garage attendant, guess what happens next?) the payoff is always able to raise chuckles. It isn’t even the love letter to the 80s I was expecting. Much of the film remains timeless and could easily be happening during any era. There are plenty of 80s throwbacks in here, but mostly as background details, such as a Simple Minds poster in Bueller’s bedroom. The only thing that betrays the timelessness is the brief musical interlude during a parade scene, which feels like filler. Of course it isn’t perfect. As stated, sometimes Bueller’s scheme seems far-fetched and based entirely on both his parents and Mr Rooney being a bit stupider than they’d ever be expected to be in reality. It was very similar to what was seen in another John Hughes-penned film, Home Alone, where Kevin’s schemes also rely on the stupidity of the adults around him. There are even frighteningly similar scenes involving a grown man sticking his head through a pet door. Sometimes the believability of these sequences is stretched to breaking point, particularly when Bueller passes by his father on a number of occasions and is ignored. Overall, Ferris Bueller is a fun comedy with a few minor flaws that is ultimately an entertaining 90 minutes. Favourite Scene: The car valets drive Cameron’s father’s fancy car through Chicago while the theme from Star Wars plays. What do you mean it’s not awesome?Scene That Bugged Me: Like Being John Malkovich, a Charlie Sheen cameo distracted me by expecting him to say “winning” at any given moment. God knows how I’m making it through Platoon. Watch it if: Bueller’s day was your dream in high schoolAvoid it if: You actually liked high school
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OWINGS MILLS, Md. — As the Ravens practiced for the final time in preparation for the Arizona Cardinals on Sunday, safety Ed Reed was back on the field. His level of activity was up for debate, however, during a very brief period of practice that was open to the media. Reed did not appear to have a helmet, but he was going through the walk-through portion of practice, but he was spotted inside the building during the closing moments of practice Friday afternoon. Coach John Harbaugh confirmed Reed’s availability against the Cardinals following Friday’s practice. “Yeah, he’ll be able to play.” Reed did not participate during Thursday’s practice and was listed with a neck injury, which likely stems from the shoulder burner he sustained late in the fourth quarter against Jacksonville. The All-Pro safety practiced fully on Wednesday. There were no changes for receiver Lee Evans (ankle), guard Ben Grubbs (toe), linebacker Dannell Ellerbe (hamstring), and running back Anthony Allen (thigh), who were all missing from the practice field for the third straight day this week. None of the four are expected to play on Sunday and will likely be ruled out when the final injury report is released Friday afternoon. Cornerback Danny Gorrer, who appeared to suffer a thigh injury during the open portion of practice on Thursday, was present on the field without a helmet and did not appear to be practicing. He was listed as limited on Thursday’s injury report. Defensive backs Chris Carr (hamstring) and Tom Zbikowski (head) were practicing after being listed as full participants on Thursday. Harbaugh confirmed after practice that Zbikowski has been cleared for contact. ZEBRAS: Jeff Triplette and his crew will be officiating Sunday’s game between the Ravens and Cardinals. He officiated Baltimore’s playoff loss in Pittsburgh last season.
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Deus Ex Machina is the nineteenth episode of the first season of Lost, and is the nineteenth episode overall. Locke and Boone attempt to open up the hatch using their latest invention. Back at the camp, Sawyer is suffering from headaches and asks Jack for his medical opinion on what might be causing them. While in the jungle, Boone and Locke make a surprise discovery - which has tragic consequences for one of them. Plot Overview The Island After spending two weeks out at the hatch, Locke and Boone have built a trebuchet to break the hatch's glass. The trebuchet smashes into the hatch, but doesn't make a dent in it. Instead, the trebuchet shatters and a piece of metal lodges itself deep in Locke's leg. Locke pulls it out and treats the wound, but notices that he's lost all feeling in his legs. That night, Locke has a dream in which he sees a plane about to crash, Boone covered in blood, and his mother. In the morning, Locke grabs Boone and tells him about his dream and that he now knows where to go to open the hatch. The two make their way through the jungle to where Locke saw the plane crash in his dream, and discover the remains of a Nigerian priest with a gun. As they continue, Locke finds it more and more difficult to walk until he's barely able to. He tells Boone that he was paralyzed and wheelchair-bound for four years, but that the island changed him. Boone helps him keep going until they come across a Beechcraft perched halfway off the top of a cliff. Boone climbs up and enters the plane, finding maps of Africa and Virgin Mary statues. Boone drops one down to Locke and it shatters, revealing baggies full of heroin. He tells Locke they're drug smugglers and that's all that is in the plane. He heads to the cockpit and tries to radio for help, but someone else comes over the radio telling him they're the survivors of Oceanic flight 815. Locke yells at Boone to get out, but the plane's weight shifts too much and it crashes to the ground with Boone inside. Locke picks up Boone and carries him back to the caves, telling Jack that he fell off a cliff while they were hunting. While working on Boone, Jack asks Locke to tell what exactly happened, but Locke has vanished. Back at the hatch, Locke pounds on it and asks it why it did this to him. A light turns on inside. At Sun's garden, Sawyer questions Sun about a herb that's not been helping him. Kate asks Sun what he was talking about, and Sun tells her he's been having headaches that aspirin hasn't helped. Kate approaches Jack and tells him about Sawyer's problem. He goes to talk to Sawyer, but Sawyer rebuffs his attempts to help him and Jack leaves. Kate eventually forces Sawyer to go to the caves and get looked at by Jack. After humiliating Sawyer in front of Kate through a series of medical questions, Jack tells her that he needs glasses. He eventually tells Sawyer that he's far-sighted and it can develop later in life, especially with all the reading he's been doing. He starts handing Sawyer various pairs of glasses to find the ones he needs and Sayid is able to melt two halves together to make one pair of glasses for Sawyer. The Flashback Flashback: Locke A younger Locke is working as an assistant manager at a large store and notices a woman watching him. After getting off work, Locke notices the same woman is following him in the parking lot. He catches up to her and asks her why she's following him. She tells him she's his mother. The two continue their discussion at a diner and the woman tells Locke he's very special and part of a design. Locke asks about his father, but the woman tells him he has no father - he was immaculately conceived. In the store's break room, Locke meets with Frainey, a private detective he hired to investigate his supposed mother. Frainey tells him the woman is named Emily Annabeth Locke, and she is indeed his mother. She's been institutionalized several times for a type of schizophrenia, but nothing violent or criminal. He asks Frainey about his father, and Frainey hands him a red envelope containing the information about him. Locke drives up to a large house and tells the security guard, Eddie, that he's here to see his father - Anthony Cooper. Eddie tells Locke that Mr. Cooper doesn't have a son, but calls Cooper and lets him in. Cooper and Locke met, and Cooper tells him he didn't know he existed until a year after he was born. Emily told him she wasn't going to have a baby at all and dropped off the face of the planet until she showed up again asking for money and telling him she put Locke up for adoption. He asks Locke if he wants to go hunting and Locke agrees. Locke shows up at Cooper's house to shoot some birds again, but walks in and sees Cooper on a dialysis machine. Cooper tells him he's early and wasn't supposed to see this. His kidney is failing and he needs a transplant, but he's not going to let it spoil their day together. The two go hunting and Cooper tells Locke that, although his mother may be a little crazy, at least she brought the two of them together while they still have time. Later, Locke and Cooper are in a hospital being prepped for transplant surgery. Cooper tells him he still has time to back out, but Locke tells him it was meant to be. After the surgery, Locke wakes up in the hospital room but Cooper is missing. A nurse tells him Cooper already checked out and went back home under private care, but didn't leave a message for Locke. Emily shows up in his room and tells him she's sorry. She tells Locke that she needed some money and that it was all Cooper's idea to get his kidney. Locke cannot believe it and drives to Cooper's house, but Eddie tells him Cooper isn't seeing guests. Notes Mysteries How did the Nigerian smuggler's plane end up on the island? Is it really from Nigeria? Who responded to Boone's mayday? What is the light inside the hatch? Answers Arc Advancement Happenings Locke and Boone are unable to break open the hatch. Jack and Sayid help fashion a pair of glasses for Sawyer. Characters We discover that Sawyer needs glasses to help him read. Locke was only paralyzed for four years. Referbacks Trivia The Show The Gold Car: The gold colored car that hits Locke in the store parking lot is the same that struck Michael in 1x14 - Special. Behind the Scenes Location, Location, Location: The store that Locke worked at as an assistant manager was filmed at a Costco Warehouse in Waipahu on Oahu. Missing in Action: Shannon, Walt, Charlie, and Claire do not appear in this episode. Nielsen Ratings: On its original airing this episode scored 17.6 million viewers for ABC, being the highest rated scripted series for the night and winning ABC among the night overall in viewers. Allusions and References Episode Title: Deus ex machina is Latin for "god from the machine". The term is used when an author uses some improbable plot device to work his or her way out of a difficult situation. Memorable Moments Quotes Cooper: She say anything about me?Locke: She said I didn't have a father. That I was... immaculately conceived.Cooper: Really? [laughs] Well, I guess that makes me God, huh? I didn't even know you existed until a year after you were born. She told me she wasn't even gonna have the baby, you, at all. And she drops off the face of the planet. When she turns up again she's asking for money, telling me she put you up for adoption. You gonna drink that or what? You have a family of your own?Locke: No, sir.Cooper: Me neither. I tried it a couple times. Didn't take. Do you hunt?Locke: No, no.Cooper: You're not one of those animal rights nut-jobs, are you?Locke: No. No, sir. Sawyer: My uncle... he, uh... died of a brain tumor.Jack: Yeah?Sawyer: That run in the family? Tumors?Jack: What type of tumor was it?Sawyer: The type that kills you.Jack: Do you smell anything funny? Brain tumors bring on phantom smells. Maybe like something burning.Sawyer: Just headaches.Jack: Well, I'm sure you're fine, then. Look, if this is worrying you, there's a couple of tests that I could do.Sawyer: Sorry, doc. Sounds fun, but... my insurance ran out.Jack: [chuckles] Insurance ran out. That's a good one. Jack: You ever had a blood transfusion?Sawyer: What? No.Jack: Taken pills for malaria?Sawyer: Nope.Jack: Have you ever had sex with a prostitute?Sawyer: What the hell's that got to do with anything?Jack: Is that a yes?Sawyer: Yes.Jack: And have you ever contracted a sexually transmitted disease? [Sawyer doesn't answer] I'm gonna take that as another yes. When was the last outbreak?Sawyer: Go to hell, doc. [leaves]Kate: [smiling] I know he deserved it, but...Jack: He needs glasses. Emily: It was his idea. I'm sorry, John.Locke: What are you doing here?Emily: I needed some money. He's always been good that way. Your father's always been generous.Locke: You told me I didn't have a father.Emily: Well, he said that was the only way you would give it to him. It had to be your idea. He told me where to find you. He asked me to go see you. I wanted to see you.Locke: This can't be happening. This... This is a misunderstanding. This ca- This can't happen to me. He wouldn't do this to me. He wouldn't do this to me!
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Follow CHF Health insurance: the big shift that’s left patients short This article first appeared on John Menadue's blog Pearls and Irritations here. The transformation of big health funds into for-profit business enterprises sheltered by significant government subsidy and regulations has failed to prompt a complementary response from federal governments, Coalition or Labor, to even the playing field for consumers. This century the purpose of health funds has in notable cases shifted from being principally about protecting fund members’ benefits to promoting shareholder benefits. When the federal government in 1999 expanded subsidies and other incentives to boost the private health insurance market, the changes were promoted as being in the interests of the community for both fund members and public hospital patients. Now health funds are generating substantial profits — an average 18 per cent rise in the past year — while imposing above inflation premiums and squeezing benefits to their members. As it often does, the free market falters when it comes to meeting public needs and expectations in health care. That phenomenon is graphically illustrated by the hugely expensive arrangements in the United States which has among the poorest population health outcomes of any western nation. The Australian Government has initiated a reform process by means of a review involving representatives of all of the main interested parties. Given the competing interests of the organisations represented, it is uncertain whether the review will reach an agreed solution. While the funds blame high and rising fees charged by hospitals and surgeons, the latter blame the funds for failing to provide the right cover. Left in the middle is the consumer, hit by relentlessly increasing premiums and eroding levels of cover. There is little evidence that the substantial subsidies to health insurance provided since the turn of the century have produced any lasting benefits for the increasing numbers of people coaxed into taking insurance. While the initial 30 per cent rebate fueled a “rush for cover”, the savings to consumers of the rebate have long ago been swallowed by rising premiums. The most notable development in this period has been the inexorable above-inflation increases in premiums, year after year. The Government appears not to be swayed by the transformation of big health funds from community benefit organisations into for-profit shareholder companies and the impact this is having on policy holders. The Health Minister, Greg Hunt, has indicated that he wants to see more people sign up for private cover. That will only happen when health insurance delivers better for consumers. In the meantime, we can expect consumers to vote with their feet as average families weigh up the competing demands on their already stretched household budgets. While the smaller, not-for-profit health funds enjoy higher rates of customer satisfaction, health insurance for many Australians today presents a bleak picture compared to the early days of health insurance when community mutual funds were established on a self-help basis to meet the expenses of medical care. That was achieved without the mediation of the share market. The transformation of big health funds into for-profit business enterprises sheltered by significant government subsidy and regulations has failed to prompt a complementary response from federal governments, Coalition or Labor, to even the playing field for consumers. The current review, installed by the previous minister, Sussan Ley, has terms of reference aimed at improving health fund policies, including more simplified consumer “products”, standardised offerings and better consumer information to ensure transparency and the like. These are all areas of significant need for reform. However the most potent levers available for the Government to stimulate change — the health insurance rebate and associated tax arrangements — are excluded from consideration by the review. Depending on how you count it the overall cost of these provisions has been estimated to cost the taxpayer between $6 billion and $11 billion a year. The Consumers Health Forum has for the past 18 months urged the Government to deploy the rebate as a means of spurring change in health insurance to drive improvements in policy direction by requiring funds to shape up or lose the right to the rebate on their policies. CHF has told a Senate inquiry into health insurance and out of pocket costs that government outlays to health insurance continue to increase despite the lack of any conclusive evidence that this investment is providing sufficient returns. CHF is calling for a Productivity Commission inquiry into the benefit of government involvement in health insurance. It also seeks a robust public benefit test to ensure the community is gaining from this investment. These are reasonable calls when, remarkably, government funding of health insurance — one of the most heavily subsidised sectors in Australia — has not been subject to any penetrating scrutiny since the1999 funding infusion. Evidence-based health care goes without saying. What is needed now is evidence-based health insurance Get updates from CHF Our monthly newsletter 'Consumers Shaping Health' will keep up to date with our activities and opportunities for you be involved and have your say. You can choose to hear from us about new opportunities, events, webinars and more. Email Subscriptions * Consumers Shaping Health monthly newsletter Webinars Media Releases Consumer Representative Opportunities Events Surveys First Name * Last Name * Email * Leave this field blank Consumers Health Forum of Australia receives funding from the Australian Government as the peak national healthcare consumer organisation under the Health Peak and Advisory Bodies Programme.
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Good morning. On behalf of the Gravely and Passyn families, thank you for coming today to show your love and support for our amazing little man Thomas Arthur, Jr., a "Superman" in the truest sense of the word. Of course, the words "amazing" and "super" to describe our Baby Thomas cannot possibly encapsulate his true essence, which profoundly manifested itself during his seven months here on this Earth, and the warmth and joy that he gave to our hearts. As many of you observed during the viewing last evening, our Thomas today is proudly wearing his Superman outfit, equipped with a cape and all, which he wore for Halloween this past year. At the risk of being perceived as silly parents for dressing their son's body in a Superman costume for all eternity, we nevertheless found it a fitting tribute to his life; because if there ever was a soul deserving of the Superman moniker, it was our precious Thomas. This is Thomas’s inspiring story. Nearly a year ago to this day, Elizabeth and I received devastating and heartbreaking news that no expecting parent should ever have to hear. Shortly after Elizabeth's 20 week sonogram, we learned prenatally that our baby Thomas had been diagnosed with an extremely rare chromosomal disorder. In layman's terms, Little Thomas did not have all of the genes that he was supposed to have due to a deletion of a portion of his DNA. This condition affected, in some shape or form, every single living cell in his body. This we knew would result in several brain abnormalities and, as the medical experts would say, other physiological "anomalies." We were told that even if he did survive birth, he could very well have a trifecta of disabilities — blindness, deafness and severe mental retardation. In other words, think of Helen Keller, but without the mental capacity. We were very scared. The doctors gave us a wide range of possible outcomes for Thomas. Although no one was absolutely sure what to expect, at least one doctor informed us that Thomas’s chromosomal condition was "not compatible with life," and that he didn't expect the pregnancy to make it full term. Needless to say, Elizabeth and I were despondent, lost, angry and depressed. We were particularly angry with God at the time, and the thought crossed our minds that perhaps we were somehow being punished by his divine influence. Sure, many family members, friends and support groups reminded us that many parents in our situation go through the similar emotions. Of course they were right, but words of comfort could not take away the pain and anguish that we felt. Thomas’s diagnosis notwithstanding, we remained steadfast in our decision to honor the dignity of Thomas’s life, and we carried on with the pregnancy. We placed Thomas’s fate in God's hands, and we figured that God had a plan for Thomas. But on July 13, 2011, our Baby Thomas was born kicking, punching, crying and sporting a rather sanguine skin tone (and yes, that was a daddy trait), and much to the astonishment and amazement of the team of doctors on hand in the delivery room, our Baby Thomas was alive! After six days in the NICU, we were finally able to take our Thomas home, which quite honestly, was not something we had prepared for given Thomas’s very poor prognosis. What we initially thought of as a curse, turned out to be the greatest blessing from God that we had ever received. Our Baby Thomas was truly a miracle. Soon after birth, we did learn that Thomas was certainly going to have challenges, but we also knew from the very moment he was born that he demonstrated a strong propensity and desire to live, despite his various syndromic ailments. We vowed that we would do everything within our power as parents to provide a loving environment for Thomas in which he could thrive and flourish. During the course of Thomas’s life, he had numerous doctors visits, treatments and hospitalizations. I will not belabor you today with the details of Thomas’s many courageous battles during his short time here, because it is ultimately not important, and we would be here, quite literally, all day. What is important is that Thomas fought each obstacle thrown his way with fierce tenacity, and he was triumphant each step of the way. He was a warrior with a strong, yet soft and loving, heart. Those who had the chance to meet Thomas immediately fell in love with his peaceful demeanor. He was such a good boy, with a pleasant disposition. He had the innate ability to instantly make you feel happy and at peace even if you were in the worst of moods. Thomas did have some vision and hearing impairment, the degree of which we were never really able to determine for sure, but we knew that Thomas could hear our voices, he knew who his parents were, and he was particularly responsive to music, whether it was Coldplay or Beethoven. He knew that he was loved, and he certainly had many happy moments as evidenced by his gleaming smile and soft cooing. We also knew that he was very alert mentally. This gave us hope that Thomas would someday be able to live a fruitful and productive life despite his sensory disabilities. As late as Thursday of last week, and after several promising doctors appointments, we had every reason to be very optimistic about Thomas’s progress and his future. Then this past Friday morning, Baby Thomas suddenly passed away. Elizabeth and I watched in despair as a team of ER doctors and staff desperately tried to resuscitate him, but they were not able to do so. I immediately flashed back to the way Elizabeth and I felt last February when we first learned the news about Thomas’s condition...powerless and confused. How could this have happened? Why did it happen? It was as if we were just pawns in some “game” (for lack of a better word) that we didn't understand, and no matter how hard we tried or how much effort we invested, in the end we could not save our Thomas. As parents, we were devastated because Thomas had shown so much progress and development in recent weeks, and we were looking forward to raising Thomas and watching him continue to exceed expectations. Yet, as I stated earlier, God had a plan for Thomas. And for reasons only the Lord knows, Thomas was taken from us. Since Thomas’s passing, I have relied heavily on the words of the serenity prayer to make sense of what transpired last week. Although it is a Christian prayer, I believe its message transcends nearly all faiths and systems of beliefs. I'm paraphrasing, but it goes as follows: "God grant us the serenity to accept the things that we cannot change; the courage to change the things that we can; and the wisdom to know the difference." Granted, easier said than done....but poignant words nonetheless. Although I do not pretend to have God's omniscient abilities, I have spent considerable time during the past few days pondering the meaning and true purpose of Thomas’s life, putting his life into perspective and reflecting on the experiences of the past year with our son and with others...I suppose in a way that only a father can. What was the meaning of Thomas’s life? What purpose did it serve for God to place Thomas on this Earth for nearly 7 months, only to take him away from us much too soon? At first, I didn't have an answer, but right or wrong, I eventually came to my own conclusion after some introspection. And my explanation necessarily begins and ends with the very people sitting within these walls this morning. You see, Thomas was the epitome of love, in its most perfect and purest form. His life's experiences inspired and united so many people, including many of you, whether you realize it or not. It is, in part, why you are here today in support of his memory. Could it be that Baby Thomas was a messenger? Again, only God knows, but if so, what was Thomas’s “message?” Perhaps, he was a reminder to us and our community about the importance of love, and the importance of tolerating imperfection in a society where imperfection has increasingly become intolerable....the importance of valuing all human life. Thomas’s story certainly sparked discourse among us about the importance of love, commitment, and self-sacrifice. I know, because I've had conversations with many of you about what you would do if you were "in our shoes," and if you were faced with the prospect of having a child as special as Thomas. To be able to think about these kinds of issues introspectively, in my opinion, makes one a more compassionate person and makes one appreciate more the fragility of human life and the important role that family and friends play in our lives. This in of itself, certainly gives meaning to Thomas' life. Some of who communicated to us that you could not possibly understand or comprehend what we were going through, and that you couldn't imagine going through the "burden" of raising a child with Thomas’s condition. Yes, last February, Elizabeth and I shared many of these feelings as well...and those feelings are perfectly understandable. But as I stand before you today, and I know Elizabeth feels the same way, I can tell you that having Thomas in our lives was not a burden, not for a moment, and we enjoyed every minute of our time with him, whether it was at home or in the hospital. He truly was a blessing from God. Thomas made me a loving father, a better husband and a better person. For that I am thankful for Thomas, and I am thankful to God for giving him to us, albeit for a brief time. I was reminded of the importance of family constantly during the past year, where on many occasions I experienced the value of a loving wife, as well as many close and caring family members and friends, including medical professionals, who went beyond the call of duty to assist Baby Thomas. I was able to witness my beautiful wife, Elizabeth, blossom into motherhood before my very eyes. I am thankful to God for having her in my life, and she was certainly "Supermom" to Little Thomas in every sense of the word. The experiences we shared together with Thomas during this past year reaffirmed why I fell in love with her in the first place, and our love is even stronger now thanks to Thomas. Could that also have been part of God's plan? I would like to think so. Thank you Elizabeth, for your enduring love and support throughout all of this. I couldn't have made it this far without you. I love you. Elizabeth and I would also like to thank our many family members, friends and work colleagues for their love, support and invaluable advice during this past year. I cannot possibly name everyone, but you certainly know who you are. Thomas’s true miracle is not that he exceeded doctors’ expectations, but that he united our families and friends through his love and our love for him. Ultimately, I believe that this was Thomas’s purpose on this Earth. Although there are genes that determine how tall we are, what color eyes and hair we will have, or whether or not we will even be able to see or hear, I do know that there is no gene for love, and there is certainly no gene for the human spirit. Thomas had both in droves and a power that transcended his bodily form. He is a true Superman. And as promised, I will conclude my vision of Thomas’s legacy with where I began, with all of you with us today. All that I ask is that you remember Thomas and his story. How he touched and inspired so many lives and taught so many the importance of love, tolerance and affection. For those of you who have young children, hug them just a little bit tighter before they go to bed tonight. Please make them understand that your love for them is unconditional and that you will always fight for them with all of your ability. You, as parents, are their number one advocates. That is what Thomas taught us. And finally, I must say goodbye to my Thomas. I was honored to be your father. You made me so very proud, and I will never forget what you have taught me. Thank you my son. I will always love and cherish you, and I look forward to the day when we can hopefully meet again in the kingdom of Heaven. God bless you. Comments our editors find particularly useful or relevant are displayed in Top Comments, as are comments by users with these badges: . Replies to those posts appear here, as well as posts by staff writers. To pause and restart automatic updates, click "Live" or "Paused". If paused, you'll be notified of the number of additional comments that have come in. Comments our editors find particularly useful or relevant are displayed in Top Comments, as are comments by users with these badges: . Replies to those posts appear here, as well as posts by staff writers.
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Russia’s Dynamic Duo Hits the Slopes ABC's Alexander Marquardt reports from Moscow: While the American president and vice president escaped Washington’s winter by heading for the islands (Hawaii and the US Virgin Islands, respectively), Russia’s leadership embraced their country’s bitter cold and hit the slopes. President Dmitry Medvedev and Prime Minister Vladimir Putin bundled up on Sunday for a day of skiing together at the Krasnaya Polyana ski resort, one of the venues for the 2014 Sochi Winter Olympics. The political “tandem” also indulged in some tandem snowmobiling, with Medvedev going notably helmet-less as he raced around the Black Sea resort with Putin seated behind him. As is always the case when the pair is together, the question of who actually leads Russia arose, though this time from an unexpected corner. “Where is the president?” a young boy asked Medvedev. “That’s me!” Medvedev laughed. The president is spending the holidays with his family at the resort where the 2014 Olympics alpine skiing events will be held, state-run RIA Novosti reports. Russia plans to spend more than $33 billion on the Games which organizers plan to be the greenest ever. Sunday’s photo-op had Russia’s two most powerful men glad-handing with tourists, sipping tea in a mountain cafe and engaging in serious-looking conversation. “Action Man” Putin is no stranger to highly-produced photo shoots highlighting his athletic prowess: two weeks ago he was filmed sparring with Russia’s national judo team and over the summer he was photographed shirtless riding a horse in Siberia.
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Life in France seen through the round window of a straw-built grand design. Willkommen Bienvenue Welcome Welcome, gentle readers. This is an everyday tale of regular folk, who moved from Sheffield to the deepest Corrèze in France Profonde and thence to the rather more cosmopolitan Lot in search of something… different. We certainly found it. The Lot is an area of outstanding natural beauty. Reputedly, a famous TV globetrotter was asked where, of all the places in the world he had visited, he might return to. He answered, ‘The Lot’. Fans of Channel 4’s Grand Designs will know that we built a somewhat quirky straw bale house-with-a-view here in the Lot, not far from the celebrated Dordogne river. You can read all about it in my book, Bloody Murder On The Dog's Meadow, or watch the re-runs of the programme on More 4, or view it on You Tube. After a break in the proceedings to write a book or two, this blog now takes the form of an everyday journal. Sometimes things happen, sometimes they don't (but the art school dance goes on forever). I hope it will give you an entertaining insight into what it's like to live in a foreign country; what it's like in the slow lane as an ex-pat Brit in deepest France. I shall undertake to update this once or twice a week, unless absent on leave. Comments always welcomed, by the way, but I do tend to forget what buttons to click in order to answer them. Sunday, April 22, 2012 Back Home Dear Mrs. Wynburn, I am sorry that Mark was unable to write his blog last weekend, but he was back home in the UK, celebrating his parents’ 60th wedding anniversary. I hope that he will be back in action soon. Yours sincerely, Stella Sampson (Mrs.). My mum used to write similar notes to my gym teacher at primary school in Belfast, so I wouldn’t have to swim in the outdoor pool. I appreciated it at the time, because the water looked about as uninviting as the mid Atlantic in January. Had she not pandered to my distaste, however, my backbone might have toughened up at an earlier age – and I might even have learnt to swim properly. Our gym teacher, who had the gruff voice of a chain-smoker, employed an interesting education technique: she would lasso you around your middle and kind of tow you along through the icy water. I suppose it was one step up from ‘sink or swim’. Anyway, now I’m the adult and my parents have reverted to childhood. Both are in their mid 80s and becoming increasingly dependent on their four children. Typically, my sisters bear the brunt of the burden: I live many miles away across the Channel, and my brother – a busy plumber who lives in a flat where the water from the sink drains into an old plastic rubbish bin dubbed ‘The Ganges’ – rarely finds the time to drive the 40 miles or so to my parents’ Southampton home. So it goes, as Kurt Vonnegut would have said. I do my bit whenever I go back home, but it’s little substitute for my sisters’ almost daily drop-in visits. My mum is getting more than a little forgetful these days and it seems that, every time I go home, I have to try to decipher the French national character for her and to pinpoint the main cultural differences between England and France. It does at least make you think about things that you tend to take for granted. My dad and I can watch Final Score together and moan about what’s gone wrong with Arsenal, the team that he has supported since he was a little boy. With my limited knowledge of computers, I can also make myself useful by trying to fix glitches in his laptop, on which he orders groceries from Asda and talks to me on Skype. This time, for example, I installed about 50 Windows updates that he must have managed to park somewhere in cyberspace. Cut the cake! We gathered on Sunday last to celebrate their Diamond Jubilee. Given that my dad’s culinary repertoire is not wide and cooking for more than four would set his dodgy heart a-fluttering, and given that my mother is one of the worst cooks on earth, God love her, my sisters offered to do the cooking. They also brought with them glasses, plates and cutlery on the basis that home hygiene is suspect. The official line was that my parents wouldn’t have to worry about mess or washing up after we’d gone. They do, in fact, own a dishwasher – it came with the house – but have never used it for anything other than storing rags and shoe-polishing paraphernalia. They prefer to wash up with lukewarm water and ineffectual detergent. We all clubbed together to buy them the type of present my mother couldn’t file away in her ‘bottom drawer’. (My wife and I gave up trying to come up with practical, thoughtful presents for her after witnessing her converting the winter-weight tights we’d bought her one Christmas into ‘pop-socks’. The French would call it perhaps a ‘re-looking’. It was about as cack-handed as Mickey Rourke’s adventures with Botox.) The younger of my two sisters has an Italian partner and he has been working relentlessly on my father to persuade him that their telly needed updating. So we bought them a 26” Sony FST with stand that would just fit into its allotted space. My dad was very moved, but my mother – with three glasses of pink champagne inside her – was later heard berating the Italian partner, on the grounds that she liked the old telly and found the new one too bright, too loud, too big, too black and too vulgar. As my brother observed, ‘Good to know that the present was a success, then’. By the next day, though, she had tempered her views and the audio-visual re-looking was a fait accompli. The following evening, I helped the older of my two sisters celebrate 30 years of marriage with her husband. It was a rather more muted affair involving dinner in their local pub, which underlined just how expensive it is now to eat out in the UK. Or the south of England, anyway. I sat opposite my younger sister, who told me all about her new hobby of researching family trees on the internet. My paternal grandfather’s grandfather, it seems, was a detective in Victorian London. I wondered about teaming up with Andrew Lloyd Webber to write a fabulously successful musical about the man. My sister promised to delve deeper. After all this socialising, it was a relief to return to the peace and quiet of rural France. Getting back to my sanctuary meant travelling with Ryan (unf)Air. After all my diatribes about Mr. O’Leary’s airline, I found myself meekly checking that my one bag could sit inside one of their intimidating metal ‘guides’. At least the weight of my shame and hypocrisy didn’t tip things over the 10kg allowance. I had remembered not to wear boots for the trip across – so didn’t have to bear the indignity of removing my footwear – but forgot that a jar of aubergine pickle counts as a liquid. With a righteous scowl, I suggested to the customs man that he give it to someone who liked Indian cuisine. His reply that it would be thrown away didn’t improve my mood. Since the running dogs didn’t confiscate my two packets of crumpets and my one packet of creamed coconut, I gave thanks for small mercies. Later, I gave bigger thanks when we landed safely in Limoges. We arrived 15 minutes ahead of schedule, which triggered that irritating recorded clarion call, so the airline can crow about its winning percentage of on-time flights. Alas, on queuing up to show our passports, the French officers were nowhere to be seen. We waited patiently, as good Brits do, for 10 minutes before a pair of lugubrious uniformed men showed up for duty. Welcome to France. My brother and I collect specious strap lines (along the lines of Rotherham – another way of doing things) and it struck me that it’s maybe time for someone to come up with a one-line equivalent of the famous Gallic shrug. How about, for example, France – where we do not give a monkey’s? 1 comment: I had a very similar experience at Limoges. Leaving East midlands well ahead of schedule and with prevailing conditions we arrived at Limoges a good 20 to 25 mins early,only to stand in the 'cattle' racks infront of immigration watching the two immigration officers drinking coffee through the glass door ( absolutely true) while we listened to an announcement saying that because of our early arrival immigration were not yet ready! When they did saunter in to a slowish hand clap they took their bows ( they just don't get irony!! ) Camp Street About Me Born in London, raised in Belfast, further-educated at Exeter and Sussex universities, I'm a professional dilettante, a family man and tireless dog-walker. You can listen to Lost & Found, my monthly radio show on www.expatsradio.com and check out my author page on Amazon.
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Earn from Excess Energy with Nissan Earn from Excess Energy with Nissan Today, car manufacturer Nissan revealed it will be trialling a new scheme, which will allow electric vehicle (EV) owners to sell excess energy from their car or van’s battery back the UK grid. Nissan’s innovative project is the first of its kind in the UK. The Vehicle-To-Grid (V2G) trial scheme, which is a joint venture between the car manufacturer Nissan and multinational power company Enel, involves 100 private and fleet customers of the Nissan LEAF and e-NV200 electric vans. The system works by allowing Nissan EV owners to connect to the grid to charge at low-demand, cheap tariff periods, with an option to then use the electricity stored in the vehicle’s battery at home and at work when costs are higher, or feed that electricity back to the grid, so generating additional revenue for the EV owner. The companies believe the V2G scheme could revolutionise how energy is supplied to the grid. They have estimated that if all 18,000 Nissan EVs currently on the UK’s roads were connected to the energy network, they would generate the equivalent output of a 180 MW power plant. If that was scaled up in a future where all the vehicles on UK roads are electric, vehicle-to-grid technology could generate a virtual power plant of up to 370 GW. This energy capacity could power three countries the size of the UK, Germany and France. Nissan see EVs as being mobile energy hubs of the future, helping to enable a smarter energy grid and paving the way for more renewables. The company also unveiled a brand new residential energy storage unit using former EV batteries as domestic storage units. The ‘xStorage’ solution, in partnership with power management leader Eaton, provides a sustainable ‘second life’ for Nissan’s electric vehicle batteries after their first life in cars is over. Powered by twelve Nissan LEAF battery cells, the new unit can save customers money on their utility bills by charging up when renewable energy is available or energy is cheaper (e.g. during the night) and releasing that stored energy when demand and costs are high. Customers can also generate additional revenues by selling stored energy back to the grid when demand and costs are high. The announcements were made at the Nissan Futures event in central London. It is the first of a series of events taking place across Europe which aims to break new ground in the quest for next generation mobility solutions. Nissan also used the event to announce that its flagship European manufacturing plant in Sunderland saw the 50,000th all-electric Nissan LEAF roll off its production line. This is a watershed moment for Nissan. Five years ago, the Nissan LEAF was the very first mass-market electric vehicle and it remains the best-selling EV of all time with in excess of 200,000 vehicles sold worldwide.
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886 F.2d 1497 29 Fed. R. Evid. Serv. 506 UNITED STATES of America, Plaintiff-Appellee,v.Martin F. HOGAN, Defendant-Appellant. No. 88-3116. United States Court of Appeals,Seventh Circuit. Argued May 26, 1989.Decided Oct. 13, 1989. Thomas M. Durkin, Scott T. Mendeloff, Asst. U.S. Attys., Office of the U.S. Atty., Chicago, Ill., for U.S. Patrick A. Tuite, Tuite, Mejia & Giacchetti, Chicago, Ill., for Martin Hogan. Before WOOD, Jr., MANION, and KANNE, Circuit Judges. HARLINGTON WOOD, Jr., Circuit Judge. 1 Defendant-appellant Martin F. Hogan, Jr. was an associate judge for the First Municipal District of the Circuit Court of Cook County. He was assigned to Branch 64, known informally as Auto Court, from approximately May 1981 to June 1983. A jury found that it was in this capacity as the presiding judge in Branch 64, and occasionally Branch 29, that he had committed the crimes of bribery, the aiding and abetting of bribery, and conspiracy to engage in bribery in violation of the Racketeer Influenced and Corrupt Organizations (RICO) statutes. 18 U.S.C. Secs. 1961-1968. The jury also convicted him of filing false tax returns. 26 U.S.C. Sec. 7206(1). He now appeals his conviction. We affirm. I. FACTUAL BACKGROUND 2 On October 16, 1987 a federal grand jury indicted Hogan and five codefendants for racketeering, racketeering conspiracy, and the filing of false tax returns.1 The district court granted Hogan's motion for a separate trial, and on August 9, 1988 a three-week trial commenced in which Hogan was the sole defendant. We begin by describing the general framework of the bribery scheme as presented by the government and add details pertinent to specific issues as we address them. 3 According to the government, Judge Hogan entered a court system that was notable for the zeal with which some of its members embraced pay-offs and bribery, rather than their allegiance to justice. Under the watchful eye of Chief Judge Richard LeFevour,2 five attorneys and the Chief Judge's cousin, police officer James LeFevour, devised a plan that would allow the attorneys to solicit legal business in the First Municipal courtrooms in return for a monthly fee paid to the Chief Judge. 4 Ironically, they devised this plan in response to an expose in the Chicago Lawyer magazine titled "Hustling." "Hustling" in the legal profession connotes the practice of directly approaching defendants and asking them if they need legal representation. The court rules and ethics code prohibited attorneys from hustling, and the Chicago Lawyer article criticized the prevalence of the unethical practice in the Cook County Circuit courts. See Rule 0.5(a) of the Circuit Court of Cook County; Ill.Rev.Stat. ch. 110A, Rule 2-103. 5 Although Judge LeFevour had willingly permitted hustling during his tenure at Traffic Court (presumably because attorneys paid him money to ignore their activities), he was cut off from the action when he was promoted to chief judge. The article gave him the means to "put the squeeze" on the hustling attorneys, and he righteously ordered his cousin, assigned to police officer duties in the First Municipal courtrooms, to stop the lawyers from hustling. James LeFevour began to hassle the hustlers who loitered in the hallways outside the First Municipal courtrooms. Eventually, the persistent harassment convinced five lawyers, who later became known as the Hustlers' Club, to pay Chief Judge LeFevour through his cousin James to leave them alone.3 James was known in the court system as Judge LeFevour's "bagman" and, in that noble capacity, he agreed to carry the money to Chief Judge LeFevour. 6 In return for the monthly payments, Chief Judge LeFevour agreed to assign to the "high volume" First Municipal courtrooms those judges who would allow the attorneys to hustle and generally treat the attorneys favorably.4 At trial, various participants in the plan testified that willing judges would "steer" defendants who could afford to make bond but lacked legal representation to the attorneys, ignore the hustling that took place in the courtroom, and generally rule in favor of the attorneys' clients. The attorneys would then on "good days" (days on which the attorneys made a certain percentage of money through hustling and steering) "see" the sitting judges and leave a small payment of $100-$200 for them. 7 Enter Judge Hogan. Judge Hogan, a young appointee to the bench at the age of thirty-nine, quickly learned the ways of the First Municipal courts under Chief Judge LeFevour's tutelage. Chief Judge LeFevour appointed Judge Hogan to Branch 64 soon after the system of bribe payments was set up, and James LeFevour visited Judge Hogan to explain the plan. James LeFevour told Judge Hogan that Chief Judge LeFevour said that the five attorneys who paid him monthly should be permitted to hustle in Branch 64. He also told Judge Hogan that Neal Birnbaum promised that the lawyers would "see" the sitting judges after they made a certain profit, to which Judge Hogan replied "fine." 8 Neal Birnbaum, Martin Schachter, and Lee Barnett, three members of the Hustlers' Club, testified that, in keeping with the plan, they each paid Judge Hogan sums of approximately $100-$200 between 1981 and 1983. Neal Birnbaum paid Judge Hogan approximately $100 on ten different occasions; during that time Neal Birnbaum won on each of eleven contested motions argued before him. Likewise, Lee Barnett paid Judge Hogan $100 on two occasions, for which, Barnett testified, the judge steered cases to him and ignored his hustling. Martin Schachter testified that he paid Judge Hogan $100-$200 approximately twelve times. He described the technique that he and Judge Hogan had developed for making most of the payments. The judge would walk to the door of his chambers and look out over the courtroom. Schachter would then ask, "Are things clear?" When Judge Hogan replied affirmatively, Schachter would place the money in the judge's desk drawer and Judge Hogan would often respond with a "thank you." 9 These three members of the Hustlers' Club were not the only persons who testified that they paid Judge Hogan. Police officer Francis Chimpoulis, who was the court sergeant in Branch 64, stated that he carried white envelopes and cash from an attorney who practiced in Branch 64 to Judge Hogan on four to six occasions in return for $10-$20 for himself. Judge Hogan also received additional visits from James LeFevour. James LeFevour testified that at three different times he visited Judge Hogan and informed him that "Judge LeFevour [is] interested in this case." Government witnesses testified that this meant that Judge Hogan was to treat the defendant favorably. James LeFevour stated that on one of these three visits he slipped $100-$200 in Judge Hogan's coatpocket and informed Judge Hogan that he had left something in his coat hanging in the Branch 64 chambers, to which Judge Hogan replied, "fine." 10 The first time James LeFevour visited Judge Hogan involved an attorney named Dean Wolfson. Wolfson had approached James LeFevour in the summer or fall of 1981 and asked James LeFevour to speak to Judge Hogan about the case, for which Wolfson would pay Chief Judge LeFevour through cousin James. When James LeFevour told Judge Hogan that the chief judge was interested in the case, Judge Hogan responded, "all right." Judge Hogan ruled in Wolfson's client's favor and Wolfson paid James LeFevour $550 after the case was resolved. 11 The second and third incidents involved undercover FBI agent Terry Hake. In October 1982 Terry Hake, then posing as a corrupt defense attorney, told James LeFevour that he needed a stolen auto case "disposed of." After James LeFevour spoke to Judge Hogan and Judge Hogan dismissed the case as Terry Hake requested, Terry Hake paid James LeFevour $500 in the washroom next to Branch 64. Similarly, in December 1982 Terry Hake informed James LeFevour that he needed Judge Hogan to find his client not guilty in a criminal trespass to auto case. James LeFevour visited Judge Hogan; Judge Hogan responded to LeFevour's comments by stating that "he would see what he could do." At the trial James LeFevour stood approximately five feet behind the bench as Judge Hogan proceeded to find Terry Hake's client not guilty. Terry Hake then paid James LeFevour $400. 12 With regard to the tax charges, the government presented evidence that from 1981 to 1983 Judge Hogan reported income only from his judicial salary and savings account interest. Using a cash method, the government calculated that Judge Hogan's unreported income in 1981 was $2,370. In 1982 it was $4,775.74 and in 1983 it totalled $13,367.48. 13 On August 29, 1988 the jury convicted Hogan5 on all five counts of the indictment. The district court sentenced Hogan to ten years in prison on Counts 1 and 2 (the substantive RICO charge and the conspiracy count) to run concurrently, and five years probation on Counts 7, 8, and 9 (the tax fraud charges) to run consecutive to the sentence. II. DISCUSSION 14 Hogan raises five distinct issues on appeal. He first contests his conviction with regard to three charges of aiding and abetting the commission of a bribe, Racketeering Acts 4, 6, and 7 of the RICO count.6 He argues that the district court improperly admitted tape-recorded conversations under the co-conspirator exception to the hearsay rule and failed to sever the tax counts from the underlying RICO counts. He also challenges the method used by the government to prove Hogan's unpaid tax liability. Finally, he disagrees with the district court's decision to exclude as hearsay the testimony of Tempel (Tim) Smith, Jr., a friend and witness for Hogan. 15 A. Aiding and Abetting the Commission of a Bribe 16 Hogan challenges Racketeering Acts 4, 6, and 7 of Count 2, which include the three charges of aiding and abetting bribe activity involving Dean Wolfson, Terry Hake, and James LeFevour. According to Hogan, the evidence did not sufficiently establish that he knew that Dean Wolfson and Terry Hake paid the LeFevours bribes in connection with three cases upon which he ruled in their favor. Hogan argues that, without knowledge that money changed hands, he did not aid and abet bribery as defined by state law. He also contends that under Illinois law, he is not accountable for facilitating bribes because his conduct was "inevitably incident" to the commission of the bribe. We will address Hogan's challenge to the sufficiency of the evidence first. 1. Sufficiency of the Evidence 17 In assessing a challenge to the sufficiency of the evidence, we review the evidence in the light most favorable to the prosecution and draw all reasonable inferences in its favor. United States v. Douglas, 874 F.2d 1145, 1151 (7th Cir.1989). "If any rational trier of fact could have found the essential elements of the crime beyond a reasonable doubt," we must affirm. Jackson v. Virginia, 443 U.S. 307, 319, 99 S.Ct. 2781, 2789, 61 L.Ed.2d 560 (1979) (emphasis in the original); see also United States v. Floyd, 882 F.2d 235, 239 (7th Cir.1989). Because Hogan received a jury trial, we must on review defer to reasonable inferences drawn by the jury and the weight it gave to the evidence. United States v. Draiman, 784 F.2d 248, 251 (7th Cir.1986). Likewise, we leave the credibility of witnesses solely to the jury's evaluation, absent extraordinary circumstances. United States v. Muskovsky, 863 F.2d 1319, 1322 (7th Cir.1988), cert. denied, --- U.S. ----, 109 S.Ct. 1345, 103 L.Ed.2d 813 (1989). 18 Hogan claims that he had no knowledge that the LeFevours financially benefitted when he ruled in favor of Dean Wolfson's and Terry Hake's clients. He contends that he believed that Chief Judge LeFevour was concerned about the outcome of the cases and that James LeFevour's comment that the chief judge was "interested in the case" was an informal "character reference" for the defendant. Emphasizing only the testimony of James LeFevour and Terry Hake, he asserts that the government failed to establish that he knew about the bribe. 19 As Hogan has insisted, to convict a defendant for facilitating a bribe, the government must show that the defendant had the requisite intent and that something of value changed hands. In Illinois, a defendant is legally accountable for an act of bribery committed by another if he intends to promote or to facilitate the commission of the bribe and aids or abets the person in its commission. See Ill.Rev.Stat. ch. 38, paragraphs 5-2, 33-1. To convict a defendant of the underlying charge of bribery, a jury must find that "property or personal advantage" was tendered to a potential bribe-taker. Ill.Rev.Stat. ch. 38, p 33-1. 20 Although Hogan accurately restates the law, he ignores the circumstantial evidence presented at trial that could have led a reasonable juror to conclude that he knew that the LeFevours accepted money from Dean Wolfson and Terry Hake. Several witnesses at trial attested to James LeFevour's reputation as a "bagman" for Chief Judge LeFevour; a term they defined as someone who carried bribes to a judge for attorneys. Martin Schachter testified that he had discussed with Judge Hogan three or four times James LeFevour's relationship with the hustling attorneys and complained that James LeFevour was not "doing his job" because he did not prevent the nonpaying attorneys from taking away the hustlers' business. Neil Birnbaum stated that Martin Schachter told him that Schachter had mentioned the bribery arrangement to Judge Hogan. James LeFevour explained to Judge Hogan that five members of the Hustlers' Club would hustle in Branch 64 and "see" Judge Hogan occasionally. This evidence indicates that Hogan knew that James LeFevour carried money to Chief Judge LeFevour for several attorneys and that, between the LeFevours and the attorneys, a bribery relationship had been established. 21 Hogan compares his knowledge to that of the employee-defendants in Ingram v. United States, 360 U.S. 672, 79 S.Ct. 1314, 3 L.Ed.2d 1503 (1959). In Ingram the Supreme Court held that the evidence was insufficient to establish that two employees in a gambling conspiracy knew that their employers had also unlawfully withheld income tax. The government in Ingram cited the employees' connection to the gambling business, the secrecy of their conduct, and their knowledge that the business was profitable as evidence that they knowingly withheld taxes, but the Supreme Court rejected the evidence because the inferences were too remote. See id. at 678-79, 79 S.Ct. at 1319-20. Unlike the prosecutor in Ingram who failed to show that the employees knew anything about the tax liability of the gambling operation, the government demonstrated that Judge Hogan was aware of a bribery scheme involving the LeFevours. The jury need not infer Hogan's knowledge of the Wolfson and Hake payments from his knowledge of a tangential illegal activity, but from his knowledge of bribery that was taking place in the First Municipal courts. The inference that Hogan knew that the LeFevours accepted bribes from Dean Wolfson and Terry Hake is not remote or tenuous as it was in Ingram. 22 Furthermore, Judge Hogan's own bribe-taking activities suggest that he was aware that money was the means to obtaining favorable treatment in a courtroom. Judge Hogan knew what a "bagman" was because he himself had one in the person of Francis Chimpoulis. Judge Hogan knew that money was paid for favorable treatment because he himself took money from attorneys and steered cases to them in return. In fact, James LeFevour insisted that he slipped $100-$200 into Judge Hogan's coatpocket for his favoritism in one of the three cases involving Terry Hake and Dean Wolfson. This evidence indicates that Hogan knew that judges were often compensated for favoritism. 23 Finally, Judge Hogan knew that James LeFevour and the bribing attorneys expected him to give them favorable treatment. James LeFevour testified that he told Judge Hogan that Chief Judge LeFevour was "interested" in the Wolfson and Hake cases and, at one point, even hovered next to the judge's bench to ensure that Judge Hogan treated Terry Hake favorably. Hogan himself admitted that he remembered two of these conversations. 24 The evidence established that Hogan knew that attorneys were systematically paying bribes to the LeFevours, that bribes were given for favoritism in the courtroom, and that he was expected to rule favorably in the Wolfson and Hake cases. Based on these facts, a reasonable jury could infer that Hogan knew that Terry Hake and Dean Wolfson paid the LeFevours money in return for favorable treatment. 2. Accountability 25 Hogan argues that, even if there is sufficient evidence to show that he had knowledge of the bribe payments, he is not accountable for facilitating bribes under Illinois law. The Illinois statutes provide that a person is not legally accountable for the conduct of another if "the offense is so defined that his conduct of another if "the offense is so defined that his conduct was inevitably incident to its commission." Ill.Rev.Stat. ch. 38, p 5-2(c)(2). Hogan argues that his conduct was "inevitably incident" to the commission of a bribe because, without his favorable rulings in the Wolfson and Hake cases, the elements of a bribe would not have been satisfied. 26 Unfortunately for Hogan, a defendant may not claim that his conduct was "inevitably incident" to the offense if the statute is written to include the incidental conduct. The law may be extended, for example, to a bribe-taker as well as a bribe-giver. As the Committee Comments explain: 27 Should a bribe-taker be guilty of bribery? ... In many situations, the scope of criminal liability, if extended in this fashion, might make law enforcement more difficult. In any event, subsections (c)(1) and (c)(2) do not prevent the extension of liability to such persons by provision in the particular statutes if this is desired. Thus, if it be decided that a bribe-taker should be treated as guilty of bribery, this can be provided in the bribery section. 28 Ill.Rev.Stat. ch. 38, p 5-2 (Committee Comments). The Illinois bribery statute covers both persons receiving and giving bribes. Ill.Rev.Stat. ch. 38, p 33-1(a), (d). Obviously the Illinois legislature intended for the law to apply to each aspect of the bribery act but failed to envision the creative methods used by Judge Hogan to advance the bribe transactions. Nevertheless, Hogan placed himself in the shoes of the bribe-taker, who is explicitly covered by the statute, when he showed partiality toward the Hake and Wolfson defendants. He aided and abetted the bribe-taker by permitting himself to be influenced in his position as a judge. The Illinois bribery statute explicitly prohibits a bribe-taker from taking money in return for favoritism. See Ill.Rev.Stat. ch. 38, p 33-1(d). Hogan's conduct is specifically prohibited by the bribery statute and therefore comes within the scope of the statute. Where the statute covers the incidental conduct, the "inevitably incident" defense does not apply. B. Admission of Tape-recorded Conversations 29 Hogan argues that the district court erred when it admitted into evidence as nonhearsay tape recordings of two conversations between Terry Hake and an attorney named Harlan Becker. On October 14, 1982 Harlan Becker spoke to Terry Hake about James LeFevour and suggested that LeFevour might try to pocket the bribe that Terry Hake had just paid to LeFevour and intended for Judge Hogan.7 Harlan Becker stated that if Terry Hake had given him the money he would have ensured that the judge "got it all." In the second conversation on November 12, 1982 Becker again warned Terry Hake that James LeFevour would pocket bribes intended for the judges. 30 Hogan contends that the government failed to allege, charge, or prove that he and Harlan Becker were co-conspirators. He argues that, at most, the government established that he and Becker were members of a conspiracy to pay bribes for the privileges of hustling and steering. He claims that the government did not establish that they had conspired to "fix" cases. 31 The district court allowed the government to play the recorded conversations between Terry Hake and Harlan Becker pursuant to Rule 801(d)(2)(E) of the Federal Rules of Evidence. Rule 801(d)(2)(E) provides that statements by a co-conspirator during and in furtherance of the conspiracy are not hearsay. To satisfy Rule 801(d)(2)(E), the government must show (1) that a conspiracy existed; (2) that the defendant and declarant were members of the conspiracy; and (3) that the offered statement was made during the course of and in furtherance of the conspiracy. United States v. Hooks, 848 F.2d 785, 794 (7th Cir.1988). On review of a district court's findings regarding the existence of these elements, we will reverse only if the findings are clearly erroneous. Id. at 794. 32 Contrary to Hogan's assertions, the government adequately alleged and charged in Count 1 that Hogan conspired with Harlan Becker to be influenced in the performance of his duties as a judge in exchange for bribes. This description of the conspiracy adequately includes the activity of "fixing" cases. Although Harlan Becker was not specifically named as a member of the conspiracy in Count 1, the indictment stated that Hogan conspired with both unknown and known co-conspirators. Further, Count 1 incorporated by reference Count 4 of the indictment, which identified Harlan Becker as a member of the conspiracy and described his conversation with Terry Hake. Although slightly circumspect in its approach, the government adequately alleged and charged that Hogan conspired with Harlan Becker to provide favoritism in his judicial decisionmaking in exchange for bribes. 33 Likewise, the government sufficiently proved that Harlan Becker and Hogan were co-conspirators. If in dispute, the government must prove that a conspiracy existed between the declarant and the defendant by a preponderance of the evidence. Bourjaily v. United States, 483 U.S. 171, 175, 107 S.Ct. 2775, 2778, 97 L.Ed.2d 144 (1987). Because conspiracies are secretive by nature, the government often must rely on circumstantial evidence. United States v. Mealy, 851 F.2d 890, 896 (7th Cir.1988). Circumstantial evidence and reasonable inferences drawn therefrom may serve as proof. Id. The district court may also consider the alleged hearsay to determine whether a conspiracy existed between the out-of-court declarant and the defendant. Bourjaily, 483 U.S. at 177-78, 107 S.Ct. at 2779-80. 34 Although the evidence that Hogan and Harlan Becker were members of the same conspiracy was not overwhelming, we find that the district court did not clearly err by admitting the tape-recorded conversations. "The parties involved in a conspiracy do not have to ... participate in every aspect of the conspiracy," but must knowingly embrace a common criminal objective. United States v. Davis, 838 F.2d 909, 913 (7th Cir.1988). The evidence showed that Judge Hogan steered cases to Harlan Becker and to Martin Schachter, a known member of the Hustlers' Club, in the same fashion. Harlan Becker's bond totals in Judge Hogan's courtroom, which indicate the number of paying clients he represented, were inordinately high, corroborating Schachter's testimony that he saw Judge Hogan steer cases to Harlan Becker. Also incriminating were the comments made by Harlan Becker in the tape recordings themselves. Becker insinuated that he was paying judges and could act as a conduit for Terry Hake in making payments to Judge Hogan. His comments, in addition to evidence that he was receiving an extraordinary amount of business from Judge Hogan, indicate that Harlan Becker and Hogan were members of the same conspiracy.8 35 Unlike Hogan who prefers to categorize hustling, steering, and fixing cases into different conspiracies, we find that these activities were all aspects of the same conspiracy. That conspiracy, detailed in the indictment, was a conspiracy to accept payment in exchange for unlawful forms of favoritism in the First Municipal courtrooms. Evidence that Judge Hogan steered cases to Harlan Becker implies that Becker and Judge Hogan had this as their mutual objective and Becker's recorded comments to Terry Hake confirm that this was their goal. Therefore we find that the district judge did not err in finding Becker and Hogan to be members of the same conspiracy. C. Severance of the Tax Counts 36 Hogan directs his next challenge to the charges of filing false tax returns listed in Counts 7, 8, and 9. He argues that the district court should have severed the tax charges from the RICO charges. Hogan contends that the government's tax experts, using an indirect method of proof called the cash method, established that he owed approximately $20,000 in taxes for tax years 1981, 1982, and 1983. In comparison, he notes that the government established through direct evidence that he took at most $4,400 in bribes during those years. Because these totals do not correlate, he contends that the district court should have granted his motion to sever the tax counts from the RICO counts. 37 Although Hogan does not indicate which rule of law he believes pertinent, the government assumes that Hogan is raising the issue of severance pursuant to Rule 14 of the Federal Rules of Criminal Procedure.9 We therefore consider the issue of severance under Rule 14 because Hogan does not contradict the government's characterization. Cf. West Allis Memorial Hosp., Inc. v. Bowen, 852 F.2d 251, 257 (7th Cir.1988) (appellant has duty of presenting authority for its contentions). 38 Pursuant to Rule 14 of the Federal Rules of Criminal Procedure, the district court may order separate trials on individual counts if it appears that a defendant is prejudiced by joinder of the offenses. We will reverse the district court's decision to deny or grant a motion for severance under Rule 14 only for an abuse of discretion. United States v. Turk, 870 F.2d 1304, 1306 (7th Cir.1989). To establish an abuse of discretion, the defendant must show that he suffered actual prejudice. United States v. L'Allier, 838 F.2d 234, 241 (7th Cir.1988). In determining whether joinder caused the defendant actual prejudice, we determine whether evidence supporting one count could also have been admitted in a trial solely on the other count. See, e.g., id. at 241. If the evidence would have been admissible on either count, the defendant cannot claim that he was prejudiced by joinder. We also consider whether the district judge gave limiting instructions with regard to the evidence and the counts. See, e.g., United States v. Oakey, 853 F.2d 551, 555 (7th Cir.1988); L'Allier, 838 F.2d at 242. 39 The government claims that evidence that Hogan took bribes and engaged in a bribery conspiracy would have been admissible in a tax trial to show that Hogan received actual income that he did not report. With this we agree. See, e.g., United States v. Palmer, 809 F.2d 1504, 1505 (11th Cir.1987); United States v. Abodeely, 801 F.2d 1020, 1025 (8th Cir.1986); United States v. Rothstein, 530 F.2d 1275, 1279-80 (5th Cir.1976). It was entirely appropriate for the government to submit both direct and indirect proof of Hogan's tax liability. Through the direct proof that Hogan took bribes that were not listed on his tax returns, the government established the falsity of his returns. 40 Whether evidence that Hogan had $20,000 in unreported income would have been admissible in a trial based solely on the bribery charges is, however, a closer call. A large amount of unreported income is not the same as a great deal of cash on hand. Proof that a defendant failed to report income is prejudicial in a bribery case because it involves illegal activity. The government offers several reasons why the evidence of a $20,000 tax deficiency would nevertheless have been admissible. According to the government, the evidence demonstrates that Hogan had a large amount of cash during the time he allegedly took bribes. The government also argues that the evidence indicates that Hogan knew that taking money from attorneys was illegal because he neglected to report the money he received on his tax returns. Finally, the government says that the tax discrepancy corroborates the testimony of witnesses who stated that they paid Judge Hogan bribes. 41 A district judge, evaluating whether to admit in a bribery trial evidence that a defendant failed to report $20,000 of taxable income, would need to consider Rules 403 and 404 of the Federal Rules of Evidence. Rule 403 permits the trial court to exclude relevant evidence if its probative value is outweighed by the danger of unfair prejudice. Rule 404 states that "evidence of other crimes, wrongs, or acts is not admissible to prove the character of a person in order to show action in conformity therewith" but may be "admissible for other purposes, such as proof of motive, opportunity, intent, preparation, plan, knowledge, identity, or absence of mistake or accident." Fed.R.Evid. 404(b). In analyzing the admissibility of evidence under Rules 403 and 404(b) a trial judge would first consider whether the evidence was directed toward establishing a matter in issue other than the defendant's propensity to commit the offense. United States v. Shackleford, 738 F.2d 776 (7th Cir.1984). The district court would also evaluate whether the other act was similar enough and close enough in time to the offense charged, id. at 779, and whether the act occurred and the defendant was the actor, Huddleston v. United States, 485 U.S. 681, 108 S.Ct. 1496, 99 L.Ed.2d 771 (1988). Finally, the court would weigh the probative value of admitting the evidence against the danger of unfair prejudice. Shackleford, 738 F.2d at 779. 42 Although the tax evidence is prejudicial in the bribery context, we cannot say that the prejudice so outweighs its relevance that a district court would have abused its discretion by admitting the evidence. The government revealed Hogan's tax deficiency only for the years in which he also was accused of taking bribes.10 The evidence established that Hogan had unreported income on hand during 1981, 1982, and 1983. We have previously held that evidence of wealth may be admissible to establish that a person engaged in a cash-intensive criminal enterprise, even if there is another explanation for the extra money. See United States v. Bowie, 515 F.2d 3, 9 (7th Cir.1975); United States v. Higgans, 507 F.2d 808, 813 (7th Cir.1974); see also United States v. Magnano, 543 F.2d 431, 437 (2d Cir.1976), cert. denied, 429 U.S. 1091, 97 S.Ct. 1101, 51 L.Ed.2d 536 (1977); United States v. Tramunti, 513 F.2d 1087, 1105 (2d Cir.), cert. denied, 423 U.S. 832, 96 S.Ct. 54, 46 L.Ed.2d 50 (1975); cf. United States v. Davis, 838 F.2d 909, 921 (7th Cir.1988) (court holds harmless error to admit large quantities of cash to show defendants were involved in large-scale drug conspiracy). Evidence that the money came from another source goes to the weight and not the admissibility of the evidence. See Davis, 838 F.2d at 921. Furthermore, evidence that Hogan did not report the money he received from attorneys suggests that he knew that the payments were unlawful. Potentially prejudicial evidence, intended to show a defendant's knowledge, is specifically admissible under Rule 404(b). The evidence of $20,000 of undeclared income would arguably have been admissible in a trial for bribery. We believe that the district court in these circumstances did not abuse its discretion by refusing to sever the tax and RICO counts. 43 Even if the district court had abused its discretion in joining the RICO and tax counts, joinder of a tax claim to another charge, when the underlying charge generated only a portion of the unreported income, does not require automatic reversal. See United States v. Anderson, 809 F.2d 1281, 1288-89 (7th Cir.1987). The government sought to prove both directly and indirectly that Hogan took bribes that were not reported as income on his tax returns. The jury found Hogan guilty of accepting bribes. As the district court instructed, this direct proof alone established that Hogan falsified his tax returns. Likewise, the evidence that Hogan took bribes was compelling; the tax evidence did little more than substantiate the testimony of numerous witnesses who stated that they paid Judge Hogan money for favorable treatment.11 44 The district court provided additional safeguards by instructing the jury to consider each count separately. See United States v. Berardi, 675 F.2d 894, 901 (7th Cir.1982). The court explained the method that the government had used to devise its tax figures and noted that the government had used both direct and indirect methods of proving tax liability. Defense counsel extensively cross-examined the government's tax experts and pointed out the inconsistency between the government's evidence of tax liability using the cash method analysis and the evidence that Judge Hogan took bribes. The jury could then weigh the reliability of the evidence. Because the court adequately instructed the jury and defense counsel thoroughly explored the discrepancies in the evidence, we are satisfied that joinder of the RICO and tax counts did not prejudice Hogan. D. "Cash Method" Proof of Undeclared Income 45 In addition to raising the severance issue, Hogan challenges the admissibility of testimony regarding the cash method. He attacks four aspects of the tax testimony. According to Hogan, the cash method is not reliable because the amount of money taken as bribes ($4,400) does not correlate to the amount of unreported income ($20,000) established through the cash method. He also asserts that the cash method is an unapproved method for establishing tax liability; that the government failed to clarify the amount of money with which Hogan began 1981, a necessary prerequisite to using an indirect method of proof; and that the government failed to include Rae Hogan, Hogan's wife, as a source of cash in its analysis. We commit issues concerning the admissibility of evidence to the sound discretion of the trial court. United States v. Rein, 848 F.2d 777, 781-82 (7th Cir.1988). Unless the appellant can show that the court abused its discretion, we will not reverse its decision. Id. With that in mind, we consider each of Hogan's arguments. 1. Lack of Correlation 46 We can easily dispose of Hogan's first contention. As we acknowledged earlier, evidence that the defendant had more unreported income than proven directly through evidence supporting the underlying substantive charge is not inadmissible as a matter of law. Cf. Anderson, 809 F.2d at 1288-89. The inconsistency between the cash method figures and the amount that witnesses testified was given in bribes is a matter appropriate for argument, affecting the weight but not the admissibility of the evidence. The jury heard the evidence and defense counsel extensively cross-examined the tax experts regarding the flaws and inconsistencies in the cash method. Defense counsel also emphasized in its closing argument the inconsistency in the evidence. The court advised the jury that it was the jury's duty to evaluate the credibility of the witnesses, including the tax experts. The jury, therefore, was free to reject the government's cash method based on the lack of correlation between the government's figures. Because of these safeguards, we reject Hogan's argument that the discrepancies in the evidence render the cash method wholly unreliable and inadmissible. 2. Unapproved Method of Proof 47 Hogan next challenges the cash method as an untested and "unapproved circumstantial method of proof." Unlike other methods of proof upheld by the courts, Hogan contends, the cash method fails to account for all of the taxpayer's assets. Used correctly, however, the cash method should account for all of the taxpayer's known sources and uses for cash. It is a variation on the "cash expenditures" method, which we and other courts have upheld as a reliable method for indirectly proving unreported income. See United States v. Marrinson, 832 F.2d 1465 (7th Cir.1987); United States v. Caswell, 825 F.2d 1228 (8th Cir.1987); United States v. Abodeely, 801 F.2d 1020 (8th Cir.1986); Taglianetti v. United States, 398 F.2d 558 (1st Cir.1968), aff'd, 394 U.S. 316, 89 S.Ct. 1099, 22 L.Ed.2d 302 (1969). The cash expenditures method determines the amount of unreported income by "establishing the amount of [defendant's] purchases and services which are not attributable to the resources at hand at the beginning of the year or to non-taxable receipts during the year." Taglianetti, 398 F.2d at 562. If the amount of purchases and services exceeds defendant's reported income, resources on hand, and nontaxable receipts, the jury may infer that the defendant underreported income. 48 Like the cash expenditures method, the cash method focuses on the taxpayer's sources and uses of income. Unlike the cash expenditures method, however, the tax expert considers only coin and currency when using the cash method, ignoring assets and purchases that do not generate cash.12 The tax expert need not establish the taxpayer's opening and closing net worth except when that net worth contains assets that have been converted into sources for cash. Cf. Marrinson, 832 F.2d at 1469. Sources for cash include cash returned on deposits, checks written to "cash," cash withdrawn from checking and savings accounts, cash contents of safe deposit boxes, in addition to money on hand at the beginning of the taxable year. The expert then adds cash received from nontaxable sources of income--including loans, advances from credit cards, gifts, and inheritances--to cash generated by sources and compares this total to the amount of purchases and services for which the taxpayer paid cash. If the cash expenditures exceed the sources, the tax expert infers that the taxpayer failed to report income. 49 Apparently no other court has assessed the reliability of the cash method for identifying whether a taxpayer has failed to report taxable income. We, however, hold that under appropriate circumstances the cash method is an admissible method of proof if the government satisfies criteria similar to those used to evaluate the traditional cash expenditures method. Hogan reported on his returns that he only received taxable income from his judicial salary and from interest payments. Hogan deposited this income in bank accounts. Because Hogan had limited known sources of income and deposited the income from those sources in a bank account where noncash uses could be traced, the circumstances are particularly appropriate for the government to use a cash method of proof. Purchases made by means other than cash, such as payments made by check or credit card, can easily be traced and eliminated from the analysis, leaving only cash purchases to be analyzed through the indirect cash method. Where the defendant does not rely on noncash sources of income and channels money through a banking institution, the cash method is a particularly appropriate method for analyzing unreported income. 50 In a cash expenditures case, the government must show with "reasonable certainty" (1) defendant's opening net worth and cash on hand at the beginning of the period for which he was indicted and (2) defendant's expenditures during the period in question. Caswell, 825 F.2d at 1232. The government must also demonstrate a likely source of the allegedly unreported income or negate all reasonably possible nontaxable sources of income. Id. at 1231. To negate nontaxable sources of income, the government must investigate all reasonable leads. Using these criteria for guidelines, we address Hogan's remaining contentions. 3. Failure to Identify Cash on Hand 51 To establish a taxpayer's opening net worth in a cash expenditures case, the government is not required to present a formal net worth statement but to reasonably assess income and resources in the opening year. Marrinson, 832 F.2d at 1470. Although formal proof of net worth is not required, one court has stated that it is "essential" to establish cash on hand. United States v. Citron, 783 F.2d 307, 316 (2d Cir.1986). If a defendant volunteers a cash source for the allegedly unreported income, the government must show that it investigated the taxpayer's claim. See id. at 316. In a cash method case, therefore, the government must reasonably assess the cash on hand and sources of cash available at the beginning of the first year for which defendant is prosecuted. Hogan identifies the government's failure to establish his financial starting point as his third criticism of the cash method. 52 The government, however, adequately established that Hogan had no cash on hand at the beginning of 1981. An IRS agent testified that he investigated possible cash sources of income for Hogan and discovered no gifts, inheritances, or other nontaxable income in 1980. He also testified that Hogan appeared to take cash out of his account only as needed in 1980 and that Hogan had outstanding car and boat loans and credit card debts at the beginning of 1981. According to the agent, Hogan was paying interest on several loans and accounts at that time. Hogan admitted on cross-examination that he often received late payment notices from credit card companies and that one credit card company had placed his account in the hands of its collection department. Given this testimony, the jury could have found with reasonable certainty that Hogan did not have any cash on hand at the beginning of 1981. As stated in United States v. Marrinson, "it is possible to arrive at the conclusion that a taxpayer had no cash on hand, using the source and application of funds analysis, by demonstrating that a taxpayer simply spent more than he otherwise had available to him during that time." 832 F.2d at 1470. 4. Failure to Consider All Sources of Cash 53 Hogan also claims that the government failed to consider all of his cash sources in determining his cash income for 1981, 1982, and 1983. Specifically, he complains that the government did not consider his wife as a source of cash. As we stated earlier, the government is obligated to investigate all reasonable leads volunteered by the defendant and conduct a reasonable search for other cash sources to ensure that its analysis is thorough. Holland v. United States, 348 U.S. 121, 135-36, 75 S.Ct. 127, 135-36, 99 L.Ed. 150 (1954). 54 The government's tax expert testified that he considered all known sources of cash income in analyzing Hogan's tax records. The government provided testimony that it had reviewed the federal and state tax returns of Hogan and his wife, Hogan's salary checks, records from the judges' retirement system, Hogan and his wife Rae's banking records, loan and investment documents, Hogan's economic statement of interest, third-party checks, credit card records, travel documents, and Illinois Department of Conservation records. The government also subpoenaed institutions and persons to whom Hogan wrote checks and produced witnesses who testified regarding Hogan's purchases. Furthermore, the government interviewed Hogan's relatives and friends to determine whether the Hogans had nontaxable sources of cash. From this evidence a jury could infer that the government conducted a reasonable investigation to uncover all known sources of cash. 55 Although Hogan argues that the government should have included Rae Hogan as a source of cash, the government provided evidence concerning the effect her income would have on the unreported income figures presented and explained why it believed the jury should not consider her income in the analysis. The government developed a "Joint Cash Schedule" that showed the combined taxable income and unreported income of Hogan and his wife, in addition to the schedule analyzing only Hogan's cash income. The government's tax expert described each chart to the jury. The tax expert then explained that, based on Rae Hogan's cash expenditure pattern, her substantially smaller income, and the couple's bill payment practices, he did not consider Rae Hogan a source of income for her husband. Defense counsel thoroughly cross-examined the tax expert regarding his opinion that Rae Hogan was not a source of cash for Hogan and again emphasized this point in closing argument. 56 Hogan contends that cross-examination cannot rectify the damage caused by the omission of Rae Hogan's income from the government's primary analysis. In United States v. Citron, 783 F.2d 307, 316 (2d Cir.1986), the Second Circuit reversed a conviction for income tax evasion because the prosecution failed to lay a proper foundation for a chart that summarized the defendant's opening net worth. The Second Circuit rejected the argument that cross-examination could correct the error because the jury could not determine how the government derived the figures. See id. at 317. Unlike the prosecution in Citron, however, the government's tax expert explained the entries on the charts submitted, including the Joint Cash Schedule. The government identified why it thought the chart illustrating only Hogan's income was more accurate. The distinctions between the joint income chart and Hogan's chart were not complicated. The jury needed no special expertise to understand the government's presentation. We therefore find that cross-examination sufficiently exposed the alleged flaws in the government's dual presentation and that the district court did not abuse its discretion by admitting evidence of Hogan's tax liability exclusive of Rae Hogan's income. E. Hearsay Testimony of Tim Smith 57 Finally, Hogan contends that the district court erred in excluding certain testimony of Tim Smith, the son of the deceased Tempel Smith, Sr. who was a millionaire industrialist and Hogan's friend. In a proffer outside the jury's presence, Tim Smith testified that he overheard the following conversation during the summer or fall of 1979: his father told Tim's cousin that he wanted to give Hogan some money; Tim's cousin replied that Tempel Smith, Sr. could not give Hogan money because Hogan was a judge; Tempel Smith, Sr. responded that he could give Hogan money if it was a gift and not payment for services. 58 The district court excluded this testimony as hearsay, but Hogan argues that it is admissible under the state of mind exception, Rule 803(3) of the Federal Rules of Evidence. He contends that the testimony was offered to show Tempel Smith, Sr.'s desire to give him a gift or to prove that Tempel Smith, Sr. actually gave a gift of $5,000 to him in September 1979. An out-of-court statement is inadmissible hearsay if offered "to prove the truth of the matter asserted." Fed.R.Evid. 801. There is little question that the testimony offered by Hogan was hearsay because Hogan offered the testimony to ultimately prove that Tempel Smith, Sr. gave him cash as a gift. 59 Rule 803(3), however, excepts from the hearsay rule "statement[s] of the declarant's then existing state of mind, ... (such as intent, plan, motive, design, mental feeling, pain, and bodily health), but not including a statement of memory or belief to prove the fact remembered or believed." Fed.R.Evid. 803(3). Hogan contends that the testimony is admissible under the rule of Mutual Life Ins. Co. v. Hillmon, 145 U.S. 285, 12 S.Ct. 909, 36 L.Ed. 706 (1892), preserved in the advisory committee notes to Rule 803(3). In Hillmon the Supreme Court held that statements of a declarant's future intent are admissible to show that the declarant acted in conformity with his intention. Id. at 295, 12 S.Ct. at 912; see United States v. Peak, 856 F.2d 825, 833 (7th Cir.), cert. denied, --- U.S. ----, 109 S.Ct. 499, 102 L.Ed.2d 535 (1988). 60 The district court held that the testimony regarding the overheard conversation was inadmissible because it failed to show that Tempel Smith, Sr. specifically intended to give Hogan a cash gift in September 1979. We agree with the district court that Tempel Smith, Sr.'s comments were too speculative and vague to infer that he would immediately offer money to Hogan. As the Supreme Court stated in Hillmon: 61 When the intention to be proved is important only as qualifying an act, its connection with that act must be shown, in order to warrant the admission of declarations of the intention. But whenever the intention is of itself a distinct and material fact in a chain of circumstances, it may be proved by contemporaneous oral or written declarations of the party. 62 The existence of a particular intention in a certain person at a certain time being a material fact to be proved, evidence that he expressed that intention at that time is as direct evidence of the fact, as his own testimony that he then had that intention would be. 63 145 U.S. at 295, 12 S.Ct. at 912. As Hillmon and subsequent case law indicate, these statements derive reliability and probative value from their nexus to the act itself. See, e.g., United States v. DiMaria, 727 F.2d 265, 271 (2d Cir.1984) (statement admissible because it conveyed immediate state of mind); United States v. Williams, 704 F.2d 315, 321-22 (6th Cir.) (no abuse of discretion to exclude statements of intent that depended on the fulfillment of conditions subsequent), cert. denied, 464 U.S. 991, 104 S.Ct. 481, 78 L.Ed.2d 679 (1983). To identify that nexus, courts will consider the contemporaneous nature of the statements and the act, the chance for later reflection, and the relevance of the statements. See United States v. Ponticelli, 622 F.2d 985, 991 (9th Cir.), cert. denied, 449 U.S. 1016, 101 S.Ct. 578, 66 L.Ed.2d 476 (1980). The contemporaneous nature of the statements and the act preclude problems of perception and memory. See Oberman v. Dun & Bradstreet, Inc., 507 F.2d 349, 352 (7th Cir.1974). 64 Tempel Smith, Sr.'s comments to his nephew did not contain these indicia of reliability. It was unclear from his comments whether he actually intended to give Hogan cash or was merely considering the possibility. He did not indicate when he intended to give Hogan the money, and in fact, his comments suggest his uncertainty as to whether such a gift would be proper. This speculation indicates that, given a chance to reflect on the matter, Tempel Smith, Sr. may have reconsidered his proposal. Likewise, Tim Smith testified that he thought the conversation occurred in the summer or fall of 1979 but could not specify the month or the amount of money that his father was considering as a gift. The comments themselves and the surrounding circumstances simply do not indicate to us that the statements were a reliable indication of Tempel Smith, Sr.'s state of mind at the time that Hogan testified that Tempel Smith, Sr. actually gave him the money. 65 Even if the district court had erred in excluding Tempel Smith, Sr.'s comments, we would reverse a criminal conviction for an erroneous evidentiary ruling only if the ruling affected a defendant's substantial rights. See Peak, 856 F.2d at 834; see also Fed.R.Crim.P. 52(a); Fed.R.Evid. 103(a). We will reverse if the error " 'had substantial and injurious effect or influence in determining the jury's verdict.' " United States v. Lane, 474 U.S. 438, 449, 106 S.Ct. 725, 732, 88 L.Ed.2d 814 (1986) (quoting United States v. Kotteakos, 328 U.S. 750, 776, 66 S.Ct. 1239, 1253, 90 L.Ed. 1557 (1946)); see also Peak, 856 F.2d at 834. When the erroneous exclusion of evidence precludes or impairs the presentation of a defendant's sole means of defense, we deem the exclusion to have had a substantial and injurious effect on the jury. Peak, 856 F.2d at 834-35. 66 The exclusion of Tim Smith's testimony regarding the overheard conversation did not affect substantial rights. Hogan offered Tim Smith's testimony regarding his father's conversation to refute the government's cash method proof that Hogan had approximately $20,000 in unreported income. The government did not, however, rely solely on this indirect method of proof to establish that Hogan lied on his income tax returns. The government provided direct proof that Hogan took bribes that were excluded from his tax returns. The jury found Hogan guilty of taking bribes. This evidence alone established Hogan's tax deficiency and the cash method evidence was supplementary. Therefore any attack on the cash method evidence had only a mild impact on the overall case against Hogan regarding the tax charges. III. CONCLUSION 67 We find that the evidence was sufficient to support a conviction for aiding and abetting a bribe and that the district court properly admitted tape-recorded conversations between Terry Hake and Harlan Becker. We also believe that the district court committed no error on the issues of severance and the admissibility of the cash method evidence. Nor do we find merit in the argument that Tempel Smith, Sr.'s conversation with his nephew was admissible. For these reasons, we AFFIRM. A true Copy: 1 The grand jury subsequently returned two superseding indictments. Hogan was ultimately convicted under the second superseding indictment. The manner in which Hogan was indicted is not at issue on appeal 2 Chief Judge LeFevour was convicted of violating the RICO statutes, committing mail fraud, and filing false income tax returns and sentenced to twelve years in prison. We affirmed his conviction in United States v. LeFevour, 798 F.2d 977 (7th Cir.1986) 3 Neal Birnbaum, Martin Schachter, and Lee Barnett, three members of the Hustlers' Club, testified that they initially turned over $500 per person each month to James LeFevour but later reduced that amount to $250 because of competition from other attorneys in the courtrooms 4 Chief Judge LeFevour was only partially successful. Numerous witnesses testified that Judge Odas Nicholson, assigned to Branch 40, prohibited attorneys from hustling in her courtroom. Judge Thaddeus Kowalski, assigned to several First Municipal courtrooms, also testified that he attempted to rid his courtroom of hustling. We do not suggest that all judges in the First Municipal courts were parties to the activities supervised by Chief Judge LeFevour 5 Hogan was relieved of his duties as an associate judge in the Cook County circuit courts in June 1987 6 Hogan is not attempting to obtain a reversal on the RICO conviction. He concedes that the jury found two or more predicate acts, independent of the acts challenged, needed to support a RICO charge. See United States v. Holzer, 840 F.2d 1343, 1350-51 (7th Cir.1988). He suggests, however, that a finding of error with regard to Acts 4, 6, and 7 might influence the district court to reconsider his sentence 7 Becker referred to the judge as "he" on the tapes and the district court refused to let Terry Hake speculate on who Harlan Becker meant by "he." The inference most favorable to the government, however, is that Harlan Becker was referring to Judge Hogan 8 We need not consider whether the government could have shown a conspiracy between Becker and Hogan solely by introducing the out-of-court conversations. See United States v. Silverman, 861 F.2d 571, 577 (9th Cir.1988). The government provided corroborative testimony from Martin Schachter and documented proof that Becker had high bond totals. Becker's statements to Terry Hake were not the only evidence of the conspiracy 9 Rule 8 of the Federal Rules of Criminal Procedure also applies to questions of joinder but governs only allegations in the indictment. Once the indictment is found to meet the criteria for joinder in Rule 8, all further issues of joinder are controlled by Rule 14. See United States v. Garner, 837 F.2d 1404, 1412 (7th Cir.1987), cert. denied, --- U.S. ----, 108 S.Ct. 2022, 100 L.Ed.2d 608, --- U.S. ----, 108 S.Ct. 2914, 101 L.Ed.2d 945, --- U.S. ----, 109 S.Ct. 244, 102 L.Ed.2d 232 (1988); see also United States v. Lane, 474 U.S. 438, 447, 106 S.Ct. 725, 731, 88 L.Ed.2d 814 (1986). Hogan does not claim that the indictment was defective, therefore Rule 14 appears appropriate 10 The government used tax returns from prior years to impeach Hogan on cross-examination. Hogan, however, does not challenge the admission of those returns for the limited purposes of impeachment 11 Contrary to Hogan's contention, this case is distinguishable from United States v. Halper, 590 F.2d 422 (2d Cir.1978). In Halper, the Second Circuit held that the district court should have severed medicaid fraud charges from a tax evasion count. The prosecution in Halper provided no proof that the defendant excluded profits from the medicaid fraud from his tax returns. Id. at 429. Unlike the prosecution in Halper, the government showed that Hogan did not report income he received from attorneys as bribes on his tax returns. The charges were therefore related 12 Although the term "cash" is often intended to include purchases made with checks, the cash method, as defined by the government, does not include checks as a type of cash. Therefore, when we use the term "cash" we are only referring to coin and currency
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Football 101: Definitions and TermsBy Malamute, last updated 12 April 2004 This document presents the definitions of terms used in the Football-101 section of this website (see left navigation bar). This list of definitions is a work in progress that will be updated and expanded on a regular basis. Reference Figure 1, below, for the nomenclature used in the defensive alignments discussed within the terms and definitions. Confused by the following football terminology, I enlightened myself by doing some googling and studying. I hope this document will be an enlightenment; however, be forewarned that I've never played football, other than the sandlot variety. Triple option – The triple option, a three pronged attack, involves four players: the fullback, the play-side guard, the quarterback and a trailing back. After the play is underway and the quarterback takes the snap, the quarterback looks for the play-side guard who may or not be visible. If the quarterback can’t see the guard, he gives the ball to the fullback to follow the guard up field. If the guard remains in the blocking pattern, the quarterback veers along the line of scrimmage reading the DE’s shoulders—in this case, the DE has been left unblocked. If the DE’s shoulders are not square to the quarterback, the quarterback keeps the ball and cuts inside of the DE. If the DE’s shoulders are square to the quarterback, the QB pitches the ball to the trailing back who has maintained a five-yard separation with the QB. Variations of the triple option include, the inside veer option, outside veer option, and midline option. Then there are the double option plays, plays run off triple option action, with variations such as the speed option (with no fake hand-off to the fullback). Pistol Formation The quarterback lines up four yards behind the center, which is much closer than the seven-yard setback in a traditional shotgun formation. The running back then lines up three yards directly behind the quarterback, which is in contrast to the shotgun, where they are beside each other. (See the following link) Wildcat formation The Werewolf formation figuratively sucks the life's blood out of an opposing defense, while the Wildcat formation can add life to an offense. Seriously, in the Wildcat formation, the quarterback is replaced with a running back -- think single wing. The ball is snapped directly to the running back, with no time wasted handing the ball off; also, there is an extra blocker. The running back has the option to pass, making the formation even more difficult to defend. (See the following link). Speed Option If the pitch key (e.g., the DE above) takes the quarterback, the QB pitches the ball to the pitch back. If the pitch key takes the pitch back, the QB keeps the ball, plants his back foot and cuts vertically up field. If the the pitch key attacks the quarterback quickly, then the quarterback does not have to attack the pitch key, just pitches the ball. A benefit of the option attack is that it leaves one player unblocked, a simplifying factor. Bubble Screen Unlike a normal screen, in which a running back receives a short pass with offensive linemen blocking in front of him, the bubble screen uses a wide receiver receiving a pass behind a wall of offensive players lined up wide, often being other receivers and, perhaps, a tight end. (See the following link). Spread Offense As its name implies, the spread offense spreads a defense horizontally with the threat of an option game (double and triple options) and vertically because of the threat of 3 or 4 quick wide receivers. The spread formation features five basic runs (the zone dive; the trap; the trap option, the triple option; and the speed option). The passing game consists of play action and sprint out passes. The quarterback must be able to run and pass. "Because an opposing defense is unable to stack the line of scrimmage with eight men due to the four and five wide receiver sets, the quarterback has a smorgasbord of options with the running game alone. You will see the quarterback run the ball himself on draw plays, traps where the offense guard will pull and be a lead blocker, and even an occasional quarterback sweep." [Smith]. The threat of the passing game forces a defense into nickel and dime packages, making it easier to run against. The offense allows teams with weaker personnel to move the ball against superior players because all of them need not be blocked. Cover-2 – The Cover-2 defense, a response to the West Coast Offense and its short passing game, requires the two safeties to defend the deepest portion of the field, which is split in half, each safety defending half of the field, the "2" part of the defense. The three line backers and two cornerbacks “cover” the middle portion of the field, which has been divided into zones. It’s paramount that the four defensive linemen put a strong rush on the quarterback. Tampa Bay Defense - It all begins with a front four that penetrates quickly, forcing the offense to secure the line of scrimmage. Paying extra attention to the quick penetration allows the linebackers, who are all gifted, to roam free and make plays; the secondary lines up in a cover 2. It’s all about speed, and speed kills. This defense allows the offensive coordinator to be conservative in his quest to win the field-position battle, a battle aimed at controlling the middle of the field between the thirty-fives. Once mid-field is secured, the noose is tightened, until the opposing team is helplessly driven back towards its own goal line. After that, a multiplicity of bad things can happen to it, ranging from block punts to interceptions, leading ultimately to certain defeat. Same in ice hockey, good teams control center ice with strong fore-checking. Same in chess; a good chess player controls the middle of the board, i.e., the d4, e4, d5, and e5 squares. Gaps The open spaces between players on the line of scrimmage. For example, the gap between the center and guard is called the "A" gap. See Figure 1 below. X, Y, Z Receivers The x receiver, or the split end, aligns on the weak side of the formation. The z receiver, or the flanker, aligns on the strong side of the formation, maybe a couple of steps off the line of scrimmage in the slot. The tight end functions as the y receiver, but often on passing plays functions as another wide receiver. Slot Receiver The basic offensive formation has the tackle and tight end closely positioned and receivers positioned wide near the sidelines. That leaves a gap -- a slot -- between each receiver and the line. When a receiver lines up in that gap, he is called the slot receiver. Horse Collaring Pulling an opponent down by the back of his shoulder pads and riding him to the ground. Horse collaring an opponent will draw a flag in both college and pro football. Blitz The linebackers and defensive backs keep their hands off the ground, although a hand may need a “wipe” during the game (see USA’s “Monk” TV series for the definition of obsessive-compulsive behavior). When a linebacker(s) and/or defensive back(s) joins the defensive linemen in rushing the quarterback, it is called a blitz. One, two, three, or four of them may blitz the quarterback, overwhelming the offensive linemen. Cagey quarterbacks look for blitzes, anticipating vacant areas to throw to, maybe to a "hot receiver," such as the tight end. Zone Blitz In a standard zone blitz, a linebacker rushes the quarterback while a defensive lineman -- usually on the other side of the field -- drops back into pass coverage. Defensively, it can overwhelm an offense on one side of the ball and leave it with no one to block on the other side. Traditional blitzes leave a defense short handed, forcing it to play man-to-man. Since a defensive lineman has dropped back into coverage in the zone blitz, the defense can play zone coverage. Problems result when the defensive lineman isn’t as quick as the receiver he might cover or when the pass rush is not as effective because of his absence. Bootleg An offensive play in which the quarterback fakes a handoff to a running back, then sprints out in the opposite direction, looking to run or pass. Play-action Pass In play action, a quarterback fakes a handoff to running back while he's dropping back to pass. The quarterback hopes to slow down the defensive rush and force the defensive backs to make a wrong decision, hoping for them to come up to help stop the run. Skinny Post Wiley Post was a skinny Post, but he's not involved in this play. Any pass-receiving route that is directed towards the goal posts is called a “post pattern.” For example, a receiver may run down a sideline before angling towards the middle of the field, which in the case of a post pattern is defined by a vertical swath (the width of the goal posts) running from the line of scrimmage to the attacking goal posts. In a skinny post, or a “glance,” the route is shorter in length and quicker than a deep post, which may cover 30 or 40 yards. A color announcer may refer to the skinny post as a "glance in" or a "bang eight." (See Wikipedia for diagram) Computing a hypothetical per game offensive line efficiency rating Since the offensive line is arguably the most important positional unit on a team, a way of measuring its performance efficiency is needed. Otherwise, as they say, the quarterback gets too much credit for winning and too much blame for losing. Our hypothetical measure is a function of a team's passing efficiency rating, its rushing yards per carry, its rushing touchdowns, its offensive line's penalty yards and its sacks allowed. That is, (*) The normalizing numbers X=20.57 and Y=5.09 were chosen so that YPC plus RT would be equivalent to a Passing Efficiency Rating of 100. X and Y are the averages for the Pac-12 stats involving YPC (X = 90/4.375) and RT (Y = 10/1.96) for the 2013 season. The numbers 90 and 10 were chosen so that YPC would have more weight in the computation than RT; the numbers 4.375 and 1.96 are the Pac-12 averages for YPC and RT. To guard against a meaningless rating resulting from a limited number of carries, the normalizing number x needs to be restricted. For one, if the number of carries is less than z then set x=1, with the value of z yet to be determined. Alternatively, the value of the factor ypc * x could be controlled in a similar way to the limits placed on the NFL's passer rating computation. This defense involves a defensive back who covers a receiver individually (one on one), with no one to help him out if he gets beat, usually a cornerback in that case. Off Tackle Running Play We used to run this play in the school yard. Gil Dobie, Washington's unbeaten coach (59-0-3; 1908-1916), worked on off-tackle plays in practices until the cows came home and ate all the grass off Denny Field, leaving it a field of rocks and mud. Basically, the tailback runs to the strong side, where the tight end lines up. A hole is created by the tight end, the tackle and the fullback, who leads the play. The fullback's job is to take out the outside linebacker, giving the tailback room to run. 5-Technique A defensive alignment, whereby the defensive player aligns outside-eye to outside-shoulder of the tackle. (See Figure 1 below). Encroachment Like a 5-yard offside penalty. However, defensive contact is made with the offensive player before the snap. Pass Efficiency Rating A measure of the quarterback's effectiveness in the passing game. To determine pass-efficiency ratings points, multiply a passer's yards per attempt by 8.4; add the number obtained by dividing pass completions by pass attempts, multiplied by 100; add the number obtained by dividing touchdowns by pass attempts, multiplied by 330; and subtract the number obtained by dividing interceptions by pass attempts, multiplied by 200. A passer rating of 100 or better is considered terrific in the NFL. A rating of 158.3 is considered perfect in the NFL. However, certain percentages in the NFL are capped, although the same measures are used. The NCAA formula is shown below. A convicted criminal may receive a sentence ranging from a nickel to a dime (5 to 10 years). In football, nickel and dime packages refer to the number of defensive backs employed in an obvious passing situation, when the offense spreads the defense with receivers. The nickel package adds a fifth defensive back (called the nickel back), usually a cornerback. Six defensive backs comprise a dime package. Free Safety This sounds like a form of birth control, but it is not. A defensive player who lines up deepest in the secondary. He defends the deep middle of the field and seldom has man-to-man responsibilities. Strong Safety This sounds like...forget the joke. Like the free safety, the strong safety also plays deep, but he usually lines up on the same side as the tight end and has more responsibility in the run defense. A strong safety usually is bigger and more physical than a free safety. Cut and Chop Blocks A cut block involves a block below the knees, most often used by offensive linemen against defensive linemen and linebackers. Two players double-teaming a defensive player, one blocking high and one blocking low is called a chop block, which is illegal because it can lead to injury. Trap Block As its name implies, a defensive player is baited and then trapped. He is allowed through the offensive line only to be blocked by another player behind the line, usually a tight end, who is often put in motion on a trap block so that he gets to the area behind the line of scrimmage where the defensive player is coming through the line. On a "trap play," the running back attacks the hole left by the vacated lineman. Zone Blocking In zone blocking schemes, the offensive linemen team up to protect an area of the field, particularly against teams that stunt or slant to a defensive gap on the snap of the ball. Because of the myriad of defenses an offense is likely to face, it is necessary to reduce blocking to its simplest elements rather than have a blocking scheme for every defense that an offense might face. Hence, the introduction of blocking rules and the concept of team blocking. For example, a tackle and guard may team up to block a linebacker and defensive tackle, the blocking scheme for each offensive player depending on whether the linebacker and tackle play straight up or the linebacker stunts inside. Zone blocking depends on the concept of team blocking, and its principles are built by getting movement off the line of scrimmage, blocking all gaps and seams, and securing an area to the play-side of the hole. Underneath Coverage A defensive scheme in which one or more linebackers drop back into pass coverage, but the safeties remain positioned behind them. If a defense is playing underneath coverage, the quarterback's passing lanes may be filled and he will have to dump the ball off to a running back. Weak-side and Strong-side Weak-side refers to the side of the line of scrimmage opposite the alignment of the tight end, while strong-side refers to the side of the line of scrimmage whereby the tight end is positioned. The right side of the formation in Figure 1 below would be called the strong side, providing the player "LE" was aligned to create a marked "C" gap between himself and the left tackle (LT). Red Zone The area on the playing field between the opponent's 20-yard line and the opponent's goal line, an area where the offense is expected to score a touchdown or at the least, a field goal. Statistical percentages involving red-zone offense and red-zone defense provide analysts with a strong measure for rating the quality of a football team. Recursive Formation See recursive formation. (Just a dumb joke for Geeks who like football, the Geek/liking of which may be an oxymoron). Tenets of the West Coast Offense -- According to Bill Walsh, in the ideal setup, the wide receivers would catch 15 passes a game, the running backs would catch 10 and the tight ends would catch 5. A team is looking for 25 first downs a game. These quantities are referred to as "Walsh's numbers." -- Players must have more discipline; they have little opportunity for freelancing. -- Use the pass to set up the run. The most successful WCO teams run the ball well. -- If a team gains 7-8 yards per run, it can run as little as one out of four plays; otherwise, the WCO calls for an equal number of running and passing plays. -- The quarterback must be mobile, be able to throw a touch pass with accuracy, and be intelligent. He must throw on rhythm and timing. As Steve Young says, "In contrast, the West Coast offense as it originated with Bill Walsh is any play or set of plays that tie the quarterback's feet to the receiver's route so there is a sense of timing." -- In the 2-WR, 2-RB, 1-TE base set, any of these five players can be the primary receiver at any given time. -- Defenses are given a variety of looks, with an offense attacking a defense with more receivers than it can cover. Mismatches and confusion are created on defense by using 2 TE sets, 4 WR sets, and 3 WR sets, etc. -- Using motion forces a defense to cover players with inappropriate players for coverage, i.e., it creates mismatches. -- Throw the football on any down or distance. -- To maintain ball control, short passes to the tight end and swing passes to running backs are key. Use tight ends who can catch better than block if there is a question of personnel. Tight ends are key to a red zone attack. -- The quarterback must be able to release the ball quickly and accurately on timing after a 3-step drop. Receivers run precision routes. The offense is designed to keep the quarterback healthy. -- After the QB drops 3-steps back, one of the receivers should be open to catch a pass if necessary. Ron Jenkins calls him the HOT receiver. -- Power running behind zone blocking to minimize negative yardage plays. This is a departure from the 49ers version of the WCO that used man-blocking and cut blocks and misdirection.
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Q: Bootsrap col-* does not work when col-*-* present, but it should be the default EDIT: It works with the new Version of Bootstrap, at least for me I am working on a webpage with Boostrap 4. As far as I know col-xs-* got deprecated with 4.0 and the default for 0px up is now col-*. I have set "col-6 col-md-12" but its always 12 columns wide. <script src="https://stackpath.bootstrapcdn.com/bootstrap/4.0.0/js/bootstrap.min.js"></script> <link href="https://stackpath.bootstrapcdn.com/bootstrap/4.0.0/css/bootstrap.min.css" rel="stylesheet" type="text/css"> <div class="container-fluid" style="height: 100%"> <div class="row trenner"> <div class="col-6 col-md-12 logout"> <button class="logout"><i class="fa fa-sign-out-alt"></i><label class="btnLbl">Abmelden</label></button> </div> <div class="col-6 text-right wagenMobil"> <ul id="drop-dummy"> <button id="wagen-button"><i class="fas fa-shopping-cart"></i></button> </ul> </div> </div> Screenshot small Device If I set only "col-6" it works. If I do "col-6 col-sm-6 col-md-12" it will be 12 Columns wide until the breakpoint for sm, then its 6 and goes back to 12 when the breakpoint for md is reached. "col-xs-*" does not work with bootsrap 4 anymore. How do I get my Column to be 6 wide for xs devices? A: It was Chromes responsive view that caused the problem. As seen in the screenshot all elements have a calculated width of 980px no matter how small you resize it. If I don't use the responsive view in the dev options and resize the actual Browser window it works. PS: almost lost my mind over this what I guess is a bug.
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Q: Loop binding to find number of loops I could not find this in the buzz.js documentation but is there any bindings for the loop event. Something like soundObject.bind('looping', function(e){ }); I am looking to see how many times the sound object has looped, if anyone with knowledge around this library has a workaround that would also help. I tried to bind to the ended event but that doesn't work? EDIT: I am thinking as a hack that i could bind to the playing event and use the getPercent() method to see when i have hit 100 and keep a counter to find number of loops? A: Since there are no events that trigger with the loop option, then why not implement your own loop functionality by binding to the ended event and than calling play() again, this way you know when each play has finished. var loopCount = 0; var mySound = new buzz.sound("my_cool_sound").bind('ended', function () { loopCount++; this.play(); }).play(); Demo fiddle
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Top Events Sierra Vista, Arizona Event Tickets Sierra Vista is one of the greatest cities in the world. Whether on vacation or a current resident, you'll never get tired of all the things that are available in Sierra Vista, Arizona, and the surrounding areas!
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Preparation and up-conversion luminescence properties of LaOBr:Yb3+/Er3+ nanofibers via electrospinning. LaOBr:Yb(3+)/Er(3+) nanofibers were synthesized for the first time by calcinating electrospun PVP/[La(NO3)3 + Er(NO3)3 + Yb(NO3)3 + NH4 Br] composites. The morphology and properties of the final products were investigated in detail using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), X-ray diffractometry (XRD) and fluorescence spectroscopy. The results indicate that LaOBr:Yb(3+)/Er(3+) nanofibers are tetragonal in structure with a space group of P4/nmm. The diameter of LaOBr:Yb(3+)/Er(3+) nanofibers is ~ 147 nm. Under the excitation of a 980-nm diode laser, LaOBr:Yb(3+)/Er(3+) nanofibers emit strong green and red up-conversion emission centering at 519, 541 and 667 nm, ascribed to the (2)H11/2, (4)S3/2 → (4) I(15/2) and (4)F9/2 → (4)I(15/2) energy-level transitions of Er(3+) ions, respectively. The up-conversion luminescent mechanism of LaOBr:Yb(3+)/Er(3+) nanofibers is advanced. Moreover, near-infrared emission of LaOBr:Yb(3+)/Er(3+) nanofibers is obtained under the excitation of a 532-nm laser. The formation mechanism of LaOBr:Yb(3+)/Er(3+) nanofibers is proposed. LaOBr:Yb(3+)/Er(3+) nanofibers could be important up-conversion luminescent materials.
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An informed and thought-provoking analysis of what lies behind the headlines and headaches of business ethics and corporate social responsibility Tuesday, May 25, 2010 Should companies police for child pornography Few issues arouse as much public condemnation as child pornography.Asa visual record of child sexual abuse, itsproduction and disseminationscarsinnocent livesforever.It is illegal in virtually all developed countries to produce, distribute, and receive child pornography. So despitea criminal online trade in child pornography worthbillions ofdollars, nolegitimatecompany would knowinglygo anywhere nearthe practice. But should companies play a larger role in actively stamping out child pornography? And if so, how far should they go? Translate Follow by email Andrew Crane [L] and Dirk Matten [R] Welcome to the Crane and Matten blog - for informed commentary and expert analysis on the everchanging world of corporate responsibility. We are two business school professors best known for our books and research articles on business ethics and corporate citizenship. We wrote the Crane and Matten blog from 2008-2015, offering unique insight on a range of issues from across the globe. Andrew Craneis Professor of Business and Society in the School of Management, University of Bath. Dirk Matten is the Hewlett Packard Chair in Corporate Social Responsibility in the Schulich School of Business, York University.
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Pura Vida! The Ticos tandem of Ronald Matarrita and Rodney Wallace received the good news today. Both players have been called in to Óscar Ramírez’s Costa Rican preliminary World Cup squad that will train and play friendly matches before the squad is whittled down to the final 23. The schedule is strong and the stage couldn’t be bigger for two of our Boys in Blue. Costa Rica’s run up to the World Cup should provide the tests necessary to get the squad in gear. La Sele have signed up for friendly matches across Europe against Northern Ireland, England, and Belgium ahead of making camp in Russia. At the tournament, La Sele is slated to take on Serbia on June 17 (8 AM ET), Brazil on June 22 (8 AM ET), and Switzerland on June 27 (2 PM ET) to determine if they can make it to consecutive knockout rounds and better their previous best of a last 8 finish in Brazil just four years ago. Costa Rica qualified for the World Cup in dramatic fashion thanks to a late goal from Kendall Waston against Honduras that sealed their spot in Russia after successfully navigating the Hexagonal round with 16 points and a second place finish. Big wins over Trinidad & Tobago, and the United States drove La Sele through, and even a loss to first-place finisher Mexico couldn’t keep them out of Russia. The 23 year-old left-back Matarrita is fairly new to the senior set up, having represented Costa Rica at U-17, U-20, ad U-22 levels before making the jump to the senior side on September 5, 2015 in a friendly against Brazil. He scored his first goal for Costa Rica in a 3-1 win over Panama, in a World Cup qualification match. The 29 year-old MLS veteran winger Wallace has been a mainstay in the Costa Rica set up since making his international debut on September 2, 2011 – where he scored the only goal in a 1-0 victory over the US Men’s National Team at the Stubhub Center in Carson, California. Rodney earned five caps in World Cup Qualifying to help Costa Rica through to the finals. This is just the fifth time ever that Costa Rica have qualified for the World Cup, and their underdog nature coupled with the inclusion of City Boys Matarrita and Wallace will mean supporters at home and abroad. Congratulations to Ronald and Rodney! We can’t wait to watch you rep for the city on the highest level. SCHEDULE
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62 Cal.App.4th 780 (1998) BRUCE KASPER et al., Plaintiffs and Appellants, v. CEDARS-SINAI MEDICAL CENTER et al., Defendants and Respondents. Docket No. B094459. Court of Appeals of California, Second District, Division One. March 26, 1998. *781 COUNSEL Ronald M. Takehara for Plaintiffs and Appellants. Rushfeldt, Shelley & Drake, Kathryn S.M. Mosely, Barbara M. Reardon, O'Flaherty & Belgum, O'Flaherty, Cross, Martinez, Ovando & Hatton, C. Snyder Patin, Robert M. Dato and Stephanie C. Brenan for Defendants and Respondents. OPINION VOGEL (Miriam A.), J. Bruce Kasper and Nicole Pascale sued Cedars-Sinai Medical Center and Dennis Goldfinger, M.D., for damages. Defendants answered, then moved for summary judgment. On February 23, 1995, Defendants' motion was granted and a minute order to that effect was entered. On March 6, Plaintiffs filed a motion for reconsideration. On March 24 (before the reconsideration motion was heard), the trial court signed and entered a judgment in favor of Defendants. On March 28, Defendants served notice of entry of the judgment. On May 30, the trial court heard and denied Plaintiffs' motion for reconsideration. On June 23 and June 26 (87 days and 90 days after the March 28 notice of entry of judgment), Plaintiffs separately filed notices of appeal. We have no jurisdiction to consider these untimely appeals. *782 DISCUSSION (1) As relevant, rule 2(a), California Rules of Court, provides that "a notice of appeal from a judgment shall be filed on or before ... 60 days after the date of service of a document entitled `notice of entry' of judgment by any party upon the party filing the notice of appeal...."[1] Plaintiffs' notices of appeal were filed 87 and 90 days after notice of entry of judgment, 27 and 30 days too late. As a result, we have no jurisdiction to consider these appeals. (Stratton v. First Nat. Life Ins. Co. (1989) 210 Cal. App.3d 1071, 1078 [258 Cal. Rptr. 721].) To avoid this result, Plaintiffs point to rule 3(b) and contend their notices of appeal were timely because they were filed within 30 days after the date on which the trial court denied Plaintiffs' motion for reconsideration. Rule 3(b) does not apply to the facts of this case. When a motion for reconsideration is "filed by any party on any ground within the time in which, under rule 2, a notice of appeal may be filed, or such shorter time as may be prescribed by statute, the time for filing the notice of appeal from the judgment is extended for all parties until the earliest of 30 days after entry of the order denying the motion [for reconsideration]; or 90 days after filing the [motion for reconsideration]; or 180 days after entry of the judgment." (Rule 3(b).) Viewed from one perspective, Plaintiffs' motion for reconsideration of the non-appealable minute order did not trigger rule 3(b) because their motion did not seek reconsideration of an appealable order. (Eisenberg et al., Cal. Practice Guide: Civil Appeals and Writs (The Rutter Group 1997) Appealability and Standing to Appeal, ¶¶ 2:241, 2:241.1, p. 2-102.) Viewed differently, the trial court's entry of judgment on March 24 operated as an implied denial of the pending reconsideration motion, triggering the 30-day time period of rule 3(b) and making the notices of appeal 61 and 64 days late rather than 27 and 30 days late. (Ramon v. Aerospace Corp. (1996) 50 Cal. App.4th 1233, 1238 [58 Cal. Rptr.2d 217]; Nave v. Taggart (1995) 34 Cal. App.4th 1173, 1176-1177 [40 Cal. Rptr.2d 714].) Plaintiffs' reliance on Stratton v. First Nat. Life Ins. Co., supra, 210 Cal. App.3d 1071 is misplaced. In Stratton — where the motion for reconsideration was heard before the judgment was entered — this division held that motions for reconsideration attacking appealable judgments and orders are governed by rule 3(b), and that those attacking interim, nonappealable orders are governed by rule 2. (Stratton v. First Nat. Life Ins. Co., supra, 210 Cal. App.3d at pp. 1082-1083.) To the extent Stratton discusses the rules that might apply where, as here, the motion for reconsideration is heard after the *783 judgment is entered, the commentary is pure dicta.[2] Plaintiffs' reliance on Ten Eyck v. Industrial Forklifts Co. (1989) 216 Cal. App.3d 540, 545-546 [265 Cal. Rptr. 29], is also misplaced. Ten Eyck held that a "valid" motion for reconsideration extends the time for filing a notice of appeal, and that rule 2, not rule 3(b), applied there because the motion for reconsideration filed in that case was untimely. On the sequence of events presented by this case, the timeliness of the notice of appeal is governed by rule 2, not rule 3(b). DISPOSITION The appeals are dismissed. Defendants are awarded their costs of appeal. Ortega, Acting P.J., and Masterson, J., concurred. NOTES [1] All rule references are to the California Rules of Court. [2] For the reasons stated by our colleagues in the Fifth District, we agree that the Stratton dicta is based upon a false premise. (Nave v. Taggart, supra, 34 Cal. App.4th at pp. 1176-1177.)
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[Effectiveness of ketonal and diclofenac in spondylarthrosis complicated with spinal pain]. The article compares efficacy and safety of ketonal used in a dose 300 mg/day and diclofenac in a dose 150 mg/day in patients with primary spinal pain. The treatment of 60 patients aged 35 to 70 years (mean age 42.7 +/- 12.4 years) showed high efficacy of ketonal in spinal pain and low rate of side effects induced by this drug. Diclofenac was also effective.
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Introduction {#sec1} ============ Pain is a critical factor in dentistry because it is the primary cause of dental anxiety.[@bib1] Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or a sensation described in terms of such damage.[@bib2] Odontogenic pain is generated through complicated pathways; tissue damage results in action potential generation towards the central nervous system, which occurs in conjunction with inflammatory reactions at the affected site.[@bib3] It is a common belief that root canal treatment is the most painful type of dental treatment,[@bib4] and fear of postoperative pain affects many patients. Therefore, accurate knowledge regarding pain after root canal treatment and related factors will enable clinicians to predict and effectively manage postoperative pain.[@bib5] Furthermore, knowledge regarding the prevalence, severity, and management of postoperative pain after nonsurgical root canal treatment will reduce the occurrence of tooth removal and enable evidence-based guidelines for general practitioners to manage postoperative pain.[@bib4] Although root canal treatment alleviates long-term pain, postoperative pain immediately following root canal treatment is commonly reported.[@bib6], [@bib7], [@bib8] Therefore, effective prevention and management of such pain is essential to improve patient outcomes. The present study aimed to determine the effects of nonsurgical root canal treatment on postoperative pain and to determine predictive and related factors. We also assessed the effects of recent advances in postoperative pain management using a systematic review approach. To achieve these aims, the following specific questions were addressed in relation to the effects of nonsurgical root canal treatment on postoperative pain in adult patients.1)Does root canal treatment produce postoperative pain, and if so, what are the prevalences, severities, possible causes, and related factors?2)Are there relationships between recent advances in endodontics and postoperative pain?3)How can postoperative pain be prevented, reduced, and managed? Materials and Methods {#sec2} ===================== An electronic literature search was performed using the PubMed, ScienceDirect, and Cochrane databases to identify relevant peer-reviewed articles published between 1990 and 2016. Search keywords included "postoperative pain", "nonsurgical treatment", "single visit", "recent advances in endodontics", and "management of postoperative pain of endodontic treatment." We included original studies published in English. Editorials, reviews, brief notes, conference proceedings, and letters to editors were excluded ([Table 1](#tbl1){ref-type="table"}). The initial search identified 4941 articles, which were then assessed for eligibility and filtered using the selection criteria ([Figure 1](#fig1){ref-type="fig"}). Sixty-five studies met the inclusion criteria and were included in the present review.Table 1Article inclusion and exclusion criteria.Table 1InclusionExclusionArticle published in EnglishSystemic reviewStudy conducted using permanent teeth with fully formed apexesCase report or expert opinionClinical trial that randomly evaluated the influence of several factors on pain after root canal treatmentStudy based on endodontic retreatment casesFigure 1Article selection process.Figure 1 Results {#sec3} ======= The results of this systematic review revealed that the incidence of postoperative pain during the first 24--48 hours ranges from 3 to 69.3%.[@bib1], [@bib8], [@bib9], [@bib10], [@bib11], [@bib12], [@bib13], [@bib14], [@bib15], [@bib16], [@bib17], [@bib18], [@bib19] Mild to moderate pain has been observed in some studies,[@bib1], [@bib12], [@bib13], [@bib17], [@bib18], [@bib19], [@bib20], [@bib21] and moderate to severe pain has been observed in other studies.[@bib1], [@bib8], [@bib11], [@bib22] A strong relationship exists between preoperative and postoperative pain. Patients with acute preoperative pain are likely to experience more severe postoperative pain.[@bib16], [@bib23], [@bib24] The majority of studies revealed that patient age is not related to pain after nonsurgical root canal treatment;[@bib12], [@bib16], [@bib25], [@bib26] women experience more pain after this treatment than men.[@bib21], [@bib23], [@bib27], [@bib28] The incidence of pain after nonsurgical root canal treatment is also higher in the mandibular arch and in molar teeth.[@bib5], [@bib27] Intracanal medication is also related to pain after root canal treatment. No definitive evidence exists indicating that there are significant differences in postoperative pain between single-visit and multiple-visit root canal treatments. Recent advances in endodontics have resulted in reduced postoperative pain in terms of both intensity and duration.[@bib29], [@bib30], [@bib31] Providing patients with information regarding expected postoperative pain and managing pain using prescription medications are methods to improve patient confidence, increase patients' pain thresholds, and improve their perspective regarding future dental treatments.[@bib32], [@bib33] Pretreatment analgesia administered 30 minutes before root canal treatment reduces postoperative pain and may be useful, especially in patients with low pain thresholds.[@bib34] NSAIDs are most commonly used to control pain after root canal treatment.[@bib35] A flexible drug administration plan for pain control is recommended ([Figure 2](#fig2){ref-type="fig"}) and should be determined according to pain severity.[@bib36]Figure 2Drug administration protocol for postoperative pain management.Figure 2 Discussion {#sec4} ========== Postoperative pain prevalence and severity {#sec4.1} ------------------------------------------ The incidence of postoperative pain during the first 24--48 h ranged from 3% to 69.3%.[@bib1], [@bib8], [@bib9], [@bib10], [@bib11], [@bib12], [@bib13], [@bib14], [@bib15], [@bib16], [@bib17], [@bib18], [@bib19] Mild to moderate pain was observed in some studies,[@bib1], [@bib12], [@bib13], [@bib17], [@bib18], [@bib19], [@bib20], [@bib21] and moderate to severe pain was observed in other studies.[@bib1], [@bib8], [@bib11], [@bib22] In addition, several studies have reported severe postoperative pain after 12--24 h.[@bib14], [@bib16], [@bib23], [@bib24] Pain typically lasts for 24--48 h, although some patients report pain that continued for 3--9 days following root canal treatment.[@bib5], [@bib12], [@bib13], [@bib21] The variability in results can be explained by the use of different criteria to assess postoperative pain, the use of different materials and techniques for root canal treatments, and failure to consider preoperative pain as a variable.[@bib25] Factors resulting in postoperative pain {#sec4.2} --------------------------------------- Microorganisms are the most common factor associated with postoperative pain after nonsurgical root canal treatment,[@bib1], [@bib26] as pain typically results from the acute inflammation of periradicular tissues. Other causes of postoperative pain include mechanical or chemical damage to periradicular tissues.[@bib17], [@bib27] Specifically, mechanical factors such as overinstrumentation or extrusion of root canal obturation materials are associated with pain after endodontic treatments,[@bib6] and sodium hypochlorite (NaOCl) extrusion produces severe pain, swelling, and tissue injury when used as an irrigant for the periapical tissues.[@bib28] Factors related to postoperative pain {#sec4.3} ------------------------------------- Postoperative pain following nonsurgical root canal treatment is a multifactorial phenomenon and is related to the presence of periapical pathosis, missed canals, inadequate cleaning and shaping, apical extrusion of debris, apical patency during instrumentation, irrigant and intracanal medication extrusion, and overbite restorations,[@bib29] as well as tooth type[@bib5], [@bib30] and gender.[@bib31] There is a strong relationship between preoperative and postoperative pain. Patients who have acute preoperative pain are likely to experience more severe postoperative pain.[@bib16], [@bib32], [@bib33] However, there are inconsistent findings regarding the relationship between pulpal status and postoperative pain. Several studies have reported that pulpal status contributes to postoperative pain,[@bib25], [@bib34] whereas other studies have not demonstrated an influence of pulpal status.[@bib32], [@bib35] Peripheral and central sensitization resulting from inflammatory mediators during pulpitis and apical periodontitis may also increase pain severity.[@bib36] The majority of studies have found that patient age was not related to pain after nonsurgical root canal treatment.[@bib12], [@bib16], [@bib37], [@bib38] However, other studies have indicated a negative correlation between increasing age and treatment outcome,[@bib31] with patients \>35 years of age experiencing less pain than younger patients.[@bib34] There is no definitive evidence to prove that increasing age is associated with progressive loss of nociceptive sensitivity.[@bib39] Thus, decreased pain sensitivity with increasing age is not related to changes in physiological pain systems. However, pulp chamber recession complicates root canal treatment in older patients and results in more severe postoperative pain.[@bib5] Women experience more pain after nonsurgical root canal treatment than men.[@bib21], [@bib25], [@bib32], [@bib40] The biological differences between men and women resulting from changes in serotonin and non-adrenalin hormones may underlie gender differences.[@bib41] Similarly, cortisol modulates pain sensation and is secreted in higher quantities in men than in women.[@bib42], [@bib43] Other factors such as oestrogen, the menstrual cycle, lifestyle, and societal expectations may also contribute to gender differences in physiological reactions to pain.[@bib44] The incidence of pain after nonsurgical root canal treatment is also higher in the mandibular arch and in molar teeth.[@bib5], [@bib40] This difference may result from the dense trabecular pattern of the mandibular bone, which decreases blood circulation and concentrates infection, thereby delaying healing.[@bib32] Similar effects are associated with the complex anatomy of the lower molars.[@bib31], [@bib45] The maintenance of apical patency during root canal instrumentation had no significant influence on pain after root canal treatment.[@bib46], [@bib47] However, apical foramen enlargement due to over instrumentation during root canal treatment may increase the incidence and intensity of postoperative pain.[@bib48] Intracanal medication is also related to pain after root canal treatment. Compared to when no dressing is used, dressing the necrotic canals with chlorhexidine alone or with calcium hydroxide plus chlorhexidine reduces postoperative pain.[@bib49] In addition, postoperative pain associated with acute apical periodontitis is effectively managed by intracanal dressing with Ledermix paste, which is a mixture of a glucocorticoid (triamcinolone) and an antibiotic (demeclocycline).[@bib50] Ledermix efficiently and quickly relieves pain and is superior to calcium hydroxide for pain relief.[@bib51] Number of clinic visits and postoperative pain {#sec4.4} ---------------------------------------------- For the last few decades, more than 70% of dental schools have recommended single-visit root canal treatment.[@bib52], [@bib53] Recent advances in endodontics, such as nickel titanium rotary instrumentation, reliable apex locators, ultrasonics, microscopic endodontics, digital radiography, newer obturation systems, and biocompatible sealing materials, have facilitated more efficient endodontic procedures and enabled single-visit rather than multiple-visit root canal treatments.[@bib54], [@bib55] However, some studies report that many clinicians perform root canal treatments over multiple visits.[@bib16], [@bib38] Although single-visit root canal treatment is an efficient and clinically effective procedure, the incidence of postoperative pain is concerning,[@bib56] even though the majority of studies found no significant differences in postoperative pain between single-visit and multiple-visit root canal treatments.[@bib1], [@bib32], [@bib33], [@bib57], [@bib58] However, other studies have reported that postoperative pain increased for single-visit root canal treatments,[@bib59], [@bib60] which contrasts with reports that postoperative pain is reduced for single-visit root canal treatments.[@bib61], [@bib62] These discrepancies may result from differences in sample size, treatment techniques (such as rotary instrumentation vs. manual instrumentation or lateral condensation vs. vertical conization obturation), pulp status, whether teeth are single- or multi-rooted, and pain measurement techniques. [Table 2](#tbl2){ref-type="table"} Summarizes the relationship between the number of clinic visits and pain after root canal treatment.Table 2Summary of the relationship between the number of clinic visits and pain after root canal treatment.Table 2Study and reference no.Type of toothPulp statusNo. of teeth or patientsPercentage of casesIncidence of postoperative painSingleMultiplePatil et al.[@bib63]Maxillary central incisorVital and nonvital66 teeth100%n/aThere was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsOnay et al.[@bib62]All typesVital and nonvital1819 teeth31%69%The incidence of postoperative pain was minimal after single-visit root canal treatmentsWong et al.[@bib64]All typesVital and nonvital538 teeth51%49%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsPrashanth et al.[@bib57]All teethVital and nonvital32 patients50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsSingh et al.[@bib34]Single-rooted teethVital and nonvital200 teeth50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsWang et al.[@bib35]Permanent anterior teethVital100 teeth50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsEl Mubara et al.[@bib16]All typesVital and nonvital230 patients50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsBayram et al.[@bib1]All typesVital and nonvital306 patients50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsRisso et al.[@bib13]MolarsPulp necrosis118 teeth48%52%Postoperative pain was greater after 2-visit root canal treatment compared to single-visit treatment, although the differences were not statistically significantAl-Negrish et al.[@bib21]Central incisor teethNonvital120 teeth50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsOginni et al.[@bib59]All teethVital and nonvital107 teeth45.8%5.2%Pain after single-visit root canal treatment was greater than pain after multiple-visit root canal treatmentDiRenzo et al.[@bib65]Permanent molarsVital and nonvital72 patients54%46%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatmentsImura and Zuolo[@bib61]All typesVital and nonvital1012 patients57.5%42.5%Pain after multiple-visit root canal treatment was greater than after single-visit root canal treatmentFava 1994[@bib58]Maxillary central incisorsVital60 patients50%50%There was no significant difference in postoperative pain between single- and multiple-visit root canal treatments Effects of recent advances in postoperative pain management {#sec4.5} ----------------------------------------------------------- Recently, the practice of endodontics has benefitted from several new technologies that have improved treatment efficiency, safety, and quality.[@bib55], [@bib66] In addition, recently developed endodontic techniques and devices, such as operative microscopes, electronic apex locators, and rotary nickel titanium systems, have reduced procedure durations and increased the success rates of endodontic treatments.[@bib67], [@bib68] For example, the crown-down technique for cleaning and shaping root canal systems, which approaches the apical end starting from the coronal third and progressing towards the apical third, reduces extrusion of debris through the apical foramen. This reduction is significant because periapical debris extrusion is a major contributor to pain after root canal treatment.[@bib69], [@bib70] In addition, nickel--titanium engine-driven instrumentation extrudes less debris than manual stainless steel K-files.[@bib70] Hence, these instruments have dramatically decreased the incidence of postoperative pain.[@bib71], [@bib72], [@bib73] Similarly, advances in root canal instrumentation reciprocating systems have resulted in less postoperative pain in terms of both intensity and duration.[@bib70], [@bib74], [@bib75] Irrigant activation is an effective method to reduce postoperative pain,[@bib76] and the use of a negative apical pressure irrigation device can significantly reduce postoperative pain.[@bib6] However, one study found that there were no significant differences in postoperative pain between the use of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions.[@bib77], [@bib78] Preventive management of postoperative pain {#sec4.6} ------------------------------------------- Pain relief is often more important to patients than successful root canal treatment.[@bib79] Therefore, the prevention and management of postoperative pain after nonsurgical root canal treatment is a component of successful outcomes. Providing patients with information regarding expected postoperative pain and managing pain by prescribing medications improves patient confidence, increases patients\' pain thresholds, and improves patients\' views of future dental treatments.[@bib80], [@bib81] Pretreatment analgesia administered 30 min before root canal treatment reduces postoperative pain and may therefore be useful, especially in patients with low pain thresholds.[@bib82] Pretreatment analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs) before endodontic treatment blocks the cyclooxygenase (COX) pathway and may therefore block pain signals prior to sensation.[@bib83] One study found that premedication with a single dose of ibuprofen did not relieve postoperative pain after root canal treatment.[@bib84] However, the study sample was small (39 patients), and information was not provided regarding whether the pulp was vital or necrotic. Furthermore, a preoperative single oral dose of prednisolone (30 mg) or dexamethasone (4 mg) substantially reduces postoperative pain[@bib85], [@bib86] Administration of an enduring local anaesthetic (bupivacaine) during treatment can also significantly reduce postoperative pain after nonsurgical root canal treatment,[@bib87], [@bib88] and this effect is hypothesized to occur by blocking nociceptive impulses for a long enough duration of time to prevent central hyperalgesia in the early stages of inflammation after root canal treatment.[@bib89] Intracanal cryotherapy using 2--4 °C saline irrigation for 5 min as the final irrigant may significantly reduce postoperative pain.[@bib90], [@bib91] Cryotherapy restricts tissue metabolism and blood flow to tissues, thereby producing vasoconstriction.[@bib92] The resulting decreased external root surface temperature may constrain inflammatory reactions, reduce the release of pain-producing substances, and reduce edema in the periapical region. Localized inflammation has a crucial role in odontogenic pain development,[@bib3] and pain after root canal treatment results from periapical tissue inflammation.[@bib17] NSAIDs, including ibuprofen, aspirin, flurbiprofen, ketorolac, and etodolac,[@bib94] are most commonly used to control pain after root canal treatment.[@bib93] Prostaglandin synthesis is prevented by NSAIDs by reducing the enzyme activities of COX 1 and 2.[@bib46] Furthermore, moderate to severe pain is ideally managed using a combination of 2 or more drugs to enable a lower dose of each drug, which minimizes side effects.[@bib95] For example, the combination of an NSAID and acetaminophen can improve analgesia for dental pain.[@bib96] Similarly, a combination of ibuprofen and paracetamol effectively reduces pain following root canal treatment when taken immediately following the procedure.[@bib97] However, when NSAID combinations are not effective pain management strategies, a narcotic analgesic should be considered.[@bib98] Therefore, a flexible drug administration plan for pain control is recommended ([Figure 2](#fig2){ref-type="fig"}) and should be determined on the basis of pain severity.[@bib99] Furthermore, drugs should be administered four times per day until the pain subsides. The effects of reducing occlusion to relieve postoperative pain after root canal treatment are inconclusive. In teeth with symptomatic apical periodontitis, reducing occlusion did not have any effect on pain after root canal treatment.[@bib100], [@bib101] However, another study revealed that occlusal reduction of teeth with tenderness on biting effectively reduced postoperative pain.[@bib102] Pain on biting may result from inflammatory mediators stimulating periradicular nociceptors, and occlusal reduction may disrupt the continuous mechanical stimulation of the sensitized nociceptors.[@bib103] Conclusions {#sec5} =========== Pain after root canal treatment typically ranges from mild to moderate and can occur even after optimally performed root canal treatments. Recent advances in endodontics have reduced the incidence of pain after root canal treatment and improved patient satisfaction regarding postoperative pain. The effective management of postoperative pain is often considered an indicator of clinical excellence. However, further research is required to understand the physiology of pain and the mechanisms of relief associated with drugs and therapy. Conflict of interest {#sec6} ==================== The authors declare that there are no conflicts of interest regarding this article. Funding {#sec7} ======= No funding source had an influence on the study design, the data analyses, or the decision to publish this work. Peer review under responsibility of Taibah University.
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Let’s Explore 2019 Performance Framework Senior Spotlight Vol. 22 Naomi McMillan This afternoon we focus the Senior Spotlight on Naomi McMillan. This young lady has been a Grizzly since kindergarten. During her high school years, she was a multi-sport athlete competing on the Varsity Volleyball, Soccer, and Basketball Teams. Naomi also participated on the CGS Dance Team and was a member of the Spanish Club and FCA (Fellowship of Christian Athletes). She was also nominated to Homecoming Court during her sophomore, junior, and senior years. After graduation, Naomi plans to attend Alamance Community College and then transfer to the University of North Carolina at Greensboro where she will pursue a degree in psychology. As Naomi reflected on her years as a Grizzly she had a hard time choosing just memory as a favorite. Instead she stated, “My favorite CGS memory was every memory ever spent in the school, between the loving souls and the not so loving souls…I’ll always love to be known as a Graduating Grizzly.” Your Clover Garden family is also very glad to call you a Graduating Grizzly! When asked what she felt the Class of 2020 would be remembered for Naomi replied, “pretty sure we can say we set the record for senior skip day.” Very true! After reflecting on the people she felt had made a significant impact on her time as a Grizzly Naomi replied, “I would thank Harold mostly. Besides Harold, I’d like to think Every. Single. One. Of. You. <3 Thank you ALL for helping me become the person I am today.” Congratulations Naomi! We are very proud of you and your commitment to helping others as you pursue a career in psychiatry!
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AB-362 Personal income taxes: exclusion: health insurance.(2013-2014) Bill Start An act to add and repeal Section 17141 of the Revenue and Taxation Code, relating to taxation, to take effect immediately, tax levy. [ Approved by Governor October 01, 2013. Filed with Secretary of State October 01, 2013. ] LEGISLATIVE COUNSEL'S DIGEST AB 362, Ting. Personal income taxes: exclusion: health insurance. The Personal Income Tax Law imposes taxes based upon gross income, and defines gross income as all income from whatever source derived, unless specifically excluded. This bill, until January 1, 2019, would also exclude from gross income any amount received by an employee from an employer to compensate for specified federal income tax liability incurred by the employee. This bill would take effect immediately as a tax levy. Digest Key Vote: MAJORITY Appropriation: NO Fiscal Committee: YES Local Program: NO Bill Text The people of the State of California do enact as follows: SECTION 1. Section 17141 is added to the Revenue and Taxation Code, to read: 17141. (a) Gross income shall not include any amount received by an employee from an employer to compensate for the additional federal income tax liability incurred by the employee because, for federal income tax purposes, the same-sex spouse or domestic partner of the employee is not considered the spouse of the employee under Section 105(a) or Section 106(a) of the Internal Revenue Code, including any compensation for the additional federal income tax liability incurred with respect to those amounts. (b) This section shall remain in effect only until January 1, 2019, and as of that date is repealed. SEC. 2. This act provides for a tax levy within the meaning of Article IV of the Constitution and shall go into immediate effect.
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Introduction {#s1} ============ Data from the Centre for Disease Control indicate that in 2008, almost 20% of children between ages 6--11 were considered obese, and many of the females in this group are likely to remain obese through their childbearing years [@pone.0033370-Eriksson1]. In fact, epidemiological studies report that 15--20% of women of reproductive age in Canada, US, Australia and the UK are now clinically obese (BMI\>30 kg/m^2^) [@pone.0033370-Becker1]--[@pone.0033370-Ehrenberg1]. With obesity rates on the rise, it is clear that the consequences of life-long obesity on pregnancy outcomes need to be addressed. There is compelling evidence that obese women are at increased risk for many pregnancy-related complications to their own health, such as gestational diabetes and preeclampsia [@pone.0033370-Smith1]--[@pone.0033370-Rowlands1]. In addition to maternal health issues, there is also a considerable increase in the risk of fetal complications such as spontaneous abortions, fetal asphyxia, and stillbirth [@pone.0033370-Froen1], as well as increased risk of delivery of both small for gestational age (SGA) and large for gestational age (LGA) babies [@pone.0033370-Becker1], [@pone.0033370-Baeten1], [@pone.0033370-Rode1]. Pre-gravid obesity also contributes to reduced fertility in women [@pone.0033370-Arendas1], [@pone.0033370-Zain1], [@pone.0033370-Fretts1]. This may be due to disruptions in oocyte function [@pone.0033370-Igosheva1] or a chronic state of inflammation associated with obesity [@pone.0033370-Schmatz1], which may contribute to impaired implantation of the blastocyst [@pone.0033370-Bellver1]. While the mechanisms behind the obesity-mediated reduction in fecundity are not clearly understood, current speculation suggests that altered levels of cytokines and adipokines, as well as hormones such as insulin, may impact ovulation and implantation (reviewed in [@pone.0033370-Brewer1]). Maternal obesity is also associated with a number of metabolic disturbances such as insulin resistance, elevated serum triglycerides, and increased blood pressure (reviewed in [@pone.0033370-Hajer1]). In addition to these systemic effects, obesity has also been associated with tissue specific changes in mitochondrial function and elevated production of reactive oxygen species (ROS) leading to increased oxidative stress [@pone.0033370-Furukawa1], [@pone.0033370-Fujita1]. Some of these changes associated with maternal obesity may lead to alterations in placental development or function. Of critical importance to proper placental development is the establishment of the vascular architecture between maternal and fetal circulatory systems. Functional deficiencies at this interface can contribute to intrauterine growth restriction (IUGR) and pre-eclampsia (reviewed in [@pone.0033370-Arroyo1]), as well as a significant increase in premature fetal demise [@pone.0033370-Arendas1], [@pone.0033370-Nohr1], [@pone.0033370-Kristensen1]. While previous epidemiological studies have linked increased BMI with placental dysfunction and adverse obstetrical outcomes [@pone.0033370-Becker1], [@pone.0033370-Ray1] the mechanisms for such associations have not been fully elucidated. The majority of animal models that attempt to address the consequences of maternal obesity focus on postnatal outcomes [@pone.0033370-Howie1] or subject the dams to short-term high fat (HF) diets just prior to pregnancy or during gestation [@pone.0033370-Shankar1], [@pone.0033370-Samuelsson1]. This has resulted in a relative paucity of data regarding the consequences of long-term maternal obesity on placental function and fetal development. We have developed a rodent model which addresses the consequences of life-long obesity on the development of the placenta. Our model suggests that a life-long high fat diet results in altered vascularization of the placenta and this has adverse consequences for fetal survival. We observe increased numbers of stillbirths and reduced weight at birth, as well as reduced neonatal survival. These poor fetal and neonatal outcomes may be due to increased placental hypoxia and a trend towards increased oxidative stress as a consequence of altered development of the placental vasculature. Results {#s2} ======= HF-diet results in increases in the biomarkers associated with obesity {#s2a} ---------------------------------------------------------------------- HF-fed dams were 22% heavier by 19 weeks of age ([Figure S1](#pone.0033370.s001){ref-type="supplementary-material"}) and had 3-fold greater levels of serum leptin compared CON-fed dams ([Table 1](#pone-0033370-t001){ref-type="table"}). To assess the body fat composition in dams prior to pregnancy, CT scans (n = 7 in each group) were performed at 19 weeks of age ([Figures 1A and 1B](#pone-0033370-g001){ref-type="fig"}). The total body fat content for the area between the bottom of the lungs and the top of the sacroiliac joint was approximately 7 fold higher in the HF-fed dams as compared to the CON-fed dams ([Figure 1C](#pone-0033370-g001){ref-type="fig"}). In addition, abdominal fat pad weight during pregnancy (GD15) was found to be 2.5-fold greater in HF-fed animals (10.08±0.49% vs. 4.24±0.25% of total body weight; [Figure 1D](#pone-0033370-g001){ref-type="fig"}). ![CT analysis demonstrates that a HF-diet leads to increased subcutaneous and abdominal fat.\ Fasted rats were anesthetized and subjected to CT scanning. A. Representative CT-scan of a CON-fed dam; B. Representative CT-scan of a HF-fed dam. Adipose tissue is characterized by a lower intensity signal (darker regions on the image). The area occupied by the abdominal fat (AB) and subcutaneous fat (SQ) are indicated; scale bar = 1 cm. C. Adipose tissue absorption in the area between the bottom of the lungs and the top of the sacroiliac joint was calculated with Amira software using attenuation thresholds of −150 to −400 Hounsfield units. The values represent mean ± SEM. \* p\<0.01; n = 7 in each group. D. The mass of total abdominal adipose tissue during pregnancy (GD15) was also quantified and expressed as a percentage of body weight. The total pool includes gonadal, retroperitoneal and mesenteric fat. Values represent mean ± SEM; \*p\<0.01, n≥18 in each group.](pone.0033370.g001){#pone-0033370-g001} 10.1371/journal.pone.0033370.t001 ###### Pre-pregnancy metabolic parameters of fasted dams. ![](pone.0033370.t001){#pone-0033370-t001-1} Outcome measure CON-fed Dams HF-fed Dams P --------------------------- -------------- ------------- ----------------------------------------- Fasting Glucose (mmol/L) 4.9±0.3 5.7±0.2 0.03[\*](#nt102){ref-type="table-fn"} Fasting Insulin (ng/mL) 1.0±0.2 1.2±0.3 0.64 Glucose AUC 290.1±47.1 247.7±55.2 0.56 Insulin AUC 150±4.4 167±7.0 0.01[\*](#nt102){ref-type="table-fn"} HOMA-IR 0.11±0.02 0.11±0.05 0.79 Triglyceride (mg/dL) 72.5±13.9 131.8±19.0 0.02[\*](#nt102){ref-type="table-fn"} NEFA(mmol/L) 0.5±0.1 0.6±0.1 0.41 Total Cholesterol (mg/dL) 110.2±7.3 106.0±7.8 0.34 Leptin 3.55±0.51 12.72±1.69 0.0001[\*](#nt102){ref-type="table-fn"} Values are mean ± SEM, significantly different between CON-fed and HF-fed dams. In order to determine if increased body weight prior to pregnancy was associated with pre-pregnancy dysglycemia, we determined fasting glucose, insulin and HOMA-IR levels at 17 weeks of age ([Table 1](#pone-0033370-t001){ref-type="table"}). Fasted glucose levels were significantly elevated in HF-fed dams prior to mating (CON: 4.9±0.3 mmol/L vs. HF: 5.7±0.2 mmol/L, p\<0.05); however, fasted insulin levels and HOMA-IR were not significantly different. Interestingly, while the oral glucose tolerance test in these animals did not exhibit a significant difference between the two groups of dams, the insulin tolerance test demonstrated that HF-fed dams had a significantly greater area under the curve (AUC; [Table 1](#pone-0033370-t001){ref-type="table"}) compared to CON-fed dams. Prior to mating, HF-fed dams had significantly higher levels of fasting serum triglycerides (1.8 fold higher than CON-fed dams). Leptin levels were 3.5 fold greater in the HF-fed dams as compared to the CON-fed dams. Circulating non-esterified fatty acids (NEFA) and cholesterol levels were not different between the two groups. Elevated gestational blood pressure in HF-fed dams {#s2b} -------------------------------------------------- HF-fed dams had significantly higher systolic, diastolic and mean arterial pressure (MAP) at GD15 relative to normal weight dams ([Figure 2](#pone-0033370-g002){ref-type="fig"}). The difference in the MAP between HF-fed and CON-fed animals, was 21 mmHg (138±2.8 vs 117±1.7 mmHg). While the HF-dams did exhibit a higher blood pressure prior to pregnancy they also demonstrated a greater increase in their blood pressure over the course of their pregnancy as compared to the CON-fed dams ([Figure S2](#pone.0033370.s002){ref-type="supplementary-material"}). The greatest degree of difference between the two groups was evident between GD15 and GD20. ![Arterial Blood Pressure in elevated in obese dams at GD 15.\ Blood pressure was determined at GD15 using tail cuffs. Animals were gently restrained in cages warmed to 37°C using a heating pad. The hatched bars represent CON-fed animals, while the solid black bars represent HF-fed animals. Values are mean ± SEM; ^\*^p\<0.05, n≥23 in each group. The animals underwent 5 acclimatization cycles and 20 measurement cycles. The reported values are the mean of these 20 cycles.](pone.0033370.g002){#pone-0033370-g002} Life-long HF-diet affects obstetrical outcomes {#s2c} ---------------------------------------------- A HF-diet for 4 months prior to mating impacted a number of obstetrical and fetal outcomes ([Table 2](#pone-0033370-t002){ref-type="table"}). Time to copulation was significantly longer for HF-fed dams relative to CON-fed dams (3.80±0.41 vs. 2.59±0.39 days for CON-fed dams). Furthermore, the mating success for HF-fed dams was reduced by 32.4%, while the fertility index for this group was 22.1% lower. A significantly higher proportion of the offspring of HF-dams were small for gestational age (CON: 0.7% - 3/383 pups vs. HF: 4.7% -11/234 total pups). Most interestingly, there was a dramatic shift in the male/female ratio for HF-fed dams. The sex ratio (M/F) for CON-fed dams was 1.19±0.14; in contrast, the ratio for HF-fed dams was 0.67±0.11 (p = 0.008) indicating that significantly fewer males were born to this group of mothers. 10.1371/journal.pone.0033370.t002 ###### Obstetrical outcomes of CON and HF fed dams. ![](pone.0033370.t002){#pone-0033370-t002-2} Obstetrical Outcome CON-fed Dams HF-Fed Dams P -------------------------------- -------------- ------------- ---------------------------------------- Body Weight Prior to Pregnancy 303±5.9 412±11.9 0.001[\*](#nt104){ref-type="table-fn"} Average time to copulation (d) 2.59±0.39 3.80±0.41 0.03[\*](#nt104){ref-type="table-fn"} Mating success (%) 100 67.6 0.004[\*](#nt104){ref-type="table-fn"} Fertility Index (%) 73.8 51.7 0.03[\*](#nt104){ref-type="table-fn"} Live Birth Index 98.9±0.6 87.7±4.9 0.03[\*](#nt104){ref-type="table-fn"} LGA 11/383 0/234 0.003[\*](#nt104){ref-type="table-fn"} SGA 3/383 11/234 0.009[\*](#nt104){ref-type="table-fn"} Sex Ratio (M/F) 1.19±0.14 0.67±0.11 0.008[\*](#nt104){ref-type="table-fn"} Values are mean ± SEM, significantly different between CON-fed and HF-fed dams. Maternal obesity leads to compromised fetal growth and poor neonatal health {#s2d} --------------------------------------------------------------------------- Life-long maternal obesity impacts fetal growth and development. Obese dams not only had 30% fewer pups per litter ([Figure 3B](#pone-0033370-g003){ref-type="fig"}) but individual pup weights, both males and females, were reduced by 12% ([Figure 3A](#pone-0033370-g003){ref-type="fig"}). Even more striking was the significant increase in the number of HF-fed dams that gave birth to stillborn pups. 45% of the HF-fed dams compared to only 10% of CON-fed dams delivered stillborn pups ([Figure 3C](#pone-0033370-g003){ref-type="fig"}). Furthermore, the live pups born to HF-fed dams had reduced survival to post-natal day 4, an indicator of poor neonatal health [@pone.0033370-Johnson1]. Indeed, only 25% of the pups born to HF-fed dams survived past PND4 ([Figure 3D](#pone-0033370-g003){ref-type="fig"}). ![Neonatal health outcomes for pups born to CON or HF-fed dams.\ A. The body weight of offspring of CON-fed (hatched bar) or HF-fed (solid black bar) dams on postnatal day 1 (PND1). B. The average number of pups per litter born to CON-fed or HF-fed dams. C. The percentage of CON-fed or HF-fed dams giving birth to at least one stillborn pup. D. The percentage of the total number of live pups in the litter that survived to PND4. E. The fetal/placental weight ratio was calculated for CON-fed and HF-fed dams. F. The average number of resorption sites for CON-fed and HF-fed dams at GD15. Values represent mean ± SEM; ^\*^p\<0.05; n≥12 dams per group.](pone.0033370.g003){#pone-0033370-g003} *In utero* fetal development was also affected by maternal obesity. Evidence of premature fetal demise in the HF-fed dams was indicated by an almost 3-fold increase in the number of uterine absorption sites ([Figure 3F](#pone-0033370-g003){ref-type="fig"}). Furthermore, the fetal to placental weight ratio also exhibited a 12% reduction in this group of dams (p\<0.05) ([Figure 3E](#pone-0033370-g003){ref-type="fig"}). The placenta of HF-fed dams are characterized by altered vascular development {#s2e} ----------------------------------------------------------------------------- Maternal obesity affected blood vessel density and maturity ([Figure 4](#pone-0033370-g004){ref-type="fig"} and [5](#pone-0033370-g005){ref-type="fig"}) in the labyrinth. There was an almost 2 fold increase in the CD31 positive area, an endothelial cell marker, in the placenta of HF-fed dams compared to controls ([Figure 4C](#pone-0033370-g004){ref-type="fig"}). Accordingly, the blood vessel density within the placenta (number of CD31-positive blood vessels per field) was higher ([Figure 4D](#pone-0033370-g004){ref-type="fig"}). However, there was a 30% decrease in the number of blood vessels that stained positive for smooth muscle actin (SMA), a marker expressed by vascular smooth muscle cells and found in mature blood vessels ([Figures 5](#pone-0033370-g005){ref-type="fig"}). ![The labyrinth layers of placentas from HF-fed dams exhibit increased expression of endothelial cell markers at GD15.\ Representative images, acquired at 100× magnification, of GD15 placenta from CON-fed (A) and HF-fed dams (B) immunostained with CD31 antibody are shown. Scale bar = 50 µm; the labyrinth (L) and junctional zone (JZ) are indicated for reference. Four distinct regions from each histological section were quantified and averaged in determining percent immunopositive area. Images from an individual dam represent a single statistical unit. C. The percentage of area immunopositive for CD31 in the labyrinth of GD15 placenta based on the analysis of cross sections from CON-fed and HF-fed dams sacrificed at GD15. D. The number of blood vessels per field for CON-fed or HF-fed dams at GD15. All values mean ± SEM, ^\*^p\<0.05; n = 5 dams for each group.](pone.0033370.g004){#pone-0033370-g004} ![The labyrinth layers of placentas from HF-fed dams exhibit fewer SMA positive blood vessels at GD15.\ Representative images, acquired at 200× magnification, of GD 15 placenta from CON-fed (A) and HF-fed dams (B) immunostained with an antibody to SMA are shown. The SMA positive area within the labyrinth (L) of each group of animals was quantified. C. The average number of vessels per field of view staining positive for smooth muscle actin (SMA) in placentas from CON-fed and HF-fed dams. D. All values mean ± SEM; ^\*^p\<0.05, n = 5 dams for each group.](pone.0033370.g005){#pone-0033370-g005} The placentas of HF-fed dams are characterized by reduced tissue oxygenation {#s2f} ---------------------------------------------------------------------------- The levels of carbonic anhydrase within the placenta were evaluated as an indicator of tissue hypoxia [@pone.0033370-Said1]. Carbonic anhydrase-immunopositive tissue in HF placenta was increased by 47% over CON placenta ([Figure 6A--C](#pone-0033370-g006){ref-type="fig"}). ![The labyrinth layers of placentas from HF-fed dams exhibit increased levels of carbonic anhydrase staining at GD15.\ Representative images, acquired at 200× magnification, of GD 15 placenta from CON-fed (A) and HF-fed dams (B) immunostained with an antibody to carbonic anhydrase are shown. C. The average staining intensity in placentas from CON-fed and HF-fed dams was calculated. All values mean ± SEM, ^\*^p\<0.05; n = 5 dams for each group.](pone.0033370.g006){#pone-0033370-g006} Since hypoxia is known to increase oxidative damage in the placenta [@pone.0033370-Hung1] we assessed whether there was a change in the level of systemic oxidative damage in obese pregnant dams by quantifying urinary 8-hydroxy- 2-deoxyguanosine (8OH-2-dG). This is a well characterized marker of oxidative damage, and its increase in obesity has been reported in both humans [@pone.0033370-Devries1] and rodents [@pone.0033370-Shen1]; therefore we carried out a one-tailed Students T-test with respect to the significance of this data. Urinary 8OH-2-dG levels in the HF-fed animals were 25% higher relative to the CON-fed dams; however this did not reach statistical significance (p\<0.1) ([Figure 7](#pone-0033370-g007){ref-type="fig"}). There was also an increase in the mean levels of 4-HNE (p\<0.1) in whole placental homogenates of GD15 HF-fed dams ([Figure 8A and B](#pone-0033370-g008){ref-type="fig"}). Interestingly, a mitochondrially enriched fraction isolated from the placentas of HF-fed also exhibited increases in the levels of protein carbonyls, a marker of oxidative protein damage ([Figure 8C and D](#pone-0033370-g008){ref-type="fig"}; p\<0.1). While neither of these markers of oxidative damage were statistically different in the placenta of CON-fed vs HF-fed animals, the mean levels are consistently higher in the HF-fed dams. ![8-hydroxy 2-deoxyguanosine, a marker of systemic oxidative damage, is not significantly increased in the HF-dams.\ Levels of 8-OH-2-dG were quantified in urine collected from GD15 CON-fed and HF-fed dams at sacrifice using a competitive EIA kit. 8-OH2-dG was normalized to the concentration of creatinine in urine. All values mean ± SEM, n = 15 for CON and n = 10 for HF-fed dams. ^†^p\<0.1 by one tailed Students T-test.](pone.0033370.g007){#pone-0033370-g007} ![Markers of tissue specific oxidative damage are not significantly increased in placentas from HF-fed dams at GD15.\ A. 10 µg of total whole placental homogenate was separated on a 12.5% SDS-PAGE and subjected to Western blot analysis. The average content of 4-HNE was normalized to total protein (using Ponceau-S staining) in CON (hatched bars) or HF-fed (solid black bars) dams. B. Representative lanes containing 10 µg placental homogenates, developed using the 4-HNE monoclonal antibody. C. The relative content of protein carbonyls was quantified using a polyclonal antibody directed towards 2,4-dinitrophenylhydrazine (DNPH). This quantification was carried out using 5 µg of placental homogenate enriched for mitochondria. D. Representative lanes containing 5 µg of protein, enriched for mitochondria, prepared from CON or HF-fed dam placenta were separated on a 12.5% SDS-PAGE and developed using the anti DNPH polyclonal antibody. Values represent mean ± SEM; ^†^p\<0.10, n = 6 per group.](pone.0033370.g008){#pone-0033370-g008} Discussion {#s3} ========== The effects of maternal obesity on pregnancy outcomes in humans are well documented. Despite the plethora of epidemiological data surrounding the consequences of maternal obesity, the mechanistic understanding of the cellular signaling that mediates poor health outcomes for both mother and fetus are far from clear. These adverse outcomes include metabolic complications in the offspring [@pone.0033370-Boney1], obstetrical complications in the mother [@pone.0033370-Baeten1], [@pone.0033370-Nohr1] and abnormal fetal growth [@pone.0033370-Kristensen1], [@pone.0033370-Leddy1]. The lack of a mechanistic understanding of these processes may be due, in part, to the difficulty of developing animal models that emulate all the complications of obesity during pregnancy in humans. The majority of rodent models designed to address the consequences of maternal obesity have been focused on understanding metabolic reprogramming in offspring and have not focused on factors responsible for premature fetal demise and poor neonatal health. Our rodent model of life-long maternal obesity is characterized by the well accepted hallmarks associated with obesity such as elevated serum leptin and triglycerides and increased body fat. An evaluation of glucose homeostasis prior to pregnancy demonstrated that the HF-fed dams had a small but significant increase in their fasting glucose levels and were insulin resistant (i.e., had an increased area under the curve following an insulin challenge). This is to be expected with such obese animals. However the results of the glucose tolerance test did not prove to be significantly different between the groups. This suggests that the pancreas has been able to modulate insulin secretion to maintain glucose homeostasis and these animals have not yet developed overt type 2 diabetes mellitus. Taken together the data suggest that there is partial loss of glycemic control in the HF-fed animals which may become aggravated during pregnancy. We did not conduct OGTT measurements during pregnancy due to the possibility compromising fetal health. The model also demonstrates many of the fetal and maternal complications seen in human pregnancies associated with obesity; increased blood pressure during pregnancy, reduced fetal growth, and increased fetal/neonatal demise [@pone.0033370-Kristensen1], [@pone.0033370-Leung1]. In addition to the parallels in fetal outcomes, we also observed obstetrical complications associated with obesity in reproductive age women such as reduced fertility [@pone.0033370-Arendas1]. Interestingly, the majority of epidemiological studies report that obese women are at significantly greater risk for delivering large for gestational age (LGA) babies, yet there is also an elevated risk for small for gestational age (SGA) babies which has also been noted in humans, primates and rodents [@pone.0033370-Rode1], [@pone.0033370-Leung1], [@pone.0033370-Akyol1]. An evaluation of singleton pregnancies between 1978--1997 in Missouri (over 310,000 pregnancies) found that SGA babies born to obese mothers were at significantly greater risk for neonatal death [@pone.0033370-Salihu1] compared to LGA babies born to this group. Furthermore, the risk of premature death for these neonates increased with degree of their mother\'s obesity [@pone.0033370-Howie1], [@pone.0033370-Samuelsson1]. Since the mechanisms for such phenomenon are not well understood it underscores the importance for developing an animal model for elucidating the pathways leading to premature fetal demise and poor neonatal health. Reduced fetal growth and premature fetal demise, as a consequence of obesity during pregnancy, may implicate placental dysfunction. Similar outcomes have been connected with placental dysfunction in preeclampsia and IUGR [@pone.0033370-Nash1]. While higher rates of preeclampsia are associated with obesity [@pone.0033370-Granger1], it has been argued that this is a uniquely human condition and may not be accurately emulated in rodent models [@pone.0033370-Nama1]. Two recent studies have also reported poor fetal growth in association with maternal obesity, but have not evaluated premature fetal demise in their respective models. Grove and colleagues [@pone.0033370-McCurdy1] demonstrated that a life-long high-fat diet in Japanese macaques resulted in fetal growth retardation. Similarly, in a rodent model, Akyol et al. showed that Sprague-Dawley dams fed a cafeteria diet prior to and during pregnancy had lower fetal and placental weights, as well as a lower fetal∶placental weight ratio at GD20 of pregnancy [@pone.0033370-Akyol1]. In agreement with these observations, the birth weight of the pups from our cohort of HF-fed dams was reduced by 12%, and we also observed a decreased fetal∶placental weight ratio at GD15. However, this growth retardation was not as profound as has been reported in rodent models of chemically induced pre-eclampsia (more than a 30% decrease in pup birth weight) [@pone.0033370-Nash1]. The current model of maternal obesity is also characterized by a significant increase in the number of HF-fed dams delivering stillborn pups, as well as an increase in the number of fetal resorption sites; further evidence of premature uterine demise. Epidemiological data suggest that the mechanisms behind a large percentage of reported stillbirths are not well understood [@pone.0033370-Froen1]. Our rodent model clearly points to a role for maternal obesity-associated placental dysfunction in increasing the risk of stillbirths and supports the existing epidemiological data [@pone.0033370-Fretts1]. In humans, epidemiological data has been used to suggest a correlation between metabolic syndrome and placental dysfunction [@pone.0033370-Ray1]. It is important to note that while the temporal relationships in placentation differ between rodents and humans, the early processes leading to the establishment of the maternal-fetal interface are common, making rats a good model for placental studies [@pone.0033370-Caluwaerts1]. In order to understand why the fetuses of HF-fed dams failed to thrive, we analyzed the histomorphology of the placenta at mid-gestation (GD15). We observed an increase in CD31 staining in the labyrinth of placentas from HF-fed dams indicating the presence of greater numbers of blood vessels, an observation supported by recent data which has demonstrated that vascularization is also dysregulated in the placental cotyledons of the obese ewe [@pone.0033370-Akyol1]. Interestingly, the increase in blood vessel density, observed in our model, was inversely proportional to the staining with SMA, an indicator of blood vessel maturity [@pone.0033370-Cimpean1]. A reduction in the presence of SMA staining surrounding endothelial cells in the labyrinth has been associated with increased gestational blood pressure and reduced fetal growth in a mouse model of preeclampsia [@pone.0033370-Furuya1]. Together this suggests that placenta of HF-fed dams may have significant deficits in the processes involved with blood vessel maturation. The poor development of the placental vasculature in the placenta of obese dams may result in reduced blood flow to the placenta, an observation which is consistent with the evidence of hypoxia in the placenta of HF-fed dams. In humans, changes in vascularization and hypoxia in the placenta are associated with several disorders of pregnancy, including IUGR, SGA fetuses and preeclampsia [@pone.0033370-Khankin1]. Hypoxia is known to be a signal for the production of VEGF [@pone.0033370-Loboda1] which may trigger increased angiogenesis and would be consistent with the increased CD31 staining observed in the placenta\'s of our HF-fed dams. Hypoxia is also associated with increased oxidative stress [@pone.0033370-Hung1] which in turn can result in significant placental pathology [@pone.0033370-Zusterzeel1]. Furthermore, systemic increases in the markers of oxidative stress have also been reported in obese humans [@pone.0033370-Devries1] as well as rodents [@pone.0033370-Shen1]. In general, oxidative stress results from an imbalance between increased cellular ROS production and cellular antioxidant defenses. If ROS production overwhelms cellular defenses then this can result in either increased cellular damage or adaptive changes mediated by free radical signaling [@pone.0033370-Raha1]. We therefore assessed the level of oxidative damage in our HF-dams by using several markers of systemic as well as tissue specific oxidative damage. While our HF-fed dams did not exhibit a statistically significant increase in systemic oxidative damage, the mean level of urinary 8OH-2-dG (a marker of oxidative damage to DNA), was higher in this group. In addition to being associated with obesity, increases in 8OH-2-dG in maternal mid-gestational urine has been associated with reduced fetal weight at birth in humans [@pone.0033370-Min1]. Oxidative stress results from the production of superoxide radicals from a number of cellular sources, including mitochondria, which ultimately contribute to the formation lipid peroxides, protein carbonyls, or 8OH-2-dG [@pone.0033370-Raha1], [@pone.0033370-Raha2]. These represent markers of lipid, protein and DNA damage respectively. The consequence of such increases in ROS are dictated by the reactivity and lifetime of the reactive species (reviewed in [@pone.0033370-Myatt1]). Interestingly, recent work by Myatt and colleagues suggests that the majority of the oxygen free radicals formed in the pre-eclamptic placenta is converted to peroxynitrite and this results in an increase in protein nitration and perhaps a decrease in overall markers of oxidative damage [@pone.0033370-Myatt2]. Our attempts to compare the level of nitrotyrosine modification in the GD15 placental homogenates of CON-fed vs. HF-fed dams demonstrated that while there was an increase in the mean of the level of protein residues modified by nitrotyrosine the values did not reach statistical significance ([Figure S3](#pone.0033370.s003){ref-type="supplementary-material"}). We also observed a small increase in the mean levels of lipid damage (4-hydroxy-2-noneal) in the placenta of HF-fed dams (p\<0.1). We therefore examined whether oxidative damage may be more evident in isolated mitochondria because they are considered to be one of the primary producers of cellular superoxide. Due to the limited diffusion distance of superoxide, the probability of damage proximal to the site of production may be greater. We demonstrate in this study that the mitochondria isolated from whole placenta of HF-fed dams also exhibited increased mean levels of protein damage (protein carbonyls) but these did not reach statistical significance. While we cannot conclude that there is an increase in the level of oxidative stress in the placenta of obese dams, it is interesting to note that three separate markers of oxidative damage all exhibited increased mean levels in the placenta of obese dams. Furthermore, we cannot exclude the absence of oxidative stress because of the possibility that diet may have resulted in increased expression of ROS defense proteins which may attenuate the level of damaging radical species. The altered vascular development and associated hypoxia in the placentas of HF-fed dams may contribute to poor fetal growth and neonatal survival. Our model demonstrated that the offspring of HF-fed dams exhibited increased neonatal death. A link between reduced fetal growth *in utero* and poor neonatal health has been suggested based on the observation that SGA babies born to obese women exhibit reduced post-natal survival [@pone.0033370-Salihu1]. However, neonatal demise may be the result of a number of perinatal, as well as postnatal factors. For example, epidemiological studies have pinpointed maternal obesity as a predictor of delayed onset of lactation as well as a reduced intention to breastfeed [@pone.0033370-NommsenRivers1], [@pone.0033370-Amir1]. Recent work by Bautista et al. suggest that maternal obesity, in a rat model, results in reduced breast milk production higher fat and leptin content [@pone.0033370-Bautista1]. Our current experimental design does not allow for the delineation of the extent to which such postnatal factors contribute to the early demise of the neonates. Taken together our model of life-long maternal obesity in rodents exhibits many of characteristics demonstrated clinically in obese humans including premature fetal demise and reduced fetal growth. Our data is consistent with the view that excess adiposity during pregnancy alters the development of the placental vasculature and this reduces tissue oxygenation. Using examples of undernutrition during pregnancy, it been suggested that the fetus adapts to increased uterine stress and hypoxia by sparing the growth of the brain and reducing body growth [@pone.0033370-Yu1], [@pone.0033370-Barker1]. It is possible that this increased uterine stress, as a result of maternal obesity, facilitates the development of defects in the pathways responsible for the proper development of the placental vasculature. In fact, it has been suggested that failure to remodel the spiral arteries may be associated with increased oxidative stress and pregnancy failure in humans [@pone.0033370-Myatt3]. It will therefore be important to delineate the mechanisms by which obesity can affect development of placental vasculature. The elucidation of these pathways will contribute to understanding how maternal obesity affects poor fetal development and premature death. Materials and Methods {#s4} ===================== Animal protocol and sampling of histological preparations {#s4a} --------------------------------------------------------- All animal procedures for this study were approved by the McMaster University Animal Research Ethics Board (Animal Utilization Protocol 07-07-40) in accordance with the guidelines of the Canadian Council of Animal Care. Female Sprague-Dawley rats, aged 21 days (84--100 g), were purchased from Charles River Laboratories (Willmington, MA). Rats were maintained under controlled lighting (12 hr light -- dark cycle) and temperature (22°C) with *ad libitum* access to food and water. Dams were randomly assigned to receive either standard rat chow (CON) (16% kcal fat, 3.82 kcal/g; Harlan Teklad, Madison, WI) or a high fat (HF) diet (45% kcal fat, 4.70 kcal/g; Research Diets, New Brunswick, NJ) ([Table - S1](#pone.0033370.s004){ref-type="supplementary-material"}). Body weights of each dam were monitored biweekly. Dams were maintained on their respective diets for 16 weeks before being mated with age-matched Sprague-Dawley males fed the CON diet. Copulation was confirmed by the presence of sperm in a vaginal flush; the day of copulation was designated gestational day 0. A subset of dams (CON n = 20, HF n = 18) underwent laparotomy at GD15, exposing the uterine cavity with the fetuses. Resorption sites were counted and each fetus and its corresponding placenta were separated and weighed. Placental tissue samples were snap-frozen in liquid nitrogen storage or placed in 10% neutral buffered formalin for immunohistochemical analysis. The remaining dams (CON n = 25, HF n = 20) were allowed to give birth normally. Measures of obstetrical outcomes {#s4b} -------------------------------- A number of obstetrical outcomes including average time to copulation (number of days cohabited to achieve a sperm positive vaginal flush), mating success (sperm positive dams/total number of cohabiting pairs), fertility index (number of confirmed pregnancies/sperm positive dams), live birth index (number of live pups/total number of pups for each litter), sex ratio (M∶F) and litter size were determined. We also determined the number of pups that were either large for gestational age (LGA; birth weight greater than 2 standard deviations above the average birth weight of control pups) or small for gestational age (SGA; birthweight less than 2 standard deviations below the average birthweight of control pups). CT Scanning and Analysis {#s4c} ------------------------ To determine the amount of visceral and subcutaneous fat accumulation in the abdominal area, a subset of the animals in each group were fasted for 16 hr at 19 weeks of age (CON = 7 and HF = 7) and CT scanning was carried out using the X-SPECT small animal imaging system (Gamma Medica, Northridge, CA, USA). The midsection of the rat was scanned and the area between the bottom of the lungs and the top of the sacroiliac joint was selected for fat quantification. This area contained approximately 100 slices, each 0.5 mm apart. Densitometric quantification of fat was carried out using Amira software with attenuation thresholds of −450 to −150 Hounsfield units (HU) to select for fat tissue. Air bubbles in the intestines were first removed from the image, and the total fat (subcutaneous+abdominal) was then quantified by integrating all voxels (a 3-dimensional pixel) between −450 and −150 HU. Blood pressure analysis {#s4d} ----------------------- Blood pressure measurements were taken prior to pregnancy as well as at GD15 and GD20. The animals were placed in mouse cages, warmed to 37°C, and wrapped in a surgical towel to minimize stress due to forcible restraint. Two cuffs (occlusion cuff and volume pressure recording cuff) were attached to their tails. Mean arterial blood pressures, diastolic and systolic blood pressure and heart rate readings were measured for each animal (Coda6, Kent Scientific, Torrington, CT). The animals underwent 5 acclimatization cycles and 20 measurement cycles. The reported values are the mean of these 20 cycles. Maternal metabolic parameters: Pre-pregnancy measures {#s4e} ----------------------------------------------------- Glucose tolerance was determined in CON- and HF-fed dams prior to pregnancy following a 16 hr fast. Animals were given 2 g/kg body weight D-glucose by gavage. Blood was sampled from the saphenous vein at 0, 30, 60 and 120 min. Insulin tolerance tests were carried out following a 16 hr fast. Animals were injected with 1 U/kg of human insulin (Novolin ge, Novo Nordisk, Bagsvared, Denmark) and blood was sampled from the saphenous vein at 0, 30, 60, 120 min. The fasting blood glucose (Pointe Scientific, Canton, MI), serum triglycerides (Pointe Scientific Inc, Canton, MI), non-esterified fatty acids (NEFA; Roche Diagnostics, Indianapolis, IN) and total cholesterol (Pointe Scientific Inc, Canton, MI) were quantified using colorimetric assays according to manufacturers\' instructions. Insulin was measured using a high-sensitivity rat insulin ELISA (Crystal Chem Inc, Downers Grove, IL) while leptin was quantified using a direct rat leptin ELISA kit (Crystal Chem Inc, Downers Grove, IL). Calculation of HOMA-IR {#s4f} ---------------------- The homeostatic model of insulin resistance (HOMA-IR) was calculated [@pone.0033370-Mather1] from fasting insulin and glucose concentrations using the formula HOMA-IR = fasting glucose (mmol/L)×fasting insulin (mU/L)/22.5. Immunohistochemistry {#s4g} -------------------- Formalin-fixed whole placenta were embedded and sectioned at a thickness of 5 µm. Sections were de-paraffinized in xylene and rehydrated in graded alcohol solutions. Immunohistochemistry (IHC) was performed to determine localization and expression of CD31 (an endothelial cell marker), smooth muscle actin (SMA, a marker of blood vessel maturity), and carbonic anhydrase (CA, a marker of tissue hypoxia). Endogenous peroxidase activity was inhibited using 1% hydrogen peroxide for 10 minutes at RT. Antigen retrieval was achieved by immersing slides in 10 mM citrate buffer at 90°C for 12 minutes. Tissues were blocked using 5% BSA for 10 minutes at RT. Tissues were incubated with anti-CD31 (BD Biosciences Pharmingen, San Diego, CA) or rabbit anti-carbonic anhydrase-IX (1∶500 dilution; Abcam, Cambridge MA) overnight at 4°C in a humidified chamber. The following day, sections were incubated with anti-mouse (CD31) biotinylated secondary antibody (Sigma-Aldrich Canada Ltd., Oakville, ON) or biotinylated goat anti-rabbit (CA) (1∶500 dilution; Vector Labs, Burlingame CA) for 2 hours at RT. Tissues were then exposed to ExtrAvidin® (Sigma-Aldrich Canada Ltd., Oakville, ON) for 1 hour at RT and antibodies were visualized using DAB (Sigma-Aldrich Canada Ltd., Oakville, ON). Tissue was counterstained with Carazzi\'s Hematoxylin, dehydrated and mounted on coverslips. Slides were imaged using brightfield microscopy. Blood vessel density and maturity were quantified using the Metamorph integrated morphometry software (Molecular Devices, Downingtown, PA). For the determination of vessel density, a minimum of 4 fields of view per tissue section were used. We quantified sections from 5 individual animals per group. All analysis was carried out in a blinded fashion. Mature blood vessels were characterized as having pericyte coverage (SMA positive vessels) [@pone.0033370-Furuya1]. To quantify the level of tissue hypoxia, the percentage of tissue immunopositive for carbonic anhydrase was measured. Western blotting {#s4h} ---------------- Whole placental tissue samples were homogenized in a 1∶25 ratio of tissue to homogenization buffer (5 mM HEPES, pH 7.2, 100 mM KCl, 70 mM sucrose, 220 mM mannitol, 1 mM EGTA) with protease inhibitor cocktail tablets (Roche diagnostics, Indianapolis IN). Levels of 4-hydroxynonenal (4-HNE) and nitrotyrosine were quantified using Western blotting, as previously described [@pone.0033370-Robertshaw1]. Briefly, 20 µg of placental homogenate was separated on a 12.5% SDS-PAGE gel and transferred to nitrocellulose membranes. Membranes were blocked in 5% bovine serum albumin (BSA; Roche, Indianapolis, IN) in Tris buffered saline (TBST: 137 mM NaCl, 2.7 mM KCl, 25 mM Tris-Cl, pH 8.0) supplemented with 0.1% Tween-20 overnight at 4°C. Membranes were then incubated with anti-4-HNE (1∶1000; Abcam Inc, Cambridge, MA) or anti-nitrotyrosine (1∶5000; Millipore, Billerica, MA) in 5% BSA in TBST for 24 hours and washed with TBST before incubation with anti-mouse IgG secondary antibody (1∶5000; GE Healthcare, Mississauga ON) in 5% BSA in TBST. Blots were developed using enhanced chemiluminescence (ECL) (Millipore, Billerica, MA) and densitometric quantification was carried out using ImageJ software (ImageJ, Version 1.37, NIH, Bethesda, MD, USA). Measurement of 8-hydroxy-2′-deoxyguanosine (8-OH-2-dG) in urine {#s4i} --------------------------------------------------------------- 8-OH-2-dG, a marker of oxidative DNA damage, was measured in urine samples from GD15 dams using a commercially available EIA kit (Cayman Chemical, Ann Arbor, MI) and normalized to urinary creatinine (Assay Designs, Ann Arbor, MI). Measurement of protein carbonyls in isolated mitochondria {#s4j} --------------------------------------------------------- Protein carbonyls, a marker of oxidative damage to proteins were measured in mitochondria isolated from whole placental homogenates. Placental tissues were homogenized at a ratio of 1∶5 with homogenization buffer (5 mM HEPES, pH 7.2, 100 mM KCl, 70 mM sucrose, 220 mM mannitol, 1 mM EGTA, 2 mg/mL fatty acid free BSA) plus protease inhibitor cocktail tablets (Roche diagnostics, Indianapolis, IN) for 20 sec using a Polytron homogenizer. These homogenates were rehomogenized manually using a dounce homogenizer (Wheaton, Millville, NJ), and centrifuged (Avanti J-301, Beckman Coulter, Fullerton, CA) at 1200× g for 10 minutes at 4°C. The supernatant was centrifuged at 12,000× g for 10 minutes at 4°C. The pellet was then washed in 1 mL of homogenization buffer without 2 mg/mL BSA, twice. The final pellet was resuspended in 250 µl of homogenization buffer without BSA [@pone.0033370-Raha3]. Total protein carbonyl content in mitochondrially enriched fractions prepared from GD15 placental homogenates was determined using a commercially available kit (Oxyblot Protein Oxidation Detection Kit, Chemicon International, Inc, Temecula, CA, USA), according to the manufacturer\'s instructions. Statistical Evaluation {#s4k} ---------------------- All statistical analysis was performed using GraphPad v4.0 for Windows (GraphPad Software, San Diego, CA). Outcome measures (continuous variables) between CON and HF groups were compared using Student\'s t-test (alpha = 0.05) and categorical variables were compared using Fisher\'s exact test. Each dam represents a single statistical unit. All data were tested for normality and homogeneity of variance. Supporting Information {#s5} ====================== ###### **Weight gain prior to pregnancy.** Weight gain of CON-fed (triangle) vs. HF--fed (black circle) dams prior to pregnancy. Values represent mean ± SEM; n≥29. (TIF) ###### Click here for additional data file. ###### **Gestational blood pressure changes.** Mean arterial blood pressure changes were measured 7 days prior to mating (indicated at gestation day −7) in CON-fed (open triangle) vs. HF--fed (black circle) dams as well as at GD15 and GD20. The initiation of gestation is indicated by the arrow. Blood pressure values represent mean ± SEM; n≥17; \*p\<0.05. (TIF) ###### Click here for additional data file. ###### **Nitrotyrosine damage in the placenta of obese dams is not significantly increased at GD15.** A. 10 µg of whole placental homogenate was separated on a 12.5% SDS-PAGE and subjected to Western blot analysis. The average content of nitrotyrosine was normalized to total protein (using Ponceau-S staining) in CON-fed and HF-fed dams. B. Representative lanes containing 10 µg placental homogenate developed using an antibody directed towards nitrotyrosine. Values represent mean ± SEM; n = 15 for CON and n = 10 for HF-fed dams. (TIF) ###### Click here for additional data file. ###### **Nutrient composition of rodent diets.** (DOCX) ###### Click here for additional data file. We would like to extend our appreciation to Chantal Saab and Rod Rhem at the McMaster University Pre-Clinical Imaging Facility, for technical assistance with the CT scanning and image processing. We would also like to thank Fereshteh Tabatabaeiyazdi and Ali Shami as well as Daniel Tessier for their expert technical assistance. **Competing Interests:**The authors have declared that no competing interests exist. **Funding:**The funding sources for this submission are Joint Funding-Sick Kids Foundation/CIHR (\#XG09-45R), McMaster University Start-up Funding (\#2007h00407), and Hamilton Health Sciences, New Investigator Fund (\#N08-175). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. [^1]: Conceived and designed the experiments: SR ACH AG. Performed the experiments: EKH AL JJP YS SPP QD IAS MM SR. Analyzed the data: EH AL JJP AG ACH SR. Contributed reagents/materials/analysis tools: JJP AG SR. Wrote the paper: EKH AL ACH SR.
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Q: Why does :s command regex not understand '?' When you try to remove html tags from a line, one possible way of doing it, is to use the :s command and write a regex that understands the beginning and the end of a tag at the same time. My go for it was: :s %</?center>%%g But this way, vim says it doesn't find anything. So I had to use the following instead, which worked: :s %</*center>%%g Why is that one works but the other doesn't? Shouldn't ? say "the character before can come once or maybe not at all"? A: You need to escape ? with \. Refer help-page: :h pattern-overview
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Q: Remove element from std::map based on the time of insertion I need to erase elements from an std::map based on the time of insertion (or something else more efficient than that). The map will probably hold thousands of elements and if I store the time and iterate the map to check each elements time, it will probably end up being quite time consuming. Does anyone have any good idea how to erase elements from a std::map when they are getting old? A: The std::map<> type has no notion of when an element was inserted. It only serves to hold a key / value pair mapping. It also has no notion of insert order so it can't even provide a relative type of insert. To do what you want you'll need to add an association between the elements and the time they were inserted. If all you want is relative order then you could use a std::queue paired with the map. Every time you insert into the map you insert into the std::queue as well. Elements at front of the queue are older than the back and you can use that for relative age A: Pretty close to LRU Cache. The Boost.MultiIndex library shows an example of MRU Cache (Most Recently Used), so adapting it to LRU should be trivial. Basically the idea is to maintain two data structures in parallel: a map with the items in a deque with references into the map Basic code: static double const EXPIRY = 3600; // seconds std::map<Key, Value> map; std::deque<std::pair<std::map<Key, Value>::iterator, time_t>> deque; bool insert(Key const& k, Value const& v) { std::pair<std::map<Key, Value>::iterator, bool> result = map.insert(std::make_pair(k, v)); if (result.second) { deque.push_back(std::make_pair(result.first, time())); } return result.second; } // to be launched periodically void clean() { while (not deque.empty() and difftime(time(), deque.front().second) > EXPIRY) { map.erase(deque.front().first); deque.pop_front(); } } Of course, those structures need be synchronized if the intent is to get multi-threaded code.
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Introduction {#sec1} ============ Ultraviolet germicidal irradiation (UVGI) has been used to "scrub" the air in health care facilities and laboratories for many decades. UVGI is known to be efficacious to varying degrees in controlling the circulation of airborne infectious particles. Approximately 60% of all UVGI air disinfection systems are installed in health care facilities. According to Kowalski and Bahnfleth,[@bib1] this equates to 41% in hospitals and 19% in clinics. Until recently, most of the experimental data that led to the development of UVGI systems were decades old. Aside from anecdotal observations, little information about the actual performance of these systems in hospital rooms was available. Although UV light is known to inactivate microorganisms, limiting their ability to grow and multiply when inhaled or picked up on surfaces, there is insufficient evidence on which to base a decision to rely solely on UVGI as an engineering control for preventing health care-associated tuberculosis (TB) transmission.[@bib2] Numerous laboratory studies, dating back to the 1930s, have been conducted to analyze the efficacy of UVGI for various microorganisms in a range of temperature and humidity conditions; few studies have evaluated the practical application of UVGI in health care buildings, however.[@bib3] Most of the existing evidence comes from laboratory investigations conducted under simulated conditions. Our search revealed only one study that has been conducted in a physically realistic setting under controlled conditions.[@bib4] That study served as the basis for the 2009 National Institute for Occupational Safety and Health (NIOSH) technical guidance document on the use of UVGI systems to protect health care providers from occupational TB infection.[@bib5] This review examines the gaps in existing evidence and highlights design and operational factors that can significantly impact the efficacy of UVGI systems. Overview of airborne and short-range droplet transmissible agents {#sec2} ================================================================= *Myocobacterium tuberculosis,* an obligate inhalational airborne pathogen, is inactivated by UVGI systems, which are most often are installed in the upper portion of rooms to disinfect air. Today UVGI is receiving renewed interest, given the emergence of new infectious diseases such as pandemic strains of influenza, the ongoing threat of bioterrorism, and increased controls for aerosol-generating procedures.[@bib6] In addition, highly drug-resistant strains of *M tuberculosis* have been reported in several countries.[@bib7] Others have also highlighted problems from pathogens known to survive in the environment, such as multidrug-resistant *Acinobacter baumannii, Clostridium difficile,* and others, which are increasingly the cause of invasive infections and outbreaks in a various settings.[@bib8], [@bib9], [@bib10], [@bib11], [@bib12] Four technological methods can be used to reduce the risk of airborne transmission: pressurization, dilution, filtration, and purification. **Pressure.** Differential pressurization refers to measurable differences in air pressure that creates a directional airflow between adjacent spaces. For example, airflow into airborne infection isolation rooms (AIIRs) ensures that the rooms are negative with respect to adjacent spaces, such as corridors. Positive pressure, or airflow out of a defined space, is also common in facilities, used to mitigate the entrance of contaminants from adjacent areas into spaces in which invasive procedures are performed, such as an operating and procedure rooms. **Dilution.** High ventilation rates, in terms of high values of air changes/hour (ACH), control particles by removal through ventilation. Current guidelines suggest a value of 12 ACH for new facilities when designing an AIIR, with 6 ACH the absolute minimum value. The trade-off with this means of control is that increasing the ventilation rate results in diminishing returns in terms of removal; that is, there is increased removal of particulates with ACH \>12, but at a cost of greater energy consumption. Thus, the incremental benefit to prevent cross-transmission is much more difficult to demonstrate beyond 12 ACH. For other spaces, such as operating rooms, national guidelines recommend 20 ACH. **Filtration.** Filters are a key element of air-handling units (AHUs) that supply air to occupied spaces. There are two banks of filters: a prefilter of approximately 30% particle removal efficiency (defined in terms of a minimum efficiency reporting value \[MERV\] as MERV 7), followed by a final filter of 90%-95% efficiency (MERV 14). High-efficiency particulate air (HEPA) filtration can be used to supplement other recommended ventilation measures by providing a minimum removal efficiency of 99.97% of 0.3-μm particles. HEPA filters are typically used in ventilation systems that recirculate the air from an AIIR or from a portable device. HEPA filters also are used to filter special care areas for highly immunocompromised patients, such as a protective environment room as part of a bone marrow transplantation unit. Proper installation, maintenance, and monitoring of the HEPA filters is essential. **Purification.** Purifying the air through UVGI destroys the infectious agents in the air through exposure to ultraviolet (UV) radiation, which damages the nucleic acid of bacteria and viruses, including *M tuberculosis*, preventing replication.[@bib13] For spores, UV-C exposure is postulated to result in the formation of lethal photoactive products. Airborne transmission {#sec2.1} --------------------- Airborne transmission of infectious agents involves droplets that are expelled by sneezing or coughing or are otherwise distributed into the air. Although the liquid/vapor around the infectious agent evaporates, the residue (or droplet nuclei) may remain in the air for long periods, depending on such factors as particle size, velocity, force of expulsion, particle density, infectivity (ie, viability of the microorganism when exposed to the environment and its ability to cause infection when a susceptible host is subsequently exposed), humidity, and rate of air flow. Roy and Milton[@bib14] suggested that transmission of infectious agents does not correlate solely with the size of the microbes in droplet nuclei or larger droplets. The size can range from obligate inhalational airborne pathogens, such as *M tuberculosis*, to preferential inhalational transmission, such as measles virus or varicella-zoster (VZV) (based on the ability to cause infection in distal airways), to opportunistic pathogens like SARS-CoV that take advantage of unique environmental and clinical circumstances that permit dissemination over several meters. For *M tuberculosis*, the prototype obligate inhalational pathogen, airborne droplet nuclei containing this agent can travel via air currents, aided by the ventilation system, and be spread over a wide area. The disease-causing organisms then are inhaled and cause infection. Droplet transmission {#sec2.2} -------------------- Opportunistic dissemination can be accomplished from respiratory droplets generated during such procedures as suctioning, endotracheal intubation, and induction of cough by chest physiotherapy. There is theoretical chance that pathogen-laden droplets expelled during these procedures might travel further distances and reach deeper into the respiratory tract of susceptible persons. Concerns over the protection of health care personnel performing these types of procedures on patients with H1N1 2009 infection led to recommendations for higher facepiece filtering devices, such as N95 respirators. The latter have traditionally been required only to protect health care personnel against occupational exposure to *M tuberculosis.* Droplet transmission involves relatively short-range movement of the infectious agent, over a distance of 1-2 m. Some of these agents (eg, influenza virus) also can be transmitted by direct and indirect contact. With droplet transmission, respiratory droplets containing infectious pathogens travel directly from the respiratory tract of the infectious individual to another susceptible person through deposition on mucosal surfaces of the recipient. The distance that droplets travel depends on the velocity and mechanism by which respiratory droplets are propelled from the source, the density of respiratory secretions, environmental factors such as temperature and humidity, and the ability of the pathogen to maintain infectivity over that distance. Droplets in dry air evaporate quickly, shrink in size, and fall to the ground more slowly. The changing size of a droplet affects how it responds to airflow patterns and how quickly it settles. Dynamics of transmissible agents in health care facilities {#sec3} ========================================================== Small pressure differences, induced by natural forces such as thermal buoyancy due to air temperature differences, the wind, or mechanical fans, can generate air flows that move air from one room to another. Air filtration aims to reduce airborne concentrations to well below infectious doses. In a hospital setting, patients lie in bed much of the time. The direction of an exhalation jet from a standing or seated person and that from a lying person can be different (eg, the latter may face up). The upward thermal plume generated by a standing or seated person is much stronger than that generated by a lying person. Thus, some differences between the behaviors of breathing flows in hospital and other indoor environments are expected. The exhalation jet from a lying patient can behave differently in different ventilation systems, and also can be affected by other factors, such as the mode of contaminant release and the thermal plume generated by the human body or other heat sources. Understanding breathing flows from a patient lying supine with different ventilation systems is useful for developing an effective ventilation method for minimizing the risk of cross-infection via airborne transmission. Droplet nuclei \<5 μm in diameter exhibit a settling velocity of \<1 m/h (88 feet per minute in still air, and can follow the exhalation flows as well as the ambient air flows in a hospital ward. Clinically applicable distinctions are made between short-range airborne infection routes (between individuals, generally \<1 m apart) and long-range routes (within a room, between rooms, or between distant locations, generally distances \>1 m). Fennelly et al[@bib15] and Bjorn and Nielsen[@bib16] set the following size definitions:•Large droplet: diameter \>60 μm•Small droplet: diameter \<60 μm•Droplet nuclei: diameter \<10 μm. Small droplets also may participate in short-range transmission, but they are more likely than larger droplets to evaporate to become droplet nuclei and then be considered to have the potential for long-range airborne transmission. True long-range aerosol transmission becomes possible when the droplets of infectious material are sufficiently small to remain airborne almost indefinitely and to be transmitted over long distances. Pathogens that are not transmitted routinely by the droplet route can be dispersed into the air over short distances. For example, as reported by Bassetti et al,[@bib17] although *Staphylococcus aureus* is most commonly transmitted by the contact route, viral upper respiratory tract infection has been associated with increased dispersal of *S aureus* from the nose into the air over a distance of 4 feet under both outbreak and experimental conditions, known as the "cloud baby" and "cloud adult" phenomena. Effect of environment on transmission of infectious aerosol {#sec4} =========================================================== Once infectious droplets are released, the main factors that determine how they move are their size and the airflow patterns that carry them around. Droplet size changes with time, depending on the environmental conditions. Droplets in dry air evaporate quickly, shrink in size, and fall to the ground more slowly. The changing size of a droplet affects how it responds to airflow patterns and how quickly it settles. Movement of people in a room plays a significant part in disturbing airflow and also in transporting infected air from one place to another. Thus, room airflow is governed primarily, but not solely, by mechanical ventilation. Other influences include temperature, humidity, movement of personnel and patients, and equipment. The varying combinations of these factors make the route and suspension time of an infectious particle very difficult to predict in a dynamic, real-world environment of a health care facility. Measles and chickenpox (VZV) are both lipid-enveloped and sensitive to changes in temperature, relative humidity (RH), and UV radiation. According to Cox,[@bib18] Stephenson et al,[@bib19] and Ijaz et al,[@bib20] viruses without a lipid envelope (eg, poliovirus) generally survive longer at high RH (\>50%), but lipid-enveloped viruses (eg, influenza, Lassa fever virus, human coronavirus \[hCV\] 229E) survive longer in low RH (\<50%).[@bib18], [@bib19], [@bib20] Data on hCV 229E indicate that when airborne, this virus has a survival half-life of about 3 hours at an RH of 80%, 67 hours at an RH of 50%, and 27 hours at an RH of 30% at 20 °C, suggesting that high RH (\>80%) is most detrimental to the survival of this coronavirus. Bean et al[@bib21] reported that influenza can survive for 24-48 hours on hard, nonporous surfaces such as stainless steel and plastic, but for less than 8-12 hours on cloth, paper, and tissues. In addition, influenza virus can survive for up to 5 minutes on hands, and can be transferred to hands from these nonporous surfaces for 24 hours and from tissues for 15 minutes.[@bib21] More recently, Lai et al[@bib22] demonstrated that SARS CoV can survive in alkaline diarrhea stools for up to 4 days and can remain infectious in respiratory specimens for more than 7 days at room temperature. Similarities with other viruses of nosocomial importance (eg, other RNA lipid-enveloped respiratory viruses, such as influenza) suggest that such organisms can survive long enough in aerosols to cause disease, especially when associated with biological fluids such as mucus, feces, and blood. This sensitivity to environmental conditions also might help explain the seasonality of some viral infections. Regarding influenza transmission, Brankston et al[@bib23] concluded that natural influenza transmission in humans occurs via droplets and contact over short distances as opposed to long distances. Although none of the studies that they reviewed could specifically rule out airborne transmission, the authors believed that the airborne route is neither the predominant mode of transmission nor a frequent enough occurrence to be of significant concern when considering control measures for most clinical settings.[@bib23] A recent epidemiologic investigation confirmed their conclusions.[@bib24] Microbiocidal activity of UVGI in air and environmental surfaces: Efficacy and limitations {#sec5} ========================================================================================== A recent systematic review by Li et al[@bib25] demonstrated that adequate or inadequate ventilation has an effect on the risk of infection via infectious aerosols. An inefficient ventilation system causes the spread of airborne disease, whereas an efficient ventilation system can help mitigate the spread of infectious particles and thereby reduce transmission of disease.[@bib25] Even before the 2003 SARS epidemic, there was strong evidence that ventilation and building finishes are important determinants of the nosocomial transmission of tuberculosis. According to the Centers for Disease Control and Prevention\'s (CDC) *Guidelines for Environmental Infection Control in Health-Care Facilities*, only TB, measles (rubeola virus), and chickenpox (VZV) should be considered "true" airborne infectious diseases.[@bib26] However, other infectious agents, such as SARS CoV, are sometimes called "opportunistic," because they might be transmissible over short distances (eg, 1-2 m), given a favorable environment.[@bib14] Effectiveness on microbes {#sec5.1} ------------------------- All viruses and almost all bacteria (excluding spores) are vulnerable to moderate levels of UVGI exposure, but the magnitude of the effect is extremely species-dependent.[@bib27] Spores, which are larger and more resistant to UVGI than most bacteria, can be effectively removed through high-efficiency air filtration without UVGI. Some UGVI systems are installed in conjunction with high-efficiency filtration. This combination design can be very effective against biological agents in certain situations. Smaller microbes that are difficult to filter out tend to be more susceptible to UVGI, whereas larger microbes, such as spores, which are more resistant to UVGI, tend to be easier to filter out ([Fig 1](#fig1){ref-type="fig"} ).[@bib29] Fig 1Relative sensitivity of selected airborne microorganism to UVGI. The higher the *z* value, the greater the microorganism\'s sensitivity to UVGI.The data sources are indicated by superscript letters: (a) Kethley 1973[@bib28]; (b) Ko et al 2000[@bib33]; (c) Miller et al 2002[@bib4]; (d) Peccia 2001[@bib39]; (e) Riley et al 1976.[@bib38] Reprinted with permission.[@bib5] A recent Taiwanese study found that the effectiveness of UVGI depends strongly on the type of virus nucleic acid, and that viruses with dsRNA or dsDNA are significantly less susceptible to UV inactivation.[@bib30] For 90% airborne virus inactivation, the UVGI dose was approximately 2-fold higher for dsRNA and dsDNA viruses than for ssRNA and ssDNA viruses. The microorganism susceptibility factor was the highest for the viruses, similar to that for fragile bacteria, but 13-20 times higher than that for endospore bacteria or fungal spores. The susceptibility factor for the viruses was higher at 55% RH than that at 85% RH, possibly because under high RH, water adsorption onto the virus surface might provide protection against UV-induced DNA or RNA damage.[@bib30] UVGI applications for disinfection of air in health care facilities {#sec6} =================================================================== Supplemental control {#sec6.1} -------------------- UVGI has been used as a supplement to mechanical ventilation to inactivate airborne infectious agents to protect the health of building occupants. Upper-room UVGI installations are frequently used to provide ACH equivalent or effective (e-ACH) to that recommended by the CDC for AIIRs. However e-ACH is not acceptable for meeting CDC recommendations as a primary environmental control against *M tuberculosis.* UVGI generally refers to a UV wavelength of 253.7 nm (UV-C). Exposure to UV light at this wavelength is a practical and cost-effective method of inactivating airborne viruses, mycoplasma, bacteria, and fungi on clean surfaces.[@bib31] Upper-room air lamps {#sec6.2} -------------------- The most widely used application of UVGI is in the form of passive upper-room fixtures containing UVGI lamps that provide a horizontal layer of UV energy field above the occupied zone. These fixtures are designed to inactivate bacteria that enter the upper irradiated zone, and their efficacy is highly reliant on, among other factors, the airflow field conditions in the room. The survival probability of bacteria exposed to UV irradiance depends on the susceptibility of the target microorganism and the dose and duration of UV-C to which it is exposed.[@bib32] Lamps used to produce UV-C are located relatively high up in the room (8 ft), to prevent exposure to occupants by a specially designed fixture. There are two basic designs: a "pan" fixture with UVGI unshielded above the unit to direct the irradiation upward, and a fixture with a series of parallel plates that direct the irradiation outward while preventing the light from reaching the eyes or unprotected skin of the room\'s occupants. Germicidal activity is dependent on air mixing via convection between the room\'s irradiated upper zone and the lower patient care zones.[@bib32] This was confirmed in an investigation by Miller et al[@bib4] that involved installation of upper-room UVGI units and evaluation of these units\' impact on culturable airborne bacteria. More than 90% of the bacteria detected were inactivated; however, the rate was lower for more-resistant bacteria and fungal spores. That investigation also clearly demonstrated that room air must be mixed for UVGI to effectively inactivate microorganisms. When warm air entered the room via a duct close to the ceiling (which can occur in the winter when the heating system is turned on), the warm air simply "rested" on the much cooler air below, and the efficacy of the UVGI system was dramatically diminished because the microbes did not move up for exposure to the UV-C irradiation. No mixing fans were turned on during the experiment, but moderate ventilation was present. The cleanliness of UV light bulbs and age of UV lamps should be checked periodically (approximately every 6 months) to ensure sufficient UV light intensity for germicidal activity (UV-C). The intensity of germicidal wavelength light decreases with age, and bulb ratings (hours of use) may vary by manufacturer.[@bib13] Upper-room UVGI is often seen as a cost-effective measure to supplement the general ventilation system in a room; however, the combination of the general ventilation system and UV lamps might not necessarily be implemented correctly within a room. For example, if the ventilation rate is too high, the particles may not be sufficiently exposed to the UV-C irradiation to ensure complete inactivation, or if the ventilation system does not provide good mixing within the room, airborne particles containing microbes might not even be exposed to the UV-C irradiation.[@bib13] A well-designed upper-room UVGI system may effectively kill or inactivate most airborne droplet nuclei containing *Mycobacterium* spp if designed to provide an average UV fluence rate (ie, irradiance from all angles that is incident on a small region of space; a more accurate term than "UV dose") in the upper room in the range of 30-50 μW/cm^2^, provided that the other criteria stipulated in the CDC\'s TB guidelines are met.[@bib2] The fixtures should be installed to provide as uniform a UVGI distribution as possible in the upper room.[@bib5] Schafer et al[@bib33] developed a method to measure fluence rate and used it to verify that this rate varied as much as 3-fold in a typical room, depending on proximity to the lamp, and found that lamp failure was common. This reinforces the need to monitor the efficacy of the lamps used in UVGI fixtures. Under experimental laboratory conditions with mechanical ventilation rates of up to 6 ACH, the rate at which microorganisms are killed or inactivated by UVGI systems appears to be additive with mechanical ventilation systems in well-mixed rooms.[@bib2] For other infectious agents, such as SARS-CoV and influenza, the mode of transmission is by droplets, which do not remain suspended in air for long periods of time, but fall out within a 2-m radius from a coughing/sneezing person. Even the most robust HVAC system is unlikely to achieve sufficient air mixing to provide efficient kill of microbes transmitted by droplets. These particles never reach the upper-room UV zone; thus, an alternate method of disinfection is needed.[@bib34] Escombe et al[@bib35] recently investigated impact of upward-facing UV light fixtures installed in ceilings of a negative-pressure TB isolation ward and ceiling-mounted air ionization fixtures in an animal enclosure chamber, using a guinea pig air sampling model that involved exposure of the animals to exhaust air from the isolation ward. With this animal model, 35% of controls exposed to untreated exhaust air from the TB ward developed TB infection, whereas frequency was reduced to 14% and 9.5% with use of an ionizer and UVGI, respectively. They concluded that "provided there is adequate mixing of room air, an upper-room UVGI fixture is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings."[@bib35] Key variables {#sec6.3} ------------- Critical factors that affect the efficacy of UVGI include temperature, RH, and lamp output. A number of studies have indicated that the effectiveness of upper-room UVGI systems decreases as humidity increases. For optimal efficiency, RH should be controlled to 60% or less when upper-room UVGI systems are installed. Temperature should be kept between 68°F and 75 °F (20 °C-24 °C). Both of these suggestions are consistent with 2010 Facility Guidelines Institute (FGI) and the American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) recommendations in ASHRAE Standard 170 (now part of the FGI Guidelines Standards).[@bib36] The ASHRAE Handbook also provides comprehensive recommendations for installation and operation of UVGI systems.[@bib37] Experimental upper-room UVGI systems used in rooms with aerosolized bacteria (including surrogates of *M tuberculosis*) have shown that the higher the UV fluence rate produced in the upper air of a room, the greater the effectiveness of the system.[@bib4], [@bib38], [@bib39] Based on the results of experiments with upper-room UVGI systems and aerosolized bacteria in bench-scale reactors, it is apparent that the greater the UV fluence rate in the irradiated zone, the more effective the system.[@bib40], [@bib41] However, there appears to be an upper threshold after which an increase in UVGI does not directly correspond to an increase in the system\'s ability to kill or inactivate microorganisms.[@bib4], [@bib13], [@bib42], [@bib43] Miller et al[@bib4] reported decreased effectiveness of the UVGI system when the UV fixtures were placed on only one side of the room. This is consistent with the findings of Riley and Permutt,[@bib44] who reported that a wider distribution of low-irradiance UV lamps was more efficient compared with the use of one centrally located high-irradiance UV lamp. This suggests that upper-room UVGI systems should be installed to provide the most uniform UVGI distribution in the upper air possible. Experimental conditions {#sec6.4} ----------------------- In most of the studies that form the basis of the irradiance guidelines, the bacteria studied were primarily single cells aerosolized in deionized water. This lack of a mucus coating could possibly make these bacteria more sensitive to UVGI compared with bacteria in droplet nuclei from an infected host.[@bib45] The killing or deactivation of 63% of droplet nuclei in a room by UVGI is equivalent to 1 ACH in terms of reduced total droplet nuclei concentration in the room.[@bib3] This reduction of droplet nuclei by a method other than mechanical ventilation is termed eACH. AHUs including in-duct applications {#sec6.5} ----------------------------------- UVGI lamps can be installed in a various locations in a HVAC system. One possible location is inside the AHU, typically in front of the cooling coils and drip pan. There are anecdotal reports that this configuration results in energy conservation and maintenance cost savings, but more rigorous study is needed to reproduce and validate these claims. Some manufacturers of these systems have also made claims of reduced incidence of health care-associated infections (HAIs) with the use of UVGI in AHUs. To date, however, there is little, if any, supportive evidence in the peer-reviewed scientific literature. Many of the published investigations rely on environmental surface or air sampling cultures or laboratory-based animal studies for inferential support. Our assessment of the available literature indicates claims of reduced HAIs from AHU-installed UVGI in health care facilities remain unfounded. There is some evidence of fewer complaints related to indoor air quality in buildings with systems containing UVGI inside the AHU.[@bib46] Levetin et al[@bib47] provided some evidence for this by demonstrating a significantly lower concentration of fungal spores on a floor of a building with an in-duct UVGI system compared with a floor in the same building without such a system. The spores recovered in the building were the same as from insulation material in the ventilation ducts, however. The authors concluded that few spores from the outdoors passed through filters in the AHUs, but that the spores developed when the HVAC system was turned on and off. Notably, they noted that "as a result, we cannot say that the UV-C radiation had a direct effect on spores in the air stream. The effectiveness of UV-C lamps seemed to be localized, because visual inspection indicated there was conspicuous fungal growth in the downstream duct insulation lining."[@bib47] UV lamps also can be placed inside supply or return air ducts to disinfect the air before it is supplied to an occupied space or when recirculated. Air cleaning? {#sec6.6} ------------- UV irradiation by itself does not clean air. The microorganisms are still there, and in the case of some microorganisms, might still contain the ability to cause noninfectious (eg, allergenic) disease. Although UV potentially can destroy allergenic sites on the surface of a bioaerosol, this ability has yet not been documented or quantified.[@bib47] Bacterial inactivation studies using Bacillus Calmette-Guérin (BCG; a strain of *Mycobacterium bovis*) and *Serratia marcescens* have estimated the effect of UVGI as equivalent to 10-39 ACH.[@bib34] However, another study suggested that UVGI may result in fewer equivalent ACH in the patient-care zone, especially if the mixing of air between zones is insufficient.[@bib48] The use of fans or HVAC systems to generate air movement and good mixing might increase the effectiveness of UVGI by ensuring exposure of airborne microorganisms to the light energy for a sufficient length of time.[@bib35] UVGI surface disinfection in health care facilities {#sec7} =================================================== UVGI has been used for disinfection of water, but that application is not addressed in this review. It has also been used to disinfect surfaces. One study found that the effectiveness of this application is limited by the low penetrating power of UVGI, and thus it is currently limited to decontaminating surfaces when conventional methods, such as the use of liquid chemical disinfectants, are not feasible.[@bib31] Some studies also have explored disinfection of medical devices and other high-frequency touch surfaces. Sweeney and Dancer[@bib49] found that UVGI disinfection of computer keyboards without mechanical friction from cleaning had no impact on bioburden for 72% of the 68 keyboards in their study, and concluded that physical cleaning is of greatest importance before the use of UVGI. Kac et al[@bib50] found that UVGI effectively disinfected endocavitary ultrasound probes, but only if used in combination with a surface disinfectant applied with a cloth and with mechanical friction. Interestingly, both of these investigations highlight the adjunctive impact of UVGI following traditional cleaning and disinfection for medical devices and other surfaces, whivch is consistent with use of UVGI for disinfection of air. More recently Rutala et al[@bib51] presented unpublished results of their study of "no-touch" full room disinfection with an automated, portable UV-C device that uses mirrors to "bounce" UVGI around a room to reach all surfaces, including those not directly exposed to fluence. They reported substantial log reductions in vegetative bacteria (3-4) within 15 minutes of exposure and in spore-forming bacteria, such as *C difficile* (2-3), after 50 minutes of exposure. Analytical model for UV dose evaluation using computational fluid dynamics {#sec8} ========================================================================== An analytical model for evaluating the UV dose in steady-state conditions using the Eulerian system was proposed by Memarzadeh et al.[@bib48] Computational fluid dynamics (CFD) was used to study the efficacy of inactivation of airborne bacteria by upper-room UVGI in a test room. Several UV lamp configurations were used in the model. Compared with available experimental data, the proposed model closely predicts the percentage of particles inactivated by UVGI. The proposed model was used to study the effects of ventilation flow rate and UV fixture configuration on inactivation of airborne bacteria in a test chamber. The Lagrangian system model was also applied in the same test chamber for a similar scenario. This CFD model demonstrates that the percentage of UVGI inactivation is higher when the ventilation flow rate is lower. Increasing the ventilation flow rate from 2 to 6 ACH reduces the residence time of a pass through the UV zone from 24.7 to 8.3 seconds. In the latter case, the dosage is then only ˜35% of the total dose received in the former case. For upper-room UVGI to be effective, the aerosolized infectious particles must be moved from the lower part of the room, where they are produced by a person coughing or sneezing, to the germicidal zone in the upper room. Practical considerations prohibit the ideal situation of UVGI cleansing of all infectious particles in a single pass when they move through the upper-room UVGI zone. Another consideration is how rapidly microorganisms proceed through the UVGI zone. A higher frequency of ACH limits the exposure time of the infectious particles to the UVGI and thus is likely to have less effective antimicrobial activity. In practice, the effectiveness of a UVGI installation is determined by the following factors:•Fixture used to house the UV-C lamp. This determines how much of the radiation discharged from the UV lamp is actually emitted from the fixture and how it is distributed.•Environmental sustainability issues. Most UV-C lamps use low-pressure mercury, have a limited life span, and require environmental precautions for disposal.•Distance from the UV-C lamp. The distance of airborne infectious agents from the fixture will determine the irradiance level and thus the germicidal efficacy.•Airflow pattern. This affects how long the bacteria and viruses are exposed to the UV radiation.•Humidity. The humidity of the atmosphere is key, because water makes the infectious agent less susceptible to damage from UV radiation. The higher the RH, the less likely an aqueous aerosol will dry out. For maximum effectiveness of UVGI, RH should be \<75%.[@bib34] Human health considerations with UVGI {#sec9} ===================================== According to an American Biological Safety Association position paper, biological effects in humans from overexposure to UV-C radiation vary with wavelength, photon energy, and duration of exposure.[@bib52] In general, adverse effects are limited to the skin and eyes. Erythema (eg, reddening of the skin, as in sunburn) is the most commonly observed skin effect. Chronic exposure to UV radiation can accelerate the skin aging process and increase the risk of skin cancer. The National Toxicology Program (NTP) classifies UV-C as a probable human carcinogen. Excessive exposure to UV-C radiation can adversely affect the eyes, causing photokeratitis and/or conjunctivitis. Based on the current guidelines, repeated exposure at or below the current guideline would not be expected to cause adverse health effects; however, it should be emphasized that UV radiation has been implicated in both skin cancer and cataracts in humans. Outcome of a case study on UVGI for operating room air disinfection {#sec9.1} ------------------------------------------------------------------- On May 18, 2007, NIOSH received a request from the Director of Environmental Affairs at Brigham and Women\'s Hospital (BWH) in Boston, Massachusetts. Some BWH orthopedic surgical staff members were concerned about unspecified skin and eye symptoms, which they attributed to germicidal UV-C radiation produced by ceiling-mounted UVGI lamps in orthopedic operating rooms (ORs). The use of UVGI in orthopedic ORs was investigated by the Occupational Safety and Health Administration (OSHA) on January 19, 2007, in response to a formal complaint submitted after staff discovered that the UVGI lamp controls in an OR had been tampered with and set at an inappropriately high setting. After an inspection, OSHA recommended that BWH provide annual UV-C and personal protective equipment (PPE) training and medical screening for all affected employees, as well as ensure that all affected employees use the required PPE. In July 2008, BWH moved the orthopedic operating suite to an area equipped with laminar airflow and discontinued the use of UVGI for intraoperative infection control. NIOSH investigators recommended the use of alternative infection control technologies, such as laminar airflow.[@bib53] UVGI disinfection for air in operating rooms {#sec10} ============================================ The use of direct UVGI as an air-cleaning method for intraoperative infection control is a relatively uncommon application that has been used by some surgeons since the 1930s.[@bib54], [@bib55], [@bib56] Some evidence suggests that the use of UVGI in this manner might reduce the incidence of surgical site infections by minimizing intraoperative levels of airborne bacterial contaminants. This design differs from upper-room devices in that the UV-C irradiation is directed down to expose the entire OR. Eye protection and other attire are required for those in the OR. The relative efficacy of direct UVGI on intraoperative air quality and prevention of infection has not been well defined, however, because studies that have examined its use did so at a variety of UV intensities in association with other infection prevention methods and surgical techniques. In addition, most studies have been observational, before--after investigations, which are limited by biases and other confounding variables. Investigators have reported that UVGI is usually used not alone, but rather in conjunction with laminar airflow or body exhaust techniques, with discrepancies in wound rates under the same conditions.[@bib56] The CDC recommends against using UVGI to prevent surgical site infections.[@bib26] Overall, for general ventilation effectiveness, there is little advantage to increasing the effectiveness of the UVGI beyond 4-6 ACH. UVGI is effective when at low ACH, and its efficacy diminishes as ACH increases, because the kill rate is dependent on the duration of exposure to the UV dose. With high ACH, exposure time is significantly decreased. For personnel safety, NIOSH strongly encourages employers to protect employees using a hierarchy of controls approach. The objective of this approach is to minimize the risk of failure of preventive measures, resulting in a hazardous exposure. According to the hierarchy, initial efforts should be made to eliminate the hazardous agent or source of exposure. With regard to intraoperative UVGI use, this could be achieved by substituting other infection prevention methods or technologies, such as vertical laminar air flow, before implementing direct UVGI inside the OR.[@bib53] It should be noted that a more recent design for the OR uses nonaspirating diffusers with unidirectional airflow over the surgical site but at lower velocities than traditional high-velocity laminar sir flow, thereby minimizing the risk of hypothermia. This design is now required in the 2010 FGI guidelines[@bib36] and is described in detail elsewhere.[@bib57] Design considerations {#sec11} ===================== Given the foregoing discussion, we recommend that UVGI system designers take the following considerations into account:•Apply safety factors to their designs, particularly as they depart from operating modes for which they have performance data and field experience.•Know the actual lamp output under the most challenging operating conditions.•Avoid relying solely on design equations to determine the performance of their systems. Actual testing with the contaminants of interest is highly recommended.•View claims regarding UVGI systems\' high level of inactivation of pathogenic bioaerosols with caution. Whereas the microbiological science underlying these conclusions applies to pathogenic bioaerosols as well as environmental organisms, much greater caution is required in the former case. It would be irresponsible to claim a high inactivation rate for a pathogenic bioaerosol without substantial testing. Even with substantial testing, design failures may occur. User considerations when relying on a UVGI system for disinfection {#sec12} ================================================================== Health care buildings {#sec12.1} --------------------- Although many laboratory studies have been conducted to analyze the efficacy of UVGI for numerous microorganisms in a range of temperature and humidity conditions, little has been done to evaluate the practical application of UVGI in health care buildings.[@bib3] In fact, Beggs et al[@bib58] concluded that "the knowledge base that exists on UVGI and its application is relatively small, and health care authorities have few guidelines on which to make decisions." Laboratory versus actual conditions {#sec12.2} ----------------------------------- As discussed earlier, potentially infectious droplet nuclei emitted from an infected host might be coated with mucus and consist of more than one bacterium. Study bacteria, aerosolized in deionized water and lacking a mucus coating, may be more sensitive to UVGI compared with bacteria in droplet nuclei from an infected host.[@bib44] Installation and maintenance {#sec12.3} ---------------------------- UVGI is associated with human health risks and unpredictable results. UV rays can cause harm to building occupants if not properly installed and maintained. Installation techniques widely vary among manufacturers and currently are not regulated by a governing body to ensure proper efficacy of UVGI after installation. Manufacturers {#sec12.4} ------------- UVGI lamp manufacturers (eg, Philips PLD), acknowledge that some important information is not available. For example, regarding to the sizing of UV lamps for installation in ductwork systems, a Philips technical document on UV disinfection states that "in the calculation...it should be emphasized that it results only in a rough estimation; we did not incorporate the possible effects of humidity and temperature on the killing rate. Philips is not a specialist in that field; we always advise to contact qualified authorities to evaluate the bacteriological aspects."[@bib59] The use of CFD models and improved distribution studies on UVGI lamps and fixtures is moving the industry in the right direction. The CFD models characterize the room and air distribution in coordination with any UVGI systems applied within the space to evaluate the effectiveness quantitatively.[@bib3] For UVGI applications in AHU and ductwork, maintenance personnel may be at increased risk even if their exposure time to the UVGI irradiation is short, because they will be in close proximity to the UVGI source. Personnel precautions {#sec12.5} --------------------- Service personnel and occupants are at risk without special care measures. Service staff need to ensure that the system is turned off when working. The need to wear protective clothing and eyewear should be stressed to prevent any possibility of harm to workers. Room occupants may be exposed to higher doses of UVGI irradiation if the fixtures are not located or installed properly within the space. Health care providers are at a greater risk because they occupy the space for longer periods than most patients. UVGI overexposure has the potential to cause unpleasant eye and skin irritations; however, these effects appear to be temporary and have involved no known long-term consequences to date.[@bib60] Research needs {#sec13} ============== Additional areas of research needed to determine the most effective upper-room UVGI systems include UVGI measurements, air mixing, the effect of low humidity, microbial sensitivity, and testing and validation of upper-room UVGI systems. More research is also needed on the ability of UVGI systems to kill or inactivate microorganisms in respirable droplet nuclei of variable sizes and droplet nuclei coated with actual or simulated sputum.[@bib5] Methods for determining whether existing room air mixing is sufficient for UVGI effectiveness are needed, and research should explore whether the use of mixing fans has a negative impact on the intended design of the mechanical ventilation systems or a negative impact on other infection control measures. Humidity and ventilation {#sec13.1} ------------------------ There is some indication that low RH (\<25%) might adversely affect the ability of UVGI systems to kill or inactivate airborne bacteria. Additional research is needed in this area. Research in full-scale rooms to better ascertain the effects of high humidity (eg, 80% RH) on airborne microorganisms is needed as well. Experimental research has indicated that mechanical ventilation of up to 6 ACH does not have a significant effect on the effectiveness of upper-room UVGI systems; studies are needed to examine whether mechanical ventilation \>6 ACH decreases the effectiveness of upper-room UVGI systems. Standardization {#sec13.2} --------------- Tests to determine the relative sensitivity of microorganisms to UVGI are not standardized among laboratories. Laboratory testing guidelines are needed to ensure that these tests are reproducible and reflect real-world situations. Laboratory tests of the efficacy of UVGI upper-room systems should be standardized as well. Protocols for testing and validating upper-room UVGI systems are needed to ensure that the systems perform as designed.[@bib1] Experimental versus real-world conditions {#sec13.3} ----------------------------------------- Guidelines are needed to determine the most practical method for planning effective UVGI systems in a variety of rooms or areas. Theoretically, CFD modeling can be used to evaluate many of the variables associated with installing an upper-room UVGI system and provide an estimate of the UVGI dose received by droplet nuclei. Experiments involving photoreactivation of microorganisms in full-scale test rooms should be conducted, as should tests of the effectiveness of UVGI on airborne bacteria over a wide range of temperatures. In real-world situations, potentially infectious droplet nuclei will vary in size and may be coated with sputum. Both of these factors can decrease the effectiveness of UVGI. Although some laboratory research has been done to evaluate these parameters,[@bib34], [@bib44], [@bib61] more work is needed to further characterize microbial susceptibility to UVGI based on the size of respirable (up to 5 μm) droplet nuclei and droplet nuclei coated with actual or simulated sputum. Conclusions and discussion {#sec14} ========================== Data for real-world applications {#sec14.1} -------------------------------- As this and previous literature reviews have shown, although numerous studies address the efficacy of UVGI, there remains a lack of definitive epidemiologic data demonstrating that these systems prevent HAIs endemic to health care facilities. Also lacking is objective, reproducible evidence of improved energy efficiency of coils and fans with UVGI systems installed in AHUs. The efficacy of an upper-room UVGI application depends strongly on sufficient exposure of microorganisms to UV-C, which can occur if there is good mixing of upper and lower air in the room or area where installed. Furthermore, there are many marketing claims suggesting that such systems, as well as mobile systems, will protect occupants against emerging diseases such as SARS CoV, influenza, *M tuberculosis*, and bioterrorism agents. These claims have not been substantiated by the existing data, however, and must be weighed against the many variables discussed in this literature review. For TB, there is ample laboratory and reasonable evidence from animal studies, but the key question remains the relative role of UVGI in the context of the hierarchy of controls to prevent health care-associated TB. Bioterrorism {#sec14.2} ------------ Some of the agents that might be used for bioterrorism, such as anthrax spores, are not very susceptible to UV-C. Because the clinical effectiveness of UV systems may vary, UVGI is not recommended for air management before air recirculation from airborne isolation rooms. It also is not recommended as a substitute for HEPA filtration, local exhaust of air to the outside, or negative pressure. Portable and in-duct units {#sec14.3} -------------------------- The use of UV lamps and HEPA filtration in a single unit offers only minimal infection control benefits over those provided by the use of a HEPA filter alone. Duct systems with UVGI are not recommended as a substitute for HEPA filters when the air from isolation rooms must be recirculated to other areas of the facility. Regular maintenance of UVGI systems, involving keeping the bulbs free of dust and replacing old bulbs as necessary, is crucial. Safety issues associated with the use of UVGI systems are described in guidelines. Supplemental engineering controls {#sec14.4} --------------------------------- When UVGI units are required for air cleaning, as demonstrated by a risk assessment of the AII area, the units should be installed in the exhaust air ducts of the HVAC system to supplement HEPA filtration. When UVGI is used as a supplemental engineering control, fixtures should be installed on the wall near the ceiling or suspended from the ceiling as an upper-air unit, in the air-return duct of an AII room, or in designated enclosed areas or booths for sputum induction. In summing up the role of UVGI in today\'s health care facilities, UVGI should continue to be viewed not a routine replacement for ventilation, but rather as a supplement when needed under the conditions and parameters described in this review. It does not appear to have a role in the OR, where air changes are well above 4-6 ACH, or in properly designed AII rooms. Many questions remain regarding how to achieve a balance between utility and safety; hopefully, the necessary research will continue. STATEMENT OF CONFLICT OF INTEREST: The authors report no conflicts of interest. Publication of this article was made possible by unrestricted educational grants from The Clorox Company, the American Society for Healthcare Engineering, and the Facility Guidelines Institute.
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Attitudes towards interprofessional collaboration among primary care physicians and nurses in Singapore. Interprofessional collaboration (IPC) has been shown to improve patient outcomes, cost efficiency, and health professional satisfaction, and enhance healthy workplaces. We determined the attitudes of primary care physicians and nurses towards IPC and factors facilitating IPC using a cross-sectional study design in Singapore. A self-administered anonymous questionnaire, based on the Jefferson Scale of Attitudes toward Physician-Nurse Collaboration (JSAPNC), was distributed to primary healthcare physicians and nurses working in National Healthcare Group Polyclinics (N = 455). We found that the mean JSAPNC score for physicians was poorer than that for nurses (50.39 [SD = 4.67] vs. 51.61 [SD = 4.19], respectively, mean difference, MD = 1.22, CI = 0.35-2.09, p = .006). Nurses with advanced education had better mean JSAPNC score than nurses with basic education (52.28 [SD = 4.22] vs. 51.12 [SD = 4.11], respectively, MD = 1.16, CI = 0.12-2.20, p = .029). Male participants had poorer mean JSAPNC score compared to females (50.27 [SD = 5.02] vs. 51.38 [SD = 4.22], respectively MD = 1.11, CI = 0.07-2.14, p = .036). With regression analysis, only educational qualification among nurses was independently and positively associated with JSAPNC scores (p = .018). In conclusion, primary care nurses in Singapore had more positive attitudes towards IPC than physicians. Among nurses, those with advanced education had more positive attitudes than those with basic education. Greater emphasis on IPC education in training of physicians and nurses could help improve attitudes further.
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The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS. The human immunodeficiency virus (HIV) gp120 and gp41 envelope proteins and Staphylococcus aureus protein A (SPA) all have Fc receptor (FcR)-like immunoglobulin binding factor (IBF) activity for the Fc constant fragments of human immunoglobulin G (IgG). Viral IBF may contribute to the pathology of HIV by jamming the network of FcR signals that control FcR-dependent immunity. Conversely, the bacterial IBF SPA has anti-retroviral activity that may involve antagonism of the immunopathological action of viral IBF, strongly suggesting IBF may act as a double-edged sword that might be turned against viral invaders.
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(2008) GLORY WEALTH SHIPPING PTE LTD., Plaintiff, v. INDUSTRIAL CARRIERS, INC., Weaver Investments, Inc., Itro Corporation a/k/a Itiro Corporation, Blue Coast Navigation SA, Diamant Co. Ltd., Sergey Baransky, and Vladimir Tarasov, Defendants. No. 08 Civ. 8425. United States District Court, S.D. New York. December 16, 2008. MEMORANDUM OPINION & ORDER RICHARD J. HOLWELL, District Judge. On November 6, 2008, this Court ordered the issuance of maritime attachment against all defendants in this matter except Industrial Carriers, Inc. ("ICI"), which the Court had earlier determined was present in this district. On November 10, 2008, at the request of defendants, this Court ordered that plaintiff Glory Wealth Shipping Pte Ltd. ("Glory Wealth") show cause as to why the attachment should not be vacated with respect to ITRO Corp. a/k/a ITIRO Corp. ("ITIRO") and Diamant Co. Ltd. ("Diamant"). After hearing oral argument on November 13, 2008, the Court vacated the attachment with respect to ITRO Corp. a/k/a ITIRO Corp., but reserved judgment with respect to Diamant Co. Ltd. After further consideration, the Court vacates the attachment with respect to Diamant Co. Ltd. as well. Courts must vacate a maritime attachment where the plaintiff fails to carry its burden of demonstrating that: 1) it has a valid prima facie admiralty claim against the defendant; 2) the defendant cannot be found within the district; 3) the defendant's property may be found within the district; and 4) there is no statutory or maritime law bar to the attachment. Aqua Stoli Shipping Ltd. v. Gardner Smith Pty Ltd., 460 F.3d 434, 445 (2d Cir.2006). Only the second requirement is disputed by the parties in this case. "[T]he requirement is said to present `a two-pronged inquiry: First, whether (the respondent) can be found within the district in terms of jurisdiction, and second, if so, whether it can be found for service of process.'" Seawind Compania, S.A. v. Crescent Line, Inc., 320 F.2d 580, 582 (2d Cir.1963) (quoting United States v. Cia. Naviera Continental S.A., 178 F.Supp. 561, 563 (S.D.N.Y. 1959)). The parties agree that the Court should look to the day the complaint against the defendants was filed to determine whether this requirement has been satisfied. (November 13, 2008 Hearing Tr. at 9.) With its original request for a maritime attachment against Diamant, counsel for Glory Wealth submitted an affidavit affirming that Diamant was not then registered with the New York Department of State as a foreign corporation, that it had not appointed an agent for service of process, and that it had no commercial ties to this district. Diamant has not come forward with any affidavits or other evidence contradicting these assertions. Ordinarily, this would be the end of the matter. Diamant, however, argues that because the Court has found ICI to be present in the district, and because Glory Wealth has alleged that Diamant is the alter ego of ICI, it necessarily follows that plaintiff has pled facts that would establish Diamant's presence in the district, thereby negating one of the predicates of an attachment. The Court agrees. Where one defendant is subject to personal jurisdiction and service of process, its alter egos are subject to personal jurisdiction and may be served by serving it. See Wm. Passalacqua Builders, Inc. v. Resnick Dev. S., Inc., 933 F.2d 131, 142-43 (2d Cir.1991). The corollary to this rule is that if one defendant is present in the district for the purposes of issuing a maritime attachment, its alter egos are present as well. To the extent Glory Wealth is arguing that alter egos cannot be served by serving the primary defendant, it is incorrect. King v. Galluzo Equipment & Excavating, Inc., No. 00 Civ. 6247(ILG), 2001 WL 1402996, at *6 (E.D.N.Y. Nov. 8, 2001) ("In New York, the law is clear that service on the alter ego of a corporation constitutes effective service on the corporation."). The issue remains, however, of what consequence this legal rule has where, as here, alter ego status is merely alleged and not proven. For obvious reasons, Diamant does not wish to concede alter ego status, and the parties have not produced sufficient evidence to sustain such a factual conclusion. The question thus becomes who has the burden of demonstrating that Diamant is an alter ego of ICI. Supplemental Rule E of the Federal Rules of Civil Procedure puts the burden on Glory Wealth to demonstrate that Diamant is not present in the district. Fed.R.Civ.P. Supp. E(4)(f) & advisory note. Ordinarily, this is done by submitting an affidavit declaring that the defendant is not registered as a foreign corporation and has no commercial ties to, or offices and agents in, the district. Glory Wealth submitted such an affidavit with its application for a maritime attachment and appears to take the position that doing so satisfies its burden. Given that the Court has held that ICI is present in the district, however, this submission is simply not sufficient. Because alter egos of a defendant present in the district are present in the district, Glory Wealth can satisfy its burden only if it concedes that its alter ego allegation is baseless. Glory Wealth could make this concession is the alternative, but either way it loses. If Diamant is an alter ego, it is found in the district; if Diamant is not an alter ego, there is no valid prima facie maritime claim to support an attachment. See Aqua Stoli Shipping Ltd., 460 F.3d at 445. Glory Wealth attempts to resist this conclusion by arguing that Diamant should bear the burden of proving alter ego status because it is relying on such status in its motion to vacate. (Pl. Br. at 5-7.) The case relied on by Glory Wealth, Cannon Mfg. Co. v. Cudahy Packing Co., 267 U.S. 333, 45 S.Ct. 250, 69 L.Ed. 634 (1925), is not a maritime case, however, and considers only the situation where plaintiff has the burden of proving jurisdiction. Glory Wealth offers no reason why the burden should shift in the case at bar, and therefore its argument fails. Accordingly, Diamant's motion to vacate the attachment against it in this matter is GRANTED. The Court notes that this holding does not include a finding that Diamant is an alter ego, and Diamant is still free to advance this defense in the future. Owing to its representations at oral argument, Diamant is likely estopped from denying that this Court has personal jurisdiction over it, but that issue is not before the Court. SO ORDERED.
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Early Reviews Of Fox World Cup Coverage Lean Negative On Social Fox kicked off its coverage of the FIFA World Cup today with the opening match between Saudi Arabia and host country Russia, and early reaction on Twitter leaned negative. MSNBC's Ayman Mohyeldin: "I can tell already it’s gonna be a long month watching Fox’s commentary and coverage of the @FIFAWorldCup." SEC Country's Matthew Speakman: "Fox Sports‘ trash announcers always make the champions league painful and now they’re gonna make the World Cup painful." Quartz editor Mike Murphy: "It’s 2018 and the Fox website to watch the #WorldCup is trying to force me to enable Flash to watch the games." Rochester-based WHEC-NBC's Brennan Somers: "I'd rather spend the next month watching the #WorldCup on Telemundo versus listening to Alexi Lalas on FOX." The Athletic's Richard Deitsch: "When Cantor is on the call, I am going more with Telemundo. And that's no disrespect to John Strong, who I think is terrific." But some observers struck a more positive tone. NBC Sports' Men In Blazers: "Godspeed to @RobStoneONFOX and @AlexiLalas and all our colleagues at Fox. To broadcast a World Cup is both an honor and a grueling endeavor. We wish them Courage and are looking forward to making great memories." The MMQB's Albert Breer: "This is a pretty good weekend for Fox. Both the NBA and NHL end early, and they've got the World Cup and US Open. Just like you'd draw it up." EARLY RETURNS: The availability of pregame coverage was an issue in some markets. Deadspin's Timothy Burke tweeted 19 Fox affiliates in the U.S. "do not have #WorldCupFever, have elected to air local news, infomercials, or Wendy Williams instead of live network coverage from Russia." USA Today Network photojournalist Adam Wesley: "@FOXSoccer has already dropped the ball. Their pregame show going on right now for the opening match of #WorldCup2018 is not airing on my local Fox in Green Bay (and other markets). Good thing I have cable & Telemundo but c'mon, Fox" (TWITTER.com, 6/14). INTERESTING TEST: In Austin, Kevin Lyttle wonders if the positive momentum soccer is enjoying in the U.S. is "enough to justify" Fox' $400M "broadcast-rights gamble" for the World Cup. Author Michael MacCambridge said "everything is working against" the World Cup being a "big event" this year in the U.S. MacCambridge: "Because of the time difference in Russia, most of the matches will be occurring in the morning. For the first time in the memory of most American soccer fans, ESPN isn't broadcasting it. And the U.S. isn't playing. If, in the face of all that, the tournament still gets substantial viewership numbers -- and dominates sports talk for the next month -- that would be telling." Fox' Stuart Holden acknowledged the lack of the U.S. means "decreased ratings" for the World Cup. However, he said he thinks soccer has "grown up enough in the U.S. to weather the storm" (AUSTIN AMERICAN-STATESMAN, 6/14). In Atlanta, Mark Bradley wrote a "changing U.S. will pay attention to the World Cup, even without U.S. involvement and the latest games from Russia starting" at 2:00pm ET. He predicted that Fox' ratings "will be better than you'd think" (ATLANTA JOURNAL-CONSTITUTION, 6/9). QUESTIONABLE DECISION: In N.Y., Hannah Withiam noted Fox is "sending just two broadcast pairs to Russia" while the rest of the on-air talent will be "calling games from Fox's studios" in L.A. Fox World Cup Exec Producer David Neal "wouldn't say whether the U.S. team's absence factored into the decision to do most of the group-stage games 'off-tube.'" From the quarterfinals on, all games "will be broadcast" from Russia. Neal: "You have to get the most out of your resources, and one of the things that I did as I was analyzing where we were gonna spend our resources was that soccer is a game that's uniquely done this way" (N.Y. POST, 6/11). The GUARDIAN's Aaron Timms wrote the idea of calling World Cup games from a studio in L.A. is "ludicrous." There is "no comparison between what you experience at the stadium ... and the restricted, antiseptic view offered by TV." It is "not hard to see why Fox has gone down this road -- viewership of the World Cup is likely to be lower than if the U.S. had qualified, mandating a slimmer spend on tournament coverage -- but understanding the decision does not make it any better" (GUARDIAN, 6/12). In Boston, Chad Finn writes it is "difficult to blame Fox for cutting a financial corner or two upon the U.S. team's failure to qualify," as that is "going to have a significant effect on viewership stateside." However, it "opens up the question" of whether Fox is as "committed this year as it will be in eight years, when the matches are played in North America, and the U.S., presumably, will be a playing participant" (BOSTON GLOBE, 6/14). FERNANDO MANIA? YAHOO SPORTS' Leander Schaerlaeckens wrote people watching the World Cup will get to know Fox' Fernando Fiore "soon enough," as fans will "hardly be able to miss his outsized personality and comedy routine on the wall-to-wall Fox Sports broadcasts." Fiore is "known to break into song during live shows, while his colleagues pick apart plays and stats." Schaerlaeckens: "He dances. He wears funny hats. He mimics. He demonstratively rolls his eyes." Fiore has "carefully cultivated his persona, consciously setting himself apart from your milquetoast, dime-a-dozen soccer analyst" (SPORTS.YAHOO.com, 6/10). In Philadelphia, Jonathan Tannenwald writes Fiore is "charismatic, loud, and a passionate lover of the world's game." His World Cup broadcast presence will mean "a lot of people will cast judgement on Fiore who haven't before" (PHILADELPHIA INQUIRER, 6/14). VOICES CARRY: In N.Y., Andrew Marchand wrote Aly Wagner, who will "become the first woman World Cup game analyst, is a rising star." It is "too bad she will be calling games from a studio in LA instead of on-sight." Wagner has "stood out for her insights and by being opinionated without making it all about herself" (N.Y. POST, 6/13). Meanwhile, in S.F., Bruce Jenkins writes ESPN during previous World Cups had the "good sense to employ a number of British announcers, an absolutely crucial element for international events." Fox this year has "enlisted only two ... leaving the rest to Americans" (S.F. CHRONICLE, 6/14). LIKE YOU'RE THERE: N.Y.-based tech startup LiveLike has partnered with Fox Sports to produce the World Cup for fans in social VR with all 64 games during the tournament available through the Fox Sports VR app for free. The production also includes sponsorship integration with Adidas (THE DAILY).
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Dimorphism and inclusion compounds of N,N'-di(benzenesulfonyl)-p-phenylenediamine Crystal structures of a new polymorph of N,N'-(p-phenylene)bis(benzenesulfonamide) (C18H16N2O4S2) and of two inclusion compounds with acetone [(CH3)2CO] and dimethyl sulfoxide [2(CH3)2SO], respectively, have been determined at 150 K. For a more reliable comparison, the structure of the already known polymorph of N,N'-di(benzenesulfonyl)-p-phenylenediamine has been redetermined under identical conditions. In addition, the phase transformation behavior has been examined by differential scanning calorimetry and the crystallization conditions of both polymorphs including their formation by weathering of the inclusion compounds were investigated.
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Wolfenstein 2: 21 important facts about the shooter The publisher Bethesda has published a list of 21 facts that you should know about the upcoming shooter “Wolfenstein 2: The New Colossus”. Topics include the history, the gameplay mechanics and the opponents. Bethesda is preparing for the release of “Wolfenstein 2: The New Colossus”, which is still a few months to come and mid-October for PlayStation 4, Xbox One and PC. Meanwhile, the company fills an official list of 21 points, which you should know about the shooter. In this, the publisher is concerned with some background to the story. In addition, information on the gameplay mechanics as well as the opponents of the protagonist B.J. Blazkowicz. One of the points is devoted to the new opponents. For example, you should pay attention to the commandos, who jump through the game sections as a fast regime cyborg and shoot laser beams. The complete list of all 21 points can be found on the official website of “Wolfenstein 2: The New Colossus”. Below is a small copy-paste extract: 1. Roll command. He may be sitting in the wheelchair at the beginning of the game, but that can not stop a BJ Blazkowicz. “It is very important to us how the player controls the wheelchair,” explains Executive Producer Jerk Gustafsson, “You can move forward and backward, turn, and even sideways in the wheelchair, you have full control over this means of travel Shoot and throw grenades. ” 2. Caution! But OK, there are a few restrictions. You start with a maximum of 50 health points (instead of the usual 100) and you can not even climb stairs. But the clever level design pays for itself: from “conveyor belts” to “huge rotating gears” the “Hammerfaust” offers all possible alternatives for stairs climbing. “Steps or ladders are, of course, a real problem when you sit in a wheelchair,” says Gustafsson, “but there are a lot of different ways I find super-fun and entertaining.” 3. Where there is a will. That BJ The New Colossus begins in a wheelchair is due to his condition at the end of predecessor The New Order. It also shows Blazkowicz’s indomitable spirit: “BJ may be so badly wounded, mentally you will never break him,” says Gustafsson, “He always pulls his thing through”. 4. Strong partner. Anya is back again. She is now pregnant with twins, which does not keep her from vigorously. At the end of the first mission Reunion, we get a first impression: Anya frees BJ from a hairy situation by shooting a regime soldier. “In the first game, Anya wanted to fight the regime, but she did not know how,” said Creative Director Jens Matthies, “But then this warrior entered her life and she could learn a lot from BJ in this game Anya see. ” 5. Angel of death. There is another woman in BJ’s life, which reappears. But this is Mrs. Engel, who still has a chicken with our hero to pluck. How abominably angry she is, you can already see how she treats her leash-tested daughter Sigrun. Just look at the scene towards the end of “The Reunion”, where Frau Engel Sigrun harassed for her diary (and certain dietary habits).
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Q: Xslt for each with xpath and condition I have a xslt template and a xml document like below: Normally any data inside xml is exported like this: <Cell><Data ss:Type="String">sss</Data></Cell> I want to make some change inside xslt that: if any value inside record object contains <br/>, it should export data like this: <Cell ss:StyleID="s62"><Data ss:Type="String">sss</Data></Cell> Can anyone help me about that? Xslt template: <xsl:stylesheet version="1.0" xmlns="urn:schemas-microsoft-com:office:spreadsheet" xmlns:xsl="http://www.w3.org/1999/XSL/Transform" xmlns:msxsl="urn:schemas-microsoft-com:xslt" xmlns:user="urn:my-scripts" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:x="urn:schemas-microsoft-com:office:excel" xmlns:ss="urn:schemas-microsoft-com:office:spreadsheet"> <xsl:template match="/"> <Workbook xmlns="urn:schemas-microsoft-com:office:spreadsheet" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:x="urn:schemas-microsoft-com:office:excel" xmlns:ss="urn:schemas-microsoft-com:office:spreadsheet" xmlns:html="http://www.w3.org/TR/REC-html40"> <Styles> <Style ss:ID="s62"> <Alignment ss:Vertical="Bottom" ss:WrapText="1"/> </Style> </Styles> <xsl:apply-templates/> </Workbook> </xsl:template> <xsl:template match="/*"> <Worksheet> <xsl:attribute name="ss:Name"> <xsl:value-of select="local-name(/*/*)" /> </xsl:attribute> <Table x:FullColumns="1" x:FullRows="1"> <Row> 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<BITIS_TARIH>2013-11-16T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>4912.66</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>4655.07</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-13T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-13T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>2313.17</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>2211.51</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-14T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-14T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>4061.73</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>3867.42</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-23T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-23T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO>101000018166873</CF_ONCEKI_POLICE_NO> <CF_SUM_BRUT_PRIM>257.79</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>230.61</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-25T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-25T00:00:00</BITIS_TARIH> 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<BASLAMA_TARIH>2012-11-01T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-01T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>2061.93</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>1967.81</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-18T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-18T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>2580.77</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>2453.35</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-30T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-30T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>729.09</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>705.05</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-15T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-15T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>1862.96</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>1772.08</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-14T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-14T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO>101000018058939</CF_ONCEKI_POLICE_NO> <CF_SUM_BRUT_PRIM>281.53</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>251.8</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-03T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-03T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO>101000018058942</CF_ONCEKI_POLICE_NO> <CF_SUM_BRUT_PRIM>431.24</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>385.48</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-26T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-26T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>585.76</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>558.39</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-07T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-07T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>1162.81</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>1105.44</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-24T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-24T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO>101000018058929</CF_ONCEKI_POLICE_NO> <CF_SUM_BRUT_PRIM>281.53</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>251.8</CF_SUM_NET_PRIM> </record> <record> <BASLAMA_TARIH>2012-11-11T00:00:00</BASLAMA_TARIH> <BITIS_TARIH>2013-11-11T00:00:00</BITIS_TARIH> <CF_ONCEKI_POLICE_NO /> <CF_SUM_BRUT_PRIM>2004.01</CF_SUM_BRUT_PRIM> <CF_SUM_NET_PRIM>1908.58</CF_SUM_NET_PRIM> </record> A: One way to do it would be <xsl:template match="/*/*/*"> <Cell> <xsl:if test=".//br"> <xsl:attribute name="ss:StyleID">s62</xsl:attribute> </xsl:if> <Data ss:Type="String"><xsl:value-of select="." /></Data> </Cell> </xsl:template> adding the ss:StyleID attribute conditionally based on the presence/absence of descendant <br> elements. However the <br> will not appear in the generated <Data> element because you're using <xsl:value-of> (which just gives you a plain text string value). You might want to use <xsl:copy-of select="node()"/> instead, which will preserve the element structure of the children.
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Share 6 6 Shares The following is adapted from Maimonides’ Guide for the Perplexed. The concept that God puts people through trials is the most debated idea in the entire Bible. Most people assume (incorrectly) that God afflicts individuals not in response to their own sins but to provide them with an opportunity to earn reward. Trials are discussed six places in the Torah but only one of them supports such a hypothesis at face value (Deuteronomy 8:16, which we’ll discuss shortly). Rather, the Torah’s teaching dismisses such an understanding as “He is a faithful God; there is no injustice in Him” (Deuteronomy 32:4). The Sages taught likewise that “there is no death without sin and no suffering without transgression” (Shabbos 55a). A thinking person must therefore not attribute any wrongdoing to God by suggesting that He has afflicted a righteous person with undeserved suffering. Rather, in the six instances of trials in the Torah, we see that trials are the tests through which God demonstrates the faith of individuals or nations. This idea may be a little difficult to process. After all, no one witnessed the binding of Isaac except for God and Abraham, and God even said, “Now I know that you fear God…” (Genesis 22:12). Elsewhere, the Torah says, “Hashem your God tests you to know whether you love…” (Deuteronomy 13:4). This makes it seem as if trials are for God’s benefit, which is baffling as God already knows all. So what is the real meaning of the tests we endure? We see from the Torah that the sole purpose of trials is to teach a person what he should do or what he should believe. The trial itself is not the goal, it’s the means to an end. The verb la’daas doesn’t mean “to know” in such verses as Genesis 22:12, it means “to make known.” This is clearly its meaning in some other places, like Exodus 31:13, “to make it known that I am God Who sanctifies you” – surely God already knows that He is the One Who sanctifies them! Rather, it is for the benefit of others. Similarly, our tests make it known whether those tested love God and defer to His will. In the case of the false prophet (Deuteronomy 13), the Torah says outright that when such a person arises, it is a test through which we can prove our dedication to God (verse 4). This meaning of la’daas applies wherever the Torah discusses the purpose of trials. This includes such verses as Deuteronomy 8:2, “to test you and make known what was in your heart, whether you would keep His commandments or not.” But what of Deuteronomy 8:16, which says regarding manna that it was “to test you in order to do good for you in the future?” This verse appears to support the idea that God does indeed put people through trials so that they might earn reward. Again, the Rambam tells us that a verb doesn’t mean what we might think it does. In this case, the verb nasosecha doesn’t mean “to do good for you,” it means “to get you used to it.” (A similar use occurs in Deuteronomy 28:56, “She has not accustomed the sole of her foot to tread on the ground.”) The idea of Deuteronomy 8:16, then, is that God put the nation through trials in order to get them used to hardship, which was a skill they would require upon entering the land of Israel. Had they spent 40 years in luxury and comfort, they would have been ill-prepared for the hardships of combat that awaited them. Abraham’s binding of Isaac reveals two important principles. First, it shows the extent to which we must take our reverence for God. Abraham was asked to bind his own son as a sacrifice, something that goes against human nature in general and Abraham’s merciful nature in particular. Not only had Abraham longed for a son, only to finally receive one after abandoning all hope, he had been promised that a nation would descend from Isaac. The command to bind Isaac must have been utterly incomprehensible but Abraham subordinated himself – emotionally, logically, and in all other ways – to God’s will. To further this, Abraham was commanded to do so after a three-day journey. His mind wasn’t reeling from shock and he wasn’t acting impetuously. Rather, he had ample opportunity to contemplate the gravity of his undertaking. Nevertheless, he saw it through without hesitation. The second thing we see is the degree of faith that the prophets placed in the messages they received. Whatever a prophet saw in a vision, he knew to be true; there was no doubt or confusion in his mind whatsoever. We see this from the fact that Abraham consented to undertake this mission; had there been anything less than perfect clarity, he would not have had the strength to see it through. This is the correct way to understand trials. We must not delude ourselves that God tests us in order to discover something that He did not know before. (This is an impossibility, given that He knows all.) Rather, it is to lay the groundwork for our faith and practice, as we see from the trial of Abraham binding Isaac. * * * * * * * * * * * * * * * * A note from Allison: This article is excerpted from Rabbi Jack Abramowitz’s new book, “The God Book,” which you can purchase here. Rabbi Abramowitz, who we have been blessed to call a member of our team for several years now, gave me the honor of writing the foreword for this book. A book about God. A subject strangely not present enough in Jewish education. Rabbi Abramowitz not only has an incredible knack for tackling some of the most challenging topics in the Torah and Talmud – I go to him when I am personally perturbed by something – he is extremely patient. Besides his articles, which we regularly publish on JewintheCity.com, Rabbi Abramowitz has responded to countless emails from our readers over the years and responds and responds until the questioner feels satisfied. We as an organization and we, the Jewish people, are blessed to have him around. May Hashem grant him many long and healthy years to continue making Torah palatable for all who are searching. Share 6 6 Shares
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Introduction {#sec1-1} ============ HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome) is a major problem in India with more than 6 million recorded cases by the end of 2005.([@CIT1]) Patients with HIV are prone to developing a panorama of diseases during their lifetime. AIDS represents the most severe squeal of immunosuppression caused by HIV and is a constellation of diseases reflecting the late manifestation of HIV infection. Immunosuppression caused by HIV infection leads to the development of severe opportunistic infections and otherwise rare tumors. Among them, diarrhea is a significant cause of morbidity observed in a majority of studies.([@CIT2][@CIT3]) In fact, it is the second leading cause of hospital visits in developing nations and makes its place in the top ten worldwide.([@CIT4]) Reports indicate that diarrhea occurs in 30-60% of patients with AIDS in developed countries and in about 90% of such patients in developing countries.([@CIT5]) In tropical countries, chronic diarrhea associated with weight loss (slim disease) is often the presenting illness of HIV-1 infected individuals.([@CIT6]) This diarrhea wasting syndrome in association with a positive HIV-1 serology test is an AIDS-defining criterion, according to the World Health Organization (WHO) classification.([@CIT7]) HIV infection and AIDS are fast becoming a major threat in India. Patterns of enteric infections in developing countries like ours, where hygiene is poor and intercurrent infection rates are high, may differ in several important ways from patterns of developed countries. Knowledge of the pattern of the infection can often guide therapy when resource limitations hamper the exact diagnosis of the etiological agent in HIV-associated diarrhea. The primary objectives of this study were to define the microbial etiologies of diarrhea in HIV-1 infected individuals and compare them with those of HIV seronegative diarrheal patients and HIV-1 infected individuals without diarrhea. Materials and Methods {#sec1-2} ===================== Study population and study design {#sec2-1} --------------------------------- This study was conducted prospectively between April 2007 and July 2007 at the HIV and Diarrhea and Parasitology Laboratory, Department of Microbiology, Maulana Azad Medical College attached to Lok Nayak Hospital, New Delhi, which is a tertiary care hospital with 1500 beds catering to the health needs of people in Delhi and the adjoining states of North India. After receipt of informed consent from patients and approval from the ethical committee, 150 stool samples were taken as follows: Fifty stool samples from HIV seropositive cases with diarrhea (study group). Fifty stool samples from HIV seropositive cases without diarrhea (control group I). Fifty stool samples from HIV seronegative cases with diarrhea (control group II). Each patient was interviewed using a questionnaire concerning general demographic characteristics, type of illnesses, and clinical symptoms. Inclusion criteria {#sec2-2} ------------------ An episode of diarrhea was defined as the occurrence of an average of at least three liquid bowel movements daily for at least 1 week before the visit to the hospital. Exclusion criteria {#sec2-3} ------------------ Persons who had received antibiotics/antiparasitic treatment for diarrhea within the past 14 days were excluded. Laboratory studies {#sec2-4} ------------------ Diagnosis of HIV infection and microbiological diagnosis of enteric infection in stool samples were done in all 150 cases. Diagnosis of HIV infection {#sec2-5} -------------------------- The diagnosis of HIV infection was done by following the standard protocol at our voluntary counseling and testing center (VCTC) that employs pre test and post test counseling and obtains informed consent before HIV testing. Three different immunoassays (Micro ELISA, J. Mitra and Co. Pvt. Ltd, India; Retroquic, Qualpro Diagnostics, India; and Capillus, Trinity Biotech, USA) were used following the standard manufacturer\'s instructions. Diagnosis of enteric infections {#sec2-6} ------------------------------- Stool specimens were collected fresh and processed in the Diarrhea and Parasitology Laboratory within 4 hours of collection. Parasite detection was done by direct examination after formalin-ether-concentration of stool specimens as wet saline and iodine mount techniques for the detection of protozoan trophozoites and cysts and helminthic eggs and larva. Additionally, all samples were subjected to Gram stain and a modified acid-fast stain for coccidian oocysts.([@CIT8]) A part of the stool sample was processed for the detection of bacterial pathogens using selective and differential media as per standard protocol.([@CIT9]) For detection of *Clostridium difficile* toxin in stool samples, the *Clostridium difficile* Toxin A + B Antigen Detection Microwell ELISA (IVD Research Inc., Carlsbad, CA 92008 USA) was used following the manufacturer\'s instructions. For detection of the Cryptosporidium antigen in stool samples, the Cryptosporidium Antigen Detection Microwell ELISA (IVD Research Inc., Carlsbad, CA 92010 USA) was used following the manufacturer\'s instructions. Results {#sec1-3} ======= This prospective study was conducted between April 2007 and July 2007. A total of 150 patients were examined in this study; 50 from HIV seropositive cases with diarrhea (study group), 50 from HIV seropositive cases without diarrhea (control group I), and 50 from HIV seronegative cases with diarrhea (control group II). The age and gender profile of the study and the control subjects is presented in [Table 1](#T0001){ref-type="table"}. In the study group, the age range of 31-40 years old was the most predominant in overall size (46%). The age range of 21-30 years old and 0-10 years old had the maximum number of cases with 42% and 78% in control groups I and II, respectively. Males outnumbered females in the study group and control group II subjects with a male to female ratio of approximately 1:4 and 3:2, respectively. However, no such gender difference was observed in control group I. ###### Age and gender distribution of the study and control subjects Age groups (years) HIV seropositive with diarrhea study group (n=50) HIV seropositive without diarrhea control group I (n=50) HIV seronegative with diarrhea control group II (n=50) -------------------- --------------------------------------------------- ---------------------------------------------------------- -------------------------------------------------------- ----- ---- ---- ---- ----- ---- ---- ---- ----- 0-10 2 2 4 8 1 1 2 4 23 16 39 78 11-20 0 0 0 0 4 1 5 10 2 3 5 10 21-30 10 6 16 32 5 16 21 42 1 1 2 4 31-40 12 11 23 46 11 6 17 34 3 0 3 6 41-50 3 1 4 8 2 1 3 6 0 0 0 0 51 + 2 1 3 6 2 0 2 4 1 0 1 2 Total 29 21 50 100 25 25 50 100 30 20 50 100 From the study, the overall prevalence of enteric parasitosis in the study group, control group I, and control group II were found to be 20%, 2%, and 18%, respectively. The overall prevalence of enteric parasites in males was 6% (9/150) and 7.3% (11/150) in females. The proportion of protozoan parasites in the study group was 70% as compared with 100% and 66.7% in control groups I and II, respectively. The distribution of different enteric parasites in the study group and control subjects is depicted in [Table 2](#T0002){ref-type="table"}. ###### Prevalence of specific intestinal parasites among the study and control subjects Parasites detected HIV seropositive with diarrhea study group (n=50) frequency (%) HIV seropositives without diarrhea control group I (n=50) frequency (%) HIV seronegative with diarrhea control group II (n=50) frequency (%) ----------------------------- ----------------------------------------------------------------- ------------------------------------------------------------------------- ---------------------------------------------------------------------- *Ascaris lumbricoides* 2 (20) 0 2 (22.2) Hookworm 0 0 1 (11.1) *Hymenolopsis nana* 0 0 0 *Entamoeba histotytica* 2(20) 0 1 (11.1) *Giardia lamblia* 2(20) 0 5 (55.5) *Blastocystis hominis* 0 0 0 *Cryptosporidium parvum* 2 (20) 1 (100) 0 *Isospora belli* 1 (10) 0 0 *Cyclospora cayetanensis* 0 (0) 0 0 *Strongyloides stercoralis* 1 (10) 0 0 *Trichuris trichuria* 0 0 0 Total 10 1 9 The bacteria identified in the stool of HIV seropositive individuals with diarrhea were *Escherischia coli* in 12 (24%) cases, *Clostridium difficile* in 5 (10%) cases, Salmonella species in 2 (4%) cases, *Vibrio cholerae* in 2 (4%) cases, and Shigella species in 1 (2%) case. In HIV seropositive individuals without diarrhea, *Escherischia coli* again was the most predominant bacteria identified in stool samples (10%) followed by *Clostridium difficile* in 4% cases. In HIV seronegative individuals with diarrhea, whereas *Clostridium difficile* was not seen, *Escherischia coli* was found in 22% of the cases. In addition, *Vibrio cholerae* was isolated in 26% of the cases with 69.2% and 30.8% belonging to Ogawa and Inaba subtypes, respectively \[[Table 3](#T0003){ref-type="table"}\]. ###### Enteric microbial pathogens other than parasites identified in stool samples of study and control subjects Pathogen other than parasite HIVseropositive with diarrhea study group (n=50) number (%) HIV seropositive without diarrhea control group I (n=50) number (%) HIV seronegative with diarrhea control group II (n=50) number (%) ------------------------------------- ------------------------------------------------------------- --------------------------------------------------------------------- ------------------------------------------------------------------- Candida species 18 (45) 6 (46.2) 1 (4) Salmonella species 2 (5) 0 0 Shigella species 1 (2.5) 0 0 *Vibrio cholerae*  Ogawa 2 (5) 0 9 (36)  Inaba 0 0 4(16) *Clostridium difficile* 5 (12.5) 2 (15.4) 0 Enteropathogenic *Escherishia coli* 8 (20) 3 (23.1) 9 (36) Enteroinvasive *Escherishia coli* 4 (10) 2 (15.4) 2 (8) Total 40 13 25 As far as fungal pathogens are concerned, the Candida species was identified in 36%, 12%, and 2% of the cases in the study group, control group I, and control group II subjects, respectively. Discussion {#sec1-4} ========== Although HIV/AIDS and water-borne infections, exemplified by diarrhea, are the leading causes of morbidity and mortality in developing countries, their association has received only cursory attention. Identification of the etiological agent of diarrhea in a patient with AIDS is very important as it can help in the institution of appropriate therapy and the reduction of morbidity and mortality in these patients. This study was therefore conducted to ascertain the scope and frequency of potential enteric bacterial pathogens isolated from stool samples of HIV-positive and -negative individuals with and without diarrhea. The etiology for such diarrhea could be parasitic, bacterial, fungal, enteric viruses, or HIV itself may contribute to diarrhea. In addition to microbes, other factors such as medication, immune deregulation, autonomic dysfunction, and nutritional supplementation play a substantial role in diarrhea of patients with HIV/AIDS.([@CIT5]) Shigellosis, Campylobacter infections, and Cryptosporidiosis occur relatively more frequently in HIV-1 infected persons than in persons without HIV-1 infection. Some agents produce diarrhea almost exclusively in HIV-1 infected persons (e.g., *Mycobacterium avium* complex, Cytomegalovirus, and HIV-1enteropathy). Others cause more severe, more prolonged, or more often recurrent diarrhea in the presence of HIV-1 infection (e.g., Cryptosporidiosis species, Isospora species, Salmonella species, Astrovirus, Adenovirus, Calcivirus and perhaps Microsporidium species, *Cyclospora cayetanensis*, Shigella species, and Campylobacter species). Some agents apparently have unaltered courses but occur commonly in HIV-1 infected persons (e.g., *Clostridium difficile*).([@CIT10]) Among persons with HIV infection, 40-80% of diarrheal illnesses have an identifiable cause and a bacterial etiology is common.([@CIT11][@CIT12]) Diarrheal illnesses due to parasites in patients infected with HIV is on the rise. Many studies have highlighted the emergence of important protozoan parasites and helminths as a major cause of morbidity and mortality in patients with AIDS.([@CIT2][@CIT13][@CIT14]) In resource limited countries such as India, enteric infections remain common in the general population and for those people infected with HIV, with geographic differences in the reported prevalence of individual pathogens reflecting differences in pathogen prevalence, standards of hygiene, and diagnostic methods used.([@CIT2]) There are many reports regarding the frequency of various pathogens causing diarrhea from different parts of India.([@CIT2][@CIT15]) Some studies also demonstrated regional variability of pathogens,([@CIT16]) as well as changing trends of etiology in the same population.([@CIT11]) With the myriad of etiologies and sometimes-altered natural history of enteric infections in HIV-1 infected persons with diarrhea, it remains uncertain how well clinical manifestations or risk factors predict microbial etiology or are able to guide the empirical choice of therapy for an individual patient. In our study 31-40 years old, 21-30 years old, and 0-10 years old were the most predominant age groups in overall size affected with 46%, 42%, and 78% of the cases, respectively. Previous studies have also indicated HIV prevalence to be most common in the 21-30 year old age group([@CIT17][@CIT18]) and in the non HIV infected group, diarrhea is more commonly seen in children than in adults in developing countries. Our study shows a male preponderance in HIV infected patients with diarrhea similar to previous studies;([@CIT20]) however, others have reported more females than males in this population.([@CIT17]) We found an overall prevalence of enteric parasitosis in the study group, control group I, and control group II to be 20%, 2%, and 18%, respectively. A previous study reported that a potential enteric pathogen was isolated from all (100%) of the HIV-positive individuals with diarrhea and 68 (52.3%) without diarrhea.([@CIT17]) Another study reported a prevalence of enteric parasitosis of 36% and 14% in patients with HIV with and without diarrhea, respectively,([@CIT18]) whereas others have reported a higher percentage of enteric parasitosis in Indian patients with HIV with diarrhea.([@CIT19]) Studies in Africa have reported a prevalence of intestinal parasitosis varying from 19 to 33%.([@CIT21][@CIT22]) A recent study conducted in Chennai reported 13% enteric parasitosis among HIV-positive individuals and normal individuals without diarrhea.([@CIT23]) In our study, the overall prevalence of enteric parasites in males was 6% (9/150) and 7.3% (11/150) in females. A previous study from Nepal reported 56% and 44% enteric parasitosis in male and female groups of patients with HIV/AIDS, respectively.([@CIT24]) Our study shows that the proportion of protozoan parasites in the study group was 70% as compared with 100% and 66.7% in control groups I and II, respectively. Previous authors have also reported a higher prevalence of protozoa as compared with helminthes in enteric parasitosis([@CIT18][@CIT22][@CIT24]) in HIV/AIDS. In HIV-positive patients with diarrhea, out of 10 cases of enteric parasitosis, we isolated helminthes in 3 cases (*Ascaris lumbricoids* in 2 and *Strongyloides stercoralis* in 1) and protozoa in 7 cases (*Entamoeba histolytica, Giardia lamblia*, and *Cryptosporidium parvum* in 2 each and Isospora belli in 1). In HIV-positive patients without diarrhea, we isolated only *Cryptosporidium parvum* in 1 case. In HIV-negative individuals with diarrhea, out of 9 cases of enteric parasitosis, helminthes were found in 3 cases (*Ascaris lumbricoids* in 2 and *Ancylostoma duodenale* in 1) and protozoa were detected in 6 cases (*Entamoeba histolytica* in 1 and *Giardia lamblia* in 5). These findings suggest that patients with HIV/AIDS had more intestinal parasite infections than the control groups and the only parasites clearly more prevalent in this population were *Cryptosporidium parvum, Isospora belli,* and *strongyloides stercoralis*. A recent study from North India reported that of the emerging parasites, *Isospora belli* was most frequently detected followed by *Cryptosporidium; Blastocystis hominis* and *E. histolytica* were the most frequent conventional pathogen followed by *Giardia lamblia.*([@CIT25]) Few other Indian studies have also reported *Isospora belli* followed by *Cryptosporidium parvum* as the most common pathogen among enteric parasites in HIV associated diarrhea.([@CIT19][@CIT23]) The high rate of infection with *Isospora belli* poses a threat to HIV-positive patients. Diagnosed cases of *Isospora belli* were considerably fewer in this study, which could possibly be either due to more sensitive detection methods used in studies reporting a higher prevalence or a reflection of low prevalence in this study population. The actual rate of this infection in immunocompetent individuals and patients with AIDS is likely to be underestimated due to asymptomatic shedding of oocysts and treatment with trimethoprim - sulphamethoxazole for other infections in AIDS cases, which may confer some protection against this parasite. Other studies have reported *Cryptosporidium parvum* as the most common pathogen among enteric parasites in the HIV/AIDS population.([@CIT12][@CIT24][@CIT26]) HIV opportunistic infections, cryptosporidiosis inclusive, tend to vary from one locality to another and from one country to the another depending on the level of contamination in the water, food, and contact with animals, which are important factors in the dissemination of the parasite. Finally, the small unfilterable size (3-5 Lm) of oocysts, their resistance to chlorine disinfections, and low infective dose are the major infective potential of *Cryptosporidium parvum*. No *Microsporidia* and *Cyclospora* were detected in our study similar to a few other studies,([@CIT25]) though other studies from India have reported a low prevalence of cyclosporidiasis([@CIT15][@CIT18][@CIT23]) and microsporidiosis.([@CIT19][@CIT23]) Thorough investigations on a large number of patients are required to know the exact role of these pathogens in HIV-related diarrhea in India. Our findings tend to support the view that the more 'common' parasites (*Ascaris lumbricoides, Ancylostoma duodenale, Giardia lamblia*, and *Entamoeba histolytica*) are not opportunistic in patients with AIDS and identification of these common parasites in up to 60% of patients with AIDS and the controls is a reflection of poor environmental hygiene. Until recently, more frequently-associated parasites with diarrhea were: *Giardia lamblia, Entamoeba histolytica, Balantidium coli,* etc. Since the onset of the AIDS epidemic, the number of parasitic pathogens recognized and the frequency with which they are encountered in clinical practice have increased. These parasites can cause self-limiting diarrhea of short duration in healthy individuals, but in the immunocompromised host, including patients with AIDS, diarrhea is usually chronic and, sometimes, life-threatening. The high proportion of patients with AIDS who had diarrhea in the absence of identified parasite infections strongly indicates the existence of other diarrheaogenic agents or mechanisms. The detection of these will require more comprehensive and better controlled studies. On bacterial culture of stool, the common organisms associated with diarrhea in HIV-infected individuals in our study were *Escherichia coli* (30%), *Clostridium difficile* (12.5%), Salmonella species (5%), *Vibrio cholerae* (5%), and Shigella species (2.5%). Whereas only *Escherichia coli* (38.5%) and *Clostridium difficile* (15.4%) were found in the stool of HIV-infected individuals without diarrhea, the stool of HIV seronegative individuals with diarrhea showed *Vibrio cholerae* and *Escherichia coli* in 52% and 44% of the total bacterial isolates in this group. Previous studies in India have also reported the isolation of similar organisms with slightly variable frequencies in the stool of such patients;([@CIT18][@CIT23]) however, in one of these studies, no bacterial pathogens other than *Escherichia coli* and Klebsiella species were isolated from stool specimens of HIV-positive individuals without diarrhea and normal individuals without diarrhea.([@CIT23]) Another study from Thailand found that the isolation rates of bacterial enteropathogens causing diarrhea in AIDS patients with diarrhea (APD) (18%, 62/350) were considerably lower than those in non AIDS patients with diarrhea (NAPD) (43%, 152/350) (*P*\<0.05).([@CIT27]) As far as fungal pathogens are concerned, we isolated the *Candida* species in 18 cases (36%), 6 cases (12%), and 1 case (2%) of the 50 cases each in the study group, control group I, and control group II, respectively. In a previous study in India, the *Candida* species was identified in 2.6% of the cases consisting of one case in acute diarrhea, one in control group and two cases in chronic diarrhea. Conclusion {#sec1-5} ========== Enteric parasitosis might be one of the major health problems among patients infected with HIV, particularly those with AIDS. Studies from various parts of the world show contrasting prevalence rates with marked geographical variations.([@CIT28][@CIT29]) This emphasizes the need for thorough investigations of these patients to identify pathogens for proper management. Opportunistic enteric pathogens, for which there is no effective treatment, the emergence of new opportunistic infections, and the enlarging pattern of drug resistance continues to be a challenging task. However, better understanding of HIV-1-induced mucosal immunosuppression, sound clinical management, careful diagnostic evaluation, the development of newer antimicrobial agents, and judicious patient management should help to meet this challenge and may help to reduce morbidity and untimely mortality for patients with HIV/AIDS in India. **Source of Support:** Nil **Conflict of Interest:** None declared.
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Q: Difference between anonymous class and IDictionary for htmlAttributes in ASP.NET MVC? For example if you check these two extension methods the only difference is type of htmlAttributes so you can pass your htmlAttributes in two different ways: public static MvcHtmlString TextBoxFor<TModel, TProperty>( this HtmlHelper<TModel> htmlHelper, Expression<Func<TModel, TProperty>> expression, IDictionary<string, object> htmlAttributes); public static MvcHtmlString TextBoxFor<TModel, TProperty>( this HtmlHelper<TModel> htmlHelper, Expression<Func<TModel, TProperty>> expression, object htmlAttributes); And use them in either of these ways: @Html.TextBoxFor(model => model.TagLine, new { @placeholder = "We live to make art." }) @Html.TextBoxFor(model => model.TagLine, new Dictionary<string, object> { { "placeholder", "We live to make art." } }) I have checked MVC source code and I know in the background they use same method, but the one which accepts the anonymous object uses HtmlHelper.AnonymousObjectToHtmlAttributes(htmlAttributes) to make the anonymous object a dictionary. In my point of view, views are cleaner to use anonymous object. What do you think guys? Are there any drawbacks to using an anonymous object? A: There's not too much difference, however using the anonymous object is a cleaner and more readable syntax for the caller, and now considered more standard practice. There might be a slight, negligible performance benefit to using IDictionary if you're a fan of micro-optimisation. The IDictionary overload option has probably stuck since ASP.NET MVC 1.0 CTP days when C# 3.0 and anonymous objects were still quite new. Eilon Lipton's blog post proposing Using C# 3.0 Anonymous Types as Dictionaries gives some background.
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Download Emeril's Delmonico: A Restaurant with a Past by Emeril Lagasse PDF By Emeril Lagasse For greater than a hundred years, Delmonico has embodied the spirit of recent Orleans. First opened in 1895, Delmonico eating place and Bar in New Orleans reopened its doorways a century later to great acclaim as Emeril's Delmonico. In his newest cookbook, America's favourite star chef provides a set of recipes which are tailored and simplified for domestic chefs, that includes a mixture of Creole classics and Emeril's kicked-up creations. Emeril's Delmonico is filled with recipes for hearty, cutting edge meals steeped in New Orleans type. Illustrated with either modern full-color and classic black-and-white images, Emeril's Delmonico paints a full of life, evocative portrait of Emeril's vintage delicacies and the wealthy culinary historical past of recent Orleans. For greater than a hundred years, Delmonico has embodied the spirit of recent Orleans. First opened in 1895, Delmonico eating place and Bar in New Orleans reopened its doorways a century later to great acclaim as Emeril's Delmonico. In his newest cookbook, America's favourite star chef provides a set of recipes which are tailored and simplified for domestic chefs, that includes a mixture of Creole classics and Emeril's kicked-up creations. Emeril's Delmonico is filled with recipes for hearty, cutting edge meals steeped in New Orleans type. Illustrated with either modern full-color and classic black-and-white images, Emeril's Delmonico paints a full of life, evocative portrait of Emeril's vintage delicacies and the wealthy culinary historical past of recent Orleans. <p class="MsoNormal" style="margin: 0in 0in 0pt">While “bread” as soon as implied an easy, sliced white loaf from the grocery store, shoppers have began to contemplate the product in a extra subtle gentle. Bread fans are extra conscious of the varied array of top of the range breads than ever sooner than and are trying to find out home made artisan items at neighborhood farmers’ markets, natural grocery shops, area of expertise shops…even the web. This first-ever cookbook from excessive instances magazine—the world's such a lot depended on identify by way of getting stoned—is the deliciously definitive advisor to cannabis-infused cooking. effortless, available recipes and recommendation demystify the adventure of cooking with grass and provide a cornucopia of irie appetizers and entrees, stoner chocolates, hashish cocktails, and high-holiday feasts for any social gathering, from Time Warp Tamales and Sativa Shrimp Spring Rolls to Pico de Ganja Nachos and Pineapple convey Upside-Down Cake. Supply Achatz's occupation as a chef has been equipped on beating the percentages, time after time. From humble Midwestern beginnings, he struck out into the culinary global and rose to super-stardom in Chicago, the place his iconoclastic imaginative and prescient helped rework the yankee fine-dining adventure. alongside the best way, he fought a dramatic conflict with melanoma that briefly stripped him of his skill to style. In the end, the significant other cookbook to the hit YouTube cooking exhibit with recipes for one hundred twenty easy, scrumptious Italian-American classics When Laura Vitale moved from Naples to the us at age twelve, she cured her homesickness by way of cooking up unending pots of her nonna’s sauce. She went directly to paintings in her father’s pizzeria, but if his eating place abruptly closed, she knew she needed to locate her long ago into the kitchen. with her husband, she introduced her net cooking express, Laura within the Kitchen, the place her enthusiasm, attraction, and impossible to resist recipes have gained her hundreds of thousands of lovers. In her debut cookbook, Laura makes a speciality of easy recipes that any one can achieve—whether they've got somewhat time to spend within the kitchen or are looking to create a magnificent banquet. listed below are a hundred and ten all-new recipes for quick-fix suppers, equivalent to Tortellini with red Parmesan Sauce and One- Pan poultry with Potatoes, Wine, and Olives; leisurely entrées, together with Spinach and Artichoke-Stuffed Shells and Pot Roast alla Pizzaiola; and 10 fan favorites, like tacky Garlic Bread and No-Bake Nutella Cheesecake. Laura checks her recipes dozens of occasions to excellent them so the implications are continually impressive. With transparent directions and greater than a hundred colour images, Laura within the Kitchen is the correct advisor for somebody seeking to get cozy on the range and feature enjoyable cooking. Line two cookie sheets with parchment paper. Remove one piece of dough from the refrigerator. Place the dough between two pieces of waxed paper and roll to ⅛ in/3 mm thick. Using cookie cutters, cut out as many shapes as possible. The dough is oily, so the cutter shouldn’t stick to the dough. 5 cm apart. Bake until the cookies are dark brown, about 15 minutes. Remove to wire racks to cool completely. Let the sheets cool completely and repeat with the remaining dough. TO MAKE THE ROYAL ICING / In a large bowl, whisk the egg whites until foamy. In a small bowl, whisk the egg white until foamy, about 30 seconds. Add the sugar and whisk for 10 seconds. Add the oil and the water and whisk until combined. Add the vanilla and orange zest and whisk until combined. Add the flour and the salt and whisk until the mixture is smooth. Spoon the batter by teaspoonfuls onto the prepared sheet. 5 cm in diameter (no larger). The batter will look uneven, with some spots having more batter than others. Just try to make it as even as you can. Repeat to make another circle of batter, spacing it at least 2 in/5 cm from the first circle. Once the cookies are baked, the outsides stay crunchy, while the insides are a bit chewy. When I add toasted nuts to the meringue, my preference is for pecans. You can use the leftover yolks to make Thumbprint Cookies (page 58). ABOUT 45 SMALL COOKIES OR 30 BIG COOKIES Preheat the oven to 300°F/150°C/gas mark 2. Line two cookie sheets with parchment paper. In the bowl of a stand mixer fitted with the whisk attachment, beat the egg whites on medium-high speed until foamy. Add the cream of tartar and beat for a few seconds to combine.
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Q: Comando para definir um valor padrão para uma coluna no SQL Server Olá, desejo saber o comando para definir um valor como default no SQL server. O nome da tabela é "Tabela" e o nome da coluna que desejo alterar é "COLUNA2". A: Para definir um valor padrão de uma coluna da tabela você deve utilizar o operador DEFAULT. Você pode informá-lo na criação da sua tabela: CREATE TABLE tabela ( id INT NOT NULL PRIMARY KEY, coluna1 VARCHAR(100), coluna2 INT DEFAULT 1 ); Ou para alterar a coluna: ALTER TABLE tabela ADD CONSTRAINT coluna2_default DEFAULT 1 FOR coluna2; Nos exemplos acima o valor 1 será definido na coluna caso não seja informado na inserção: INSERT INTO tabela(id, coluna1) VALUES(1, 'blablabla'); Resultando no registro: | id | coluna1 | coluna2 | | --- | --------- | ------- | | 1 | blablabla | 1 | Usar o Transact-SQL para especificar um padrão Há várias maneiras pelas quais você pode especificar um valor padrão para uma coluna usando o SSMS para enviar o T-SQL.
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Queensland election 2015: Clive Palmer maintains PUP can snatch balance of power Updated Federal MP Clive Palmer maintains his political party can snatch the balance of power in Queensland at this month's state election. Premier Campbell Newman and Opposition Leader Annastacia Palaszczuk have both ruled out doing deals with the crossbench to form a minority government. But Mr Palmer told AM that his party had a lot of support throughout Queensland and predicted the LNP would lose seats to PUP. "Before the last federal election they said my support was 0.1 of 1 per cent," Mr Palmer said. "I had all these stupid interviews with journalists saying how badly we're going, and then I won 50.3 per cent of the seat of Fairfax and I got the balance of power in Australia. "We've got around 50 candidates standing in every region of the state. "I think we'll achieve the balance of power in Queensland and stand as the last centurion of the gates to protect the sale of our schools and hospitals. "And we would hold the balance of power because both parties want to sell the state's assets. Anna Bligh tried to do it. "That's why Campbell Newman got elected and now Campbell Newman is trying to do it." Independent senator Jacqui Lambie, who quit the PUP last year, said she did not think the party would do very well in the state election. "Unfortunately for Clive he still hasn't learnt his lesson from when he ran for the state election down here," she said. "You cannot get runners up four weeks before the election. "Those runners - he knew there was a state election coming out, he should have had their faces out there, he should have been able to give the candidates half a chance." Palmer denies candidates dominated by friends, family Meanwhile, Mr Palmer said it was wrong to suggest PUP candidates were dominated by his friends and employees. The former Queensland leader of PUP, Alex Douglas, quit last year because he said Mr Palmer had been endorsing friends and relatives to run in the state election. The wife of PUP senator Glenn Lazarus, Tess Lazarus, is running for the PUP in the seat of Buderim. Mr Palmer said there were two candidates who were either a relative or close friend of his. "There's never been more than a couple, so it's just been a media beat-up to be honest with you and it's just designed to make us think we're a party that hasn't got anyone but my friends, which is just bullshit," he said. Mr Palmer also denied his party's election campaign had been affected by trusted media adviser Andrew Crook being charged over the unlawful detention and coercion of a National Australia Bank executive. Mr Newman was scheduled to campaign in North Queensland on Wednesday and was expected to announce funding to help the construction of a new sports stadium in Townsville. Ms Palaszczuk, meanwhile, was in Cairns in the state's far north for the second time in a week. Topics: elections, political-parties, clive-palmer, qld, buderim-4556, maroochydore-4558 First posted
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Problem gambling is a risky behavior that when engaged in with problem drinking and eating disorders can potentially multiply its detrimental effects on individuals. The associations between the three behaviors remain unclear, although some studies, predominantly among university students, have theorized possible commonalties. For instance, a study conducted with a sample of 246 psychology students found that urgency (no specification whether negative or positive) is the impulsivity-related construct that best predicts alcohol drinking, gambling, and binge eating behavior (Fischer and Smith [@CR15]). Another study with 301 university students showed that problematic gambling and drinking behaviors among students had great similarities, but failed to find any significant underlying cause with eating problems (Hodgins et al. [@CR24]). Also within a higher education context, another study reported that problem student gamblers were more likely to be heavy drinkers than non-problem gamblers (Engwall et al. [@CR12]), an association also identified in nationally representative samples among adolescents in the USA (Barnes et al. [@CR1]). In fact, there is a large literature on the relationship between alcohol and gambling (see Bohaine et al. \[[@CR3]\] for a review) but not in relation to their association in advertisements (also referred to as "adverts" or "commercials"). At a pathological level, problem gambling is more common among individuals with alcohol use disorder (Grant et al. [@CR17]). Gambling and eating disorders rarely occur simultaneously, although lifetime prevalence of gambling disorder is slightly higher among people with eating disorder (Jiménez-Murcia et al. [@CR25]). However, among individuals with eating disorders underlined by impulse control disorders, such as those with bulimia nervosa, co-morbidity rates with pathological gambling are higher, ranging from 16 to 23% (Jiménez-Murcia et al. [@CR25]), suggesting that purging/binge type of eating and gambling problems might have common environmental and biological risk factors (Claes et al. [@CR5]). Moving away from the biopsychological underpinnings of gambling interaction with alcohol drinking and eating, other factors also contribute to the association of gambling with similarly risky behaviors. Situational factors (Griffiths [@CR19]) help explain why different environmental settings can affect differently otherwise similar individuals. For instance, comparative studies in Finland and France have shown that the symbolic understanding of problem gambling, alcohol drinking, and eating varies, influencing the way social workers in each country conceptualize each behavior and seek for a solution to those problems (Egerer [@CR10]). One of the most prominent situational factors is arguably advertising and marketing. The present paper examines sports betting adverts to explore the association of gambling behavior with alcohol drinking and low nutritional value food (LNVF) eating (i.e., eating "junk food"). The study complements the paradigm of individually motivated risky behavior by focusing on the effects that media representation of behavior---by means of repeated patterns of characters, situations, and/or actions in adverts---might have on the imitation and normalization of gambling behavior. Here, the underlying assumption is that sports betting advertising depicts specific gambling behaviors, sometimes in conjunction with LNVF eating and alcohol drinking, creating a symbolic understanding of what gambling on sports means (Lopez-Gonzalez and Griffiths [@CR32]). This is especially relevant for new products, such as online sports betting, which over the last few years has been legalized in many European jurisdictions (European Commission [@CR14]). New products entail new behavioral patterns that advertisers hope consumers will adopt. Furthermore, advertising plays a major role in communicating socially acceptable ways of consuming such products, as has been noted in prior alcohol and food advertising research (Castonguay et al. [@CR4]; Engels et al. [@CR11]; Mathios et al. [@CR35]). The available evidence on the interaction of alcohol drinking and LNVF eating in gambling advertising is scarce. Maher and colleagues have argued that sport sponsorship has become a prominent marketing tool for alcohol, gambling, and LNVF. The playing of sport conveys positive healthy connotations to products that pose risks to health (Maher et al. [@CR34]). By specific products (such as alcohol-based drinks, LNVF, and gambling games) associating their brand with sports, companies obscure the risk components of their products, aligning them with the beneficial attributes of physical exercise (McDaniel and Heald [@CR36]). Additionally, gambling venues have been categorized as meeting places where gamblers eat and drink to celebrate their team's losses and wins (Dyall et al. [@CR9]). A major concern regarding sports-related marketing of gambling, alcohol, and LNVF is the attraction of children to sport content (Lopez-Gonzalez et al. [@CR33]; Kelly et al. [@CR26]). Although minors are typically protected from viewing gambling adverts (such as screening them on television only after the 9pm), many jurisdictions specifically permit betting promotions during sport events, even if these events are broadcast before 9 pm (Lopez-Gonzalez and Griffiths [@CR31]). Research investigating three televised sporting events in Australia in 2012 found that spectators were exposed to gambling, alcohol, or LNVF products for about two thirds of the overall broadcast time, resulting in 4062 episodes of alcohol marketing, 322 for gambling, and 51 for LNVF, including different marketing forms such as match commentary, banners, shirt sponsors, adverts, and on-screen messages (Lindsay et al. [@CR30]). Interviews with children aged 10--14 years have shown that they are more likely to recall food than non-food sponsors of sport teams, while children aged 10--11 years thought it was important to buy food or beverages from sport sponsors to "return the favor" (Kelly et al. [@CR27]). In experiments with 85 children aged 5--12 years, one study found that the most liked teams were associated in children's minds to junk food products, and that continued exposure to gambling, and that food and drink adverts fostered connections between consuming those products and sport (Bestman et al. [@CR2]). Although some sport codes prohibit the depiction of alcohol drinking in adverts, past research has demonstrated that fans can associate drinking with sport even when characters in the adverts are not shown physically drinking, due to the depiction of scenarios or situations that evoke alcohol drinking in their minds (Zwarun and Farrar [@CR42]). Also, drinking alcohol is usually represented as being associated with friendship and camaraderie (Zwarun and Farrar [@CR42]), an association that mirrors that of gambling adverts (Deans et al. [@CR7]; Hing et al. [@CR23]; Sproston et al. [@CR38]). Building on these findings, two exploratory research questions (RQs) were proposed in the present paper to understand how sports betting advertising represents bettors' behavior. RQ1: How is eating LNVF and drinking alcohol in sports betting adverts represented in sport culture. In particular, this question seeks to explore whether sports betting adverts present gambling, eating LNVQ, and drinking alcohol in association with emotionally charged situations, such as watching live sport. RQ2: How is drinking alcohol and eating LNVF portrayed in sports betting adverts in relation to friendship building. Method {#Sec1} ====== Sample {#Sec2} ------ Sports betting television adverts (*N* = 135) were sampled from a larger cross-sectional study. Advertisements with an upload date from June 2014 to November 2016 were downloaded from the official *YouTube* channels of 29 different betting brands. These brands were primarily selected based on their presence as sponsors, official partners, or regular advertisers in sport events. All adverts met the following inclusion criteria: (i) only those advertising soccer were included, thus excluding horse and dog racing as well as other sports whose popularity is more country-specific; (ii) only advertisements from Spain and the UK were selected because these were the two languages that the authors could understand as native speakers, and the representativeness of La Liga and Premier League competitions in European soccer (first and third, respectively, in Union of European Football Associations \[UEFA\] ranking); (iii) the advertisements belonged to companies with a legal license to operate in one or both of the countries analyzed; (iv) the adverts had to have a televisual and temporal format (between 20 and 60 s duration). This latter inclusion criterion excluded made-for-internet promotions that typically allow informal shooting or discussion-like videos including tipsters sponsoring a brand. Also, longer advertisements were excluded because they were unlikely to have been shown on television; and (v) for the purpose of assessing new behavioral patterns attached to new products, the advertisements had to focus on online sports betting, excluding those addressing offline betting. Further details of the adverts analyzed can be obtained from the first author on demand. To check if the *YouTube* sample corresponded to the actual adverts shown on television, an additional sample of nine UEFA Champions League, English Premier League, and Spanish La Liga soccer matches (including pre- and post-match advert breaks) was recorded from May to June 2016. The results confirmed that every television advertisement was made accessible, sometimes with a few weeks' delay, via the operator's *YouTube* profile. Also, the electronic banners around the soccer field were analyzed to make sure no betting brand being promoted was excluded from the study sample. Procedure {#Sec3} --------- The initial analysis was conducted by three coders. Coder 1 rated the whole sample of advertisements. For reliability purposes, a sub-sample composed 23 adverts (17.03%) was randomly generated and coded independently by coders 2 and 3. Interrater reliability was calculated using ReCal3 software, which is especially designed for situations with three or more coders analyzing nominal data wherein Cronbach's alpha is not useful. In the present study, a solid interrater reliability was found. Krippendorff's alpha coefficients ranged from 0.78 to 1, with all except one variable punctuating below the 0.80 cut-off point generally recommended for acceptable reliability, but enough for exploratory analysis (Krippendorff [@CR28]). Given the exploratory nature of the study, a mixed-methods approach was favored by the researchers for the second round of analysis. Thus, once the betting adverts portraying alcohol and LNVF consumption were identified, coder 1 conducted additional qualitative coding on them to deepen the exploratory questions that guided the initial analysis. The definition of LNVF included snacks (e.g., crisps, popcorn, etc.), sugary drinks, pizza, hamburgers, and French fries. To assess the association between alcohol and LNVF with sports culture (RQ1), characters in the adverts consuming alcohol or LNVF were hypothesized to be associated with (1) having a sentimental bond with sport (e.g., team loyalty); (2) being depicted as in an emotional state; (3) appearing celebrating a goal; (4) betting while viewing sport (i.e., in-play betting); (5) being offered by the advert free bets, money back, or similar promotions; and (6) showing satisfaction from the outcome of a bet or a game. To explore RQ2, namely the association between unhealthy food and alcohol with friendship building, variables 1 to 6 were hypothesized to vary depending on the number of characters in adverts portrayed drinking alcohol; and similarly on the number of characters in adverts portrayed eating LNVF. Additionally, adverts were analyzed in terms of (7) the type of drink consumed, under the assumption that drinking beer (e.g., lager, cider) will be more likely to occur in group settings in contrast to drinking wine or spirits. Chi-square tests were performed between the variables outlined above using IBM SPSS 23 for Mac. Fisher's exact test (one-sided) was used when the distribution expected cell counts were below 5. Considering the exploratory purpose of the study, and given the scarcity of scientific literature in the field and the mixed-methods approach, a threshold *p* value lower than 0.05 was accepted as statistically significant without controlling for multiple comparisons error. Results {#Sec4} ======= Initial analysis of the 135 adverts identified 36 betting adverts depicting LNVF consumption (26.7%), and 30 betting adverts depicting alcohol consumption (22.2%). The incidence of simultaneous alcohol drinking and LNVF eating was relatively low, comprising only 11 adverts (8.14%). LNVF eating behavior showed little association with any of the variables analyzed. Sentimental identification with the team, emotionally charged scenes, in-play betting situations, and free bet promotions, had no statistically significant association with LNVF eating behavior. Only two variables were suggestive of an association. More specifically, (i) LNVF eating was associated with the characters in the advert celebrating a goal (*χ* ^2^\[2, *N* = 36\] = 6.401, *p* \< .041); and (ii) the number of characters in the advert eating LNVF was associated with showing satisfaction to what could be implied as a satisfactory game or bet outcome (*χ* ^2^\[6, *N* = 36\] = 16.107, *p* \< .013). In contrast, alcohol drinking showed several associations with sports betting behavior. The presence of alcohol in the advert co-occurred with (i) the appearance of characters with a sentimental bond (*χ* ^2^\[1, *N* = 135\] = 5.310, *p* \< .026); (ii) the characters in the advert watching live sport while betting (i.e., in-play betting) (*χ* ^2^\[1, *N* = 135\] = 6.199, *p* \< .011); (iii) any of the characters celebrating a goal (i.e., only fans, excluding those characters playing the part of a footballer) (*χ* ^2^\[1, *N* = 135\] = 3.978, *p* \< .042); and (iv) the character showing satisfaction for what appears to be the outcome of a bet or a game (*χ* ^2^\[2, *N* = 135\] = 6.603, *p* \< .033). The provision of free bets (or other similar promotions) and how emotionally charged the main character appeared to be did not yield any statistically significant relationship with alcohol drinking behavior. Further analysis showed that a higher number of characters in the adverts that depicted alcohol drinking was associated with (i) the main character being more emotionally involved (*χ* ^2^\[3, *N* = 30\] = 19.566, *p* \< .001); (ii) the characters celebrating a goal (*χ* ^2^\[2, *N* = 30\] = 6.589, *p* \< .037); (iii) the characters watching live sport while betting (*χ* ^2^\[3, *N* = 30\] = 9.830, *p* \< .020); and (iv) the advert offering free bets (*χ* ^2^\[3, *N* = 30\] = 9.037, *p* \< .029); and (5) drinking beer (*χ* ^2^\[3, *N* = 30\] = 13.083, *p* \< .004). The number of characters drinking was not statistically associated with the (i) appearance of characters with a sentimental bond, or (ii) showing of satisfaction due to bet or game outcome. Alcohol type was further analyzed, binary coding whether the adverts portrayed beer drinking (e.g., lager, cider) as opposed to wine/spirits drinking. Those adverts with characters drinking beer were associated with (i) a higher number of overall characters in the advert (*χ* ^2^\[3, *N* = 30\] = 13.083, *p* \< .004); (ii) free money offers (*χ* ^2^\[1, *N* = 30\] = 4.751, *p* \< .043); and (iii) characters celebrating a goal (*χ* ^2^\[1, *N* = 30\] = 9.455, *p* \< .003). Contrary to what was hypothesized, in-play betting, emotional involvement of the main character, and sentimental identification were not statistically associated with beer drinking. However, among the 11 adverts showing both alcohol and LNVF consumption, drinking beer was not only associated with eating LNVF (*χ* ^2^\[1, *N* = 11\] = 5.687, *p* \< .020), but also with a higher number of characters eating LNVF in the advert (*χ* ^2^\[2, *N* = 11\] = 11.000, *p* \< .004). Among the 11 adverts showing wine/spirits drinking, only one (9.09%) also depicted LNVF consumption, whereas among the 19 adverts with characters drinking beer, 10 also consumed LNVF (52.63%). Discussion {#Sec5} ========== The present study provides a preliminary and tentative understanding of how sports betting adverts depict gambling in interaction with eating and drinking behavior. Approximately one-quarter of the analyzed sample depicted alcohol (22.2%) and LNVF (26.7%) consumption. However, when combined, 55 out of 135 adverts (40.7%) depicted at least one of the two behaviors. Gambling, like consuming LNVF and alcohol, is largely considered a risky product whose marketing and advertising must be limited (Hing et al. [@CR20], [@CR21], [@CR22]). Characters in gambling narratives, as seen in the adverts sampled, can help to create a representational atmosphere of normality regarding the simultaneous use of two or more of such potentially risky products. Also, the transmission of such adverts does not happen in isolation. On the contrary, they add to existing alcohol and food products, which are also heavily advertised in the context of sport events (Bestman et al. [@CR2]; Lamont et al. [@CR29]; Sproston et al. [@CR38]; Thomas et al. [@CR40]). Under the assumptions for RQ1, alcohol drinking was hypothesized to be associated with sports culture. The analyses showed that betting adverts portraying alcohol consumption, as opposed to those without alcohol, showed (i) more frequently sentimental bonds between characters and sport; (ii) more frequent betting while watching a live game; (iii) more goal celebrations; and (iv) in general, characters demonstrating greater satisfaction for the outcome of the games or bets. These activities were examined in order to explore the representation of bettors' behavior in emotionally charged situations. Sport is far from being an emotionally neutral content, and often entails identity and belonging aspects (Giulianotti et al. [@CR16]; Wenner [@CR41]). Thus, betting advertising appears to capitalize on such sentiments arising from sports culture and aligns them with betting culture, corroborating recent research on the field (Deans et al. [@CR6], [@CR8]). In addition, emotionally charged situations such as betting while viewing a game or celebrating a goal are arguably more likely to be associated with instant decision-making and urgency, potentially harming those with impulse control disorders (Hodgins et al. [@CR24]). Obviously, the advertising and marketing industry is a manufacturer of happy-ending stories, and as such, gambling, eating, and drinking are unlikely to be portrayed in a context of excessive or disordered consumption. However, against a gambling backdrop, the simultaneous representation of emotional situations and alcohol consumption, even moderate, could also encourage disinhibition. Friendship building was also hypothesized in relation to the number of characters drinking alcohol in the adverts, as proposed in RQ2. Simply put, those adverts that depicted alcohol drinking featured (on average) more characters in their narratives than those adverts with no alcohol drinking. Solitary gambling, similar to solitary alcohol drinking, exposes individuals to greater risks of developing problems (Griffiths [@CR18]). However, studies have raised concerns regarding the misconception that drinking, especially beer, when done socially cannot be harmful (Strate [@CR39]), reminiscent of the bettors' idea that gambling in group is *safer,* as expressed in previous qualitative research (e.g., Deans et al. [@CR7]). In this context, betting with friends might also add to the security component of offers such as guaranteed money back or free bet coupons, explaining why they are more likely to be offered in such circumstances. Bonding with peers has been previously been proposed as a major component of gambling advertising, both in sports (Lindsay et al. [@CR30]) as well as in other forms of gambling (McMullan and Miller [@CR37]). Prototypical betting advertising representations continue to portray betting and sport viewing as a communal experience, an image that appears to be more aspirational than realistic considering that the majority of people consume sport alone (ESPN [@CR13]). Group behavior, contrary to the idea implied in betting adverts sampled in the present study, could facilitate the feedback and normalization of a vicious circle of risky behaviors, as suggested by the fact that adverts with more characters drinking also were more likely associated with LNVF eating. The relatively small sample of adverts analyzed cannot be ignored when acknowledging the limitations of the study. The data here can only be interpreted as a preliminary and tentative examination of the simultaneous presence of gambling, alcohol, and LNVF in social representations that have the capacity to affect bettors' behavior, particularly those more vulnerable such as problem gamblers and minors. Future research will need to evaluate whether new forms of advertising are having an impact on the co-occurrence of these three behaviors. Conclusion {#Sec6} ========== To the authors' knowledge, this is the first research study that has explored the interaction of drinking alcohol and eating unhealthy food in gambling adverts. It is argued that situational factors such as the advertising and marketing of gambling can help to shape betting behavior, by means of depicting specific scenarios and actions, while ignoring others, that show characters drinking alcohol and betting, and less frequently, eating unhealthy food. It has been further argued that drinking alcohol is typically shown in betting adverts in clear association with sports culture and gambling. Similarly, betting advertising might be resorting to characters drinking alcohol, largely beer, to enhance the message of friendship bonding that appears to be inherently associated with the enjoyment of sport. Media and advertising regulators (as well as policymakers more generally) should be cognizant and react to the symbolic linkage of independent risky behaviors, particularly in contexts of enhanced emotions and impulses, such as popular sports, and considering the appeal of such content to children. Conflict of Interest {#FPar1} ==================== Hibai Lopez-Gonzalez, Ana Estévez, Susana Jiménenez-Murcia, and Mark D. Griffiths declare that they have no conflict of interest. Mark D. Griffiths declares that he has received funding for a number of research projects in the area of gambling education for young people, social responsibility in gambling and gambling treatment from the Responsibility in Gambling Trust, a charitable body which funds its research program based on donations from the gambling industry. He also undertakes consultancy for various gaming companies in the area of social responsibility in gambling. Funding Information {#FPar2} =================== This work was supported by the Government of the Basque Country, Spain, under grant reference (Eusko Jaurlaritza, POS_2015_1\_0062).
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Share this: After months of speculation culminating in several weeks of deliberaterumor-stoking, the wait is over. Congressman Dave Reichert (WA-8) will not run for Washington state governor… again. In a statement released Friday, Reichert expressed concern for the state under current Democratic Gov. Jay Inslee’s leadership, but said he believes he can best serve the people by seeking re-election to represent Washington’s 8th Congressional District. Reichert wrote: Like so many of you, I have been extremely disappointed in the decisions coming out of the Governor’s Office — regarding our schools, the health of our children, and most recently a decision to give the Green River serial killer a chance to enjoy life in a nicer prison. We deserve better. Yet, I believe I can better serve you now, today, in another Washington where politicians are more interested in fighting each other than fighting for America; where leadership has been in retreat, and courage has been on recess. The fifth-term congressman and former King County Sheriff’s displeasure with Inslee’s performance seems to be shared by voters. The governor’s job approval rating in some non-published polls is soft — hovering in the mid-40s — and the most recent Elway Poll finding that only 30 percent of voters would definitely vote to give the governor a second term each indicate weakness. Reichert’s decision to remove his name from consideration leaves Republican candidate for governor and Seattle Port Commissioner Bill Bryant with an open field to run in toward the primary, at least for now. (The absence of any mention of Bryant in Reichert’s statement was noticed by some Republican insiders.) Seattle Port Commissioner and candidate for governor Bill Bryant Bryant knew his cue and quickly blasted an email to supporters complimenting Reichert for his public service and sending the signal that his campaign was shifting into a higher gear. Bryant wrote: My campaign for governor of Washington State now moves into a new phase; a phase focused on the challenges confronting our kids, teachers & classrooms, on the challenges confronting communities across Washington that need family wage jobs, and on the challenges facing the Puget Sound and the salmon runs that are part of our history, culture and economy. Our campaign needs to make some noise, offer the people an alternative leadership style, one that not only articulates a vision, but that is capable of building coalitions that gets stuff done. State Republican Party Chairwoman Susan Hutchison issued her own statement giving praise to both Reicher and Bryant. Hutchison wrote: Congressman Reichert has an exemplary record of public service, and the people of his district, Washington State, and the country will be well served by him focusing on his current role. Republican Bill Bryant is running a strong campaign for Governor, meeting voters across the state and building support to replace the Governor who can’t govern, Jay Inslee. The relatively minimal statements of Hutchison, Reichert and Bryant marked an important plot point in a story stretching back nearly three years. Chatter among Republicans as to who could beat Inslee in 2016 began not long after Election Night 2012. Conversations took place at conferences, in coffee shops and among groups gathering through social media, but along the GOP grapevine Bryant’s name wasn’t registering in those early discussions as the top-tier choice of Republicans. Reichert, however, was mentioned often as an A-list option, a candidate with considerable name identification and a persona that matched up against Inslee’s protector archetype. In certain circles, prospects for a run by state Senator Andy Hill (R-Redmond) generated proportional excitement, originating largely from his calm leadership under fire during budget battles in Olympia and his record of winning in part of King County. Meanwhile, Bryant went to work to build and strengthen his reach across Washington, crisscrossing the state and subjecting himself to the rigors of rubber chicken dinners at Lincoln Day events in nearly every county. He recruited grassroots activists into his campaign and racked up a significant list of endorsements including leading state legislators from both sides of the Cascades, port commissioners, as well former Gov. Dan Evans and former U.S. Sen. Slade Gorton. Since launching his official campaign this May, Bryant has also drawn financial support, raising more than $575,000 in the doldrums of the 2nd and 3rd quarters of this year. [Bryant’s accumulated campaign finances may have been one factor in Reichert’s decision. Reichert’s federal campaign coffers hold just over $607,000 as of Sept. 30, which would put him slightly ahead of Bryant in the fundraising contest, but the procedure for sweeping those monies over for use in a state race is tedious and could reduce the total available. (See “Inslee Discloses Details of Disputed $200K Transfer from Fed Account, Several Donors Over the Max,” Northwest Daily Marker, 9/3/11.)] Bryant still has a lot of work to do to catch up to Inslee in fundraising. Even contending with several financing blackouts during regular legislative sessions, overtimes and triple overtimes, Inslee has amassed almost $2.4 million, though it’s worth noting that $320,000 of Inslee’s contributions in 2015 came as transfers from the state Democratic machine. Without those as early and necessary cash transfusions, Inslee’s fundraising edge in 2015 narrows to less than $280,000. Not a photo finish, for sure, but neither is it a runaway for the incumbent. Nevertheless, Team Bryant’s early totals are a respectable ante to play in the contest ahead. As an incumbent holding statewide office, Inslee’s name identification is high and Bryant’s is relatively low; closing the gap will require more than just the candidate’s shoe leather and an army of enthusiastic volunteers. The question of exactly how much money Bryant will need to raise depends largely on whether he remains the only candidate drawing on Republican and conservative votes in the primary. On the conservative right, there has been very little buzz about potential entrants into the primary who might appeal to voters whose tastes tend more toward Clint Didier, leaving some wondering if a challenge to Bryant from the right could still emerge late in the race. Share this: Related Bryan has been writing about local and national politics since 2008. In addition to writing for The Northwest Daily Marker (nwdailymarker.com) – the digital journal of politics he launched in 2011 – he has been published by American Thinker, Crosscut, Red State and the Everett Herald and explosive stories broken by The Northwest Daily Marker have generated headlines in regional, national and international major media. Bryan is a lifelong Washingtonian and a proud University of Washington alumnus.
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--- abstract: 'Many meson processes are related to the $U_A(1)$ axial anomaly, present in the Feynman graphs where fermion loops connect axial vertices with vector vertices. However, the coupling of pseudoscalar mesons to quarks does not have to be formulated via axial vertices. The pseudoscalar coupling is also possible, and this approach is especially natural on the level of the quark substructure of hadrons. In this paper we point out the advantages of calculating these processes using (instead of the anomalous graphs) the Feynman graphs where axial vertices are replaced by pseudoscalar vertices. We elaborate especially the case of the processes related to the Abelian axial anomaly of QED, but we speculate that it seems possible that effects of the non-Abelian axial anomaly of QCD can be accounted for in an analogous way.' address: - | Rudjer Bošković Institute, P.O.B. 180, 10002 Zagreb, Croatia\ [email protected] - | Physics Department, Faculty of Science, University of Zagreb\ P.O.B. 331, 10002 Zagreb, Croatia\ [email protected] - | Physics Department, University of Arizona\ Tucson Az 85721 USA\ [email protected] author: - DALIBOR KEKEZ - 'DUBRAVKO KLABUČAR[^1]' - 'M. D. SCADRON' title: BYPASSING THE AXIAL ANOMALIES --- Introduction ============ Numerous processes in meson physics are related to the Adler-Bell-Jackiw (ABJ) axial anomaly [@Adler69; @BellJackiw69] appearing in the fermion loops connecting certain number of axial (A) and vector (V) vertices. Concretely, in this paper we will deal with the processes related to the AVV (“triangle", Fig. \[fig:triangle\]) and VAAA (“box", Fig. \[fig:box\]) anomaly, exemplified by the famous $\pi^0 \to \gamma\gamma$ and $\gamma \to \pi^+ \pi^0 \pi^-$ transitions. ![The triangle graph and its crossed graph relevant for the interaction of the neutral pseudoscalar meson of momentum $P$ with two photons of momenta $k$ and $k^\prime$. The quark-photon coupling is in general given by dressed vector vertices $\Gamma_\mu(q_1,q_2)$, which in the free limit reduce to $e {\cal Q} \gamma_\mu$.[]{data-label="fig:triangle"}](triangle.eps){height="40mm"} ![One of the box diagrams for the process $\gamma \to \pi^+ \pi^0 \pi^-$, studied by the pseudoscalar coupling method in, e.g., Refs. 3, 4. There are six different contributing graphs, obtained from the above graph by the permutations of the vertices of the three different pions. The position of the $u$ and $d$ quark flavors on the internal lines, as well as $Q_u$ or $Q_d$ quark charges in the quark-photon vertex, varies from graph to graph, depending on the position of the quark-pion vertices. The physical pion fields are $\pi^\pm=(\pi_1\mp i \pi_2)/\sqrt{2}$ and $\pi^0\equiv\pi_3$. The momenta flowing through the four sections of the quark loop are conveniently given by various combinations of the symbols $\alpha, \beta, \gamma = +, 0, -$ in $k_{\alpha\beta\gamma} \equiv k + \alpha p_{1} + \beta p_{2} + \gamma p_{3}$.[]{data-label="fig:box"}](box.eps){height="40mm"} Suppose one wants to describe such processes using QCD-related effective chiral meson Lagrangians [@seeGeorgi; @Georgi:1985kw] without adding ad hoc interactions of mesons with external gauge fields to reproduce empirical results. For example, one can add by hand $$\Delta {\cal L} = g_{\pi\gamma\gamma} \pi^0 \epsilon_{\mu\nu\rho\sigma} F^{\mu\nu} F^{\rho\sigma} \, , \label{L_pi2gamma}$$ and this would reproduce the observed $\pi^0 \to \gamma\gamma$ width for the favorable value of the $\pi^0\gamma\gamma$ coupling $g_{\pi\gamma\gamma}$. However, if one does not want to add such ad hoc terms in the effective meson Lagrangians, one must describe such “anomalous” processes through the term derived by Wess and Zumino [@WZ]. On the other hand, if one wants to utilize and explicitly take into account the fact that mesons are composed of quarks, another way of describing these processes is optimal in our opinion, and the main purpose of this paper is to stress and elucidate this. Axial vertices in the anomalous graphs such as the AVV and VAAA ones, couple the quarks with pseudoscalar mesons. Instead of anomalous graphs, another way to study the related amplitudes involving pseudoscalar mesons, is to calculate the corresponding graphs where axial vertices (A) are replaced by pseudoscalar (P) ones. Thereby, for example, the $\pi^0 \to \gamma\gamma$ decay amplitude due to the AVV “triangle anomaly", $$F_{m_\pi=0}(\pi^0\to 2\gamma) = \frac{e^2 N_c}{12\pi^2f_\pi}~, \label{pi2gammaAmp}$$ is reproduced by the calculation of the PVV triangle graph. \[Eq. (\[pi2gammaAmp\]) pertains to the chiral limit, where the pion mass $m_\pi=0$. Also, $f_\pi\approx 93~{\mbox{\rm MeV}}$ is the pion decay constant, $e$ is the proton charge, and $N_c=3$ is the number of quark colors.\] The PVV triangle graph calculation of Eq. (\[pi2gammaAmp\]) can most simply be done essentially [*[\` a]{} la*]{} Steinberger [@S49], that is, with a loop of “free” constituent quarks with the point pseudoscalar coupling (i.e., $g \gamma_5$, where $g = constant$) to quasi-elementary pion fields. However, since the development of the Dyson-Schwinger (DS) approach to quark-hadron physics [@Alkofer:2000wg; @Maris:2003vk], the presently advocated method becomes even more convincing. Namely, the DS approach clearly shows how the light pseudoscalar mesons simultaneously appear both as quark-antiquark ($q\bar q$) bound states and as Goldstone bosons of the dynamical chiral symmetry breaking (D$\chi$SB) of nonperturbative QCD. The solutions of Bethe-Salpeter (BS) equations for the bound-state vertices of pseudoscalar mesons then enter in the PVV triangle graph instead of the point $g \gamma_5$ coupling, and the current algebra result (\[pi2gammaAmp\]) is again reproduced exactly and analytically, which is unique among the bound-state approaches. That the (almost massless) pseudoscalars are (quasi-)Goldstone bosons, is also a unique feature among the bound-state approaches to mesons. A reason why the P-coupling method is simpler both technically and conceptually is that the PVV triangle graph amplitude is [*finite*]{}, unlike the AVV one, which is divergent and therefore also ambiguous with respect to the momentum routing. Reference gives a more detailed discussion of the P-coupling method and why is that it is equivalent to the anomaly calculations, and illustrates this on the examples of the famous decay $\pi^0 \to \gamma \gamma$ and processes of the type $\gamma \to \pi^+ \pi^0 \pi^-$. Also, the PVV quark triangle amplitude leads to many (over 15) decay amplitudes in agreement with data to within 3% and not involving free parameters [@Delbourgo; @Delbourgo:1993dk; @Bramon:1997gg]. This will be elaborated in more detail in Sec. \[manyProc\]. Additional advantages of this method is that its treatment of the $\eta$-$\eta'$ complex and resolution of the $\rm U_A(1)$ problem, goes well with the absence of axions (which were predicted to solve the strong CP problem but have [*not*]{} yet been observed [@PDG2004]) and with the arguments of Ref. , that there is really no strong CP problem. All this will be discussed in Sec. \[sec:CommRelToGlounAnom\]. We state our conclusions in Sec. \[sec:summary\]. Processes Going Through the Quark Triangle {#manyProc} ========================================== In this section we calculate the amplitudes for a number of processes using the quark triangle graphs. Figures \[fig:triangle\] and \[fig:PVVdiagrams\] show three such PVV processes. First we consider $\pi^0\to \gamma\gamma$ decay via the $u$ and $d$ quark triangle graph for $\pi^0=(\bar{u}u-\bar{d}d)/\sqrt{2}$, $N_c=3$ and Goldberger-Trieman relation leading to the pion decay constant: $f_\pi=\hat{m}/g_{\pi qq}$. This amplitude is finite and for the experimental value of the pion decay constant, $f_\pi = (92.42\pm 0.26) \, {\mbox{\rm MeV}}$ [@PDG2004], gives [@Delbourgo] the chiral-limit amplitude (\[pi2gammaAmp\]) of magnitude ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ![Two examples of the PVV triangle graphs where just one of the vector vertices couples to a photon, whereas the other couples to a vector meson. These two graphs describe the decays of $\omega$ and $\rho$ mesons into a photon and a pion.[]{data-label="fig:PVVdiagrams"}](OmegaToPi0Gamma.eps "fig:"){height="26mm"} ![Two examples of the PVV triangle graphs where just one of the vector vertices couples to a photon, whereas the other couples to a vector meson. These two graphs describe the decays of $\omega$ and $\rho$ mesons into a photon and a pion.[]{data-label="fig:PVVdiagrams"}](RhoToPi0Gamma.eps "fig:"){height="26mm"} ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- $$|F_{m_\pi=0}(\pi^0\to 2\gamma)| = \frac{e^2}{4\pi^2 f_\pi}=0.0251~{\mbox{\rm GeV}}^{-1}$$ very close to experimental data [@PDG2004] $$|F_{\rm exp}(\pi^0\to 2\gamma)| = \left[\frac{64\pi\Gamma(\pi^0\to\gamma\gamma)}{m_\pi^3}\right]^{1/2} = (0.0252\pm 0.0009)~{\mbox{\rm GeV}}^{-1}~.$$ Likewise, the $u$, $d$ quark triangles for $\rho\to\pi\gamma$ decay give [@Delbourgo] $$|F(\rho\to\pi\gamma)|=\frac{e g_\rho}{8\pi^2 f_\pi} = 0.206~{\mbox{\rm GeV}}^{-1}$$ for $g_\rho=4.965\pm 0.002$ found from $\rho^0\to e^-e^+$ decay [@PDG2004]: $$\Gamma(\rho^0\to e^-e^+) = \frac{e^4 m_\rho}{12\pi g_\rho^2} = (7.02\pm 0.11)~{\mbox{\rm keV}}~.$$ The calculated $|F(\rho\to\pi\gamma)|$ is also near data [@PDG2004], $$|F_{\rm exp}(\rho\to\pi\gamma)| = \left[\frac{12\pi\Gamma(\rho\to\pi\gamma)}{q^3}\right]^{1/2} =(0.225\pm 0.011)~{\mbox{\rm GeV}}^{-1}~,$$ where $q=(m_\rho^2-m_\pi^2)/(2m_\rho)$ is the photon momentum. \[Actually, the above value is a weighted average of $F_{\rm exp}(\rho^0\to\pi^0\gamma)$ and $F_{\rm exp}(\rho^\pm\to\pi^\pm\gamma)$ amplitudes.\] Next we predict the $u$, $d$ quark triangle amplitude for $\omega\to\pi\gamma$ taking $\omega$ as 99% nonstrange [@PDG2004] ($\cos^2\phi_V \approx 0.99$) $$|F(\omega\to\pi\gamma)| = \frac{\cos\phi_V\, e\, g_\omega}{8\pi^2 f_\pi} = 0.705~{\mbox{\rm GeV}}^{-1} \label{FOmegaToPi0Gamma}$$ for $g_\omega=17.06\pm 0.28$ found from $\omega\to e^-e^+$ decay. The mixing angle is[^2] $$\begin{aligned} \phi_V &=& \theta_V - \arctan(\frac{1}{\sqrt{2}}) = \arctan\sqrt{\frac{\frac{1}{3}(4 m_{K^\star}^2 - m_\rho^2) - m_\varphi^2 } {m_\omega^2-\frac{1}{3}(4 m_{K^\star}^2 - m_\rho^2) } } -\arctan(\frac{1}{\sqrt{2}}) \nonumber \\ &=& (5.208\pm 0.092)^\circ~. \label{phiV}\end{aligned}$$ Again this theory in Eq. (\[FOmegaToPi0Gamma\]) is near data $(0.722\pm 0.012)~{\mbox{\rm GeV}}^{-1}$ [@PDG2004]. Other PVV photon decays involve the $\eta$ and $\eta^\prime$ mixed non–strange and $\bar{s}s$ pseudoscalar mesons. Again the quark triangle amplitudes are a close match with data [@Delbourgo; @Delbourgo:1993dk; @Bramon:1997gg]. The quark–triangle (QT) calculation gives reliable predictions also for the $\eta$ and $\eta^\prime$ two–photon decays: $$\begin{aligned} |F(\eta\to\gamma\gamma)| = \frac{e^2}{4\pi^2 f_\pi} \frac{N_c}{9} (5 \cos\phi_P - \sqrt{2} \frac{\hat{m}}{m_s}\sin\phi_P) = 0.0255{\mbox{\rm GeV}}^{-1}~, \\ |F(\eta^\prime\to\gamma\gamma)| = \frac{e^2}{4\pi^2 f_\pi} \frac{N_c}{9} (5 \sin\phi_P + \sqrt{2} \frac{\hat{m}}{m_s}\cos\phi_P) = 0.0345~{\mbox{\rm GeV}}^{-1}~.\end{aligned}$$ This should be compared with the experimental data: $$\begin{aligned} |F_{\rm exp}(\eta\to\gamma\gamma)| = \left[\frac{64\pi\Gamma(\eta\to\gamma\gamma)}{m_\eta^3}\right]^{1/2} =(0.02498\pm 0.00064)~{\mbox{\rm GeV}}^{-1}~, \\ |F_{\rm exp}(\eta^\prime\to\gamma\gamma)| = \left[\frac{64\pi\Gamma(\eta^\prime\to\gamma\gamma)}{m_{\eta^\prime}^3}\right]^{1/2} =(0.03133\pm 0.00055)~{\mbox{\rm GeV}}^{-1}~,\end{aligned}$$ where $\Gamma(\eta\to\gamma\gamma) =(0.5108\pm 0.0268)~{\mbox{\rm keV}}$ and $\Gamma(\eta^\prime\to\gamma\gamma) =(4.29\pm 0.15)~{\mbox{\rm keV}}$. The ratio of the constituent quark masses is $m_s/m=2f_K/f_\pi-1=1.445\pm 0.024$ for $f_{\pi^\pm}=(92.4\pm 0.3)~{\mbox{\rm MeV}}$ and $f_K=(113.0\pm 1.0)~{\mbox{\rm MeV}}$ [@PDG2004]. The mixing angle is [@Jones:1979ez; @Kekez:2000aw] $$\begin{aligned} \phi_P &=& \theta_P + \arctan({\sqrt{2}}) = \arctan \sqrt{ \frac {(m_{\eta'}^2 - 2m_K^2 + m_\pi^2) (m_\eta^2 - m_\pi^2)} {(2m_K^2 - m_\pi^2 - m_\eta^2) (m_{\eta'}^2 - m_\pi^2)} } \nonumber \\ &=& (42.441\pm 0.019)^\circ~. \label{phiP}\end{aligned}$$ Next, we can calculate the $\rho^0\to\eta\gamma$ amplitude employing the quark–triangle diagram, $$|F(\rho^0\to\eta\gamma)| = \frac{e g_\rho}{8\pi^2 f_\pi} 3\cos\phi_P =0.456~{\mbox{\rm GeV}}^{-1}~.$$ Again, this is close to the experimental data, $$|F_{\rm exp}(\rho^0\to\eta\gamma)| = \left[\frac{12\pi\Gamma(\rho^0\to\eta\gamma)}{q^3}\right]^{1/2} =(0.48\pm 0.03)~{\mbox{\rm GeV}}^{-1}~,$$ where $q=(m_\rho^2-m_\eta^2)/(2m_\rho)=(194.5\pm 0.4)~{\mbox{\rm MeV}}$ is the photon momentum and $\Gamma(\rho^0\to\eta\gamma) =(45.1\pm 6.0)~{\mbox{\rm keV}}$. A similar situation is with the $\eta^\prime\to\rho\gamma$ amplitude, for which the quark–triangle calculation gives $$|F(\eta^\prime\to\rho^0\gamma)| = \frac{e g_\rho}{8\pi^2 f_\pi} 3\sin\phi_P = 0.417~{\mbox{\rm GeV}}^{-1}~.$$ The corresponding experimental value is $$|F_{\rm exp}(\eta^\prime\to\rho^0\gamma)| = \left[\frac{4\pi\Gamma(\eta^\prime\to\rho^0\gamma)}{q^3}\right]^{1/2} =(0.411\pm 0.017)~{\mbox{\rm GeV}}^{-1}~,$$ where $q=(m_{\eta^\prime}^2-m_\rho^2)/(2m_{\eta^\prime}) =(164.7\pm 0.4)~{\mbox{\rm MeV}}$ is the photon momentum and $$\Gamma(\eta^\prime\to\rho^0\gamma\,\,\,\mbox{\rm including non--resonant}\,\,\, \pi^+\pi^-\gamma) =(60.0\pm 5.0)~{\mbox{\rm keV}}$$ is the experimental decay width [@PDG2004]. The $\eta\to\pi\pi\gamma$ amplitude is $$|M^{\mbox{\rm\scriptsize VMD}}_{\eta\to\pi\pi\gamma}| = |\frac{2g_{\rho\pi\pi} M^{\mbox{\rm\scriptsize QT}}_{\rho^0\to\eta\gamma}} {m_\rho^2-s}| =9.80~{\mbox{\rm GeV}}^{-3}$$ where $s=m_\pi^2$. The $\eta\to\pi\pi\gamma$ decay width is $$\Gamma(\eta\to\pi\pi\gamma) = \frac{|M_{\eta\to\pi\pi\gamma}|^2}{(2\pi)^3} m_\eta^{7} Y_\eta =56.2~{\mbox{\rm eV}}~,$$ where $Y_\eta = 0.98\cdot 10^{-5}$ [@thew]. This is in a good agreement with the experimental value $$\Gamma(\eta\to\pi\pi\gamma) =(60.4\pm 3.6)~{\mbox{\rm eV}}~,$$ revealing that the vector meson dominance is the main effect, while the coupling through VPPP quark box loop (“contact term") contributes little. It is known that $\omega\to 3\pi$ decay is dominated by $\rho$–meson poles. The required $\omega\to\rho\pi$ amplitude can be estimated as $$|M^{\mbox{\rm\scriptsize VMD}}(\omega\to\rho\pi)| = \left(\frac{g_\rho}{e}\right) |F(\omega\to\pi^0\gamma)| \sim 12~{\mbox{\rm GeV}}^{-1}~,$$ but cannot be measured because there is no phase space for this process. The $\omega\to\rho\pi$ amplitude is more precisely defined with QL, additionally enhanced with a meson loop associated with sigma exchange [@Delbourgo:1993dk; @Bramon:1997gg; @freund-nandi-rudaz], $$|M(\omega\to\rho\pi)|_{\mbox{\rm\scriptsize QT}} = \frac{3 g_{\rho\pi\pi}^2}{8\pi^2 f_\pi} \approx 15~{\mbox{\rm GeV}}^{-1}~.$$ The scalar amplitude $M^{\mbox{\rm\scriptsize VMD}}(\omega\to 3\pi)$ is dominated by the $\rho$ meson in each of the three possible channels [@gell-mann], $$\begin{aligned} |M^{\mbox{\rm\scriptsize VMD}}(\omega\to 3\pi)| &=& 2 g_{\rho\pi\pi} |M(\omega\to\rho\pi)| \left[ \frac{1}{m_\rho^2-s} + \frac{1}{m_\rho^2-t} + \frac{1}{m_\rho^2-u} \right] \nonumber \\ &\approx& 1480~{\mbox{\rm GeV}}^{-3}~.\end{aligned}$$ Following Thew’s phase space analysis [@thew], we get $$\Gamma(\omega\to\ 3\pi) = \frac{|M^{\mbox{\rm\scriptsize VMD}}(\omega\to 3\pi)|^2}{(2\pi)^3} m_\omega^7 Y_\omega = 7.3~{\mbox{\rm MeV}}$$ where $Y_\omega = 4.57\cdot 10^{-6}$ is used. The predicted value is close to the experimental value [@PDG2004] $$\Gamma(\omega\to 3\pi) = (7.6\pm 0.1)~{\mbox{\rm MeV}}~.$$ Here we have taken $\omega$ as pure NS, although it is about 99% NS, since $\phi_V=(5.208 \pm 0.092)^\circ$ from our Eq. (\[phiV\]). In the quark–level $\sigma$–model a quark box diagram contributes to the $\omega\to 3\pi$ decay. This box diagram can be interpreted as a contact term. It is shown that the contact contribution is small by itself, but can be enlarged through the interference effect [@Lucio-Martinez:2000ea]. Using $\phi_P=(42.441\pm 0.019)^\circ$ from our Eq. (\[phiP\]), we predict the tensor $T\to PP$ branching ratios for $a_2(1320)$: $$\begin{aligned} \begin{array}{ll} \mbox{\rm BR}(\frac{\textstyle{a_2\to\eta\pi}}{\textstyle{a_2\to K\bar{K}}}) =\left(\frac{\textstyle{p_{\eta\pi}}}{\textstyle{p_{K}}}\right)^5 2 \cos^2\phi_P=2.996 & (\mbox{\rm data}\,\,\,\, 2.96\pm 0.54)~, \\ \mbox{\rm BR}(\frac{\textstyle{a_2\to\eta^\prime\pi}} {\textstyle{a_2\to K\bar{K}}}) =\left(\frac{\textstyle{p_{\eta^\prime\pi}}}{\textstyle{p_{K}}}\right)^5 2 \sin^2\phi_P=0.1113 & (\mbox{\rm data}\,\,\,\, 0.108\pm 0.025)~, \\ \mbox{\rm BR}(\frac{\textstyle{a_2\to\eta^\prime\pi}} {\textstyle{a_2\to\eta\pi}}) =\left(\frac{\textstyle{p_{\eta^\prime\pi}}}{\textstyle{p_{\eta\pi}}}\right)^5 \tan^2 \phi_P=0.0371 & (\mbox{\rm data}\,\,\,\, 0.0366\pm 0.0069)~, \end{array}\end{aligned}$$ for center of mass momenta $p_{\eta\pi}=535~{\mbox{\rm MeV}}$, $p_{\eta^\prime\pi}=287~{\mbox{\rm MeV}}$, $p_{K}=437~{\mbox{\rm MeV}}$. The above data branching ratios follow from $a_2(1320)$ recent fractions [@PDG2004]: $\mbox{\rm BR}(a_2\to\eta\pi) =(14.5\pm 1.2)\%$, $\mbox{\rm BR}(a_2\to K\bar{K}) =( 4.9\pm 0.8)\%$ and $\mbox{\rm BR}(a_2\to\eta^\prime\pi)=( 5.3\pm 0.9)\cdot 10^{-3}$. Comments Related to the Gluon Anomaly {#sec:CommRelToGlounAnom} ===================================== The approach using the pseudoscalar coupling is, in our opinion, also relevant for the effects related to the non-Abelian, “gluon" ABJ axial anomaly. Here, we comment on this only briefly, and direct the reader to the original references for details. Goldstone structure and $\eta$-$\eta'$ phenomenology ---------------------------------------------------- The first point concerns the $\eta$-$\eta'$ complex and the $U_A(1)$ problem related to it. In the chiral limit $m_\pi = m_K = m_{\eta_8} = 0$, since all members of the flavor-SU(3) pseudoscalar meson octet are massless in this theoretical, but very useful limit. The only non-vanishing ground-state pseudoscalar meson mass in this limit is the mass of the SU(3)-singlet pseudoscalar meson $\eta_1$. This is thanks to the non-Abelian, gluon ABJ axial anomaly, i.e., to the fact that the divergence of the SU(3)-singlet axial current $$A^\mu_0(x) = \overline\Psi(x) \gamma^\mu \gamma_5 \Psi(x) \, ,$$ receives the contributions from both the finite quark masses and gluon fields $G_a^{\mu\nu}$: $$\partial_\mu A^\mu_0 = 2 {\rm i} m_u \, \overline{u} \gamma_5 u + 2 {\rm i} m_d \, \overline{d} \gamma_5 d + 2 {\rm i} m_s \, \overline{s} \gamma_5 s + \frac{3 \, g^2 }{32 \pi^2} \epsilon_{\mu\nu\alpha\beta} G_a^{\mu\nu} G_a^{\alpha\beta}\, . \label{divGanom}$$ This removes the $U_A(1)$ symmetry and explains why only eight pseudoscalar mesons are light, and not nine; i.e., why there is an octet of (almost-)Goldstone bosons, but not a nonet. The physically observed $\eta$ and $\eta'$ are then the mixtures of the anomalously heavy $\eta_1$ and (almost-)Goldstone $\eta_8$ in such a way that $\eta'$ is predominantly $\eta_1$ and $\eta$ is predominantly $\eta_8$. This is how the gluon anomaly can save us from the $U_A(1)$ problem in principle, and the details of how we achieve a successful description of the $\eta$-$\eta'$ complex, are given in Refs. . Here we just sketch some important points. The mass matrix squared $\hat{M}^2$ in the quark basis $|u\bar{u}\rangle$, $|d\bar{d}\rangle$, $|s\bar{s}\rangle$ is $$\hat{M}^2 = \hat{M}_{\mbox{\rm\scriptsize NA}}^2 + \hat{M}_{\rm A}^2 = \left[ \begin{array}{ccc} m_{u\bar{u}}^2 & 0 & 0 \\ 0 & m_{d\bar{d}}^2 & 0 \\ 0 & 0 & m_{s\bar{s}}^2 \end{array} \right] + \beta \left[ \begin{array}{ccl} 1 & 1 & X \\ 1 & 1 & X \\ X & X & X^2 \end{array} \right]~,$$ where $\hat{M}_{\mbox{\rm\scriptsize NA}}^2$ is the non-anomalous part of the matrix, since $m_{u\bar{u}}^2=m_{d\bar{d}}^2=m_\pi^2$ and $m_{s\bar{s}}^2=2m_K^2-m_\pi^2$ would be the masses of the respective “non-strange" (NS) and “strange" (S) pseudoscalar $q\bar{q}$ mesons if there were no gluon anomaly. In the NS sector, in the isospin symmetry limit (which is very close to reality), the relevant combinations are $| \pi^0 \rangle = | u\bar{u} - d\bar{d} \rangle / \sqrt{2}$ as the neutral partner of the charged pions $| \pi^\pm \rangle$ in the isospin 1 triplet, and the isospin 0 combination $ | u\bar{u} + d\bar{d} \rangle / \sqrt{2} $. In the absence of gluon anomaly, but with an $s$-quark mass heavier than the isosymmetric $u$ and $d$ ones, $\eta$ would reduce to $|{\rm NS}\rangle=|u\bar{u} + d\bar{d} \rangle / \sqrt{2}$ with the mass $m_{\mbox{\rm\scriptsize NS}} = m_\pi$, and $\eta'$ to $|{\rm S}\rangle = | s\bar{s} \rangle $ with the mass $m_{\mbox{\rm\scriptsize S}} = m_{s\bar{s}}$. Both of these assignments are in conflict with experiment. The realistic contributions of various flavors to $\eta$ and $\eta'$ and their masses (i.e., the realistic $\eta$-$\eta'$ mixing) are obtained only thanks to $\hat{M}_{\rm A}^2$, the anomalous contribution to the mass matrix. In $\hat{M}_{\rm A}^2$, the quantity $\beta$ describes transitions $|q\bar{q}\rangle\to|q^\prime\bar{q}^\prime\rangle$ ($q,q^\prime=u,d,s$) due to the gluon anomaly and $X$ describes the effects of the SU(3) flavor symmetry breaking on these transitions. In Refs. , as the first step in solving the $U_A(1)$ problem, we extract $\eta_8$, $\eta_1$ masses from the $\eta$, $\eta^\prime$ via $$\begin{aligned} m_{\eta_8}^2=(m_\eta\cos\theta_P)^2+(m_{\eta^\prime}\sin\theta_P)^2 =(572.73~{\mbox{\rm MeV}})^2~, \label{meta8} \\ m_{\eta_1}^2=(m_\eta\sin\theta_P)^2+(m_{\eta^\prime}\cos\theta_P)^2 =(943.05~{\mbox{\rm MeV}})^2~, \label{meta1}\end{aligned}$$ where $\theta_P=\phi_P-\arctan(\sqrt{2})=(-12.295\pm 0.019)^\circ$. The mesons $\eta_8$ and $\eta_1$ are defined as $$\begin{aligned} |\eta_8\rangle &=& \frac{1}{\sqrt{6}} (|u\bar{u}\rangle + |d\bar{d}\rangle - 2 |s\bar{s}\rangle)~, \\ |\eta_1\rangle &=& \frac{1}{\sqrt{3}} (|u\bar{u}\rangle + |d\bar{d}\rangle + |s\bar{s}\rangle)~.\end{aligned}$$ The $\eta_8$ meson mass (\[meta8\]) $m_{\eta_8}=572.73~{\mbox{\rm MeV}}$ is 4.56% greater than the observed [@PDG2004] $m_\eta=(547.75\pm 0.12)~{\mbox{\rm MeV}}$. The singlet $\eta_1$ mass (\[meta1\]) $m_{\eta_1}=943.06~{\mbox{\rm MeV}}$ is only 1.56% below the observed $m_\eta^\prime=(957.78\pm 0.14)~{\mbox{\rm MeV}}$ and close to the nonstrange–$\bar{s}s$ mixing $U_A(1)$ mass dictated by phenomenology [@Jones:1979ez; @Kekez:2000aw; @Klabucar:2000me] $$m_{U_A(1)} \equiv (3\beta)^{1/2} = \left[ \frac{3}{4} \frac{(m_{\eta^\prime}^2 - m_\pi^2) (m_\eta^2 - m_\pi^2)} {m_K^2-m_\pi^2} \right]^{1/2} = 915.31~{\mbox{\rm MeV}}~, \label{secondU1Amass}$$ (This is also close to $912~{\mbox{\rm MeV}}$, which is the mass found in the analogous DS approach [@Kekez:2000aw; @Klabucar:2000me].) We call the quantity (\[secondU1Amass\]) the “mixing $U_A(1)$ mass" since the mass matrix (which is especially clear in the nonstrange-strange quark basis) reveals that $m_{U_A(1)}$ induces the mixing between the nonstrange isoscalar $(|\bar{u}u\rangle+|\bar{d}d\rangle/\sqrt{2}$ and $\bar{s}s$ quark-antiquark states. Equivalently, $m_{U_A(1)}$ can be viewed as being generated by the transitions among the $\bar{u}u$, $\bar{d}d$ and $\bar{s}s$ pseudoscalar states; via quark loops, these pseudoscalar $\bar{q}q$ bound states can annihilate into gluons which in turn via another quark loop can again recombine into another pseudoscalar $\bar{q}'q'$ bound state of the same or different flavor. The quantity $\beta$ appearing in Eq. (\[secondU1Amass\]) is then the annihilation strength of such transitions, in the limit of an exact SU(3) flavor symmetry. (The realistic breaking of this symmetry is easily introduced and improves our description of the $\eta$-$\eta'$ complex considerably.) The “diamond” graph in Fig. \[fig:diamond\] gives just the simplest example of such an annihilation/recombination transition. Since these annihilations occur in the nonperturbative regime of QCD, all graphs with any even number of gluons instead of just those two in Fig. \[fig:diamond\], can be just as significant in annihilating and forming a $C^+$ pseudoscalar $\bar{q}q$ meson. Indeed, this nonperturbative $U_A(1)$ mass scale, Eq. (\[secondU1Amass\]), is still 3 times higher than the gluon “diamond” graph evaluated perturbatively [@Choudhury]. Thus, we cannot calculate $\beta = m_{U_A(1)}^2/3$ and the situation is much more complicated and less clear than in the Abelian case, as explained in [@Kekez:2005kx]. Can it then be founded to think that the annihilation graphs with the pseudoscalar meson-quark coupling, such as the “diamond” graph in Fig. \[fig:diamond\], give rise to the anomalous term $({3 \, g^2 }/{32 \pi^2}) \epsilon_{\mu\nu\alpha\beta} G_a^{\mu\nu} G_a^{\alpha\beta}$ in the divergence (\[divGanom\]) of the SU(3)-singlet current $A^\mu_0(x)$, and thus ultimately to the large mass of $\eta_0$ (and of the observed $\eta'$)? Well, this conjecture may remain a speculation since we cannot calculate $\beta$ due to the nonperturbative nature of the problem. Nevertheless, when we use it in our approach as a parameter with the value given by Eq. (\[secondU1Amass\]), we obtain a very good description of the $\eta$-$\eta'$ complex phenomenology [@Jones:1979ez; @Kekez:2000aw; @Klabucar:1997zi; @Klabucar:2000me; @Klabucar:2001gr]. This includes not only the masses of $\eta$ and $\eta'$, but also their $\gamma\gamma$ decay widths, and the mixing angle $\theta_P \approx -13^\circ$ consistently following from the masses and $\gamma\gamma$ widths. This gives a strong motivation for the above conjecture. ![Nonperturbative QCD annihilation of a quark-antiquark bound state illustrated by the diagram with two-gluon exchange. The $\bar{q}q$ pseudoscalar $P$ is coupled to a quark loop, whereby it can annihilate into gluons which in turn recombine into the pseudoscalar $P'$ having the flavor content $\bar{q'}q'$.[]{data-label="fig:diamond"}](DiamondGraph.eps){height="30mm"} Taming of strong CP problem --------------------------- We should also note that our conjecture in the previous subsection goes well with the arguments of Banerjee [*et al.*]{} [@Banerjee:2000qw], that there is really no strong CP problem. They find that one does [*not*]{} need vanishing $\Theta_{\rm eff} = \Theta - {\rm tr}\ln {\cal M}_q$ (where ${\cal M}_q$ is the quark mass matrix). Thus, one does not need any fine-tuning, and all CP violation in the QCD Lagrangian can be avoided by having $\Theta = 0$ in its CP-violating term $${\cal L}_\Theta = - \Theta \, \frac{ g^2 }{64 \pi^2} \epsilon_{\mu\nu\alpha\beta} G_a^{\mu\nu} G_a^{\alpha\beta}\, . \label{ThetaQCD}$$ This term in the QCD Lagrangian breaks the $U_A(1)$ symmetry and corresponds to the anomalous term $\propto \epsilon_{\mu\nu\alpha\beta} G_a^{\mu\nu} G_a^{\alpha\beta}$ in the divergence (\[divGanom\]) of the singlet current. The term (\[ThetaQCD\]) is allowed by gauge invariance and renormalizability, but apparent nonexistence of the strong CP violation, and also of axions, is the solid reason to have it vanishing. Our conjecture, that P-coupled annihilation graphs reproduce the effect of the gluon ABJ anomaly, naturally agrees with the vanishing of this term and with putting the case of the strong CP problem to rest [*à la*]{} Banerjee [*et al.*]{} [@Banerjee:2000qw]. Summary/Discussion {#sec:summary} ================== We have presented and surveyed in detail the method of pseudoscalar coupling of pseudoscalar mesons to the “triangle" and “box" quark loops. We have reviewed how this method gives the equivalent results to the anomaly calculations. The P-coupling method has also been illustrated on the example of many decay amplitudes. The AVV anomaly [@Adler69; @BellJackiw69] involves 10 invariant amplitudes (reduced to 1 or 2 amplitudes for $\pi^0\to \gamma\gamma$ decay using additional Ward identities). If instead one considers the PVV transition with a pseudoscalar coupling, then the PVV quark triangle amplitude is finite and leads to many decay amplitudes (over 15) then in agreement with data to within 3% and not involving free parameters [@Delbourgo]. To solve instead the former AVV decay problem, very light axion bosons have been predicted but have [*not*]{} yet been observed [@PDG2004]. Also, there is the $U_A(1)$ and $\Theta$ problem involving gluons whereby strong interaction QCD leads to CP violation, definitely a “strong CP problem” because CP violation is known to occur at the $10^{-3}$ weak interaction amplitude level [@PDG2004]. Physicists have tried to circumvent this “$U_A(1)$ – strong CP problem” either via the topology of gauge fields or by investigating the $\Theta$–vacuum for this strong CP problem [@Banerjee:2000qw]. In this paper we have circumvented the need to deal directly with the above photon or gluon AVV anomalies by studying instead (finite) PVV quark triangle graphs. Then we have given our phenomenological results – which always are in approximate agreement with the data. Next we return to the $U_A(1)$ problem and again use quark triangle diagrams coupled to 2 gluons. Invoking nonstrange–strange particle mixing, the predicted $U_A(1)$ mass is within 3% of data [@Jones:1979ez; @Kekez:2000aw; @Klabucar:2000me]. Thus we circumvent both photon and, admittedly on a much more speculative level, also the gluon ABJ anomaly without resorting either to unmeasured axions or to a strong CP violating term in the QCD Lagrangian. [100]{} S. L. Adler, [Phys. Rev.]{} [**177**]{}, 2426 (1969). J. S. Bell and R. Jackiw, [Nouvo Cim. A]{} [**[60]{}**]{}, 47 (1969). B. Bistrović and D. Klabučar, Phys. Rev. D [**61**]{}, 033006 (2000) \[arXiv:hep-ph/9907515\]. 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R. Delbourgo and M. D. Scadron, Mod. Phys. Lett. A [**10**]{}, 251 (1995) \[arXiv:hep-ph/9910242\]. A. Bramon, Riazuddin and M. D. Scadron, J. Phys. G [**24**]{}, 1 (1998) \[arXiv:hep-ph/9709274\]. S. Eidelman [*et al.*]{}, Phys. Lett. B [**592**]{}, 1 (2004). H. Banerjee, D. Chatterjee and P. Mitra, Phys. Lett. B [**573**]{}, 109 (2003) \[arXiv:hep-ph/0012284\]. K. Hagiwara [*et al.*]{}, Phys. Rev. D [**66**]{}, 010001 (2002). H. F. Jones and M. D. Scadron, Nucl. Phys. B [**155**]{}, 409 (1979). D. Kekez, D. Klabučar and M. D. Scadron, J. Phys. G [**26**]{}, 1335 (2000) \[arXiv:hep-ph/0003234\]. R. L. Thews, Phys. Rev. D [**10**]{}, 2993 (1974). P. G. O. Freund and S. Nandi, Phys. Rev. Lett. [**32**]{}, 181 (1974); S. Rudaz, Phys. Lett. B [**145**]{}, 281 (1984). M. Gell-Mann, D. Sharp and W. Wagner, Phys. Rev. Lett. [**8**]{}, 261 (1962). J. L. Lucio-Martinez, M. Napsuciale, M. D. Scadron and V. M. Villanueva, Phys. Rev. D [**61**]{}, 034013 (2000). D. Klabučar and D. Kekez, Phys. Rev. D [**58**]{}, 096003 (1998) \[arXiv:hep-ph/9710206\]. D. Klabučar, D. Kekez and M. D. Scadron, arXiv:hep-ph/0012267. D. Kekez, D. Klabučar and M. D. Scadron, J. Phys. G [**27**]{}, 1775 (2001) \[arXiv:hep-ph/0101324\]. S. R. Choudhury and M. D. Scadron, Mod. Phys. Lett. A [**1**]{}, 535 (1986). [^1]: Senior Associate of Abdus Salam ICTP [^2]: We use quadratic mass formulae for mesons (See, e.g., Ref.  and earlier). However, the input experimental meson masses are newest, taken from Ref. .
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"(DOG BARKS)" "Go and get a sharper one." "David?" "~ David!" "~ I've finished!" "You're supposed to clear up with the girls." "They didn't ask." "You are going to earn yourself such a thrashing!" "Give him a chance." "He's a 10-year-old boy." "That's no excuse." "I'd better go." "~ You won't stay for dinner?" "~ No, the Duke is back tomorrow, so I've got to finish getting the house ready." "I'll walk you home." "It's only just down the hill." "I need some air." "What's she done?" "Come here." "That's better." "It'll get better." "I'm just seeing Auntie Sarah home and then I'm off to the Navy Yards." "Whoa." "I have to go to Islington on Sunday to pick up some more firewood if you fancy a day out." "Thomas Farriner, you certainly know how to show a girl a good time!" "Oi!" "Come here!" "Leave it, Tom." "Someone's got to fight his corner." "That's not going to help him." "They've been teasing him, saying his father's been killed in the war." "He'll be back." 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"Make a sound or move a muscle and I'll put this blade right between your shoulders." "(APPLAUSE)" "How did you get in here?" "Let me guess." "You're a Catholic and you are here to return our great Kingdom to the path of the true religion?" "I am proud of my faith." "I am sure you are." "Where did you get this?" "I am justice!" "And I am Lord Denton, His Majesty's intelligence officer." "He claims to have been acting alone." "Don't they always?" "He was a fanatic." "A lunatic, nothing more." "And the city's full of them." "I assumed I'd at least be safe in my own palace." "It's been taken care of." "Now, Denton says he used to work for the Duke of Hanford." "Hanford employs just about every Catholic down on his luck." "But he is not a rebel, let alone an assassin." "What makes you so sure?" "Instinct." "(APPROACHING FOOTSTEPS)" "(KNOCK AT THE DOOR)" "~ Mr Wickes." "~ Oh, Edward by now, surely." "I wasn't expecting you." "Forgive the intrusion." "I brought this for David." "For you to borrow, Mr Wickes means, and to look after carefully." "For as long as you like." "What do you say?" "Thank you." "A young boy hungry for knowledge." "Perhaps provision could be made for him to go to school." "And as a boy can't eat books, I thought you'd appreciate some mutton." "Mr Wickes, that is very kind, sir." "Thank you." "But I cannot accept that." "There's no shame in accepting a little help." "What harm can it do?" "Besides, he looks as if he could do with feeding up." "Thank you." "So your employer is about to return?" "Yes." "Lord Hanford returns tomorrow." "Mm." "Well, enjoy your dinner." "I bid you good night, mistress." "Thomas!" "Who's that?" "He's just someone from church." "Will the miller give you flour against next week's order?" "I doubt it." "Think the navy will be buying bread from me next week?" "I knocked the man's bloody wig off." "Hannah'll be furious with me." "We're down to the bone anyway." "Without the navy contract..." "It's fine, Tom." "We'll work it out." "I don't know how your gentleman friend expects you to cook this without an oven." "Perhaps he knows I have a brother-in-law who's a baker." "Well, watch him." "I'll bring it back in the morning." "Whoa!" "Whoa!" "Thank you, Carter." "Good morning, Sarah." "My lord Hanford." "How was your journey?" "Long and tiresome, but for the company." "Hanford calls him Romero." "He's a Spaniard, and from the way he carries himself, I'd say he's a soldier." "~ Who did they meet?" "~ No-one." "They travelled alone, dined alone, very careful not to be overheard discussing anything of substance." "We stayed half a day behind them all the way." "They don't suspect a thing." "We've caught an assassin." "He left Hanford's employ three years ago." "Maybe he brought the Spaniard to make sure he finishes the job." "They always say Catholic wenches make the best whores." "I'll see what the footman has to say." "What time is it?" "I'm not sure." "Half past seven?" "God's blood, woman, didn't I tell you to wake me at seven?" "I'm going to be late!" "It's a game of Pall Mall, Samuel." "I'm sure it can wait." "The King waits for no man, as well you know." "Are these sufficient for sport, do you think?" "The brocade is smarter, but rather stiff." "Please tell me you do not wish to carry on this argument." "My terms have started." "Oh, Lizzie." "Seven weeks." "I really thought I was with child." "You are young and healthy." "There is no reason for your failure to continue." "(BELLS CHIMES THE HOUR)" "Eight o'clock!" "You have made me late!" "Do you have to go?" "Tell Ruth to prepare you a poultice." "It would be courteous to let me win, Pepys." "Particularly in this heat." "I was told you like competition." "Whoever told you that is a brazen liar." "My God, it's hot." "WOMAN:" "Here we are again." "Is she not the most lovely thing you've ever seen?" "I have always admired my Lady Castlemaine." "~ She has the benefit of a ready wit..." "~ Not Castlemaine." "I mean Frances." "Yes, she's... comely, my lord." "Comely?" "Really, Pepys, is that the best you can do?" "I hear you once said the poor folk who used to toast my health on their knees outside the gates" "~ were "a little too much"?" "~ Yes." "Why?" "You don't need sycophancy." "I wouldn't be so sure." "The alternative to sycophancy is contempt, which, if you are a king, can lead to very unhappy consequences." "Forgive me, but the alternative to sycophancy is respect." "Which is a sounder basis for government." "But the people do respect me." "Do they not?" "That is what my courtiers always tell me." "I think that would be true if the people saw a little more of you." "Explain." "An increasingly common view is you are consumed by the pursuit of pleasure and surrounded by sycophants who will not dare tell you you are bankrupting the country." "If the people wanted austerity, they would have stuck with Cromwell's bastard sons." "We are here to provide something to aspire to, a canvas onto which they can project their dreams." "Yes, Majesty." "But even the purveyors of dreams must control their outgoings." "The people removed my father's head and lived with the consequences." "~ They will not wish to repeat the experience." "~ The people are fickle." "I doubt they fear a new republic as much as your advisers claim." "WOMAN:" "Oh." "(POLITE APPLAUSE)" "A King can have many things he wants, Samuel." "But someone who is prepared to beat him at his favourite game, perhaps that is what he needs." "I... ~ Don't worry, John." "Give it to me next week." "~ Thank you, Tom." "I appreciate that." "Father, we're not a charity." "~ He's a good customer." "~ Not if he doesn't pay." "What are we going to do about flour?" "That was the last sack." "The rest of it went on that bloody order for the navy." "First, no cursing." "Second, trust me." "It'll be all right." "How?" "I'm 13, Father, not five." "And you're my daughter, not my wife." "So leave it to me." "See you later." "(SIGHS)" "David will be happy." "Good." "And there'll be plenty for you and the girls." "Could I ask a favour, Sarah?" "Would you write to the Navy Board for me?" "One look at the shape of my letters, he'll dismiss my case." "But you know how to put things." "~ Of course, Tom." "~ Thank you." "To..." "To Mr Pepys himself..." "I have to get the navy contract back or I'm in trouble." "How should I address him?" "His full title, which is Surveyor General of Victualling... .. and Clerk of the Acts to the Navy Board." "Do you think your title gets longer the less effective you are?" "If you do manage to speak to him, you'll ask about Will?" "I've got nowhere with the clerks." "I can't stand another 16 months of this, Tom." "I know." "I know." "I'll ask him." "Hey..." "~ I do not really have time for this, Mr... ~ Farriner, sir." "Farriner, but you are lucky to catch me in excellent humour." "Well?" "I cannot buy the flour to bake for the King's navy if the King's navy will not pay its bills, sir." "It's regrettable but shouldn't you share the pain with your suppliers like everyone else?" "I've tried." "But if I have no flour, I have nothing to bake with and if I cannot bake, then... ~ Then I've nothing to feed my family on, sir." "~ We are at war." "It's an expensive business and I cannot pay you with money I do not have." "The King's finances are stretched." "Have you received your pay this month, Mr Pepys?" "You are, by all accounts, a good man, Farriner." "You work hard." "I have no intention of taking the navy contract away from you." "Thank you, sir." "But there is nothing I can do on the question of payment." "You will have to find a way to hold on." "For King and country." "Is there something else?" "Well, I seek news of my brother, William Farriner, sir." "He was on His Majesty's ship the Charity at the battle of Lowestoft and we heard these reports that men were picked from the water." "If so, wouldn't he have returned by now?" "Sir, he has a wife and a son..." "and they're waiting for news of him." "She needs to know, sir." "~ Robins." "~ Sir?" "I want to check the records for the Charity." "I shall write your sister-in-law a letter." "Unfortunately I do not have good news." "How did it go?" "Oh." "They're not going to take the navy contract away." "~ Well, will they pay what's owed?" "~ No." "What is it?" "I need to go and talk to Auntie Sarah." "~ Do you want me to rake out the ovens?" "~ No, no." "It's early yet." "~ I'll do it later." "~ I can do it before I go to sleep." "Hannah!" "Hannah!" "Yes, mouse, what is it?" "When people die, and you see them again in heaven, do they look exactly the same?" "Yes, I reckon so." "I don't think I'd recognise Mother." "Course you wouldn't." "She died when you were born." "How would she recognise me, then?" "In heaven." "She just would." "Stay, just for a little while." "♪ Jockey was a Piper's Son" "♪ And fell in love when he was young" "♪ But all the tunes that he could play" "♪ Was over the Hills and Far Away" "♪ Over the Hills and Far Away" "♪ Far away, far away" "♪ Over the Hills and Far Away" "♪ Was all that he could play" "David!" "Oh, my God." "Mr Wickes." "~ Where's David?" "~ That's everywhere, my lord." "Nothing." ""My lord"?" "What's going on?" "What is your business here?" "The King's business, Sarah." "What have you done with David?" "A penny for the pie shop." "I thought it better to work uninterrupted." "Forgive me, I have deceived you." ""Edward Wickes" is an invention." "My name is Lord Denton and I'm a servant of the King." "Now, I know that you work for the Duke of Hanford." "It's no secret that he employs every papist waif and stray in London." "I am no Catholic." "The Duke gave me work with no thought of my faith when we'd been thrown out on the streets." "He's a good man." "Your employer is a seditious sectarian bigot who's in league with our foreign enemies." "He has shown me nothing but kindness." "I'll bet." "Sarah, if you will agree to help me, it would make it easier to believe you've not been drawn into Hanford's treacherous web." "You see, he arrived back this morning with a Spanish soldier called Romero and there's every chance he intends to make an attempt on the King's life." "How am I to know you speak the truth?" "Your person, the interest you showed in David, that was all lies." "It was a necessity." "Now I need to know where this man Romero goes and who he speaks to." "I wish to be informed of everything that happens inside that house." "The Duke trusts me." "I can see you need time to compose your thoughts." "Now, you may present yourself to me at the Star Inn on Fish Street before midnight - hmm?" " and I will give you your full instructions." "You will not wish to be acquainted with the consequences of refusal." "(DOG BARKS)" "Fire!" "Fire!" "Hannah!" "Hannah!" "Mary!" "Mary!" "Hannah!" "Wake up!" "Mary!" "Mary!" "Hannah, Mary, wake up!" "Wake up!" "Fire!" "Fire!" "~ Daddy!" "~ We've got to go!" "~ Check the ovens?" "~ Now!" "~ Well, did you?" "~ Quickly!" "Quickly!" "(COUGHING) Father, no!" "It's no good." "Up to the attic." "Quick, come on!" "Here we go, here we go." "Here we go." "~ Cover your eyes." "~ Be careful." "What are you doing?" "Father!" "Right, we go over to the next roof." "~ Use the ledge." "~ Be careful." "~ Don't go." "Please!" "~ Father, don't leave us." "Stay there." "~ Hannah, help Mary onto my back." "~ I'm scared." "Help her, Hannah." "That's it, that's it, that's it." "Now, I've got you." "Hold on." "Try to be brave." "That's it." "Now, wrap your legs around me." "All right." "It's all right." "I've got you." "Now, we can do this." "~ All right?" "Now hold on." "~ Father!" "There, see, see?" "Going to be fine." "Hold tight." "~ I'm slipping." "~ No, you're not." "No, you're not." "Just hold tight." "Just hold on." "I'm going to jump, Mary." "Hold on." "Father, no!" "(SCREAMS)" "Sit on the ledge." "Sit on the ledge." "That's it." "That's it." "That's it." "Now, stay there, stay there." "Hannah!" "Hannah!" "I can't come back." "You're going to have to do it yourself." "Just climb out!" "Now come to me." "Come to me, Hannah." "Hannah, that's it, use the ledge." "Use the ledge." "That's it." "I can see you." "I can see you." "I can see you, Hannah." "Now just keep coming." "Come to me, Hannah." "Hannah." "Hannah, come on." "Come on!" "That's it, that's it." "Don't look down, don't look down." "Just focus on me." "Now you're going to have to jump!" "Now, reach for my hand." "Reach." "Hannah, reach." "I can't." "You're too far." "Reach for my hand, Hannah." "Reach, Hannah, please." "~ (SHRIEKS) ~ Reach..." "Quick." "Reach for my hand!" "That's it!" "Reach." "Reach!" "You can do it." "Hannah, please." "Jump." "Jump, Hannah!" "~ (SCREAMS) ~ No." "Don't let me go." "~ Hold on." "~ Please!" "That's it." "Pull yourself." "(That's it." "That's it.)" "(That's it.)" "Take Mary to Auntie Sarah's." "I'll be there as soon as I can." "~ Please, come with us." "~ I have to make sure the fire doesn't spread." "Tom!" "We have to dig down, find the water pipes." "Hannah, go, go, go." "Lizzie." "The day has quite simply been a stunning success." "The King's favour... (LIZZIE LAUGHS)" "Signor Alfredo is here, sir." "Madam's dance lesson." "(LIZZIE LAUGHS)" "(HUMS TUNE)" "(BELL RINGS OUT)" "Where are you going?" "Go back to sleep." "Go back to sleep." "Lie down, go on." "You warm enough?" "Go back to sleep." "Send word for Mayor Bludworth." "The street's on fire." "Hurry, man, if you want to save your premises!" "(KNOCK AT DOOR)" "Hannah." "There was a fire." "We've lost everything." "Where's your father?" "~ Is he all right?" "~ He's trying to stop it spreading." "You're safe now." "That's all that matters." "Hannah, Hannah, you're safe." "Tom!" "Tom, the mayor's here." "Shall we pull down the houses either side, my lord?" "To stop it spreading." "Are you out of your mind?" "An old woman could piss it out!" "(MEN LAUGH)" "An hour." "You seem to have found some stamina about you, Mr Pepys." "I asked for carriage, not entertainment." "(RAPPING AT DOOR)" "Make sure you lift him if he starts to cough." "I don't suppose there was any luck, sir, down the yards?" "I have asked." "I can turn my hand to anything." "I'll see what I can do." "(PANTING)" "(PANTING INTENSIFIES)" "I thought you weren't going to visit again." "Would you rather I didn't?" "That's not what I said." "This way." "Over here!" "That's it." "(SHOUTING)" "Water!" "We need water!" "~ Get some water!" "~ Out of the way!" "They says there's a fire in Pudding Lane." "Not a good omen in this heat and wind." "Who cares if the poor burn, eh, Pepys?" "I care." "It is my city." "Without London, there's no commerce, country or King." "Without London, we are nothing but a nation of sheep farmers." "Well, maybe it'll flush out some of the papist vermin." "If it wasn't them who started this fire." "Wilson, you well know the King demands tolerance of our Catholic brethren." "The King should enforce the law." "The King only cares for his pleasure." "I hear things down here on my river, Mr Pepys." "You hear the sound of the wind whistling through the space where your brain should be." "(SNIFFS)" "(BELL RINGS)" "Mr Ambassador." "We thank you for your hospitality." "Our guest awaits." "In nomine Patris, et Filii, et Spiritus Sancti." "Amen." "Welcome." "How did you acquire so many knots?" "Ow!" "Take pity." "It is important to look beautiful for the King." "He seems to require no special effort." "You are wrong." "And it's your duty under God, no less." "We will not harm you, my child." "No." "No, I do not want this." "Frances." "Frances." "Now, come on." "No harm was intended." "Now don't be cross, you're too beautiful." "Am I really so deficient, so ugly?" "The whole world knows you are handsome." "Then what can I do to persuade you to change your mind?" "Sir, since you can have everything, you know the value of nothing." "(NEIGHING)" "(SHOUTING)" "Tom!" "(SHOUTING)" "Tom!" "(PROTESTS MUFFLED)" "Go on, get in there." "~ Get her in." "~ Get in there, go on." "Tom!" "Tom!" "Tom!" "Mama!" "Sarah!" "Mama!" "Sarah!" "You are in serious trouble, Sarah." "Where is the rescue effort?" "A fire in the poorest quarter of the city, on the hottest night of the year." "Chaos, panic, confusion." "What better time to strike against the King?"
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1. Genomic Organization of Chicken PPARS (cPPARs) {#sec1} ================================================= The mechanisms of lipid and glucose metabolism for energy storage and homeostasis differ between species in ways that are not fully understood. To improve food production, comprehending the molecular basis for lipid and glucose metabolism in domestic animals is a significant issue. In avian species, lipids, especially triglycerides, are thought to be stored in adipocytes, hepatocytes, and growing oocytes. Excessive accumulation of lipids in the adipose tissue of broilers is a major concern for producers, because excessive fat deposits result in lower meat yields. In 2000, we reported the cloning of three chicken PPAR subtype genes (*α*, *β*, and *γ*) from cDNA libraries prepared from 2.5-day-old chicken embryos and adult adipose tissue \[[@B1]\]. For cPPAR*γ*, amino acid residues predicted for phosphorylation by MAP kinase \[[@B2]\] (Ser82 in cPPAR*γ*) and Cdk5 \[[@B3]\] (Ser243 in cPPAR*γ*) were conserved between mammals and chicken PPAR*γ*. Moreover, predicted SUMOylation target residues (Lys77 and Lys365 in cPPAR*γ*) were also conserved in cPPAR*γ* \[[@B4]\]. This shows the possibility that the transcriptional activity of cPPAR*γ* regulates growth factors and that cPPAR*γ* activation has an anti-inflammatory effect. However, we were unable to isolate the PPAR*γ*2 splicing variant identified in mammals \[[@B5], [@B6]\]. This variant is likely absent in chickens because Sato et al. also could not isolate chicken PPAR*γ*2 by 5′-RACE \[[@B7]\] and because no sequence similar to a PPAR*γ*2 isoform has been found in the chicken genome database ([Figure 1](#fig1){ref-type="fig"}). The PPAR*γ*2 isoform has not been reported in *Xenopus* and zebrafish either. Furthermore, while the structural organization of PPAR*α* and *β*/*δ* genes is largely conserved from humans to chickens, the PPAR*γ* isoform is not. The cPPAR*γ* gene (Ensembl ID: ENSGALG00000004974) has 6 exons and extends across \~50 kilobases (kb) of genomic DNA ([Figure 1](#fig1){ref-type="fig"}, upper panel). In contrast, the human PPAR*γ* gene (Ensembl ID: ENSG00000132170) consists of 8 and 7 exons for the *γ*1 and *γ*2 subtypes, respectively, and extends across more than 160 kb of genomic DNA ([Figure 1](#fig1){ref-type="fig"}, lower panel). Other species such as squirrel (Ensembl ID: ENSSTOG00000012778), hedgehog (ENSEEUG0000006334), Chinese softshell turtle (ENSPSIG00000011100), and Anole lizard (ENSACAG00000013360) have the chicken-type organization of PPAR*γ* genes. In mammals, several polymorphisms of PPAR genes have been associated with metabolic disorders. In chicken, single nucleotide polymorphism (SNP) analysis has been conducted to find the association with lean and fat broilers \[[@B8]\]. In this study, PPAR*γ* c-75G\>A is reported to be associated with abdominal fat weight and also correlates with SNPs of other lipid metabolism-related genes (Fsbp4, C/ebp*α*, etc.). Promoter analysis of the cPPAR*γ* gene revealed that transcription factor binding sites (such as C/EBP*α*, Sp1 and AP1) exist as is the case with mammalian PPAR*γ*1 and PPAR*γ*2 promoters. Interestingly, structure of cPPAR*γ* promoter is more similar to the mammalian PPAR*γ*2 promoters compared to PPAR*γ*1 promoters \[[@B9]\]. These results suggest that C/EBP*α*-PPAR*γ* pathway is conserved across the species and that PPAR*γ*2 gene first appeared in the course of evolution when additional PPAR*γ* isoforms have been acquired. 2. Expression Patterns of cPPAR mRNAs {#sec2} ===================================== The mRNA expression patterns of cPPARs are similar to rodents and primates. In adult chicken, cPPAR*α* is highly expressed in the heart, liver, and kidney \[[@B10]\]. As is the case for PPAR*β* or *δ* in other species, cPPAR*β* is expressed ubiquitously. Meanwhile, high expression of cPPAR*γ* is observed in fat tissue as well as the kidney, heart, brain, liver, and intestine \[[@B7], [@B11]\]. Recent studies using renal-specific PPAR*γ* knockout mice have shown that the gene regulates body weight by controlling water channel activities \[[@B12]\]. Thus, cPPAR*γ* may also regulate body weight in chickens. Hojo et al. examined cPPAR mRNA expression patterns in digestive organs during embryonic development in chickens \[[@B13]\]. In embryonic day 6 (E6), E9, and E12 embryos, PPAR*α* is expressed in the epithelium, smooth muscle, and small intestine. PPAR*β* is expressed in the epithelium and moderately in mesenchymal tissue on E6, E9, and E12. PPAR*γ* is weakly expressed in the epithelium on E9 and E12 and expressed in the medial and basal parts of the small intestine villi, the villi of PH3 and 14, and the crypt epithelium of the large intestine. 3. Regulators of cPPAR mRNAs {#sec3} ============================ PPAR mRNA levels are known to be regulated in aging, metabolic disorder, and cancer \[[@B14]\]. In general, mRNA levels of PPARs or their target genes are upregulated in obesity because of increased fatty acids. Several regulators of PPAR mRNAs have recently been identified in chicken. In adipocyte, accumulation of nonesterified fatty acids (NEFA) induces cPPAR*γ* mRNA, and a cPPAR*γ* downstream gene (adipocyte fatty acid binding protein (A-FABP)) controls the concentration of lipid and NEFA \[[@B15]\]. In fatty broiler chickens, cPPAR*γ* mRNA expression is induced in liver but not in adipose \[[@B16]\]. Because PPAR*γ* mRNA is induced in adipose tissue of obese mammals \[[@B17], [@B18]\], the result indicates a divergence of PPAR signal transduction mechanisms between avians and mammals. Regulation of cPPAR*α* mRNA is also reported. Comparison of gene expression profiles in the intramuscular fat of two broiler lines showed that PPAR*α* and MAPK pathway are enhanced in both Beijing-you (BJY), which is a slow-growing Chinese breed possessing high meat quality, and Arbor Acres (AA), a commercial fast-growing broiler line \[[@B19]\]. Upon feed restriction, mRNA expression levels of cPPAR*α* and one of its target gene, peptide transporter 1 (PepT1), are induced in the jejunum \[[@B20]\]. In myoblasts, isoproterenol (a *β*-adrenergic receptor agonist) and fatty acid enhance the phosphorylation of cPPAR*α*. The mRNA of UCP3 is induced through cPPAR*α* and AMPK-PKA pathway \[[@B21]\]. In spleen, cPPAR*α* and *γ* mRNAs are induced by lutein, a plant carotenoid, and reduced by lipopolysaccharide (LPS) \[[@B22]\]. These results indicate that some regulators of cPPARs mRNA expression are conserved between chicken and mammals. 4. Comparison of the Amino Acid Sequences between Chicken and Mammalian PPARs {#sec4} ============================================================================= The amino acid sequence in the DNA binding domain (DBD) of cPPARs shows high similarity with mammals (cPPAR*α* versus hPPAR*α*: 95%; cPPAR*β* versus hPPAR*δ*: 98%; cPPAR*γ* versus hPPAR*γ*: 100%). The similarity of the ligand binding domain (LBD) is also high for PPAR*α* and PPAR*γ* (cPPAR*α* versus hPPAR*α*: 96%; cPPAR*γ* versus hPPAR*γ*: 96%). However, the LBD of cPPAR*β* shows lower similarity between chicken and humans (90%), mice (86%), and *Xenopus* (78%). Because this diversity implies different ligand responses, we conducted luciferase reporter assays to examine the ligand-inducible transcriptional activity of cPPARs. 5. Transcriptional Activities of cPPARs {#sec5} ======================================= We first generated cDNA expression vectors of cPPAR LBDs fused to GAL4 DBD. The ligand-inducible transcriptional activities of them were examined by luciferase reporter assays. We used serum-free conditions ((DMEM/ITB; DMEM with 5 *μ*g/mL insulin, 5 *μ*g/mL transferrin, and 0.01% fatty acid-free bovine serum albumin (BSA)) to reduce the effect of lipids contained in serum. Rhesus monkey kidney CV-1 cells cultured in 24-well cluster tissue culture plates were transfected with expression vectors carrying GAL4-cPPAR LBDs (25 ng/well), pCMX-*β*GAL (100 ng/well, as a control for transfection efficiency), and the MH100X4-tk-luc reporter plasmid (150 ng/well) using calcium phosphate precipitation method \[[@B23]\]. Interestingly, GAL4-cPPAR*γ* LBD showed high transcriptional activity without exogenous ligands ([Figure 2](#fig2){ref-type="fig"}, left panel). This activation was also observed for full-length cPPAR*γ* ([Figure 2](#fig2){ref-type="fig"}, right panel), indicating that this activation is cPPAR*γ* dependent. Moreover, cPPAR*β* suppressed basal transcriptional activity without ligands in DMEM/ITB ([Figure 2](#fig2){ref-type="fig"}, both panels). These findings show the possibility of a distinct ligand-independent transactivation function of cPPARs. We next investigated the effect of serum on the transcriptional activities of cPPARs. It was found that adult bovine serum induces cPPAR*α* transcriptional activities to a greater extent than fetal bovine serum and calf serum ([Figure 3(a)](#fig3){ref-type="fig"}). Interestingly, chicken serum (ChS) highly potentiated the transcriptional activities of cPPAR*α* and *β* as compared to bovine serum. ChS also activated the transactivation function of hPPARs ([Figure 3(b)](#fig3){ref-type="fig"}). Furthermore, using lipid extracts from chicken serum by a previously established method \[[@B24]\], we showed that the lipid extracts retain the enhancement effects of chicken serum for the transcriptional activities of cPPAR*α* and *β* ([Figure 3(c)](#fig3){ref-type="fig"}). These results show that serum from adult animals (chicken and bovine) contains more endogenous PPAR*β* ligands than that from fetal or young animals (bovine). Although the identity of PPAR*β* ligand(s) in adult serum has not yet been revealed, fatty acids and their derivatives are strong candidates. 6. Bezafibrate Is a Ligand for Avian and *Xenopus*PPAR***β*** {#sec6} ============================================================= We next examined the effect of known PPAR activators (including fibrates and thiazolidinediones) on the transactivation function of cPPARs. Bezafibrate, a known ligand for *Xenopus* PPAR*β* (xPPAR*β*) \[[@B25]\], enhanced the ligand-inducible transactivation function of xPPAR*β* in our hands (data not shown) and cPPAR*β*, but not hPPAR*δ* \[[@B1]\]. This result shows that bezafibrate selectively activates cPPAR*β* despite the relatively high structural similarity between cPPAR*β* and hPPAR*δ* LBDs. We looked for the amino acids that are conserved between human and mouse PPAR*δ*, but not chicken PPAR*β* and found that 15 amino acid residues were altered between chicken and mammals ([Figure 4(a)](#fig4){ref-type="fig"}). To identify the amino acid residue(s) critical for bezafibrate-dependent activation, we generated cDNA expression vectors carrying point mutations of relevant hPPAR*δ* and cPPAR*β* residues. Luciferase reporter assays in CV-1 cells were performed, and it was found out that a single amino acid alteration in cPPAR*β*(Val419Met0029 abrogates bezafibrate-dependent activation. When the corresponding Met residue in hPPAR*δ* was changed to Val, the mutant, hPPAR*δ*(Met417Val) enhanced bezafibrate-dependent activation. Human PPAR*α* has a Val residue at this position and when a point mutation was introduced, hPPAR*α*(Val444Met) abrogated bezafibrate responsiveness ([Figure 4(b)](#fig4){ref-type="fig"}). However, another PPAR*β*/*δ* activator, carbaprostacyclin, activates both hPPAR*δ*(Met417Val) and cPPAR*β*(Val419Met). These results suggest that the cPPAR*β* gene evolutionarily changed into the PPAR*δ* type, which is restricted to fibrate responsiveness. Although distinct endogenous ligands for chicken PPAR*β* and human/mice PPAR*δ* have not been identified, this amino acid change may reflect the difference between chicken and mammals in the regulation of energy storage \[[@B26]\]. Moreover, identification of amino acid residues involved in ligand interactions will help to generate PPAR*δ*-specific ligands and facilitate the development of drugs to treat metabolic syndromes. Thus, investigation of species-selective PPAR ligand activity is significant for understanding species-specific lipid metabolism and development of new drugs. 7. Effects of Fibrate on Hens {#sec7} ============================= There are few *in vivo* analyses of chickens fed with PPAR ligands. A previous report showed that hens treated with clofibrate (cPPAR*α* ligand) had lower food intake and lost body weight during the 5-week feeding period, which in turn reduced egg production due to the absence of large follicle(s) and the presence of few small yellow and white follicles in the ovary \[[@B27]\]. Moreover, triglyceride levels in the livers of clofibrate-treated hens were reduced and mRNA levels of known PPAR*α* target genes such as Acyl-CoA oxidase (ACO), hepatic lipase, and lipoprotein lipase (LPL) were induced. In contrast, mRNAs of insulin-induced genes (Insig-1, SREBP-2, FAS, HMG-CoA reductase, and LDL receptor) were downregulated by clofibrate treatment. These results show that, as with mice and humans, cPPAR*α* regulates lipid metabolism in the liver and controls appetite \[[@B28]\]. 8. Conclusions {#sec8} ============== In this paper we discussed the properties of chicken PPARs based on their genomic structural organization and ligand-inducible and -independent transactivation functions. Evolutionary changes in the PPAR*γ* genomic structure may be one critical factor for species-dependent lipid homeostasis. Because there are few reports concerning the promoter activity of PPAR*γ* gene in chickens and other nonmammals, more detailed analyses will be required. Interestingly, the ligand-inducible transcriptional activities of cPPARs do differ from mammalian PPARs. Because a single amino acid change leads to a selective ligand response, the spectrum of endogenous ligands of PPARs in avian species may be different from that of mammals. As such, further analysis will be required to understand the comparative endocrinology and this information will be useful for industrial applications in the poultry and other food industries. This work is supported in part by a Grant-in-Aid for Basic Research on Priority Areas (Immunological Self), Grant-in-Aid for Young Scientists (B) (23791622), Japan Society for the Promotion of Science, Japan, and The Cell Science Research Foundation. This study was mainly conducted under the direct supervison of late Professor K. Umesono at Kyoto University. For the publication of a part of the results (Mol. Endocrinol. 14 : 733-740, 2000), invaluable help by Drs. R. T. Yu and S. A. Kliewer and Professor R. M. Evans is acknowledged. The authors thank Drs. H. Ogawa, F Grün, and Mr. H. Ohizumi and other members of the Umesono Laboratory for helpful discussion during the study. The authors also thank Professors K. Matsuo, A. Yoshimura, and S. Kato for their instructions in writing the paper. This paper is dedicated to Dr. Yumi Yamamoto. ![Structural organization of chicken (upper panel) and human (lower panel) PPAR*γ* genes. Exons are shown as green boxes with the *γ*2-specific exon colored in yellow.](PPAR2013-186312.001){#fig1} ![Transactivation function of cPPARs in serum-free media. After transfection with each plasmid mixture, cells were cultured for 36 hrs, lysed, and luciferase reporter assays were performed. MH100X4-luc is a GAL4 responsive luciferase reporter, and PPREX3-luc is a PPAR responsive luciferase reporter. Data are derived from triplicate points from two independent experiments and represented as the mean ± SE; *n* = 6. The results presented in this figure have been published \[[@B1]\].](PPAR2013-186312.002){#fig2} ![Effect of serum on the transactivation function of cPPARs. (a), (b). Effects of serum on the transactivation function of PPARs. Serum-induced transactivation function of cPPARs (a) or hPPARs. (b) After transfection with each plasmid mixture, cells were cultured with indicated serum conditions for 36 hrs, then lysed, and luciferase reporter assays were performed as described previously \[[@B1]\]. FBS: fetal bovine serum, CBS: calf bovine serum, BS: adult bovine serum, and ChS: chicken serum. (c) The effect of lipid extract from chicken serum (ChS) on the transactivation function of cPPARs. After being transfected with each plasmid mixture, cells were cultured for 36 hrs in DMEM/10%FBS with or without 5% ChS or ChS lipid extract equivalent of 2% ChS. Then cells were lysed and luciferase assays were performed. Data are derived from triplicate points from two independent experiments and represented as the mean ± SE; *n* = 6.](PPAR2013-186312.003){#fig3} ![(a) Alignment of amino acid residues of chicken, mouse, and human PPAR*β*/*δ* LBDs. LBD is located at the C-terminus of chicken (amino acid residues 243 to 441) and mammalian (245 to 443) PPAR*β*/*δ* proteins. Amino acid residues conserved between mouse and human but not in chicken are highlighted in orange (mammals) and green (chicken). The amino acid residues critical for bezafibrate-dependent response of PPAR*β*/*δ* are indicated by a purple box. Accession numbers are as follows: cPPAR*β*, AAF80480; mPPAR*δ*, NP_035275; hPPAR*δ*, NP_001165289. (b) Bezafibrate (Beza) and carbaprostacyclin (cPGI) responsiveness of point mutated chicken PPAR*β*(Val419Met), human PPAR*α*(Val444Met), and PPAR*δ*(Met417Val) as previously reported \[[@B1]\].](PPAR2013-186312.004){#fig4} [^1]: Academic Editor: Juan J. Loor
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SUMMARY Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in the developed world. Smoking is an important risk factor for the disease, but genetics determine outcome and disease severity. A significant and broad challenge in establishing the causal molecular mechanism from genetic association data is the fact that a majority of COPD-associated variants map to non-coding regions of the human genome. One of the genes strongly associated with COPD is SERPINA1, which encodes the a-1 antitrypsin protein. The SERPINA1 gene is remarkably complex: It has eleven splice variants, all of which change the 5'-untranslated region (5'-UTR) without altering the sequence of the encoded protein. We found that translation efficiencies of the mRNAs varied by orders of magnitude due to the strengths of upstream RNA structure and of open reading frames (uORFs). uORFs are found in roughly 50% of human genes and tend to function to reduce translation of the downstream gene but, other than this observation, are poorly understood mechanistically. We have developed and parameterized a structure-based leaky scanning model of translation that considers alternative splicing, uORF Kozak sequence strength, the RNA structure at the initiation site of uORFs, and the efficiency of translation of the primary open reading frame. We propose in our first aim to define how RNA structure and alternative splicing control expression of a-1 antitrypsin and extend this approach to two other COPD-associated genes. In our second aim we will comprehensively characterize the RNA structural elements in the SERPINA1 mRNA 5'-UTRs and in two other COPD-related mRNAs that control translation efficiency, without and with uORFs. These experiments will establish accurate and broadly impactful frameworks to define the RNA structural features that modulate translation efficiency in 5'-UTRs and will refine ribosomal leaky scanning models to better predict tissue-specific expression of COPD-associated proteins.
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Ferrite Magnets Ferrite magnets are sintered permanent magnetic materials, composed of barium and strontium iron body, this kind of magnetic material in addition to a strong anti-demagnetization performance, there are advantages of low cost. Ferrite magnets are rigid and brittle and require special machining processes. The opposite magnets are magnetized in the direction taken in the direction of their manufacturing direction, and their homogeneous magnets can be magnetized in any direction because they are not oriented, although a slightly stronger magnetic induction is found on the side where the compression surface is often the smallest. The magnetic energy product ranges from 1.1MGOe to 4.0MGOe. Due to the low cost, ferrite magnets have a wide range of applications, from motors, speakers to toys, handicrafts, and thus is currently the most widely used permanent magnet materials. Ferrite Magnets Using powder metallurgy method of production, residual magnetization is low, the magnetic permeability is small. Coercive force is strong, strong anti-demagnetization ability, especially suitable for dynamic working conditions of the magnetic circuit structure. The material is hard and brittle and can be used for cutting tools with emery tools. The main raw material is oxide, it is not easy to corrosion. Operating temperature: -40 ° C to + 200 ° C. Ferrite magnets are divided into the opposite sex (heterosexual) and the same sex (isotropic). The isotropic sintered ferrite permanent magnet material has a weak magnetic properties but can be magnetized in different directions of the magnet. The anisotropic sintered ferrite permanent magnet material has strong magnetic properties but can only follow the magnet Fixed magnetization direction. Ferrite Magnets In the actual production of ferrite magnets, the chemical composition of good raw materials, and sometimes may not be able to obtain a good performance and microstructure of ferrite magnets, the reason is the physical properties of the impact. The physical properties of the listed iron oxides include the average particle size APS, the specific surface area SSA, and the bulk density BD. As the manganese zinc ferrite magnets in the formula accounted for about 70% of iron oxide, so its APS value of ferrite magnets powder APS value has a great impact. In general, the iron oxide APS value is small, ferrite magnets powder APS value is also small, is conducive to speed up the chemical reaction speed. However, taking into account the fine powder particles is not conducive to post-press suppression and sintering easy to crystallize the situation, APS value should not be too small. Obviously, when the iron oxide APS value is too large, in the calcination, due to the larger particle size, only the spinel phase diffusion reaction, can not be further grain growth process. This inevitably leads to an increase in the activation required during sintering, which is detrimental to the solid phase reaction.
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Terracotta tile cleaning and polishing Chelsea Bridge Our local Chelsea Bridge cleaning teams could offer you full list of services when it comes to tile, ceramic and terracotta cleaning and polishing. Our experts are fully trained to bring your tile's shine back. Don't hesitate any longer, contact us and get your free offer. We guarantee you perfect result. You have selected: Terracotta tile cleaning and polishing Chelsea Bridge, London We know how to treat your tile floor and make it shine. Don't hesitate any longer and contact our Chelsea Bridge local cleaning team. Get your free no obligation offer now. Ceramic tile floor cleaning and polishing Chelsea Bridge Ceramic tile is the most common flooring materials nowadays. It is durable, easy to install and maintain. Our many years experience is the reason we are fully prepared to choose the proper way to clean and polish your ceramic tile floor. Contact our local Chelsea Bridge cleaners and you will be fascinated by the result. Nation Wide Cleaning 4U professional cleaning teams are fully trained to restore and seal your terracotta and terrazzo tile floor. First of all they will have to remove the previous products. We prefer to chemically remove the existing floor finish. The dissolved seal and dirt we collect in special machinery. After this Nation Wide Cleaning 4U Chelsea Bridge experts will allow a sufficient drying time. Finally they will apply 2 or 3 coats of specialist terracotta floor tile seal to preserve your floor. Quarry tiles cleaning and restoration Chelsea Bridge Quarry tiles are almost similar to terracotta tiles. The difference is that they are thinner and less porous. Our Chelsea Bridge professional cleaners will follow those described under terracotta above. They will examine the tiles and will propose you a customised programme for their regular restoration, seal and maintenance. Nation Wide Cleaning 4U Chelsea Bridge cleaning experts are fully licensed and insured so you won't have to worry at all. Don't put it off any longer, please get in touch with one of our local Ceramic Tile Restoration Experts on 0800 1123430 or via our booking form 24/7 and get the best of the best when it comes to Ceramic Tile Restoration Chelsea Bridge, Tile Cleaning & Sealing Chelsea Bridge and Polishing Services Chelsea Bridge.
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Friday, April 20, 2007 there's Carson Street runnin' through the yardand I'm a bad boy, 'cause I don't give a shit about them steelersI'm a bad boy because I peed on my terrible towelFreeeeeeeeefallinnnnnngg(Tiff could write this better) We are all free falling, but if you think we are going anywhere you're on angel dust.Way too much going.But times are tough..................................................................... In the aforementioned game five Buffalo was up 4-1 cruising.But Ted Nolan rallied the troops, leaving us to wonder what if the Pens played like that.Nevermind.Isles Down 4-3 here comes Satan down on Ryan Miller. Not much to see in this game anyway.All Marty Brodeur all the time.Yahoo's NHL Photos= sick The game ended with a words between coaching staffs.New Jersey leads the series 3-2. ................................... Great game in Nashville tonight.Too bad everyone was at a Hank Williams Jr. concert. For everyone that was their they saw Barry Trotz finally getting eaten by the sharks.Disappointing end for Nashville. ................... Little house cleaning: We will be here every day/night for the rest of our lives. So don't be strangers. We are going to start recapping other games until the playoffs end, maybe tv shows, and maybe the nightly news to stay sharp. Two minutes left to go in the newscast, is their any other anchor you'd rather have in the chair then Ken Rice.He makes David Johnson look like a freshman journalism major. Playoff brackets will be posted this weekend Photoshops are always in play, its a long off season so stay sharp. ...................... Some interesting notes from SI.com about the Pens.If this didn't say "Fred Shero" it would have been something.Come on SI.com.Wow.Make no mistake though if the Pens get Ryan Smyth.This is Smythblog next year. Who are the other Pens players, besides Gary Roberts, that are at the end of their contract? It was a great season for these young guys. My vote for the Pens MVP would have been John LeClair. If he hadn't hurt Malkin in the pre-season, Staal wouldn't have had a chance to show us he belonged here. Even though I think that Therriean should get serious consideration for coach of the year, I don't think that he played his best guys in the last few weeks of the season or in the 5 playoff games. I think that Recchi should have been scratched several times to play Ekman, Thorburn, or Petrovicky. Did you see Petro join the PCP line in Game 4! Why scratch him in Game 5? George sure didn't look like he belonged out there. Why not play Naserdine? He had the best plus/minus on the team. I'm sorry to say but in the end, Mark Eaton looked terrible. Here is my wish list for adding talent for 07/08: At least 1 really good face-off guy (right-handed is preferred). Two punishing defensemen with some hockey sense (prefer 1 be right-handed). A backup goalie that is decent and makes half of Thibault's salary because MAF will be playing at least 60 games per season. Last couple of things. Who remembers bio-rhythms from the 1980's? Ottawa is good, but come on! They were unbelievable at always being in the right place at the right time to block a shot or break up a pass. These guys were all peaking on the same cycle like sorority sisters! I'll be surprised if they can keep that level of play up against the Devils or Rangers in Round 2. I want 2 teams to be in the finals that have never won the Cup before. I'm thinking that it might be Buffalo versus San Jose. The Steelers rule. Why do you guys bash them all the time? You live in Pittsburgh don't you? They won the superbowl coming in as the lowest seed. Not to mention, they're from the Burgh. So what the hell? anonymous 4/21/2007 1:58 AM, Leclair as MVP was funny when Guy Junker wrote an article about it. But you did bring back a good point. Crazy how the stars line up sometimes, huh?I don't really mind anymore about people bashing the Bucs and Steelers, as long as they make valid points. But as far as moaning about the Steelers getting so much coverage in the local media, on Post-Gazette.com's website the day after the series ending loss, on of their top five most emailed stories was Alan Faneca not reporting to voluntary mini-camp. Not one story about the Pens was in that top five, at least when I looked. So yeah, Pittsburgh is a drinking city with a football problem. Who gives a shit. And about that SI.com rumor article about us possibly getting Ryan Smyth? As our Scottish friends would say...fat fookin' chance. I'd rather see us get a couple of mid-range guys than one big ticket free agent. However, in Ray Shero we trust... letang will be nice, but it's hard to count on young defensemen. we all remeber how bad whit looked at times the past few years. plus, isn't he more of an offensive d-man anyway? that would be more of the same (except for the righthanded shot) flames got absolutely dominated in detroit but won both games at home. why you ask? because all of there fans wore red and that makes for one intimidating venue. Can't help but wonder what might of been if the pens management organized the blackout. The Petty song reminded me of something (not that its of much relevance now) but is anyone here a Dropkick Murphys fan? They have a great hockey song called 'Time to Go'. I encourage you to look up the lyrics to it. It would be a great song to put in the blog for opening night next season. The song is originally for the Bruins, but with a few modifications it becomes a pens song. (Rancourt is the b's anthem singer so substitute jimmerson in there and change 'causeway' to 'parkway' and i think youve got a solid pens anthem) Sorry not to give you guys a shout out until now...I have been in Austin Texas without internet access since last Thursday. Awesome blog...best hockey blog, period. It's been a fantastic year. You guys gave me somewhere to vent when we lost, celebrate when we won, and an excuse to bust open Photoshop and kill time in-between games. I'm most definitely hanging around during the off-season. As everyone said we just like poking fun at the Steelers and this town blah blah blah.Huge draft coming up, due to the Pens I have no idea whats going on.I heard the steelers got a new coach?hahahaha jkWe love all our sports team. i saw colby and jeff reed and greg warren (long snapper) at dinner last night. colby wasnt nearly as big as a i thought hed be although he nose was just what it looks like on tv he seemed real chill tho jeff read was hitting on some about 19 yr olds and bought 4 of their dinners the girl he was with did not seem all that happy hah
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… party politics! Party politics has stifled any adult discussion of the threat we face from IS (Islamic State) and no, it’s not ISIL (Islamic State of Iraq & Levant, the Jewish / USA version) or Daesh the Arabic acronym which actually they do not like. For a full discussion of the name(s) of this primitive barbaric organisation see here. Bombs away, Hurray! Everywhere in the media, even in our best political discussion programs, journalists and politicians consume 90% of the time discussing the party politics of the issue, the “whipping procedure”, the free vote issue, the future of Corbyn, the “new politics”, to whip or not to whip etc. yawn etc. Anything indeed, apart from the detail required to end this sad bit of history. It is nonsense of course, but leaders of IS believe a 7th century prophecy. The Syrian town of Dabiq is where the second coming of Jesus will take place imminently. That is why the IS caliphate-in-waiting is centred on Syria. The Second Coming heralds the start of the world wide caliphate and the end of all of us disbelievers. We Kuffar are anybody who is not a Muslim, and moreover, you have to be the right kind of Muslim and that is Sunni. Pleasefollow the Kuffar link (previous sentence) to read an earnest debate about whether or not Muslims should actually play basketball with the unbelievers; read and weep at the ignorance and stupidity we have to fight. What we will probably have today, after the vote in parliament, is a concerted effort to bomb Raqqa in Syria, but I suspect that IS are already decentralising as our politicians discuss the shape of the discussion table. BUT… Where is the plan for reconstruction of Syria? Who is paying? Where are the foot soldiers of Saudi Arabia, China, Russia, Germany NATO and the USA? Without them, and their money, there can be no lasting solution. We need those boots on the ground to maintain the peace once the bombing stops. We will probably need the boots on the ground for years to come. Have all these players met to discuss the long term solution? Err, no. If the last 100 years of Middle East misery have taught us any lessons at all, it is that bombing the enemy might make good copy for the journalists and gung-ho politicians, but it actually achieves nothing. Corbyn is quite right but nobody can listen to the detailed arguments he has put because he has put them so badly. The British population seem not to be ready for the new politics of discussion and the detailed thought it needs. A bombing campaign is probably required, but as a small part of the overall action we need to take, but only as support for the boots on the ground of a UN led united army. The murderous, brain-washed, teenagers who carry out the killings and those who command them follow the barbaric rules of the Qur’an to the letter. IS is not interested in discussion. Old men in beards have Allah and the Qur’an as their narrative. However, the vast majority of Muslims are not the problem, they, like you and me, just want to work, school their children and live in peace. Islam, however, is the problem along with the West’s politically correct inability to fight back with reason. I’m tired of repeating this but just read the damn book yourself, you will soon see what I mean!
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GSP identifies good Samaritan struck and killed Evan Lilly, 33, from Athens was hit and killed in Oconee Thursday night, according to Georgia State Patrol. Officers said Lilly stopped to help another driver who had broken down in the travel lane of the Athens Perimeter. Another driver swerved to avoid the broken down vehicle, according the officers, and the car hit Lilly. Sara Giles, of Athens, was driving the car that hit Lilly. Georgia State Patrol is still investigating to determine if any charges will be filed. Outgoing Atlanta mayor Kasim Reed has given mayoral candidate Mary Norwood 48 hours to apologize after she claimed voter intimidation in the December 5 run-off election between her and Keisha Lance Bottoms. Outgoing Atlanta mayor Kasim Reed has given mayoral candidate Mary Norwood 48 hours to apologize after she claimed voter intimidation in the December 5 run-off election between her and Keisha Lance Bottoms.
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Property Description Golf Course Lot, Popular Daybreak Model, 1700 Sq. Ft. 2 Bedrooms, 2 Baths and a Private Den, on a quiet, low-traffic street. Low-maintenance front and back yard. Open Great Room Floor plan w/Split Bedrooms. Home with Private Den/ or extra Bedroom! Kitchen Cabinetry w/ Pull-out shelves, All Kitchen Appliances and Washer/Dryer included. Kitchen has a Large Dining area w/Bay Window. Flooring is Tile, Wood and Carpet in all the right places.Plantation Shutters plus high-quality Hunter Douglas blinds throughout, Large Master Bedroom with Bay Window. Covered back patio with extended seating. Garage is Extended in Length, with attached Cabinets, Soft Water System. You will enjoy the lovely Golf Course Sunsets!
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A Statement on Decorum From the Speaker of the House 12/12/2012 05:37 EST | Updated 02/11/2013 05:12 EST CP As the House prepares to adjourn for the Christmas holidays, the Chair would like to make a short statement about order and decorum. In recent months, for a variety of reasons, the atmosphere in the Chamber has been difficult. This is perhaps not surprising, since the House is made up of Members who are committed and whose strongly-held views are freely expressed on a daily basis. The House is also an inherently adversarial forum that tends to foster conflict. As a result, sometimes emotions get the better of us and we quickly find ourselves in situations marked by disorderly conflict. Tone and gestures can cause as much of a reaction as the words used in debate. Lately, it appears that all sides have, at different times, strayed quite far from the flexibility, accommodation and balance that ideally ought to exist in this place. My task as Speaker is to ensure that the intensity of feeling expressed around some issues is contained within the bounds of civility without infringing on the freedom of speech that Members enjoy. The Chair tries to ensure that our rules are adhered to in a way that encourages mutual respect. But all Members will recognize that ultimately, the Speaker must depend on their collective self-discipline to maintain order and to foster decorum: my authority to enforce the rules depends on the cooperation of the House. Our electors expect all Members to make greater efforts to curb disorder and unruly behaviour. So I urge all Members to reflect on how best to return the House to the convivial, cooperative atmosphere I know all of us would prefer. This would be a great help to me and my fellow Chair Occupants, about whom I would also like to say a few words. I would like to take a moment to salute, on behalf of us all, the excellent work of our Deputy Speaker the Member for Windsor-Tecumseh (Mr. Comartin), and our Assistant Deputy Speakers, the Members for Haliburton - Kawartha Lakes - Brock (Mr. Devolin) and Simcoe North (Mr. Stanton). Often under trying circumstances, my colleagues in the Chair have soldiered on, doing their best to uphold the finest traditions of this Chamber. As all honourable Members are aware, unusual events arise frequently in the House. Thus the task of reading the will of the House is often left to Chair occupants -- whether an unexpected sequence of events occurs or an expected sequence of events does not. Since the House resumed its sittings in mid-September, we have witnessed our fair share of instances where the House has been faced with unforeseen situations but has nevertheless found its way with the help of Chair Occupants. I want to say that the three gentlemen who share duties in the Chair have in my view upheld the highest standards of professionalism and impartiality while trying to facilitate the orderly conduct of House business. Only those who have had the privilege of serving in the Chair and presiding over the deliberations in this Chamber can truly understand to what degree the role involves as much art as science. I am very proud of the way in which these Chair Occupants conduct themselves and I want, on your behalf, to thank them for their dedication to the institution and for their ongoing good work.
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Keyshawn Johnson, and Zubin Mehenti begin the hour with a correction from....Bill Parcells. The Big Tuna texted Key to correct him on a play he described. He is still getting coaching from the Tuna after all these years. Michael Collins joins the show to shed some light on Tiger and the field. Ohio State cornerback Shaun Wade joins the show to talk about him opting back in to the season now that the Big 10 is back.
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Multistakeholder perspectives on composite measures of ambulatory care quality: a qualitative descriptive study. The development of composite measures of ambulatory care quality is an area of growing practice and policy interest. Using 29 semistructured interviews, this study describes the opinions of stakeholders related to the use and development of composite measures in a multistakeholder setting. Research experts working in multistakeholder settings need to understand the perspective of various stakeholders, many of whom have varying levels of research expertise, in order to develop useful and acceptable composite measures. Findings from this study suggest that to achieve maximal stakeholder buy-in, research experts should focus on clinical area-specific composites that are designed and constructed in a simple and transparent manner. However, composite measures are not a panacea for improving the utility of public reporting. Performance measure and report card creators should continue to investigate other ways to improve the user-friendliness of their reports and to address other barriers that prevent more extensive use of reports.
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Related Tags: NEW YORK (1010 WINS) — The air throughout much of one Queens neighborhood was choked with thick, black smoke Monday as firefighters battled a persistent fire that injured four and displaced two households. A 4-alarm fire broke out around 5:30 p.m. Monday at 112-12 Jamaica Avenue, a commercial building, near 113th Street in Richmond Hill. Firefighters were still on the scene late Monday night battling pockets of fire. The flames broke out in the ceiling of a business where construction was being done. The blaze left three firefighters and one civilian with non-life threatening injuries — all four people have been hospitalized, 1010 WINS’ Glenn Schuck reported. Six businesses were also destroyed in the fire and an apartment connected to the building had to be evacuated. The Red Cross said that nine adults and two children were displaced and are being provided emergency housing. About 200 firefighters battled the huge fire. Chief of Department Ed Kilduff said there was a very close call for his men at one point. “A smoke and fire explosion occurred. It pushed the ceiling down on the members that were operating inside. The incident commander felt that members might be trapped under the ceiling debris,” he said. “We eventually got the firefighters out.” Fire marshals are talking to construction workers, who were in the ceiling of the building, to see if they had possibly started the fire.
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--- abstract: 'We present a perspective on recent observations of the photoinduced phase separation of halides in multi-component lead-halide perovskites.  The spontaneous phase separation of an initial homogeneous solid solution under steady-state illumination conditions is found experimentally to be reversible, stochastic, weakly dependent on morphology, yet strongly dependent on composition and thermodynamic state. Regions enriched in a specific halide species that form upon phase separation are self-limiting in size, pinned to specific compositions, and grow in number in proportion to the steady-state carrier concentration until saturation. These empirical observations of robustness rule out explanations based on specific defect structures and point to the local modulation of an existing miscibility phase transition in the presence of excess charge carriers. A model for rationalizing existing observations based on the coupling between composition, strain and charge density fluctuations through the formation of polarons is reviewed.' author: - 'David T. Limmer' - 'Naomi S. Ginsberg' title: Photoinduced phase separation in the lead halides is a polaronic effect --- Lead halide perovskites have emerged as a promising class of semiconducting materials for photovoltaic and light emitting devices.[@kovalenko2017properties; @beal2016cesium; @ha2014synthesis; @mcmeekin2016mixed] They are solution processable, defect tolerant, and offer a large library of potential photoactive compositions.[@de2015impact; @mcmeekin2016mixed; @stranks2013electron; @burschka2013j; @nie2015high] The chemical formula of the perovskite lattice is ABX$_3$, where the B site cation is lead, the A site cation can be inorganic, like Cs, or organic, like methylammonium (MA) or formamidinium (FA), and the X site anion is a halide, typically Cl, Br or I. Both single crystals and thin films have been synthesized containing mixtures of X site halides. Solid solutions of different halide anions are particularly attractive as their intrinsic band gaps are monotonic functions of composition, increasing across the visible spectrum from 1.5 eV for pure I to 2.9 eV for pure Cl.[@noh2013chemical; @sadhanala2015blue] However, upon continued light exposure, initially homogeneous solid solutions of mixed halides undergo spontaneous phase separation.[@hoke2015reversible] During photoinduced phase separation, low bandgap states form and act as traps with enhanced low energy luminescence. This behavior is detrimental to device performance, as the low energy trap states degrade power conversion efficiencies.[@samu2017victim] Observations of photoinduced phase separation have been made for broad ranges of composition and morphology, suggesting that this behavior is general and intrinsic to this class of material.[@slotcavage2016light; @brennan2017light] As a consequence, it has garnered significant attention for both practical and fundamental reasons. This perspective aims at summarizing existing observations of this phenomena and at reviewing a consistent framework within which these observations can be understood. The existence of photoinduced phase separation reflects an unusual interplay between the electronic and lattice degrees of freedom in the lead halide perovskites that is distinct from traditional inorganic materials and organic semiconductors. Unlike traditional inorganic semiconductors, the predominantly ionic bonding character[@egger2016hybrid] of the lead halide octahedral sub-lattice results in dynamic crystal structures that are anharmonic,[@brivio2015lattice; @marronnier2018anharmonicity] mechanically soft,[@rakita2015mechanical] accommodate high defect concentrations[@kim2014role] and correspondingly large ionic diffusivities.[@lai2018intrinsic; @kerner2017ionic; @peng2018quantification] Unlike organic semiconductors, the flexible ionic lattice structure results in large polar fluctuations and consequently high dielectric constants,[@brivio2013structural; @almora2015capacitive] facile screening of excess charges, low exciton binding energies[@d2014excitons; @miyata2015direct], and intermediate electron-phonon coupling strengths.[@soufiani2015polaronic; @wright2016electron] These unique material properties admit the emergence of novel collective behavior, such as an array of photoactive and photo-induced phase transitions.[@halder2015exploring; @matsuishi2004optical; @bischak2019liquid; @lin2018thermochromic] A number of models have been proposed to explain the collected observations of photoinduced phase separation and how it is modulated with changes in composition and large scale morphology. Initial proposals posited the phase separated state was the equilibrium state at ambient conditions.[@brivio2016thermodynamic] In such models, photoexcitation was envisioned to anneal the material towards this equilibrium, however they fail to account for the reversibility of phase separation and the ability to cycle it through alternating light and dark conditions. Other models suggest the driving force for phase separation is the band gap reduction associated with halide regions rich in one component. [@draguta2017rationalizing] While certainly an important effect, a bias towards lower band gap regions results in a linear change to the free energy as a function of composition and cannot produce emergent bistability, two stable phases, in a system initially above its miscibility critical point. If this were the only stabilizing factor for phase separation, the stabilized regions would be made up of compositions that would depend on the bulk material composition. The reversible, nonlinear changes accompanying photoexcitation have been suggested previously to proceed through the formation of polarons, which can induce excessive strain energy, destabilizing solid solutions.[@bischak2017origin] Polaronic effects in the lead-halides have been invoked broadly to rationalize the long diffusion lengths of photogenerated charge carriers and the temperature dependence of their mobility, as well as their low bimolecular radiative recombination rates.[@zhu2015charge; @miyata2017large; @neukirch2016polaron; @frost2017calculating; @miyata2017large] A thermodynamically consistent framework for changes in solid solution phase separation with polaron formation was initially proposed by Bischak et al,[@bischak2017origin] and a generalization incorporating effects from nanostructured domains was proposed by Wang et al.[@wang2019suppressed] These models clarify most of the existing observations of phase separation in the lead halides, which are summarized in the next section. The detailed mechanism of how polarons induce a self-limiting form of phase separation is reviewed, together with a discussion of the numerical techniques used to justify the assumptions of this model. We conclude this perspective by summarizing the relation of the models to the observations and by noting the remaining open questions and challenges. Overview of experimental observations {#overview-of-experimental-observations .unnumbered} ===================================== ![Schematic photoluminescence spectra, time dependence and structural charges accompanying photoinduced phase separation. The top panels illustrate the steady state photoluminescence spectra in the dark and under light soaking, as well as how the red shifted peak grows in time. Inset illustrates a cartoon of the perovskite lattice. The bottom panels are representative illustrations of photoluminescence or cathodoluminescence imaging of thin films during photoinduced phase separation.[]{data-label="Fi:1"}](fig1a.pdf){width="8.5cm"} The basic phenomenology of photoinduced phase separation in the lead halides is illustrated in Fig. \[Fi:1\]. As first observed by Hoke et. al.[@hoke2015reversible], an initially well mixed solid solution of MAPb(Br$_x$I$_{1-x})_3$, with $x$ between 0.1 and 0.9 will have a characteristic photoluminescence peak between the extremal values of a pure Br and pure I lattice, reflecting the composition dependent optical gap of the material. Upon continued exposure to light at or above this energy, the photoluminescence peak red-shifts and increases in intensity. At steady state, the location of the peak is coincident with a lattice initially prepared near $x=0.2$, independent of the initial composition. The independence from initial composition indicates the nonlinearity of the effect of illumination. The time dependent rise in the new photoluminescence peak is sigmoidal, with a characteristic timescale on the order of minutes. Importantly, nearly all observations of this process report it to be fully reversible.[@hoke2015reversible; @bischak2017origin; @bischak2018tunable; @nandi2018temperature] Provided sufficient time without light exposure, the photoluminescence peak returns to its initial energy. This reversibility indicates that the initial solid solution is stable under low light conditions, but that stability is altered under illumination. Accompanying the formation of the low energy luminescent state are dramatic changes to the lattice. Studying thin films, Hoke et al[@hoke2015reversible] reported a splitting of x-ray diffraction peaks under light soaking, and suggested that halides separated into two distinct crystalline phases. Similar x-ray studies followed, confirming that initial observation and indicated the potential for coherency strain, the strain due to lattice mismatch, between regions of different composition.[@lehmann2019phase; @fang2016photoluminescence; @byun2017light] Early work by Bischak et al., also in thin films of MAPb(Br$_x$I$_{1-x})_3$, employed cathodoluminescence imaging and found that small iodine rich aggregates form throughout the film.[@bischak2017origin] Rather than growing in size or coalescing, the density of aggregates was found to increase over time until the number reached a steady state value. See Fig. \[Fi:1\] for an illustration. At longer times, those aggregates where observed to diffuse to grain boundaries, presumably to reduce the coherency strain previously noted. Subsequent study on single crystals observed that the initial location of iodine rich aggregates was stochastic in repeated measurements.[@bischak2018tunable] These observations demonstrated that the formation of iodide rich domains was intrinsic to the material and not dependent on large scale morphology like the presence of grain boundaries. Additional work employing fluorescence imaging in single crystals and photoluminescence imaging in thin films have confirmed these studies.[@dequilettes2016photo; @mao2019visualizing; @wang2019suppressed] In all direct observations, there is no indication of macroscopic phase separation, although diffraction limitations in photoluminescence and carrier migration lengths in cathodoluminescence each preclude direct quantification of domain size. The direct imaging of phase separation demonstrated the facile means by which ions can typically move throughout the perovskite lattice. These observations are consistent with AC conductivity measurements that have long demonstrated that purely inorganic perovskites, like CsPbBr$_3$ or CsPbCl$_3$, are efficient halide conductors.[@mizusaki1983ionic] Mobile halide ions are also implicated in observations of hysteresis in cyclic voltammetry studies in hybrid perovskites with organic cations such as MA and FA.[@pellet2014mixed; @tress2015understanding] Single crystalline perovskite nanowire heterojunctions made from CsPbBr$_3$ or CsPbCl$_3$ have been studied with wide-field and confocal photoluminescence, allowing for the visualization of halide anion inter-diffusion in the absence of light soaking where the homogeneous solid solution is stable.[@lai2018intrinsic] The combination of direct imaging and simple geometry allowed for the accurate measurement of anionic lattice diffusivities, and indicated that halide diffusion was vacancy mediated. While photoinduced phase separation has been observed in a variety of different morphologies produced under disparate synthesis conditions, differing morphologies appear to change the rate of phase separation.[@zhang2017photoluminescence] By directly modulating halide vacancy levels through the exposure of excess halides, halide mobilities can be decreased and subsequently phase separation effects have been shown to become less prominent over experimental timescales.[@yoon2017shift] Similarly, photoinduced phase separation can be partially suppressed by making grains larger, [@hu2016stabilized] passivating surfaces with ligands,[@xiao2017mixed] or by employing small nanocrystals or films with high quantum yields.[@sutter2015high] Indications are thus that the stability of photoinduced phase separation is not strongly influenced by morphology but that the kinetics associated with halide inter-diffusion can be dramatically altered depending on the halide vacancy concentrations resulting from that morphology. The dependence of phase separation on composition has received significant attention as a potential route to mitigating its detrimental effects on device performance. For mixed halide perovskites with MA cations, mixtures of either Br/I or Cl/Br have both been found to undergo photoinduced phase separation across broad ranges of compositions.[@yoon2016tracking; @talbert2017bromine; @bischak2017origin; @byun2017light] Under low light conditions, mixtures of Cl and I are not stable under ambient conditions and phase separate into macroscopic domains, indicating the presence of an equilibrium miscibility transition temperature above 300 K for these most size-dissimilar halides.[@ralaiarisoa2017correlation] While the band structures and mechanical properties of lead halide perovskites are largely insensitive to changes of cation, there has been much study into its effect on mitigating photoinduced phase separation. Studies on Cs based perovskites are somewhat mixed, with indications in thin films that they are more stable to light-induced phase separation over some ranges of Br/I ratios $x_\mathrm{Br}<0.33$, though it can still occur for $x_\mathrm{Br}>0.33$.[@beal2016cesium; @bush2018compositional] Cation replacement of MA with Cs in single crystals has been shown to stabilize the mixed halide state with only transient I-rich clustering being observed and no stable phase separation.[@bischak2018tunable] Resilience to photoinduced phase separation has been demonstrated with mixed cation perovskites including mixtures of FA and Cs[@mcmeekin2016mixed] in combination with MA. Finally, replacing Pb with Sn suppresses photoinduced phase separation.[@yang2016stabilized] Most of these observations show that more polar lattices are more susceptible to photoinduced phase separation. In most of these studies, however, changes to the underlying crystal structure stability and defect concentration are not considered. As a phase transition, the dependence of photoinduced phase separation on the thermodynamic state of the material is of specific interest. The temperature dependence of the transition has been studied in both Cs and MA based materials. In MA based films, photoinduced phase separation has been found to occur throughout temperatures ranging between 200 K and 300 K.[@hoke2015reversible] Notably by measuring the initial growth rate of the new photoluminescence peak as a function of temperature, the activation energy for phase separation could be measured. It was found to be similar to the previously measured halide conductivity activation energies, indicating that phase separation itself is a diffusive process. A later study found that below 190 K, phase separation did not occur during 4 hours of illumination, indicating either the slow down of halide diffusion or the role of different structural phases that become stable at low temperature in mitigating phase separation.[@nandi2018temperature] That study also found that phase separation ceased at temperatures above 325 K, indicating the location of the light induced miscibility temperature to be just above ambient conditions. The temperature dependence has also been measured in Cs based crystals, between 150 K and 300 K, where for compositions of $x_\mathrm{Br}>0.4$ phase separation was consistently observed.[@wang2019suppressed] As in the MA films, lower temperatures required significantly longer times for phase separation to equilibrate. Very high pressures, greater than 0.9 GPa, have been found to suppress photoinduced phase separation in MA based films.[@jaffe2016high] This threshold pressure corresponds to a change in stability from the normal cubic lattice structure to a so-called $\beta$-phase where neighboring lead-halide octahedra are tilted on average away from 180$^\mathrm{o}$. The sharp thresholds in pressure, temperature and composition observed are thus consistent with canonical phase behavior, though experimentally determining the phase boundaries with high accuracy is complicated by slow, diffusive kinetics. Provided a morphology and composition where phase separation can occur, its extent and characteristic time dependence depends on the illumination intensity and light soaking protocol. Under constant, continuous wave illumination, the steady state photoluminescence intensity has been shown to be proportional to the carrier concentration, at low power.[@bischak2017origin] At high power, the photoluminescence intensity saturates, together with the carrier concentration.[@draguta2017rationalizing] The growth of photoluminescence intensity reflects a growing number of aggregates formed, as has been visualized with photoluminescence and cathodoluminescence imaging, whose number grow with the steady state carrier concentration before saturating. Most studies have shown that the time to steady state photoluminescence also depends on the illumination intensity, and Bischak et al demonstrated that it specifically scales linearly with the inverse carrier density for small densities.[@bischak2017origin] Analogously, the rate of cluster formation, as visualized with cathodoluminescence imaging, was found to be independent of carrier concentration, reflecting that each cluster forms independently. Indications that it is the steady-state concentration of charge carriers that dictates phase separation are supported by varying exposure time studies and observations of phase separation from direct current injection. Specifically, Yang et al manipulated the charge carrier concentration as a function of time by varying the repetition rate of illumination at constant average power in a pulsed laser experiment.[@yang2016light] They observed a threshold frequency of 500 Hz below which no shift of the photoluminescence peak was observed, but above which phase separation occurred. It has been observed that internal gradients in carrier concentrations produced by asymmetric illumination can affect phase separation.[@barker2017defect] A definitive measurement point to the particular role of charge carriers was carried out by Braly et al[@braly2017current] and separately by Duong et al,[@duong2017light] both of whom demonstrated that running a steady-state current through the film can also induce phase separation, when the charge injection was equivalent to that generated by 1 sun illumination. As with transient illumination, transient scanning electron beam experiments do not induce phase separation below a threshold dose. Taken together, these observations indicate that the extent of phase separation depends on the steady-state concentration of charge carriers and suggest that at low, e.g., 1 sun equivalent, intensities each localization of a charge carrier in a clustered region occurs independently. This array of experimental observations point to the specific role of excess charge carriers, generated by light or injected directly, in altering the miscibility of a mixed halide solid solution in the lead halide perovskites. Changes in initial temperature, pressure and composition, can have large effects on the extent and appearance of the photoinduced phase separation, while changes in morphology seemingly most affect its kinetics. It would seem therefore that a natural framework for rationalizing the driving force for photoinduced phase separation would be to consider how excess charges can modulate an existing, underlying phase transition. Molecular framework for photoinduced phase separation {#molecular-framework-for-photoinduced-phase-separation .unnumbered} ===================================================== In order to develop a microscopic understanding of photoinduced phase separation in lead halide perovskites, we must be able to distinguish the underlying thermodynamic driving forces that would result in phase separation stability, from dynamical effects associated with a hierarchy of disparate timescales in photo-active materials. We therefore first present a framework for considering the thermodynamics of photodinduced phase separation and then present the dynamical considerations afterwards. The thermodynamic perspective we present is based on a generalization of standard solid state solution phase transition theory, adding in a source of strain from photogenerated localized charge carriers. The dynamical perspective is simplified by assuming that halide motion is vacancy-mediated and is the rate limiting step to phase separation, as it occurs orders of magnitude slower than charge carrier and lattice relaxation. The multi-scale nature of this process requires that novel numerical tools be invented and used to test the simplifying assumptions of the theory. These we also discuss below. ![Illustration of how the phases diagram (upper-left) change under illumination, due to the change in the free energy surface (lower-left). The right cartoons illustrate the distribution of two halide species (orange and blue) in the light and dark.[]{data-label="Fig:2"}](fig2.pdf){width="8.5cm"} Thermodynamics of photoinduced phase separation {#thermodynamics-of-photoinduced-phase-separation .unnumbered} ----------------------------------------------- Given the preponderance of experimental observations pointing to the reversibility and robustness of the photoinduced phase segregation transition, a description of this process based on modulating an underlying miscibility transition was proposed by Bischak et al.[@bischak2017origin] That theory, reviewed here, builds on textbook descriptions of phase separation in solids coupling compositional fluctuations with elastic deformations,[@cahn1962spinodal] with an additional field describing the charge density fluctuations generated by free charges. In general, the thermodynamics of phase separation of a binary mixture are the result of a balance between the entropy of mixing that tends to favor homogeneous phases and specific energetics that can favor phase separation. We take the local concentration difference, $\phi({\mathbf{r}})=\rho_{X'}({\mathbf{r}})-\rho_{X}({\mathbf{r}})$, between two halide species, $X$ and $X^{'}$, at point ${\mathbf{r}}$ in a coarse-grained continuum field to be our local order parameter. For small deviations in composition from $\phi({\mathbf{r}})=0$, the simplest model capable of describing phase separation is the effective Hamiltonian or free energy function, $$\label{Eq:1} H_\phi = \int d{\mathbf{r}} \, a \phi^2({\mathbf{r}})/2 + u \phi^4({\mathbf{r}})/4+ g| \nabla \phi({\mathbf{r}}) |^2 /2$$ where the polynomial expansion of $\phi({\mathbf{r}})$ follows from the expansion of the entropy of mixing and pair interactions for small $\phi({\mathbf{r}})$, and the square gradient term accounts for interface formation, as needed for the conservative matter field considered here.[@chaikin2000principles] For simplicity we work under conditions of zero chemical potential difference between the two halides. In principle, all three parameters, $a,u$ and $g$, depend on external conditions. For simplicity, we take a Flory-like model,[@chaikin2000principles] with $a=2{k_\mathrm{B}}T- \Delta H_\mathrm{m}$, where $\Delta H_\mathrm{m}$ is the enthalpy of mixing at constant volume evaluated at $\phi=0$ in the cubic perovskite phase and ${k_\mathrm{B}}T$ is Boltzmann’s constant times temperature, $u=4{k_\mathrm{B}}T/3$, and $g$ is proportional to the surface tension between $X$ and $X^{'}$ rich domains. More generally, the average composition in the phase separated state and the local compressibility of compositional fluctuations above the miscibility temperature can be parameterized in terms of $a$ and $u$. Such a parameterization could be used to differentiate the equilibrium phase diagrams of Cs and MA based lattices, as their miscibility gaps are reported to be different.[@bechtel2018first] Minimization of this effective Hamiltonian results in a phase diagram that at low temperature supports phase separation, at high temperature predicts that the mixture is miscible, and at an intermediate temperature predicts a miscibility temperature that delineates these two regions. See for example Fig. \[Fig:2\]. Since there are large differences in the lattice constants between any two pure halide phases in cubic APbX$_3$ structures, the effects of coherency strains generated between two phase separated lattices cannot be ignored. Moreover, strain even in the lattice of well-mixed halides can play an important role in the thermodynamics of the system. Provided that there are no large scale morphological transitions accompanying phase separation and that the cubic symmetry of the perovskite lattice does not change upon changing composition, we can restrict the effects of strain to those derivable from linear elasticity. Moreover, we will employ isotropic elasticity theory for simplicity of notation, though our results are insensitive to those generalized to the cubic symmetry of the perovskite lattice with the correct average elastic constant. Under these simplifying assumptions, the contribution to the system from elastic deformations is given by the contribution to the Hamiltonian, $$\label{Eq:2} H_\Sigma = \int d{\mathbf{r}} \, K \frac{\Sigma^2({\mathbf{r}})}{2(1-\nu) }$$ where $\Sigma({\mathbf{r}})$ denotes the local strain field, $K$ is the bulk modulus in the mixed phase and $\nu$ is Poisson’s ratio. For variations in composition, and assuming the lattice is always in instantaneous equilibrium with local compositional fluctuations, the resultant strain due to the lattice mismatch is given to lowest order by $$\label{Eq:3} \Sigma({\mathbf{r}}) = 2\eta \phi({\mathbf{r}})$$ where $\eta = d \ln \ell /d \phi$ is the change in the lattice constant $\ell$ with composition, evaluated in the mixed phase. Higher order effects, like the change of the bulk modulus with composition, or the violation of Vegard’s law are neglected here.[@atourki2017impact; @weber2016phase] As first discussed by Cahn in the context of metal alloys,[@cahn1962spinodal] the excess strain due to compositional fluctuations stabilizes the well mixed solid solution by lowering the critical miscibility temperature. We refer to this transition temperature as the miscibility temperature for the lattice in the dark, $T_c^{(\mathrm{d})}$. This temperature can be computed within mean field theory as, $$\label{Eq:4} T_c^{(\mathrm{d})} = \frac{1}{2{k_\mathrm{B}}} \left ( \Delta H_\mathrm{m} - \frac{2\eta^2 K}{1-\nu} \right ),$$ which follows from functional minimization of the combined Hamiltonians in Eqs. \[Eq:1\]-\[Eq:3\] with respect to the compositional field. While the enthalpy of mixing at constant volume has not been measured experimentally, calculations have been performed at various levels of accuracy. Typical values for APbX$_3$ for mixtures of Br and I are between 2-4 kcal/mol.[@bischak2017origin; @bechtel2018first] The bulk modulus, $K$, is known experimentally for a variety of compositions and is typically close to 15 GPa.[@rakita2015mechanical] The change in the lattice constants with composition are also well known, for example for MAPbX$_3$ mixtures of Br and I, $\eta=0.08$ and for CsPbX$_3$ $\eta=$0.06.[@lehmann2019phase; @mashiyama1998disordered] Using Eq. \[Eq:4\], these material properties imply critical miscibility temperatures in the dark all below ambient conditions, in agreement with observations of stable well mixed solid solutions under those conditions. The contributions from the strain relaxation in all cases are large, with $\eta^2 K /(1-\nu) {k_\mathrm{B}}$ being on the order of 800 K, indicating the large susceptibility of the miscibility transition to strain. Under illumination, excess charge carriers change this traditional picture of phase separation in two ways. First, charges are attracted to regions rich in the component with the lower band gap. Second, provided charges form polarons, they strain the lattice, which as we have just shown, can greatly affect the stability of the mixed phase. The coupling of the charge to the composition field is straightforward, and computable from the band offset energies in two limiting pure halide lattices. Accounting for the strain of the lattice is more complicated. Polar coupling to the optical phonons is known to contribute to electron-phonon interaction in the perovskites,[@wright2016electron] and there are observations of acoustic scattering as well.[@mante2017electron; @guo2017polar] We consider the coupling of the charge to the acoustic phonons described by elasticity theory, and use deformation potential theory for electron-phonon interactions.[@whitfield1976interaction] To make the calculation tractable, we make a semiclassical approximation to decouple the electronic and lattice motions, and, as before, assume the lattice deformations are constantly in equilibrium with the local composition. Specifically, we add the lowest order coupling between excess charge density, $\psi$, and the strain and composition fields, $$H_\psi = \int d{\mathbf{r}} \, \frac{\hbar^2}{2 m} |\nabla \psi({\mathbf{r}})|^2 - \epsilon \psi({\mathbf{r}}) \phi({\mathbf{r}}) - \alpha \psi({\mathbf{r}}) \Sigma({\mathbf{r}})$$ where $\epsilon$ is the energetic bias of an excess charge to reside in different $\phi$ regions, $\alpha$ is the electron-phonon coupling constant, and $m$ is the effective mass of the excess charge and $\hbar$ is Planck’s constant divided by $2\pi$. Assuming that the electron is localized to a lengthscale, $R_\mathrm{p}$, we can integrate out its effect on the compositional fluctuations. Within a mean field approximation and working along the symmetry line where $\epsilon =0$, we can compute the critical miscibility temperature under illumination, $T_c^{(\mathrm{l})}$, due to the excess charge. The lowest order correction to Eq. \[Eq:Tcd\] appears at the level of $\alpha^2$ and is given by, $$\label{Eq:Tcl} T_c^{(\mathrm{l})} =T_c^{(\mathrm{d})} + \frac{2 m \eta^2 \alpha^2 R_\mathrm{p}^2}{h^2 {k_\mathrm{B}}} ,$$ which demonstrates that the miscibility temperature increases due to the formation of the polaron by an amount dependent on the electron phonon coupling, $\alpha$, the size of the polaron, $R_\mathrm{p}$, and the lattice mismatch, $\eta$. Under these assumptions, the stabilization of the phase separated state is due to the strain generated by the charge-lattice coupling, which reverses the reduction of the miscibility temperature upon strain relaxation in the dark. Typical values of $m=0.15 m_\mathrm{e}$,[@herz2017charge] $\alpha=4$ eV,[@mante2017electron] and $R_\mathrm{p}=2.5$ nm,[@frost2017calculating] result in a predicted enhancement of the miscibility temperature of $T_c^{(\mathrm{l})} - T_c^{(\mathrm{d})}$ = 700 K for MA based perovskites, and 350 K for Cs based materials. This predicted stability of the demixed phase is consistent with experimental observations of phase separation at room temperature under illumination and also in observing that the stability increases with electron-phonon coupling.[@bischak2018tunable] The light-induced stabilization of the demixed phase is confined to the region of the polaron, as only in its presence is there a source of strain, explaining why phase separation is observed to be self-limiting.[@bischak2018tunable] Photoluminescence measurements done at different powers have inferred a domain size to be 3 nm, assuming spherical clusters, in agreement with these predictions.[@bischak2017origin] The extent of the predicted stabilization from this simplified mean field theory is likely an overestimate, given observations of an upper-limit to photoinduced phase separation of 325 K in MA based films.[@nandi2018temperature] Corrections for fluctuations, surface tension from the finite size aggregates, and strain modulation[@wang2019suppressed] all tend to destabilize phase separation but are not accounted for in this simple theory. Nevertheless these arguments provide a useful framework for rationalizing experimental observations, and these corrections could subsequently be computed to achieve tighter agreement of the temperature dependence. ![Characteristic snapshots of an excess electron in an CsPbI$_3$ (left) and MaPbI$_3$ (right) lattice. The charge is depicted as an isodensity surface in blue.[]{data-label="Fi:2a"}](fig4a.pdf){width="8.5cm"} The above theory makes a number of simplifying assumptions to arrive at a compact expression for the modulation of the miscibility temperature by the formation of a polaron. To test these assumptions computationally, requires a way to represent an extended lattice, and a facile means to sample over different halide compositions and thermal fluctuations to compute the subsequent free energy for differing compositions. While simulations under these conditions are routine with molecular simulation, the photoinduced phase transition additionally requires a means to represent the effect of an excess charge on this free energy. While in principle *ab initio* based molecular dynamics simulations together with enhanced sampling methods could be used, such would be prohibitively computationally expensive for the system sizes required to not artificially localize the excess charge. An alternative method developed in Ref.  used a empirical forcefield for the MAPbX$_3$ lattice,[@mattoni2016modeling] together with a path integral description of the excess charge within an effective mass approximation[@shumway2004quantum] and a set of empirical pseudo-potentials.[@kuharski1988molecular; @schnitker1987electron] Such a classical simulation methodology, depicted in Fig. \[Fi:2a\], albeit in an extended phase space, afforded the ability to use robust sampling tools and a Grand Canonical ensemble to compute the free energy as a function of composition with and without the excess charge. This calculation confirmed the basic mechanism of polaron stabilized phase separation[@bischak2017origin] and, consequently how cation exchange with Cs could decrease the driving force at ambient conditions by reducing the electron-phonon coupling.[@bischak2018tunable] ![image](fig3a.pdf){width="13cm"} Timescales of photoinduced phase separation {#timescales-of-photoinduced-phase-separation .unnumbered} ------------------------------------------- The lead halide perovskites have low cohesive energies allowing for large scale motions of the lattice and its constituent components, in addition to the expected facile motion of photoexcitations and their dissociated charge carriers for a functioning photovoltaic. These disparate motions occur on vastly different timescales, spanning 15 orders of magnitude, but become coupled in the context of photoinduced phase separation. The basic processes, as well as their characteristic timescales at room temperature, are illustrated in Fig. \[Fi:3\]. While few studies have sought an integrated picture of these dynamics, individually much is known about specific dynamic processes in these materials and how they depend on morphology, chemical composition, and thermodynamic state. The fastest process relevant to photoinduced phase separation is the diffusion of photo-excited charge carriers throughout the lattice. Charge mobility has been studied by a variety of techniques and for lead halide perovskites at ambient conditions, estimates typically place it around 0.1 cm$^2$/s.[@brenner2015mobilities; @delor2019imaging] This implies a characteristic timescale to move between two units cells on the order of 0.01 ps. The precise value depends weakly on the composition, and morphology, and is contained within an order of magnitude for all of Cs-based and MA-based single crystals and thin films. These fairly large diffusivities reflect the small polaron binding energies that are not strong enough to cause the charge to self trap. At typical illumination intensities, the charge carrier lifetimes are around 100 ns, with radiative recombination acting as the largest loss channel.[@herz2016charge; @de2015impact; @wehrenfennig2014high] The origin of this low bimolecular recombination rate is currently debated.[@davies2018bimolecular] On similarly fast timescales are local lattice dynamics. The longitudinal optical modes of lead halides have frequencies between 50 cm$^{-1}$ and 100 cm$^{-1}$,[@sendner2016optical; @miyata2017lead] with characteristic timescales on the order of picoseconds. Slower octahedral tilting motions still occur on timescales of 10 ps.[@guo2017interplay] Given the more than 10 orders of magnitude separating these fast motions and the seconds-to-minutes scale of phase separation, it is clear that these degrees of freedom can be safely assumed to stay in local equilibrium with the changing halide arrangements. Halide diffusion and interdiffusion occurs on significantly longer timescales than charge or lattice motion. Halide diffusion is vacancy mediated, and thus depends on both the vacancy concentration and the activation energy to move a vacancy between two lattice sites. Vacancy concentrations, $\rho_\mathrm{v}$, depend strongly on material synthesis conditions. At room temperature, $\rho_\mathrm{v}$ has been estimated to be as low are 10$^{-9}$ per unit cell in single crystals and as high as 10$^{-4}$ per unit cell in thin films.[@walsh2015principles; @lai2018intrinsic] Activation energies for halide diffusion have been measured experimentally, and estimated theoretically, and fall within a range of 0.2 - 0.4 eV. For phase separation, halide interdiffusion is the pertinent transport process. Because halide hopping rates are significantly higher than cation hopping rates, electroneutrality dictates that the self-diffusion constants of each halide in a mixture are the same. The interdiffusion coefficient is given by $$D(\phi) =\frac{1}{2}\ell^2(\phi) \rho_\mathrm{v}(\phi) k_\mathrm{v}(\phi)$$ where $\ell$, $\rho_\mathrm{v}$, and $k_\mathrm{v}$ are the lattice spacing, the vacancy concentration per unit cell, and an effective hopping rate that all depend on the relative concentration of two different halide species.[@belova2004analysis; @lai2018intrinsic] The effective hopping rate is computable from an average of the hopping rates of each pure lattice component. The interdiffusion coefficient for CsPb(Cl$_x$Br$_{1-x}$)$_3$ has been measured in nanowires to be 10$^{-12}$ cm$^2$/s, implying a halide swaps its lattice position with a vacancy once every 1 ms on average.[@whalley2017perspective] Under typical conditions, 1 sun illumination and in thin films, phase separation occurs on a timescale of seconds to minutes.[@bischak2017origin; @hoke2015reversible] Therefore, the characteristic time to form an aggregate of one halide species is much longer than the average lifetime of a charge carrier. Moreover, the diffusion of a charge is about 12 orders of magnitude faster than the diffusion of a halide. Because of this large separation of timescales, the rate limiting step to form an aggregate is the spontaneous fluctuation of the halides creating a region of pure enough halide composition to trap a charge. Once the charge is trapped it can stabilize the aggregate and ripen it to its equilibrium composition. Within the thermodynamic model above, one charge is sufficient to stabilize an aggregate. After about 100 ns, a trapped charge will undergo radiative recombination, however under constant illumination, another charge, diffusing orders of magnitude more quickly than the halide ions, can become trapped in the aggregate and stabilize it again before the aggregate has the time to dissolve. ![Characteristic sequence of snapshots of the lattice model used to study photoinduced phase separation taken 30 seconds apart. []{data-label="Fi:3a"}](fig5.pdf){width="8.5cm"} Using transition state theory we can estimate the time to have a composition fluctuation large enough to trap a charge. The rate is given by the product of the probability to have a composition fluctuation large enough to trap a charge carrier and the characteristic timescale for a halide to swap its lattice position. Using the free energy model in the previous section, and the halide interdiffusion constant as the characteristic attempt frequency for clustering, the rate of a single spherical aggregate to form is $$k_c=\frac{2 D}{\ell^2} e^{-\beta \kappa}$$ where $\kappa=\pi \epsilon^2/3a$ is the free energy to form a cluster large enough to localize the charge. If we take $\epsilon=0.44 {k_\mathrm{B}}T$, per polaron of size $R_\mathrm{p}$, and $a$ used to predict the phase diagram for MAPb(Br$_x$I$_{1-x}$)$_3$, the barrier is about 5.5 kcal/mol. Using the interdiffusion constant of 10$^{-12}$ cm$^2$/s, the rate is 0.01 s$^{-1}$, which is in good agreement with that extracted by cathodoluminescence, where single cluster data is available.[@bischak2018tunable] Synthetic strategies that deplete halide vacancies like halide rich solution conditions, can directly modulate the time to phase separate, as the rate is directly proportional to the vacancy concentration. Under the assumption that clusters are dilute, so that clusters form independently, the rate to form $N_c$ clusters is $k = k_c N_c$. Given the thermodynamic calculation that illustrates one charge on average is sufficient to stabilize a local phase separated aggregate, this implies that the rate to reach a steady state photoluminescence will be proportional to the steady-state concentration of charges as has been observed previously.[@bischak2017origin] In order to validate the basic kinetic model, a coarse-grained lattice representation of the system was developed in Ref. . This simplified model encoded the thermodynamics of Eqs. 1-6, with vacancy mediated halide interdiffusion dynamics and explicit charge motion. Such reduced representation was necessary in order to span time and length scales of clustering, which are prohibitively large relative to those approachable from the more molecular representations used to established the underlying thermodynamic driving forces for phase separation depicted in Fig. \[Fi:3a\]. Explicit parameterizations of the elevation of the local critical temperature in the presence of the charge and a local bias to halide rich regions were both included. A Monte Carlo procedure was used to update the compositional configuration of the lattice and the location of the excess charge. This model was able to reproduce the rise in the photoluminescence intensity versus time as the characteristic time to cluster[@bischak2017origin] as well as the steady state spectra as given by the steady state overlap of the charge with the local composition.[@bischak2018tunable] Simulations of that model, shown in Fig. \[Fi:3a\], clarified that the rate limiting step of cluster formation was a transient composition fluctuation, creating an aggregate large enough to trap a charge. The localized charge thereafter stabilizes the composition fluctuation by locally placing the lattice below the critical miscibility temperature. This feedback mechanism is thus unlike either nucleation and growth or spinodal decomposition. As a charge is only trapped transiently, the dynamics are intermittent, including cycles of trapping, stabilizing aggregation, and untrapping. These cyclic dynamics are a consequence of the nonequilibiurm steady-state nature of the phase separation. This intermittentency was explored in Ref.  , and visualized directly in single crystals using cathodoluminescence.[@bischak2018tunable] Concluding remarks {#concluding-remarks .unnumbered} ================== The photoinduced phase separation of multi-component lead halide perovskites is well documented experimentally as a robust, reversible phenomena. Within the framework presented here, it emerges due to the confluence of unique material properties. The soft perovskite lattice admits high vacancy concentrations, and the ionic lead halide bonding couples to photoinduced charges, creating large polarons. When an initially homogeneous solid solution of different halides are present, the formation of a polaron generates sufficient strain to locally render phase separation thermodynamically favorable. High vacancy concentrations result in large interdiffusion coefficients, which renders phase separation observable on experimentally relevant timescales. While the framework expanded upon here includes a number of simplifying assumptions in mean field that preclude perfect agreement with experimental observations of quantities such as light/polaron-induced critical temperature shifts, these assumptions accommodate the challenging multiscale nature of the photo-induced phenomenon. The model already offers a way to rationalize all of the experimentally observed behavior consistently and also consistently describes how the behavior can be modulated by material composition, morphology and thermodynamic state. In the future, the model could be further refined to include corrections for fluctuations, surface tension from finite size aggregates, or strain modulation. Yet, with the explicit relations provided above, light-stable perovskite based materials can already be rationally designed for a variety of photophysical applications. Strategies that have and will continue to be pursued will either manipulate the stability of the phase separated state by modulating the critical miscibility temperature under illumination, or reduce the rate at which it is formed, by pursuing materials with lower vacancy concentrations. Acknowledgements {#acknowledgements .unnumbered} ================ DTL acknowledges support under the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division under Contract No. DE-AC02-05-CH11231 within the Physical Chemistry of Inorganic Nanostructures Program (KC3103). N.S.G. acknowledges support from the Science and Technology Center on Real-Time Functional Imaging, a National Science Foundation Science and Technology Center (grant DMR 1548924), the Photonics at Thermodynamic Limits Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences (award DE-SC0019140), a David and Lucile Packard Fellowship for Science and Engineering, an Alfred P. Sloan Research Fellowship, and a Camille Dreyfus Teacher-Scholar Award. References {#references .unnumbered} ========== [91]{}ifxundefined \[1\][ ifx[\#1]{} ]{}ifnum \[1\][ \#1firstoftwo secondoftwo ]{}ifx \[1\][ \#1firstoftwo secondoftwo ]{}““\#1””@noop \[0\][secondoftwo]{}sanitize@url \[0\][‘\ 12‘\$12 ‘&12‘\#12‘12‘\_12‘%12]{}@startlink\[1\]@endlink\[0\]@bib@innerbibempty @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [**** ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [ ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [“,” ]{} () @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [**]{}, Vol.  (, ) @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [**** ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [ ()]{} @noop [ ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{}
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Funding of Grants by the National Institutes of Health The National Institutes o f Health may, consistent with 31 U.S.C. § 1502(a), fund an entire research grant out of a single fiscal year’s appropriations regardless of how long it takes to complete the work under the grant. February 11, 1986 M em orandum O p in io n for th e G eneral C o un sel, D epa rtm en t of H ealth and H u m a n S e r v ic e s This responds to the request of your Office for the Department of Justice’s opinion whether the National Institutes of Health (NIH) may use the appropria­ tion for one fiscal year to fund a grant when the work under the grant may take two or three fiscal years to complete, or whether NIH must fund each year’s work from a separate appropriation. You have asked this question because the Comptroller General has concluded that: the executive branch plan to fund some 646 NIH research grants on a 3-year basis with fiscal year 1985 funds is unlawful, because in the absence of specific statutory authority, such actions violate 31 U.S.C. § 1502(a).1 For the reasons stated below, we believe GAO’s conclusion that NIH may not lawfully fund grants on a multi-year basis is incorrect. We believe, based on the pertinent statutes as well as the principles articulated in prior Comptroller General opinions, that NIH may, under the circumstances outlined below, use the appropriation for one fiscal year to fund the entire cost of a grant made during that fiscal year, regardless of how long it takes to complete work under that grant. I. Statutory Language The Comptroller General’s conclusion is based on 31 U.S.C. § 1502(a), which provides: 1 Letter to Hon. Lowell W eicker, Jr., C hairm an, Subcom m ittee on Labor, Health and H um an Services, and Education o f the Senate Com m ittee on A ppropriations from M ilton J. Socolar, Office o f the C om ptroller G eneral, G eneral A ccounting O ffice (GA O ) (M ar. 18, 1985) (GAO letter). 19 The balance of an appropriation or fund limited for obligation to a definite period is available only for payment of expenses properly incurred during the period of availability or to com­ plete contracts properly made within that period of availability and obligated consistent with § 1501 of this title. However, the appropriation or fund is not available for expenditure for a period beyond the period otherwise authorized by law. The plain language of this provision does not support GAO’s conclusion that NIH may not use funds appropriated for one fiscal year to pay for work to be done in subsequent years under a multi-year grant. Although 31 U.S.C. § 1502(a) makes no reference to grants, the statute does refer to “contracts,” and NIH research grants are a form of contract, as GAO itself has previously recog­ nized.2 Thus, under § 1502(a), the balance of an appropriation “limited for obligation to a definite period” — such as a particular fiscal year — may be used to “complete grants properly made” within that fiscal year and properly obligated consistent with 31 U.S.C. § 1501.3 In other words, § 1502(a) contains two requirements: first, that the grant be “properly made” within the fiscal year being charged and, second, that the grant be “obligated” — i.e., recorded as an obligation — consistent with § 1501. The second of these requirements — that a grant be properly obligated consistent with 31 U.S.C. § 1501 — has no bearing on the general question of NIH funding of multi-year grants, but rather concerns the handling of particular obligations. Moreover, the papers we have reviewed contain no suggestion that the particular NIH grants that gave rise to the NIH-GAO dispute were not obligated consistent with § 1501. Absent facts to the contrary, we assume that issuance of each NIH grant is supported by appropriate documentary evidence and authorized by statute. We also do not believe that GAO’s position is supported by the first require­ ment, i.e., that each grant be “properly made” within the fiscal year charged. The plain meaning of this statutory language is that it must be proper for NIH to make the grant within the fiscal year charged. Applying this interpretation, we see no reason why NIH may not make a multi- year grant during the first year of the grant. Indeed, we do not understand GAO to argue that NIH may not 2 See 50 C om p. G en. 4 7 0 ,4 7 2 (1970) (“th e acceptance o f a grant . . creates a valid contract"). See also 62 C om p. G en. 701, 702 (1983). 3 Section 1501 states in pertinent part: (a) An am ount shall be recorded a s an obligation o f the United States G overnm ent only when supported by docum entary evidence o f — * * * (5) a grant o r subsidy payable — (A ) from appropriations made fo r paym ent of, o r contributions to, amounts required to be p aid in specific am ounts fixed by law or under form ulas prescribed by law; [or] * * * (C) un d er plans approved consistent with and authorized by law . . . . There is no dispute that the N IH grants at issue here were o bligated consistent with these requirem ents. 20 make such grants at that time, but only that NIH must spread the cost over the length of the grant. The plain meaning of the “properly made” language, however, does not require such cost spreading.4 II. The GAO’s Traditional Analysis We also believe that the conclusion expressed in the GAO letter does not follow from its own prior opinions. Over the years, GAO has added a gloss to § 1502, known as the bona fid e need rule. As stated in Principles o f Federal Appropriations Law (GAO 1982) (Principles ), GAO has taken the position that “[a] fiscal year appropriation may be obligated only to meet a legitimate, or bona fid e need arising in the fiscal year for which the appropriation was made.” Id. at 4-9. This principle would appear to require that a multi-year grant meet a bona fid e need of the fiscal year whose appropriation is being charged. The GAO letter states that the NIH grants were improperly made because the work done under them in subsequent years will not meet a bona fid e need of fiscal year 1985. In arriving at this conclusion, GAO cites a series of cases involving funding for “continuous and recurring services [that] are needed on a year-to-year basis,” such as repairs of typewriters and delivery of supplies. Id. at 6-7. However, as HHS points out: Without exception, th[e] decisions [cited by GAO] deal with the provision of materials and services of a routine and recurring nature that should appropriately be funded out of a current year appropriation. None of those decisions involved grants, and none dealt with a discrete project designed to meet a current need the accomplishment of which would take longer than a single fiscal year. Id. at 6. While relying on this strained analogy between grants for scientific study and routine office expenses,5 the GAO letter makes no mention of its extensive body of opinions concerning the application of the bona fide need rule to contracts and grants that cannot be completed in one year. This body of opinions is summarized as follows in the GAO’s Principles, supra, at 4-9,4—10: Bona fid e need questions [frequently] arise where a given trans­ action covers more than one fiscal year. In the typical situation, a contract is made (or attempted to be made) in one fiscal year, with performance and payment to extend at least in part into the 4 G A O ’s position finds no support in case law. M oreover, form er A ttorneys General, in interpreting the predecessor statutes to § 1S02, sim ilarly reached the conclusion that balances o f appropriations may be used “to pay dues upon contracts properly made w ithin the form er [fiscal] year, even if the contracts be not perform ed till w ithin the latter o r current year.” 13 Op. A tt’y Gen. 288, 291 (1870). See also 18 Op. A tt’y Gen. 566, 5 6 9 (1 8 8 7 ). 5The G A O letter itse lf recognizes the w eakness o f this analogy: “ [W]e recognize that there are fundam ental differences betw een a contract for materials or services and a research grant.” 21 following fiscal year. The issue is which fiscal year should be charged with the obligation. In this context, the rule is that, in order to obligate a fiscal year appropriation for payments to be made in a succeeding fiscal year, the contract imposing the obligation'must have been made within the fiscal year sought to be charged, and the contract must have been made to meet a bona fid e need of the fiscal year to be charged. * * * It follows from the above statement of the rule that there are situations in which performance or delivery can extend into a subsequent fiscal year with payment to be charged to the prior fiscal year, as long as the need arose in the fiscal year to be charged. This principle applies even though the funds are not to be disbursed and the exact amount owed by the Government cannot be determined until the subsequent fiscal year. In deciding whether a contract should be charged to the fiscal year in which it is made, GAO has taken the following position: The fact that a contract covers a part of two fiscal years does not necessarily mean that payments thereunder are for splitting between the two fiscal years involved upon the basis of services actually performed during each fiscal year. In fact, the general rule is that the fiscal y e a r appropriation current at the time the contract is m ade is chargeable with paym ents under the con­ tract, although performance thereunder may extend into the ensuing fis c a l year. 23 Comp. Gen. 370,371 (1943) (emphasis added) (quoted in Principles, supra, at 4-13). GAO has issued many opinions reiterating this “general rule.” See, e.g., 56 Comp. Gen. 351, 352 (1977); 50 Comp. Gen. 589, 591 (1971); 21 Comp. Gen. 822, 823-24 (1951); 20 Comp. Gen. 436, 437 (1941); 16 Comp. Gen. 37, 38 (1936). It has likewise made clear “that the question of whether to charge the appropriation current on the date the contract is made, or to charge the funds current at the time services are rendered, depends on whether the services are ‘severable’ or ‘entire.’” Principles, at 4-13. Thus, the “determining factor” for whether a contract (or grant) for a multi-year project is “properly made” is whether the project “represent[s] a single undertaking” and should therefore be viewed as a single project. Id. at 4—14.6 If it is, a bona fid e need for the project arises in the first fiscal year, and that is the appropriation that should be charged. The contract at issue in the 1943 opinion, quoted above, provides an example of a contract that was viewed by GAO as a single project. Under that contract, 6 The G A O le tte r agrees that the fundamental issue is w hether the grants are single research projects or are severable annual projects. 22 individuals were to prepare the ground, plant rubber-bearing plants, and bring them to harvest. GAO concluded that this contract: involved one undertaking, which although extending over a part of two fiscal years, nevertheless was determinable both as to the services needed and the price to be paid therefor at the time the contract was entered into. Such being the case, the fiscal year appropriation current at the time the contract was made was obligated for payments to be made thereunder. 23 Comp. Gen. at 371. GAO therefore rejected a Department of Agriculture voucher that would have divided the cost between the two fiscal years it took to complete the contract. GAO opinions treating a variety of other contracts as single projects are also illustrative. For example, when the Government contracted in 1938 to have cattle inspected and slaughtered if infected with tuberculosis, GAO concluded that the 1938 appropriation should be charged for recompense paid to farmers for diseased animals found and slaughtered in later years. 18 Comp. Gen. 363 (1938). The need to test the animals arose in fiscal year 1938, and therefore any liability under the contract, regardless of when discovered, had to be charged to the 1938 appropriation. Id. at 365. More recently, in 1980, GAO insisted that a 1977 appropriation be charged for the cost of printing a book for the Commission of Fine Arts even though the printing took three years, from 1977 to 1979. 59 Comp. Gen. 386, 387-88 (1980). GAO explicitly rejected the Commission’s argument that the printing costs should be charged against the 1977, 1978, and 1979 GAO appropriations in proportion to the amount of work done each year. GAO said: [T]he fact that performance under a contract extends over more than one fiscal year does not mean that payments are to be split among the fiscal years on the basis of services actually per­ formed. Rather, the general rule is that payments due under a Government contract are to be charged to the fiscal year appro­ priation current at the time the legal obligation arose; that is, the fiscal year in which a bona fide need for the goods or services arose and in which a valid contract or agreement was entered into. 59 Comp. Gen. at 387-88. See also 50 Comp. Gen. 589, 591-92 (1971) (lawyers hired for case must be GAO paid from the appropriation for the year in which they were hired, no matter how protracted the litigation); GAO Opinion B-141839-O.M. (May 2, 1960) (NIH contracts for cancer research with Stanford University are “an entire job” and must be paid out of appropria­ tion for fiscal year in which contracts were signed, “even though the period of performance may extend beyond the fiscal year until the object thereof is accomplished.”); 31 Comp. Gen. 608, 610 (1952) (FY 1952 appropriation reimbursing states for civil defense expenditures charged although states did 23 not buy equipment until subsequent years); 23 Comp. Gen. 82, 83 (1943) (FY 1942 appropriation charged although printing of legal opinions not completed until FY 1943); 21 Comp. Gen. 574, 577 (1941) (FY 1940 appropriation charged although telescopes not shipped until FY 1941); 20 Comp. Gen. 436 (1941) (FY 1940 appropriation charged for cost of move although move not completed until FY 1941). This general rule has also been applied by GAO to grants. For example, GAO concluded in 1940 that all expenses incident to a fellowship granted to South Americans for the study of public health in the United States could be charged “to the fiscal-year appropriation current and available at the time the fellowship is awarded” even though the fellowship extended into the succeed­ ing fiscal year and some expenses, such as travel and maintenance, would not be incurred until the next year. 20 Comp. Gen. 185, 189 (1940). See also GAO Opinion B-37609, 267 Manuscript Series 1039 (1943) (grants for cultural programs with South America);7 GAO Opinion B-34477, 261 Manuscript Series 1960 (1943) (grants to Chinese professors for study in the United States);8 39 Comp. Gen. 317 (1959). In this last opinion, the National Science Foundation sought GAO’s opinion on issues relating to the obligation of certain appropriations. GAO stated: It is explained in the letter that the major portion of funds appropriated to the National Science Foundation is obligated and expended in the form of grants to educational institutions for the purpose of conducting basic scientific research activities. It is stated — and correctly so — that such grants are adminis­ tratively recorded as obligations at the time the funds are for­ mally granted to the grantee by letter, and that there is no deobligation of any unexpended portion of the grants as of June 30 [the end of the fiscal year]. See 31 Comp. Gen. 608. 7 The 1943 opinion states- By decision o f A p n l 3, 1942, B -2 4 2 7 ,. . . it was held, in substance, that a grant o f funds . . . constituted a legal obligation o f th e am ount granted, even though the final obligation and expenditure for definite projects in th e various American republics w as [sic] to be accom plished by the said corporation in the follow ing fiscal y e a r .. . In the said decision, it was stated: “H aving in view the authority given by the C ongress to the Coordinator to make grants . . . the conclusion appears ju stified that funds so granted . . . were not intended to rem ain subject to the fiscal y ear lim itation o f the appropriations from which the funds were derived, and that, insofar as concerns the C oordinator o f Inter-A m encan A ffairs, such funds are legally obligated w hen form ally granted to an authorized grantee. . . . Cf. 21 C om p. Gen. 498 ” * * * [YJour above-quoted letter appears to be so sim ilar . . as to warrant a sim ilar conclusion — that is, that funds form ally granted or form ally agreed to be furnished to an institution or facility . . . are legally obligated at the time o f th e said grant or agreem ent to grant and properly may be made available and expended thereafter by the grantee institution or facility without regard to the fisca l year limitation o f the appropriations from which the funds were derived. 267 M anuscript Series at 1041, 1042 (citations om itted; em phasis added). 8 “It should seem obvious that all expenses connected with the second phase of the program — the bringing o f C hinese professors to this country — a re chargeable to the funds in question [i.e., to funds from the fiscal year in w hich the grant w as ma d e ] . . . 2 6 1 M anuscript S eries at 1963 24 39 Comp. Gen. at 318 (1959) (emphasis added). See also 48 Comp. Gen. 186, 190 (1968) (FY 1968 appropriation “would be the only appropriation legally available to pay amounts due the grantee as a result of any required upward adjustment” in later years); 20 Comp. Gen. 370, 373 (1941) (grants may be used to pay for courses extending over two fiscal years). GAO has embodied this rule for grants in Principles, supra: In order to properly obligate an appropriation for an assistance program, some action creating a definite liability against the appropriation must occur during the period of the obligational availability of the appropriation. In the case of grants, the obli­ gating action will usually be the execution of a grant agreement. * * * Once the appropriation has been properly obligated, perfor­ mance and the actual disbursement of funds may carry over beyond the period of obligational availability. Id. at 13-16, 13-17 (citations omitted). In sum, GAO’s opinions and Principles hold that § 1502 permits contracts and grants to be charged against the appropriation for a single fiscal year even though payments may extend over more than one year. They also hold that a grant may meet the bona fid e need of an agency for a single fiscal year, even though work under the grant extends over more than one year. Our review of § 1502 and of GAO’s opinions thus leads us to conclude that GAO’s recent determination that NIH may not fund multi-year grants from a single appro­ priation is incorrect. You have also asked whether a certifying officer who does not follow the Comptroller General’s opinion would be liable under 31 U.S.C. § 3528(a)(4).9 We believe that he would not be liable as, in our view, 31 U.S.C. § 1502 permits NIH lawfully to charge the entire cost of a grant against the appropria­ tion for the fiscal year in which the grant was made. Because payment of the grant is not illegal, the provisions of § 3528(a)(4) are not applicable, and we would so inform GAO if they referred the matter to this Department. Finally, you have asked whether charging the grant to the appropriation for one fiscal year would violate.the Anti-Deficiency Act, 31 U.S.C. § 1341.10 As 9 That section provides. (a) A certifying official certifying a voucher is responsible for * * * (4) repaying a paym ent (A ) illegal, improper, or incorrect because o f an inaccurate or m isleading certificate; (B) prohibited by law , or (C) that does not represent a legal obligation under the appropriation or fund involved 1031 U.S.C. § 1341 provides in relevant part: (a) (1) An officer or em ployee o f the U nited Slates G overnm ent or of the District o f Columbia governm ent may not — (A) make o r authorize an expenditure o r obligation exceeding an amount available in an appropriation o r fund for the expenditure o r obligation; or (B) involve either governm ent in a contract o r obligation for the paym ent of money before an appropriation is made unless authorized by law. 25 we have concluded that charging the grant to the appropriation for a single fiscal year is lawful, we do not believe a grant official following our opinion would violate this section. Conclusion For the reasons stated above, we believe that NIH may charge the appropria­ tion for a single fiscal year with the entire cost of a single grant. C harles J. Cooper Assistant Attorney General Office o f Legal Counsel 26
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What does the crazy start for US markets, the USD, and gold mean for investors? Peter Hanks, Analyst at DailyFX joins me to share his thoughts on the crazy start to 2020 for US markets, the US dollar, and gold. We discuss the major drivers, outside of the geopolitical issues, and how such aspects like the Fed and trade will remain key throughout 2020.
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Enhancement of Brønsted acidity in zeolitic catalysts due to an intermolecular solvent effect in confined micropores. Solid-state NMR and DFT calculation studies certified the presence of an intermolecular solvent effect for molecules confined in microporous zeolite, leading to a notable increase in Brønsted acidity of the solid acid catalyst.
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Vascularised fatty tissue: its role in prevention of the symptoms of Frey syndrome after parotidectomy. We studied 37 consecutive patients who had parotidectomies between 2008 and 2017 and who had vascular fat flaps inserted to replace the excised parotid tissue and prevent Frey syndrome. They were followed up for 1-9 years to check for the relevant symptoms. We studied 17 female and 20 male patients, mean age 52 (range 19-78) years. The flaps took a maximum of 17minutes to dissect. There was no donor site morbidity, the vascular fat flap was stable in all cases for up to nine years, and none of the patients complained of symptoms of Frey syndrome.
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EUROPE: Siemens and Vestas have announced contrasting fortunes in the second quarter, with one boasting a record order book and the other a €41 million loss. Siemens' reported loss may come as a surprise given that it was labelled the world's biggest manufacturer in 2014 by Make Consulting.
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Image caption Nato supply vehicles were set ablaze in the attack, blocking the supply route from Pakistan Taliban militants have attacked a US base in eastern Afghanistan, sparking a lengthy gun battle in which three insurgents were killed. Reports say the attack on Torkham base in Nangarhar province unfolded after militants torched Nato supply trucks on the highway leading to the base. Officials said that no Afghan or US soldiers died in the raid. The attackers did not enter the base. But officials say the financial cost of the attack is likely to be immense. Many Nato supply vehicles on the road to the base were left badly burned on the highway. Officials closed the Jalalabad-Torkham road - a key route for these vehicles - after the attack. A Taliban spokesman told the BBC that the group was behind the raid. Isaf said the attack was unsuccessful: "Our initial assessment of this morning's events, which occurred in the vicinity of a forward operating base located in Nangarhar province, is that it was an attempted but unsuccessful co-ordinated attack by enemy forces." The base is home to some of the 66,000 US troops serving in Afghanistan along with forces from other countries. Officials say the base was also an important stopping point for Nato vehicles. There has recently been a spate of attacks across the country, claiming dozens of lives - most of them civilians. The violence is being interpreted by some as an attempt by the Taliban to assert their presence and test the strength of Afghan forces ahead of the planned withdrawal of US-led forces at the end of next year, the BBC's Karen Allen in Kabul reports.
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Richard J. Samuels Richard J. Samuels (born November 2, 1951) is an American academic, political scientist, author, Japanologist, Ford International Professor of Political Science and director of the Center for International Studies at the Massachusetts Institute of Technology. Early life Samuels was born in Brooklyn, New York and grew up in Westbury on Long Island. He graduated from Colgate University in 1973, received his master's degree from Tufts University in 1974, and was awarded his PhD from the Massachusetts Institute of Technology in 1980. Career Samuels's teaching career at MIT has been interrupted periodically for visiting professorships in Tokyo, Rome, Berlin, and elsewhere. He served as head of the MIT Department of Political Science between 1992 and 1997. Samuels has also served as vice-chairman of the Committee on Japan of the National Research Council, and as chairman of the Japan-US Friendship Commission, an independent federal grant-making agency that supports Japanese studies and policy-oriented research in the United States. He served concurrently as the chair of the U.S. CULCON Panel (U.S.-Japan Conference on Cultural and Educational Interchange), a binational advisory panel to the U.S. and Japanese governments. In 2005 he was elected a member of the American Academy of Arts and Sciences and in 2011 he received the Order of the Rising Sun, Gold and Silver Star, an imperial decoration awarded by the Emperor of Japan and the Japanese Prime Minister. He is one of only three scholars (Japanese or foreign) to have produced more than one scholarly monograph recognized by the Nippon Foundation as one of the top "one hundred books for understanding contemporary Japan". In 2015 he was named an Einstein Fellow at the Free University of Berlin. Currently Samuels is director of MIT Center for International Studies. Select works In a statistical overview derived from writings by and about Richard Samuels, OCLC/WorldCat encompasses roughly 90+ publications in 4 languages and 3,000+ library holdings The Politics of Regional Policy in Japan: Localities Incorporated (Princeton University Press, 1983) Getting America Ready for Japanese Science and Technology (University Press of America, 1986) The Business of the Japanese State: Energy Markets in Comparative and Historical Perspective (Cornell University Press, 1987) Winner-1988 Masayoshi Ohira Memorial Prize. The Political Culture of Foreign Area and International Studies: Essays in Honor of Lucian W. Pye (Brassey's, 1992) (co-editor with Myron Weiner) Rich Nation, Strong Army: National Security and the Technological Transformation of Japan (Cornell University Press, 1994) Winner-1996 John Whitney Hall Prize of the Association of Asian Studies and 1996 Arisawa Memorial Prize of the Association of American University Presses. Machiavelli's Children: Leaders and their Legacies in Italy and Japan (Cornell University Press, 2003) Winner-2003 Marraro Prize from the Society for Italian Historical Studies and the 2004 Jervis-Schroeder Prize for the best book in International History and Politics, International History and Politics section of the American Political Science Association. Crisis and Innovation in Asian Technology (Cambridge University Press, 2003)(co-editor with William Keller) Encyclopedia of United States National Security (Sage, 2006) Securing Japan: Tokyo's Grand Strategy and the Future of East Asia (Cornell University Press, 2007) Finalist-2008 Lionel Gelber Prize for the best book in international affairs. 3.11: Disaster and Change in Japan (Cornell University Press, 2013) Special Duty: A History of the Japanese Intelligence Community (Cornell University Press, 2019) Named one of the “Best of Books 2019” by the Council on Foreign Relations’ journal, Foreign Affairs. His articles have appeared in Foreign Affairs, International Security, Foreign Policy, Washington Quarterly, International Organization, Political Science Quarterly, The Journal of Modern Italian Studies, The National Interest, The Journal of Japanese Studies, Daedalus, and other policy and scholarly journals. Honors Albert Einstein Foundation Fellow, 2015. American Academy of Arts and Sciences, 2005. American Political Science Association Jervis-Schroeder Book Prize, 2004. Edwin McClellan Visiting Fellow in Japanese Studies, Yale, 2004. Abe Fellowship, Social Science Research Council, 1998 Association for Asian Studies, John Whitney Hall Book Prize, 1994. Council on Foreign Relations, 1992- National Science Foundation Fellowship, 1991-1992 Fulbright Fellowships: 1991-1992, 1983–1984, 1977–1978 Notes External links , interview with Einstein Foundation Policy Change in a Post-Crisis Japan, Q&A with Richard J. Samuels (March 2012) Japan after Kan: Implications for the DPJ’s Political Future, Q&A with Richard J. Samuels (August 2011) Social Science Research Council Category:1951 births Category:Living people Category:American Japanologists Category:Massachusetts Institute of Technology faculty Category:Fulbright Scholars Category:Fellows of the American Academy of Arts and Sciences Category:American political scientists
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Q: Is there a Django reference? I am new to Django. I have found the official topic guides https://docs.djangoproject.com/en/1.3/ an excellent place to learn from. But now I am in a place where I need quick reference to see what methods an object has, what arguments it takes, what it returns etc, kind of like the Python docs or Java docs. More of a reference than a tutorial. The official docs are tutorial style and do not necessarily have reference to all the methods. Am I missing something here? Do the Django official docs suffice for everyone? A: Python has a built-in mechanism for that: docstrings. Example: >>> import django.forms >>> help(django.forms.ModelForm) Help on class ModelForm in module django.forms.models: class ModelForm(BaseModelForm) | Method resolution order: | ModelForm | BaseModelForm | django.forms.forms.BaseForm | django.utils.encoding.StrAndUnicode | __builtin__.object | | Data and other attributes defined here: | | __metaclass__ = <class 'django.forms.models.ModelFormMetaclass'> | | | ---------------------------------------------------------------------- | Methods inherited from BaseModelForm: | | __init__(self, data=None, files=None, auto_id='id_%s', prefix=None, initial=None, error_class=<class 'django.forms.util.ErrorList'>, label_suffix=':', empty_permitted=False, instance=None) | | clean(self) | | save(self, commit=True) | Saves this ``form``'s cleaned_data into model instance | ``self.instance``. | | If commit=True, then the changes to ``instance`` will be saved to the | database. Returns ``instance``. | | validate_unique(self) | Calls the instance's validate_unique() method and updates the form's | validation errors if any were raised. | | ---------------------------------------------------------------------- | Methods inherited from django.forms.forms.BaseForm: | | __getitem__(self, name) | Returns a BoundField with the given name. | | __iter__(self) | | __unicode__(self) | | add_initial_prefix(self, field_name) | Add a 'initial' prefix for checking dynamic initial values | | add_prefix(self, field_name) | Returns the field name with a prefix appended, if this Form has a | prefix set. | | Subclasses may wish to override. | | as_p(self) | Returns this form rendered as HTML <p>s. | | as_table(self) | Returns this form rendered as HTML <tr>s -- excluding the <table></table>. | | as_ul(self) | Returns this form rendered as HTML <li>s -- excluding the <ul></ul>. | | full_clean(self) | Cleans all of self.data and populates self._errors and | self.cleaned_data. | | has_changed(self) | Returns True if data differs from initial. | | hidden_fields(self) | Returns a list of all the BoundField objects that are hidden fields. | Useful for manual form layout in templates. | | is_multipart(self) | Returns True if the form needs to be multipart-encrypted, i.e. it has | FileInput. Otherwise, False. | | is_valid(self) | Returns True if the form has no errors. Otherwise, False. If errors are | being ignored, returns False. | | non_field_errors(self) | Returns an ErrorList of errors that aren't associated with a particular | field -- i.e., from Form.clean(). Returns an empty ErrorList if there | are none. | | visible_fields(self) | Returns a list of BoundField objects that aren't hidden fields. | The opposite of the hidden_fields() method. | | ---------------------------------------------------------------------- | Data descriptors inherited from django.forms.forms.BaseForm: | | changed_data | | errors | Returns an ErrorDict for the data provided for the form | | media | Provide a description of all media required to render the widgets on this form | | ---------------------------------------------------------------------- | Methods inherited from django.utils.encoding.StrAndUnicode: | | __str__(self) | | ---------------------------------------------------------------------- | Data descriptors inherited from django.utils.encoding.StrAndUnicode: | | __dict__ | dictionary for instance variables (if defined) | | __weakref__ | list of weak references to the object (if defined) Then you can look up the docstrings of individual methods: >>> help(django.forms.ModelForm.is_valid) Help on method is_valid in module django.forms.forms: is_valid(self) unbound django.forms.models.ModelForm method Returns True if the form has no errors. Otherwise, False. If errors are being ignored, returns False. A: I may be incorrect but I've been using django for over a year now and never found such a guide. Slightly unfortunate - I would like to have a function reference like you mentioned. However, as an additional resource the http://www.djangobook.com/ is very good. I've always considered building one, but I'm very lazy. There is also another reference you may use when you're stuck http://www.thedjangoforum.com
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INTRODUCTION ============ Frailty is characterized as an energy decline syndrome resulting from changes that occur due to aging. These changes predispose the elderly to a marked reduction in muscle mass and to a chronic inflammatory state, which, when associated with diseases, immobility or other extrinsic factors, results in a decrease in the energy reserve and an increase in physical vulnerability[@B1]. Different studies show that this syndrome is associated with advanced age[@B1] ^-^ [@B4] and worse socioeconomic conditions, such as insufficient income and low educational levels[@B1] ^,^ [@B5] ^,^ [@B6]. Moreover, frailty is related to the presence of chronic diseases and disability, either by predisposing to them or resulting from them[@B1]. In Brazil, the aging process occurs under unfavorable economic, social and health conditions[@B7]. This scenario creates conditions conducive to the development of serious health complications as people age[@B8]. In the last decade, due to the rapid aging of the population and the increase in the costs related to the health of the elderly, there has been an increase in scientific interest in the study of frailty[@B4] ^,^ [@B9]. Population-based frailty studies in Brazil were conducted in cities previously selected as part of the Elderly Frailty (FIBRA) and the Health, Wellbeing and Aging (SABE)[@B4] ^,^ [@B9] projects. Therefore, there are no studies to establish a national estimate of the prevalence of frailty and the factors associated with this condition. These factors deserve to be evaluated by virtue of the different conditions in which people grow old in the country. In clinical practice, evaluating and identifying the frailty syndrome in the elderly can help prevent the progression of this syndrome and minimize its adverse consequences[@B5] ^,^ [@B10]. Knowledge about the epidemiological profile of frailty will allow future assessments of the impact of services and policies for the prevention and control of this syndrome. Thus, the objective of the present study was to estimate the prevalence of frailty and to evaluate the factors associated with this condition in a national representative sample of the population aged 50 years or older. METHODS ======= A cross-sectional study was conducted with data from the baseline of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) conducted between 2015 and 2016. ELSI-Brazil is a prospective cohort study, conducted in a representative sample of the Brazilian population aged 50 years or older, living in 70 municipalities in the five major geographic regions of the country. This nationally representative sample used a multistate stratified cluster sampling design. All residents in the selected households, aged 50 years or older, were eligible for interviews, anthropometric evaluation, blood pressure measurements, and strength, balance and gait tests (n = 9,412). More details can be seen on the research website[^a^](#fna){ref-type="fn"} and previously published[@B11] *.* Study Variables --------------- ### Dependent variable Frailty was defined as the presence of three or more of the following components: weight loss, weakness, low gait speed, exhaustion and low level of physical activity[@B1]. In the present study, each of these components was defined according to the criteria presented in a previous publication[@B12]. Weight loss was assessed by self-report of weight loss in the last three months. Weakness was measured by the force of the hand grip using a manual dynamometer on the dominant upper limb. Each participant was asked to apply the highest possible force in three attempts, considering the best performance. Weakness was defined by the strength of the hand grip in the lower quintile \[after adjusting for gender and body mass index (BMI) quartiles\], as well as the condition of being bedridden and the inability to perform the test. The gait speed was measured by a timer to record the time spent (in seconds) to walk three meters, considering the smallest measure between two measurements. Low gait speed was defined by the highest quintile of time, stratified according to gender and height, as well as the inability to perform the test[@B13]. Exhaustion was defined by responses to the following questions from the Center for Epidemiological Studies' (CES-D) depression questionnaire: "In the last week, how often did you feel that you could not carry things forward (started something but could not finish)?"; "In the last week, how often did your routine activities require a major effort to be completed?". Exhaustion was attributed to those with frequencies greater than 3-4 days[@B14]. The physical activity score was calculated in metabolic equivalents per week and expressed in kilocalorie (kcal) based on the Short Form of the International Physical Activity Questionnaire (IPAQ)[@B15]. The IPAQ questions seek to evaluate the time (minutes and hours) and the intensity (mild, moderate and vigorous) of physical activity practices performed during the last week, based on work activities, to get from one place to another, in leisure, as a sport, as an exercise or as part of household chores[@B15]. Individuals in the lower quintile of expenditure in weekly kcal, stratified by gender, were considered to have a low level of physical activity. In the present study, the dependent variable was categorized as frail (three or more components) and not frail (two or fewer components). More details can be seen in a previous publication[@B12]. ### Covariates The covariates of this study included sociodemographic characteristics (age, sex, years of schooling, marital status, and perception of income sufficiency for household expenses), health behaviors and conditions \[current tobacco consumption, self-rated health, multimorbidity, and ability to perform basic activities of daily living (BADL)\]. Current smoker status was attributed to those who reported smoking daily. Self-rated health was assessed by the standard question "How would you judge the state of your general health?". The respondents used a five-point scale to answer, which were categorized into three groupsgood or very good, regular and poor or very poor. Multimorbidity was defined as the presence of two or more chronic diseases (*versus* one or none) as previously proposed[@B16] ^,^ [@B17]. The number of chronic diseases was defined by a history of medical diagnosis of the following diseases: hypertension, diabetes, heart disease, chronic lung disease, stroke, arthritis, asthma, cancer, and kidney disease. The variable functional disability was constructed by reporting any difficulty (unable, some or little) in performing one or more BADL, including bathing, dressing, feeding, using the toilet, getting out of bed, and crossing a room on the same floor[@B18]. Statistical Analyzes ==================== The analyses of the associations between the independent variables and the outcome variable were based on prevalence ratios and 95% confidence intervals estimated using the univariate and multivariate Poisson regression. All the independent variables were included simultaneously in the final multivariate model. A Venn diagram was developed to describe the concomitance between frailty, BADL limitations, and multimorbidity (two or more chronic diseases). In addition, imputation analysis was performed using the MICE (multiple imputation using chained equations) procedure. A total of 10 imputed datasets were created to assess the influence of missing data on the estimates of the final frailty prevalence.For the imputation, the following variables were considered: age, gender, marital status and perception of income sufficiency. The analyses were performed using the Stata 14.0 program (Stata Corp., College Station, USA), using the svy command, which allows us to consider the complex structure of the sample, including the assignment of sample weights. Ethical Considerations ====================== ELSI-Brazil was approved by the Research Ethics Committee of the Oswaldo Cruz Foundation, Minas Gerais (CAAE 34649814.3.0000.5091). All participants signed an informed consent form at the time of the interview. RESULTS ======= Among the 9,412 participants in the ELSI-Brazil baseline survey, 8,556 had complete information for all variables and were included in the present analysis. The average age of participants was 62.7 years (95%CI 61.9--63.5) and 53.4% were women. The prevalence of weight loss in the last three months, weakness, low gait speed, exhaustion and low level of physical activity were 7.4%, 22.6%, 20.5%, 28.6% and 19.8%, respectively. The overall prevalence of frailty was 9.0%. Other characteristics of study participants are shown in [Table 1](#t1){ref-type="table"}. Table 1Characteristics of study participants. The Brazilian Longitudinal Study of Aging (ELSI-Brazil), 2015-2016. (n = 8,556)Variable%95%CI^a^Age (years)  50--5948.744.6--52.860--6929.827.9--31.770 or older21.519.0--24.3Female53.450.4--56.4Lives with a partner64.861.8--67.6Education (years of schooling)  0--331.828.5--35.24--731.629.0--34.28--1128.325.8--31.012 or more8.37.2--9.6Perceived income sufficiency  Always enough33.030.5--35.7Sometimes it's enough26.124.4--27.8Never enough40.937.7--44.2Current smoker17.015.6--18.5Two or more chronic diseases^b^35.934.0--37.8Difficulty performing BADL^c^  No85.584.1--86.7Yes14.513.3--15.9Self-rated health  Good43.941.3--46.5Regular44.742.8--46.7Poor11.410.2--12.7Frailty components  Weight loss in the last 12 months7.46.6--8.3Weakness22.620.7--24.5Low gait speed20.518.2--23.1Exhaustion28.626.5--30.8Low physical activity19.817.8--21.9At least 3 of the above listed9.08.0--10.1[^3][^4][^5] The prevalence of frailty gradually increased with age, from 9.0% (95%CI 8.0--10.1) in the age group of 50 years or older, to 13.5% (95%CI, 11.9--15, 3) in the age group of 60 years or older, and finally to 16.2% (95%CI 14.3--18.3) at age 65 or older ([Figure 1](#f01){ref-type="fig"}). Figure 1Prevalence of frailty according to age groups. The Brazilian Longitudinal Study of Aging (ELSI-Brazil), 2015--2016. The results of the unadjusted analysis ([Table 2](#t2){ref-type="table"}) show statistically significant associations between frailty and age, living with a partner, education, income sufficiency perception, self-rated health, multimorbidity, and difficulty to perform one or more BADL. Gender and smoking status were not statistically associated with frailty. Table 2Results of the unadjusted analysis of the association between frailty and sociodemographic characteristics, health behaviors and conditions. The Brazilian Longitudinal Study of Aging (ELSI-Brazil), 2015--2016.VariablePrevalencePrevalence ratio%95%CIPR^d^95%CI^e^Age (years)    50--594.33.7--5.11 60--698.16.9--9.51.871.49--2.34^b^70 or older20.918.1--24.04.823.99--5.83^b^Gender    Male8.57.3--9.81 Female9.58.2--11.01.120.94--1.34Lives with a partner    No11.610.2--13.01 Yes7.66.7--8.70.660.59--0.74^b^Education (years of schooling)    0--314.512.4--16.81 4--78.47.3--9.70.580.47--0.71^b^8--115.34.0--6.90.360.28--0.47^b^12 or more3.31.8--6.10.230.13--0.43^b^Perceived income sufficiency    Always enough7.86.4--9.41 Sometimes it's enough8.36.9--10.01.070.84--1.37Never enough10.59.2--11.91.351.14--1.61^c^Current smoker    No9.07.9--10.21 Yes9.27.8--10.81.030.87--1.21Self-rated health    Good4.43.4--5.51 Regular9.07.9--10.22.071.64--2.61^a^Poor27.024.1--30.26.215.03--7.67^a^Number of chronic diseases^f^    One or none5.84.7--7.21 Two or more14.713.2--16.52.542.05--3.15^a^Difficulty performing BADL^g^    No5.84.9--6.81 Yes28.125.2--31.14.874.06--5.83^a^[^6][^7][^8][^9][^10][^11][^12] [Table 3](#t3){ref-type="table"} presents the results of the multivariate analysis. Positive and statistically significant associations were observed for age (PR = 1.69 for the 60--69 age group and PR = 3.49 for those 70 years or older), worse self-rated health (PR = 1.65 for reasonable and PR = 3.17 for poor or very poor), had two or more chronic diseases (PR = 1.34), and had difficulty performing BADL (PR = 2.68). Negative associations were observed for living with a partner (PR = 0.78) and educational level (PR = 0.80, 0.72 and 0.51 for 4--7, 8--11 and 12 years or more, respectively). Table 3Results of the multivariate analysis of factors associated with frailty. The Brazilian Longitudinal Study of Aging (ELSI-Brazil), 2015-2016.VariableAdjusted PR^d^95%CI^e^Age (years)  50--591 60--691.691.37--2.09^a^70 or older3.492.82--4.32^a^Lives with a partner  No1 Yes0.780.67--0.91^b^Education (years of schooling)  0--31 4--70.800.66--0.97^c^8--110.720.55--0.93^c^12 or more0.510.28--0.93^c^Self-rated health  Good1 Regular1.651.34--2.05^a^Poor3.172.56--3.93^a^Number of chronic diseases^f^  Uma ou none1 Two or more1.341.08--1.66^b^Difficulty performing BADL^g^  No1 Yes2.682.23--3.22^a^[^13][^14][^15][^16][^17][^18][^19] [Figure 2](#f02){ref-type="fig"} is the Venn diagram, which shows the overlap between frailty, chronic diseases and difficulty to perform BADL. Of the participants with frailty, 28.0% had two or more chronic diseases; 14.7% had limitations to perform BADL; and 26.7% did not have any of these conditions. Figure 2Venn diagram showing the overlap between frailty, chronic diseases and limitations to perform basic activities of daily living (BADL) among older Brazilians. The Brazilian Longitudinal Study of Aging (ELSI-Brazil), 2015--2016. The additional analysis shows that the estimated prevalence of frailty, using imputed data to compensate for the information loss of 9% of those eligible for the study, was similar (9.5%; 95%CI 8.4--10.6) to that without imputation previously shown. It is noteworthy that this same analysis showed that the factors associated with frailty are the same as presented in [Table 3](#t3){ref-type="table"} (data not shown). DISCUSSION ========== This was the first study to estimate the prevalence of frailty in the Brazilian population aged 50 years or older. The results show a prevalence of 9% of frailty in this population. This prevalence increases with age and reaches 20.9% among those aged 70 years or older. Frailty was associated with less education and different health conditions. In addition, it was observed that about a quarter of the participants presented frailty in the absence of multimorbidity or limitations to perform BADL. The prevalence of frailty varies markedly among populations. The comparison between the studies should be done with caution because of the different definitions used and the age brackets considered in each of them. In this study, prevalence rates were estimated for different ages, in order to allow comparisons with other investigations, using similar criteria to define the outcome. The prevalence of frailty in this analysis for the 65 years or older age group (16.2%) was similar to that observed in SHARE (The Survey of Health, Aging and Retirement in Europe) conducted in 10 European countries (17.0%)[@B6], but higher than in the FIBRA study, conducted in seven Brazilian cities, which identified prevalence rates between 7.7% and 10.8%[@B2]. The prevalence found in this analysis was lower than that observed in other Latin American countries (19.6%)[@B3], but higher than that observed in the SABE study (8.5%), conducted in the city of São Paulo[@B12]. Frailty is one of the major syndromes associated with aging[@B19] because as people age, they accumulate deficiencies in various physiological systems and become increasingly vulnerable to disease complications. With age, there's an increase in the likelihood of neuromuscular changes, neuroendocrine dysregulation, and dysfunctions in the immune system. Thus, the likelihood of the development of disabilities and of chronic diseases onset also increases[@B1] ^,^ [@B4] ^,^ [@B20]. These conditions, as well as frailty, undergo the cumulative effects of risks present throughout life, associated, for example, with age and gender[@B1] ^,^ [@B4]. In the present study, there was a positive association between frailty and age, but there was no association with gender. The results of this study corroborate the relationship between frailty and the presence of disabilities and chronic diseases[@B1] ^,^ [@B4] ^,^ [@B9]. However, as observed in previous studies[@B1] ^,^ [@B21], our results show a significant proportion (26.7%) of individuals with frailty do not present multimorbidity, nor limitations to perform BADL. This proportion is comparable to those found in the United States (26.6%)[@B1] and in Hong Kong (23.1%)[@B21]. These findings reinforce the hypothesis that frailty is a distinct condition associated with physiological dysregulation and that functional diseases and limitations are not necessarily synonymous with frailty[@B1] ^,^ [@B20]. In this analysis, the poor self-rated health was associated with a higher prevalence of frailty, confirming the evidence available in the literature[@B1] ^,^ [@B4] ^,^ [@B5]. Self-rated health has been used as an important marker for the assessment of frailty since the self-perception of good general health is associated with protective effects on the neurological, immunological and endocrine systems[@B22]. People who negatively assess their own health usually invest less in self-care, do not practice physical activity, go less to the doctor, have no healthy eating habits and exhibit low psychosocial development. Thus, they are more likely to develop frailty[@B23]. The results of this study show that the frailty is associated with lower levels of education. As evidenced in other studies[@B1] ^,^ [@B5] ^,^ [@B6] ^,^ [@B24], individuals with lower education had a higher prevalence of frailty. Education is a social determinant of health often used in inequity analyses. The low level of education in Brazil compromises access to health and also to better employment and financial conditions, interfering with the style and quality of life of the individual. Consequently, individuals with a lower educational level have higher levels of unhealthy behaviors and develop more chronic diseases, which have an influence on the process of developing frailty[@B25]. The association between lower prevalence of frailty and living with a partner calls attention to the importance of social relations and social support for the prevalence[@B4] ^,^ [@B9] and the incidence of frailty[@B26]. Among the possible explanations for the lower prevalence of frailty and the presence of marital relationship, we can highlight the favorable effects of structural support from social relations. Moreover, part of the association between marital status and health comes from positive affection and happiness, and not only from social support[@B27]. The presence of a partner may also favor health care, such as increasing adherence to medication treatment[@B28]. This study has strengths and limitations. The main advantage of the study is its large population base, which allows for the estimation of prevalence rates for the Brazilian population. In addition, frailty was measured using a well-known and standard method, allowing comparisons with other investigations. The limitations are related to the cross-sectional nature of the study, which limits the assessment of causality between associated factors and frailty. In sum, the prevalence of frailty among Brazilians aged 65 years or older is similar to that observed in the corresponding age group in European countries. Worse health conditions, functional limitation and lower education emerge as the factors most strongly associated with the frailty in this population. The results also show that frailty can occur in the absence of multimorbidity and functional limitations. These findings constitute the first estimate of frailty for the Brazilian population and can provide important information for the planning and implementation of health care interventions and actions to promote better quality of life and active aging among older Brazilians. Fundação Oswaldo Cruz. Brazilian Longitudinal Study of Aging. Rio de Janeiro; c2015 \[cited 2017 Nov 28\]. Available from: <http://elsi.cpqrr.fiocruz.br> **Funding:** The ELSI-Brazil baseline study was supported by the Brazilian Ministry of Health (DECIT/SCTIE -- Department of Science and Technology from the Secretariat of Science, Technology and Strategic Inputs (Grant 404965/2012-1); COSAPI/DAPES/SAS -- Healthcare Coordination of Older Adults, Department of Strategic and Programmatic Actions from the Secretariat of Health Care) (Grants 20836, 22566 and 23700); and the Brazilian Ministry os Science, Technology, Innovation and Communication. [^1]: **Authors' Contribution:** JMA, FCDA, FBA participated in the study concept and design, data analysis and interpretation, drafting of the manuscript. YAOL, LCA, MFLC, PRBJ participated in data interpretation, drafting of the manuscript. All authors approve the final submitted version. [^2]: **Conflict of Interest:** The authors declare no conflict of interest. [^3]: ^a^ Estimated 95% confidence intervals. [^4]: ^b^ History of medical diagnosis of hypertension, diabetes, heart disease, chronic lung disease, stroke, arthritis, asthma, cancer, and kidney disease. [^5]: ^c^ Difficulty in performing one of the following basic activities of daily living (BADL): bathing, dressing, eating, using the toilet, getting out of bed, crossing a room on the same floor. [^6]: ^a^ p \< 0.001 [^7]: ^b^ p \< 0.01 [^8]: ^c^ p \< 0.05 [^9]: ^d^ Prevalence ratio. [^10]: ^e^ Estimated 95% confidence intervals. [^11]: ^f^ History of medical diagnosis of hypertension, diabetes, heart disease, chronic lung disease, stroke, arthritis, asthma, cancer, and kidney disease. [^12]: ^g^ Difficulty in performing one of the following basic activities of daily living (BADL): bathing, dressing, eating, using the toilet, getting out of bed, crossing a room on the same floor. [^13]: ^a^ p \< 0.001 [^14]: ^b^ p \< 0.01 [^15]: ^c^ p \< 0.05 [^16]: ^d^ Prevalence ratio adjusted by gender and income sufficiency. [^17]: ^e^ Estimated 95% confidence intervals. [^18]: ^f^ History of medical diagnosis of hypertension, diabetes, heart disease, chronic lung disease, stroke, arthritis, asthma, cancer, and kidney disease. [^19]: ^g^ Difficulty in performing one of the following basic activities of daily living (BADL): bathing, dressing, eating, using the toilet, getting out of bed, crossing a room on the same floor.
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The present invention pertains generally to devices and methods for separating and segregating the constituents of a multi-constituent material. More particularly, the present invention pertains to devices for efficiently initiating and maintaining a multi-species plasma in a chamber and then separating the ions in the multi-species plasma according to their respective mass to charge ratios. The present invention is particularly, but not exclusively, useful as a filter to separate the high mass particles from the low mass particles in a plasma that is initiated and maintained by high frequency wave heating. There are many reasons why it may be desirable to separate or segregate mixed materials from each other. One such application where it may be desirable to separate mixed materials is in the treatment and disposal of hazardous waste. For example, it is well known that of the entire volume of nuclear waste, only a small amount of the waste consists of radionuclides that cause the waste to be radioactive. Thus, if the radionuclides can somehow be segregated from the non-radioactive ingredients of the nuclear waste, the handling and disposal of the radioactive components can be greatly simplified and the associated costs reduced. Indeed, many different types of devices, which rely on different physical phenomena, have been proposed to separate mixed materials. For example, settling tanks which rely on gravitational forces to remove suspended particles from a solution and thereby segregate the particles are well known and are commonly used in many applications. As another example, centrifuges which rely on centrifugal forces to separate substances of different densities are also well known and widely used. In addition to these more commonly known methods and devices for separating materials from each other, there are also devices which are specifically designed to handle special materials. A plasma centrifuge is an example of such a device. As is well known, a plasma centrifuge is a device which generates centrifugal forces to separate charged particles in a plasma from each other. For its operation, a plasma centrifuge necessarily establishes a rotational motion for the plasma about a central axis. A plasma centrifuge also relies on the fact that charged particles (ions) in the plasma will collide with each other during this rotation. The result of these collisions is that the relatively high mass ions in the plasma will tend to collect at the periphery of the centrifuge. On the other hand, these collisions will generally exclude the lower mass ions from the peripheral area of the centrifuge. The consequent separation of high mass ions from the relatively lower mass ions during the operation of a plasma centrifuge, however, may not be as complete as is operationally desired, or required. Apart from a centrifuge operation, it is well known that the orbital motions of charged particles (ions) in a magnetic field, or in crossed electric and magnetic fields, will differ from each other according to their respective mass to charge ratio. Thus, when the probability of ion collision is significantly reduced, the possibility for improved separation of the particles due to their orbital mechanics is increased. For example, U.S. Pat. No. 6,096,220, which issued on Aug. 1, 2000 to Ohkawa, for an invention entitled xe2x80x9cPlasma Mass Filterxe2x80x9d and which is assigned to the same assignee as the present invention, discloses a device which relies on the different, predictable, orbital motions of charged particles in crossed electric and magnetic fields in a chamber to separate the charged particles from each other. In the filter disclosed in Ohkawa ""220, the magnetic field is oriented axially, the electric field is oriented radially and outwardly from the axis, and both the magnetic field and the electric field are substantially uniform both azimuthally and axially. As further disclosed in Ohkawa ""220, this configuration of fields causes ions having relatively low mass to charge ratios to be confined inside the chamber during their transit of the chamber. On the other hand, ions having relatively high mass to charge ratios are not so confined. Instead, these larger mass ions are collected inside the chamber before completing their transit through the chamber. The demarcation between high mass particles and low mass particles is a cut-off mass Mc which is established by setting the magnitude of the magnetic field strength, B, the positive voltage along the longitudinal axis, Vctr, and the radius of the cylindrical chamber, xe2x80x9caxe2x80x9d. Mc can then be determined with the expression: Mc=ea2(B)2/8Vctr. Generally, for most plasma related applications, energy must be expended to initiate and maintain the plasma. Considerable effort has been made to minimize the energy required to initiate and maintain the plasma. Heretofore, electron cyclotron heating (ECH) processes, wherein an electromagnetic wave is launched into a plasma chamber to initiate and maintain the plasma, have been developed for plasma deposition applications (see for example, Principles of Plasma Discharges and Materials Processing, by Lieberman, Wiley Interscience, pgs. 412-415). The general dispersion relation for a wave propagating in plasma can be written: Tan2xcex8=xe2x88x92K∥(N2xe2x88x92Kr)(N2xe2x88x92K|)/((N2xe2x88x92K∥)(Kxe2x8axa5N2xe2x88x92K|Kr))xe2x80x83xe2x80x83[1] where xcex8 is the angle of the wave propagation relative to the magnetic field, B, N is the index of refraction (i.e., N=ck/xcfx89) where c is the speed of light, k is the wave vector, ne is the electron density, e is the electron charge, and xcfx89 is the wave frequency); and for frequencies much greater than ion cyclotron and ion plasma frequencies: Kr=1xe2x88x92xcfx89p2/(xcfx89(xcfx89xe2x88x92xcfx89c)) K|=1xe2x88x92xcfx89p2/(xcfx89(xcfx89+xcfx89c)) K195=1xe2x88x92xcfx89p2/(xcfx892xe2x88x92xcfx89c2)) K∥=1xe2x88x92xcfx89p2/xcfx892 where wc=eB/mc=1.8xc3x971011 B and wp2=ne2/(xcex50mc)=57 n1/2 are the electron cyclotron and electron plasma frequencies. For propagation along the magnetic field, xcex8=0, the numerator of Eq, [1] must vanish and for propagation at xcex8=xcfx80/2 the denominator must vanish. These solutions give the principal waves. The right-hand polarized wave rotates in synchronism with the electrons when xcfx89=xcfx89ce leading to resonant energy absorption. Collisional absorption can also be effective and can be estimated by substituting xcfx89=xcfx89+ixcexd. The physics of high frequency wave propagation and absorption lead to two approaches for heating the plasma 5 mass filter with electron cyclotron waves. The first approach utilizes a resonant wave that is launched along the magnetic field with the magnetic field chosen to decrease away from the launcher and the resonant field is located axially at a point where the heating is desired. The second approach utilizes a wave propagating radially in a cavity perpendicular to the magnetic field, (xcex8=xcfx80/2); this requires a high frequency wave above the electron plasma frequency and relies on collisional absorption. For the case of xcex8=0, choosing the wave synchronous with the electrons allows Eq. [1] to be written: k2/k02=1xe2x88x92xcfx89p2/(xcfx89(xcfx89xe2x88x92xcfx89c))xe2x80x83xe2x80x83[2] where k0=w/c and for perpendicular propagation, xcex8=xcfx80/2, the dispersion relation can be written: k2-/k02=K1Kr/K195 xcx9c(1xe2x88x92xcfx89p2/xcfx892) for xcfx89 greater than xcfx89c.xe2x80x83xe2x80x83[3] For the case of a wave launched along the magnetic field from one end of the device, xcex8=0. The dispersion relation shows that for regions where xcfx89 less than xcfx89c, the circularly polarized wave propagates at any plasma density and for regions where xcfx89=xcfx89c, the circularly polarized wave is strongly damped. For regions where xcfx89=xcfx89c, a resonance zone occurs and ionization and heating of gas/plasma occurs. Furthermore, the placement of the resonance zone within the chamber can be controlled by the proper distribution of the magnetic field within the chamber. For example, consider a chamber having a magnetic field that diverges from a first end of the chamber where the magnetic field is B1 to the middle of the chamber where the magnetic field is B0, and where B1 greater than B0. When a circularly polarized wave having a frequency, xcfx89, xcfx89=eB0/mxe2x80x83xe2x80x83[4] is launched from the first end toward the middle of the chamber, the circularly polarized wave propagates to the resonance zone. This is because xcfx89 less than xcfx89c for regions where B greater than B0. Furthermore, the circularly polarized wave is strongly absorbed at the resonance zone where B=B0 and xcfx89=xcfx89c. At the resonance zone, heating and ionization of the plasma occurs because the rotating electric field of the circularly polarized wave matches the gyrating orbits of the plasma electrons. Thus, the electrons receive essentially a static electric field which imparts a large acceleration on the electrons. Collisions between the accelerated electrons and other electrons and ions result in heating. For an exemplary circularly polarized wave of frequency 2.45 GHz (i.e. a wave in the microwave spectrum), the resonance field is approximately B0=0.085 T. For a plasma density, n, of 1018mxe2x88x923 the plasma frequency is xcfx89p=5.7xc3x971010/s. For the case of a wave launched perpendicular to the magnetic field, xcex8=xcfx80/2, the frequency has to be chosen high enough to insure wave propagation and the absorption is not resonant, but collisional. Since collisional absorption is generally not strong for conditions of interest, it is important to have the plasma immersed in a high Q cavity in order to get efficient heating. A choice of frequency just above the electron plasma frequency at the desired operating point is a good choice. The electron collision frequency for 1eV electrons is about xcexdxcx9c2.9xc3x9710xe2x88x9211n, or about 2.9xc3x97107 for a density n of 1018 mrxe2x88x923 giving a ratio of xcexd/xcfx89pxcx9c5xc3x9710xe2x88x924. An estimate of the damping length from the imaginary part of the wave vector for xcfx89 greater than xcfx89p greater than xcfx89c gives: ki=(xcexd/2c)xcfx89p2)/w2)/(1xe2x88x92xcfx89p2/w2)1/2xcx9c(xcexd/2c)(xcfx89p2/xcfx89p2)xcx9c5xc3x9710xe2x88x9220 n(xcfx89p2/w2)mxe2x88x921xe2x80x83xe2x80x83[5] Hence, the damping length is of order 100 m, so it is desirable to have the cavity Q high enough to allow on the order of 103 transits of the wave to insure adequate damping. In light of the above, it is an object of the present invention to provide devices and methods suitable for the purposes of efficiently initiating and maintaining a multi-species plasma in a chamber and then separating the ions in the multi-species plasma according to their respective mass to charge ratios. It is another object of the present invention to provide a heating source for a plasma mass filter in which the location within the plasma of the effective heating zone can be adjusted by varying the magnetic field distribution within the filter. It is still another object of the present invention to provide a heating source for a plasma mass filter that does not require high voltage components inside the plasma chamber that would otherwise be subject to breakdown in poor vacuum conditions. Yet another object of the present invention is to provide devices and methods for separating the constituents of a multiconstituent material which are easy to use, relatively simple to implement, and comparatively cost effective. In overview, the present invention is directed to devices and methods for separating and segregating the constituents of a multi-constituent material. In particular, for the operation of the present invention, a multi-species plasma is first created from the multi-constituent material using high frequency wave heating. Once the multi-species plasma is created, crossed electric and magnetic fields are used to separate ions in the plasma having a relatively low mass to charge ratio from ions in the plasma having a relatively high mass to charge ratio. In greater detail, the device in accordance with the present invention If includes a chamber having a substantially cylindrical wall that extends between a first end of the chamber and a second end of the chamber. The cylindrical wall is centered on a longitudinal axis. Magnetic coils are selectively arranged on the outside of the chamber wall and are activated to generate a magnetic field inside the chamber that is directed substantially along the longitudinal axis. In a first embodiment, a magnetic field is established in the chamber that diverges from a magnitude B1 at the first end of the chamber to a magnitude B0 at a zone between the first end and the second end of the chamber, with B1 being greater than B0 (B1 greater than B0). From the zone where the magnitude is approximately B0, the magnetic field can converge to the second end where the magnetic field has a magnitude B2, with B2 being greater than B0 (B2 greater than B0), and accordingly (B1 greater than B0 less than B2). In one implementation, the magnetic field has substantially the same magnitude at both the first and second ends of the chamber (B1=B2). With this cooperation of structure, the magnetic field decreases in magnitude from the first end of the chamber to the zone, while also decreasing in magnitude from the second end of the chamber to the zone. Importantly for this embodiment, a zone having a magnetic field strength of magnitude of B0 is created in the chamber between the first and second end of the chamber wall. Continuing with the first embodiment, one or more launchers are provided at the end(s) of the chamber to launch circularly polarized electromagnetic wave(s) into the chamber in a direction substantially parallel to the longitudinal axis. For the present invention, the circularly polarized electromagnetic wave(s) are created having a frequency xcfx89, where xcfx89=eB0/m and e/m is the electron charge/mass ratio (e/m=1.8xc3x971011 coul/kg). Furthermore, the rotation direction of the E vector of each circularly polarized wave is chosen to coincide with the rotation direction of the electron orbits in the magnetic field. In accordance with the dispersion relationship described above, the circularly polarized electromagnetic wave(s) of frequency xcfx89, are able to propagate from the chamber end to the zone where the magnetic field is approximately B0. When a feed, which can be any mixture having both high mass and low mass constituents, is introduced into the chamber it will be subjected to ECH. Specifically, at the zone where the magnetic field is approximately B0 (i.e. the resonance zone), electrons in the zone are accelerated by the circularly polarized electromagnetic waves. The accelerated electrons then collide with neutrals, ions and other electrons from the feed and the collisions result in the ionization of neutrals and the heating of the electrons. The ionization and heating at the resonance zone initiates and maintains a multi-species plasma having ions of relatively high mass to charge ratio (M1) and ions of relatively low mass to charge ratio (M2) in the chamber. The device further includes one or more electrodes for creating an electric field that is radially oriented within the chamber. Specifically, the electrode(s) establish a positive voltage (Vctr) along the longitudinal axis and a substantially zero potential at the wall of the chamber. With the crossed electric and magnetic fields, ions having a relatively low mass to charge ratio (M2) generated at the resonance zone are confined inside the chamber and transit through the chamber exiting at one of the chamber ends. On the other hand, ions generated at the resonance zone having a relatively high mass to charge ratio (M1) are not so confined. Instead, these larger mass ions strike a high mass ion collector mounted on the inside of the wall near the resonance zone before completing their transit through the chamber. Specifically, for a high mass ion collector that is at a distance xe2x80x9cacxe2x80x9d from the longitudinal axis, ions having a mass (M1) that is greater than a cut-off mass, Mc (M1 greater than Mc) will be collected at the wall near the resonance zone, where Mc=eac2(Bc)2/8Vctr wherein xe2x80x9cexe2x80x9d is the ion charge and Bc is the magnetic field at the ends of the high mass ion collector. In another embodiment of the present invention, a radial electric field is generated in a chamber as described above. Also, coils are provided to generate an axially aligned, uniform magnetic field having magnetic field strength, B0, in the chamber. In this embodiment, a high frequency, polarized electromagnetic wave is launched into the chamber along a substantially radial path to initiate and maintain a plasma in the chamber via collisional absorption. A pair of spaced apart reflectors are positioned to surround the plasma and establish a high Q cavity therebetween. With this cooperation of structure, the electromagnetic wave can be launched into the chamber for travel back and forth between the reflectors. Each time the wave travels between reflectors, it interacts with the plasma, heating the plasma via collisional absorption. Once generated, the plasma is separated in the crossed electric and magnetic fields as described above.
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AHNAK Neuroblast differentiation-associated protein AHNAK, also known as desmoyokin, is a protein that in humans is encoded by the AHNAK gene. AHNAK was originally identified in 1989 (in bovine muzzle epidermal cells) and named desmoyokin due to its localization pattern (that resembled a yoke) in the desmosomal plaque. AHNAK has been shown to be essential for pseudopod protrusion and cell migration. Interactions AHNAK has been shown to interact with S100B. References Further reading External links
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John Nesbitt Kirchhoffer John Nesbitt Kirchhoffer (May 5, 1848 – December 22, 1914) was a Canadian politician. Born in Ballyvourney, County Cork, Ireland, the son of the Reverend Richard B. Kirchhoffer, Rector of Ballyvourney Parish, he was educated at Marlborough College and came to Canada in 1864. Kirchhoffer served as an Ensign in the Fenian raids in 1866 and subsequently was Captain of one of the Companies of the Port Hope (46th) Battalion. He was called to the Ontario Bar in October 1871 and practiced law in Port Hope, Ontario with his uncle, Nesbitt Kirchhoffer. He moved to Manitoba in 1883, and was called to the Manitoba Bar in 1884. Kirchhoffer founded the town of Souris, Manitoba and the Plum Creek settlement, and served as Reeve and Mayor of Souris. He was a member of the Legislative Assembly of Manitoba from 1886 to 1888 representing Brandon West. Kirchhoffer also served on the Western Judicial District Board, representing Brandon and Dennis counties. He was called to the Senate on December 16, 1892 on the advice of John Sparrow David Thompson representing the senatorial division of Selkirk, Manitoba. A Conservative, he was Chairman of the Senate Divorce Committee in 1895 and 1896, and of the Senate Contingent Committee in 1897. He served 22 years until his death in 1914. Kirchhoffer was also a keen cricketer, representing Canada in a match against the United States on the Germantown Cricket Club Ground, Nicetown, Philadelphia in 1880, scoring one run and taking two catches in a drawn match. He served as president of the Ontario Cricket Club and of the Canadian Zingari cricket club. In 1881 and 1882, Kirchhoffer captained Canadian International cricket teams which played against the United States. References Sources Adams, P. (2010) A history of Canadian cricket, lulu.com. . Category:1848 births Category:1914 deaths Category:Politicians from County Cork Category:Cricket players from County Cork Category:People of the Fenian Raids Category:Canadian senators from Manitoba Category:Conservative Party of Canada (1867–1942) senators Category:Irish emigrants to pre-Confederation Ontario Category:Progressive Conservative Party of Manitoba MLAs Category:Mayors of places in Manitoba Category:People educated at Marlborough College Category:Canadian cricketers Category:Immigrants to the Province of Canada Category:People from Souris, Manitoba
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Incident Description Which type of area was your bike stolen from?: Other situation, please describe below. How long was the bike locked in this location?: 7 hours Incident Description: Leaving work at Rush, heading towards where I had locked the bike (bike rack located at the south end of the Rush Professional Building, next to the valet parking lot) only to find the bike missing and the u-lock cut through with an angle grinder.
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Major Cities Often the Safest Places in the U.S., Penn Medicine Study Finds Overall risk of injury death is lower in urban areas compared to outside of cities PHILADELPHIA — Overturning a commonly-held belief that cities are inherently more dangerous than suburban and rural communities, researchers from the Perelman School of Medicine at the University of Pennsylvaniaand The Children’s Hospital of Philadelphia (CHOP) have found that risk of death from injuries is lowest on average in urban counties compared to suburban and rural counties across the U.S. The new study, which appears online ahead of print in the Annals of Emergency Medicine, found that for the entire population, as well as for most age subgroups, the top three causes of death were motor vehicle collisions, firearms, and poisoning. When all types of fatal injuries are considered together, risk of injury-related death was approximately 20 percent lower in urban areas than in the most rural areas of the country. Related Links “Perceptions have long existed that cities were innately more dangerous than areas outside of cities, but our study shows this is not the case” said lead study author, Sage R. Myers, MD, MSCE, assistant professor of Pediatrics, Perelman School of Medicine and attending physician, Department of Emergency Medicine at CHOP. “These findings may lead people who are considering leaving cities for non-urban areas due to safety concerns to re-examine their motivations for moving. And we hope the findings could also lead us to re-evaluate our rural health care system and more appropriately equip it to both prevent and treat the health threats that actually exist.” The study examined county-level data on all injury deaths across the U.S. from 1999-2006 (because of their unusual nature, deaths from the 9-11 terrorist attacks were excluded). Findings from the study support prior work showing that overall homicide rates are lower in rural areas than urban areas. This was found to be true in all age groups, except the oldest adults (over 65 years old). Suicide rates, on the other hand, showed an increase with rurality, but the increased rate of suicide death in rural areas only reached statistical significance for the two youngest age groups: 0-14 years and 15-19 years. However, the magnitude of homicide- and suicide-related deaths, even in urban areas, is far outweighed by the magnitude of unintentional-injury deaths – such as those from car crashes and falls – in nonurban areas, especially in rural nonurban areas. Specifically, the rate of unintentional-injury death is over 15 times that of homicide for the entire population and the risk of unintentional-injury death is 40 percent higher in the nation’s most rural counties compared to the most urban. The research team found that the bulk of unintentional injury deaths result from motor vehicle crashes, with motor vehicle injury-related deaths occurring at a rate that is more than 1.4 times higher than the next leading mechanism of injury death. In rural areas, this difference is even more pronounced, where motor vehicle injury-related death rates are twice that of the next leading injury mechanism. Across the rural-urban continuum, the risk of motor vehicle-related injury death is 2 times more likely in rural areas as compared to the most urban. “We think our work serves as a reminder that injury is an important health issue for Americans, wherever they live. Our findings can inform both targeted prevention efforts and strategic efforts to improve trauma care in the U.S. This work provides a real opportunity to build systems of medical care that are positioned to best care for the populations that depend upon them for life and limb saving treatment in their time of need,” said senior study author Brendan G. Carr, MD, MSHP, assistant professor Emergency Medicine and Biostatistics and Epidemiology at Penn. The researchers note that next steps in this line of research should focus on creating local injury priority scores – a relatively simple and objective tool that uses data available in trauma center registries to rank injury causes according to both frequency and severity – and considering innovative ways to continue to develop the U.S. emergency and trauma care system to assure that all Americans receive the best emergency and trauma care possible. “Trauma has been a leader in planning for care from the population perspective,” says Carr, referencing the interactive trauma system mapping tool created at Penn, “but we’ve still got work to do.” The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.
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A straightforward method for measuring the range of apparent density of microplastics. Density of microplastics has been regarded as the primary property that affect the distribution and bioavailability of microplastics in the water column. For measuring the density of microplastis, we developed a simple and rapid method based on density gradient solutions. In this study, we tested four solvents to make the density gradient solutions, i.e., ethanol (0.8 g/cm3), ultrapure water (1.0 g/cm3), saturated NaI (1.8 g/cm3) and ZnCl2 (1.8 g/cm3). Density of microplastics was measured via observing the float or sink status in the density gradient solutions. We found that density gradient solutions made from ZnCl2 had a larger uncertainty in measuring density than that from NaI, most likely due to a higher surface tension of ZnCl2 solution. Solutions made from ethanol, ultrapure water, and NaI showed consistent density results with listed densities of commercial products, indicating that these density gradient solutions were suitable for measuring microplastics with a density range of 0.8-1.8 g/cm3.
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1. Introduction {#Ch1.S1} =============== Methane (${CH}_{4}$) is a by-product of microbial fermentation processes in ruminants (Henderson et al., 2015) and a potential greenhouse gas. Furthermore, ${CH}_{4}$ emissions reflect an unused proportion of gross energy intake (Johnson and Ward, 1996; Baker, 1999). Fodder is the major cost factor in sheep production systems (Ellison et al., 2017). Hence, there is an increasing interest to breed animals with improved productivity and feed efficiency (i.e., feed intake in relation to body weight gain), possibly via selection on low individual ${CH}_{4}$ emissions (Paganoni et al., 2017). Pickering et al. (2015) and Paganoni et al. (2017) indicated genetic variation and small to moderate heritabilities for ${CH}_{4}$ traits in dairy cows and sheep, and Rösler et al. (2018) described an individual variation in enteric ${CH}_{4}$ emissions in female goats. Furthermore, the economic benefits from selection scenarios including ${CH}_{4}$ traits (Robinson and Oddy, 2016) suggest consideration of ${CH}_{4}$ or of ${CH}_{4}$ indicator traits into overall sheep breeding goals. In this regard, respiration chamber calorimetry is the "golden standard" to determine ${CH}_{4}$ emissions in sheep. Nevertheless, respiration chamber measurements imply strong efforts regarding logistics, associated with a substantial cost component. In consequence, only a small number of sheep can be phenotyped for ${CH}_{4}$ using the respiration chamber technique. In addition, respiration chambers reflect an artificial environment, which is not representative of sheep kept in pasture-based production systems. Animals might show abnormal behavior (e.g., reduced dry matter intake, DMI) in the chamber, possibly influencing a ${CH}_{4}$ emission pattern (Kabreab et al., 2006; Bickell et al., 2014). Thus, Knapp et al. (2014) and Huhtanen et al. (2015) requested alternative reliable and cost-efficient methods for ${CH}_{4}$ recording, especially under field conditions. In such a context, approaches based on feed supplements were unsuitable under grazing conditions (Baker, 1999). Predictions of ${CH}_{4}$ via deterministic modeling usually require a large amount of input data, e.g., DMI, dietary or milk components, which are difficult to record (Kabreab et al., 2006; Yin et al., 2015). Further indirect methods for ${CH}_{4}$ emission predictions based on the ruminal microbiome composition but associations between ${CH}_{4}$ production and microbiome characteristics were inconsistent (Shi et al., 2014; Ellison et al., 2017). The portable handheld laser methane detector (LMD) was suitable for ${CH}_{4}$ recording in dairy cattle under field conditions, with low inter-observer variability (Chagunda et al., 2009b). In validations, correlations between LMD ${CH}_{4}$ and ${CH}_{4}$ measurements from the respiration calorimetric chamber were large (Chagunda and Yan, 2011). With regard to associations between ${CH}_{4}$ output and other breeding goal traits, Zetouni et al. (2018) estimated negative genetic correlations between ${CH}_{4}$ production (g d$^{- 1}$) and body conformation traits in Danish Holstein cows. Nevertheless, there is a gap of knowledge addressing "across generation studies", i.e., association analyses between indicators for energy balances of ewes (including ${CH}_{4}$ emissions) and body weights of their lambs (LBW; also characterizing productivity of the ewe). The objective of the present study was to focus on such intergenerational aspects, considering ${CH}_{4}$ measurements from ewes (recorded via LMD) as energy balance indicators. The ${CH}_{4}$ databases were used (i) to define and to evaluate different ${CH}_{4}$ measurement characteristics, (ii) to estimate genetic parameters for ${CH}_{4}$ measurements, and (iii) to correlate phenotypically and genetically ewe ${CH}_{4}$ measurements with other breeding goal traits from a within- and transgenerational perspective. 2. Materials and methods {#Ch1.S2} ======================== 2.1. Ethics statement {#Ch1.S2.SS1} --------------------- The housing and treatment of the animals were carried out in accordance with national and international laws. The study was restricted to routine on-farm observations. All presented methods were non-invasive. Therefore, they did not cause the included animals pain, suffering or harm, in compliance with the German Animal Welfare Act $\mathit{§}\ 7$. Nevertheless, the presented procedures have been approved for a subsample of ewes that were used for additional blood parameter analyses by the regional board of Giessen (V 54-19 c 20 15 h 01 GI 18/14 Nr. G 62/2017). 2.2. Production system {#Ch1.S2.SS2} ---------------------- For trait recording, we focused on sheep from the University of Giessen research station "Oberer Hardthof", reflecting a mixture of grazing (spring to fall) and high-input (fall to spring) sheep production system. The farm is located 200 m above sea level in the federal state Hesse in the middle of Germany. The average annual temperature is 8.8 $^{\circ}$C, and the average precipitation amount is 695 mm per year. The farm comprises 70 ha for a flock including 630 ewes, 7 rams and 98 hoggets of Merinoland (ML) and Rhön sheep (RH). During the lambing season, the flock was fed hay ad libitum. The hay quality was as follows: 90.3 % dry matter (DM), 40.2 % crude fiber (CF), 6.8 % crude protein (CP), 1.3 % crude lipid (EE) and 7.8 MJ metabolizable energy (ME) per kg in DM. Ewes within the last third of gestation received additional concentrates up to 1 kg d$^{- 1}$. The concentrates were composed of barley, wheat, rapeseed meal extract, wheat bran and triticale (6.8 % CF, 18 % CP, 2.6 % EE, 10.8 ME MJ per kg DM). The calculated daily ration for a twin-suckling ewe with an average body weight of 85 kg contained 1.8 kg hay and 900 g concentrates (21.84 MJ ME per ewe and day). Lambs had ad libitum access to concentrates at an age of 21 to 28 d. They were weaned group-wise at a mean age of $65.35 \pm 5.35$ d with an average body weight of $26.10 \pm 4.91$ kg. 2.3. Animals and traits {#Ch1.S2.SS3} ----------------------- Data recording spanned a period from 2017 to 2018. The study considered 330 ewes (253 ML, 77 RH) and their purebred 629 lambs (478 ML, 151 RH). The age of ewes ranged from 22.1 to 96.8 months (mean $=$ $51.3 \pm 18.2$ months). In a subset of 177 ewes (133 ML, 44 RH), the whole pattern of traits was recorded: ewe body weight (EBW) (digital scale: model 703, TRU-TEST Group, Auckland, New Zealand), ewe body condition score (BCS), ewe backfat thickness (BFT) in millimeters (mm), and the individual ${CH}_{4}$ concentrations ($µ$L L$^{- 1}$) in the exhaled air. Body condition score was assessed by palpating the transverse and spinous processes of the lumbar region around the backbone. Scores ranged on a scale from 1.0 (emaciated) to 5.0 (obese) with increments of 0.5 (Russel et al., 1969). Backfat thickness was measured on the right side directly behind the 13th rib (Silva et al., 2006; Gernand and Lenz, 2005), using a mobile ultrasound transducer (EasiScan ultrasound scanner, 4.5--8.5 MHz linear, BCF Technology Ltd., Bellshill, Scotland). Individual ${CH}_{4}$ concentrations in the exhaled air were measured using an LMD (Crowcon LaserMethane Mini, Tokyo Gas Engineering Co Ltd., Tokyo, Japan). Lamb body weight was recorded from 281 offspring (216 ML, 65 RH). A further subset for genetic analyses considered only EBW and BCS of an additional 153 ewes (120 ML, 33 RH) and LBW of their 348 lambs (262 ML, 86 RH). We generated a longitudinal data structure, implying ewe trait and LBW recording on the same days in intervals of 3 weeks from parturition until weaning. 2.4. Laser methane detector method and ${CH}_{4}$ data preparation {#Ch1.S2.SS4} ------------------------------------------------------------------ According to Ricci et al. (2014), the interval between feeding and LMD ${CH}_{4}$ recording comprised 3--5 h. Ricci et al. (2014) identified substantial impact of meteorological data on individual ${CH}_{4}$ emissions. Consequently, we selected a wind-still environment, and we accounted for temperature and humidity in genetic-statistical modeling. In order to guarantee standardized trait recording, ewe ${CH}_{4}$ measurements were performed after weighing in the weighing facility, and additionally an assistant fixated the ewes during ${CH}_{4}$ recording. Hence, we always had a distance of exactly 1 m between the operator (i.e., the LMD) and the sheep\'s nostrils, and we avoided noisy data because of an uncontrolled movement (Ricci et al., 2014; Huhtanen et al., 2015). ![Example for a ${CH}_{4}$ measurement profile of one ewe recorded via laser methane detector (LMD) and corrected for background ${CH}_{4}$. Values under the threshold describe ${CH}_{4}$ emissions during respiration and values above the threshold describe ${CH}_{4}$ emissions during eructation.](aab-63-113-g01){#Ch1.F1} The LMD recorded ${CH}_{4}$ concentrations in intervals of 0.5 s in the exhaled air. Methane concentrations were directly displayed in parts per million-meter (ppm-m) (Tokyo Gas Engineering Co. Ltd., 2013). Because the distance between the LMD and the ewe\'s nostrils was exactly 1 m in the present study, the ${CH}_{4}$ concentration was expressed in microliters per liter (Ricci et al., 2014). Ongoing ${CH}_{4}$ data preparation in R 3.3.2 (R Development Core Team, 2016) is based on the protocol as suggested by Ricci et al. (2014): the minimum ${CH}_{4}$ concentration of each measurement was set as a background ${CH}_{4}$ concentration, i.e., to reflect environmental ${CH}_{4}$ influence (overall mean background ${CH}_{4}$ $=$ 6.82 $µ$L L$^{- 1}$). Afterwards, background ${CH}_{4}$ was subtracted from the remaining ${CH}_{4}$ records. Because the LMD detection is based on ${CH}_{4}$ in the exhaled air, we considered the dynamics of the respiratory cycle (Chagunda, 2013). In this regard, Fig. 1 illustrates the ${CH}_{4}$ measurement profile for one ewe. Every dot represents a detected ${CH}_{4}$ concentration in microliters per liter. The ${CH}_{4}$ emission profile represents small increases in ${CH}_{4}$ concentration (mini-peaks; solid dots) due to exhalation or eructation. Before and after one mini-peak, mini-troughs (open dots) represent small ${CH}_{4}$ concentration decreases due to ${CH}_{4}$ diffusions. Only mini-peak data (solid dots) were log-transformed (natural logarithm) and used for further analyses (Chagunda et al., 2009b). Because mini-peaks reflect two different possibilities of ${CH}_{4}$ excretion -- (i) ${CH}_{4}$ absorption from the rumen or lower digestive tract and emission via the lungs (respiration) and (ii) ${CH}_{4}$ emissions directly from the rumen (eructation) (Murray et al., 1976) -- a double normal distribution for mini-peaks was assumed. The dashed line in Fig. 1 shows the defined threshold at 95 % cumulative probability (35.87 $µ$L L$^{- 1}$) for the lower normal distribution from all ${CH}_{4}$ mini-peak observations. Consequently, all mini-peaks (solid dots) under the dashed line belong to ${CH}_{4}$ emitted during respiration. All mini-peaks (solid dots) above the threshold represent ${CH}_{4}$ concentrations during eructation. A group of solid dots including more than two mini-peaks above the dashed line was defined as one eructation event. Each normal distribution (respiration ${CH}_{4}$; eructation ${CH}_{4}$) represents a separate ${CH}_{4}$ dataset with separate mean and maximum. Based on the data preparation protocol, the following ${CH}_{4}$ traits were defined: ${CH}_{4_{r + e}}$: mean ${CH}_{4}$ concentration during respiration and eructation,${CH}_{4_{r}}$: mean ${CH}_{4}$ concentration during respiration,${CH}_{4_{rsum}}$: sum of ${CH}_{4}$ concentrations per minute during respiration,${CH}_{4_{rmax}}$: maximum ${CH}_{4}$ concentration during respiration,${CH}_{4_{e}}$: mean ${CH}_{4}$ concentration during eructation,${CH}_{4_{esum}}$: sum of ${CH}_{4}$ concentrations per minute during eructation,${CH}_{4_{emax}}$: maximum ${CH}_{4}$ concentration during eructation,${CH}_{4_{event}}$: number of eructation events per minute. Descriptive statistics for the defined ${CH}_{4}$ traits are given in Table 1. ###### Descriptive statistics for ewe body weight (EBW), ewe body condition score (BCS), ewe backfat thickness (BFT) and ${CH}_{4}$ traits in the breeds Merinoland (ML) and Rhön sheep (RH). Breed Trait$^{*}$ No. Mean SD Median Minimum Maximum ------- ------------------------------------------------ ------ ------ ------ -------- --------- --------- ML EBW (kg) 1133 94.5 11.5 94.5 57.0 130   BCS 1133 3.35 0.78 3.50 1.00 5.00   BFT (mm) 513 5.78 2.39 6.00 1.00 12.0   ${CH}_{4_{r + e}}$ ($µ$L L$^{- 1}$) 555 32.8 12.1 31.5 7.92 70.0   ${CH}_{4_{r}}$ ($µ$L L$^{- 1}$) 555 18.5 4.48 18.1 7.92 33.2   ${CH}_{4_{rmax}}$ ($µ$L L$^{- 1}$) 555 33.8 1.82 35.0 25.0 35.0   ${CH}_{4_{rsum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 555 427 97.5 413 0.00 767   ${CH}_{4_{e}}$ ($µ$L L$^{- 1}$) 555 90.9 36.1 84.2 0.00 279   ${CH}_{4_{emax}}$ ($µ$L L$^{- 1}$) 555 292 193 244 0.00 975   ${CH}_{4_{esum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 555 522 342 470 0.00 1865   ${CH}_{4_{event}}$ (no. min$^{- 1}$) 555 0.95 0.55 0.96 0.00 3.38 RH EBW (kg) 360 70.6 8.36 69.5 54.0 92.5   BCS 360 2.99 0.65 3.00 1.00 4.50   BFT (mm) 183 6.38 1.56 6.00 2.00 11.0   ${CH}_{4_{r + e}}$ ($µ$L L$^{- 1}$) 175 31.4 12.0 30.1 7.03 67.5   ${CH}_{4_{r}}$ ($µ$L L$^{- 1}$) 175 16.5 3.92 16.7 7.03 27.6   ${CH}_{4_{rmax}}$ ($µ$L L$^{- 1}$) 175 33.4 2.01 34.0 26.0 35.0   ${CH}_{4_{rsum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 175 381 84.2 375 196 796   ${CH}_{4_{e}}$ ($µ$L L$^{- 1}$) 175 93.8 36.7 87.2 0.00 242   ${CH}_{4_{emax}}$ ($µ$L L$^{- 1}$) 175 277 181 230 0.00 893   ${CH}_{4_{esum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 175 513 335 463 0.00 1706   ${CH}_{4_{event}}$ (no. min$^{- 1}$) 175 0.99 0.58 0.99 0.00 3.67 $^{*}$ ${CH}_{4_{r + e}}$: mean ${CH}_{4}$ concentration during respiration and eructation; ${CH}_{4_{r}}$: mean ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rmax}}$: maximum ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rsum}}$: sum of ${CH}_{4}$ concentrations per minute during respiration; ${CH}_{4_{e}}$: mean ${CH}_{4}$ concentration during eructation; ${CH}_{4_{emax}}$: maximum ${CH}_{4}$ concentration during eructation; ${CH}_{4_{esum}}$: sum of ${CH}_{4}$ concentrations per minute during eructation; ${CH}_{4_{event}}$: number of eructation events per minute. {#Ch1.S2.SS5} The impact of ewe ${CH}_{4}$ emissions on EBW, BFT, BCS and LBW was studied via mixed model applications as implemented in the software package SAS Studio Version 3.71 (SAS Institute Inc., 2017). In matrix notation, the statistical model Eq. (1) was defined as follows: $$\mathbf{y}\mspace{2mu} = \mspace{2mu}\mathbf{X}\mathbf{b} + \mathbf{Z}\mathbf{u} + \mathbf{e},$$ where $\mathbf{y}$ is a vector of observations for the traits EBW, BFT, BCS and LBW; $\mathbf{b}$ is a vector of fixed effects including the combined effect of birth type (single, twin, triplet) and sex of the lamb (male, female), breed (ML, RH), the combined month--of-the-year effect, ewe BCS (1--5) (apart from the models where BCS and BFT are the traits of interest), and the fixed regression of the lamb age (0 to 73 d) within breed modeled with Legendre polynomials of fourth order. Furthermore, vector $\mathbf{b}$ included in consecutive runs the different ${CH}_{4}$ traits ${CH}_{4_{r + e}}$- ($\leq 25$ $µ$L L$^{- 1}$; 26--35 $µ$L L$^{- 1}$; $\geq 36$ $µ$L L$^{- 1}$), ${CH}_{4_{r}}$- ($\leq 15.5$ $µ$L L$^{- 1}$; 15.6--19.5 $µ$L L$^{- 1}$; \> 19.5 $µ$L L$^{- 1}$), ${CH}_{4_{rsum}}$- ($\leq 360$ $µ$L L$^{- 1}$ min$^{- 1}$; 361--439 $µ$L L$^{- 1}$ min$^{- 1}$; $\geq 440$ $µ$L L$^{- 1}$ min$^{- 1}$), ${CH}_{4_{rmax}}$- ($\leq 34$ $µ$L L$^{- 1}$; \> 34 $µ$L L$^{- 1}$), ${CH}_{4_{e}}$- ($\leq 72$ $µ$L L$^{- 1}$; 73--99 $µ$L L$^{- 1}$; \> 99 $µ$L L$^{- 1}$), ${CH}_{4_{esum}}$- ($\leq 310$ $µ$L L$^{- 1}$ min$^{- 1}$; 311--620 $µ$L L$^{- 1}$ min$^{- 1}$; \> 620 $µ$L L$^{- 1}$ min$^{- 1}$), ${CH}_{4_{emax}}$- ($\leq 170$ $µ$L L$^{- 1}$; 171--315 $µ$L L$^{- 1}$; \> 315 $µ$L L$^{- 1}$), and ${CH}_{4_{event}}$ class ($\leq 0.96$ min$^{- 1}$; \> 0.96 min$^{- 1}$). $\mathbf{u}$ is a vector for the random ewe or lamb effect considering up to four repeated measurements per ewe and lamb, $\mathbf{e}$ is a vector of random residual effects, and $\mathbf{X}$ and $\mathbf{Z}$ are incidence matrices for $\mathbf{b}$ and $\mathbf{u}$, respectively. 2.6. Genetic parameters for ewe ${CH}_{4}$ emissions and body weight traits {#Ch1.S2.SS6} --------------------------------------------------------------------------- Genetic (co)variance components for all trait combinations including EBW, BCS, BFT and LBW were estimated by applying the software package DMU (Madsen and Jensen, 2013) and using the AI-REML algorithm for multiple-trait animal models. For the ${CH}_{4}$ traits ${CH}_{4_{r + e}}$, ${CH}_{4_{r}}$, ${CH}_{4_{rmax}}$, ${CH}_{4_{rsum}}$, ${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$ and ${CH}_{4_{event}}$, single-trait animal models were applied. Multiple-trait models converged properly for EBW, BCS, BFT and LBW due to the larger dataset, but some convergence problems occurred when additionally including ${CH}_{4}$ traits from the smaller subset of phenotyped ewes. This was the reason for the application of single-trait animal models for ${CH}_{4}$ traits. The statistical model Eq. (2) for genetic analyses in matrix notation was defined as follows: $$\mathbf{y} = \mathbf{X}\mathbf{b} + \mathbf{Z}\mathbf{a} + \mathbf{W}\mathbf{p}\mathbf{e} + \mathbf{e},$$ where $\mathbf{y}$ is a vector of observations for EBW, BCS, BFT and LBW and ${CH}_{4}$ traits; $\mathbf{b}$ is a vector of fixed effects including all effects as introduced in model (1) and the fixed effects for the temperature class ($\leq 4$, 4.1--8.5, 8.6--11, \> 11 $^{\circ}$C) and for the humidity class ($\leq 43$ %, 44 %--55 %, 56 %--64 %, \> 64 %); $\mathbf{a}$ is a vector of random additive genetic effects considering the genetic relationships from an animal model; $\mathbf{p}\mathbf{e}$ is a vector of random permanent environmental effects for repeated measurements; $\mathbf{e}$ is a vector of random residual effects; and $\mathbf{X}$, $\mathbf{Z}$ and $\mathbf{W}$ are incidence matrices for $\mathbf{b}$, $\mathbf{a}$ and $\mathbf{p}\mathbf{e}$, respectively. Correlations among estimated breeding values (EBVs) for ${CH}_{4}$ traits (EBV from the single-trait models), and between EBV for ${CH}_{4}$ traits and EBV for EBW, BCS, BFT and LBW (EBV from the multiple-trait model) were transformed into genetic correlations according to Calo et al. (1973): $$r_{g1,\mspace{2mu} 2\mspace{2mu}} = \frac{\sqrt{\left( {\sum_{i}R_{i1}} \right) \cdot \left( {\sum_{i}R_{i2}} \right)}}{\sum_{i}\left( {R_{i1} \cdot R_{i2}} \right)} \cdot r\left( {{EBV}_{1},{EBV}_{2}} \right),$$ where $R$ was the EBV reliability for an individual $i$ in trait $j$. For the genetic correlation approximations, we only considered EBV from ewes with phenotypic records. 3. Results and discussion {#Ch1.S3} ========================= 3.1. Strategies of ${CH}_{4}$ trait definitions {#Ch1.S3.SS1} ----------------------------------------------- The introduced ${CH}_{4}$ data preparation strategy is very complex. Nevertheless, a separation of respiration and eructation ${CH}_{4}$ is physiologically reasonable and considers environmental air movements. We identified a high agreement between statistically defined eructation events and ewe eructation during trait recording (own visual inspections of eructation events during ${CH}_{4}$ recording). In our data, during the 3 min recording interval, 95 % of ewes eructated at least once. The eructation probability in the study by Ricci et al. (2014) was slightly lower (92 %), but they considered a 2 min recording interval. Hence, a minor disadvantage for specific ${CH}_{4}$ eructation trait definitions is the small percentage of ewes (5 %) which had to be excluded from data processing. Chagunda et al. (2009b) introduced a further transformation of LMD output data ($µ$L L$^{- 1}$) into daily ${CH}_{4}$ production (g d$^{- 1}$) but without distinguishing into respiration and eructation. The data processing procedure by Chagunda et al. (2009b) also required complex equations including approximations for, for example, individual respiratory tidal volume or for the daily animal activity level. Methane traits as defined in our study reflect "pure" ${CH}_{4}$ emissions, whereas ${CH}_{4}$ predictions by Chagunda et al. (2009b) depend on body trait or physiological characteristics. Hence, in quantitative genetic studies, and following a deterministic ${CH}_{4}$ prediction strategy, the estimated heritability does not fully reflect the individual ${CH}_{4}$ genetic background (Yin et al., 2015). In genome-wide association studies, Manzanilla-Pech et al. (2016) found an overlap for 19 % of SNP markers being significantly associated with DMI, body weight and individual ${CH}_{4}$ production in dairy cattle. In consequence, they suggested consideration of residual ${CH}_{4}$ emissions that are additionally pre-corrected for ${CH}_{4}$ indicator traits (e.g., for DMI and for body weight). Moreover, our ${CH}_{4}$ trait separation into respiration and eructation provides deeper insights into the different physiological mechanisms associated with ${CH}_{4}$ output. The ${CH}_{4}$ separation strategy allows studying the isolated influence of either respiration or eructation on ewe body condition traits and on LBW. Nevertheless, our approach depends on the individual threshold definition for the two normal distributions (respiration and eructation). ![Least-squares means for lamb body weight (LBW) depending on ewe mean ${CH}_{4}$ concentration during respiration (${CH}_{4_{r}}$ class; model 1). Different letters represent significant differences ($P\mathit{<}0.01$).](aab-63-113-g02){#Ch1.F2} {#Ch1.S3.SS2} Among all ${CH}_{4}$ traits, the inclusion of ${CH}_{4}$ mean concentration during respiration (${CH}_{4_{r}}$) as class effect in model (1) gave the lowest value for the Akaike information criterion (Akaike, 1973) (Table 2). Hence, ${CH}_{4_{r}}$ consideration indicated statistical modeling superiority. The ${CH}_{4_{r}}$ class effect significantly influenced LBW ($P\mathit{<}0.05$) and EBW ($P\mathit{<}0.01$) (model 1). Ewes with low mean ${CH}_{4}$ emissions during respiration reared heavier lambs than ewes with high ${CH}_{4}$ emissions ($P\mathit{<}0.001$; Fig. 2). Simultaneously, low mean ${CH}_{4}$ emissions during respiration were associated with larger estimates for EBW during lactation ($P\mathit{<}0.001$; Fig. 3). EBW during lactation for ewes from the low ${CH}_{4_{rmax}}$ class was significantly higher (0.74 kg, $P\mathit{<}0.05$) compared to EBW from ewes with high ${CH}_{4_{rmax}}$ emissions (${CH}_{4_{rmax}}$ class \> 34 $µ$L L$^{- 1}$). In cattle, Johnson and Johnson (1995) identified high ${CH}_{4}$ emissions as major contributors to energy losses, comprising 5 %--12 % of the gross energy intake. Consequently, limited energy is available for milk production, explaining the lower LBW of lambs from ewes with high ${CH}_{4}$ output during lactation. Kandel et al. (2017) and Chagunda et al. (2009a) confirmed such unfavorable associations between ${CH}_{4}$ emissions and milk yield in cattle. Interestingly, the ${CH}_{4}$ eructation traits represent larger ${CH}_{4}$ emissions than the respiration traits (Blaxter and Joyce, 1963), but only the respiration ${CH}_{4}$ traits ${CH}_{4_{r}}$ and ${CH}_{4_{rmax}}$ significantly influenced LBW and EBW. An explanation for the significant impact of "low-level ${CH}_{4}$" (${CH}_{4_{r}}$, ${CH}_{4_{rmax}}$) on LBW and EBW might be due to the short recording interval of only 3 min. For a small recording interval, the percentage of respiration in relation to eructation is larger, compared to, for example, accumulate 24 h measurements. ![Least-squares means for ewe body weight (EBW) depending on ewe mean ${CH}_{4}$ concentration during respiration (${CH}_{4_{r}}$ class; model 1). Different letters represent significant differences ($P\mathit{<}0.01$).](aab-63-113-g03){#Ch1.F3} ###### Akaike information criterion (AIC) for model (1) with the dependent traits of lamb body weight (LBW) or ewe body weight (EBW), considering different ${CH}_{4}$ class effects.   AIC -------------------- ------ ------ ${CH}_{4_{r + e}}$ 4567 4484 ${CH}_{4_{r}}$ 4564 4476 ${CH}_{4_{rmax}}$ 4571 4485 ${CH}_{4_{rsum}}$ 4569 4487 ${CH}_{4_{e}}$ 4571 4488 ${CH}_{4_{esum}}$ 4572 4488 ${CH}_{4_{emax}}$ 4572 4488 ${CH}_{4_{event}}$ 4571 4488 $^{*}$ ${CH}_{4_{r + e}}$: mean ${CH}_{4}$ concentration during respiration and eructation; ${CH}_{4_{r}}$: mean ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rmax}}$: maximum ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rsum}}$: sum of ${CH}_{4}$ concentrations per minute during respiration; ${CH}_{4_{e}}$: mean ${CH}_{4}$ concentration during eructation; ${CH}_{4_{emax}}$: maximum ${CH}_{4}$ concentration during eructation; ${CH}_{4_{esum}}$: sum of ${CH}_{4}$ concentrations per minute during eructation; ${CH}_{4_{event}}$: number of eructation events per minute. Least-squares means for BFT declined with increasing ewe ${CH}_{4}$ emissions. In this regard, ewes representing the medium ${CH}_{4_{r + e}}$, ${CH}_{4_{emax}}$ and ${CH}_{4_{esum}}$ class had 0.38 to 0.43 mm less BFT than ewes from the low ${CH}_{4}$ classes ($P\mathit{<}0.05$) (Fig. 4). An increase of ${CH}_{4}$ emissions was associated with inefficient feed conversion, both contributing to energy deficiency during the early lactation stage (Hegarty et al., 2007; Paganoni et al., 2017). Hence, for energy deficiency compensation due to mammary requirements during lactation (intensified through ${CH}_{4}$ emissions), ewes are forced to increase the mobilization rate of their own body fat depots (Bell, 1995), explaining the EBW and BFT decline. Such initiated catabolic processes depend on liver glycogen levels, which represent an important glucose (energy) body resource. Physiologically, catecholamine and glucagon blood levels are increasing, initiating the hydrolysis of body fat deposits (triglycerides) (Lawrence and Fowler, 2002). Ewes from the present study received concentrates but also responded with a BFT decline during lactation. Weston (1996) indicated the general problem of energy deficiency of lactating ewes, especially in pasture based production systems. Consequently, we suggest selection strategies on low ${CH}_{4}$ emissions, in order to avoid further energy losses. Bielak et al. (2016) suggested plasma levels of non-esterified fatty acids (NEFAs) as indicators for body fat mobilization. In lactating dairy cows, Bielak et al. (2016) identified a negative relationship between ${CH}_{4}$ production per DMI and NEFA plasma levels. Nevertheless, intensified body fat mobilization with decreasing ${CH}_{4}$ emissions in cows is in contradiction with the identified associations in the present study for sheep. Summarizing the phenotypic relationships, low values for ${CH}_{4_{r + e}}$, ${CH}_{4_{r}}$, ${CH}_{4_{rmax}}$, ${CH}_{4_{emax}}$ and ${CH}_{4_{esum}}$ in ewes were favorably associated with maternal body fat storage during lactation, and with increasing LBW. {#Ch1.S3.SS3} In previous studies, variation of individual ${CH}_{4}$ emissions was due to the diet composition and feeding system characteristics (Chagunda et al., 2009a; Pinares-Patiño et al., 2011; Bell et al., 2016), ruminal microbiome (Shi et al., 2014) and host genetic compositions (Pinares-Patiño et al., 2013). Genetic variation for ${CH}_{4}$ emissions indicates the general possibilities for genetic selection, but this variation was only detected for ${CH}_{4_{rsum}}$ and ${CH}_{4_{emax}}$ (Table 3). Correspondingly, heritabilities for ${CH}_{4}$ traits (Table 3) were close to zero, with the largest estimate for ${CH}_{4_{rsum}}$ (0.03). Pickering et al. (2015) and Paganoni et al. (2017) estimated heritabilities for ${CH}_{4}$ in a comparable range from 0.05 to 0.14 in dairy cattle and sheep, respectively. For ${CH}_{4}$ recordings, Paganoni et al. (2017) used portable accumulation chambers, and they applied the technique to lambs at post-weaning age and hoggets. Hence, ${CH}_{4}$ heritabilities in ruminants are generally quite low, irrespective of the utilized measurement technology and the age of animals. Quite large residual variances (as also indicated in Table 3 for the traits in the present study) due to further environmental effects, which were not considered in statistical modeling, e.g., the individual stress level during measurement or the exhalation rate (Wu et al., 2018), might explain the generally small ${CH}_{4}$ heritabilities in sheep. Large residual variances and small heritabilities indicate only minor selection response when aiming on reduced ${CH}_{4}$ emissions. Besides, some ewes did not show any eructation during short time measurements. For the inclusion of eructation ${CH}_{4}$ traits (${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$, ${CH}_{4_{event}}$) into overall breeding goals, it is imperative to consider repeated measurements per animal, in order to guarantee at least one eructation per measurement. ![Least-squares means for ewe backfat thickness (BFT) depending on ewe mean ${CH}_{4}$ concentration during respiration and eructation (${CH}_{4_{r + e}}$ class), maximal ${CH}_{4}$ concentration during eructation (${CH}_{4_{emax}}$ class), and sum of ${CH}_{4}$ concentrations per minute during eructation (${CH}_{4_{esum}}$ class) (model 1). Definition of ${CH}_{4}$ classes: low ${CH}_{4}$ class: ${CH}_{4_{r + e}}$ $\leq 25$ $µ$L L$^{- 1}$; ${CH}_{4_{emax}}$ $\leq 170$ $µ$L L$^{- 1}$; ${CH}_{4_{esum}}$ $\leq 310$ $µ$L L$^{- 1}$ min$^{- 1}$; medium ${CH}_{4}$ class: ${CH}_{4_{r + e}}$ 26--35 $µ$L L$^{- 1}$; ${CH}_{4_{emax}}$ 171--315 $µ$ L L$^{- 1}$; ${CH}_{4_{esum}}$ 311--620 $µ$L L$^{- 1}$ min$^{- 1}$; high ${CH}_{4}$ class: ${CH}_{4_{r + e}}$ $\geq 36$ $µ$L L$^{- 1}$; ${CH}_{4_{emax}}$ \> 315 $µ$L L$^{- 1}$; ${CH}_{4_{esum}}$ \> 620 $µ$L L$^{- 1}$ min$^{- 1}$. Different letters represent significant differences ($P\mathit{<}0.01$).](aab-63-113-g04){#Ch1.F4} ###### Heritabilities (h$^{2}$) with standard errors (SE), additive genetic variances ($\mathit{\sigma}_{a}^{2}$), permanent environmental variances ($\mathit{\sigma}_{pe}^{2}$) and residual variances ($\mathit{\sigma}_{e}^{2}$) for lamb body weight (LBW), ewe body weight (EBW), ewe body condition score (BCS), ewe backfat thickness (BFT) and ${CH}_{4}$ traits.     Variance component ------------------------------------------------ ------------- -------------------- ------ --------- LBW (kg) 0.37 (0.16) 3.29 1.64 3.12 EBW (kg) 0.56 (0.12) 51.9 27.8 13.6 BCS 0.37 (0.10) 0.16 0.11 0.16 BFT (mm) 0.25 (0.13) 0.74 0.62 1.62 ${CH}_{4_{r + e}}$ ($µ$L L$^{- 1}$) 0.00 (0.04) \< 0.01 6.12 132 ${CH}_{4_{r}}$ ($µ$L L$^{- 1}$) 0.00 (0.04) \< 0.01 0.23 14.7 ${CH}_{4_{rsum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 0.03 (0.04) 185 0.00 7125 ${CH}_{4_{rmax}}$ ($µ$L L$^{- 1}$) 0.00 (0.04) \< 0.01 0.00 3.08 ${CH}_{4_{e}}$ ($µ$L L$^{- 1}$) 0.01 (0.04) 8.46 38.9 1049 ${CH}_{4_{esum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 0.00 (0.04) 54.4 4051 105 677 ${CH}_{4_{emax}}$ ($µ$L L$^{- 1}$) 0.01 (0.04) 408 957 3236 ${CH}_{4_{event}}$ (no. min$^{- 1}$) 0.02 (0.05) 0.01 0.02 0.25 $^{*}$ ${CH}_{4_{r + e}}$: mean ${CH}_{4}$ concentration during respiration and eructation; ${CH}_{4_{r}}$: mean ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rmax}}$: maximum ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rsum}}$: sum of ${CH}_{4}$ concentrations per minute during respiration; ${CH}_{4_{e}}$: mean ${CH}_{4}$ concentration during eructation; ${CH}_{4_{emax}}$: maximum ${CH}_{4}$ concentration during eructation; ${CH}_{4_{esum}}$: sum of ${CH}_{4}$ concentrations per minute during eructation; ${CH}_{4_{event}}$: number of eructation events per minute. Heritabilities for body condition traits were 0.56 for EBW, 0.37 for BCS, 0.25 for BFT and 0.37 for LBW (Table 3). Pinares-Patiño et al. (2013) and Borg et al. (2009) estimated similar heritabilities for live weight of 0.46 and 0.38, respectively. Jonker et al. (2018) estimated a heritability of 0.35 for LBW at 4 to 13 months of age, confirming our estimate of 0.37. The BFT heritability reflects estimates by Gernand et al. (2008) and Brito et al. (2017), but in both studies, the authors considered records from lambs instead of ewe traits. ###### Genetic correlations between lamb body weight (LBW), ewe body weight (EBW), ewe body condition score (BCS) and ewe backfat thickness (BFT) with standard errors (in brackets), and approximated genetic correlations between LBW, EBW, BCS, BFT and ${CH}_{4}$ traits.   Genetic correlations ------------------------------------------------ ---------------------- ------------- ------------- ------------- LBW (kg)   0.78 (0.14) 0.52 (0.23) 0.67 (0.29) EBW (kg)     0.78 (0.09) 0.79 (0.18) BCS       0.96 (0.13) BFT (mm)         ${CH}_{4_{r + e}}$ ($µ$L L$^{- 1}$) $-$0.35 $-$0.44 $-$0.42 $-$0.67 ${CH}_{4_{r}}$ ($µ$L L$^{- 1}$) $-$0.07 $-$0.14 0.10 0.05 ${CH}_{4_{rsum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) 0.01 $-$0.05 0.28 0.12 ${CH}_{4_{rmax}}$ ($µ$L L$^{- 1}$) 0.01 $-$0.35 $-$0.20 $-$0.08 ${CH}_{4_{e}}$ ($µ$L L$^{- 1}$) $-$0.17 $-$0.27 $-$0.34 $-$0.51 ${CH}_{4_{esum}}$ ($µ$L L$^{- 1}$ min$^{- 1}$) $-$0.28 $-$0.32 $-$0.81 $-$0.49 ${CH}_{4_{emax}}$ ($µ$L L$^{- 1}$) $-$0.18 $-$0.34 $-$0.30 $-$0.72 ${CH}_{4_{event}}$ (no. min$^{- 1}$) $-$0.22 $-$0.23 $-$0.44 $-$0.32 $^{*}$ ${CH}_{4_{r + e}}$: mean ${CH}_{4}$ concentration during respiration and eructation; ${CH}_{4_{r}}$: mean ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rmax}}$: maximum ${CH}_{4}$ concentration during respiration; ${CH}_{4_{rsum}}$: sum of ${CH}_{4}$ concentrations per minute during respiration; ${CH}_{4_{e}}$: mean ${CH}_{4}$ concentration during eructation; ${CH}_{4_{emax}}$: maximum ${CH}_{4}$ concentration during eructation; ${CH}_{4_{esum}}$: sum of ${CH}_{4}$ concentrations per minute during eructation; ${CH}_{4_{event}}$: number of eructation events per minute. {#Ch1.S3.SS4} For the definition of overall sheep breeding goals including ${CH}_{4}$, knowledge about genetic correlations and covariances with other economically important traits (e.g., LBW) is imperative. Genetic correlations between ${CH}_{4}$ traits and EBW were slightly (${CH}_{4_{r}}$, ${CH}_{4_{rsum}}$) or moderately negative (${CH}_{4_{r + e}}$, ${CH}_{4_{rmax}}$, ${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$, ${CH}_{4_{event}}$), indicating that breeding on low ${CH}_{4}$ emissions increases EBW and vice versa (Table 4). Generally, genetic correlation estimates between ${CH}_{4}$ traits and EBW were in agreement with the phenotypic associations from model (1). In contrast to our results, Pinares-Patiño et al. (2013) estimated a differing genetic correlation of 0.80 between ${CH}_{4}$ production (g d$^{- 1}$) and body weights of lambs at the age of 8 months. In the present study, BCS was moderately negatively correlated with all ${CH}_{4}$ traits reflecting eructation (${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$, ${CH}_{4_{event}}$; Table 4). Also, genetic correlations between BCS with ${CH}_{4_{r + e}}$ and ${CH}_{4_{rmax}}$ were negative. Zetouni et al. (2018) estimated a similar genetic correlation of $-$0.28 between ${CH}_{4}$ production and BCS in Danish Holstein cows. Regarding BFT, a decline in ${CH}_{4_{r + e}}$, ${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$ and ${CH}_{4_{event}}$ was genetically associated with an incline in BFT. The genetic correlations between the respiration ${CH}_{4}$ traits (${CH}_{4_{r}}$, ${CH}_{4_{rmax}}$, ${CH}_{4_{rsum}}$) and BFT were close to zero. In contrast to the phenotypic associations, genetic relationships between respiration ${CH}_{4}$ traits (${CH}_{4_{r}}$, ${CH}_{4_{rsum}}$, ${CH}_{4_{rmax}}$) and LBW were quite low in the range from $-$0.07 to 0.01. On a genetic basis, among all ${CH}_{4}$ traits, ${CH}_{4_{r + e}}$ had the strongest genetic correlation ($-$0.35) with LBW. Genetic correlations among EBW, BCS, BFT and LBW were positive, indicating an incline in LBW when selecting heavy ewes with high values for BCS and BFT. However, a strict selection on increasing EBW, BCS and BFT for indirect improvements of LBW might be associated with insulin resistance and hormone dysregulation in the future F1 and F2 generations (Pankey et al., 2017). Furthermore, adipose ewes were susceptible for dystocia (Peel et al., 2012). In summary, the ${CH}_{4}$ traits ${CH}_{4_{r + e}}$, ${CH}_{4_{e}}$, ${CH}_{4_{esum}}$, ${CH}_{4_{emax}}$ and ${CH}_{4_{event}}$ were genetically favorably correlated with LBW, indicating an increase in LBW and simultaneously improvements of EBW, BCS and BFT when selecting on low ${CH}_{4}$ emissions, particularly during eructation. Nevertheless, small ${CH}_{4}$ heritabilities indicate only slight selection response. Hence, in breeding goals or selection indices, it is imperative to consider the low heritability ${CH}_{4}$ traits with high economic values (König et al., 2009). 4. Conclusions {#Ch1.S4} ============== ${CH}_{4}$ recording via LMD technique was successfully implemented in sheep under field conditions. On a longitudinal trait basis, we developed statistical strategies for distinguishing ${CH}_{4}$ emissions in respiration and eructation. Large ewe ${CH}_{4}$ emissions during respiration were associated with lower EBW as well as with impaired body weight development of their lambs. Additionally, a significant ewe BCS and BFT decrease after lambing was detected in ewes with high levels of ${CH}_{4}$ emissions during eructation. Heritabilities for ${CH}_{4}$ traits were close to zero ($h^{2}$ $\mathit{<}0.01$ to 0.03). Nevertheless, the genetic correlations between ${CH}_{4}$ traits ${CH}_{4_{r + e}}$, ${CH}_{4_{e}}$, ${CH}_{4_{emax}}$, ${CH}_{4_{esum}}$ and ${CH}_{4_{event}}$ and energy efficiency indicators (e.g., LBW) suggest consideration of ewe ${CH}_{4}$ emissions in overall sheep breeding goals when aspiring to feed efficiency improvements. We proved that the utilization of LMD equipment is an appropriate non-invasive method to measure ${CH}_{4}$ emissions in sheep rapidly, easily and cost-efficiently. Furthermore, the differentiation between respiration and eructation ${CH}_{4}$ emissions provides insights into physiological dynamics of ${CH}_{4}$ emissions. Nevertheless, environmental (e.g., micrometeorology) and physiological (e.g., respiratory volume, behavior) factors can influence results from the applied ${CH}_{4}$ recording technique and should be considered in future statistical modeling approaches. The authors are grateful to the H. Wilhelm Schaumann Stiftung for providing a scholarship to Jessica Reintke. Data availability ================= The data that support the findings of this study are available from the authors upon reasonable request. Author contributions ==================== SK, AW and HW designed the experiment and supervised the research. SK supported JR in writing and data validation. JR was responsible for phenotyping activities, supported by PE. JR, KB and TY were responsible for data preparation and genetic statistical analyses. All authors read and approved the manuscript. Competing interests =================== The authors declare that they have no conflict of interest. Financial support ================= This open-access publication was funded by Justus Liebig University Giessen. Review statement ================ This paper was edited by Manfred Mielenz and reviewed by Angela Schwarm and one anonymous referee.
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Using an In-House Approach to Computer-Assisted Design and Computer-Aided Manufacturing Reconstruction of the Maxilla. Computer-assisted design (CAD) and computer-aided manufacturing (CAM) techniques are in widespread use for maxillofacial reconstruction. However, CAD/CAM surgical guides are commercially available only in limited areas. To use this technology in areas where these commercial guides are not available, the authors developed a CAD/CAM technique in which all processes are performed by the surgeon (in-house approach). The authors describe their experience and the characteristics of their in-house CAD/CAM reconstruction of the maxilla. This was a retrospective study of maxillary reconstruction with a free osteocutaneous flap. Free CAD software was used for virtual surgery and to design the cutting guides (maxilla and fibula), which were printed by a 3-dimensional printer. After the model surgery and pre-bending of the titanium plates, the actual reconstructions were performed. The authors compared the clinical information, preoperative plan, and postoperative reconstruction data. The reconstruction was judged as accurate if more than 80% of the reconstructed points were within a deviation of 2 mm. Although on-site adjustment was necessary in particular cases, all 4 reconstructions were judged as accurate. In total, 3 days were needed before the surgery for planning, printing, and pre-bending of plates. The average ischemic time was 134 minutes (flap suturing and bone fixation, 70 minutes; vascular anastomoses, 64 minutes). The mean deviation after reconstruction was 0.44 mm (standard deviation, 0.97). The deviations were 67.8% for 1 mm, 93.8% for 2 mm, and 98.6% for 3 mm. The disadvantages of the regular use of CAD/CAM reconstruction are the intraoperative changes in defect size and local tissue scarring. Good accuracy was obtained for CAD/CAM-guided reconstructions based on an in-house approach. The theoretical advantage of computer simulation contributes to the accuracy. An in-house approach could be an option for maxillary reconstruction.
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Don Mateo Wines started with three global entrepreneurs, a passion for wine making and a vision to become world class. So, what’s so special, you ask, lots of aspiring winemakers out there. Yes, but how many have won four awards at the recent Wine and Spirits Wholesalers of America (WSWA) convention? And, how many have had a journey that began in China? I first met the partners running Don Mateo Wines in late 2010 and was immediately struck by their business acumen, gained in global trading, and applied to the wine world. Their story is interesting. Andy Lam and his brother Matthew were successful exporters of various products and commodities to Chile from China. Over the years, the currency exchange swings hurt their business and so they turned the ship around and began importing wine from Chile. Their passion about wine helped, and they began buying vineyards and wineries. Added to that was the patience and tenacity to develop top quality wines. They hit the Chinese wine market at the right point in time and the business flourished. You can’t be a global wine player without the US market, so a third partner, Peter Loucks, entered the picture and applied his overall business skills to the wine business. Peter is smart and a quick learner so it’s not surprising that he soon realized that, unlike China, the supply of wine (Chilean and others) exceeded the demand. Consequently, growth here would be an uphill battle. Further, the mandatory wholesaler tier has become more and more difficult to deal with, as in “take on another wine brand, are you kidding?” But, he knew that despite the hurdles, he had some key brand equities and assets. For one thing, Don Mateo is a memorable brand name for a Chilean wine and the brand symbol is both interesting and notable to consumers. As you can see, the symbol/logo is the Moai (pr. mo-eye). These Moai are the monolithic statues of Easter Island, off the coast of Chile. According to their website“they reflect our commitment to discovery, craftsmanship and passion. These three elements have been the guiding principles for Don Mateo wines from Chile.” Might even stand for the three partners behind the venture. You never know. If you asked the brand owners what is the single most important asset of their wines, their answer is most likely to be, the wine. Trust me folks, these are outstanding wines. But, in case you don’t believe it, think about the medals they won at the WSWA – three silver and a double gold. Here’s the irony. Despite the entrepreneurial approach, despite their marketing and branding and, despite the high quality and good value, you would think wholesalers would be beating a path to their door. Instead, getting wholesalers to take on the line has been slow and difficult. Such is the state of the booze business and the plethora of brands on the market. But, hey, the Moai on Easter Island have stood the test of time, so why shouldn’t Don Mateo Wines. For you former Seagram folks out there… It might interest you to know that Jim Reichardt introduced me to them and their New Jersey wholesaler is Sam Ellias.
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Q: Extract floats from string to create multiple/multidimensional arrays to manipulate data First off, I am very weak programmer, and new to python and this site. Sorry for my mistakes. So here goes, my data file looks like this: http://pastebin.com/60E84azv there are 6221 lines in total in the paste bin file. For testing, I limited the line numbers to a maximum of 1000. I am trying to read in the float values in the number lines, with the main columns being 1 and 2. So far i have written this code to extract the lines i want from the file: f = open('Sample Data.txt',"r") num=0 line = f.readlines() for n in range (107, 1000, 1): #6621 if (n>108): print line[n] which works pretty well, printing the numbers in each line as a string. (Each number has 4 spaces by which it is separated from the next, except the first number in each column which has 2 spaces.) I now wish to convert the string into an array or list so that I can work with the individual numbers and eventually plot a graph with column 2 on the y axis. I've written the following to split and convert the string into floats: for i in range(108,1000,1): line[i].split(' ') float(line[i]) = X[i] print(X[i]) When I run this, it comes back with the following error: Traceback (most recent call last): File "<pyshell#25>", line 2, in <module> print(X[i]) NameError: name 'X' is not defined I've broken it down, and the line[i].split(' ') seems to kind of work, because when I test printed the line it gave 3 separate strings which look like: [' 5070.74537037 -0.003382', '0.009507\n'] I have no idea why there is this error. I thought X[i] was the new array that i was supposed to be creating with the floats but for some reason it doesn't seem to want to work. I've read somewhere that when using large data sets it's good to use multidimensional arrays... If I cannot even understand one dimensional, I have no chance at the other ones! Is there any way I can create an array or maybe two one dimensional arrays which will allow me to manipulate the x or y column of the potential graph independently? Thank you for your time! A: The reason you are getting that error is because you need to declared X as a list before the for loop: X = list() for i in range(108,1000,1): line[i].split(' ') float(line[i]) = X[i] print(X[i]) I think this will give the output you want: f = open('Sample Data.txt',"r") num=0 line = f.readlines() X = [] for n, lines in enumerate(line, 0): #6621 # make it 109 to remove the first line "['# Column 3: Magnitude error\n']" if (n > 109): linSplit = lines.split(' ') joined = ' '.join(linSplit) # apply the float function to every item in joined.split # create a new list of floats in tmp variable tmp = map((lambda x: float(x)), joined.split()) X.append(tmp) print X[0] # print first element in the list Output: [5061.58148148, 0.079304, 0.011018]
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Click to email this to a friend (Opens in new window) The core mystical moment of Islam took place in the year 610, or “half the world and almost half of history away,” as Lesley Hazleton, biographer of Muhammad, puts it. On a hot desert night, this previously ordinary man received the first revelation of the Koran on a mountain outside Mecca. Lesley Hazleton: The doubt essential to faith “What struck me even more than what happened was not what did not happen,” says Hazleton in today’s talk, given at TEDGlobal 2013. “Muhammad did not come floating off the mountain as though walking on air. He did not run down shouting, ‘Hallelujah. Bless the lord.’ He did not radiate light and joy. There were no choirs of angels, no elation, no ecstasy, no golden aura surrounding him. No sense of an absolute foreordained role as the messenger of God. That is, he did none of the things that might make it easy to cry foul and put down the whole story as a pious fable.” No, according to Muhammad’s writings, he was convinced that the moment had to have been a hallucination, or the result of possession. He felt a deep sense of fear and even contemplated ending his life, says Hazleton: “He was overwhelmed not by conviction, but by doubt.” While Hazleton points out that some Islamic theologians reject these accounts of Muhammad’s doubt, she says that it’s exactly this whirlwind of emotions that brought him alive for her. “It allowed me to begin to see him in full,” says Hazleton, whose biography of him, The First Muslim, was published in January 2013 after five years of research. “The more I thought about it, the more it made sense that he doubted,” she continues. “Because doubt is essential to faith.” To hear what Hazleton means by this bold statement — and its implications for fundamentalists of all religions — watch this blistering talk, which points out that true faith takes deep internal wrestling. It’s a call for all religions to take back the public ground from hardliners who offer pat answers and dogma in place of an individual struggle with hard questions. In honor of Hazleton’s powerful talk, below, watch six more talks from TED stages that give surprising, subtle understandings of Islam. This post was originally published as a collection of six talks in December of 2012. It was updated to include Hazleton’s latest talk in June of 2013.
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The anatomical basis for the cerebellar infarcts. Very little can be found in the literature concerning the variation of the irrigation area of the cerebellar arteries, as well as the characteristics of anastomoses among these vessels. The anatomical features may determine certain features of cerebellar infarcts. Consequently, we examined the irrigation area of and the anastomoses among the cerebellar arteries. The anatomical features of the posterior inferior cerebellar artery (PICA), the anterior inferior cerebellar artery (AICA), and the superior cerebellar artery (SCA) were studied in 26 cerebella injected with india ink, while their irrigation areas and anastomoses were examined in 8 of these cerebella. The PICA, which most often (82%) arose from the vertebral artery, was found most commonly (81.3%) to supply the largest part of the occipital surface of the cerebellar hemisphere, the caudal or caudomedial part of the tentorial surface, and the inferior vermis. The AICA, which usually (92%) arose from the basilar artery, commonly (68.8%) supplied most of the petrosal surface of the hemisphere and the flocculus. The SCA, which divided into the medial and the lateral trunks, always irrigated most of the tentorial surface of the cerebellum, the superior vermis, and the dentate nucleus. The PICA, AICA, and SCA were always interconnected by anastomoses, which ranged from 40 microns to 420 microns in diameter. Cerebellar infarcts were documented by computed tomography (CT) or magnetic resonance imaging (MRI) examinations in 10 patients. The infarcts were located in the PICA territory (60%) or the SCA region (40%). The authors compared the obtained anatomic data to the features of the cerebellar infarcts in these patients.
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The F/A-18E, assigned to Carrier Air Wing 2, was on final approach to the Carl Vinson when the incident occurred. The carrier was conducting flight operations while transiting the Celebes Sea in the Western Pacific, south of the Philippines and east of the island of Borneo. The carrier Carl Vinson is currently on its way to the Korean Peninsula as a show of force amid North Korea's recent long range missile tests and reports of planned nuclear weapons tests. The strike group made news this week when Defense News reported that the carrier was actually heading in the opposite direction from the peninsula some 3,500 miles away. Having redirected to the Sea of Japan off of the Korean Peninsula, the carrier strike group is expected to arrive in the region next week.
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Bogoria coat of arms Bogoria is a Polish coat of arms. It was used by several szlachta families in medieval Poland and later under the Polish-Lithuanian Commonwealth, branches of the original medieval Bogoriowie family as well as families connected with the Clan by adoption. History The coat of arms was first attributed to Michał Bogorya, whose name was first recorded in the papers of Trzemeszno monastery, when he was given the title of count, and in a decree granting privileges to the Holy Cross monastery near Sandomierz around 1069. According to legend, Bolesław II the Bold (Bolesław Śmiały), armed with only 3,000 of his cavalry, attacked a much larger band of Polovtsy near Snowskie, striking down their leader. During the battle a colonel called Michał Bogorya proved extraordinary courage and bravery, bearing several wounds and arrows in his body. Bolesław, upon returning from the battle and hearing of his bravery, saw Bogorya and extracted the arrows from his chest, broke them with his own hands and conferred them on Bogorya and his descendants as an eternal honour. Blazon The coat of arms consists of two broken white (or silver) arrows pointing in opposite directions—one up and one down—on a red (or blue/green) field. The helm bears a peacock with its tail spread and its beak pointing to the shield's right, holding an arrow likewise broken and twisted upward. Notable bearers Notable bearers of this coat of arms include: Bogoriowie (knights) Jarosław z Bogorii i Skotnik Piotr z Bogorii i Skotnik Stanisława z Bogorii i Skotnik Mikołaj z Bogorii i Skotnik Wojciech z Bogorii i Żminogrodu The family of Mstislav Rostropovich, famous Russian cellist and conductor. Marcjan Dominik Wołłowicz Andrzej Mokronowski Władysław Wołłowicz Franciszek Bohomolec Ostafi Wołłowicz Gallery </center> Paintings </center> See also Polish heraldry Heraldic family List of Polish nobility coats of arms Bibliography Kasper Niesiecki, Jan Nepomucen Bobrowicz: Herbarz polski Kaspra Niesieckiego S. J. T. 3. Lipsk: Breitkopf i Haertel, 1841, s. 194-198. Tadeusz Gajl: Herbarz polski od średniowiecza do XX wieku : ponad 4500 herbów szlacheckich 37 tysięcy nazwisk 55 tysięcy rodów. L&L, 2007. . Alfred Znamierowski: Herbarz rodowy. Warszawa: Świat Książki, 2004, s. 91. . Józef Szymański: Herbarz średniowiecznego rycerstwa polskiego. Warszawa: PWN, 1993, s. 86-88. . Józef Szymański: Herbarz rycerstwa polskiego z XVI wieku. Warszawa: DiG, 2001, s. 209. . References Bogorya *
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