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Tater tots and fry sauce The front of the Y-Stop is a small store and the back, past the coolers, is an even smaller restaurant area. We aren’t here more than once-a-year but we know the drill. “Is anyone cooking?” I ask the grey-haired man behind the counter. It’s sort of like the Idaho Hotel in Silver City. Or the Sourdough Lodge near Lowman. Or the J&E up north in Clarkia. Just because the door is open and there’s a restaurant doesn’t mean someone is around to cook for you. | Low | [
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Stronger Loving World Thursday, May 06, 2004 Reality Studios The lights are out. The electricity bills haven't been paid in months. My roommate has been arguing for a long time with our electric company, in fact, when I moved in, I was told they were at a stand-off. I haven't paid one electric bill since I moved into my apartment. Now the lights are off. Adequately, the day the lights went off is the day I hit up my WI-FI for the first time. I met my friend Philee at Union Square last night and she gave me the used G3 I bought from her, airport card installed. I was sitting against the wall of Virgin Records reading "The Ticket That Exploded" to myself. When I get the chance to, I always read Burroughs out loud. It's lyrical, it's sexy, and it feels like a good pop song. Today I looked for some free wireless nodes in the city on www.nycwireless.net, and I decided to try it out in Thompson Square Park. When those little arcs started up and I saw that I was connected, and when I finally launched the browser with my twelve inch notebook on my lap, it felt like some kind of magic trick. Here I am, on the Internet, and there are fucking birds chirping and attempting to poop on me, I can feel the wind, an old black man is playing guitar on the bench next to me. This has always been such an intensely private, personal experience. Now I'm connected to the world, and, at the same time, I'm still...connected to the world. I'm so excited now that I've decided to join up with nycwireless, a grassroots community creating free wireless hotspots all over the city, as a volunteer and hopefully a board member over the summer. I won't attempt to theorize since I'm clearly 'discovering' this 3 or 4 years after everyone else has, but I will talk about what creeps me out about the word 'wireless'. When radios were originally marketed at the begining of the 20th century, they were given the name 'wireless'. They were originally intended as two-way communication devices, in the sense of a walkie-talkie. Instead, wireless, which was referred to as 'radiophony' and later as 'radio', developed a top-down, hierarchical model. Entertainment and culture industries dominated, receiver's became passive. I'm not suggesting this was a bad thing, I love old radio broadcasts. It's definately something I want to explore more. But technologies don't make themselves open to networks, nor do they create social structures. The Internet is not inherently decentralized. Yes, it was created specifically as a decentralized media, but it has only remained so because its consumers and adherents actively decide to keep it communal and, for the most part, inter-personal and active. This is why it is difficult to politicize technology. It's not even a matter of who controls the means of production, or the ideology that a technology supposedly articulates and sublimates into the discourse( Marcuse's 'technological rationalism') it's about the niche that has been opened for a technology once it arrives, and the niche it chooses to carve out for itself. Burroughs' The Ticket that Exploded is a book about The Tape Recorder. It takes the form of a tape recorded conversation-broken, decontextualized, recombinated, no subject speaking. It is an attempt to redefine the novel after the tape recorder makes many of the novel's functions obsolete. The book belongs to Burroughs' Nova Trilogy, preceded by The Soft Machine and concluded in The Nova Express. Loosely, the pieces of story that fragment in and out of the book are about The Nova Mob, a group of aliens controlling the engines of reality by monopolizing the means of signification, or the production of meaning. The Nova Police counter the semiotic hegemony with what today would be called 'culture jamming', ie. guerilla semiotics. They key points Burroughs believes he is making: the tape recorder reifies the disassociation of the subject. It allows the subject to realize it is discursively produced and a product of a relation within a semiotic system. When Burroughs' MrBradley-MrSmith says "better than the real thing? Maya, there is no real thing", it is because he sees signification as a parlor trick, a house of mirrors, a 'veil'. The dualism Burroughs constructs is not between 'real' and 'unreal', but between signal and noise--the signals are part of a vast, arbitrary construction-The 'Reality Studio'. What Burroughs suggests is that the tape recorder, in its displacement of the subjects' voice and rupturing of the semiotic chain, produce pure noise-chaos, symbolic and physical. Frankfurt to Luxemburg--Frankfurt to Luxemburg--The Americans are inserting us into their blooper reels! "Both governments can record speeches, ultimatums, orders and counterorders-So record the whole war with its battles and sieges, victories and efeats, monumental fuc-ups and corny songs-You understand nobody hsa to bee there at all-So why ask questions and why answer?..-Why not leave your tape with her tape and dispense with sexual contact?" The last line is of course comical, but with all of Burroughs' humor, the terror is in the reality of the joke, the sublimated desires that show on the surface, causing awkward tension. The dry and mordant tone of Burroughs' descriptions of sexual acts alternately make it perverse and distant, ironic and inquisitive to the point of physical discomfort. I said that 'the tape recorder is the greatest invention since the condom', and here's why-the tape recorder, at least this early 60's myth of the portable tape recorder, can produce subjects, initiate a discourse simply by extending itself spatially and temporally, disassociating from the context of a human face, of a human life. The magnetic strip is filled with iron, stripped in different directions, valenced, energized, dancing. Magnetic energy makes the human voice immortal. Recording technologies extend the most obvious signifiers of subjectivity, superficial functions we most associate with living, such as auditory and optical signals. Morever, Burroughs uses the tape recorder to reify the cut-up technique, splicing voices together to produce subjects speaking with several voices. This addresses the intersubjective nature of consciousness, the fact that the subject is a product of differentiations, ruptures that demarcate where I end and you begin. 'Cut-up' is a precursor to the avant-garde pastiche that constitutes later postmodern novels. I would argue, however, that it transcends any argument made by 'postmodern' authors by removing agency from the text. Rather than a convergence of linguistic codes, Burroughs' texts is a radiophonic experience, beginning not in the corpus of literature but outside literature, in the radio waves that pulse through the body and produce the information that constitutes written information. In his recognition of radiophony and magnetic tape as destabalizing forces, Burroughs adresses a point still ignored in contemporary literary studies: the text does not begin in the producer of the message or the receiver, the text is not an autonomous thing, whole only in its de-contextualized isolation from culture, and texts are not 'intertextual', engaging and playing only with a corpus of literature which the observers and receivers have dabbled in and whose symbolic matrix they are programmed with. Rather, the text as radiophonic or magnetic is an 'inter-informational' experience; information courses every second through every piece of the atmosphere. Radiowaves, microwaves, signals, pulses, satellite transmissions, Military satellites, cell phones, radiation, wireless nodes coursing around and through us like gas. It is incorrect to separate the experience of the written word from instant information-written language codes information that is produced and transformed elsewhere. Words are not things in themselves. In an article from the journal 'Postmodern Culture' entitled 'Language out of Language: Excavating the Roots of Culture Jamming and Postmodern Activism from William S. Burroughs', theorist Todd Tietchen creates an opposition between the politics of Burroughsian 'culture-jamming' and what he calls "Frankfurt School Anxiety." In his words: "The roots of Frankfurt School Anxiety can be discvered in 'The Culture Industry: Enlightenment as Mass Deception", in which Horkheimer and Adorno reject the politicsl possibilties of art in Wester society on the grounds that ny mass-produced aesthetic is complicit in the master formula of production, even when it attempts to deploy an alternate discourse..any discourse that participates in the formula and technologies of production-noo matter how revolutionary or radical that discourse may seem to be-reifies the very system it hopes to challenge or negate." Tietchen suggests that the tactics deployed in The Ticket that Exploded provide an avenue out of "Frankfurt School Syndrome". The Nova Mob spread ideology by encrypting it into the word-which Burroughs continually warns us is actually a virus. (Though this was one of Burroughs' favorite catchphrases, the idea that "language is a virus" is more and more congruent with contemporary scientific models--much of Burroughs' off the wall assertions about the hyper-programmable state of the mind and analogies from virology--which paint the human brain as a spot of colonization and infestation rather than rational agency-are supported by memetics; [Dawkins' model of cultural evolution, butressed by game thoery, in which units or conglomerations of information spread, or reproduce, in a way identical to living organisms.]) The Nova Police defy this script by reifying the idea that the sign system that the The Nova Mob use to create and replicate reality within the reality studio is arbitrarily constructed. Morever, its acceptance is dependent on a total act of will, "to agree to be real is to be real". Tietchen believes that this, the equivalent of Situationist Detournment, obviates the need to create an oppositional model to capitalist ideology. By re-branding the existing codes of the capitalist framework, or 'culture jamming', the discourse is not reinscribed but rather decentered, its ownership falling out of an us-them binary and into an open battle field of guerilla semioticians. If I can go off on a tangent, the opposition of Burroughs' tape recorder-as-guerilla-warfare and the Frankfurt School poetically addresses some of the founding features of the tape recorder. One of the most interesting aspects of magnetic tape is that it was perfected, as many technologies are, in the midst of war. And of course, the spoils went to the victors--in 1945 American and British technical investigators "discovered" the Magnetophon--the earliest functional prototype of a magnetic tape recorder-- in Luxembourg, France, and other places formerly occupied by the Germans. By Spring, these investigators begin gathering information about the production of tape recorders and tape, and the U.S. Department of Commerce published the information. The U.S. Alien Property Custodian seized German patent rights on the technology. One of the technology's first uses, thanks to a veteran named John Mullin was that of entertainment device, by way of Bing Crosby. Crosby struggled to popularize the form, which later became a staple of recorded American media. Throughout its existence, magnetic tape and the radio have always been kinds of reality studios--viral hotspots where the culture industry reproduces itself. In the crucial moment when American luxury and extravagance discovered German efficiency, the engines of reality were set into motion. An early magneto-phone I don't think Burroughs' form of culture-jamming was as political as believed, and while there may indeed by a line of connection from Dadaism to cut-ups to Adbusters, I think that it misses the poetic energy of Burroughs' concepts to trace their lines and oppose them to capitalist ideology. The Nova Police don't negate the Nova Mob--more often than not, they are fucking them. The disastrous and grotesque sex in Burroughs novels, a consistent reminder of his disgust with the human body and what he sees as the asymmetry of nature, also articulates Burroughs' fascination with magnetic tape. The technological fetishist redirects the libido into capitalist commodities. But Burroughs' tape recorder is the subject, object, and the means of sex--rather than clumsily attempt to occupy the same "three dimensional coordinate points", we can get down to the psychic frenzy, the ontological orgy, without having anything as clumsy and burdensome as our bodies present. "Lovers exchange tapes-You understand nobody has to be there at all-So why ask questions and why answer?-Why give orders and why make speeches?-Why not leave your tape with her tape and dispense with sexual contact" As Mcluhanesque 'extensions of the central nervous system', the tape recorder is a displacement of 'sense', of being, of presence. Burroughs wants us to not only imagine a world where this presence is mechanized and exchanged freely, but to imagine a world where presence itself is removed from the human experience. Why be here--"why be anywhere?" Not signals, but noise. Not beliefs, but radiations of sense. From the left a soft hum and light rattle, from the right the rattlesnake bites. The radio is wireless. The tape recorder is bodiless. Intelligence is formless. It's sometimes not enough to hold technology and think 'where can this take me', but to ask, 'why be here?' why be anywhere? "Last round over-Remember i was the ship gives to flesh identity-lips fading-silence to say good bye-" See the action, BJ? This Hassan I Sabbah really works for Naval Intelligence and...Are you listening BJ?" | Mid | [
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Q: Why doesn't aria-labelledby fetch values for a div from outside of it? So I am trying to access a label for a div that is focusable via tabIndex. However, for some reason (since the label is outside the div), the label is not being fetched. However, the label is being fetched for an input that has the same aria-labelledby. Any idea how I can get my div to fetch from outside of itself similar to the input? Obviously if I include the label inside the div, it works. Code can be seen here: https://jsfiddle.net/b1ca7tm9/1/ I want the div to also fetch labels outside of itself. FYI: You can view/hear the label being read/displayed for the input but not for the div. You can verify this via voiceover on mac, or NVDA on windows. A: Based on the code you provided the most likely issue is that even though you have made the div focusable with tabindex it's role is still a div which is a non-interactive element. While the ARIA spec implies that aria-labelledby can be used on any element, in practice most screen readers and browsers only honor it for interactive elements and select non-interactive elements. This is because aria-labelledby will be read by the screen reader instead of the content of the element, which in most cases would not be good for screen reader users. If the element receives focus, it's most likely intended to be interactive, so the fix would be to give it an aria role that corresponds with its intended functionality (e.g button). If it's truly non-interactive, it should probably not be in the tab order. If you provide some more context about the purpose of the div, I could give some more detailed advice on what role would be best On another note, tabindex="0" is usually better than declaring a specific position in the tab order. Tabindex="0" will allow the element to receive focus, but doesn't force a specific position (it will just fit into the tab order wherever it would if it were natively focus-able). This way you don't have to go around adding tabindexes to every interactive element on the page | Mid | [
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Improving the performance of poly(3,4-ethylenedioxythiophene) for brain-machine interface applications. Conducting polymers, especially poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, are important for developing highly sensitive and microscale neural probes. In the present work, we show that the conductivity and stability of PEDOT can be significantly increased by switching the widely used counter anion poly(styrenesulfonate) (PSS) to the smaller tetrafluoroborate (TFB) anion during the electrodeposition of the polymer. Time-dependent impedance measurements of polymer modified implantable microwires were conducted in physiological buffer solutions under accelerated aging conditions and the relative stability of PEDOT:PSS and PEDOT:TFB modified microwires was compared over time. This study was also extended to carbon nanotube (CNT) incorporated PEDOT:PSS which, according to some reports, is claimed to enhance the stability and electrical performance of the polymer. However, no noticeable difference was observed between PEDOT:PSS and CNT:PEDOT:PSS in our measurements. At the biologically relevant frequency of 1kHz, PEDOT:TFB modified microwires exhibit approximately one order of magnitude higher conductivity and demonstrate enhanced stability over both PEDOT:PSS and CNT:PEDOT:PSS modified microwires. In addition, PEDOT:TFB is not neurotoxic and we show the proof-of-concept for both in vitro and in vivo neuronal recordings using PEDOT:TFB modified microelectrode arrays and chronic electrodes, respectively. Our findings suggest that PEDOT:TFB is a promising conductive polymer coating for the recording of neural activities. | High | [
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{ "name": "F6S Network Ltd", "displayName": "F6S Network", "properties": [ "f6s.com" ] } | Low | [
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Introduction ============ Gastric emptying is a tightly regulated process, which is influenced by a number of physiological (e.g., satiety and stress) and pathophysiological (e.g., autonomous neuropathy, surgery and drugs) processes. Gastric emptying studies are needed for better understanding of these interactions, and are also an important tool in the development of drugs for several gastrointestinal disorders. Small animals like rats or mice are frequently used in pathophysiological and pharmacological studies, but studies of gastric motility are hampered by the lack of an easily applicable and repeatable gastric emptying test for these models. Numerous approaches have been reported for evaluating gastric emptying in rats. The most frequently used procedure consists of evaluation of marker contents in various gastrointestinal sites after sacrificing the animal.[@B1]-[@B4] This technique is labor-intensive and requires a large number of animals for each scheduled sampling time point, to assess the temporal evolution of gastric emptying. Other studies used serial or double sampling procedures in which gastric volume was estimated by aspiration of gastric contents.[@B5]-[@B7] Depending on the technique used, repeated measurements in the same animal are possible both during a single experimental session and over several experimental sessions. However, this approach has several disadvantages. First, the technique can only measure liquid gastric contents. Second, repeated handling of the animal is required for instillation and recovery of the test meal through oral gavage or via an indwelling gastric canula, and handling is known to increase plasma cortisol and catecholamines,[@B8] making stress a potentially relevant confounding factor. Third, surgery is required to install an indwelling gastric canula in some of these techniques. Houghton et al[@B9] demonstrated that even minor abdominal surgery caused delayed gastric emptying for up to 2 months after laparotomy. Scintigraphic methods, the gold standard in humans, are also reported in rats.[@B9]-[@B11] These techniques involve the use of expensive equipment and ingestion of radioactive isotopes. They also require immobilization of the rat, either by mechanical or chemical restraints, both of which can influence gastric emptying. Immobilization is necessary to maintain a constant distance of the marker-meal to the gamma camera, in order to avoid misinterpreting changes in attenuation of the gamma emissions as changes in retention of radioactivity.[@B12] The present study was performed to adapt the ^14^C-octanoate solid gastric emptying breath test,[@B13],[@B14] for application in rats and to validate it against a radioscintigraphic method. The advantages of a breath test over radioscintigraphy consist in the use of less expensive equipment and in the less strict immobilization requirements. Similar to scintigraphy, the test meal can be solid and mimic the composition of a normal diet; the test is also repeatable. The breath test takes advantage of the characteristics of octanoic acid, an 8-chain fatty acid.[@B15]-[@B18] This molecule is passively and rapidly absorbed by the intestinal but not the gastric mucosa, transported without prior esterification via the portal vein to the liver and oxidized to ^14^CO~2~. The rate at which ^14^CO~2~ is expired, is therefore proportional to the rate of arrival in the intestine. Materials and Methods ===================== Test Meal --------- The test meal, which was freshly prepared on the day of the test, consisted of 0.5 g scrambled egg yolk. This was doped with 3 mCi ^99m^Tc-albumin colloid (Ultra Technicow, Malinkrodt Medical, Petten, The Netherlands), 2 µCi ^14^C-octanoic acid, and sodium salt (DuPont, NEN Research, Boston, MA, USA) and then baked. Subsequently, the baked yolk was mixed with 9.5 g standard rat chow (4352 Muracon G, Nutreco Belgium NV, Gent, Belgium). Tap water (1:1) was added to form a homogenous paste (fat 6.26%, carbohydrates 33.73%, proteins 20.84% and 1.37 kcal/g). The paste was divided in aliquots of 0.5 g. From previous (unpublished) observations we knew that this amount was rapidly ingested by most animals after an overnight fast. Animals ------- Twenty-six male Wistar rats (250-400 g) were housed in wire-mesh bottom cages in a restricted access room with a 12-hour light-dark cycle. Standard laboratory rat chow was available ad libitum until the night before the test, when it was removed. Tap water was freely available at all times, except during the test. Test Procedures --------------- ### Protocol 1: Standard breath test emptying protocol After an overnight fast, 10 rats spontaneously ate the 0.5 g test meal, while 4 rats were given 0.5 g of the test meal by gavage. Immediately after ingestion of the test meal, the rat was placed in an airtight container through which a continuous airflow (80% N~2~ and 20% O~2~) of 0.5 mL/min was maintained ([Fig. 1](#F1){ref-type="fig"}). The dimensions of the container (diameter 6 cm and length 23 cm) were chosen to allow forward and backward movements of the rat whilst keeping the stomach-camera distance relatively constant. The container was placed on a single head gamma camera (Pho/Gamma IV, Searle, Nuclear Chicago Division, Des Plaines, IL, USA). The gas outflow of the container was bubbled through a tube filled with a solution containing 2 mmol hyamine hydroxide, a CO~2~-trapper, and thymolphthaleine as indicator. Decoloration of the fluid indicated saturation with CO~2~; this never occurred with a sampling time of 5 minutes, therefore, all the CO~2~ expired during this time was captured. Preliminary tests with 2 tubes in series showed that more than 95 percent of CO~2~ was retained in the first tube; hence only 1 tube was used in the present study. A hyamine hydroxide tube was connected to the container for a period of 5 minutes before the meal, at every 5 minutes during the first half hour and every 15 minutes for the remainder of the test period. After the initial image immediately after ingestion of the test meal, images were obtained at every 5 minutes for the first hour, then every 10 minutes for the following hours depending on the propagation of the meal by visual inspection. The test was ended when no discernible region of interest remained in the gastric area. By this time, ^14^CO~2~-excretion was tailing off with bulk of it being already past ([Fig. 2](#F2){ref-type="fig"}). ### Protocol 2: Immobilization protocol To minimize variability in the scintigraphic data due to incomplete immobilization, a second series of tests were performed. After an overnight fast, 8 rats spontaneously ate the 0.5 g test meal at the same session and 1 rat was given 0.5 g of the test meal by gavage. Immediately after ingestion of the test meal the rat was placed in a restraining device, which was inserted into the airtight container, while taking care to keep the position of each rat identical in respect to the gamma camera. After an initial image immediately after ingestion of the test meal, images were obtained at every 5 minutes for the first hour, then at every 15 minutes for the remainder of the test period. Once before the test meal and then every 5 minutes during the first half hour and every 15 minutes for the remainder of the test period, the hyamine hydroxide vial was connected to the container for a period of 5 minutes. Again, the test was ended when there was no longer any discernible region of interest in the gastric area. ### Protocol 3: Pharmacological intervention To investigate the effect of inhibition of cholinergic blockade, 3 rats were given atropine sulphate (Sigma Chemical Company, St. Louis, MO, USA) of 5 mg/kg intraperitoneally after an over-night fast. Twenty minutes afterwards they spontaneously ate the 0.5 g test meal. The rest of the procedure was identical to test 2, except that it was terminated 7 hours after ingestion of the test meal. All procedures were approved by the Animal Care and Use Committee of the university. Analysis of the ^99m^Tc-albumin Colloid Gastric Retention Curve --------------------------------------------------------------- The region of interest was drawn for every image and its amount of radioactivity was measured (Paragon™, Medasys, Ann Arbor, Michigan, USA). ^99m^Tc gastric retention curves were fitted to the data, using the following model: y = 1-(1-e-αt)β. The y is the fractional dose of radioactivity retained in the stomach at time; t is the time in minutes; α and β are regression estimated constants, with α the gastric emptying rate per minute.[@B19],[@B20] From the best fit the following parameters were calculated: T~r1/2~ (time at which 50% of the original amount of ^99m^Tc remained in the stomach) as (-1/k) ln(1-0.5^1/β^); and T~r10%~ (time at which 10% of the original amount of ^99m^Tc remained in the stomach ) as (-1/k) ln(1-0.9^1/β^). Analysis of the ^14^C-octanoate Gastric Emptying Breath Test ------------------------------------------------------------ After adding 10 mL of scintillation solution (Hionic Fluor, Packard Instrument Company, Dowers Grove, IL, USA), the amount of ^14^CO~2~ in the solution was counted using a liquid scintillation spectrometer system (model 2450 Packard; Packard Instrument Company). ^14^CO~2~ excretion curves were fitted to the data, using models given by the following formulas: y = mkβe^-kt^(1-e^-kt^)^β-1^ or y = at^b^e^-ct^.[@B13],[@B14] The y is the ^14^CO~2~ excretion in breath per hour; t is the time in hours; m, k, β, a, b and c are regression estimated constants, with m the total amount of ^14^CO~2~ recovered when time is infinite. From the best fit the following parameters were calculated: T~e1/2~ (time at which 50% of the total amount of ^14^CO~2~ was excreted) as (-1/k) ln(1-0.5^1/β^) × 60; T~e90%~ (time at which 90% of the total amount of ^14^CO~2~ was excreted) as (-1/k) ln(1-0.91^1/β^) × 60; and gastric emptying coefficient (GEC, global index for the gastric emptying rate) as ln(a). The lag phase has been defined in different ways over time: originally it represented the initial delay in gastric emptying of solids as compared to liquids. Later, its value was determined as the point of inflection of the cumulative excretion curve, corresponding to the time when the peak of the excretion curve was reached or even as the time at which 10% of the total amount of ^14^CO~2~ was excreted.[@B13],[@B14],[@B19]-[@B22] Statistical Methods ------------------- T~r10%~, T~e90%~, T~r1/2~, T~e1/2~ and GEC were calculated (mean ± SEM). Regression analysis (correlation coefficient, R-square and *P*-value) between T~r10%~ and T~e90%~ was performed on the pooled data of all 26 rats and on the immobilized and free group separately. According to the method proposed by Bland and Altman[@B23],[@B24] for determination of the limits of agreement, 2 plots for visual analysis were made: the breath test results against the scintigraphic ones and the difference in measurements against the average of the 2 measurements. The same procedures were followed for T~r1/2~ and T~e1/2~. Regression analysis was also performed between T~r1/2~ and GEC; but no limits of agreement could be determined since the units of measurement were different (minutes versus a mathematical parameter). To study the effects of immobilization and gavage we performed *t* tests of all emptying parameters between spontaneously fed free and immobilized rats and between spontaneous and gavage fed animals. We also performed *t* tests between atropine pretreated and not pretreated immobilized animals. Results ======= Pooled Data Scintigraphic T~r10%~ and Breath Test T~e90%~ --------------------------------------------------------- For all 26 rats, the scintigraphic T~r10%~ was 355 ± 64 minutes; T~e90%~ for the breath test was 325 ± 106 minutes. Their correlation coefficient was 0.71; R-square 0.50 and *P* \< 0.0005 ([Fig. 3](#F3){ref-type="fig"}). We also plotted the difference in measurements against the average of the 2 measurements, according to the method proposed by Bland and Altman ([Fig. 3](#F3){ref-type="fig"}).[@B23],[@B24] This figure shows the scatter of differences increasing as the average increases. As a consequence of this, the limits of agreement would be wider apart than necessary for the smaller values and narrower than they should be for larger values; we did not perform a formal analysis on the limits of agreement. In the 14 free moving rats from the first test, the scintigraphic T~r10%~ was 328 ± 68 minutes; T~e90%~ for the breath test was 147 ± 18 minutes. Their correlation coefficient was 0.59; R-square 0.35 and *P* \< 0.05. The 12 immobilized rats from test 2 had a scintigraphic T~r10%~ of 388 ± 117 minutes; T~e90%~ for the breath test was 532 ± 219 minutes. Their correlation coefficient was 0.84; R-square 0.71 and *P* \< 0.001. The large variability in these rats was caused by much higher values of emptying times after atropine (cfr. infra): 904 ± 307 versus 216 ± 49 minutes and 1461 ± 684 versus 223 ± 35 minutes for T~r10%~ and T~e90%~, respectively. Pooled Data of Scintigraphic T~r1/2~ and Breath Test T~e1/2~ ------------------------------------------------------------ For all 26 rats, the scintigraphic T~r1/2~ was 124 ± 28 minutes; T~e1/2~ for the breath test was 114 ± 32 minutes. Their correlation coefficient was 0.83; R-square 0.69 and *P* \< 0.00005 ([Fig. 4](#F4){ref-type="fig"}). Again, the plot of difference in measurements against the average of 2 measurements showed an increased scatter of differences with increasing averages: no formal analysis of the limits of agreement was attempted ([Fig. 4](#F4){ref-type="fig"}). In the 14 free rats from the first test, the scintigraphic T~r1/2~ was 89 ± 19 minutes; T~e1/2~ for the breath test was 61 ± 8 minutes. Their correlation coefficient was 0.79; R-square 0.62 and *P* \< 0.001. The 12 immobilized rats from test 2 had a scintigraphic T~r1/2~ of 165 ± 54 minutes; T~e1/2~ for the breath test was 175 ± 67 minutes. Their correlation coefficient was 0.84; R-square 0.71 and *P* \< 0. 001. Again, the large variability was caused by the much higher values after atropine (cfr.infra): 432 ± 117 versus 76 ± 17 minutes for T~r1/2~ and 473 ± 190 versus 76 ± 14 minutes for T~e1/2~, respectively. Scintigraphic T~r1/2~ and Breath Test Gastric Emptying Coefficient ------------------------------------------------------------------ GEC in immobilized rats was 7.23 ± 0.28 ([Fig. 5](#F5){ref-type="fig"}). It showed a comparable, though inverse, correlation to the scintigraphic T~r1/2~ as T~e1/2~ (correlation coefficient of -0.83, R-square of 0.69 and *P* \< 0.001). No correlation could be shown in the pooled data or in the free rats. Effect of Immobilization ------------------------ Parameters from 9 spontaneously fed and free-moving animals were compared by unpaired t-test with parameters from 8 spontaneously fed rats, immobilized in a restraining device. Although values tended to be higher in immobilized animals, significance was only reached with the breath test T~e90%~ ([Table 1](#T1){ref-type="table"}). Effect of Gavage ---------------- Parameters from 17 spontaneously and 5 gavage fed rats were compared by unpaired *t* tests. Values were higher after gavage, although significance was only reached in the scintigraphic data ([Table 2](#T2){ref-type="table"}). Including only data from free-moving rats did not alter the significance levels. Effect of Atropine ------------------ Unpaired *t* tests were performed on 11 spontaneously fed immobilized animals, 3 of whom pretreated with atropine. There was a significant and marked lengthening of all emptying parameters ([Table 3](#T3){ref-type="table"}). Discussion ========== In this study we adapted the ^14^C-octanoate breath test for use in rats. When compared to the human test, one of the major differences is the fact that in each sample, we captured all CO~2~ produced during the sampling period. This means that during the first half hour of the test, when the rapid rise to the peak excretion occurs, all excreted ^14^CO~2~ is captured (sampling during 5 minutes, with a new tube for every 5 minutes). Also, we did not express the ^14^CO~2~ excretion as a percentage of either the administered or the total recovered amount, but as actual amount captured during the sampling period. Furthermore, since we used ^14^C rather than ^13^C as a marker, we were certain that all excreted ^14^CO~2~ originated from the administered test meal itself. The ^14^C-octanoate breath test can be used to measure gastric emptying because the postgastric processes of intestinal absorption, transport and metabolism are thought to be constant. In humans, inter-individual but not intra-individual variations were demonstrated in healthy volunteers.[@B20],[@B21] However, these volunteers included both males and females and the age difference was as much as 51 years between the oldest and youngest volunteer. In our study, as indeed in most animal studies, same sex (usually male) and similar weight animals from the same genetic pool were used. These animals had all been living under the same conditions. Therefore inter-individual variations of octanoate metabolism are likely to be smaller. We found a good correlation between breath test and scintigraphic emptying parameters. As expected, this correlation was better for immobilized than for free-moving rats, probably attributable to the variations in meal-to-camera distance in free-moving rats. The differences between results from both tests seem to increase towards the higher values. This probably reflects amplification of errors. As Choi et al[@B21],[@B22] pointed out in their human studies, if the length of the collecting period is too short, the estimate of the regression parameter is less accurate, leading to over-estimation of breath test, emptying times. However, even if the optimal length of testing has not been established, for each individual test, it can be postulated that the test period would be long enough if its cumulative excretion curve reached a plateau instead of still being in the ascending slope. The plateau in the cumulative excretion curve corresponds to the tailing off of the descending slope towards the horizontal axis in the excretion curve ([Fig. 2](#F2){ref-type="fig"}). For most of the tested rats, this tailing off was present with the atropine treated rats being the exception. Scintigraphic emptying times in our studies were as long as or longer than their breath test counterparts. This may be due to positioning of the rat: when the stomach region of interest and first part of the duodenum overlap, the initial stages of gastric emptying are invisible on the gamma camera images while ^14^CO~2~ is already expired. Testing this hypothesis requires a dual head gamma camera, but this is not available for animal studies in our center. As a consequence, we were not able to calculate a correcting factor for the breath test emptying times, corresponding to the time needed for post-gastric emptying processing of ^14^C-octanoic acid. Thus, it must be stressed that although there is a good correlation between scintigraphic and breath test parameters, their values are not interchangeable. We also demonstrated that gastric emptying of solids, measured by the breath test, was much slower after administration of the anticholinergic agent atropine. The atropine dose we used was similar to previous studies,[@B25],[@B26] and was half the dose reported to have a full blocking effect in studies of heart rate variability.[@B27] Immobilization and gavage tended to be associated with longer emptying times, although significance was never reached in the breath test, possibly due to the relatively low number of animals studied, especially in the gavage group. In conclusion, we adapted and validated the ^14^C-octanoate solid gastric emptying breath test for application in rats. The availability of this test offers perspectives or repeated pharmacological and pathophysiological studies of gastric emptying in rats. Financial support: This study was supported by a grant from FWO Belgium (Grant No. G.0736.09), and by a Methusalem grant from Leuven University to Jan Tack. Conflicts of interest: None. Author contributions: Ingrid Demedts performed experiments, analysed and interpreted data, and wrote manuscript. Christophe Vanormelingen interpreted data and wrote manuscript. Hubert Van Billoen performed experiments, analysed and interpreted data. Tim Vanuytsel, Ricard Farré, Tatsuhiro Masaoka and Alfons Verbruggen interpreted data and reviewed manuscript. Kristien Verbeke analysed and interpreted data, and reviewed manuscript. Pieter Vanden Berghe designed studies and reviewed manuscript.Jan Tack provided funding, designed studies and reviewed manuscript. {#F1} {#F2} {#F3} {#F4} {#F5} ###### Free Versus Immobilized Animals  T~r1/2~, time at which 50% of the original amount of ^99m^Tc remained in the stomach; T~r10%~, time at which 10% of the original amount of ^99m^Tc remained in the stomach; T~e1/2~, time at which 50% of the total amount of ^14^CO~2~ was excreted; T~e90%~, time at which 90% of the total amount of ^14^CO~2~ was excreted. ###### Spontaneously Versus Gavage Fed Animals  T~r1/2~, time at which 50% of the original amount of ^99m^Tc remained in the stomach; T~r10%~, time at which 10% of the original amount of ^99m^Tc remained in the stomach; T~e1/2~, time at which 50% of the total amount of ^14^CO~2~ was excreted; T~e90%~, time at which 90% of the total amount of ^14^CO~2~ was excreted. ###### With and Without Atropine  T~r1/2~, time at which 50% of the original amount of ^99m^Tc remained in the stomach; T~r10%~, time at which 10% of the original amount of ^99m^Tc remained in the stomach; T~e1/2~, time at which 50% of the total amount of ^14^CO~2~ was excreted; T~e90%~, time at which 90% of the total amount of ^14^CO~2~ was excreted. | High | [
0.663414634146341,
34,
17.25
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A torsion damping device as described in the last preceding paragraph is described in the specification of French published patent application No. FR 2 568 638A, in which the damping device is part of a hydrokinetic torque transmitting apparatus in the form of a torque converter. In that arrangement, the torque input element consists of one of the rings of the first pair of guide rings, which is externally fixed to the wall of the torque converter casing, while the torque output element consists of the second hub, the latter being mounted on a driven shaft for rotation of the latter with it. Such a device presents certain problems, since the abutment means are located at the outer periphery of the damping device, so that the resilient members of the first series cannot be extended circumferentially to as great an extent as is desirable. In addition, the guide ring which constitutes the torque input element has a peripheral fastening flange which is somewhat large in the axial direction. This increases the axial size of the torsion damping device, and prevents resilient members of large circumferential length from being used for the first series of resilient members. | Mid | [
0.5956607495069031,
37.75,
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# Print out nicely formatted s-expressions compatible # with the compiler. # # It should be possible to feed this back into the compiler # with the appropriate switches # Class encapsulates some minor state, such as indentation level class SexpPrinter def initialize opts = {} @nest = 0 @indent = 2 @col = 0 @maxcol = 140 @brk = 105 # @maxcol * 3 / 4 @line = 0 @prune = opts[:prune] end def indent @out.print " "*(@nest * @indent) @col += @nest * @indent end def print str str = str.to_s if @col > @maxcol puts end indent if @col == 0 @col += str.length @out.print str end def puts str = "" str = str.to_s if str != "" print str # FIXME: The "ord" here is necessary because the compiler # itself currently still uses (very) old semantics for string indices. @out.puts if str[-1].ord != ?\n else @out.puts end @col = 0 @line += 1 end def print_tree(data, out = STDOUT) @out = out print "\n%s" print_node(data) puts end def print_node node, nest = 0 if node.is_a?(Array) # FIXME: Changed from @maxcol * 0.7 as compiler currently does not # support Float. puts if @col > @brk or @col > 0 && [:defun,:defm,:class,:if,:let].include?(node.first) print "(" old_line = @line if @prune if node.first == :class || node.first == :defun || node.first == :module node = node[0..2] node << "..." end end node.each_with_index do |n,i| print " " if i > 0 && @col > 0 @nest += 1 puts if n.is_a?(Array) && i == 0 print_node(n) @nest -= 1 if node.first == :do or node.first == :if or node.first == :when or node.first == :case or node.first == :let && i > 0 puts end end puts if [:defun,:defm,:class,:do,:case].include?(node.first) && @line > old_line print ")" elsif node.is_a?(String) print "\"#{node}\"" else print node end end end def print_sexp data, out = STDOUT, opts = {} SexpPrinter.new(opts).print_tree(data,out) end | Mid | [
0.633204633204633,
41,
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Yesterday, a federal judge in Phoenix granted our request to throw out a lawsuit filed by Arizona Gov. Jan Brewer seeking to strike down her own state’s voter-approved medical marijuana law that would allow sick patients access to the medicine they need. In May, Gov. Brewer filed a lawsuit asking a federal court to invalidate Prop. 203, a law Arizona voters passed in 2010 that allows terminally and seriously ill patients to use medical marijuana with a doctor's recommendation. She argued in the lawsuit that state officials fear federal prosecution for implementing the law, despite Arizona’s former top federal prosecutor saying publicly the federal government has “no intention of targeting or going after people who are implementing or who are in compliance with state law.” The ACLU, representing the Arizona Medical Marijuana Association, asserted that the lawsuit was a misguided attempt to undermine the will of Arizona voters and deny thousands of sick Arizonans the medicine their doctors believe is most effective for them, and argued for its dismissal. In yesterday’s ruling, U.S. District Court Judge Susan R. Bolton said there is no genuine threat of imminent federal prosecution of state officials who carry out the law. Now state officials should heed this decision and get down to the long-overdue business of implementing the law — the will of the majority of voters — so that thousands of patients can access the medicine their doctors believe is most effective for them. Learn more about medical marijuana: Sign up for breaking news alerts, follow us on Twitter, and like us on Facebook. | Mid | [
0.5895196506550211,
33.75,
23.5
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<?php /* For licensing terms, see /license.txt */ $cidReset = true; require_once __DIR__.'/../inc/global.inc.php'; $xajax = new xajax(); $xajax->registerFunction('search_users'); // setting the section (for the tabs) $this_section = SECTION_PLATFORM_ADMIN; $id_session = intval($_GET['id_session']); SessionManager::protect_teacher_session_edit($id_session); // setting breadcrumbs if (api_is_platform_admin()) { $interbreadcrumb[] = [ 'url' => 'index.php', 'name' => get_lang('Administration'), ]; $interbreadcrumb[] = [ 'url' => 'session_list.php', 'name' => get_lang('Session list'), ]; $interbreadcrumb[] = [ 'url' => "resume_session.php?id_session=".$id_session, "name" => get_lang('Session overview'), ]; } $allowTutors = api_get_setting('allow_tutors_to_assign_students_to_session'); $extra_field_list = []; if ('true' == $allowTutors) { // Database Table Definitions $tbl_session = Database::get_main_table(TABLE_MAIN_SESSION); $tbl_course = Database::get_main_table(TABLE_MAIN_COURSE); $tbl_user = Database::get_main_table(TABLE_MAIN_USER); $tbl_session_rel_user = Database::get_main_table(TABLE_MAIN_SESSION_USER); // setting the name of the tool $tool_name = get_lang('Subscribe users to this session'); $add_type = 'unique'; if (isset($_REQUEST['add_type']) && '' != $_REQUEST['add_type']) { $add_type = Security::remove_XSS($_REQUEST['add_type']); } $page = isset($_GET['page']) ? Security::remove_XSS($_GET['page']) : null; // Checking for extra field with filter on $extra_field_list = UserManager::get_extra_fields(); $new_field_list = []; if (is_array($extra_field_list)) { foreach ($extra_field_list as $extra_field) { //if is enabled to filter and is a "<select>" field type if (1 == $extra_field[8] && 4 == $extra_field[2]) { $new_field_list[] = [ 'name' => $extra_field[3], 'variable' => $extra_field[1], 'data' => $extra_field[9], ]; } } } function search_users($needle, $type) { global $id_session; $tbl_user = Database::get_main_table(TABLE_MAIN_USER); $tbl_session_rel_user = Database::get_main_table(TABLE_MAIN_SESSION_USER); $xajax_response = new xajaxResponse(); $return = ''; if (!empty($needle) && !empty($type)) { //normal behaviour if ('any_session' == $type && 'false' == $needle) { $type = 'multiple'; $needle = ''; } // xajax send utf8 datas... datas in db can be non-utf8 datas $charset = api_get_system_encoding(); $needle = Database::escape_string($needle); $needle = api_convert_encoding($needle, $charset, 'utf-8'); $order_clause = api_sort_by_first_name() ? ' ORDER BY firstname, lastname, username' : ' ORDER BY lastname, firstname, username'; $cond_user_id = ''; //Only for single & multiple if (in_array($type, ['single', 'multiple'])) { if (!empty($id_session)) { $id_session = intval($id_session); // check id_user from session_rel_user table $sql = 'SELECT user_id FROM '.$tbl_session_rel_user.' WHERE session_id ="'.$id_session.'" AND relation_type<>'.SESSION_RELATION_TYPE_RRHH.' '; $res = Database::query($sql); $user_ids = []; if (Database::num_rows($res) > 0) { while ($row = Database::fetch_row($res)) { $user_ids[] = (int) $row[0]; } } if (count($user_ids) > 0) { $cond_user_id = ' AND user.user_id NOT IN('.implode(",", $user_ids).')'; } } } switch ($type) { case 'single': // search users where username or firstname or lastname begins likes $needle $sql = 'SELECT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user WHERE (username LIKE "'.$needle.'%" OR firstname LIKE "'.$needle.'%" OR lastname LIKE "'.$needle.'%") AND user.status<>6 AND user.status<>'.DRH.''. $order_clause. ' LIMIT 11'; break; case 'multiple': $sql = 'SELECT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user WHERE '.(api_sort_by_first_name() ? 'firstname' : 'lastname').' LIKE "'.$needle.'%" AND user.status<>'.DRH.' AND user.status<>6 '.$cond_user_id. $order_clause; break; case 'any_session': $sql = 'SELECT DISTINCT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user LEFT OUTER JOIN '.$tbl_session_rel_user.' s ON (s.user_id = user.user_id) WHERE s.user_id IS NULL AND user.status <>'.DRH.' AND user.status <> 6 '.$cond_user_id. $order_clause; break; } if (api_is_multiple_url_enabled()) { $tbl_user_rel_access_url = Database::get_main_table(TABLE_MAIN_ACCESS_URL_REL_USER); $access_url_id = api_get_current_access_url_id(); if (-1 != $access_url_id) { switch ($type) { case 'single': $sql = 'SELECT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user INNER JOIN '.$tbl_user_rel_access_url.' url_user ON (url_user.user_id=user.user_id) WHERE access_url_id = '.$access_url_id.' AND (username LIKE "'.$needle.'%" OR firstname LIKE "'.$needle.'%" OR lastname LIKE "'.$needle.'%") AND user.status<>6 AND user.status<>'.DRH.' '. $order_clause. ' LIMIT 11'; break; case 'multiple': $sql = 'SELECT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user INNER JOIN '.$tbl_user_rel_access_url.' url_user ON (url_user.user_id=user.user_id) WHERE access_url_id = '.$access_url_id.' AND '.(api_sort_by_first_name() ? 'firstname' : 'lastname').' LIKE "'.$needle.'%" AND user.status<>'.DRH.' AND user.status<>6 '.$cond_user_id. $order_clause; break; case 'any_session': $sql = 'SELECT DISTINCT user.user_id, username, lastname, firstname FROM '.$tbl_user.' user LEFT OUTER JOIN '.$tbl_session_rel_user.' s ON (s.user_id = user.user_id) INNER JOIN '.$tbl_user_rel_access_url.' url_user ON (url_user.user_id=user.user_id) WHERE access_url_id = '.$access_url_id.' AND s.user_id IS null AND user.status<>'.DRH.' AND user.status<>6 '.$cond_user_id. $order_clause; break; } } } $rs = Database::query($sql); $i = 0; if ('single' == $type) { while ($user = Database::fetch_array($rs)) { $i++; if ($i <= 10) { $person_name = api_get_person_name($user['firstname'], $user['lastname']); $return .= '<a href="javascript: void(0);" onclick="javascript: add_user_to_session(\''.$user['user_id'].'\',\''.$person_name.' ('.$user['username'].')'.'\')">'.$person_name.' ('.$user['username'].')</a><br />'; } else { $return .= '...<br />'; } } $xajax_response->addAssign('ajax_list_users_single', 'innerHTML', api_utf8_encode($return)); } else { $return .= '<select id="origin_users" name="nosessionUsersList[]" multiple="multiple" size="15" style="width:360px;">'; while ($user = Database :: fetch_array($rs)) { $person_name = api_get_person_name($user['firstname'], $user['lastname']); $return .= '<option value="'.$user['user_id'].'">'.$person_name.' ('.$user['username'].')</option>'; } $return .= '</select>'; $xajax_response->addAssign('ajax_list_users_multiple', 'innerHTML', api_utf8_encode($return)); } } return $xajax_response; } $xajax->processRequests(); $htmlHeadXtra[] = $xajax->getJavascript('../inc/lib/xajax/'); $htmlHeadXtra[] = '<script> function add_user_to_session (code, content) { document.getElementById("user_to_add").value = ""; document.getElementById("ajax_list_users_single").innerHTML = ""; destination = document.getElementById("destination_users"); for (i=0;i<destination.length;i++) { if(destination.options[i].text == content) { return false; } } destination.options[destination.length] = new Option(content,code); destination.selectedIndex = -1; sortOptions(destination.options); } function remove_item(origin) { for(var i = 0 ; i<origin.options.length ; i++) { if(origin.options[i].selected) { origin.options[i]=null; i = i-1; } } } function validate_filter() { document.formulaire.add_type.value = \''.$add_type.'\'; document.formulaire.form_sent.value=0; document.formulaire.submit(); } function checked_in_no_session(checked) { $("#first_letter_user") .find("option") .attr("selected", false); xajax_search_users(checked, "any_session"); } function change_select(val) { $("#user_with_any_session_id").attr("checked", false); xajax_search_users(val,"multiple"); } </script>'; $form_sent = 0; $firstLetterUser = $firstLetterSession = ''; $UserList = $SessionList = []; $sessions = []; if (isset($_POST['form_sent']) && $_POST['form_sent']) { $form_sent = $_POST['form_sent']; $firstLetterUser = $_POST['firstLetterUser']; $firstLetterSession = $_POST['firstLetterSession']; $UserList = $_POST['sessionUsersList']; if (!is_array($UserList)) { $UserList = []; } if (1 == $form_sent) { //added a parameter to send emails when registering a user SessionManager::subscribeUsersToSession($id_session, $UserList, null, true); header('Location: resume_session.php?id_session='.$id_session); exit; } } $session_info = SessionManager::fetch($id_session); Display::display_header($tool_name); $nosessionUsersList = $sessionUsersList = []; $ajax_search = 'unique' === $add_type ? true : false; $order_clause = api_sort_by_first_name() ? ' ORDER BY firstname, lastname, username' : ' ORDER BY lastname, firstname, username'; if ($ajax_search) { $sql = "SELECT u.user_id, lastname, firstname, username, session_id FROM $tbl_user u INNER JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." AND $tbl_session_rel_user.session_id = ".intval($id_session)." WHERE u.status <> ".DRH." AND u.status<>6 $order_clause"; if (api_is_multiple_url_enabled()) { $tbl_user_rel_access_url = Database::get_main_table(TABLE_MAIN_ACCESS_URL_REL_USER); $access_url_id = api_get_current_access_url_id(); if (-1 != $access_url_id) { $sql = "SELECT u.user_id, lastname, firstname, username, session_id FROM $tbl_user u INNER JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." AND $tbl_session_rel_user.session_id = ".intval($id_session)." INNER JOIN $tbl_user_rel_access_url url_user ON (url_user.user_id=u.user_id) WHERE access_url_id = $access_url_id AND u.status<>".DRH." AND u.status<>6 $order_clause"; } } $result = Database::query($sql); $users = Database::store_result($result); foreach ($users as $user) { $sessionUsersList[$user['user_id']] = $user; } unset($users); //clean to free memory } else { //Filter by Extra Fields $use_extra_fields = false; if (is_array($extra_field_list)) { if (is_array($new_field_list) && count($new_field_list) > 0) { $result_list = []; foreach ($new_field_list as $new_field) { $varname = 'field_'.$new_field['variable']; if (UserManager::is_extra_field_available($new_field['variable'])) { if (isset($_POST[$varname]) && '0' != $_POST[$varname]) { $use_extra_fields = true; $extra_field_result[] = UserManager::get_extra_user_data_by_value( $new_field['variable'], $_POST[$varname] ); } } } } } if ($use_extra_fields) { $final_result = []; if (count($extra_field_result) > 1) { for ($i = 0; $i < count($extra_field_result) - 1; $i++) { if (is_array($extra_field_result[$i + 1])) { $final_result = array_intersect( $extra_field_result[$i], $extra_field_result[$i + 1] ); } } } else { $final_result = $extra_field_result[0]; } $where_filter = ''; if (api_is_multiple_url_enabled()) { if (is_array($final_result) && count($final_result) > 0) { $where_filter = " AND u.user_id IN ('".implode("','", $final_result)."') "; } else { //no results $where_filter = " AND u.user_id = -1"; } } else { if (is_array($final_result) && count($final_result) > 0) { $where_filter = " WHERE u.user_id IN ('".implode("','", $final_result)."') "; } else { //no results $where_filter = " WHERE u.user_id = -1"; } } } if ($use_extra_fields) { $sql = "SELECT u.user_id, lastname, firstname, username, session_id FROM $tbl_user u LEFT JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.session_id = '$id_session' AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." $where_filter AND u.status<>".DRH." AND u.status<>6 $order_clause"; } else { $sql = "SELECT user_id, lastname, firstname, username, session_id FROM $tbl_user u LEFT JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.session_id = '$id_session' AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." WHERE u.status <> ".DRH." AND u.status<>6 $order_clause"; } if (api_is_multiple_url_enabled()) { $tbl_user_rel_access_url = Database::get_main_table(TABLE_MAIN_ACCESS_URL_REL_USER); $access_url_id = api_get_current_access_url_id(); if (-1 != $access_url_id) { $sql = "SELECT u.user_id, lastname, firstname, username, session_id FROM $tbl_user u LEFT JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.session_id = '$id_session' AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." INNER JOIN $tbl_user_rel_access_url url_user ON (url_user.user_id=u.user_id) WHERE access_url_id = $access_url_id $where_filter AND u.status<>".DRH." AND u.status<>6 $order_clause"; } } $result = Database::query($sql); $users = Database::store_result($result, 'ASSOC'); foreach ($users as $uid => $user) { if ($user['session_id'] != $id_session) { $nosessionUsersList[$user['user_id']] = [ 'fn' => $user['firstname'], 'ln' => $user['lastname'], 'un' => $user['username'], ]; unset($users[$uid]); } } unset($users); //clean to free memory //filling the correct users in list $sql = "SELECT user_id, lastname, firstname, username, session_id FROM $tbl_user u LEFT JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.id AND $tbl_session_rel_user.session_id = '$id_session' AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." WHERE u.status <> ".DRH." AND u.status<>6 $order_clause"; if (api_is_multiple_url_enabled()) { $tbl_user_rel_access_url = Database::get_main_table(TABLE_MAIN_ACCESS_URL_REL_USER); $access_url_id = api_get_current_access_url_id(); if (-1 != $access_url_id) { $sql = "SELECT u.user_id, lastname, firstname, username, session_id FROM $tbl_user u LEFT JOIN $tbl_session_rel_user ON $tbl_session_rel_user.user_id = u.user_id AND $tbl_session_rel_user.session_id = '$id_session' AND $tbl_session_rel_user.relation_type<>".SESSION_RELATION_TYPE_RRHH." INNER JOIN $tbl_user_rel_access_url url_user ON (url_user.user_id=u.user_id) WHERE access_url_id = $access_url_id AND u.status<>".DRH." AND u.status<>6 $order_clause"; } } $result = Database::query($sql); $users = Database::store_result($result, 'ASSOC'); foreach ($users as $uid => $user) { if ($user['session_id'] == $id_session) { $sessionUsersList[$user['user_id']] = $user; if (array_key_exists($user['user_id'], $nosessionUsersList)) { unset($nosessionUsersList[$user['user_id']]); } } unset($users[$uid]); } unset($users); //clean to free memory } if ('multiple' === $add_type) { $link_add_type_unique = '<a href="'.api_get_self().'?id_session='.$id_session.'&add='.Security::remove_XSS($_GET['add']).'&add_type=unique">'. Display::return_icon('single.gif').get_lang('Single registration').'</a>'; $link_add_type_multiple = Display::return_icon('multiple.gif').get_lang('Multiple registration'); } else { $link_add_type_unique = Display::return_icon('single.gif').get_lang('Single registration'); $link_add_type_multiple = '<a href="'.api_get_self().'?id_session='.$id_session.'&add='.Security::remove_XSS($_GET['add']).'&add_type=multiple">'. Display::return_icon('multiple.gif').get_lang('Multiple registration').'</a>'; } $link_add_group = '<a href="usergroups.php">'. Display::return_icon('multiple.gif', get_lang('Enrolment by classes')).get_lang('Enrolment by classes').'</a>'; ?> <div class="actions"> <?php echo $link_add_type_unique; ?> | <?php echo $link_add_type_multiple; ?> | <?php echo $link_add_group; ?> </div> <form name="formulaire" method="post" action="<?php echo api_get_self(); ?>?page=<?php echo $page; ?>&id_session=<?php echo $id_session; ?><?php if (!empty($_GET['add'])) { echo '&add=true'; } ?>" style="margin:0px;" <?php if ($ajax_search) { echo ' onsubmit="valide();"'; } ?>> <?php echo '<legend>'.$tool_name.' ('.$session->getName().') </legend>'; ?> <?php if ('multiple' === $add_type) { if (is_array($extra_field_list)) { if (is_array($new_field_list) && count($new_field_list) > 0) { echo '<h3>'.get_lang('Filter users').'</h3>'; foreach ($new_field_list as $new_field) { echo $new_field['name']; $varname = 'field_'.$new_field['variable']; echo ' <select name="'.$varname.'">'; echo '<option value="0">--'.get_lang('Select').'--</option>'; foreach ($new_field['data'] as $option) { $checked = ''; if (isset($_POST[$varname])) { if ($_POST[$varname] == $option[1]) { $checked = 'selected="true"'; } } echo '<option value="'.$option[1].'" '.$checked.'>'.$option[1].'</option>'; } echo '</select>'; echo ' '; } echo '<input type="button" value="'.get_lang('Filter').'" onclick="validate_filter()" />'; echo '<br /><br />'; } } } ?> <input type="hidden" name="form_sent" value="1" /> <input type="hidden" name="add_type" /> <div class="row"> <div class="span5"> <div class="multiple_select_header"> <b><?php echo get_lang('Portal users list'); ?> :</b> <?php if ('multiple' == $add_type) { ?> <?php echo get_lang('First letter (last name)'); ?> : <select id="first_letter_user" name="firstLetterUser" onchange = "change_select(this.value);" > <option value = "%">--</option> <?php echo Display :: get_alphabet_options(); ?> </select> <?php } ?> </div> <div id="content_source"> <?php if (!('multiple' == $add_type)) { ?> <input type="text" id="user_to_add" onkeyup="xajax_search_users(this.value,'single')" /> <div id="ajax_list_users_single"></div> <?php } else { ?> <div id="ajax_list_users_multiple"> <select id="origin_users" name="nosessionUsersList[]" multiple="multiple" size="15" class="span5"> <?php foreach ($nosessionUsersList as $uid => $enreg) { ?> <option value="<?php echo $uid; ?>" <?php if (in_array($uid, $UserList)) { echo 'selected="selected"'; } ?>><?php echo api_get_person_name($enreg['fn'], $enreg['ln']).' ('.$enreg['un'].')'; ?></option> <?php } ?> </select> </div> <input type="checkbox" onchange="checked_in_no_session(this.checked);" name="user_with_any_session" id="user_with_any_session_id"> <label for="user_with_any_session_id"><?php echo get_lang('Users not registered in any session'); ?></label> <?php } unset($nosessionUsersList); ?> </div> </div> <div class="span2"> <div style="padding-top:54px;width:auto;text-align: center;"> <?php if ($ajax_search) { ?> <button class="btn btn-default" type="button" onclick="remove_item(document.getElementById('destination_users'))" ><em class="fa fa-arrow-left"></em></button> <?php } else { ?> <button class="btn btn-default" type="button" onclick="moveItem(document.getElementById('origin_users'), document.getElementById('destination_users'))" onclick="moveItem(document.getElementById('origin_users'), document.getElementById('destination_users'))"> <em class="fa fa-arrow-right"></em> </button> <br /><br /> <button class="btn btn-default" type="button" onclick="moveItem(document.getElementById('destination_users'), document.getElementById('origin_users'))" onclick="moveItem(document.getElementById('destination_users'), document.getElementById('origin_users'))"> <em class="fa fa-arrow-left"></em> </button> <?php } ?> </div> <br /> <br /> <?php if (isset($_GET['add'])) { echo '<button class="btn btn-primary" type="button" value="" onclick="valide()" >'.get_lang('Finish session creation').'</button>'; } else { //@todo see that the call to "valide()" doesn't duplicate the onsubmit of the form (necessary to avoid delete on "enter" key pressed) echo '<button class="save" type="button" value="" onclick="valide()" >'.get_lang('Subscribe users to this session').'</button>'; } ?> </div> <div class="span5"> <div class="multiple_select_header"> <b><?php echo get_lang('List of users registered in this session'); ?> :</b> </div> <select id="destination_users" name="sessionUsersList[]" multiple="multiple" size="15" class="span5"> <?php foreach ($sessionUsersList as $enreg) { ?> <option value="<?php echo $enreg['user_id']; ?>"><?php echo api_get_person_name($enreg['firstname'], $enreg['lastname']).' ('.$enreg['username'].')'; ?></option> <?php } unset($sessionUsersList); ?> </select> </div> </div> </form> <script> function moveItem(origin , destination) { for (var i = 0 ; i<origin.options.length ; i++) { if (origin.options[i].selected) { destination.options[destination.length] = new Option(origin.options[i].text,origin.options[i].value); origin.options[i]=null; i = i-1; } } destination.selectedIndex = -1; sortOptions(destination.options); } function sortOptions(options) { newOptions = new Array(); for (i = 0 ; i<options.length ; i++) newOptions[i] = options[i]; newOptions = newOptions.sort(mysort); options.length = 0; for (i = 0 ; i < newOptions.length ; i++) options[i] = newOptions[i]; } function mysort(a, b) { if (a.text.toLowerCase() > b.text.toLowerCase()) { return 1; } if (a.text.toLowerCase() < b.text.toLowerCase()) { return -1; } return 0; } function valide() { var options = document.getElementById('destination_users').options; for (i = 0 ; i<options.length ; i++) options[i].selected = true; document.forms.formulaire.submit(); } function loadUsersInSelect(select) { var xhr_object = null; if(window.XMLHttpRequest) // Firefox xhr_object = new XMLHttpRequest(); else if(window.ActiveXObject) // Internet Explorer xhr_object = new ActiveXObject("Microsoft.XMLHTTP"); else // XMLHttpRequest non supporté par le navigateur alert("Votre navigateur ne supporte pas les objets XMLHTTPRequest..."); //xhr_object.open("GET", "loadUsersInSelect.ajax.php?id_session=<?php echo $id_session; ?>&letter="+select.options[select.selectedIndex].text, false); xhr_object.open("POST", "loadUsersInSelect.ajax.php"); xhr_object.setRequestHeader("Content-Type", "application/x-www-form-urlencoded"); nosessionUsers = makepost(document.getElementById('origin_users')); sessionUsers = makepost(document.getElementById('destination_users')); nosessionClasses = makepost(document.getElementById('origin_classes')); sessionClasses = makepost(document.getElementById('destination_classes')); xhr_object.send("nosessionusers="+nosessionUsers+"&sessionusers="+sessionUsers+"&nosessionclasses="+nosessionClasses+"&sessionclasses="+sessionClasses); xhr_object.onreadystatechange = function() { if (xhr_object.readyState == 4) { document.getElementById('content_source').innerHTML = result = xhr_object.responseText; //alert(xhr_object.responseText); } } } function makepost(select) { var options = select.options; var ret = ""; for (i = 0 ; i<options.length ; i++) ret = ret + options[i].value +'::'+options[i].text+";;"; return ret; } </script> <?php } else { api_not_allowed(); } Display::display_footer(); | Low | [
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Q: How to hint OpenMP Stride? I am trying to understand the conceptual reason why OpenMP breaks loop vectorization. Also any suggestions for fixing this would be helpful. I am considering manually parallelizing this to fix this issue, but that would certainly not be elegant and result in a massive amount of code bloat, as my code consists of several such sections that lend themselves to vectorization and parallelization. I am using Microsoft (R) C/C++ Optimizing Compiler Version 17.00.60315.1 for x64 With OpenMP: info C5002: loop not vectorized due to reason '502' Without OpenMP: info C5001: loop vectorized The VS vectorization page says this error happens when: Induction variable is stepped in some manner other than a simple +1 Can I force it to step in stride 1? The loop #pragma omp parallel for for (int j = 0; j < H*W; j++)//A,B,C,D,IN are __restricted { float Gs = D[j]-B[j]; float Gc = A[j]-C[j]; in[j]=atan2f(Gs,Gc); } Best Effort(?) #pragma omp parallel {// This seems to vectorize, but it still requires quite a lot of boiler code int middle = H*W/2; #pragma omp sections nowait { #pragma omp section for (int j = 0; j < middle; j++) { float Gs = D[j]-B[j]; float Gc = A[j]-C[j]; in[j]=atan2f(Gs,Gc); } #pragma omp section for (int j = middle; j < H*W; j++) { float Gs = D[j]-B[j]; float Gc = A[j]-C[j]; in[j]=atan2f(Gs,Gc); } } } A: I recommend that you do the vectorization manually. One reason is that auto-vectorization does not seem to handle carried loop dependencies well (loop unrolling). To avoid code bloat and arcane intrinsics I use Agner Fog's vectorclass. In my experience it's just as fast as using intrinsics and it automatically takes advantage of SSE2-AVX2 (AVX2 is tested on a Intel emulator) depending on how you compile. I have written GEMM code using the vectorclass that works on SSE2 up to AVX2 and when I run on a system with AVX my code is already faster than Eigen which only uses SSE. Here is your function with the vectorclass (I did not try unrolling the loop). #include "omp.h" #include "math.h" #include "vectorclass.h" #include "vectormath.h" void loop(const int H, const int W, const int outer_stride, float *A, float *B, float *C, float *D, float* in) { #pragma omp parallel for for (int j = 0; j < H*W; j+=8)//A,B,C,D,IN are __restricted, W*H must be a multiple of 8 { Vec8f Gs = Vec8f().load(&D[j]) - Vec8f().load(&B[j]); Vec8f Gc = Vec8f().load(&A[j]) - Vec8f().load(&C[j]); Vec8f invec = atan(Gs, Gc); invec.store(&in[j]); } } When doing the vectorization yourself you have to be careful with array bounds. In the function above HW needs to be a multiple of 8. There are several solutions for that but the easiest and most efficient solution is to make the arrays (A,B,C,D,in) a bit larger (maximum 7 floats larger) if necessary to be a multiple of 8. However, another solution is to use the following code which does not require WH to be a multiple of 8 but it's not as pretty. #define ROUND_DOWN(x, s) ((x) & ~((s)-1)) void loop_fix(const int H, const int W, const int outer_stride, float *A, float *B, float *C, float *D, float* in) { #pragma omp parallel for for (int j = 0; j < ROUND_DOWN(H*W,8); j+=8)//A,B,C,D,IN are __restricted { Vec8f Gs = Vec8f().load(&D[j]) - Vec8f().load(&B[j]); Vec8f Gc = Vec8f().load(&A[j]) - Vec8f().load(&C[j]); Vec8f invec = atan(Gs, Gc); invec.store(&in[j]); } for(int j=ROUND_DOWN(H*W,8); j<H*W; j++) { float Gs = D[j]-B[j]; float Gc = A[j]-C[j]; in[j]=atan2f(Gs,Gc); } } One challenge with doing the vectorization yourself is finding a SIMD math library (e.g. for atan2f). The vectorclass supports 3 options. Non-SIMD, LIBM by AMD, and SVML by Intel (I used the non-SIMD option in the code above). SIMD math libraries for SSE and AVX Some last comments you might want to consider. Visual Studio has auto-parallelization (off by default) as well as auto-vectorization (on by default, at least in release mode). You can try this instead of OpenMP to reduce code bloat. http://msdn.microsoft.com/en-us/library/hh872235.aspx Additionally, Microsoft has the parallel patterns library. It's worth looking into since Microsoft's OpenMP support is limited. It's nearly as easy as OpenMP to use. It's possible that one of these options works better with auto-vectorization (though I doubt it). Like I said, I would do the vectorization manually with the vectorclass. | Mid | [
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I picked up this neat little cake pop mold at JoAnn Fabrics. I was lucky to find it in the 50% section. I think it cost me maybe $3. I have never made cake pops before so it was a big learning process! First we backed a confetti cake. After the cake was done, you… I was looking over pinterest for a yummy recipe to make for dessert. Overwhelmed by so many options, I finally chose this Pumpkin Pie Cupcake. Let me tell you, these are the easiest and most delish pumpkin cupcakes I have ever had!! If your a pumpkin lover like me, you must try these! You won’t… This story has completely inspired me. I think we all know someone out there that has been affected by cancer. This amazing woman Jill, has such a positive attitude on life and the cards she has been dealt. Please watch and share this video with your friends. It has been absolutely life changing to me…. | Mid | [
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/* Author: Jason Williams <[email protected]> Copyright (c) 2014 Cromulence LLC Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions: The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software. THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. */ #ifndef __STDINT_H__ #define __STDINT_H__ typedef signed char int8_t; typedef short int int16_t; typedef int int32_t; typedef long long int int64_t; typedef unsigned char uint8_t; typedef unsigned short int uint16_t; typedef unsigned int uint32_t; typedef unsigned long long int uint64_t; #endif // __STDINT_H__ | Mid | [
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Q: no gitignore file in new rails app I created a new Rails app using version 3.0.1 (in order to follow along with a tutorial using 3.0.1), but it didn't create a gitignore file. If I create my own, what ending should I put on the file? is it an rb file? or can you explain why it might not have created this file? A: It isn't a ruby file. It is simply a list of files or directories to ignore. Simply create a file called .gitignore. There is no extension. A: .gitignore is a file used by Git version control system. It has nothing to do with Ruby and you don't need to create it unless your project uses Git as a version control system. Here is more info about gitignore if you are interested: http://gitready.com/beginner/2009/01/19/ignoring-files.html | Mid | [
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INTRODUCTION {#sec1-1} ============ Mood stabilizer is the term used for the agents which are useful in the treatment of bipolar disorders. However, the definition of this class of drugs is not yet settled. Some researchers/clinicians restrict the use the term mood stabilizer for agents, which have efficacy in reducing the frequency or severity of various type of episodes in bipolar disorder without worsening the frequency or severity of other types of episodes.\[[@ref1][@ref2][@ref3]\] Accordingly, antidepressants, which can induce manic switch and typical antipsychotics, which are shown to worsen depressive symptoms would not classify as mood stabilizers. On the other hand, some authors defined mood stabilizers as agents that have efficacy in treating both manic and depressive symptoms.\[[@ref4]\] Bauer and Mitchner\[[@ref5]\] expanded this definition and defined mood stabilizer as an agent, which has efficacy in treatment of acute manic symptoms, acute depressive symptoms and can prevent development of manic and depressive symptoms.\[[@ref5]\] Although the definition is not settled, mood stabilizers are commonly understood as agents that are useful for treatment of acute episodes (manic or depressive) and prevention of relapse or recurrence of symptoms, without worsening of symptoms of either polarity. In recent times, many drugs have been evaluated as mood stabilizers. The term mood stabilizers is mostly used in relation to lithium, anticonvulsants like valproate, carbamazepine, oxcarbazepine, lamotrigine, topiramate, gabapentin etc., and atypical antipsychotic like olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Some other drugs like clonazepam, calcium channel blockers etc., have also been evaluated as mood stabilizers. In this paper, the authors would limit to use of lithium, anticonvulsants, atypical antipsychotic and benzodiazepines in subjects with bipolar disorders. BIPOLAR DISORDER: RISK OF RECURRENCE DURING PREGNANCY AND POSTPARTUM {#sec1-2} ==================================================================== Bipolar disorder is considered a severe mental disorder that usually starts in late teens and early twenties and is characterized by episodes of mania, depression, hypomania and mixed episodes. The disorder has equal prevalence in both genders. Women are exposed to the risk of an episode throughout their reproductive life because of its age of onset,\[[@ref6]\] The decision to stop drugs when women with bipolar disorder become pregnant or plan to conceive is difficult. The treating psychiatrists of such patients face the challenge of having to minimize the risk to the fetus, while at the same time, limiting the impact of maternal morbidity. Patients and their clinicians also face the reality that decisions either to use or not to use psychotropic medications can be associated with complications. Hence, concluding as to what constitutes a reasonable risk during pregnancy requires shared responsibility, but the ultimate decision rests with the informed patient. Studies have shown that female patients with bipolar disorder are at high risk of relapse of symptoms during the pregnancy\[[@ref7][@ref8][@ref9]\] and early postpartum period.\[[@ref10][@ref11][@ref12][@ref13]\] The risk of relapse during pregnancy has been estimated to be 50% or more,\[[@ref7][@ref8][@ref9]\] with recurrence risk reported to be 2.3 times higher after discontinuation of mood stabilizer. In a prospective study, it was found that women who discontinued the mood stabilizer spent about 40% of the time of pregnancy in episodes compared to 8.8% of time spent by those who continued mood stabilizer. It was also evident that the recurrence risk was higher and earlier after rapid discontinuation of mood stabilizer. The authors also found that women, who had younger age of onset, longer duration of illness, more number of previous episodes, history of rapid cycling, suicide attempts, associated comorbid disorders and antidepressant use, had higher chance of recurrence during the pregnancy. Treatment discontinuation and antidepressant use remained as independent risk factors even after adjusting for other risk factors.\[[@ref9]\] With regard to the postpartum risk, studies have shown that 40--70% of untreated bipolar women may experience postpartum episode.\[[@ref14]\] It is also known that the risk of postpartum relapse is high in those who discontinue prophylactic treatment.\[[@ref13]\] POTENTIAL RISKS OF PHARMACOTHERAPY IN PREGNANCY IN BIPOLAR DISORDERS {#sec1-3} ==================================================================== For obvious ethical reasons, it is not possible to conduct randomized placebo controlled studies on medication safety in pregnant and lactating women. Most of the information about the reproductive safety of drugs is derived from case reports, case series, and retrospective studies. Very few studies involve prospective design. Hence, knowledge regarding the risks of prenatal exposure to psychotropic medications remains far from complete. It is evident that all psychotropic medications diffuse across the placenta, which exposes the fetus to some degree of risk.\[[@ref15]\] In the past, the effects of psychopharmacological therapies was exclusively discussed in the context of their risk during the first trimester when organ formation occurs, it is now recognized that psychotropics are harmful even after organogenesis, as intrauterine exposure during the second and third trimester can lead to postnatal complications.\[[@ref16]\] Accordingly, the impact of psychotropic drugs on the fetus and new born has been studied in the form of teratogenicity (risk of congenital physical deformities over the base line rate of 2.0--2.5%), obstetrical complications (preterm delivery, low birth weight, low Apgar scores necessitating intensive care), perinatal syndrome (physical and behavioral symptoms noticed shortly after birth) and long-term behavioral sequelae (neurobehavioral abnormalities in children), including long-term neurobehavioral abnormalities in children who were exposed to psychotropics in utero.\[[@ref15]\] REPRODUCTIVE SAFETY OF MOOD STABILIZERS {#sec1-4} ======================================= No psychotropic drug has been approved by the US Food and Drug Administration (FDA) for use during pregnancy. FDA has established a classificatory system for medications based on data derived from human and animal studies.\[[@ref17][@ref18]\] According to the risk, medications are classified into 5 risk categories (A, B, C, D, and X). Medications placed in category "A" are considered safe for use during pregnancy, however, no psychotropic medication is classified as belonging to category "A." Medications placed in category X are contraindicated due to demonstrated fetal risks, which outweigh benefit to the patient. Drugs in categories B to D are considered to have intermediate risks, which are greatest in category D. Most antipsychotics are classified as category C agents for which adequate human studies are lacking and fetal effects are seen in animal studies or those in which the animal studies are also insufficient; making it difficult to rule out the fetal risks. Mood stabilizers like lithium, valproate and carbamazepine are classified as category "D" drugs.\[[@ref15][@ref17][@ref18]\] It is important to remember that this classification is not adequate for making all decisions and the psychiatrists have to rely on other sources of information when recommending the use of psychotropic medications during pregnancy.\[[@ref19][@ref20]\] MOOD STABILIZERS AND LACTATION {#sec1-5} ============================== Breast milk is considered as an ideal form of nutrition and is known to confer many advantages to the new born and the infant. In addition, breast feeding is also known to confer health benefits to mother. As per the American Academy of Pediatrics,\[[@ref21]\] human milk is known to reduce the incidence and/or severity of a wide range of infectious diseases including bacterial meningitis, bacteremia, diarrhea, necrotizing enterocolitis, otitis media, respiratory tract infection, urinary tract infection, and late-onset sepsis in preterm infants. In addition, breast feeding is also reported to be associated with reduced postneonatal infant mortality rates, decreased rates of sudden infant death syndrome in the 1^st^ year of life, lower incidence of type 1 and type 2 diabetes mellitus, Hodgkin disease, lymphoma, leukemia, overweight and obesity, hypercholesterolemia and asthma in older children and adults. Further, it is suggested that breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Breast feeding is also very important for development of emotional bond and attachment between the mother and the infant.\[[@ref22][@ref23]\] It is also known that continuation of breast feeding decreases postpartum bleeding and leads to more rapid uterine involution, decreased menstrual blood loss, increased child spacing by lactational amenorrhea, earlier return to prepregnancy weight, decreased risk of breast and ovarian cancer, and possibly decreased risk of hip fractures and osteoporosis in the postmenopausal period.\[[@ref24]\] Hence, asking the women not to feed the baby can lead to an ethical dilemma. The decision regarding continuing or not continuing breast feeding while continuing mood stabilizers is a difficult one. Ideally, a risk benefit analysis should be carried out taking into consideration the physiological and psychological benefits of breastfeeding; the potential adverse effect of untreated maternal mental illness on the infant and maternal child bonding; impact of psychotropic medication on the cognitive and behavioral development of the infant, and the consequences of untreated mental illness on the mother.\[[@ref24]\] If a decision is taken to allow continuation of breast feeding, it is important for the clinicians to have basic knowledge about the physiological aspects of milk secretion and the physiological maturation of the newborn child. The exposure of infant to various medications is dependent on the rate of absorption into maternal circulation, diffusion from maternal circulation to breast milk, and absorption of the agent in the infant. The concentration of medications in breast milk is influenced by lactose, serum albumin, lysozyme and approximately 30 other enzymes, prolactin, and minerals like calcium and phosphates. It is known that, compared with the fore milk (the milk ejected during the first half of a feeding), hind milk (the milk ejected during the second half of a feeding) has higher lipid content; hence, the milk secreted in the second half will have a higher concentration of lipid soluble maternal psychotropic medications than the first half.\[[@ref25]\] In terms of physiological maturation of the neonate, it is important to remember that the amount of neonatal cytochrome P-450 activity is about half that found in adults. Ability to conjugate various compounds develops from minimal levels to almost adult levels within 2 weeks of birth in most cases.\[[@ref26]\] Further, compared to adults, kidneys of newborn are functionally immature; hence the psychotropic medications that are predominately eliminated through kidney may accumulate. Compared with adults, the blood brain barrier in newborn is also immature, hence the lipid soluble agents can be more concentrated (10--30 times) in the cerebrospinal fluid than in serum and may be higher in infants for a given plasma concentration. In addition, compared to older infants, neonate have relatively lower fat storage sites, accordingly central nervous system (CNS) concentrations of lipid soluble substances are greater in newborns.\[[@ref25]\] EFFECTS OF PSYCHOTROPICS: PREGNANCY AND LACTATION {#sec1-6} ================================================= Lithium {#sec2-1} ------- Use of lithium in pregnancy has been a cause of concern since the beginning because of the risk for major congenital anomalies with prenatal exposure to lithium, especially cardiovascular malformations such as Ebstein\'s anomaly.\[[@ref27][@ref28][@ref29]\] As per the initial estimations, the risk for Ebstein\'s anomaly in infants with first trimester lithium was 400 times more than the background baseline rates.\[[@ref27][@ref28][@ref29][@ref30]\] Cohen *et al.*\[[@ref30]\] carried out a metaanalysis and calculated the risk for Ebstein\'s anomaly, with first trimester exposure to lithium, to be between 1/1000 (0.1%) and 1/2000 (0.05%) births.\[[@ref30]\] This risk was 10--20 times higher than the risk of Ebstein\'s anomaly in the general population. It is important to understand that the absolute risk is small (0.05--0.1%), and lithium is considered to be the safest mood stabilizer for use during pregnancy.\[[@ref30]\] Some of the recent studies suggest increased risk of miscarriage.\[[@ref31]\] In addition, use of lithium has been associated with congenital abnormalities like large for gestational age infants,\[[@ref32]\] anencephaly,\[[@ref33]\] oromandibular-limb hypogenesis\[[@ref34]\] and premature closure of arterial duct.\[[@ref35]\] Exposure to lithium during labor and delivery is associated with the risk of "floppy baby" syndrome, which is characterized by muscular hypotonia with impaired breathing and cyanosis in new born.\[[@ref36][@ref37][@ref38]\] Apart from this, there are occasional reports of neonatal hypothyroidism, nephrogenic diabetes insipidus, and polyhydramnios.\[[@ref15][@ref38][@ref39]\] Some groups recommend discontinuation of lithium several days or weeks prior to delivery to minimize the risk of neonatal toxicity.\[[@ref31][@ref37][@ref39][@ref40]\] Newport *et al.*\[[@ref41]\] evaluated the distribution of lithium concentration in umbilical cord blood to maternal blood and reported that lithium concentration was uniform (umbilical cord blood: Maternal blood ratio = 1.05; standard deviation = 0.13) across a wide range of maternal lithium concentrations (0.2--2.6 mEq/L). In the same study, higher lithium concentrations (\>0.64 mEq/L) at delivery were associated with significantly lower Apgar scores, higher rates of CNS and neuromuscular complications in infants and resultant longer duration of hospital stay. In was observed that withholding lithium therapy for 24--48 h before delivery resulted in reduction in maternal lithium concentration by 0.28 mEq/L, which the authors considered could lead to improvement in obstetrical outcome. A few reports have described adverse effects in the form of lethargy, hypothermia, hypotonia, and T-wave modifications on electrocardiogram (ECG) in newborns of mothers who continued to take lithium during the postpartum period.\[[@ref32][@ref42][@ref43]\] In a recent study, the maximum recommended dose of lithium in pregnant women, based on a physiologically based pharmacokinetic model, was estimated and reported as 400 mg thrice daily.\[[@ref44]\] Data are limited with regard to the behavioral outcomes of children exposed to lithium *in utero*. Follow-up studies of children (for 3.5--5 years) exposed to lithium during pregnancy have come up with lack of evidence for significant behavioral problems.\[[@ref41][@ref45]\] However, these studies have been limited by small sample size. One of the recent studies evaluated 15 children, exposed to lithium prenatally, at the age of 3--15 years of age and reported lower scores on the performance intelligence quotient (IQ), although overall intelligence was within normal limits. However, no abnormality was observed in growth, behavior and general development.\[[@ref46]\] Anticonvulsants {#sec2-2} --------------- Compared to lithium, higher teratogenic risk has been reported to be associated with anticonvulsants. The risk for major birth defects in infants born to women receiving anticonvulsants has been reported to be twice that seen in general population.\[[@ref47]\] Further it is seen that the increased risk for teratogenesis is associated with high maternal serum anticonvulsant levels and exposure to multiple anticonvulsants at a time.\[[@ref48][@ref49]\] Valproate {#sec2-3} --------- Valproate is now considered as a mood stabilizer. It is effective in management of acute manic and depressive episodes and is also useful in prevention of relapse of both manic and depressive episodes. Valproic acid and its various derivatives have been known to have an increased risk of causing neural tube defects in the range of 1.0--5.0%, which is about 2--10-fold higher than the general population base rates of about 0.5%.\[[@ref50][@ref51]\] These risks are of concern because neural tube formation occurs within the 1^st^ month of gestation, a time period during which the pregnancy is not even diagnosed. The neural tube defect with valproate more often involves the lumbosacral rather than the anencephalic region, suggesting the effect of valproate on the closure of neural crest.\[[@ref52]\] Prenatal exposure to valproate has been associated cardiovascular malformations, intrauterine growth retardation, genital anomalies, hydrocephalus, limb defects (radial ray effects, fibrous aplasia of lower limbs), and pulmonary atresia.\[[@ref47][@ref48][@ref49][@ref50][@ref51][@ref52][@ref53][@ref54][@ref55]\] In a prospective study, Wyszynski *et al.*,\[[@ref53]\] evaluated the rate of occurrence of major malformations at birth in infants of mothers who had taken valproate as monotherapy and had enrolled in the North American Antiepileptic Drug (AED) Pregnancy Registry. Of the 149 valproate monotherapy exposed pregnancies, major malformations were seen in 16 cases. When these data were compared with the major malformations with other anticonvulsants, it was concluded that valproate was associated with more frequent adverse effects. Another recent case--control study, which was based on European Surveillance of Congenital Anomalies antiepileptic-study database, evaluated the outcome of exposure to valproic acid monotherapy in 180 registrations. Compared to no use of antiepileptic medications, use of valproic acid during the first trimester was associated with increased risk of spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyl and craniosynostosis.\[[@ref56]\] Emerging data also suggest that the risk of malformations with valproate is dose related\[[@ref57][@ref58]\] with higher risk associated with use of valproate in excess of 1000 mg/day.\[[@ref57]\] Data based on the review of United Kingdom (UK) and Ireland Epilepsy and Pregnancy Registers have estimated the risk of major congenital malformations with valproate monotherapy to be 6.7%, which is higher than that reported for carbamazepine (2.6%) and lamotrigine (2.3%).\[[@ref59]\] Use of valproate close to delivery is associated with withdrawal symptoms of abnormal tone, feeding difficulties, irritability and jitteriness.\[[@ref54]\] In addition, neonatal complications like heart rate decelerations,\[[@ref60]\] liver toxicity,\[[@ref61]\] hypoglycemia,\[[@ref62]\] and reductions in neonatal fibrinogen levels\[[@ref63]\] have also been reported. Long-term behavioral and cognitive outcome with exposure to valproate in pregnancy has been evaluated. Meador *et al.*\[[@ref64]\] evaluated the IQ scores at the age of 3 years of 258 children who were exposed to anticonvulsants during pregnancy. IQs were lower for those exposed to valproate compared to carbamazepine, LTG, and phenytoin, after controlling for maternal IQs and blood levels of anticonvulsant medications. It was further found that maternal valproate blood level had significant inverse correlation with cognitive functioning. A follow-up of the children at 4.5 years showed the persistence of lower IQ, which was negatively associated with dose of valproate\[[@ref65]\] Subsequently, a large scale study evaluated IQ of children at the age of 6 years and provided credence to this finding.\[[@ref66]\] A study also suggested that compared to the children exposed to carbamazepine and lamotrigine, children exposed to valproate prenatally have lower cognitive fluency and originality.\[[@ref67]\] Recent studies have also reported neurodevelopmental delay in children exposed to valproate prenatally.\[[@ref68][@ref69][@ref70]\] Another cause of concern is high rate of autism spectrum disorder among the infants prenatally exposed to valproate monotherapy with absolute risk of 4.42% for autism spectrum disorder and 2.5% for childhood autism.\[[@ref71][@ref72]\] A recent review of data also suggests increase in the risk of attention deficit hyperkinetic disorder with antenatal exposure of valproate.\[[@ref73]\] With regard to secretion of valproate in breast milk, it has been shown that valproate is minimally present in breast milk. Piontek *et al.*\[[@ref74]\] evaluated the level of valproate in 6 breast-fed mother-infant pairs and reported that serum valproate levels in the infants ranged from 0.9% to 2.3% of the mother\'s serum level. In another study of 2 infants whose breastfeeding mothers were taking valproate, Wisner and Perel\[[@ref75]\] reported that valproate concentrations in the infants were 1.5% and 6%, respectively. The American Academy of Neurology and American Academy of Pediatrics support breastfeeding if the mother is taking valproate.\[[@ref76][@ref77]\] Carbamazepine {#sec2-4} ------------- Use of carbamazepine during the first trimester of pregnancy has been shown to be associated with the risk of neural tube defects at a rate of about 0.5--1.0%.\[[@ref78][@ref79]\] Infants exposed to carbamazepine prenatally are also at increased risk for craniofacial abnormalities, fingernail hypoplasia, developmental delay, growth retardation, microcephaly, spina bifida, and cardiac abnormalities.\[[@ref47][@ref80]\] Recent data suggest that the risk increases in a dose--dependent pattern with higher risk with doses 400 mg/day.\[[@ref81]\] Transient hepatic toxicity (cholestatic hepatitis and direct hyperbilirubinemia) in neonates exposed to carbamazepine during pregnancy has also been noted.\[[@ref80][@ref82]\] In terms of behavioral and cognitive outcome, studies have shown that carbamazepine exposure during pregnancy and neonatal period does not lead to significant cognitive dysfunction in childhood.\[[@ref83][@ref84]\] The data on serum concentrations of carbamazepine among breastfeeding infants are largely based on assessment of newborns of mothers who were on carbamazepine during the pregnancy. Evidence suggests that in general the concentration of carbamazepine in breast milk is much lower than the maternal serum levels, with concentrations in infants ranging from 6% to 65% of maternal levels.\[[@ref85]\] Studies that have evaluated carbamazepine exposure in nursing infants have reported occasional cases of transient hepatic dysfunction.\[[@ref80][@ref82]\] Both American Academy of Neurology and American Academy of Pediatrics support breastfeeding if the mother is taking carbamazepine.\[[@ref76][@ref77]\] Oxcarbazepine {#sec2-5} ------------- Oxcarbazepine, a congener of carbamazepine has been used for the treatment of bipolar disorders. In a review of data, Eisenschenk\[[@ref86]\] reported that, in the 248 patients identified in the literature as receiving oxcarbazepine during pregnancy, 6 malformations were reported; indicating a malformation risk of 2.4%, which is within the 2--4% malformation rate seen in the general population. It is noteworthy that in 4, out of the 6 pregnancies with congenital malformation, the mothers were also receiving adjunctive antiepileptics. The malformations reported include major cardiac malformation (adjunctive therapy with phenobarbital), ventricular septal defects (1 monotherapy and 1 adjunctive therapy with lamotrigine), facial malformations (cleft soft palate, facial dysmorphism, terminal transverse defect, disproportion of head and trunk, and extrophia vesicae) in 1 case, congenital hydronephrosis (adjunctive therapy with vigabatrin), major urinary tract defect (1 case) and 1 case of spina bifida cystica and clubfoot (adjunctive therapy with valproate and clobazam). Lamotrigine {#sec2-6} ----------- In recent time use of lamotrigine in bipolar disorders has increased. However, most of the data about its safety in pregnancy is available from its use in pregnant females with epilepsy. Newport *et al.*\[[@ref87]\] pooled the data from the available studies and reported 2.6% risk (78/2974) of major fetal anomalies following first trimester exposure to lamotrigine, which is within the range of anomalies among births reported in the general population. The obstetrical outcome information is maintained by the International lamotrigine Pregnancy Registry. Cunnington *et al.*\[[@ref88]\] reported that of the 414 first trimester exposures to lamotrigine monotherapy, about 3% (12 offspring) had major birth defects which are similar to that in general population. However, no distinctive pattern of major birth defects was apparent among the birth defects detected following exposures to lamotrigine monotherapy. They found a higher rate of major birth defects (12.5%) in 88 first trimester exposures to combination of lamotrigine and valproate. Recently, some data have emerged to suggest that exposure to LTG is associated with increase in the risk of oral clefts. Holmes *et al.*\[[@ref89]\] presented the data from North American AED Pregnancy Registry with regard to lamotrigine. Of the 684 infants exposed to lamotrigine, 16 (2.3%) had major malformations. Five infants (7.3/1000) had oral clefts (isolated cleft palate \[3 cases\], isolated cleft lip \[1 case\], and cleft lip and palate \[1 case\]). The rate among the lamotrigine-exposed infants was 10.4-fold higher in comparison to unexposed infants (*n* = 206,224) surveyed at birth at Brigham and Women\'s Hospital in Boston. However, another study based on data from UK Epilepsy and Pregnancy Register, did not confirm this finding. The authors reported data of 1229 pregnancies exposed to lamotrigine as monotherapy, resulting in 1151 live births. Twenty-eight major congenital malformations were reported with no specific pattern; of which only one male infant was born with nonsyndromic cleft lip and palate.\[[@ref90]\] Recent data suggest that the risk increases in a dose dependent pattern with higher risk with doses 300 mg/day.\[[@ref81]\] Studies in women with bipolar disorder treated with lamotrigine during pregnancy suggest lower serum level to dose ratios during pregnancy than during the postpartum period.\[[@ref91]\] Studies also suggest higher clearance level of lamotrigine during pregnancy and suggest the need for dose adjustment.\[[@ref92]\] In terms of neurobehavioral effects a follow-up study of 23 infants, reported no neurobehavioral effects with lamotrigine at 12 months of age.\[[@ref93]\] However, one recent report suggested behavioral outcomes comparable to valproate. The children had reduced nonverbal IQ scores, along with lower scores on motor and sensory measures, lower scores on executive functions, behavioral measures and attentional measures as per the parent-report.\[[@ref94]\] Few case reports and case series reported mean milk/plasma ratios ranging from 0.40 to 0.61 for lamotrigine.\[[@ref95][@ref96][@ref97][@ref98][@ref99]\] One recently published study involving 30 lactating mothers and their infants reported a mean milk/plasma ratio of 41.3% with a range of 5.7--147%. The authors also reported higher lamotrigine concentrations in breast milk 4 h after maternal dose, although this finding was not statistically significant. Compared with maternal plasma concentrations, the plasma concentrations in infants were 18.3%. Based on these findings authors reported infant lamotrigine dose to be 0.51 mg/kg/day, and compared to maternal dose and the relative infant lamotrigine dose was 9.2%. Almost all infants (7 out of 8) were found to have mild thrombocytosis at the time of serum sampling. No other adverse events were observed or reported in the breast-fed infants.\[[@ref100]\] Topiramate {#sec2-7} ---------- Animal studies have demonstrated craniofacial and skeletal abnormalities.\[[@ref101][@ref102]\] Kwarta *et al.*\[[@ref103]\] reported 2 malformations (micrognathia, phimosis) in 29 pregnancies exposed to topiramate monotherapy. Hunt *et al.*\[[@ref104]\] reported pregnancy outcome in patients receiving topiramate based on UK Epilepsy and Pregnancy Register. In the 70 pregnancies exposed to topiramate monotherapy, 3 major malformations were seen; 2 infants had cleft lip and cleft palate and 1 had hypospadias. It was also seen that women who gave birth to neonates with major malformation were receiving relatively higher doses (mean - 400 mg vs. 238 mg) compared to women who gave birth to children without malformation. It was also seen that out of 61 cases exposed to monotherapy and for whom data was available, 6 infants were born at 37 weeks of gestation or less. Further, of the 56 cases exposed to monotherapy and for whom full data on gestational age and birth weight was available, 8 (14.3%) were small for gestational age. However, in women receiving topiramate as part of polypharmacy, 13 major malformations were reported. It was observed that major malformation rates were higher when topiramate was given along with valproate than with other antiepileptics. A large sample study based on the Global Medical Safety database, reported pregnancy outcome of 589 cases. The most common outcome was a live birth, noted in 75.55% of pregnancies. However, this outcome varied based on the diagnosis for which topiramate was used, with highest proportion of live births seen in patients with epilepsy.\[[@ref105]\] The risk of major malformation with topiramate has been reported to be 4.2--9%.\[[@ref105][@ref106]\] Among the major malformations reported cleft lip or palate anomalies, limb, hand, or other skeletal anomalies and respiratory or cardiovascular anomalies were more frequently documented.\[[@ref105]\] Other reports also suggest association of first trimester use of topiramate and oral cleft lip/palate anomalies.\[[@ref107]\] Other abnormalities related with topiramate use include small for gestational age\[[@ref108][@ref109][@ref110]\] and microcephaly.\[[@ref109]\] Gabapentin {#sec2-8} ---------- Animal studies have demonstrated delayed bone ossification, hydronephrosis and increased rates of hydroureter.\[[@ref101]\] No information is available regarding its possible teratogenic effects in humans. Ohman *et al.*\[[@ref111]\] evaluated the outcome of 6 pregnancies in women receiving gabapentin during pregnancy and reported uneventful deliveries with birth to healthy children in 5 out of the 6 pregnancies. In 1 pregnancy, there was a premature delivery at 33 weeks of gestation. In terms of postdelivery complications, mild hypotonia and cyanosis was seen in 1 infant, which started 8 h after delivery. However, the infant was discharged from hospital after 4 days in a completely normal state. One recent study compared the pregnancy related outcome of 223 gabapentin exposed pregnancies with unexposed pregnancies and reported higher rate of preterm birth and low birth weight with gabapentin. Further those neonates who were exposed to gabapentin near the delivery more frequently required neonatal intensive care treatment. Two neonates exposed to gabapentin were also reported to have suffered from poor neonatal adaptation.\[[@ref112]\] With regard to transplacental transfer of gabapentin Ohman *et al.*\[[@ref111]\] reported accumulation of gabapentin with umbilical cord/maternal plasma concentration ratios ranging from 1.3 to 2.1 (mean - 1.7). However, the gabapentin plasma concentrations declined with an estimated half-life of 14 h in the newborns. Studies which have estimated the concentration of gabapentin in milk suggest that mean milk/maternal plasma concentration ratio is 1.0 (range, 0.7--1.3) from 2 weeks to 3 months. Accordingly, the infant dose is estimated to be 0.2--1.3 mg/kg/day, which is about 1.3--3.8% of the dose received by the mother. When the plasma concentrations in the breast-fed infants were estimated, it was reported that the concentration in the infant was about 12% of the mother\'s plasma levels. However, this concentration was not associated with any adverse effects. Atypical antipsychotics {#sec2-9} ----------------------- Atypical antipsychotics are quite frequently evaluated for the treatment of various phases of mood disorders. However, there is relatively little data available with regard to the safety of these agents in pregnancy and lactation. In this section, the data with regard to use of atypical antipsychotics in pregnancy and lactation is reviewed, irrespective of the disorder in which these were evaluated. Olanzapine {#sec2-10} ---------- Animal studies done in rodents did not reveal any evidence of teratogenicity with olanzapine despite the use of doses higher than those used clinically. There are few studies which have evaluated the use of olanzapine during pregnancy. Goldstein *et al.*\[[@ref113]\] reported outcomes of 37 olanzapine-exposed pregnancies ascertained prospectively. Of the 37 pregnancies, 14 were terminated by therapeutic abortions with no abnormalities reported in the fetus. In the rest of the pregnancies (*n* = 23), normal birth without complications occurred in 16 cases; spontaneous abortion occurred in 3; stillbirth in 1; prematurity in 1; postmaturity in 2 cases, with one of new born developing perinatal complications in the form of meconium aspiration after cesarean section; and no major malformation in any case. The rates of complications were less than or comparable to the range of base rates for general population. Additionally, the authors also reported 11 retrospectively identified cases, in which major malformations in the form of dysplastic kidney (1 case) and Down syndrome (1 case) was found. There were 2 spontaneous abortions and 1 fetal death. Perinatal complications were noted in 3 cases and postperinatal complications in 2 cases. Overall, out of 11 cases, no complications were observed in only 1 case. In a review, Gentile\[[@ref114]\] reviewed the data of 248 reported cases on olanzapine maintained by the manufacturer (Eli Lilly) up to December 2006. Among these, spontaneous abortion was reported in 24 cases and perinatal complications in 49 cases. Various malformations which had been recorded include renal malformation (*n* = 5), additional thumb digit (*n* = 2) and one case each of bilateral talipes, spontaneous abortion of severe deformed fetus, pretragus fibrochondroma, clubfoot, anencephaly, absent heart, cleft palate, ventricular septum defect, albino infant, esophageal atresia, myelomeningocele plus hydrocephalus, and absent fingers. However, it was also noted that some of the cases in which malformations were found had also received other concomitant medications. Further, the authors pointed out that the manufacturer concluded that the prevalence of adverse pregnancy outcome did not differ from that found in the general population. In a recent review of data maintained by Eli Lilly, outcome of data of 610 pregnancies exposed to olanzapine was presented. The authors reported normal birth in two-third (65.7%) of cases, premature birth in 9.8%, spontaneous abortion in 9.3% and congenital anomalies in 4.4% of pregnancies and perinatal complications were seen in 8% of pregnancies.\[[@ref115]\] Levinson *et al.*\[[@ref116]\] found 8 live births with no malformations, 1 spontaneous abortion, and one stillbirth. In a study which evaluated the outcome of 79 olanzapine exposed pregnancies, major malformations in the form of craniosynostosis and ureteral reflux (*n* = 1), hand/finger reduction (*n* = 1), ventricular septum defect and upper alimentary tract malformation (*n* = 1) were observed.\[[@ref117]\] In another study involving 60 pregnancies exposed to olanzapine, 1 case of major malformation (midline defects, cleft lip, encephalocele, and aqueductal stenosis) was reported.\[[@ref118]\] Various other case reports and case series have also reported birth of healthy infants without complications despite prenatal exposure to olanzapine.\[[@ref119][@ref120][@ref121][@ref122][@ref123][@ref124][@ref125][@ref126][@ref127][@ref128][@ref129][@ref130][@ref131][@ref132]\] A few case reports have reported defects in the form of atrioventricular canal defect and unilateral clubfoot,\[[@ref133]\] hip dysplasia,\[[@ref134]\] meningocele and ankyloblepharon\[[@ref135]\] and microcephaly and anophthalmos.\[[@ref136]\] In some of these studies, case series and case reports development or worsening of gestational diabetes mellitus was also noted.\[[@ref125][@ref126][@ref127]\] Perinatal syndrome reported with use of olanzapine in pregnancy includes preterm delivery, low birth weight, hypotonia, neonatal respiratory complications, neonatal cardiovascular complications,\[[@ref129]\] Erb\'s palsy, jaundice\[[@ref128]\] and high birth weight/large for gestational age.\[[@ref128][@ref129]\] With respect to the postnatal long-term effects, Gati *et al.*\[[@ref137]\] did not find any postnatal behavioral sequelae in children up to the age of 6--10 years. Few studies have evaluated the excretion of olanzapine in breast milk. The relative dose in infant has been reported to be in the range of 0.66--1.19%.\[[@ref138][@ref139]\] Data from about 40 cases are available with respect to olanzapine use during breast feeding. Goldstein *et al.*\[[@ref140]\] reported 26 cases in which breast feeding was continued for 1--8 months. Four infants developed adverse reactions in the form of jaundice and sedation (1 case), shaking, poor sucking and lethargy (1 case), protruding tongue (1 case) and diaper rash, diarrhea, and sleep disorder (1 case). Kirchheiner *et al.*\[[@ref120]\] reported temporary motor delay in a case whose mother took olanzapine 10 mg/day during the lactation. However, other case reports and case series have not reported any untoward effects on the infant with continuation of olanzapine in the dose range of 2.5--20 mg/day during breast feeding.\[[@ref128][@ref138][@ref141][@ref142]\] In the recently published study, data were available for 102 newborns/infants exposed to olanzapine through breast milk. Adverse outcome in the neonate or infant were reported in 15.6%, with commonly reported adverse events in the form of sedation (3.9%), irritability (2%), tremors (2%) and insomnia in 2% of neonates/infants.\[[@ref115]\] Studies that have followed up children exposed to olanzapine through breast milk at 1--2 years of age, report no increase in adverse outcomes when compared to control group.\[[@ref143]\] Risperidone {#sec2-11} ----------- Animal studies in rats have shown increased incidence of pup deaths and stillbirth with use of risperidone during pregnancy.\[[@ref101]\] Rosengarten and Quartermain\[[@ref144]\] reported impaired learning and disrupted short-term retention in adulthood with use of risperidone in dam during pregnancy. In their study of 49 risperidone exposed pregnancies in humans McKenna *et al.*\[[@ref118]\] did not report a single case of major malformations. Similarly, many studies have reported no major malformations with use of risperidone.\[[@ref145][@ref146][@ref147][@ref148][@ref149][@ref150]\] However, there are a few case reports of agenesis of corpus callosum,\[[@ref101]\] and spontaneous abortions.\[[@ref116]\] Reis and Källén\[[@ref117]\] reported 1 case of major malformation (anal atresia along with pulmonary malformation) in 51 risperidone exposed pregnancies. The postmarketing surveillance data of 713 pregnancies (prospective data for 516 and retrospective data for 197 pregnancies) exposed to risperidone was reported. Majority of the adverse pregnancy and fetal/neonatal outcomes were reported for pregnancies for which retrospective data was available. Among the prospectively reported, out of the 68 pregnancies with known outcome, organ malformations were observed in 3.8% and spontaneous abortions occurred in 16.9% pregnancies. When compared to the general population, the rates were comparable.\[[@ref151]\] Of the retrospectively reported outcome major organ malformations were reported in 12 pregnancies. Major malformations reported included cleft lip/palate (*n* = 2), and one case each of esophageal atresia along with ear pinna hypoplasia and slight facial dysmorphia, Ivemark syndrome, Moyamoya disease, ventricular cyst in the brain, patent foramen ovale, hypoplastic left heart, dilated cardiomyopathy, right auricular achondroplasia, mild talipes equinovarus, gastroschisis, and Pierre-Robin syndrome. However, it is important to remember that in some cases in which major malformations were seen, the mothers also received other concomitant medications.\[[@ref151]\] In terms of neonatal outcome, McKenna *et al.*\[[@ref118]\] concluded that there was no difference in the prevalence rate of poor pregnancy outcome and perinatal complications between the risperidone exposed group and a control group exposed to nonteratogens. In the postmarketing surveillance study,\[[@ref151]\] perinatal syndrome (in the form of tremor, jitteriness, irritability, feeding problems) was reported in 37 pregnancies, of which 21 cases involved behavioral or motor disorders. Other adverse pregnancy outcomes reported with use of risperidone include oligohydraminos,\[[@ref150]\] small for date,\[[@ref152]\] and gestational diabetes mellitus.\[[@ref117]\] A case report of neuroleptic malignant syndrome in a pregnant women receiving risperidone has also been documented.\[[@ref153]\] With regard to use of risperidone during lactation, studies suggest that relatively low infant dose (0.84--4.7%) of the weight adjusted maternal dose\[[@ref154][@ref155]\] and an additional 3.46% of its metabolite are transferred to infant.\[[@ref155]\] The data does not suggest any untoward neurodevelopmental problems with risperidone.\[[@ref150][@ref155][@ref156]\] Quetiapine {#sec2-12} ---------- Delay in skeletal ossifications, reduced fetal weight, and increased fetal and pup deaths have been reported with use of quetiapine in pregnancy in animal models.\[[@ref101]\] In human studies, quetiapine has been shown to have the least placental passage (23.8%) compared to both first generation antipsychotics (haloperidol) and other second generation antipsychotics (risperidone and olanzapine). Most of the human studies have not reported any major malformation or neonatal problems with use of quetiapine in pregnancy.\[[@ref157][@ref158][@ref159][@ref160][@ref161][@ref162][@ref163][@ref164][@ref165][@ref166][@ref167][@ref168]\] McKenna *et al.*,\[[@ref118]\] reported on the data maintained by the manufacturer till March 2005. A total of 446 pregnancies were exposed to quetiapine. In terms of congenital malformation, out of the 151 pregnancies for which outcome was reported, 8 pregnancies had congenital malformations; with no commonality between the malformations seen. It is important to note that concurrent medications were used in 7 of the 8 cases with congenital anomalies. In a postmarketing surveillance study, out of the 6 cases, spontaneous abortion was reported in 2 cases.\[[@ref157]\] McKenna *et al.*\[[@ref118]\] also reported the outcome of 36 pregnancies exposed to quetiapine. Although the authors did not report any specific congenital anomalies associated with quetiapine, they concluded that compared to a control group of women exposed to nonteratogenic agents, quetiapine was not associated with an increase of teratogenic risk. With regard to excretion of quetiapine in breast milk, studies suggest relatively low dose (0.09--0.43%) of the weight adjusted maternal dose in infant\[[@ref161][@ref169]\] and the quetiapine concentration in infant\'s plasma is estimated to be about 6% of the maternal drug concentration.\[[@ref169]\] Amisulpiride {#sec2-13} ------------ Data from animal studies on mice and rabbits show lack of teratogenic effect of amisulpride with doses up to 4 times the maximum recommended human dose.\[[@ref114]\] However, data on the effect of amisulpride on human pregnancies are lacking. Ziprasidone {#sec2-14} ----------- Use of ziprasidone in animals suggests its association with developmental delays, possible teratogenic effects (cardiac, renal, and skeletal), and increased still births.\[[@ref101]\] One case report presented the association of ziprasidone with cleft palate,\[[@ref170]\] whereas another case report reported on adverse outcome of use of ziprasidone along with citalopram during pregnancy and lactation.\[[@ref171]\] Aripiprazole {#sec2-15} ------------ In animal studies aripiprazole has shown developmental toxicity, including possible teratogenic effects in rats and rabbits. The main effects were delayed skeletal ossification and decreased fetal weight with 3--10 times the maximum recommended human dose.\[[@ref172]\] Only 13 case reports and 1 small case series (3 cases) have discussed the outcome of aripiprazole exposed human pregnancies.\[[@ref173][@ref174][@ref175][@ref176][@ref177][@ref178][@ref179][@ref180][@ref181][@ref182][@ref183][@ref184]\] In all cases except one, no teratogenic effects were reported. However it is important to note that in 9 out of the 16 pregnancies aripiprazole was started after first trimester of gestation. In one case minimal hip dysplasia was documented.\[[@ref184]\] In terms of neonatal and obstetrical outcome, 1 case required caesarean section due to development of unexplained fetal tachycardia.\[[@ref174]\] Sparse data are available with regard to use of aripiprazole during lactation. Animal studies suggest that aripiprazole is excreted in milk. One case report suggests failure of lactation in women treated with aripiprazole in pregnancy.\[[@ref173]\] Another case report suggested lack of aripiprazole secretion in breast milk.\[[@ref178]\] Clozapine {#sec2-16} --------- Clozapine is the only antipsychotic which belongs to category B of FDA classification. Animal studies in rats and rabbits reveal no harm to the fetus with doses of approximately 2--4 times higher than the human dose (clozapine prescribing information).\[[@ref114]\] Data with regard to use of clozapine in human pregnancy is available only in the form of case reports/series and occasional review. Waldman and Safferman\[[@ref185]\] reported at least 15 normal births following maternal exposure to clozapine in pregnancy. Many others also suggest no definitive association between maternal exposure and congenital anomalies in humans.\[[@ref186][@ref187][@ref188][@ref189][@ref190][@ref191][@ref192]\] A study which reported outcome of 61 pregnancies exposed to clozapine revealed 5 congenital malformations and 5 perinatal syndromes.\[[@ref193]\] Various other associations reported with maternal exposure are decreased variability of fetal heart rate,\[[@ref194][@ref195]\] delayed peristalsis,\[[@ref196]\] delayed speech acquisition,\[[@ref197]\] floppy infant syndrome,\[[@ref188]\] gastroesopahgeal reflux disease,\[[@ref198]\] intrauterine growth retardation with oligohydramnios and intrauterine death,\[[@ref199]\] neonatal seizures\[[@ref189]\] and new onset or worsening of gestational diabetes mellitus with shoulder dystocia.\[[@ref185][@ref187]\] However, many of these findings have been complicated by the concomitant use of other drugs, malnutrition or family history of diabetes mellitus. Clozapine overdose during pregnancy has also been shown to lead to fatal poisoning in the newborn\[[@ref200]\] and to be associated with absent fetal heart rate variability and delayed peristalsis in the newborn.\[[@ref201]\] As with other antipsychotics, data with regard to use of clozapine during lactation is sparse. In one case series, 2 out of the 4 infants breast-fed by mothers receiving clozapine, developed adverse events. In a case report, delayed speech acquisition was reported in the new born whose mother received clozapine during pregnancy and lactation. Benzodiazepines and pregnancy {#sec2-17} ----------------------------- Benzodiazepines are used commonly in subjects with bipolar disorders as adjunctive medications for mood stabilization, agitation, and sleep problems. All benzodiazepine compounds diffuse readily across the placenta to the fetus and are secreted in breast milk. The amount excreted depends on the oral bioavailability, plasma protein binding, maternal blood concentrations, ionization, molecular weight, half-life, degree of lipophilicity and pharmacokinetics of each benzodiazepine.\[[@ref202]\] The use of benzodiazepines in pregnancy has been reviewed in detail by Iqbal *et al.*\[[@ref202]\] The most important issues associated with use of benzodiazepines in pregnancy shall be discussed here. The risk of malformation is highest if the fetal exposure occurs between 2 and 8 weeks of pregnancy. Further if benzodiazepines are given at or near term, they may cause fetal dependence and eventual withdrawal symptoms.\[[@ref202]\] Diazepam {#sec2-18} -------- In a review of 599 oral clefts it was shown that use of anxiolytics, mostly diazepam, during the first trimester of pregnancy was associated with development of oral clefts.\[[@ref203]\] However, this has not been a consistent finding in the later studies, with some reporting similar association,\[[@ref204][@ref205][@ref206]\] while others not finding the same.\[[@ref207][@ref208][@ref209][@ref210]\] There are case reports of other malformations, however, some of these have been inconclusive because of use of other medications along with diazepam.\[[@ref202]\] Use of high doses of diazepam (usually more than 30--40 mg/day) during labor has been associated with withdrawal symptoms starting within a few days to 3 weeks and lasting up to several months in neonates. The withdrawal symptoms are characterized by hypertonia, hyperreflexia, restlessness, irritability, abnormal sleep patterns, inconsolable crying, tremors or jerking of the extremities, bradycardia, cyanosis, suckling difficulties, apnea, risk of aspiration of feeds, diarrhea and vomiting, and growth retardation. Other reports suggest that use of high doses may also be associated with "floppy infant syndrome" characterized by withdrawal symptoms, hypothermia, lethargy, respiratory problems, and feeding difficulties.\[[@ref202]\] Use of diazepam during late pregnancy and labor has also been associated with development of prolonged hyperbilirubinemia of the newborn and potentially to kernicterus. This has been linked to the preservative (sodium benzoate) in the diazepam formulation, which competes with diazepam for plasma protein binding.\[[@ref202]\] Although occasional reports have associated the therapeutic use of diazepam with congenital malformation, the bulk of the evidence indicates that the use of diazepam during gestation has no adverse effects on the child\'s development if used in low doses.\[[@ref202]\] However, it is to be remembered that when it is used near term, the dosage should be tapered off over weeks to avoid development of neonatal withdrawal and floppy infant syndrome. Low dose use of diazepam either just before the delivery or during postpartum by the mother is associated with sedation in the new born. In general, low concentration of diazepam has been found in breast milk; however, the concentration varies with maternal dose. Use of higher doses of diazepam during breast feeding is associated with lethargy and weight loss in the neonate, which improves after stopping breast feeding. Hence, while using diazepam during pregnancy or labor the treating doctors should be aware of the side effects and must take appropriate measures.\[[@ref202]\] Clonazepam {#sec2-19} ---------- Use of clonazepam in pregnancy has been shown to be associated with apnea, bilateral inguinal hernia, congenital heart disease, cyanosis, hip dislocation, hypotonia lethargy, paralytic ileus of the small bowel, undescended testicle, uteropelvic junction obstruction, and ventral septal defect.\[[@ref202]\] However, it is important to note that in most cases clonazepam was used along with other antiepileptics like phenytoin and barbiturates. Use of clonazepam during lactation has also shown to be associated with apnea, CNS depression, cyanosis, excessive periodic breathing and hypotonia. Hence, clonazepam should be used during pregnancy and lactation only when the clinical benefit to the mother justifies the risks to the fetus and newborn. If used, the fetus and the newborn should be closely monitored.\[[@ref202]\] Lorazepam {#sec2-20} --------- Use of lorazepam during pregnancy has been associated with anal atresia and neonatal withdrawal symptoms. The latter can be severe, because of the short half-life of lorazepam, and are characterized by low Apgar scores, depressed respiration, hypothermia, poor suckling and jaundice. Thus, injectable lorazepam should be avoided during pregnancy as far as possible.\[[@ref202]\] Oral lorazepam should be used during pregnancy only in life-threatening situations or in cases of severe disease for which other safer drugs cannot be used or are ineffective. In breast milk, lorazepam is secreted in low quantity and is considered to be relatively safe.\[[@ref202]\] Alprazolam {#sec2-21} ---------- Use of alprazolam in pregnancy has not been shown to be associated with increased risk of major malformations. However, it has been linked with malformations like ankle inversion, cat\'s eye with Pierre-Robin syndrome, cleft lip, congenital hip dislocation, cryptorchidism, Down\'s syndrome, fused lacrimal duct, hypospadias, inguinal hernia, lipomeningocele, microcephaly, patent ductus arteriosus, pyloric stenosis, strabismus, tracheoesophageal fistula, umbilical hernia and neonatal withdrawal syndrome. Thus, it should preferably not be used in first trimester and during lactation.\[[@ref202]\] MANAGEMENT OF BIPOLAR DISORDERS IN PREGNANCY AND LACTATION {#sec1-7} ========================================================== Clinicians handling the bipolar disorders are usually faced with the following situations: A patient of bipolar disorder on medications wanting to conceiveA patient of bipolar disorder already conceived (on/not on medications), but the symptoms are under-controlA patient of bipolar disorder already conceived (on/not on medications), but the symptoms are present/experiencing relpaseFirst episode mania during the pregnancyFirst episode mania during the early postpartum periodContinuation of medications during lactation. There is no single answer to all the above situations. All the decisions about continuation or initiation of treatment during pregnancy in subjects with known bipolar disorders must take into account: (i) The highly variable, but often poorly quantified risks of fetal exposure to drugs (ii) the substantial risks to the patient, fetus, and family from untreated illness in the mother; and (iii) high risk of relapse associated with discontinuation of maintenance treatment, particularly if it is done abruptly. Each of these risks should be discussed in detail with the patient and her spouse and other close family members. If a woman with bipolar disorder, who is on medication, expresses her wish to conceive, the clinician should take into consideration the illness history, acceptability and estimated safety of specific clinical interventions, which may be pharmacologic or nonpharmacologic. Specific considerations include the frequency and severity of previous episodes, past and current levels of functioning or impairment, past and recent duration of clinical stability with and without medication, the nature of prodromal symptoms that indicate an impending relapse, and average time to recovery following re-introduction of treatment. In the assessment process, it is also important to assess the usefulness of previous medication trials in terms of responses rate, adverse effects and effect of discontinuation of treatment.\[[@ref15]\] In addition to assessing the illness and the effectiveness of current and past treatments, clinicians should also take into consideration other risk factors (e.g., poor nutrition, smoking, alcohol use etc.), which can contribute to poor perinatal outcome. Emphasis should also be on promotion of healthy behaviors like adherence to a prenatal vitamin regimen and regular prenatal checkups and healthy diet.\[[@ref211]\] If a woman with bipolar disorder plans to conceive, following options can be considered: Discontinue the mood stabilizer prior to conception, continue treatment until pregnancy is verified or continue treatment throughout the pregnancy. All these decisions would depend on the severity of illness and past treatment response. Discontinuation of mood stabilizer during the pregnancy phase may be considered if there is past history of one or infrequent episodes with long period of remission. If such an attempt is made it is important to remember that the pharmacological agents should be tapered off slowly and the women should be closely monitored for conception and relapse of symptoms. An alternative strategy is to continue treatment until pregnancy is verified, and then gradually taper off the mood stabilizer. Uteroplacental circulation is not established until approximately 2 weeks postconception and the early risk of fetal exposure is minimal. The advantages of this strategy are that it minimizes fetal exposure to drugs and extends the protective treatment up to the time of conception.\[[@ref15]\] However, it is important to remember that this strategy may lead to relatively abrupt treatment discontinuation, thereby placing the patient at increased risk for relapse.\[[@ref13][@ref19][@ref29]\] In ideal situation, the patient should discuss about her plan of pregnancy and this should be when the patient is euthymic. Based on the patient\'s history, decision should be taken about continuation of medication during the period before conception and during the first trimester. If the patient is clinically stable an attempt to discontinue the mood stabilizer prior to conception should be taken. If there is recurrence of symptoms during the discontinuation trial, then a difficult choice to continue taking medication during pregnancy has to be made.\[[@ref211]\] If on the basis of history the illness is considered to be severe (chances of relapse are high without medication), then the psychiatrists should discuss with the patient and the spouse about continuation of mood stabilizer during the conception period also. In some cases, mood stabilizers could be continued till the confirmation of conception and then these could be withdrawn cautiously, but close monitoring for relapse should be done.\[[@ref211]\] For women with severe forms of bipolar disorder, for example, multiple severe episodes and especially with history of psychotic symptoms and suicidal attempts, maintenance treatment with a mood stabilizer before and during pregnancy may be the safest option. In such a situation, lowest effective dose of a medication must be used and medications which have the least teratogenic potential should be selected. However, in certain cases of refractory illness, in which the patient has responded to a newer agent for which reproductive safety data are not available or is sparse, the clinician should consider to continue the same agent after explaining the pros and cons of continuing the same medication to the patient and family.\[[@ref15]\] If the patient is on lithium, valproate or carbamazepine before conception, the risk should be discussed with patient and spouse and wherever possible these should be stopped during the first trimester or be replaced by other safer options like a typical antipsychotic. It is important to remember that typical antipsychotics increase prolactin levels and thereby disrupt the menstrual cyclicity and hence adversely affect fertility;\[[@ref211]\] so whenever possible, an agent with less effect on prolactin and better teratogenicity safety profile should be preferred. For women who tolerate discontinuation of maintenance treatment, the decision when to restart the treatment depends on the clinician and the patient. Some patients and clinicians may prefer to wait for the initial signs and symptoms to appear before restarting medication, while others may prefer to limit risk of a major recurrence by restarting treatment after the first trimester of pregnancy. If the treatment has to be restarted, the decision about the mood stabilizer should take into consideration the past history of response and the risk associated with a particular agent during the second and third trimester. It is generally considered that if a woman has done well on a particular mood stabilizer then changing the mood stabilizer for avoiding potential risk to offspring may risk the woman stability and may not be a right decision. Hence, continuation of the same mood stabilizer with informed consent of the patient and spouse should be preferred. If the recurrence of symptoms during pregnancy is in the form of mild to moderate depression, psychotherapeutic interventions may be tried before considering the mood stabilizer depending on the patient\'s motivation for such therapy and past response. However, if the depression is severe, antidepressants (a selective serotonin reuptake inhibitor \[but not paroxetine\]) or electroconvulsive therapy can be considered.\[[@ref15]\] Unplanned pregnancy {#sec2-22} ------------------- Unfortunately, about 50% of pregnancies in women with bipolar disorders are unplanned. In many instances, pregnancy is detected during or after the highest risk period for some agents has passed. Discontinuation of the medication after the risk period has passed may place the woman at risk without conferring any appreciable benefit. The variables which must be taken into account while finalizing the treatment plan include the clinical stability of the patient, duration of pregnancy, psychotropic agent which the patient is taking and treatment preferences of the patient. If the patient has not completed the first trimester and reports with confirmed pregnancy, the pros and cons about the medication continuation and abrupt stoppage of medication have to be discussed. If the patient is on anticonvulsants, then a high dose of folic acid should be prescribed for the woman. If it is not possible to stop the medication then attempt should be made to reduce the dose to minimum. If the patient has completed the first trimester of pregnancy, then the patient and the spouse should be explained about the pros and cons of continuation of pregnancy, depending on the agent, which the patient was taking. If the patient had been on polypharmacy, then the additional risk should be emphasized. If the decision to continue the pregnancy is made, the decision about the mood stabilizer should take past history of response and the risk associated with a particular agent during the second and third trimester. Continuation of the same mood stabilizer with informed consent of the patient and spouse should be preferred. However, some authors suggest that if the woman is on valproate and if there is no history of nonresponse to lithium, the switch to lithium should be considered.\[[@ref212]\] Monitoring while continuation of mood stabilizers during pregnancy {#sec2-23} ------------------------------------------------------------------ If mood stabilizers are continued during pregnancy, prenatal screening for congenital malformation with a high resolution ultrasound and fetal echocardiography is recommended around 16--18 weeks of gestation to screen for cardiac anomalies. The possibility of fetal neural tube defects should be evaluated with maternal serum alpha fetoprotein and ultrasonography. In addition, use of folic acid is recommended prior to conception and during the first trimester for women receiving anticonvulsants, although it is unknown whether supplemental folic acid can reduce the risk of neural tube defects in the setting of anticonvulsant exposure.\[[@ref49][@ref213]\] For patients who are continued on carbamazepine or oxcarbazepine, Vitamin K supplementation (10 mg/day orally) during the last month of pregnancy is recommended. The new born should also receive 1 mg of Vitamin K intravenously or intramuscularly on day 1 after delivery.\[[@ref76]\] Monitoring while continuation of mood stabilizers near the term/labor {#sec2-24} --------------------------------------------------------------------- Some experts suggest that the dose of lithium should be reduced at the onset of labor to avoid toxicity resulting from the rapid reduction of vascular volume at delivery.\[[@ref214]\] Close monitoring of symptoms and serum lithium levels are required to avoid relapse or toxicity during delivery and the immediate postpartum period.\[[@ref13][@ref29]\] Treatment during postpartum {#sec2-25} --------------------------- Puerperium is the period of heightened risk of relapse for subjects with bipolar disorders. Hence, restarting of mood stabilizer during immediate postpartum should be considered strongly in subjects with high risk of relapse, as data show that use of lithium as a prophylactic agent in the postpartum period reduces the rate of relapse from nearly 50% to \<10%.\[[@ref215][@ref216]\] First episode during pregnancy and puerperium {#sec2-26} --------------------------------------------- For women who develop first episode of mania during pregnancy, the psychiatrist is called upon to decide about which medication to start. In such a scenario, the decision about the mood stabilizer is a tricky one and should take into consideration the severity of symptoms, risk to the mother and the fetus. If the patient has not completed first trimester of pregnancy, typical high potency antipsychotic or atypical antipsychotic like clozapine, olanzapine or risperidone should be tried before considering lithium, valproate or carbamazepine. If the women has completed first trimester, then also antipsychotic should be preferred over lithium (because of risk associated during labor), valproate (long-term cognitive side effects) and carbamazepine. If one of these 3 agents has to be used during the second or third trimester, lithium should be preferred over carbamazepine and valproate. The patient and the spouse should be explained about the risk with such medications. If one has to use benzodiazepines, they should be used for shortest possible duration in minimal dose and should preferably be tapered off slowly with monitoring of fetus. Breast feeding with mood stabilizers {#sec2-27} ------------------------------------ Whether to allow breast feeding while continuing mood stabilizers is a difficult decision. Breast feeding is very important for development of emotional bond and attachment between the mother and the infant.\[[@ref22][@ref23]\] Further, it confers many physical health benefits to the mother and the newborn. Hence, risk benefit analysis should take into consideration the physiological and psychological benefits of breastfeeding, wishes of the mother, risk of infant exposure to the medication, and the possibility that a severely ill mother may forego treatment rather than give up breastfeeding.\[[@ref25]\] While continuing breast feeding with mood stabilizers, the infant should be clinically monitored to minimize the risk. Before starting breast feeding, the infant should be evaluated by a pediatrician for baseline behavior, sleep, feeding, and alertness. Parents should be alerted to the side effect profile of medications, and regular clinical monitoring should be done by the pediatrician to ensure normal development. It is to be remembered that metabolism and elimination are more efficient in older infants, who generally sleep for longer durations, permitting dosing of the mother just after nursing and before the baby\'s longest sleep interval. A close liaison must be kept with the pediatrician who can be educated about the potential side effects of medication exposure and interactions with other medications typically prescribed to infants (e.g., antibiotics, nonsteroidal antiinflammatory agents, and acetaminophen).\[[@ref25]\] While using a mood stabilizer, the clinician should titrate the dose to the minimum effective dose. However, in such an attempt clinician should not end up in using ineffective dose and exposing the neonate to the medication unnecessarily. If any medication is used on as and when required basis then short-acting agents should be preferred. Further, it is best to use medications in which the parent compound does not metabolize into several generations of active compounds.\[[@ref25]\] According to the American Academy of Pediatrics, breastfeeding should be undertaken with caution by women undergoing lithium treatment. The breast-fed infant should be monitored for serum lithium levels, electrocardiogram and complete blood counts. With regard to valproate and carbamazepine both American Academy of Neurology and American Academy of Pediatrics support breastfeeding if the mother is taking valproate,\[[@ref76][@ref77]\] but the liver function tests and blood counts of the newborn need to be monitored. With regard to lamotrigine, the emerging data suggest that it may be relatively safe during breast feeding. It should be used during lactation when other safer options are not available. Data for other anticonvulsants is preliminary. Data with regard to atypical antipsychotics are also preliminary and inconclusive. CONCLUSION {#sec1-8} ========== From the literature, it is evident that the safety of mood stabilizers in pregnancy is still unresolved. The decision to prescribe them during pregnancy should be taken in light of severity of mental disease and drugs should be prescribed only when the potential risk to the fetus from exposure to medication is outweighed by the risk of untreated maternal disorder. The choice of drug should depend on the balance between safety and efficacy profile. Whenever patient is on psychotropics, close and intensive monitoring should be done. An algorithm of treatment options should take into consideration the severity of illness and the individual patient\'s unique treatment needs. **Source of Support:** Nil **Conflict of Interest:** None declared | Mid | [
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// moment.js language configuration // language : Bahasa Malaysia (ms-MY) // author : Weldan Jamili : https://github.com/weldan (function (factory) { if (typeof define === 'function' && define.amd) { define(['moment'], factory); // AMD } else if (typeof exports === 'object') { module.exports = factory(require('../moment')); // Node } else { factory(window.moment); // Browser global } }(function (moment) { return moment.lang('ms-my', { months : "Januari_Februari_Mac_April_Mei_Jun_Julai_Ogos_September_Oktober_November_Disember".split("_"), monthsShort : "Jan_Feb_Mac_Apr_Mei_Jun_Jul_Ogs_Sep_Okt_Nov_Dis".split("_"), weekdays : "Ahad_Isnin_Selasa_Rabu_Khamis_Jumaat_Sabtu".split("_"), weekdaysShort : "Ahd_Isn_Sel_Rab_Kha_Jum_Sab".split("_"), weekdaysMin : "Ah_Is_Sl_Rb_Km_Jm_Sb".split("_"), longDateFormat : { LT : "HH.mm", L : "DD/MM/YYYY", LL : "D MMMM YYYY", LLL : "D MMMM YYYY [pukul] LT", LLLL : "dddd, D MMMM YYYY [pukul] LT" }, meridiem : function (hours, minutes, isLower) { if (hours < 11) { return 'pagi'; } else if (hours < 15) { return 'tengahari'; } else if (hours < 19) { return 'petang'; } else { return 'malam'; } }, calendar : { sameDay : '[Hari ini pukul] LT', nextDay : '[Esok pukul] LT', nextWeek : 'dddd [pukul] LT', lastDay : '[Kelmarin pukul] LT', lastWeek : 'dddd [lepas pukul] LT', sameElse : 'L' }, relativeTime : { future : "dalam %s", past : "%s yang lepas", s : "beberapa saat", m : "seminit", mm : "%d minit", h : "sejam", hh : "%d jam", d : "sehari", dd : "%d hari", M : "sebulan", MM : "%d bulan", y : "setahun", yy : "%d tahun" }, week : { dow : 1, // Monday is the first day of the week. doy : 7 // The week that contains Jan 1st is the first week of the year. } }); })); | Low | [
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A life-size replica of the Bible's Noah's Ark -- larger than a football field and holding 5,000 people -- will eventually dock in Southern California, the director of a Pasadena-based Christian fou... LOS ANGELES (CNS) - A life-size replica of the Bible's Noah's Ark - larger than a football field and holding 5,000 people - will eventually dock in Southern California, the director of a Pasadena-based Christian foundation said Wednesday. Dutch carpenter Johan Huibers built the massive, five-floor ship four years ago in the Netherlands as a religious attraction and, in partnership with the Ark of Noah Foundation, is raising money to fund a world voyage. The 410-foot, 2,500-ton facsimile is expected to travel by barge this summer 5,000 miles across the Atlantic Ocean, from the Netherlands to Brazil, stopping afterward at ports in Long Beach, San Diego, San Francisco and Seattle, according to Herald A.M.A. Janssen, the director of the foundation. "We cannot promise how long it will take, but we will come to California," Janssen said. "You get the feeling that a lot of people and animals can fit on this boat." Huibers' ark was designed as an interactive museum and event center, based on the Bible story of a man who is instructed by God to build a vessel which saves his family and pairs of all the world's animals from a catastrophic, months-long flood. In line with the story, the ark includes life-size models of giraffes, elephants, lions, crocodiles and zebras - two-by-two. "We want to eventually build Ark of Hope Centers in inland areas, places to provide outreach to those who need it," Janssen said. "We believe in doing good and now we need to put it into practice." The ship, also known as "Johan's Ark," will travel to Fortaleza, Brazil, during the 2016 Olympic Games and Rio de Janeiro for the Paralympic summer games, Janssen said. From there, organizers plan to visit various harbors around the world on its journey to North America. Janssen said it was too early to say when the ship might arrive on the West Coast. | Mid | [
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Mikhail Pervukhin Mikhail Georgievich Pervukhin (; 14 October 1904 – 22 July 1978) was a Soviet official during the Stalin Era and Khrushchev Era. He served as a First Deputy Chairman of the Council of Ministers, literally First Vice-Premier of the Soviet Union, from 1955 to 1957. Early life and career He was born on 14 October 1904 in the village of Yuryuzansky Zavod, Ufa governorate, Russian Empire to a Russian working-class family. Pervukhin became a member of the Russian Communist Party in 1919. In August to September 1919 Pervukhin was a member of the Zlatoust city commission on the nationalisation of property belonging to the bourgeoisie. He began working for the Zlatoust newspaper Borba in October 1919, and worked there until February 1920 when he started to attend after-school lessons. He fought alongside the Bolsheviks in the Russian Civil War in the South Urals. From October to November 1920 Pervukhin was a member of the Bolshevik squad quelling the anti-Bolshevik uprising in Chrysostom. From January 1921 to mid-autumn Pervukhin worked as the Executive Secretary of the Proletarian Thought. He was a member of the Bureau of the Zlatoust Komsomol District Committee, and later became the head of its Department for Political Education in April 1922. Later that year he became the Zlatoust Komsomol District Committee's Deputy Secretary, and was its Technical Secretary from April to August 1922. The Metal Workers' Union of the Zlatoust District Committee ordered Pervukhin to Moscow in the late summer of 1922 to study. He graduated in 1929 from the Electrical Department of the Plekhanov Moscow Institute of the National Economy with a degree in electrical engineering. Following his graduation, Pervukhin started work at Mosenergo, the Moscow electric power company. In May 1936 he became the Director of the Kashirskaya Power Plant. From June to September 1937, Pervukhin worked as Mosenergo's Chief Engineer, and later that year became its acting head. Pervukhin started to work for the People's Commissariat for Heavy Industry in late 1937, and was later appointed to the post of Deputy People's Commissar for Heavy Industry in 1938, and First Deputy People's Commissars for Heavy Industry in June 1937 when Lazar Kaganovich was People's Commissar for Heavy Industry. During the Great Purge Pervukhin was promoted to Deputy Head of the Moscow Electrical Power Administration Bureau, and then its head. On 24 January 1939 Pervukin was promoted to the newly established post of People's Commissar for Electric Power Stations and was given a seat in the Communist Party's Central Committee at the 18th Party Congress. World War II and the Stalin Era From 1940 to 1942, during World War II (known as the Great Patriotic War in Russia), Pervukhin served as a Deputy Chairman of the Council of People's Commissars (literally, Soviet Deputy Premier), and from 1943 until 1950 he served as the Minister of Chemical Industry. Pervukhin, alongside Boris Vannikov, was Vyacheslav Molotov's deputy on the State Defense Committee's commission responsible for the development of the Soviet atomic bomb since 1943. Along with Molotov, Pervukhin was in charge of the commission's uranium project. When Joseph Stalin signed the State Defense Committee Resolution No. 9887, he established a Special Committee with emergency powers. The Committee's main duty was to oversee the work of those who contributed to the development of the atomic bomb. Stalin personally picked the members of the committee; Pervukhin was one of nine members. Pervukhin was the Deputy Chairman under Vannikov's Chairmanship of the First Main Directorate of the Council of People's Commissars, the executive branch of the special committee. He also served as Chairman of the State Commission on the RDS-1 testing at the Semipalatinsk nuclear test site. In 1950 Pervuhkin was once again appointed Deputy Chairman of the Council of Ministers and in 1952, at the 19th Party Congress, he was elected a member of the Presidium, the renamed Politburo. At the 35th anniversary of the October Revolution in 1952, Pervukhin delivered the main speech at the Moscow Kremlin commemoration. If Stalin was absent or could not carry out his duty as Chairman of the Council of Ministers, government meetings would be chaired, in turn by Pervukhin, Lavrentiy Beria, or Maksim Saburov. Post-Stalin era As part of the changes in the post-Stalin era, a collective leadership was established with both Georgy Malenkov and Nikita Khrushchev vying for control. At the very beginning, Pervukhin, along with Georgy Zhukov and Saburov, actively participated in foreign policy decision-making. Malenkov, the Chairman of the Council of Ministers, appointed Pervukhin the post of First Deputy Chairman of the Council of Ministers on 28 February 1955. From 5 March 1953 to 17 April 1954, Pervukhin was the Minister of Power and Electrical Industry, and from December 1953 to February 1955, he was Chairman of the Bureau for Energy, Chemical and Forest Industries of the Council of Ministers. On 25 December 1956 Nikolai Bulganin, the Chairman of the Council of Ministers, removed Saburov from his post as Chairman of the State Economic Commission on Current Planning and replaced him with Pervukhin. who held the post until 10 May 1957. Pervukhin opposed Khrushchev's Regional Economic Soviet reform, whose main aim was to reduce the powers and functions of the central ministries. He told Khrushchev and other Presidium members that this reform would weaken branch administration, and that the centralisation and specialisation which had been the system's cornerstone would be lost. Instead, Pervukhin proposed to reduce the numbers of central ministries and establish territorial commissions to provide "horizontal cooperation". Later, in 1957, Pervukhin joined the Anti-Party Group in a bid to remove Khrushchev as First Secretary. Ambassadorship to East Germany Following the failed bid to remove Khrushchev, Pervukhin was demoted to a non-voting member of the Presidium, and became the Soviet Union's ambassador to East Germany in 1958. As ambassador, Pervukhin observed that "the presence in Berlin of an open and essentially uncontrolled border between the socialist and capitalist worlds unwittingly prompts the population to make a comparison between both parts of the city, which unfortunately, does not always turn out in favor of the Democratic [East] Berlin". Pervukin remained wary, until its very creation, of establishing a sectorial barrier between East and West Berlin; he believed that creating a barrier would increase anti-Soviet sympathies not only in Berlin but in Germany as well. Instead, he proposed three options: 1) "introducing restrictive measures" for East Germans to enter both East Berlin and West Berlin; 2) strengthening the border security; 3) stopping the free movement between the two cities. However, he did admit that closing the borders was a possibility, claiming that if the political situation worsened, the East German regime and the Soviets would not have another option. Walter Ulbricht, the East German leader, invited Pervukhin to his summer house to discuss the East German immigration flow to West Germany. There Ulbricht told Pervukhin that if the Soviets did not react soon, East Germany would "collapse". Pervukhin discussed other problems as well, claiming that Ulbricht but also the East German leadership in general, were opposed to the Soviet Union's plan to improve relations with West Germany. When Khrushchev gave his approval to construct what would become the Berlin Wall, Pervukhin was the first to know. Ulbricht told Pervukhin of the need to create the East–West barrier at night, and he and Khrushchev would later agree to this. At the 22nd Party Congress in 1961, Pevurkhin lost his seat in the Central Committee. He was succeeded in his post as Soviet ambassador to East Germany by Peter Abrassimov at the end of 1962. Decorations and awards Hero of Socialist Labour (1949) Five Orders of Lenin Order of the October Revolution Order of the Red Banner of Labour References Bibliography Category:1904 births Category:1978 deaths Category:People from Katav-Ivanovsky District Category:People from Ufa Governorate Category:Politburo of the Central Committee of the Communist Party of the Soviet Union members Category:People's Commissars and Ministers of the Soviet Union Category:Second convocation members of the Soviet of the Union Category:Third convocation members of the Soviet of the Union Category:Fourth convocation members of the Soviet of the Union Category:Ambassadors of the Soviet Union to East Germany Category:Russian communists Category:Anti-revisionists Category:Heroes of Socialist Labour Category:Recipients of the Order of Lenin Category:Plekhanov Russian University of Economics alumni | Mid | [
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Despite what the Mothers of the Movement believe, black lives don’t matter to Bill and Hillary Clinton. Just ask the Haitians who’ve spent years trashing the Clinton’s for screwing them over and turning the tragic earthquake that rocked the tiny Caribbean country in 2010 into a lucrative venture for their closest allies. Indeed, in the wake of the earthquake in Haiti — while 316,000 lifeless bodies lay buried under rubble, and while 300,000 Haitians suffered from injuries, with another 1.3 million displaced — Hillary Clinton’s family and monied cronies cashed in on the back of the tragedy-stricken Caribbean country. Hillary Clinton’s brother, Tony Rodham, landed a lucrative and historically rare Haitian “gold exploitation permit,” while Clinton Foundation donors, including Digicel mobile phone company founder Denis O’Brien, were winning multi-million dollar contracts that would siphon massive profits from the poorest country in the Western Hemisphere. While then-Secretary of State Hillary Clinton’s State Department was funneling billions in relief funds to rebuild Haiti, the Clinton Foundation was leveraging its influence to guide high-dollar contracts to Clinton cronies who would go on to make millions off the catastrophe that had claimed so many lives on the island. “I deal through the Clinton Foundation,” Tony Rodham said according to a transcript of his testimony during court proceedings, obtained by The New York Times. “That gets me in touch with the Haitian officials. I hound my brother-in-law [Bill Clinton], because it’s his fund that we’re going to get our money from. And he can’t do it until the Haitian government does it.” On December 5, 2014, Haitians gathered outside to protest Bill and Hillary Clinton’s “full support” of former Haitian President Michel Martelly — who placed his criminally-inclined cronies in positions of power. In March 2015, a large group of Haitians protested outside the Clinton offices in Manhattan, New York. This past January, six years after the deadly earthquake in Haiti, a group of Haitians gathered, again, in New York City at the Clinton Foundation headquarters to protest former President Bill Clinton’s role as head of the Interim Haiti Recovery Commission. “Today is the 12th of January 2016, six years after the earthquake. And for us, it was important to be in front of the Clinton Foundation, because Bill Clinton, as head of the IHRC, Interim Haiti Recovery Commission, was responsible for the $6 billion that came into his hands,” protester Dahoud Andre said at the time. “He had unlimited control of this money. Six years after the earthquake, not much has changed, and as a matter of fact, Haiti is in worse condition than it was in 2010. Only Bill Clinton can tell the world what happened with this money,” Andre added. Indeed, Twitter users blasted Hillary Clinton last month calling her a “liar” who “stole billions in donations meant to rebuild Haiti,” because she doesn’t “give a f*ck about Black people.” https://twitter.com/secondsunrising/status/740985433350377472 The Democratic National Convention has also been visited by Haitians, who’ve railed against Bill and Hillary Clinton’s transgressions against their country. “We hope that [Clinton Cash] film gets spread around so more people are informed about what’s going on there,” a female protester told Breitbart News on Monday, referencing the motion picture adaptation of the New York Times bestselling book Clinton Cash. The protester said they “basically stole the money,” when asked if she had an issue with the Clinton Foundation. “It never got to the masses,” she continued, “it never trickled down to the masses. And the Clintons have been doing evil deeds in Haiti for years.” When Bill and then-Secretary of State Hillary Clinton had the full force of the federal government at the their disposal, they squandered an opportunity to help the devastated people of Haiti and instead cashed in on their misery. Black lives didn’t matter to Bill and Hillary Clinton then, and they don’t matter to them now. Follow Jerome Hudson on Twitter: @jeromeehudson | Low | [
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Besides Andrew Miller, Dellin Betances, Chasen Shreve and whoever is not named the fifth starter, who are the other locks for an Opening Day bullpen spot? -- David F., Brooklyn, N.Y. At this point, the Yankees would tell you that there are not any definite locks, so they really may need the next few weeks of camp to iron it out -- all the way to those two final games in Miami. Shreve has looked like the guy who pitched well over the first five months of the 2015 season, so you would feel comfortable projecting him there, and Betances and Miller are secure. The loser of the fifth-starter derby between Ivan Nova and CC Sabathia could serve as the long reliever, though neither has much experience out of the bullpen -- 17 2/3 innings for Nova and none for Sabathia. That leaves three bullpen spots, assuming the Yanks plan on carrying 12 pitchers. :: Submit a question to the Yankees Inbox :: With Jacob Lindgren optioned to Triple-A Scranton/Wilkes-Barre on Sunday, the remaining contenders include Johnny Barbato, Nick Goody, James Pazos, Branden Pinder, Nick Rumbelow and Kirby Yates, with Bryan Mitchell likely to begin the year in the Minors. Veterans Vinnie Pestano and Anthony Swarzak are also in camp as non-roster options. Pinder and Rumbelow in particular seemed to earn manager Joe Girardi's attention early in camp. Regardless of who makes the cut for April 4, the Yankees will be making frequent use of the so-called "Scranton Shuttle" again this season, swapping relievers out on a regular basis. • Spring Training:Tickets | Schedule | More Does the lack of right-handed pitchers help Sabathia make the rotation, with Nova to the bullpen? -- Drew A., via Twitter Ideally, a Yankees team should always have at least one left-handed starter when playing 81 games in the Bronx. That said, the Yanks say they will bring the best five starters when they go north, regardless of salary or status. In my opinion, long relievers generally don't earn $25 million, so I would expect to see Sabathia either in the rotation or on the disabled list when the season begins. Is there any chance that Rob Refsnyder grabs the last roster spot? -- Craig W., Massapequa, N.Y. Refsnyder's chances of going north have improved greatly now that he has, thus far, shown he can passably handle third base. He will be a work in progress there and still needs to continue working at second base. But Refsnyder has impressed the Yankees with his mindset of doing whatever it takes to be in the big leagues. Girardi says that it is too early to call that race, however, mentioning Pete Kozma, Jonathan Diaz, Donovan Solano and Ronald Torreyes as legitimate contenders. Over the next few weeks, the Yanks will whittle that mix down as the regulars play more. Do you think Gary Sanchez is in danger of not making the Opening Day roster since he does not have a hit yet? -- Ryan R., New York, N.Y. Ten Grapefruit League at-bats hardly seems like enough to properly evaluate a player, so while I'm sure Sanchez would like to fatten his stats, the Yankees will more heavily weigh what they saw last year in the Minors and the Arizona Fall League. Girardi said that it's possible that Sanchez is pressing, and the Yanks are giving plenty of reps to Austin Romine and Carlos Corporan as well. Working in Sanchez's favor is that he reported in great condition -- "The best shape we've seen him in his years here," said director of player development Gary Denbo -- and that the Yankees rate his tools highly, particularly his arm strength and improved plate discipline. He's still the favorite, in my view. In 2014, the Yanks spent a bundle signing international players. Have any of them shown anything to believe they will become stars? -- Warren L., New York The most impressive of that group thus far has been switch-hitting 17-year-old Wilkerman Garcia, who signed for $1.35 million out of Venezuela and is currently rated as the Yankees' No. 5 prospect by MLB Pipeline. He appeared smooth in the Gulf Coast League, and the Yanks believe that Garcia will be able to stick as a pro shortstop. Another name to remember is shortstop Hoy Jun Park, who signed for $1 million out of Korea and played 56 games last season in Rookie ball. He's rated as the Yankees' No. 14 prospect. What are the chances of right-hander James Kaprielian being called up in 2016? -- John G., Boiling Springs, Pa. Kaprielian is on a fast track, and he impressed coaches with his poise and maturity this spring. He just turned 22 and has not pitched above Class A ball, and the Yankees seem likely to have him stay in Tampa until the weather warms up north. Kaprielian will probably reach Double-A Trenton soon after, and then his performance can dictate how quickly he can reach the bigs. It's very realistic that he could be competing for a rotation spot one year from today. Let's say it's the 14th inning, Girardi doesn't have any position players left on the bench. Who takes the field first: Alex Rodriguez at first or third, or a pitcher in the outfield? -- No name submitted Girardi was asked a similar question early in camp, and he said the only scenario where he'd play Rodriguez in the field is if he was starting to run out of players. Rodriguez has hardly picked up his glove all spring, though he did play catch once during a TV interview. Strange things happen (Carlos Beltran had to play first base once), but clearly, the Yankees would prefer that Rodriguez focuses on hitting. By the way, since Mariano Rivera declined to play that half-inning in center field, the last time a Yankees pitcher was sent to a fielding position was Aug. 18, 1983, when Billy Martin protested the conclusion of the "Pine Tar Game" by having Ron Guidry play center field. Martin also played Don Mattingly at second base that day. If we count DH as a position, though, then Martin used a pitcher on June 11, 1988, putting Rick Rhoden in his starting lineup batting seventh against the Orioles. Why? According to The New York Times, Martin explained that injuries gave the Yanks few right-handed options against lefty soft-tosser Jeff Ballard, so veterans like Claudell Washington, Mike Pagliarulo and Jose Cruz rode the pine in favor of Rhoden, who contributed a sacrifice fly in an 8-6 win. Bryan Hoch is a reporter for MLB.com. Follow him on Twitter @bryanhoch, on Facebook and read his MLBlog, Bombers Beat. | Low | [
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‘We want to be the best mobile storytellers in the world’ – Tourism New Zealand’s Andrew Fraser Tourism New Zealand has been shifting more and more of its ad spend to the digital channel over the last five years. And the organisation's marketing director Andrew Fraser says the approach is working. Tourism New Zealand finds itself in the unique position of marketing something distinctly Kiwi to everyone but Kiwis. The organisation’s entire budget is spent on convincing foreigners to visit the nation to experience the beauty that has become a familiar backdrop—and favourite advertising trope—to Kiwis. And, if the numbers are anything to go by, TNZ seems to be doing a pretty good job of getting tourists to select Aotearoa as their destination of choice. Data from May this year showed that international tourism spend in New Zealand surpassed $10 billion for the first time in a 12-month period for the year ending March 2016, driven by a 15.5 percent year-on-year increase in holiday arrivals. Due to the value of this revenue to the New Zealand economy, the government recently pledged a further $8 million to TNZ over next next four years to target key growth markets. But with that kind of money comes a high level responsibility. Tourism New Zealand is held accountable to the government—and by proxy to taxpayers—and must ensure that the money is spent in the best possible way, so that it drives impact and leads to further growth in the tourism industry. If you’re playing with the people’s money, you’d better get some decent results. One of the most important mandates the government organisation has had over the past 18 months has been to increase the number of visitors New Zealand receives during off-peak periods, the so-called shoulder seasons. “For a lot of our market, New Zealand seems a long way away,” says TNZ director of marketing Andrew Fraser, in explaining why it’s difficult to convince someone to hop onto what could be a 12- or 14-hour flight when they might not have that much vacation time. Further compounding this problem was the fact that the traditional marketing approach in tourism focuses on blasting advertising during peak periods—a trend still evident in the local market in the ad spend spike among travel companies during winter. If TNZ had an infinite budget, it could have simply increased the frequency of its above-the-line campaigns, ensuring that its brand was visible for the whole year. However, as is the case with any business (particularly those active in number of international markets), budgets are always limited, meaning TNZ had to innovate its approach. Migrating ad spend Over the past five years, TNZ has been shifting an ever-increasing percentage of its ad spend to digital to the extent that over 80 percent of its budget is now spent on the channel. But moving coins from one bag to another isn’t innovation in itself. As Visa’s global head of digital and marketing transformation Shiv Singh recently told Digiday: “Shifting money from TV to digital is a cliché. It’s really funny, because we as marketers went through a phase over the last five years where every marketer would say, ‘I’ve shifted 25 percent of my budget to digital’. And the next marketer would say, ‘I’m better than you, I’ve shifted 35 percent’. And the third would say, ‘I’ve shifted 80 percent. The point is that none of that matters.” Singh’s argument is that for a shift in spend to be truly innovative, it must drive results. And this insight also resonates with Fraser, who, during a recent interview with StopPress, reiterated time and time again how important results are to his marketing approach, regardless of the channel. To ensure his digital strategy rendered the best results, Fraser penned a partnership with Facebook around a year and half ago, giving TNZ access to both the Facebook creative and strategic teams. Paul McCrory, head of travel at Facebook Australia and New Zealand, says this partnership has been particularly well timed given the recent, very well reported, shift in media consumption habits. “Creatively, when you think about tourist organisations, they have been quite traditional in their approach, but the global trend has seen consumer behaviour shift dramatically,” McCrory says. “In the US recently, the amount of time spent consuming digital content overtook the amount of time spent consuming TV. The reason why this is important is because it’s the biggest change to have happened in a 50-year period. The last time it happened was when television overtook radio.” McCrory says that because of this change, it would’ve been very difficult for TNZ to fill its shoulder season in a traditional way. Mobile bards After striking the partnership, Fraser says it didn’t take long for him to realise a major opportunity lay in the pockets of consumers, particularly those in emerging markets. “[The partnership], has accelerated us onto mobile rapidly,” he says. And because TNZ entered this space with very little experience, Fraser understood from the beginning there would be a few mistakes along the way. “We have also shifted to a test to learn culture. It’s really agile. If we want to learn something, we have to test it and see what happens. And with the power of the platform, we’ve got insights that we couldn’t have achieved through traditional research.” Fraser says that given the importance of those glowing pocket rectangles, his aim is to make TNZ “the best mobile storyteller in the world”. But rather than being driven by aesthetic reasons, Fraser says the reason for this objective is because creativity on mobile has driven good results for TNZ. To back this claim, Fraser points to the ‘Kombi Diaries’ campaign released last year, which he says reached over 30 million people in the US alone and resulted in a 26 percent year-on-year increase in visitors during the first month of the autumn shoulder season (March). As an interesting aside, this campaign was developed in conjunction with the Facebook Creative Shop team rather than through a traditional agency. And While Creative Shop doesn't charge for its services, Tom Hyde, Facebook’s creative partner across Australia and New Zealand, recently told StopPress that the company was investing in talent to better equip the organisation to collaborate with creative agencies and clients on creative ideas.* “When something needs to be changed at Facebook, they change it,” Hyde said. “And one thing that they recognised needed to be changed was that they were a media company full of media people. And they realised that brand is the biggest opportunity for the company, because that’s where the vast majority of money is spent in advertising. So they went about employing the best people from creative agencies.” What this means is that words ‘creative shop’ are likely to become more common in the credit lists of campaigns in the near future. Or maybe not. Because as McCrory explains, sometimes Facebook plays more of a strategic role, providing advice and guiding the client in terms of the best way to achieve the desired result. “We will prioritise the best possible measurement icons, we will allocate creative resources to support mobile, and we’ll make sure that New Zealand is at the front of all the new technological developments,” McCrory says. “We don’t provide all of that to everybody, but when we have a partnership like this whereby Andrew and his team shares with us his business problem and gives us the challenge, then off the back of that it’s an interesting project for us because we will place a priority on Tourism New Zealand not only as a local, but as a global client.” Still learning McCrory says Facebook aims to share all its innovations with its global partners, so that they can be the first to experiment with them. However, Fraser says that being first isn’t always the best approach when it comes to digital, pointing to the recent launch of Canvas as an example. “When Canvas launched, we didn’t want to be first,” he says. “We wanted to be next. We first wanted to look across the globe at what had been done, and find the best. And then we based ours on that. That’s what the value of the partnership is. Facebook hasn’t published findings on creating microsites, but they will capture and apply it to our executions. As a marketer, that’s fascinating. You’re learning through doing.” Fraser has also tried his hand at marketing on Instagram, with last year’s launch of the #NZMustDo campaign (by Contagion), which led to over 15,000 tourists contributing to New Zealand’s presence on the social channel. A photo posted by BrPackers (@brpackers) on Jun 16, 2016 at 5:16pm PDT And Fraser isn’t stopping there. He says he's also becoming increasingly interested in using influencers to reach audiences in emerging markets, such as the US, China and India (wedding photos in a glowworm cave also help this cause). This has already been seen earlier this year with TNZ bringing over Chinese influencer Huang Lei over the Chinese New Year celebrations, and Fraser says he expects influencers to play a more important role as he continues to evolve TNZ’s marketing strategy. And as the nation steps further from the glow of Tolkien, the effectiveness of this strategy will play an increasingly important role in determining whether the nation’s green hills continue to attract tourists. *Correction: this story previously incorrectly stated that Creative Shop charges for its creative services. This is a community discussion forum. Comment is free but please respect our rules: If we find you doing these things, your comments will be edited without recourse and you may be asked to go away and reconsider your actions. We respect the right to free speech and anonymous comments. Don’t abuse the privilege. | Mid | [
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Q: Why doesn't grep work if a file is not specified? I have some problem with the Linux grep command, it don't work !!! I am trying the following test on my Ubuntu system: I have create the following folder: /home/andrea/Scrivania/prova Inside this folder I have created a txt file named prova.txt and inside this file I have write the string test and I have save it In the shell I have first access the folder /home/andrea/Scrivania/prova and so I have launched the grep command in the following way: ~/Scrivania/prova$ grep test The problem is that the cursor continues to blink endlessly and cannot find NOTHING! Why? What is the problem? A: You've not provided files for the grep command to scan grep "test" * or for recursive grep -r "test" * A: Because grep searches standard input if no files are given. Try this. grep test * | Mid | [
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10 Myths About Contamination Battling the spread of infectious agents in your animal facility? Here's a list of what NOT to believe. Even with improved housing and health monitoring, positive serologic or culture findings for microorganisms can and do happen in animal facilities. And as much as an animal facility wants negative laboratory results for all agents on an exclusion list, bacteria, viruses, and parasites can sidestep even the best control methodologies, infecting laboratory animal colonies. Alas, long is the list of potentially contaminating circumstances. Shipping animals between institutions can increase the risk for contamination, especially when an institution’s health status is unknown. Movement of staff from areas of low-health status to high also increases risk, as well as other factors, including unscreened biological materials and contaminated food. Knowledge of such risks helps combat the spread of infectious agents. But what if that knowledge were wrong? What if we were working with faulty assumptions? More risky than the prevalence of certain pathogens or the shipment of animals are the potential false positives in our understandings. These are the myths—things we think are true but are actually false. In this article on microbiological contamination, we’ll discuss the 10 most common. Myth #1: Contaminations don’t happen at well-run facilities. Increase the complexity of a system, and you increase the potential for biosecurity failures. Productive research facilities are highly complex operations, with numerous biosecurity variables, including research staff, animal care, and engineering/maintenance personnel. Even the best-run facilities are vulnerable to human error. In addition to supportive husbandry and research materials, there are structural variables, such HVAC systems and pest harborage areas (vertebrate and invertebrate). Even minor errors or system failures increase contamination risks. Myth #2: Soiled-bedding sentinels detect everything. Dirty bedding only transmits agents hardy enough to stay infectious in soiled bedding. Sentinels therefore can actually miss a number of important pathogens, such as those not stable in dried material or those transmitted through respiratory secretions. Some poorly transmitted agents, for example, include Pneumocystis carinii, Helicobacter spp., Pasteurella pneumotropica, and fur mites. Myth #3: The source of infection is always identifiable. An infected mouse, feed bag, clipboard, or dust mote could be long gone. Biosecurity errors may be forgotten or undiscovered as well. It never hurts to perform a thorough investigation, however, as there are usually areas where procedures have begun to drift from the ideal. Even if the smoking gun isn’t identified, increased attention to detail never hurts. Myth #4: Human cell lines don’t contain mouse viruses. Nonrodent biological material can carry infectious agents from rodents. Some viruses can infect cells of many species (e.g., Polyoma and LCMV). Others can contaminate nonrodent cell lines when rodent cells are used in co-cultivation. This is also true if rodent serum is used to feed cells or if rodent-derived basement membrane gels are used to support xenografts. In addition, serum can become contaminated if it’s processed on a column previously exposed to contaminated serum. We once detected mouse parvovirus in rabbit serum due to this, for example. Myth #5: The liquid nitrogen used in cryopreservation is sterile. There is abundant evidence that materials can become contaminated in liquid nitrogen. As such, embryos or sperm retrieved from liquid nitrogen should not be considered free of biological contaminants. The outsides of containers immersed in liquid nitrogen should be treated as if contaminated and the contents of the container considered the same health status prior to freezing. Always treat animals reconstituted from the freezer as potentially contaminated until proven otherwise. Myth #6: Pet shop rodents are NOT dirty. Such animals are often bred in close quarters with no disease control. We have detected Salmonella, Streptobacillus, lice, mites, pinworms, Hymenolepis, and LCMV in rodents from pet stores. In fact, our diagnostic lab actually uses mice from pet store suppliers as a source of positive control serum. Myth #7: Exclusion lists should be based on those of commercial vendors. Laboratory rodents are not microbiologically sterile. Like other complex organisms, mice and rats have a rich and complex microflora. Many clients prefer negative results for everything commercial vendors test for. But selecting animals based on inconsequential bacteria doesn’t allow for the chance to make selections based on important variables, such as more important infections or even good genetic management. You will save money and headaches by keeping your exclusion lists as simple as possible, and only adding agents relevant to ongoing research. Myth #8: Discovering norovirus (or the next new agent) is always something to freak out about. It’s not. It’s just more information. When a new agent is discovered in clinically normal animals, it’s typically present in a higher level in the population than “old” agents (because it’s never been controlled). For example, finding a new, nonpathogenic virus in immunocompetent animals such as norovirus is just new information about something that has likely always been present. A different story of course, would be a newly discovered agent that actually causes disease in immunocompetent lab animals. Myth #9: When concerned about parvovirus, both serology and PCR on lymph nodes (or spleen) should be performed. Both methods ask the same question—that is, has the animal ever been infected?—and almost always give the same answer. Because both tests yield little additional information when performed in tandem, money is better spent testing more animals by one method or the other. An alternative would be to also test some animals by fecal PCR, which screens for current shedding of virus. Myth #10: Laminar flow hoods always have laminar flow. They only do when they’re empty. Materials and equipment disrupt laminar flow and cause the air to swirl, which can actually spread infectious bacteria or viruses across surfaces or to other objects in the hood. To avoid contamination, clutter must be minimized and manufacturer recommendations followed. Kathleen R. Pritchett-Corning is director of research and professional services at Charles River. Charles B. Clifford is director of pathology and technical services for Charles River Research Models and Services as well as Research Animal Diagnostic Services. Jobs GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs. If you have any questions about your subscription, click hereto email us or call at (914) 740-2189. You may also be interested in subscribing to the GEN magazine, an indispensable resource for everyone involved in the business of translating discoveries at the bench into solutions that fight disease and improve health, agriculture, and the environment. Subscribe today to see why over 60,000 biotech professionals read GEN to keep current in the areas of genomics, proteomics, drug discovery, biomarker discovery, bioprocessing, molecular diagnostics, collaborations, biotech business trends, and more. | Mid | [
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Amy Schumer wants to give an Emmy to everyone on 'The Wire' Amy Schumer listened to the Emmy nominations early this morning, but didn’t know her Comedy Central show Inside Amy Schumer was nominated until a friend texted her with the news. “I was like, ‘What?’ I thought he was just confused.” But it was true: Schumer and her writing team scored a nod for outstanding writing for a variety series. “I love all our writers so much and I’m so proud of what we did this year,” Schumer told EW. One of those things they did included introducing Dumpy the Frumpy Meerkat to the world—and what a great thing that was. ENTERTAINMENT WEEKLY: Congratulations on the nomination! We’re so excited for you.AMY SCHUMER: I’m so excited. What were you doing when you found out?Honestly, I was in the makeup chair getting makeup for the movie I’m filming right now with Judd [Apatow]. And I heard the nominations and I didn’t think we got nominated and I was just sitting there, and then one of my friends texts me and was like, “We both got nominated!” And I was like, “What?” I thought he was just confused, and then he said it was for what it was for, and I could not have been happier. I love our writers so much, and I’m so proud of what we did this year, and I was, like, constantly tweeting about them this season, just how proud I am. So it’s really cool because as a performer, you’re like… If just I’d been nominated, you’d feel like, “Ugh, it’s such a collaboration, I feel like a dickhead” so it’s really exciting that it’s all of us. And knowing how hard we worked in the room. What’s been your favorite scene you’ve all written together?My sister—because of union rules she couldn’t write yet this season but she’s going to be a credited writer next season, but she actually helped produce and script the scene called “Voice-over.” It’s where I book a voice-over gig and then it winds up being that I get really excited and in over my head, and I’m celebrating my new career as a fancy voice-over artist, and I get there and the other characters are really cute little meerkats and then mine is called the Dumpy the Frumpy Meerkat and does not have pants and has an exposed vagina and it’s really, really vile and all my character says is “worms.” So that one was the hardest to get through and I laughed the most. I think that was the funniest one. One of my favorite parts of the show is the “Amy Goes Deep” segment, so I’m wondering how you guys choose the people you interview.I’ll think, “Who have I never had a real conversation with and asked all the questions I’ve always wanted to?” And then we just look for those people. I’ve been wanting to talk to somebody over 100 for both seasons, so we finally got one. I love that part of the show, too. I’m really glad people like it, because that was the part we weren’t that sure about. What show—old or new, on or off the air—would you give an Emmy to just because you love it so much? I would say everyone who worked on The Wire, down to the last grip. Every extra on the show The Wire, I want to give every Emmy to. I can’t believe that show never won one. It’s so good. It’s like Shakespeare. | Mid | [
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Q: How to reorder 1st dim of array in R (don't know total dims) I have an array whose first dimension I need to subset/ index/ reorder. For example: arr <- array(1:24, dim=c(4,3,2)) arr[4:1,,] Simple, works like a charm. However, is there a way to do this when I'm unsure how many dimensions the array has? To be clear, I will always know the size of that first dimension (i.e., I know dim(arr)[1]), I just don't know length(dim(arr)). A: Here's one possible way, though it's still a bit slow. do.call(`[`, c(list(arr, 4:1), lapply(dim(arr)[-1], seq_len))) ## , , 1 ## ## [,1] [,2] [,3] ## [1,] 4 8 12 ## [2,] 3 7 11 ## [3,] 2 6 10 ## [4,] 1 5 9 ## ## , , 2 ## ## [,1] [,2] [,3] ## [1,] 16 20 24 ## [2,] 15 19 23 ## [3,] 14 18 22 ## [4,] 13 17 21 do.call requires a list of arguments that (if unnamed) will be passed to the specified function (in this case, [) in the order in which they're supplied. Above, we pass a list, list(arr, 4:1, 1:3, 1:2) to [, which is equivalent to doing: `[`(arr, 4:1, 1:3, 1:2) (which, in turn, is equivalent to arr[4:1, 1:3, 1:2]). Timing: microbenchmark(subset=arr[4:1,,], jb=do.call(`[`, c(list(arr, 4:1), lapply(dim(arr)[-1], seq_len))), times=1E3) ## Unit: microseconds ## expr min lq mean median uq max neval ## subset 1.140 1.711 1.765575 1.711 1.711 15.395 1000 ## jb 9.693 10.834 11.464768 11.404 11.974 96.365 1000 (Ignore absolute times - my system is currently under strain.) So, it takes around ten times as long as the straightforward subset. Probably room for improvement here, though as @thelatemail comments, the timings are much more comparable on larger arrays. EDIT As suggested by @thelatemail, the index sequences can be replaced by TRUE, which will speed things up a bit. do.call(`[`, c(list(arr, 4:1), rep(TRUE, length(dim(arr))-1))) Timings again: microbenchmark(subset=arr[4:1,,], jb=do.call(`[`, c(list(arr, 4:1), lapply(dim(arr)[-1], seq_len))), tlm=do.call(`[`, c(list(arr, 4:1), rep(TRUE, length(dim(arr)) - 1))), times=1E3) ## Unit: microseconds ## expr min lq mean median uq max neval ## subset 1.140 1.711 2.146474 1.711 2.281 124.875 1000 ## jb 10.834 11.974 13.455343 12.545 13.685 293.086 1000 ## tlm 6.272 7.413 8.348592 7.983 8.553 95.795 1000 A: Here's a weird alternative. This idea is based on an implementation quirk I noticed at one point, that R seems to represent "missing" function arguments as symbols with zero-length names. One of the reasons that this is so bizarre is that R normally doesn't allow you to create symbols with zero-length names: as.symbol(''); ## Error in as.symbol("") : attempt to use zero-length variable name But through some messing around, I discovered that you can slip past R's defenses by accessing the parse tree of an expression that involves a "missing" argument, and indexing out the element of the parse tree that contains the "missing" argument. Here's a demo of some of the weird behavior you get from this thing: substitute(x[]); ## parse tree involving missing argument ## x[] as.list(substitute(x[])); ## show list representation; third component is the guy ## [[1]] ## `[` ## ## [[2]] ## x ## ## [[3]] ## ## substitute(x[])[[3]]; ## prints nothing! ## (function(x) c(typeof(x),mode(x),class(x)))(substitute(x[])[[3]]); ## it's a symbol alright ## [1] "symbol" "name" "name" as.character(substitute(x[])[[3]]); ## gets the name of the symbol: the empty string! ## [1] "" i.dont.exist <- substitute(x[])[[3]]; ## store in variable i.dont.exist; ## wha?? ## Error: argument "i.dont.exist" is missing, with no default Anyway, here's the solution we can derive for the OP's problem: arr <- array(1:24,4:2); do.call(`[`,c(list(arr,4:1),rep(list(substitute(x[])[[3]]),length(dim(arr))-1))); ## , , 1 ## ## [,1] [,2] [,3] ## [1,] 4 8 12 ## [2,] 3 7 11 ## [3,] 2 6 10 ## [4,] 1 5 9 ## ## , , 2 ## ## [,1] [,2] [,3] ## [1,] 16 20 24 ## [2,] 15 19 23 ## [3,] 14 18 22 ## [4,] 13 17 21 ## I was hoping it would outperform all the other solutions, but @thelatemail, you win this round: Aha! I realized that we can precompute a list of an empty symbol (storing an empty symbol in a variable by itself, i.e. not in a list, is not usable, as I showed above) and rep() that list in the solution, rather than incurring all the overhead of substitute() to parse out a dummy expression in every invocation of the solution. And behold the performance: straight <- function() arr[4:1,,]; jb <- function() do.call(`[`,c(list(arr,4:1),lapply(dim(arr)[-1],seq_len))); tlm <- function() do.call(`[`,c(list(arr,4:1),rep(TRUE,length(dim(arr))-1))); orderD1 <- function(x,ord) { dims <- dim(x); ndim <- length(dims); stopifnot(ndim>0); if (ndim==1) return(x[ord]); wl_i <- which(letters=="i"); dimLetters <- letters[wl_i:(wl_i+ndim-1)]; dimList <- structure(vector("list",ndim),.Names=dimLetters); dimList[[1]] <- ord; for (i in 2:ndim) dimList[[i]] <- 1:dims[i]; do.call("[",c(list(x=x),dimList)); }; rbatt <- function() orderD1(arr,4:1); bgoldst <- function() do.call(`[`,c(list(arr,4:1),rep(list(substitute(x[])[[3]]),length(dim(arr))-1))); ls0 <- list(substitute(x[])[[3]]); ls0; ## [[1]] ## ## bgoldst2 <- function() do.call(`[`,c(list(arr,4:1),rep(ls0,length(dim(arr))-1))); microbenchmark(straight(),jb(),tlm(),rbatt(),bgoldst(),bgoldst2(),times=1e5); ## Unit: nanoseconds ## expr min lq mean median uq max neval ## straight() 428 856 1161.038 856 1284 998142 1e+05 ## jb() 4277 5988 7136.534 6843 7271 1629357 1e+05 ## tlm() 2566 3850 4622.668 4277 4705 1704196 1e+05 ## rbatt() 24804 28226 31975.583 29509 31219 34970873 1e+05 ## bgoldst() 3421 4705 5601.300 5132 5560 1918878 1e+05 ## bgoldst2() 2566 3850 4533.383 4277 4705 1034065 1e+05 Just discovered that there's an easier way to get ahold of the empty symbol, which seems to have been available all along: substitute(); ## My substitute(x[])[[3]] trick now looks kind of stupid. Out of curiosity I benchmarked using substitute() directly against the other solutions, and it incurs a slight performance cost compared to bgoldst2(), making it slightly worse than tlm(): bgoldst3 <- function() do.call(`[`,c(list(arr,4:1),rep(list(substitute()),length(dim(arr))-1))); microbenchmark(straight(),jb(),tlm(),rbatt(),bgoldst(),bgoldst2(),bgoldst3(),times=1e5); ## Unit: nanoseconds ## expr min lq mean median uq max neval ## straight() 428 856 1069.340 856 1284 850603 1e+05 ## jb() 4277 5988 6916.899 6416 7270 2978180 1e+05 ## tlm() 2566 3849 4307.979 4277 4704 3138122 1e+05 ## rbatt() 24377 28226 30882.666 29508 30364 36768360 1e+05 ## bgoldst() 2994 4704 5165.019 5132 5560 2050171 1e+05 ## bgoldst2() 2566 3849 4232.816 4277 4278 1085813 1e+05 ## bgoldst3() 2566 3850 4545.508 4277 4705 1004131 1e+05 | Low | [
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Q: Events are not called when changing visibility of an element I have a page that need to toggle the visibility of a div at regular interval. The issue is that the click events related to one of the parent element are often not called. If I stop the visibility toggle or if I slow it down (for example 300ms instead of 100ms) the click events are fired normally. I have created a short example illustrating this issue. You can test it here: http://threeds.me/0xC0DE/ Clicking the blue/red square should in theory fire the click event. When there is no animation (default behaviour here) clicking the blue square will always fire the onclick event. If you click on 'play/pause' the visibility of the red square will start to toggle every 100ms. When the animation is playing the click event is not call everytime you click on the square. I would suspect that changing the visibility is somehow messing up with the DOM which as a result stop events for some milliseconds. I also tried to toggle the css visibility property to minimize the impact on the page but it has the same result. But it's not only events. If I encapsulate the whole container in an tag, clicking the element will not be always taking into account by the browser. So it's like that changing the visibility of a child element will make a parent blind for (quite) some time which I find really strange. This issue is consistent with Firefox, Chrome and Opera (all on mac, cannot test ie) so it means there is something I don't get. So even if I don't get a solution, I would like to understand what is the problem. Here the source for your immediate reference <!DOCTYPE html> <html> <head><title>Wiggle problem</title> <style> #dback { width: 200px; height: 200px; background-color: red; } #dfront { width: 200px; height: 200px; background-color: blue; } </style> <script type="text/javascript"> var run = false; function playpause() { if ( run ) { run = false; } else { run = true; update(); } } function update() { if ( run==false ) { return; } var el = document.getElementById('dfront'); if ( el.style.display != 'none' ) { el.style.display = 'none'; } else { el.style.display = ''; } setTimeout("update();", 100); } </script> </head> <body> <a href="#" onclick="playpause();">play/pause</a> <div id="container" onclick="d=new Date();t=d.getTime();document.getElementById('info').innerText='click '+t;"> <div id="dback"> <div id="dfront"></div> </div> </div> <span id="info"></span> </body> </html> A: That is really weird! However, I made some tests and fiddled with your code a bit, and now I think it has nothing to do with bubbling (you can see on my test that clicks on elements with visibility: hidden bubble just fine). Here is what I think could be going on: since your timer interval is so short, there is not enough time for an actual click to be registered – a click being a mousedown event, followed by a mouseup event, on the same element. What happens in your case is that mouseup is frequently being fired on the other element, not the same one that fired mousedown, and thus there is no click event. See the second link above, where I reduced the interval to 1 sec, and try to click on the blue square, and release the mouse button on the red square (or vice-versa). Nothing happens. I may be completely wrong, but that looks plausible. I know this is not a solution, but you said: So even if I don't get a solution, I would like to understand what is the problem. I hope this can help you find one! Last but not least, a couple of side notes on your code: The way you're calling setTimeout (passing a string) is not recommended, because it will force the use of eval internally, and eval should be avoided as much as possible. Instead of passing the string with the function call code, just pass the function itself: setTimeout(update, 100); It's considered a best practice today to use addEventListener (or attachEvent for IE) to bind an event to an element, instead of using inline events like your onclick="...". That has several advantages, like helping separate behavior, structure and layout, and making the event object automatically available to the event handler (as the first parameter to the handler function). | Mid | [
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James O'Keefe claims that the Silicon Valley social media network is engaging in censorship. James O'Keefe claims that the Silicon Valley social media network is engaging in censorship. Controversial muckraker James O’Keefe and his Project Veritas crew have dropped another hidden camera video that purports to expose ideological bias at Twitter. In the edited footage, past and present Twitter employees allegedly appear to discuss how they can mute or filter out pro-President Trump tweets. This footage comes a day after Project Video published a video containing remarks by a Twitter senior security engineer who self-described as a bleeding-heart liberal and who said that the social network would gladly hand over every Trump tweet or direct message, active or deleted, to the U.S. Department of Justice. Perhaps more concerning for ordinary users in the context of privacy, the individual also seemed to boast that Twitter engineers can access everyone’s account, including their passwords, and also obtain all private direct messages and deleted tweets. He described the extent of this reach as “terrifying.” Twitter subsequently released a statement disavowing the engineer’s comments. In the new Project Veritas video uploaded this morning, which is open to interpretation, Twitter employees allegedly talk about how they use shadow-banning techniques to hide or suppress pro-Trump or equivalent tweets without a user’s knowledge. There is also discussion of writing algorithms to suppress tweets from conservative and Republican sources based on keywords even if they are legitimate rather than generated by bots. One former employee who was involved with content review alludes to the notion that Twitter abides by unwritten rules to target users and ban accounts over political opinions other than progressive ones, given that Twitter is headquartered in the very blue state of California. That individual also seems to suggest that tweets expressing liberal views are seldom blocked by Twitter overseers. Another employee in the footage discusses an alleged Twitter initiative to down-rank “sh***y people” so that they don’t show up. Jeff Chiu/AP Images When asked by a Project Veritas undercover journalist why WikiLeaks founder Julian Assange hasn’t received a blue check verification badge, or why his account briefly disappeared recently, an engineer claims that Twitter is responding to pressure from the U.S. government, and Assange has “s**t on a lot of people.” Parenthetically, the Daily Caller claims that Google’s new fact-check procedure targets conservative-oriented news sites, but liberal sites seldom come under the same scrutiny. The O’Keefe video is the latest installment of the Project Veritas series called “American Pravda” in which the conservative group attempts to expose what it considers liberal bias at various media organizations. James O’Keefe asserts that there will be more videos forthcoming about alleged bias at Twitter. | High | [
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Saddle pulmonary embolism and in-hospital mortality in patients with cancer. Saddle pulmonary embolism (PE) has been associated with an increased risk of 1 year mortality when compared to non-saddle PE among patients with cancer. We sought to evaluate the association between saddle PE and in-hospital outcomes among patients with comorbid cancer. The 2013 and 2014 United States National Inpatient Sample was used to identify adult patients hospitalized for acute PE. Only patients with an International Classification Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code indicating comorbid cancer were included. Identified admissions were stratified into the following 2 cohorts: saddle (defined as ICD-9-CM code = 415.13) and non-saddle PE. Multivariable logistic regression was performed to determine the association between saddle PE and the odds of in-hospital mortality after adjustment for age ≥ 80 years and sex. A total of 10,660 admissions for acute PE in patients with comorbid cancer were identified. Of which, 4.5% (n = 475) had a saddle PE. Median age was 67 years (interquartile range = 58-76) and 48.9% were male. In-hospital mortality occurred in 6.1% of patients. Upon multivariable adjustment, the odds of in-hospital mortality were higher in saddle versus non-saddle PE (odds ratio = 1.51; 95% confidence interval 1.08-2.10). In this retrospective study of admissions for acute PE in patients with comorbid cancer, saddle PE was associated with a higher odds of in-hospital mortality. | High | [
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[Ultrasound-controlled percutaneous kidney biopsy]. Nephrological diseases--in special cases also unsettled forms of microhematuria--require a biopsy of the kidney. To date this intervention has mostly been performed under x-ray control by means of the Menghini or the Trucut-needle. Ultrasound opened up new perspectives, particularly after the introduction of perforated ultrasound probes. These ensure complete control of the intervention provided that appropriate puncture systems are applied. The cut biopsy needle (Otto) offers great advantages because it is thinner than the puncture systems used so far. With identical quality of the cast compared to that obtained with conventional techniques, the needle recommended is less traumatic and hence both risk and patient discomfort are reduced. Report on 52 punctures. | High | [
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ARMED SERVICES BOARD OF CONTRACT APPEALS Appeals of -- ) ) Wu & Associates, Inc. ) ASBCA Nos. 61777, 61908 ) Under Contract No. N40085-14-D-5245 ) APPEARANCE FOR THE APPELLANT: Sean T. 0' Meara, Esq. ArcherP.C. Haddonfield, NJ APPEARANCES FOR THE GOVERNMENT: Craig D. Jensen, Esq. Navy Chief Trial Attorney Russell A. Shultis, Esq. Julie C. Ruggieri, Esq. Trial Attorneys OPINION BY ADMINISTRATIVE JUDGE WILSON It is the Board's decision, pursuant to 41 U.S.C. §§ 7105(e), 7108(b), and the parties' stipulation and agreement, that the appeals are sustained. In the nature of a consent judgment, the Board makes a monetary award to appellant in the amount of $283,858.00. Interest shall be paid on this amount pursuant to 41 U.S.C. § 7109 from October 12, 2018, until date of payment. Dated: August 27, 2019 OWEN C. WILSON Administrative Judge Vice Chairman Armed Services Board of Contract Appeals (Signatures continued) l I SHACKLEFORD J\.dministrative Judge Administrative Judge Chairman Vice Chairman Armed Services Board Armed Services Board of Contract Appeals of Contract Appeals I certify that the foregoing is a true copy of the Opinion and Decision of the Armed Services Board of Contract Appeals in ASBCA Nos. 61777, 61908, Appeals of Wu & Associates, Inc., rendered in conformance with the Board's Charter. Dated: PAULLA K. GATES-LEWIS Recorder, Armed Services Board of Contract Appeals 2 | Mid | [
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[Use of anthelmintics for nematode control in sheep in West Germany: results of a survey]. A survey by questionnaires was performed on 543 (0.9% of all) sheep flocks in western Germany in 1988/89 to obtain informations about deworming practices against gastrointestinal nematodes. The major informations are: Anthelmintic treatments were associated with the reproductive status of ewes and the breeding of lambs in most of the flocks. They were performed at an epidemiologically appropriate time in many cases but were not accompanied by essential management practices. (Pro)benzimidazole compounds were the anthelmintics most frequently used by more than 95% of the farmers; 22% and 13% of the farmers additionally or exclusively administered levamisole/pyrantel and ivermectin, respectively. On average, treatment of ewes and lambs against nematodes was performed 2.5 times and 2.8 times a year, respectively. The mean frequency of deworming differed regionally and was generally greater in pedigree breeding flocks than in commercial breeding flocks; it was significantly affected by the husbandry system, the number of ewes per flock, the size of available pasture and the class of anthelmintics employed. The results of this survey revealed that many German sheep farmers obviously lack an awareness of the rationale of preventive and economic control practices against gastrointestinal nematodes. | Mid | [
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Uganda says to pull out troops from Somalia over Congo charges KAMPALA (Reuters) - Uganda will tell the United Nations it is withdrawing its forces from military operations in Somalia and other regional hotspots after the world body accused it of supporting Congolese rebels, the security minister said on Friday. Minister Wilson Mukasa said the decision was irreversible and another Cabinet minister would explain Uganda's position at the United Nations in New York. However, it was not immediately clear if an irrevocable decision had been taken. U.N. diplomats told Reuters the Ugandan delegation, which was led by Ruhakana Rugunda, special envoy and minister of information and communications technology, did not threaten to withdraw troops from international peacekeeping missions during discussions with U.N. officials in New York this week. A read-out of the Ugandan delegation's meeting on Friday with Indian Ambassador Hardeep Singh Puri, the president of the U.N. Security Council this month, also made no mention of threats to pull out troops. The information was made available to Reuters by India's U.N. mission. Ugandan troops account for more than a third of the 17,600 U.N.-mandated African peacekeepers battling al Qaeda-linked Islamist rebels in Somalia and their withdrawal could hand an advantage to al Shabaab. Its soldiers, backed by U.S. special forces, are also leading the hunt for fugitive Ugandan warlord Joseph Kony in Central African Republic, with some stationed in South Sudan. In a leaked report, a U.N. Group of Experts last month accused Uganda and Rwanda of supporting the so-called M23 rebel group commanded by Bosco Ntaganda, a warlord indicted by the International Criminal Court nicknamed "the Terminator". India's statement said the Ugandan delegation expressed "grave concern" about the report of the Group of Experts, and added that the Security Council's Congo sanctions committee had yet to formally consider the experts' report. Continued... | Mid | [
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Facts About Big Coins Revealed Facts About Big Coins Revealed Some Of Trading Bitcoin Futures In 2009, it was 50. In 2013, it had been 25, at the time of writing it's 12.5, and sometime in the middle of 2020 it will halve to 6.25. . At this speed of halving, the total number of bitcoin in circulation will approach a limit of 21 million, making the currency more scarce and valuable over time but also more expensive for miners to make. Here's the catch. In order to get bitcoin miners to actually earn bitcoin from verifying transactions, two things have to occur. To begin with, they must confirm 1 megabyte (MB) worth of transactions, which can theoretically be as little as 1 transaction but are far more often a few thousand, depending on how much data each transaction stores. 7 Simple Techniques For Is Bitcoin Mining Profitable Second, in order to put in a block of transactions to the blockchain, miners must fix a intricate computational science difficulty, also referred to as a"proof of labour ." What they are actually doing is trying to think of a 64-digit hexadecimal number, called a"hash," that is less than or equal to the target hash. Some Known Details About Coins For Sale In other words, it is a bet. . The difficulty level of the most recent block at the time of writing is all about 7,184,404,942,701. In other words, the chance of a computer producing a hash beneath the target is 1 in 7,184,404,942,701 less than 1 in seven trillion. That level is corrected every 2016 blocks, or roughly every two weeks, with the goal of keeping rates of mining constant. Is Bitcoin Mining Profitable Fundamentals Explained The reverse is also correct. If computational power has been taken off of the network, the problem adjusts downward to make mining easier. . Bitcoin Sites Can Be Fun For Anyone "Say I tell three friends I'm thinking of a number between 1 and 100, and I write that number on a piece of paper and seal it in an envelope. My friends don't need to guess the exact number, they just have to be the very first person to guess any number that's less than or equal to this number I'm thinking of. "Let us say I am thinking about the number 19. If Friend A guesses 21they lose because 21>19. If Friend B supposes 16 and Friend C supposes 12, then they have both theoretically arrived at workable answers, since 16<19 and 12<19. There is no'extra credit' for Friend B, even though B's answer was nearer to the target answer of 19. . "Now imagine that I pose the'guess what number I'm thinking of' question, but I'm not asking only three friends, and I'm not thinking of a number between 1 and 100. Rather, I am asking millions of would-be miners and I am thinking of a 64-digit hexadecimal number. Now you see that it's going to be extremely hard to guess the right answer." . If 1 in 7 trillion doesn't sound difficult enough as is, here is the grab to the grab. Not only do bitcoin miners need to think of the ideal hash, but they also must be the very first to perform it. The 2-Minute Rule for Bitcoin Sites Since bitcoin mining is essentially guesswork, arriving at the ideal answer before another miner has everything to do with how fast your computer can produce hashes. Just a decade ago, bitcoin miners can be carried out competitively on normal desktops. Over time, however, miners realized that pictures cards commonly used for video games tend to be more effective at mining than desktops and graphics processing units (GPU) came to dominate the match. The Facts About How To Trade Bitcoin Revealed These can run from $500 into the tens of thousands. . Nowadays, bitcoin mining is so competitive that it can only be done profitably with the latest up-to-date ASICs. When using desktop computers, GPUs, or elderly models of ASICs, the cost of energy consumption actually exceeds the revenue generated. Even with the newest unit my review here at your disposal, one computer is rarely enough to compete with exactly what miners call"mining pools." . A mining pool is a group of miners who combine their computing ability and divide the mined bitcoin between participants. A disproportionately high number of cubes are mined by pools rather than by individual miners. In July 2017, mining pools and companies represented approximately 80% to 90% of bitcoin computing power. . Unknown Facts About Is Bitcoin Mining Profitable Between 1 in 7 trillion odds, scaling difficulty levels, and the huge network of consumers verifying transactions, one block of transactions is verified roughly every 10 minutes. But its important to remember that 10 minutes is a target, not a guideline. The 30-Second Trick For Cryptocurrency Exchange List Getting The How To Trade Bitcoin To Work The bitcoin network can process about seven transactions per second, with transactions being logged in the blockchain every 10 minutes. Since the network of bitcoin users continues to grow, however, the number of transactions made in 10 minutes will eventually exceed the number of transactions which can be processed in 10 minutes. | Low | [
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Q: Eclipse : XML tree or Grid view I used Eclipse a year back for editing xml file, and had a tree view available.I think I used IDE for Java EE developer then. As part of other development, I installed Eclipse Classic 3.7.2, this time. Through the Help -> Install new software, I installed 1.) Eclipse XML Editors and Tools 2.) Eclipse XSL developer Tools. Even then, I only have a source/textual representation of xml. How to enable tree view? Also, is there a way to get a grid editor (similar to myeclipse "Spring Beans Editor - New Grid Mode") An ideal setup would be a very minimal eclipse installation intended for xml editing. With support for grid mode, and copy/paste/insert of nodes. A: Check your file associations. Since you started with Eclipse classic it's possible that the file associations that bind the .xml files to the XML editor were not set up. Go to Preferences -> General -> Editor -> File Associations and then select the XML editor which should give you both the text and tree view. | High | [
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Receive the latest national-international updates in your inbox While much of the world anxiously awaits what happens under U.S. President-elect Donald Trump, one factory manager in Japan is all smiles. Ogawa Studio, the only manufacturer of rubber masks in Japan, is working feverishly to catch up with a flood of orders for Trump masks since his election victory last week. The 23 workers at the plant in Saitama, a city in Tokyo's northern suburbs, are trying to produce 350 likenesses of Trump a day, up from 45 before the U.S. election, factory executive manager Takahiro Yagihara said Tuesday. The factory also produces masks of unsuccessful Democratic candidate Hillary Clinton, President Barack Obama and other Japanese and international politicians and celebrities. Trump Booed Leaving New York Times President Elect Donald Trump is booed as he walks through the lobby of The New York Times Building after a 75-minute meeting with Times journalists. The lobby of the Times building is open to the public, and a large crowd had gathered by the time he departed. (Published Tuesday, Nov. 22, 2016) The masks emphasize Trump's characteristic hair and facial expression. They are first spray-painted to add natural tan to the skin and yellowing to the hair. Then an employee hand-paints details such as blue eyes for a life-like resemblance. Yagihara said most customers wear the masks for year-end parties and other social gatherings. They cost 2,400 yen ($22) each and are available in Japan at toy and retail stores and on internet shopping sites. | Low | [
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This invention relates to phosphate-binding polymers for oral administration. People with inadequate renal function, hypoparathyroidism, or certain other medical conditions often have hyperphosphatemia, meaning serum phosphate levels of over 6 mg/dL. Hyperphosphatemia, especially if present over extended periods of time, leads to severe abnormalities in calcium and phosphorus metabolism, often manifested by aberrant calcification in joints, lungs, and eyes. Therapeutic efforts to reduce serum phosphate include dialysis, reduction in dietary phosphate, and oral administration of insoluble phosphate binders to reduce gastrointestinal absorption. Dialysis and reduced dietary phosphate are usually insufficient to adequately reverse hyperphosphatemia, so the use of phosphate binders is routinely required to treat these patients. Phosphate binders include calcium or aluminum salts, or organic polymers such as ion exchange resins. Calcium salts have been widely used to bind intestinal phosphate and prevent absorption. The ingested calcium combines with phosphate to form insoluble calcium phosphate salts such as Ca.sub.3 (PO.sub.4).sub.2, CaHPO.sub.4, or Ca(H.sub.2 PO.sub.4).sub.2. Different types of calcium salts, including calcium carbonate, acetate (such as the pharmaceutical "PhosLo.RTM."), citrate, alginate, and ketoacid salts have been utilized for phosphate binding. The major problem with all of these therapeutics is the hypercalcemia which often results from absorption of the high amounts of ingested calcium. Hypercalcemia causes serious side effects such as cardiac arrhythmias, renal failure, and skin and visceral calcification. Frequent monitoring of serum calcium levels is required during therapy with calcium-based phosphate binders. Aluminum-based phosphate binders, such as the aluminum hydroxide gel "Amphojel.RTM.", have also been used for treating hyperphosphatemia. These compounds complex with intestinal phosphate to form highly insoluble aluminum phosphate; the bound phosphate is unavailable for absorption by the patient. Prolonged use of aluminum gels leads to accumulations of aluminum, and often to aluminum toxicity, accompanied by such symptoms as encephalopathy, osteomalacia, and myopathy. Organic polymers that have been used to bind phosphate have typically been ion exchange resins. Those tested include "Dowex.RTM." anion-exchange resins in the chloride form, such as XF 43311, XY 40013, XF 43254, XY 40011, and XY 40012. These resins have several drawbacks for treatment of hyperphosphatemia, including poor binding efficiency, necessitating use of high dosages for significant reduction of absorbed phosphate. In addition, the ion exchange resins also bind bile salts. | Mid | [
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502 F.2d 784 *dPembertonv.U. S. 73-3457 UNITED STATES COURT OF APPEALS Fifth Circuit 9/17/74 1 W.D.Tex. AFFIRMED * Summary Calendar case; Rule 18; 5 Cir.; see Isbell Enterprises, Inc. v. Citizens Casualty Co. of N | Low | [
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One Medical Malpractice Bill Remains Cheyenne, Wy – The last major medical malpractice bill before the legislature will come up for a final time Wednesday and it could face some trouble. House Joint Resolution 11 would ask voters to make a medical review panel constitutional. Senator Charlie Scott added a major amendment to the proposal to make up for some bills that failed earlier in the session. But, Scott says he will try to get it removed because the amendment only had 15 supporters and the resolution needs 20 votes to pass. Scott does say the resolution could help a little, but others admit they are having second thoughts. | Low | [
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Q: Finalization on StreamWriter and StreamReader If I have this: StreamWriter cout = new StreamWriter("test.txt"); cout.WriteLine("XXX"); // here IOException... StreamReader cin = new StreamReader("test.txt"); string text = cin.ReadLine(); the clr throws an IOException because I haven't close the cout. In fact If I do this: StreamWriter cout = new StreamWriter("test.txt"); cout.WriteLine("XXX"); cout.Close(); StreamReader cin = new StreamReader("test.txt"); string text = cin.ReadLine(); I have no exception. But If I do this and then exit from the application: StreamReader cin = new StreamReader("test.txt"); string text = cin.ReadLine(); without closing cin the file can from the OS opened and written. However reading the source code of StreamReader.cs I didn't' find a destructor method (i.e. ~StreamReader(...)). So who does free that file if the garbage collector doesn't invoke Dispose and there is no finalization method? A: Internally, the StreamReader uses a FileStream: Stream stream = new FileStream(path, FileMode.Open, FileAccess.Read, FileShare.Read, DefaultFileStreamBufferSize, FileOptions.SequentialScan, Path.GetFileName(path), false, false, checkHost); The FileStream class, being the class that ultimately accesses the file and therefore needs to guarantee cleanup, does have a finalizer, which closes the actual underlying stream. The Dispose method on the StreamReader just calls the Close on the underlying FileStream. A: StreamReader and StreamWriter uses a FileStream to access the file. FileStream uses SafeFileHandle to store the underlying OS file handle. As the SafeFileHandle class controls an unmanaged resource it correctly has a finalizer (what you call a destructor) that closes the file handle. But If I do this and then exit from the application: [...] without closing cin the file can from the OS opened and written When a process terminates all resources used by that process is released to the operating system. It doesn't matter if your application forgot to close a file handle (even though SafeFileHandle will not "forget"). You will always observe the described behavior no matter how badly written your application is. I just want to point out that the best way to work with StreamReader and StreamWriter and similar classes is using: using (StreamWriter cout = new StreamWriter("test.txt")) { cout.WriteLine("XXX"); } using (StreamReader cin = new StreamReader("test.txt")) { string text = cin.ReadLine(); } This deterministically closes the files when the using block ends even if an exception is thrown while processing the file. | High | [
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Two lane closure on M6 after fatal crash A woman has died following a crash on the M6 motorway between junctions 35 and 36. The M6 southbound, from J36 A590 (Kirkby Lonsdale) and J35 A601 (M) (Carnforth) is partially closed for several hours today, so police can carry out investigations following a fatal collision just after half-past midnight this morning. The crash involved a female pedestrian and a HGV. The pedestrian was taken to hospital, but later died. The HGV driver is helping police with their enquiries. Lanes one and two of the stretch of motorway could be shut for several hours. Cameras and matrix signs show lanes one and two (of three) are closed to aid police. | Mid | [
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The great sandwich smacking of 2011. That was horrible. We were just sandwich smacked. WE BARELY GOT OUT ALIVE. It was an exploding, rotten sandwich, with icky mayonnaise sauce, coming out from everywhere like lava. This game was a mayonnaise sandwich of ultimate catastrophe. My feelings can best be expressed through the following clip from the classic 1976 movie “Network,” starring Faye Dunnaway, William Holden and Peter Finch. And YES. You have to watch the WHOLE THING. If you want to see the play-by-play torture, scroll down for drunken ramblings. In the meantime, DO WHAT THE VIDEO CLIP SAYS. LET’S GET MAD, PEOPLE! I am a human being! My life has value! Get up out of your chairs. Get to the window. Open it. Stick your head out and yell, “I’m mad as hell and I’m not going to take this anymore!!!!!!!!!!!!!!!!” I CAN’T HEAR YOU! And if I can’t hear you, HOW IS TITO GOING TO HEAR YOU???? PS- Tomorrow we start a new campaign. PUT LACKEY ON THE DL. Because I can’t take this tomorrow too. Conclusions I have drawn from this game? The Red Sox are afraid of the letter “P.” PS- You KNOW you are in trouble when Beckett is on the “what went wrong” list and BOBBY JENKS is on the “what went right” list. God help us all. —————- —————- New bar. Get here 6th inning. Yeah. I saw that. All of that. Why Josh? Why? Adding to my frustration, sandwich game is on a television that is smaller than my computer. It takes me 20 minutes (and I COUNT) to get one of the 12+ big people televisions on the game. They are watching the Florida-South Carolina game. ON EVERY TELEVISION. Really? REALLY???? So, by the time I get my computer out to fake work and really blog- it’s the bottom of the 7th. I cannot talk about the evils that I saw in the 6th. No. I cannot. And now this Morales guy is stressing me the frick out. So, new bar. Closer to where I live. Farther from Boone. I think I’m in… *gasp* local territory. Clearly, I am the only one in here with a job. Does that sound judgmental? I do try not to be judgmental. Okay, Morales. We’re cool. 9:05 p.m. — Okay. This big people tv is pissing me off too. It has all these little sparkly flaws in the screen. Is that what not-HD is like? I am going to do the bar dance. I see it. All. Around. The. Bar. The strange bar. Where I know no one. And I really think that guy’s drink is really a tobacco spittoon. Ew. Ew-ew-ew. Make. It. Stop. My bartender has to be seventeen. Has to be. Seriously. — Wow. Just got a phone call from a really sweet guy I haven’t talked to in like a year. Because he moved. It was clearly a pocket dial. But how sweet to pretend he was calling to check up on me. — NO. I DO NOT WANT A PBR. I AM DRINKING A SAM ADAMS! SEE? IF I NEEDED ANOTHER DRINK, I WOULD NOT BE PORING OVER MY COMPUTER DOING FAKE WORK AND WATCHING A GAME. This. This is called AVOIDING EYE CONTACT WITH YOU. — I think this was a bar fail. Hi, McDonald. 9:11. That strike hurt my soul. — AND another thing. There are subtitles. Which is smarmy keen, really. Except that I can’t see any stats. Or anything, really. — Hmmm. Maybe that wasn’t a pocket dial. But probably. I am conflicted. — You know. My mother (the mother that wants me to marry Reddick and not my soulmate Kevin Youkilis) says I should never go to bars alone. Of course not, I say. — Jason Varitek. He looks good today. Oh, and a close up of Kevin Youkilis. Not while Tek is batting, kids, you’ll distract me! The way the stadium just glistens off his bald head. But also about how kickass awesome the Sox offense is. Seriously. WHERE IS THAT? Padres. Pirates. Phillies. OHMYGOD. We have something against the letter “P.” I will drink another beer and analyze this revelation privately. Perhaps on a napkin. 9:16. One out. Top of the 8th. Rallyin’ time. Right? Right? — STOP TALKING ABOUT JAMES SHIELDS!!!! THIS IS A BOSTON GAME. —- The subtitle gods can’t spell. Why are you even playing? You’re like an insta-out!!!!!!! CAMERON! Add a del- before your name and call you loser. You heard me. — Not even my Boston beer can save us now. —- 9:19. Scut. Fricktastic. 2 outs. — DAMN YOU, SCUT. 9:20. — Okay. When a girl is yelling at a television screen and throwing coasters, DO NOT APPROACH HER. Tell your friends. —- I am using the commercial break to analyze this guy’s jellyfish tattoo. I asked him if I could take a picture of it so you could analyze it too (I didn’t tell him I would put it on the internet) and he was like “no.” He doesn’t seem to want to talk to me. He’d rather spit into a cup. I am delightful, I say. Not only should you want to talk to me, you should be astounded and honored that I want to take a picture of your tattoo. He opens his mouth to speak. SHHH. The game is back on. Some people. — NOOOOOOOOOOOOOOOOOOOOOOOO Bobby Fricking Jenks. NOOOOOOOOOOOOOOOOOOOOOOOO Well, now that I’ve alienated everyone around me… — Okay. Out 1. You didn’t do that Jenks. That was god. Don’t get cocky. Why????? Is John Lackey really going to pitch tomorrow? Really-really? Are you sure he’s not going to get on the DL? Maybe he’s already there and I just don’t know it. You’d tell me, right? You’d tell me? Cameron- is that a tattoo on your neck? Remind me to google that later. Is it just me or did Jenks trim his stupid goattee a bit? How do you spell goatee? Oh. — Yeah. Strike three. Sit the frick down. Yeah, I don’t know if that was a strike either. But I’m sure you deserved that call. You know, for being a bad person or something. —- 9:27. Chase Utley. You look painfully normal. Bobby Jenks. Sigh. WHAT WAS THAT, JENKS? Did the baseball dirt LOOK like a catcher’s mitt? Excuse me, random guy at bar? WHAT THE HELL DOES IT LOOK LIKE I’M WATCHING? Okay. I’m wearing a Fenway t-shirt and a sour disposition. WHO DO YOU THINK I’M ROOTING ON? Look. I can’t be expected to answer your stupid questions. Did you see that? That was my husband. MY HUSBAND. Thanks, Youk. Bobby Jenks, you should kiss his shoes. —– We have really Posada-ed ourselves, haven’t we? —- 2 outs. One on first. There is no sound. I am so confused about these mystery calls. I feel like Youkie and I are playing our own private game of baseball charades. The guy behind me has really big teeth. I’m just saying. Hi, Jason Varitek. I don’t think they’re real. The teeth. Not Jason Varitek. I should give this guy gum or something. You know. As a test. Anyone have any gum? —- 9:32. “A full cout,” subtitle says. I think you mean COUNT. Cout Dracula. Ahahahahaha. Time for another beer. NOW I’m ready for that PBR. Thanks. —- My name? Argentina. Argentina Jones. I’m a mathematician, you see. Solving mysteries through math. Like in 3-2-1 Count Down and that show called “Numbers.” Of course I’m being serious. Your name? Kip? Seriously? Don’t laugh, Lauren. That’s rude. —- Yeah. Bar fail. It is the bottom of the 8th. STILL. TWO ON BASE (THANKS, JENKS). 9:35. TWO OUTS. — Hi, FDA. I’m glad you’re out there somewhere. Like in Fievel. Commenting from afar but looking at the same moon. Except it’s not a moon. It’s Bobby fricking Jenks. Josh Beckett makes my soul cry. Now, I don’t know what happened. I was doing that job thing. So maybe they said something to you, Beckett. Maybe they insulted rocket scientists or something. I don’t know. But I’d like an essay, at least 5 paragraphs, on my desk TOMORROW, explaining exactly what happened and how you sure as frick won’t let it happen again. Cranberry girl, you do realize, don’t you, that trading the guy is even better than the DL? And yes, Theo was also drinking in a bar and watching the Sox lose when he decided to sign Lackey to that thirty-five year deal for $417 billion in the first place. And you know WHY he signed Lackey? (No, why?) To KEEP HIM AWAY FROM THE YANKEES!!! It’s actually funny, if you’re drunk enough. Well…no Carl Crawford (injured)…no David Ortiz (how about that DH rule)…playing Darnell McDonald fifth…Mike Cameron playing period…lost four or last five…Beckett having not pitched for almost two weeks because of whatever…and then there was Cliff Lee. Why Boston let him “go” on only five pitches in the first inning was puzzling. I read Adrian Gonzalez is headed to the outfield tonight so Ortiz can play first. Dustin Pedroia made a joke about having to play second, first and right. I told you folks not to worry in April and I will tell you again not to worry…let’s see what the Sox do at trading time to shore up rotation…and maybe RF. Any prospects in the farm system named “Sam Adams?” It is Bruce…and for that matter…while I know Lauren’s name is Lauren (because she’s very likely to speak to herself AND us) I don’t believe I recall YOUR real first name FDA…(wink smile). Seriously, we know the Sawx are hurting right now but we respect Boston and we’ll take any wins we can get. Hell, if you get past our starters we’re toast. The entire bullpen is on the DL. | Low | [
0.490494296577946,
32.25,
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Generally, when a heavy cargo is loaded on a truck used in a factory or the like, the worker needs to push the truck with a large force at start of conveyance, which is a heavy labor. JP2008-126900A discloses an electric truck provided with a driving device for driving the truck through a connecting member. In this electric truck, the driving device is connected to the truck through the connecting member with one end connected to the truck, the connecting member being capable of swing around a horizontal axis. | Low | [
0.5274261603375521,
31.25,
28
] |
Q: select box by simple_form in Rails - save id, not title I use Simple Form in Rails app for generate forms. Schema: create_table "product_materials", force: :cascade do |t| t.integer "product_id" t.integer "material_id" t.integer "level", default: 0 t.integer "value", default: 0 t.datetime "created_at", null: false t.datetime "updated_at", null: false end Model: class ProductMaterial < ActiveRecord::Base belongs_to :product belongs_to :material enum level: [:joinery, :grinding, :painting, :assembly] end View: = simple_form_for [:admin, @product_material], remote: true do |f| => f.hidden_field :product_id, value: @product.id => f.input :level, collection: [t('product.joinery'), t('product.grinding'), t('product.painting'), t('product.assembly')], label: false => f.association :material => f.submit t('form.save') And now is a question: How I can in select_box show some collection of names (using I18n), but save a number of selected item (integer)? A: How I can in select_box show some collection of names (using I18n), but save a number of selected item (integer)? ProductMaterial.levels should return a hash like(note a plural form levels): => {"joinery"=>0, "grinding"=>1, "painting"=>2, "assembly"=>3} You can use it, all what you need it's make an array of arrays: => ProductMaterial.levels.keys.map{ |x| t("product.#{x}") }.zip(ProductMaterial.levels.values) #> [[t("product.joinery"), 0], [t("product.grinding"), 1], [t("product.painting"), 2], [t("product.assembly"), 3]] In input: => f.input :level, collection: ProductMaterial.levels.keys.map{ |x| t("product.#{x}") }.zip(ProductMaterial.levels.values), label: false enum have a good documentation. | Mid | [
0.6366120218579231,
29.125,
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456 P.2d 996 (1969) STATE of Oregon, Respondent, v. Fredrick Elliott FETTERLY, Appellant. Supreme Court of Oregon, En Banc. Decided July 25, 1969. Argued and Submitted May 8, 1969. George O. Tamblyn, Portland, argued the cause for appellant. With him on the brief was Donald H. Crouch, Milwaukie, Thomas H. Denney, Deputy Dist. Atty., Oregon City, argued the cause for respondent. With him on the brief was Roger Rook, Dist. Atty., Oregon City. Before PERRY, C.J., and McALLISTER, SLOAN, O'CONNELL, GOODWIN, DENECKE, and HOLMAN, JJ. HOLMAN, Justice. Defendant appealed from a conviction of a violation of ORS 483.443(1), which prohibits the operation of a motorcycle without wearing protective headgear. Defendant's sole ground of appeal is that such a statute is an improper exercise of the police power of the state in that the restraint of the statute upon his personal liberty bears no relation to a legitimate public purpose and, therefore, contravenes the Ninth, Tenth and § 1 of the Fourteenth Amendments to the United States Constitution and §§ 1, 20 and 33 of Article I of the Oregon Constitution. He argues that the sole effect of the statute is to protect the motorcyclist and that an individual has the right to engage in hazardous activity so long as he constitutes no hazard to others. The extent of the authority of the state through its exercise of the police power has been described as follows: "* * * The police power may be exerted in the form of state legislation where otherwise the effect may be to invade rights guaranteed by the Fourteenth Amendment only when such legislation bears a real and substantial relation to the public health, safety, morals, or some other phase of the general welfare. * * *." Liggett Co. v. Baldridge, 278 U.S. 105, 111-112, 49 S.Ct. 57, 59, 73 L.Ed. 204 (1928). A motorcycle is a vehicle capable of great speed and its operator is in an exposed position of extreme vulnerability to objects that may be thrown up by other vehicles. It is a common experience to have a rock or other object hit the windshield of an automobile with extreme force. Such an object hitting the head of a cyclist could easily cause unconsciousness or at least momentarily render him unable to handle his vehicle. An uncontrolled vehicle has the potential to affect the safety of other motorists and members of the public adjacent the highway. The possible consequences of the momentary loss of control by a cyclist is described in Bisenius v. *997 Karns, 42 Wis.2d 42, 165 N.W.2d 377 (1969), as follows: "If the picture that flashes to mind is that of a solitary cyclist on a deserted country road losing control and hitting (sic), an affirmative answer seems plausible. But not all highways are deserted these days; in fact, few are. If the loss of cyclist control were to occur on a well-travelled highway, the separation between consequence and incidence is less sharp. Anything that might cause a driver to lose control may well tragically affect another driver. If the loss of cyclist control occurs on a crowded freeway with its fast-moving traffic, the verring (sic) of a cyclist from his path of travel may pile up a half-dozen vehicles." It is our conclusion that the regulation in question bears a real and substantial relationship to public safety. It has been suggested that if the purpose of the statute is really to deflect flying objects, a windshield requirement on motorcycle manufacturers would bear a more reasonable relationship to the objectives sought. See American Motorcycle Association v. Davids, 11 Mich. App. 351, 158 N.W.2d 72, 75 (1968). This suggestion overlooks that a determination of the over-all preferability of alternative solutions to such a problem is usually considered a legislative and not a judicial function. The defendant urges in the words of Bates v. Little Rock, 361 U.S. 516, 524, 80 S.Ct. 412, 4 L.Ed.2d 480 (1960), quoted in the concurring opinion of Goldberg, J., in Griswold v. Connecticut, 381 U.S. 479, 497, 85 S.Ct. 1678, 1689, 14 L.Ed.2d 510 (1965), that "Where there is a significant encroachment upon personal liberty, the State may prevail only upon showing a subordinating interest which is compelling, * * *." This is a recognition that a balancing test occurs between the individual rights infringed and the benefits to the public welfare. In Bisenius v. Karns, supra, the court remarked that the right to be left alone does not include the right to do "one's thing" on an expressway. The court said: "* * * There is no place where any such right to be let alone would be less assertable than on a modern highway with cars, trucks, busses and cycles whizzing by at sixty or seventy miles an hour. When one ventures onto such a highway, he must be expected and required to conform to public safety regulations and controls, including some that would neither have been necessary nor reasonable in the era of horse-drawn vehicles." While it must be recognized that the chances of causing injury to others by failure to wear protective headgear are not as great as those resulting from most conduct which is the subject of motor vehicle regulation, the danger does exist and is a real one. On the other hand, the right to operate a motorcycle without protective headgear does not, in the scheme of things, loom very large when compared with any danger to the life and limb of others. We conclude that the legislature, in passing the questioned statute, has created no unconstitutional inbalance between the personal liberty of the individual and interest of the state. The majority of the courts which have passed upon the problem have upheld similar statutes. See: State v. Burzycki (Cir. Ct.App.Div. 1969) petition for certification of appeal denied, 252 A.2d 312; Everhardt v. City of New Orleans, 253 La. 285, 217 So.2d 400 (1969), reversing 208 So.2d 423 (La. App. 1968); Commonwealth v. Howie, 238 N.E.2d 373 (Mass. 1968), cert. den. 393 U.S. 999, 89 S.Ct. 485, 21 L.Ed.2d 464 (1968); State v. Anderson, 275 N.C. 168, 166 S.E.2d 49 (1969), affirming 3 N.C. App. 124, 164 S.E.2d 48 (1968); State v. Odegaard, N.D., 165 N.W.2d 677 (1969); State v. Mele, 103 N.J. Super. 353, 247 A.2d 176 (Hudson Co.Ct. 1968); People v. Carmichael, 56 Misc.2d 388, 288 N.Y.S.2d 931 (Genesee Co.Ct. 1968), reversing 53 Misc.2d 584, 279 N.Y.S.2d 272 (Sp.Sess.Ct. 1967); People v. Newhouse, 55 Misc.2d 1064, 287 N.Y.S.2d 713 (Ithaca City Ct. *998 1968); People v. Beilmeyer, 54 Misc.2d 466, 282 N.Y.S.2d 797 (Buffalo City Ct. 1967); People v. Schmidt, 54 Misc.2d 702, 283 N.Y.S.2d 290 (Erie Co.Ct. 1967); State ex rel. Colvin v. Lombardi, 241 A.2d 625 (R.I. 1968); Bisenius v. Karns, 42 Wis.2d 42, 165 N.W.2d 377 (1969). Contra: American Motorcycle Association v. Davids, 11 Mich. App. 351, 158 N.W.2d 72 (1968); People v. Smallwood, 52 Misc.2d 1027, 277 N.Y.S.2d 429 (Sp.Sess.Ct. 1967). For comparison purposes see Illinois v. Fries, Ill., 250 N.E.2d 149 (1969). We hold that the statute was within the police power of the state and therefore constitutional. The judgment of the trial court is affirmed. | Mid | [
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Income was disguised to help Manafort, tax preparer says Friday ALEXANDRIA, Va. — One of Paul Manafort's tax preparers admitted Friday that she helped disguise $900,000 in foreign income as a loan in order to reduce the former Trump campaign chairman's tax burden. The testimony of tax preparer Cindy Laporta came as prosecutors from special counsel Robert Mueller's office focused on the heart of their financial fraud case against Manafort, with jurors hearing testimony that he inflated his business income by millions of dollars and concealed foreign bank accounts he was using to buy luxury items and pay personal expenses. Manafort's defense has sought to blame any criminal conduct on his longtime deputy Rick Gates, while witnesses for the prosecution have testified that Manafort was heavily involved in his own finances and personally directed Gates' actions. On Friday, Laporta acknowledged that she agreed under pressure from Gates during a conference call in September 2015 to alter a tax document for one of Manafort's businesses to show the $900,000 loan. When Laporta and a colleague provided an assessment of how much tax Manafort would owe, Gates responded that Manafort didn't have the money to pay it. After a back-and-forth discussion about how much income should be reclassified as a loan to aid Manafort, they settled on $900,000, she testified. The result, Laporta said, was an altered tax payment that Gates told her "could be paid by Mr. Manafort." Laporta, who testified under a grant of immunity from prosecutors, said she knew what she did was "not appropriate," adding that "you can't pick and choose what's a loan and what's income." That testimony is important as prosecutors try to rebut defense arguments that Manafort can't be responsible for financial fraud because he left the details of his spending to others. Those others include Gates, who pleaded guilty earlier this year and is expected to testify soon as the government's star witness. Manafort faces charges of bank fraud and tax evasion that could put him in prison for the rest of his life. It's the first courtroom test of Mueller's team, which is tasked with looking into Russia's efforts to interfere with the 2016 U.S. election and whether the Trump presidential campaign colluded with the Kremlin to sway voters. In Friday's testimony, and throughout the trial thus far, neither Trump nor Russia has been discussed, as evidence has focused on Manafort's work as a consultant in the years before he joined Trump's campaign in the presidential year. While the question of collusion remains unanswered, Manafort's financial fraud trial has exposed the secretive world of foreign lobbying that made him rich. It has also revealed how, when income from his Ukrainian political consulting work dried up, he struggled to pay his bills and, prosecutors say, began obtaining bank loans under false pretenses. Laporta's testimony built on that of another of Manafort's accountants, Philip Ayliff, who told jurors that Manafort denied on multiple occasions that he controlled foreign bank accounts when asked. That's why the accounts weren't reported on years' worth of Manafort's tax returns as required by federal law, Ayliff said. Ayliff also testified that he sometimes communicated with Gates about the former Trump campaign chairman's personal and business tax returns. But he said Manafort authorized those discussions, and Gates and Manafort never contradicted each other. In one instance, Ayliff testified that Manafort pressed him to tell bankers considering a loan application that one of Manafort's New York properties was being used as a personal residence when in fact he was using it to rent out. Classifying the property as a personal residence would have made it easier to obtain the mortgage. Ayliff responded to Manafort that "we have always treated it as a rental. ... Not sure where that leaves us." That email exchange occurred around the time prosecutors say Manafort was using doctored documents to secure loans. Bookkeeper Heather Washkuhn testified earlier in the trial that a series of profit-and-loss statements Manafort submitted with his loan applications were fake including one that inflated the net income of his business by about $4 million. Washkuhn also testified that Manafort never told her that millions in foreign wire transfers were coming from companies prosecutors say he controlled. "I would say he was very knowledgeable," Washkuhn told jurors. "He was very detail-oriented. He approved every penny of everything we paid." Other witnesses testifying this week said Manafort paid them millions from offshore accounts tied to foreign shell companies for landscaping, expensive clothing and even a karaoke machine. During cross examination, Manafort attorney Thomas Zehnle pressed Washkuhn to say that Gates was heavily involved in approving expenses. But Washkuhn said that while Gates dealt with some business matters for Manafort's consulting firm, "mainly Mr. Manafort was the approval source." The trial in northern Virginia is the first of two for Manafort. A second trial is scheduled for September in the District of Columbia. That case involves allegations that he acted as an unregistered foreign agent for Ukrainian interests and made false statements to the U.S. government. Associated Press writers Chad Day and Eric Tucker contributed to this report. Never miss a story Choose the plan that's right for you. Digital access or digital and print delivery. Stay Connected Original content available for non-commercial use under a Creative Commons license, except where noted. The St. Augustine Record ~ One News Place, St. Augustine, FL 32086 ~ Privacy Policy ~ Terms Of Service | Mid | [
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<?php /* * This file is part of the Symfony package. * * (c) Fabien Potencier <[email protected]> * * For the full copyright and license information, please view the LICENSE * file that was distributed with this source code. */ namespace Symfony\Bridge\Twig\Extension; use Symfony\Component\Routing\Generator\UrlGeneratorInterface; use Twig\Extension\AbstractExtension; use Twig\Node\Expression\ArrayExpression; use Twig\Node\Expression\ConstantExpression; use Twig\Node\Node; use Twig\TwigFunction; /** * Provides integration of the Routing component with Twig. * * @author Fabien Potencier <[email protected]> */ final class RoutingExtension extends AbstractExtension { private $generator; public function __construct(UrlGeneratorInterface $generator) { $this->generator = $generator; } /** * {@inheritdoc} */ public function getFunctions(): array { return [ new TwigFunction('url', [$this, 'getUrl'], ['is_safe_callback' => [$this, 'isUrlGenerationSafe']]), new TwigFunction('path', [$this, 'getPath'], ['is_safe_callback' => [$this, 'isUrlGenerationSafe']]), ]; } public function getPath(string $name, array $parameters = [], bool $relative = false): string { return $this->generator->generate($name, $parameters, $relative ? UrlGeneratorInterface::RELATIVE_PATH : UrlGeneratorInterface::ABSOLUTE_PATH); } public function getUrl(string $name, array $parameters = [], bool $schemeRelative = false): string { return $this->generator->generate($name, $parameters, $schemeRelative ? UrlGeneratorInterface::NETWORK_PATH : UrlGeneratorInterface::ABSOLUTE_URL); } /** * Determines at compile time whether the generated URL will be safe and thus * saving the unneeded automatic escaping for performance reasons. * * The URL generation process percent encodes non-alphanumeric characters. So there is no risk * that malicious/invalid characters are part of the URL. The only character within an URL that * must be escaped in html is the ampersand ("&") which separates query params. So we cannot mark * the URL generation as always safe, but only when we are sure there won't be multiple query * params. This is the case when there are none or only one constant parameter given. * E.g. we know beforehand this will be safe: * - path('route') * - path('route', {'param': 'value'}) * But the following may not: * - path('route', var) * - path('route', {'param': ['val1', 'val2'] }) // a sub-array * - path('route', {'param1': 'value1', 'param2': 'value2'}) * If param1 and param2 reference placeholder in the route, it would still be safe. But we don't know. * * @param Node $argsNode The arguments of the path/url function * * @return array An array with the contexts the URL is safe */ public function isUrlGenerationSafe(Node $argsNode): array { // support named arguments $paramsNode = $argsNode->hasNode('parameters') ? $argsNode->getNode('parameters') : ( $argsNode->hasNode(1) ? $argsNode->getNode(1) : null ); if (null === $paramsNode || $paramsNode instanceof ArrayExpression && \count($paramsNode) <= 2 && (!$paramsNode->hasNode(1) || $paramsNode->getNode(1) instanceof ConstantExpression) ) { return ['html']; } return []; } } | Mid | [
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// Copyright (c) Microsoft Corporation.
// Licensed under the MIT License.
using System;
using System.Diagnostics.ContractsLight;
using BuildXL.Cache.ContentStore.Interfaces.Logging;
namespace BuildXL.Cache.Logging.External
{
/// <summary>
/// Implements an <see cref="IOperationLogger"/> that dispatches <see cref="ILogger"/> functions to a specific
/// instance, and <see cref="IOperationLogger"/>-only operations to a different instance.
/// </summary>
/// <remarks>
/// The inner loggers are considered to not be owned by the current class. This means we do not dispose them.
/// </remarks>
public sealed class MetricsAdapter : IOperationLogger, IStructuredLogger
{
private readonly IStructuredLogger _logger;
private readonly IOperationLogger _operations;
/// <nodoc />
public MetricsAdapter(IStructuredLogger logger, IOperationLogger operations)
{
Contract.RequiresNotNull(logger);
Contract.RequiresNotNull(operations);
Contract.Requires(logger != operations);
_logger = logger;
_operations = operations;
}
/// <inheritdoc />
public Severity CurrentSeverity => _logger.CurrentSeverity;
/// <inheritdoc />
public int ErrorCount => _logger.ErrorCount;
/// <inheritdoc />
public void Diagnostic(string messageFormat, params object[] messageArgs) => _logger.Diagnostic(messageFormat, messageArgs);
/// <inheritdoc />
public void Debug(string messageFormat, params object[] messageArgs) => _logger.Debug(messageFormat, messageArgs);
/// <inheritdoc />
public void Debug(Exception exception) => _logger.Debug(exception);
/// <inheritdoc />
public void Info(string messageFormat, params object[] messageArgs) => _logger.Info(messageFormat, messageArgs);
/// <inheritdoc />
public void Warning(string messageFormat, params object[] messageArgs) => _logger.Warning(messageFormat, messageArgs);
/// <inheritdoc />
public void Error(string messageFormat, params object[] messageArgs) => _logger.Error(messageFormat, messageArgs);
/// <inheritdoc />
public void Error(Exception exception, string messageFormat, params object[] messageArgs) => _logger.Error(exception, messageFormat, messageArgs);
/// <inheritdoc />
public void ErrorThrow(Exception exception, string messageFormat, params object[] messageArgs) => _logger.Error(exception, messageFormat, messageArgs);
/// <inheritdoc />
public void Fatal(string messageFormat, params object[] messageArgs) => _logger.Fatal(messageFormat, messageArgs);
/// <inheritdoc />
public void Always(string messageFormat, params object[] messageArgs) => _logger.Always(messageFormat, messageArgs);
/// <inheritdoc />
public void Flush() => _logger.Flush();
/// <inheritdoc />
public void Log(Severity severity, string message) => _logger.Log(severity, message);
/// <inheritdoc />
public void LogFormat(Severity severity, string messageFormat, params object[] messageArgs) => _logger.LogFormat(severity, messageFormat, messageArgs);
/// <inheritdoc />
public void Log(Severity severity, string correlationId, string message) => _logger.Log(severity, correlationId, message);
/// <inheritdoc />
public void Log(in LogMessage logMessage) => _logger.Log(logMessage);
/// <inheritdoc />
public void LogOperationStarted(in OperationStarted operation) => _logger.LogOperationStarted(operation);
/// <inheritdoc />
public void LogOperationFinished(in OperationResult result)
{
// Need to call the both loggers, because the first one will write to the file and
// will emit telemetry and the operations logger will write to MDM.
_logger.LogOperationFinished(result);
_operations.OperationFinished(result);
}
/// <inheritdoc />
public void OperationFinished(in OperationResult result) => _operations.OperationFinished(result);
/// <inheritdoc />
public void TrackMetric(in Metric metric) => _operations.TrackMetric(metric);
/// <inheritdoc />
public void TrackTopLevelStatistic(in Statistic statistic) => _operations.TrackTopLevelStatistic(statistic);
/// <inheritdoc />
public void RegisterBuildId(string buildId) => _operations.RegisterBuildId(buildId);
/// <inheritdoc />
public void UnregisterBuildId() => _operations.UnregisterBuildId();
/// <inheritdoc />
public void Dispose()
{
// NOTE(jubayard): this doesn't dispose anything because it doesn't own the inner loggers.
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The rate of deliberately lit fires escalates rapidly during the school holiday period, according to an expert in arson investigations. Key points: Most fires have a human source and up to half are thought to be deliberately lit, Dr Read said Most fires have a human source and up to half are thought to be deliberately lit, Dr Read said Teens have been charged over the Peregian fire, but older arsonists are often the most dangerous Teens have been charged over the Peregian fire, but older arsonists are often the most dangerous Dr Read says arson investigations rely upon suspicious behaviour being reported The warning comes after emergency services personnel spent recent weeks battling out-of-control bushfires that raged across parts of Queensland. Dr Paul Read, co-director of the National Centre for Research in Bushfire and Arson, said the great majority of bushfires are deliberately lit by "cunning, furtive and versatile criminals". "About 85 per cent are related to human activity, 13 per cent confirmed arson and 37 per cent suspected arson," he said. "The remainder are usually due to reckless fire lighting or even just children playing with fire." Dr Read said holidays and summer were a bad combination when it came to fire starters. "School holidays are a prime time for fire bugs, but especially over summer," he said. "The kids have got time to get out there and light, and the most dangerous adults choose hot days." Bushfires that swept through Applethorpe on Queensland's Granite Belt were accidentally started by backpackers. ( ABC News: Mark Leonardi ) Taskforce Overcross, which was set up by police this month, found 23 bushfires were thought to have been deliberately or carelessly lit, with action taken against 21 juveniles and nine adults. The bushfire in the Gold Coast hinterland that destroyed 11 properties and the historic Binna Burra Lodge is still under investigation. Two teenagers were charged over the Peregian Springs blaze and there have also been "suspicious" fires at Geebung on Brisbane's northside, Pimpama on the northern Gold Coast and in central Queensland. Backpackers who accidentally started the Stanthorpe and Applethorpe fires on the Granite Belt will not be charged. Police dealt with a 12-year-old boy under the Youth Justice Act, over a deliberately lit fire that destroyed bushland in Logan and two 14-year-old girls were also questioned over a bushfire that came close to homes at Ormeau on the north Gold Coast. Firefighters battled bushfires for weeks throughout Queensland. ( Supplied: Queensland Fire and Emergency Service ) Dr Read said while it was disturbing that so many children have been involved in lighting the recent fires, it's not surprising and sometimes not malicious. "Children with autism can have a fascination with fire and we also have kids who are victims of child abuse, neglect and depression and often the fire lighting is a cry for help," Dr Read said. "There is another group that is just experimenting with fire play and it gets out of hand. "The fourth group is the difficult group who are truly malicious and heading toward developing full-blown adult psychopathy. This is the group that really needs to be handled by the justice system." Older arsonists 'more concerning' Dr Read, who is also a Research Fellow at Melbourne's Monash University, said he was more concerned about older arsonists, who are likely to light fires on high fire danger days and closer to populated areas. "These people are above the age of 30 and get more dangerous the older they get," he said. Firefighters try to douse a bushfire at night near properties in a street at Peregian Beach. ( Supplied: Wavell Bush ) "What we're dealing with are people who are pretty embittered with life, some of low intelligence and others who have issues with violence, alcohol and drugs. "They suffer depression and sometime have personality disorders, sparked by relationship breakdowns or the loss of a job." Dr Read said there was no simple answer as to why people deliberately started fires. "They say that the typical arsonist is a versatile criminal and they can be really hard to profile," he said. Ballandean rural firefighter Aaron Cox broke down after fighting to save his own house. ( Facebook: Bindi Cox ) "The more dangerous fire bugs will come out on the high fire danger days ... they're cunning, they know where to light and they know how to light a fire." A 53-year-old man was arrested and charged in Palm Grove on Thursday after allegedly trying to start a fire near Cedar Creek Falls. Seventeen houses have been destroyed since the fire crisis began last week and multiple fires are still burning around the state. Police Commissioner Katarina Carroll said Taskforce Overcross aimed to prevent, disrupt and investigate suspicious fires across Queensland. "Some of the behaviour… has been unfortunately reckless and other behaviour has been purposeful," Commissioner Carroll said. "The consequences of some of these fires are dire. "People can die, buildings and residents are being destroyed ... these are not usual conditions, they're actually quite dangerous." Commissioner Carroll said police would be relentless in investigating suspicious fires. "Arson is a very serious offence that can lead to life imprisonment." A bushfire south of Canungra approaching Lamington National Park on Queensland's Gold Coast hinterland on Friday, September 6. ( ABC News: David Higgins ) Dr Read praised the formation of the taskforce. "I absolutely commend that, it is very responsive," he said. "This taskforce will have the ability to collaborate with other departments, police and firefighters and even the community. "Arson is a very furtive crime and it's usually the community that has suspicions and that information needs to get to police." | Mid | [
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Ms Hanson has been held responsible for politicising immigration policy Australian former anti-immigration politician Pauline Hanson is selling up and heading to Britain, according to an interview with an Australian magazine. She told Women's Day that Australia was no longer a land of opportunity and she had "had enough" of living there. Ms Hanson built a career on claims that Australia was being "swamped by Asians" She was jailed briefly for fraud before the conviction was quashed. Her efforts to stage a political comeback in recent years have failed. "I'm going to be away indefinitely. It's pretty much goodbye forever," said Ms Hanson, 56. "I've really had enough. I want peace in my life. I want contentment, and that's what I'm aiming for." She told the magazine she would "never be given a chance to re-enter parliament" and wanted to "get out there" while she still had her health. "Sadly, the land of opportunity is no more applicable," she said, blaming high taxes, over-regulation and a "lack of true representation". Ms Hanson's father was born in England before emigrating to Australia, meaning she has the right to live in the UK. 'Swamped' Opposition Leader Tony Abbott said he was disappointed by Ms Hanson's decision but that it was her decision to make. "There was a time when she articulated a cry of rage from a section of the Australian population," the Herald Sun newspaper quoted Mr Abbott as saying. "But that time has passed and she's now chosen to go in different directions and that's her right." Ms Hanson was popular with some Australians in the 1990s with her anti-immigration and trade protection policies, before losing her seat in 1998. At its peak, her One Nation party attracted a million votes. In 2007, she ran unsuccessfully for a national Senate seat, switching her target from Asians to Islam and calling for an end to immigration by Muslims to protect "Australian culture". Last year, Hanson blamed her failure in the Queensland state election on the publication of raunchy photos purportedly taken by an ex-boyfriend. The pictures turned out not to be of her. Bookmark with: Delicious Digg reddit Facebook StumbleUpon What are these? E-mail this to a friend Printable version | Mid | [
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Q: Where to download the PyQt4 class reference? Is there an offline version of this PyQt4 class reference: http://doc.trolltech.com/4.3/classes.html? A: On debian based systems, there is a package called python-qt4-doc you can just install it via sudo apt-get install python-qt4-doc. Then the documentation is found in /usr/share/doc/python-qt4-doc/html/index.html and the class reference is /usr/share/doc/python-qt4-doc/html/classes.html | Mid | [
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Oscars Time: Potential Academy Awards Nominations Sneakers and Snubs Over on Twitter, a dear film friend Emi (@shruburbia) said “film twitter and the award circles have all ignored Roman J. Israel like it never happened”. Adding that she thought Denzel Washington will sneak in for Best Actor when the Oscar nominations are announced on Tuesday. Washington was of course nominated at the Screen Actors Guild, but that by no means guarantees him a place in the Academy’s five. “His performance was phenomenal,” Emi enthused, “even better by a nose over his role in Fences“. Filmotomy Podcast semi-regular Joel Melendez posted his entire Oscar predictions on Twitter. Also adding his outside bets including The Square NOT making the Foreign Language Film cut, James Franco being squandered from the Best Actor list, and predicts The Phantom Thread could stand with six nominations in total. Check out his full list on the Twitter thread here: When I asked Matt St.Clair who he thought might sneak in on Tuesday morning, he gave me four very intelligent potentials in the acting categories. Imagine Daniela Vega being named in the Best Actress line-up for A Fantastic Woman. “In a crowded Best Actress field,” Matt declared, “Chilean actress Daniela Vega has potential to be the first trans performer to be up for an acting Oscar given the foreign / arthouse contingent within the acting branch that got performances like Marion Cotillard in Two Days, One Night nominated in this category.” Ignored for Beast of No Nation a couple of years back, Matt also put forward Idris Elba as a Best Supporting Actor contender for Molly’s Game. “Idris Elba’s snub for Beasts Of No Nation still lingers, and if Jessica Chastain makes it in Best Actress, Elba could get pulled along with her given his snub and his two “Oscar clip” monologues towards the end.” Matt’s final two acting dark horses were: Tracy Letts for Best Supporting Actor in Lady Bird – a “renowned theater actor” Matt tells me, “Tracy Letts is someone who’s been building a quiet trajectory towards an Oscar nomination, having appeared in prestige films like Indignation, Lady Bird, and The Post. Which means he could surprise in this category for his portrayal of a loving father figure.” And lastly, Ben Mendelsohn in Supporting Actor for Darkest Hour. Matt’s argument incites “An Emmy-winning character actor typically typecast as villains playing King George VI in a baity British biopic? Seems like something Oscar would take note of.”. Matt St.Clair no doubt has many, many other worthy notions on his Twitter profile (@filmguy619). I’d personally add that Kristen Scott Thomas also has a great chance of making the Best Supporting Actress cut for Darkest Hour – even with limited screen time. Add to that, Catherine Keener is a long shot for Get Out in my books. Don’t act shocked, too, if you see Tiffany Haddish kick the fucking door down for actresses of color. In the Supporting Actor category, can Michael Shannon help The Shape of Water tally a record-equaling 14 nominations? Mark Rylance for Dunkirk is still not out of the question. My big hunches come in the Best Director category. When DGA announced their five it felt like that was the five for Oscar too. I’m not so sure. And I’ll hold my hands up if I am wrong. I wonder if Jordan Peele will get in. Or indeed Martin McDonagh. And what about Christopher Nolan? Imagine the internet-quake if he doesn’t got his first nomination for Best Director. Or indeed, Greta Gerwig‘s name is not read out. I agree with Joel, that Sean Baker has a terrific chance to push his way into the Director five a la Lenny Abrahamson for Room. The Florida Project is still in conversation almost everywhere, and fondly spoke of. Very much so. Those billboard posters in L.A. won’t hurt, nor will the preferential ballot voting for a beloved movie. Craig Gillespie has a slim chance of benefiting from I, Tonya‘s growing momentum at just the right time. Don’t forget about Luca Guadagnino either. Call Me by Your Name may seem like it’s sinking fast, which means it can pleasantly surprise us amidst the snubs that pull our hair out. Whatever happens when the Oscar nominations are announced, hold on tight to those movies you truly love from 2017. The Academy Awards are not everything. Not quite. | Mid | [
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Premier League 2 Tottenham Hotspur 1 (White 76) Arsenal 3 (Burton 38, Coyle 45, Tormey 90) Aided by three members of the first-team squad, Arsenal U23s secured a 3-1 victory away to rivals Tottenham Hotspur tonight as they secured their first victory since September. Following a difficult start to the game, Arsenal took the lead in the 35th minute through Robbie Burton and then made it 2-0 courtesy of Trae Coyle just before the break. Harvey White pulled a goal back for Tottenham in the second half, with the hosts threatening to get a point, but substitute Nathan Tormey ensured victory for Arsenal. Folarin Balogun missed out through injury, with Tyreece John-Jules replacing him up front, while the other changes saw first-team players Reiss Nelson and Emile Smith Rowe start at the expense of Tormey and Ben Cottrell. Konstantinos Mavropanos also started again. Hein Swanson-Mavropanos-Clarke-Bola M. Smith-Burton Coyle-Smith Rowe-Nelson John Jules Subs: Cottrell (for Nelson, 46), Tormey (for Coyle, 66), Olowu (for Swanson, 88). Not used: Hillson, Medley. There was initially some concern that the game wouldn’t go ahead due to floodlight failure at the Lamex Stadium, but, after a 15 minute delay, the match finally got underway. Tottenham started in the ascendancy, with Arsenal goalkeeper Karl Hein having to make a fine save to thwart Armando Shashoua before Shilow Tracey blasted an effort over. The lively Dilan Markanday then had an effort deflected wide, but Arsenal gradually started to assert themselves on proceedings, with Smith Rowe becoming increasingly influential. Smith Rowe had two chances in quick succession and then Arsenal took the lead, with captain Burton slotting home, while Zak Swanson deserved much praise for bursting down the right flank in the build-up to the goal. John-Jules then shot over following another slick interchange of passes and then it was 2-0, with the goal stemming from a Tottenham free-kick as Nelson pushed forward and the ball eventually found its way to Coyle, who finished well. The two-goal lead was perhaps rather harsh on Tottenham, who had been the better side for much of the first half, but Arsenal had finished the first 45 minutes very strongly indeed. Arsenal were also resolute at the back in the first half, with Mavropanos producing an outstanding display as he made several precisely-timed interceptions. Nelson, in what presumably a pre-planned change on his return from injury, was replaced by Cottrell for the start of the second half, and Arsenal had to cope with some Tottenham pressure early on, with Hein forced into another good stop. Tottenham then came close to scoring with another opportunity, but Arsenal then had chances of their own, with John-Jules shooting over after a cross from Matt Smith and Coyle having an effort saved after excellent work from Smith Rowe. Smith Rowe dragged an effort wide after exchanging passes with Tolaji Bola, and then Arsenal introduced Tormey in place of Coyle. The pressure increased on the Tottenham goal, with Mavropanos having a header saved on the line and Swanson then also being thwarted by Jonathan De Bie. The defender wanted a penalty, but referee Gary Parsons chose not to point to the spot. Tormey almost made an instant impact, with his dipping effort tipped over by De Bie, but Tottenham, rather against the run of play, pulled a goal back, with White finishing well. Joseph Olowu came on for Swanson and there were brief concerns regarding whether Arsenal would be able to see the game out, but then Tormey struck to make sure of the victory. This was a much-needed win for Arsenal and will hopefully provide Steve Bould’s side with a major injection of confidence. The first-team players involved all benefitted greatly from the experience, with Nelson getting 45 minutes under his belt and impressing in patches, while Mavropanos and Smith Rowe also caught the eye. As far as the U23 regulars are concerned, Coyle appears to be on an upward curve again after enduring a difficult couple of years, while Tormey remains rather under the radar but is continuing to make a major impact at this level. This Arsenal side are gradually becoming more effective as a unit at U23 level, and tonight’s victory could well be a major step in the right direction for them. | Low | [
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Man in shark head costume falls foul of Austria anti-veil law Published duration 9 October 2017 image copyright Getty Images image caption Street musicians in animal masks have also been issued warnings. File picture A man in a shark costume has fallen foul of an anti-burka law that recently came into force in Austria. Designed to ban the full-face Islamic veil, the law says people's faces must be visible from hairline to chin. The man in the shark mask was advertising a business in central Vienna and the business was fined. Street musicians in animal masks have also been given official warnings. Police have called for the controversial new law to be clarified. The company that had employed the man in a shark costume posted a picture of him on Facebook and announced the fine, saying officers had forced the man to take the costume head off. "Life isn't easy," they wrote. His costume reportedly came to the attention of police after a member of the public reported him for breaking the law. Full-face burka-style veils are banned in several European countries. In January Austria's ruling coalition agreed to prohibit full-face veils (niqab and burka) in public spaces such as courts and schools. It said it was considering a more general ban on state employees wearing the headscarf and other religious symbols. The measures were seen as an attempt to counter the rise of the far-right Freedom Party, which almost won the presidency in December 2016. | Low | [
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Andrew Sullivan Is Being Smug And Naive Andrew Sullivan, who like me works from home, and who unlike me has never worked in a newsroom or, to my knowledge, been on a college faculty for any length of time, says that I’m wrong to say that it is impossible now to make a “positive case” for orthodox Christian teaching on marriage, because (in my view) any opposition to same-sex marriage is seen as drive by bigotry. Andrew says that if orthodox Christians of goodwill want to be seen as not motivated by bigotry in their opposition to SSM, there’s something they can do about it: And the only way to distinguish yourself from these hateful factions is to make a positive case for your position. That’s always possible. From the very beginnings of our faith, Christians have made such a positive case, even as they were being thrown to the lions. And Rod won’t do it because someone might say something mean at the office! How delicate and sensitive these Christianists can be. But there is another major tension in this debate, facing another group: the growing number of Americans who favor gay marriage. The question for them is how to treat those who disagree with them. Piers Morgan’s CNN segment on Tuesday night was a vivid illustration of this tension. Morgan invited Ryan T. Anderson, a 31-year-old fellow from The Heritage Foundation, on his program to debate the issue. But Morgan did not have Anderson to sit at a table with him and Suze Orman, the 61-year-old financial guru, who is gay. Instead, Anderson was placed about 15 feet away from Morgan and Orman, among the audience, and had to debate from a distance. The message, in both the language used by Morgan and Orman, and the physical placement of Anderson on the set, was clear: they thought him morally inferior. Marc Shaiman, the Tony Award-winning composer (“Hairspray”), called Mr. Eckern last week and said that he would not let his work be performed in the theater. “I was uncomfortable with money made off my work being used to put discrimination in the Constitution,” Mr. Shaiman said. He added, however, that the entire episode left him “deeply troubled” because of the potential for backlash against gays who protested Mr. Eckern’s donation. “It will not help our cause because we will be branded exactly as what we were trying to fight,” said Mr. Shaiman, who is gay. “But I do believe there comes a time when you cannot sit back and accept what I think is the most dangerous form of bigotry.” Nobody reported that Eckern had been guilty of treating people in the workplace with bigotry. When it became known that he did not support SSM, and gave money to the campaign to stop it, he was compelled to resign, or see the institution he worked for ruined. Actress Susan Egan, who started the anti-Eckern protest, responded to the resignation: But she did not intend to force Eckern to resign. “I don’t think it was anybody’s goal,” she said. “I’m really sad. I think Scott is a good man. I think he genuinely cares about the theatre. I think he’s good at his job.” She added that had he not resigned, however, “I know there are people who would not have been satisfied.” Nice career you have there, Mr. Eckern. Sure would be a shame for something to happen to it. Nice business you have there, Mormon Restaurant Manager Lady. Sure would be a shame to have it destroyed. Sullivan’s complaint is disingenuous. I hear all the time from religious conservatives in various fields — in particular media and academia — who are afraid to disclose their own beliefs about same-sex marriage because most people within those fields consider opposition to SSM to be driven solely by hatred. Earlier this year, I had a conversation with a man who is probably the most accomplished and credentialed legal scholar I’ve ever met, someone who is part of this country’s law elite. The fact that I can’t identify him here, or get into specifics of what he told me, indicates something important about the climate within law circles around this issue. On this issue, he lives in the closet, so to speak, within his professional circles, and explained to me why it has become too dangerous to take a traditionalist stand in law circles, unless one is prepared to sabotage one’s career. In the near future, law degrees coming from law schools that don’t adhere full-on to the new orthodoxy on gay rights (if any exist) will be taken as seriously by the legal profession as degrees from Bob Jones University are. He also said that religious conservatives really don’t understand the McCarthyism that’s about to come at them. Simply affirming what their faith teaches about sexuality in context of the gay rights debate really is, and will increasingly be, seen not as evidence of one’s poor thinking, but rather as evidence of one’s personal evil. I told him that I understand it, because I’ve seen the same thing play out in my profession. I mentioned someone I know who works in a New York newsroom, at a senior level, who lives in the closet as an Evangelical, out of fear of her colleagues learning the truth — this, given their openly-expressed spite for Evangelicals. I mentioned another friend, a gay-marriage supporter from another New York newsroom, who told me not long ago that there is no room there for dissent on same-sex marriage. All opposition to the new orthodoxy is taken as a confession of one’s bigotry. Does Andrew Sullivan not know this? There have been plenty of people in the recent past willing to make arguments for the traditional Christian view of sex and sexuality, but the place these arguments are made in our culture — in the media — has been indifferent or hostile to them. I point Andrew to the Pew Center’s study from last year, showing that media coverage on same-sex marriage from a critical period they studied favored the pro-SSM position by five-to-one. This kind of thing happens when the media have decided that the other side has no position worth listening to. Has Andrew ever been threatened by a potentially career-ending complaint that expressing his beliefs create a “hostile work environment”? It has happened to me (though not about gay issues); I’ve heard from others — readers of this blog and people I have met elsewhere — who have faced similar reactions when it emerged in their places of employment that their personal views don’t agree with the new race-sex-gender orthodoxy. A tenured professor who is a Christian told me recently that if his colleagues knew that he disagreed with gay marriage, he would not lose his job (tenure protects him), but he would be ostracized within his college as a bigot. It’s very, very easy for the self-employed Andrew, who is on the power-holding side of this cultural equation, to demean as “delicate and insensitive” people who face real and significant professional consequences for their religious dissent. It may fall to them to martyr their careers to stand up for what they believe to be true. But if they are going to do that, they should at least have a reasonable hope that their arguments will be seriously considered. That’s a ridiculous thing to hope for in our media climate today. But it is unjust of Andrew to write as if his side is not imposing a real cost on people who even he recognizes are not true bigots, simply for expressing their Christian beliefs. Christians and other traditionalists were wrong to have demonized gay people in the past, and forced them to live in the closet for fear of their careers. Team Andrew Gay rights activists did a lot of good work to end this climate of fear, and to wake the rest of us up to the humanity of our gay brothers and sisters, and to increase tolerance for them. But it is to Team Andrew’s their great discredit that they have created a climate of intolerance and, yes, hatred, that sends traditionalist Christians into professional closets of their own. It would do Andrew good to step outside of his NYC-Provincetown-DC bubble, and listen to Catholics and other Christians who are not Westboro fundamentalists, and who are afraid to stand up for what they believe in because of the consequences they believe the new McCarthyism is likely to impose. But I’m also troubled by the equally stunning lack of charity, magnanimity, and tolerance displayed by many gay marriage advocates. This very much includes Mark Joseph Stern, Henry Farrell, and others who are cheering them on. Roughly speaking, for all of recorded human history until a couple of decades ago, virtually no one even entertained the possibility that homosexuals might seek to marry, let alone advocated it. In that brief span of time — a figurative blink of an eye in cultural terms — gay marriage has gone from being an oxymoron to a lived reality in several states and an institution accepted by majorities or pluralities in most demographic categories. If that isn’t a cultural revolution, then nothing is. Yes, it’s still underway. But at this rate, Nate Silver’s 2009 prediction that gay marriage would be accepted in all 50 states by 2024 is going to prove to be too pessimistic. And yet, that appears to be insufficient for some gay marriage proponents. They don’t just want to win the legal right to marry. They don’t just want most Americans to recognize and affirm the equal dignity of their relationships. They appear to want and expect all Americans to recognize and affirm that equal dignity, under penalty of ostracism from civilized life. UPDATE.2: Listen, I’m not going to publish any more statements in the comboxes of this thread arguing whether or not Christian opposition to SSM is driven by bigotry. If you want to join that discussion, there are plenty of threads on this blog in which to do it, and there will no doubt be plenty more. This thread is about how gay rights supporters should treat those who disagree with them. I’m not trying to suppress your opinion because I disagree with it, but rather keep the discussion focused. Please don’t waste your time writing a general comment about supposed Christian bigotry, because I’m not going to post it. MORE FROM THIS AUTHOR Hide 237 comments 237 Responses to Andrew Sullivan Is Being Smug And Naive “I can’t provide you with any statistics about gay people losing jobs for being gay, but I know of multiple instances where it has happened. Some are people I have known personally. I also have a straight friend who is an employment lawyer. She has had multiple individuals come to her with such claims.” Thanks for recounting your knowledge of people who’ve been fired because they were gay. I’d still be interested in knowing how widespread the problem is. I’d also be curious to know that circumstances surrounding the firings of the people you mentioned. Did most result simply from prejudice or were there extenuating circumstances that made the situations less clear-cut? “There seem to be any number of subjects that one can be right about and yet receive vituperation and condemnation for believing.” A woman sees on the news that someone is driving the wrong way on the freeway. She knows her husband is commuting on that same freeway, so she calls his cell phone and tells him to watch out for a driver going the wrong way. He says, “Oh, it’s worse than that! There’s hundreds of them!” Erin: “I admit to finding it a bit rich that I’m supposed to squelch a part of who I am to avoid offending other people who are insisting that in order to be who *they* are they have to redefine marriage and reshape society” Were people saying that you’re “supposed” to squelch this part of yourself, or were they suggesting how you might be a better advocate for your side? You can certainly dismiss that as concern trolling, but you might also consider that these suggestions were sincerely made in the interest of fostering better conversation. A civil tone is rarely a moral imperative (or if it is it’s a pretty low-priority one), but that doesn’t make it unimportant. As an example, the set of propositions you put to SSM supporters seems to be premised on the idea that what people are objecting to is the content of your ideas, and that if they agree with your characterization of those ideas then they must admit that you’re not being snide to say, “there will be no compromise offered to those of us who refuse to chant ‘Two men are the same as a man and a woman. Two women are the same as a man and a woman. Children do not need a mother and a father. Gay sex acts are the moral equivalent of holy matrimony…’ ad infinitum.” But doesn’t it strike you that “chant ad infinitum” in itself is exactly what people find snide? Sarcastic hyperbole is just a really sour form of expression. “Yeah, that really bugs me too. I’m not sure why so many of the anti-SSM crowd seem to think being gay is reduced to sexual “acts”. There’s certainly much more of my being attracted to women than “sex acts”.” Because that is the only unique characteristic of difference. Intimacy- among can be as deep and profound as heterosexual unions on an emotional level. Men have intimate communication with each other all the time, but are not in any manner engaged in a relational dynamic. Intellectual communion — again men can and do have profound communion on an intellectual, but do not in any manner have physical relations or desire them. The aspect that is unique hinges on relational intimacy and what that means. So point of fact, that’s what it boils down to. I can agree with Ampersand that many, perhaps most, of those with a consistent sexual preference for their own sex did not CHOOSE to be that way. There may be various reasons that some people move from one preference to the other, or experience both, and some of these may be environmental, experiential, or even chosen, rather than genetic. Its not really well understood, probably rather complex, and most research is done by people with an ax to grind, one way or the other. Let’s talk about freedom of speech. It is true that the First Amendment, per se, restrains only the acts of congress, and, since the ratification of the Fourteenth Amendment of blessed memory, the legislatures of the states. The United States Supreme Court has also ruled that in ratifying the First Amendment, it may hardly be supposed that there was intention to allow the courts or the president (or governors) to limit speech that congress could not limit. The First Amendment does not per se prevent me from punching someone in the face for speech I disagree with, but assault and battery laws do. The First Amendment definitely does not restrain me from denouncing your speech, or you from denouncing my speech. The denunciations themselves are free speech. So, I can say that the plaintiffs in Elane Photography are being petty and petulant and narcissistic, and they can call me a petty insensitive bigot who doesn’t understand their pain. The first amendment allows neither to be suppressed. BUT, what is really at issue here is offended individuals calling upon STATE ACTION to suppress freedom of speech. If a public accomodations law, or a hate speech law (those aren’t allowed under the First Amendment) is employed to suppress speech considered undesirable, THAT is state action. Analogy, for illustrative purposes only, not as evidence of any fact: Before the passage of the 1968 equal housing act, individual property owners were perfectly free to refuse to sell to persons of this or that color, race, religion, etc. The Supreme Court ruled that this was not “state action” and therefore not barred by any constitutional provision or existing civil rights law. However, when a property owner chose to violate a covenant, written into the title deed, never to sell to anyone not of the Caucasian race (only Chechnyans need apply?), and neighboring propery owners tried to take them to court to enforce the convenant, the Supreme Court ruled that courts were without jurisdiction to enforce such covenants, because the enforcement would be state action. So, whatever action may be taken against someone’s freedom of speech, it may not make any use of any state office, including the courts, and it may not violate any criminal laws. Libel and slander do exist in our civil law, but invoking them is a very high bar, and the more public one’s profile, the higher the bar. Is everyone happy now? Who agreed to this definition? From my perspective, it seems like a very male viewpoint. I am a heterosexual female, and I can assure you that male porn does absolutely nothing for me from a sexual response aspect. I could look at it all day (not that I would want to, mind you), and it would do nothing but make me laugh. Sexual orientation is far more than a reaction to porn–at least I hope it is, because if not, I must be completely asexual. My husband would argue otherwise, though, as we have a very healthy love life. Orientation is about more than excited sex organs, and sex is about far more than the orgasm. I can’t speak for anybody but myself, but I can definitely say that I have spoken to other women who feel the same way, so I don’t think I am some sort of weird one-off on this subject. Arguments like this lose me from the very beginning, as my experience doesn’t reflect orientation as “one’s unconditioned sexual response to porn.” I suspect these arguments lose a lot of other people at the same point. How much of that increase can be attributed to bisexuals who feel they can now experiment with the love that was once forbidden? The population from which they can find a suitable partner without fear of condemnation or a jail sentence has gone up. “The population from which they can find a suitable partner without fear of condemnation or a jail sentence has gone up.” That may be true, but my use of the word experiment is not something I came up with on my own – it’s the word I’ve heard other people use, and not necessarily the ones doing the “experimenting” but often friends with those “experimenting.” So, perhaps you’re right. However, in college many students who otherwise would not be attracted to drugs experiment with drugs and probably other things as well. “The Girgis/George book is not a bad argument, but one would need to accept most of the other political assumptions of the Whig Thomists for it to make sense. Essentially, you’d need to become a Catholic neo-conservative.” I disagree. The issue is what defines marriage itself. For instance, I live with a community of women, we share close friendships, legally share property etc. Have made each other our next of kin. But, none of these obligations make us married. Proponents of SSM, argue that marriage is whatever two people decide it is. And, then turn around and agree that not all relationships classify legally as marriage, even if they might share things in common with a marriage. So what is marriage is the question? The state should not be defining marriage when nobody can make up their mind about what marriage is. I step away from the Interwebz for a break, and y’all go hog-wild on this poor thread. 😉 Extend your time frames. Make them a gestalt view over time and note the changes… and for all the gods’ sakes, get your temporal syntax correct. Homosexuals until relatively recently routinely suffered a variety of sanctions — ridicule, shunning, loss of jobs, physical violence and sometimes death — just for having others be aware of their sexual orientation. An actual act of sexual relations was simply unnecessary for most of that to happen. They were the targets of bullying and oppression. And this part is the point seemingly lost in the entire suffle: That’s the way they saw it, and continue to see it with the entire “bigotry” issue. Don’t want to suffer the consequences of someone else dicatating the rhetoric? Then do something about it, and starting with a mere acknowledgemen of the past is good and valid. Does that mean everyone will sigh, take a deep breath and start being more civil? If anyone believes that, I’ve got this bridge for sale cheap… But using that to claim failure in this dialogue is an excuse, and the worst kind. If my child spent 15 minutes on a sticky problem — one which, with my elder’s perspective of how long some problems take to solve — and declared failure I’d hit the childe with the very same problem some time later, and expect it to be solved. Time is always a factor. Expecting things like culture to shift and change overnight is not only naive, it speaks to the emotional immaturity of those with that expectation. Yes, that’s a direct criticism to my LGBT friends. I fervently hope they take it to heart, and do just one thing with me: Recognize that gloating is one of the ugliest displays of ego known to human experience. My dear, and sometimes beloved opponents to SSM, nothing is ever changed without harm. Nothing. Ever. It’s up to you to decide where to draw this line, but I truly believe that no longer having the privilege of expecting your religion to rule culture is going to be your lot in life, in the lives of your children and their children. Start now finding your peace with it, because you’ll have one of two outcomes that I can see: Your children will become violently opposed to it, or they will abandon your faith. It’s your anger that comes out first, and children will either take it up and expand it, or flee its toxicity. One personal note: that point I made about bullying… Often, bullies don’t see themselves in that light. That perspective is worth nothing when those who see you as bullies treat you as such. You have no grounds to complain when they obtain the position to bully you. If you believe, as I do, that bullying is an objective wrong, your efforts should be towards reconciling that, helping them find some sort of healing around it. It’s more than just complaints about the missing Christian compassion of the past. It’s about helping them find that compassion within themselves, in the Christian vernacular helping them discover forgiveness. As a supporter of SSM, I actually can see where the author and Damon Linker is coming from. a lot of the new age “gender pioneers” do not want tolerance- they want submission. They want to fully stomp out any disagreement about the righteousness of their position, and as a result, sometimes their position is inherently illiberal. It does have a certain facist element to it. I strongly believe in equality under the law for all citizens but I also believe in freedom, which is why it is ok with me if people in Alabama, for example, decide they do not want SSM in their state. That is the patriotic position to take. Trying to force a position onto people via education camps, “my way or the highway” rhetoric is contrary to a liberal society. Not everyone who disagrees with SSM is a bigot- my father is not the most supportive of it and he is not an intolerant man Sigh. So “chant ad infinitum” is snide. Is it snide to point out that you will expect people like me to mutter those things in job interviews, in the public square, in any social setting, etc. because to be silent is automatically going to be taken as homophobia? Because that IS where we are headed, and yet even to mutter those things would be, for me, a lie–a lie I won’t ever voice. This thread is about how gay rights supporters should treat those who disagree with them. My Mormon congregation disagreed with me. I was married to a female who knew before we married I was gay. I had **never** acted on my sexual orientation in my life. When I confided in my ward bishop, I was removed from my job as ward secretary and publicly shunned by every single member of my congregation. I wasn’t waving the rainbow flag. I was getting the weight of a lie off my soul and trusting my congregation to be compassionate and merciful. I was asked to stand before a excommunication committee and name every single incident of my sin. That was a snap. Affection in my heart for a man I was fond of and, yes, I desired him sexually but I never touched the man. The committee wasn’t satisfied. They thought I lied about my sins. They were wrong. One thinks that a little reciprocal compassion is in order in such a case. I never experienced any and it drove me from my church and into a divorce. Then, the gentle Christian who was the principle of my daughter’s elementary school outed me after my second grade daughter make a valentine in class that said, “Dad loves Ted”. He mocked and shamed up in the teachers lounge and my daughter’s teacher was shocked with me we couldn’t even have a parent-teacher conference. The gentle Christian principle then called the principal of the school I was teaching at and told him: you better watch him around the children. How am I supposed to show respect to that brand of “Christian”? After I was outed and the news spread though out my daughter’s school, in her middle school and high school years people were coming by shooting bullet holes in my house and car. They vandalized my property on two DOZEN occasions, and they spray painted the word “fa**ot” on my driveway in big block letters about six feet tall. They pulled their cars into my yard and destroyed my flower beds and dug ruts into my lawn. They would walk by my house and scream “fa**ot” at me while I was working in my yard. God’s gentle people. We’re supposed to respect them. I was DEAF. These thing happened to me and I lay in my bed at night wondering if my family would be shot in their beds without me being able to hear the sound. Or maybe they would burn my house to the ground with us all in it. All of that horror trickled down from a devote Christian who was a school principal. My kid was bullied and taunted the entire way through school and she was STRAIGHT. We had to pull her out of school to keep her safe. I don’t know what kind of persecution you could ever have that would compare with what me and my little family went though for 12 year but you sound like a whiner. You don’t know persecution until you’ve shaken and shuddered in you bed at night waiting for the next bullet to destroy the people you love. The golden era of Christianity is most likely before 313AD, when Constantine legalized the cult and made it the state religion. It has become less spiritual and more secular, or earthbound, ever since. It’s very funny that professional Christian scolds are finding it hard in this so-called new era of less bigotry to find his moorings and so expects to feel persecuted. Why are they so reluctant to be more like Jesus—on the outs with society, wearing the hair shirt, being penitent, being humble, identifying with the downtrodden? Why is it so hard for him and others to be, well, more Christian, like the good old days? Gay rights supporters should absolutely treat opponents of equal rights with the distain due to bigots everywhere. Bigotry should never be tolerated, no matter whether that bigotry is against religion, sexual orientation, race, or gender. I’ve never heard a gay person say “you should not be free to worship your god”, but I’ve heard many a religious person say “you should not be free to marry the one you love.” And note that those who say this are usually very willing to tell other religions that they CANNOT practice how they would like and marry gay couples. [NFR: You say that no one should be bigoted (“bigoted”) toward someone of another religion, but aren’t you promoting bigotry, if bigotry is understood as irrational prejudice? You can’t say you’re tolerant if you only tolerate those who agree with you. — RD] Back in 1990 I was hired for a temp position. Two weeks later I got a letter saying I was “un-hired.” I called my friend who worked at the company and learned that someone at the company had learned I was gay and another temp worker was a lesbian, and he immediately “un-hired” us. That was the sole reason. Lucky for me, my friend went to his boss and told him what had happened, and since the individual got himself hired (they were already looking for a reason). I now live in Arizona. In almost the entire state it is legal to fire someone for being LGBT. No other reason is needed. In contrast, right there on the Attorney General’s website it states you cannot discriminate based on religion. This column by Dreher- hypothetical whining. There is no campaign to fire conservative Christians. I know many gay people who have been discriminated against at work and elsewhere. I could care less whether someone goes to church. I don’t check up on people’s religious beliefs when I hire them or socialize with them. On the other hand, try to force me to live by your Biblical standards- I will fight you in any way I can. Ron, if bigotry is not to be tolerated, there must be a precise and universally accepted definition of bigotry, so that all persons subject to intoleration will have reasonable notice of the behavior expected of them, and of the behavior(s) to be prescribed by ostracism, banishment, or summary execution. The problem is, for all your facile use of the word, there is no such definition. Note that not one civil rights law uses the word “bigotry.” Laws require precision, and even in the 1960s, bigotry had no common definition so precise as to make good law. Ray Harwick’s story is entirely credible, and no doubt there is a circle in hell reserved for those who subjected him and his daughter to the treatment he describes. That doesn’t translate instantly into a prima facie case for SSM, nor does it mean that anyone who questions SSM is equally cruel. It is a case for everyone to take a deep breath, recognize that life is complicated, and stop taking themselves (in this case, the teachers, principals, and Mormon officials) so seriously. It’s very, very easy for the self-employed Andrew, who is on the power-holding side of this cultural equation, to demean as “delicate and insensitive” people who face real and significant professional consequences for their religious dissent. Ah, but if religious descent was all we ever had to deal with, we wouldn’t be having this conversation. One reason Andrew Sullivan and countless other gays are “self-employed” is that we learned after getting our heads knocked around in the world of employment, we really didn’t like “dissent” in the form of being fired or having a glass ceiling surrounding us. I have no such talent as the intellectuals in this argument but before I became a school teacher I spent eight years in the U.S. Air Force with my mouth shut and ears open to the most vile, filthy horrendous charges about gays and I knew if I made one peep about about being gay, I would have been THROWN to the unemployment gutter. No. There would have been no opportunity for polite disagreement with my work colleagues. That wasn’t allowed by the UCMJ. I was a case where I would have been told to leave in absolute disgrace even while I had a mortgage to pay and **PERFECT** performance reports and had won the highest honor my technical speciality bestowed to enlisted administrators. I competed again nearly 10,000 people for that honor and it wouldn’t have done me one bit of good if I had had a lapse in judgement and casually mention I was gay. I’d have gone the way of Technical Sergeant Leonard Matlovich who, you may recall, now has a headstone in a grave yard that says, “They gave me a medal for killing a man and a discharge for loving one.” When I decided to become a teacher I was determined that I would not be in the closet because I did not want to re-live the experience I had for eight years in the Air Force where I virtually suffocated myself to keep my homosexuality a secret. I came out in college and I did it so I would know for certain that if I were hired to teach, my employer would know what he was getting. I didn’t want to go into a job and wonder if I would have to stifle details of my personal life. I wanted the discussion to begin and end at my job interview. It didn’t. I never got hired. I worked in 54 elementary schools as a substitute teacher right after graduation and in the second year of that experience I got my first interview. I told readers in a previous comment that my daughter’s school principal outed me. He did more than that. He somehow managed to flag my application for employment. So after two years as a sub, when my **first* ever job interview came up, I was not prepared for what would happen. I had excellent recommendations from my substitute work, and this was after graduating in the top ten percent of my class. I received an “Excellent” rating in my first student teaching experience and an “Outstanding” rating in the second one. In my first interview, you would have thought I had shown up stark naked from the reaction of the principal who interviewed me. He literally screamed at me. He wanted to know why I had only received an “Excellent” in my first student teaching experience. That experience was the one I mentioned that my daughter’s school principal had called my supervising principal and had warmed him to watch me around the children I was in charge of. That Christian principal from my daughter’s school did that and it became immediately clear in my first interview he’d done something more than that. I’m GLAD I made the decision to be out of the closet. Short being my own boss, like Andrew, being out was the only thing I had to protect me from getting fired if I got a job while closeted. Nobody could say I didn’t tell them and at the least I could have the dignity of appealing a dismissal on the grounds of anti-gay discrimination. When I was eleven years old and living on a farm with my family, I learned something about having to keep my mouth shut – in the very same way that is at the heart of your complaint today. On a beautiful day when my family had worked in our fields together and then sat under a shade tree to shell black-eyed peas, my parents were in an lighthearted mood and my father ask his five children a playful question that I took very seriously. He asked: When you grow up, who do you want to marry? When it was my turn to answer I made the mistake of being honest. I told my father I wanted to marry the man we rented our farm from. But replying like that, I leaned how much respect a devout Pentecostal Holiness father will show. My father took off his leather belt and bloodied my back and legs with it. I was so terrified I ran off into the woods and cried for hours. I’m certain my father thought he’d beaten that impulse out of me because I never, ever shared my personal inner life with him for the rest of his life. Well into my adulthood, I could not sleep with my back to a bedroom door because I feared I might have to run for my life from my father’s anger with me. And you think it’s uncomfortable to have to nuance your language around other people? Try sealing your entire life from age eleven to age 30, Rob. You don’t have any problems. Nobody is going beat you bloody or throw you to the gutter of unemployment. Once you’ve lived a life in which you can’t say ONE f-ing word about yourself honestly, then you’ll understand something about the nature of persecution in the real world. The case I am most familiar with is that of Scott Eckern, and I fail to see how it is “persecution” for religious beliefs. He was being held accountable for doing material harm to LGBT people around, by donating to a ballot initiative that made them legally unequal (for 5 years, until it was struck down by the courts). Marc Shaiman had it right – he did not want his work funding injustice. If Eckern had donated to a ballot initiative to ban interracial marriage, no one would question why there would consequences. Your failure to recognize or acknowledge that harm is evidence is simply willful blindness, and smacks of intellectual dishonesty. Rod, without engaging in what has already been an ongoing and vibrant argument, I’m curious how you square religious freedom with the argument that civil marriage should not be recognized for members of the same gender. You are an Orthodox Christian, and as a member of the Orthodox Church, you are under absolutely no obligation to recognize a same-sex marriage, a divorce, or a remarriage following a divorce. These are theological and philosophical views motivated by religion, and anyone, particularly backers of marriage equality, who tries to take that right away from you is simply wrong-headed. But what, I am curious, of religions, specifically Christian denominations, that affirm the right of same-sex couples to marry or be partnered? What of UCCs, Episcopalians, (some) Presbyterians, (some) Lutherans, and even Unitarian Christians? Are they not entitled to their religious beliefs as well? Obviously, that question is rhetorical, because I have been reading you for a long time (though this is my first comment!), and I know you believe your right to practice your religion as you choose to be one of those fundamental inalienable rights. But being that that’s the case, how can you advocate that the government recognize one religion’s definition of marriage over another’s? That is, why are Episcopalians like me wrong, but Orthodox Christians like you right? I feel that it would be far more consistent, from that viewpoint, to get the government out of the marriage business altogether, and instead allow religions to sort it out themselves, as they’ve done for centuries. But that would also be a much more radical reinterpretation of marriage than simply allowing for civil marriage between two individuals. I also think it’s rather odd that you play this form of victimology from a social, rather than governmental, perspective. You worry about having to be “in the closet,” as it were, as someone opposed to marriage equality. But that’s often the case at workplaces — we don’t show our true faces, because our true faces would get our butts fired. In a previous job, for example, I worked for a cancer charity. While I support efforts to curb cancer, I have an intrinsic problem when people’s rights are curtailed dramatically. I ran into this exact problem when my workplace started advocating for banning smoking in private cars. But where I to say something, were I to raise an objection to this, I would have been shamed and castigated by my coworkers. I didn’t feel it necessary to “come out” to them, so I instead kept my mouth shut. That’s what society is, Rod. And for millennia, gays were told to do the same thing: sit down, shut up, keep it to yourself, be “normal.” Thing is, society has changed in that regard. In modern society, being gay is not problematic. And so, you are left with a choice: continue to fight this sociological change, or accept it and move on. But you cannot simultaneously find it acceptable that for thousands of years of history society kept gays in the closet, but unacceptable that a sociological change is now making that type of animus obsolete. I want to be clear that holding a religious tenet dear and holding that government should enforce what you believe religiously are two different things. If I’m not mistaken, the Orthodox Church also vehemently condemns divorce. That being the case, would you advocate for an end to civil divorce? It would behoove you to remember that LGBT people have experienced real – and oftentimes direct – harm that has been couched in anti-gay bais. I’m not going to argue about your personal animus, or potential animus driving the movement. However, I rarely meet another gay person who doesn’t have at least one story about their “hateful Christian mom/dad/aunt/uncle” who refuses to talk to them since they came out. In the transgender community the faith-based nature of this hurt is even stronger – many of us lose our families the moment we come out of the closet and start living authentic lives, and that cutoff is often rooted in a family’s “biblical disagreement” with the unfortunate lot we’ve been dealt in gender identity. I know it sucks to have your opinions misconstrued as hateful or bigoted. (I’ve had my opinions marked as “perverted” for years by Christians.) However, you might get more sympathy if you consider that the people you’re trying to convince have complex relationships with faith, and have suffered personal, professional, and familial harm due to beliefs you say aren’t rooted in hate. Hate or no hate, those wounds still sting and they still ring of thumping bibles. You cannot come _close_ to changing the dialogue if you’re not willing to recognize that history. For gay people this is a personal fight – not just an abstract debate. The more you recognize that, the more you’ll prosper in finding common ground. Hell, you might even want to try listening to the hurt that’s been caused by your school of thought regarding traditional families and gender roles. I think it’d be an eye-opener – at the very least it’d explain the mean streak you’re seeing from gays who are finally – finally! – getting a leg up on their oppressors. But then you get the argument by Christians et al. that you are just perpetuating bigotry by suggesting they should not follow their beliefs as fervently as they wish, with no social consequences. Look, I am fully within my 1st Amendment rights to say that I enjoy “crush” films (as determined by the SCOTUS). That does not mean that I am free from people around my telling me that that is a really demented thing to enjoy. I believe people are confusing their freedom to say something and have whatever beliefs they wish with the freedom to not be criticized for it. Their is no freedom of acceptance, as those who have historically been discriminated against know full well. So here’s a question for folks from a real life example: My wife and I chose to not take our son to an orthodontist who had, financially and publicly, supported Prop 8. Is the argument presented here that finding a different orthodontist because of that criteria was a form of bigotry? “My Mormon congregation disagreed with me. I was married to a female who knew before we married I was gay. I had **never** acted on my sexual orientation in my life. When I confided in my ward bishop, I was removed from my job as ward secretary and publicly shunned by every single member of my congregation.” Well, I cannot challenge what the church did. A violation of the faith is a violation of the faith and it would be odd that they support something they believe God does not. So a church secretary in such an organization is going to be held by that standard. It’s a shame the method perhaps, but it does make sense and appropriate. As for the narrative about you, if this is a public school, I would find it highly inappropriate. And perhaps even breaching an ethical code. That is unfortunate. _____________________________________________ I have read these personal narratives as personal stories of hurt. And while I might empathize they only highlight my principle charge, legalized same sex marriage for tax purposes is not going to resolve those issues. There are no Christians parading the streets demanding that homosexual practitioners be rounded up and imprisoned. When someone who practices this means of expression is assaulted or any other manner harmed by another. There is no evidence that they investigations are shrifted. There are arrests and prosecutions. Those instances have no bearing on marriage. Those who engage in heterosexual expression get beaten get beaten up as well. “I didn’t want to go into a job and wonder if I would have to stifle details of my personal life. I wanted the discussion to begin and end at my job interview.” Ohh come now, everyone stifles details of their personal lives. For most of my life the only people who knew I was celibate was me and any women who was interested or those close to me. Try being celibate around men in the military —- laughing. And if they made fun of me — what’s to do? And so what? Unless there is a “hostile” environment created and that is a high threshold for me. L’est, several institutions would now be parking lots as I would own them outright and make them money breeders. Of course for folks who believe in limited government same sex marriage is a non-issue. Why? Because government should not be involved in marriage at all. The same sex marriage advocates do not make a doctrinal argument (generally) why some denomination should embrace same sex marriage (e.g I have never seen Mr. Sullivan explain why Islam should embrace same sex marriage). Same sex marriage advocates have explained why government should embrace same sex marriage, the whole way begging the question why government need be involved at all. Fact is, government regulation of marriage is “big state” nannyism. Genuine advocates of smaller government want government out of the marriage game entirely. When foes of big state government take the time to OPPOSE same sex marriage they get sucked into FAVORING big state oppressive government. The correct answer on same sex marriage is always get government out of the marriage business entirely. Leave marriage to the church. The comments on here that are most useful are the ones exhorting Rod to identify his enemies properly. It’s not the small subset of gays and pro-SSM advocates who would sue a baker or florist or scream bigot at anyone opposed to SSM. It’s also not the entire media world (and now the legal profession, I guess), both political parties, magazines, etc. If you keep pretending that those who support SSM are mindless “followers” of media outlets or legal scholars, you’ll keep losing. Try assuming they have come to their position thoughtfully. Your “enemies” (how sad that you’ve made them thus) are the neighbors, parents, friends, coworkers, siblings and cousins of happy gay couples. This group is growing rapidly, whether SSM is legal or not. They are not turning to Fox or MSNBC to figure out how to feel about SSM. They don’t care what Andrew thinks. They live everywhere and work in every profession. And they reject out of hand everything Erin claims they believe if they support SSM. They do not believe men and women are the same, children don’t need moms and dads, or that someone else’s SSM changes their own “definition” of marriage nor fundamentally reorders society. “We can’t support civil SSM because it doesn’t fit with what we think is the best way for people to marry” might work, though it’s a little weak. “We can’t support civil SSM because it would mean men are the same as women, babies don’t need mommies, and it completely reorders all of the foundations of society” definitely won’t work. Andrew has some influence and he’s used it to repeatedly call for compassion and tolerance for the religious viewpoint. But he also thinks your evidence for widespread persecution is flimsy. Citing an event from 6 years ago, when opponents were actively trying to REPEAL SSM where it was legal, doesn’t help your case. There is one big difference between conservative Christians and GLBT and their supporters. While many of us do have disdain for conservative Christians and their beliefs – I will freely admit that I do, and that I would prefer to not have to work with or associate with them — nobody is trying to prevent Christians from practicing their religion or from being able to marry who they want to. And I’m sorry; having to live with the fact that a lot of people disagree with you and think you are backwards is not being persecuted. When Christians are enslaved or put into concentration camps and gassed by the millions, then you can start talking to me about how you are persecuted. For what it’s worth, I can accept that Christians may hold their beliefs sincerely, and can be opposed to same-sex marriage out of more than simple bigotry; but that does not exempt those beliefs from scrutiny or criticism. [NFR: I’ll restate that for you: 1) I can’t stand the likes of you and wish I never had to deal with you; 2) “practicing your religion” is what I say it is; 3) what are you complaining about, we’re not killing you en masse? If this is supposed to make us less worried about the fate of religious liberty, it’s not working. — RD] I think Andrew Sullivan has a point, even if he did pose it somewhat gracelessly. How can you and other same-sex marriage opponents expect the disastrous course of events that you foresee to be averted if you are unwilling to make a positive argument in favor of your beliefs? If your position is that your beliefs do not amount to bigotry, you presumably have positive arguments for your position that cannot be easily characterized as such. If so, then you should not be afraid to engage with critics; certainly some people are unreasonable about their own beliefs and will not accept your positive arguments, but that is true of virtually any polarizing issue. On the other hand, for every one of those types, there should be others who are at least willing to hear you out and entertain your arguments without immediately assuming you are merely a bigot, even if they continue to disagree with you. As I said, every polarizing issue is bound to produce a range of reactions in people. There will always be people whose first and often only reaction is to demonize those who don’t agree with them. Personally, I don’t hold with such responses when observed in others, but I can’t deny that even I tend toward such a reaction over an issue that I am sufficiently emotionally invested in. Being aware of this tendency, I make a conscious effort to step on my emotional reactions and try to understand the other person’s point of view even if I don’t always succeed at doing so, but not everyone is so self-aware. The problem though, is that if you and other same-sex marriage opponents don’t even try to advocate your point of view, you have no chance of altering public perceptions. Elsewhere you have decried the efforts of SSM advocates to shout down those who oppose SSM, but what you don’t seem to realize is that they have little choice but to loudly and publicly oppose efforts to protect what they see as anti-gay discrimination. If they don’t do so, they risk allowing a public perception to settle in that such efforts are acceptable, even normal. Well, this paradigm holds for you and other SSM opponents as well. If you do not want to be marginalized and you feel that you are becoming a persecuted minority, then it is no less than your duty to stand up and make your argument as loudly and publicly as possible. I’m sure it will be difficult. It’s been no less difficult for gay rights advocates in years past. However, if you aren’t a bigot, then you presumably have reasonable arguments to make beyond “Homosexuality is immoral because God said so.” So make them. And if some people are willing to assume the worst about you in spite of your reasoning, well then they probably aren’t people whose respect you really want or need. I have respect for Andrew Sullivan. He was one of the earliest proponents of gay marriage during the HIV/AIDs crisis. Gay marriage and its long term monogomous relationships was the solution for an incurable multi-generational plague. But this was before the gay radicals labelled any opposition to gay marriage as hate and bigotry. But this was before the gay radicals started forcing gay marriage and gay rights to normalize the exact same nihilistic, transient, self centered, fetishist subculture in the public sphere. If you watch modern family, the gay parents are just as normal and as ordinary a family unit as every other family and that was what Andrew Sullivan advocated for 30 years ago. Fast forward to today and the fight for gay marriage and gay rights isnt about fighting HIV/AIDs and public health, its not about mental/emotional wellness of gay men and lesbians either. Its now about letting pedophile men use transgender rights to use female restrooms, gym lockers and appear naked in front of pre-adolescent children in local health clubs. Its about defending SanFrancisco rights to public nudity and public sex…in other words normalizing a fetishist subculture into the main stream. Thats the real opposition and the real fight and there is no hate or bigotry involved at all. ZERO. The public deserves the right to decide public exposure to sexuality and frankly so do parents. I can see why even Pope Francis is willing to open a discussion on Civil Unions. As a gay man, I support civil unions but I also respect my christian faith and others of christian faith even if they do not accept homosexuality. I am far more repulsed by the West Coast politicization of sex and gender politics than I am by what should be a mundane equal access law for 2 people to share resources, to be caretakers for each other, to be companions for each other. Its how the left fights their wars…by taking 2 separate issues apples and oranges and then calling them the same thing. There’s a pity war going on in the comments: gays and Christians both trying to prove that they’re the more marginalized group. It’s not clear to me that the issue of discrimination against gays is relevant to whether opponents of SSM are or should be marginalized. But I don’t see the problem with the marginalization of SSM opponents. Surely SSM supporters can choose whether to patronize establishments run by SSM opponents. If they don’t want to go into business with a SSM opponent, that’s their right. Sure, it’s frustrating when people don’t like you for their views, but that’s the price of holding an increasingly unpopular opinion. “But I don’t see the problem with the marginalization of SSM opponents….Sure, it’s frustrating when people don’t like you for their views, but that’s the price of holding an increasingly unpopular opinion. So are you saying that it was fine to marginalize gay people when gay rights were unpopular? | Low | [
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INTRODUCTION {#sec0005} ============ The Apolipoprotein E (*APOE*) gene has been strongly implicated in Alzheimer's disease (AD) and in longevity. *APOE* has three polymorphic forms, *ɛ*2, *ɛ*3, and *ɛ*4, which have a frequency in the general worldwide population of 8.4%, 77.9%, and 13.7% \[[@ref001]\]. Carriers of the *APOE* *ɛ*4 allele are at a higher risk of AD \[[@ref002]\] whereas those who carry the *APOE* *ɛ*2 allele are thought to be protected from the disease (relative to *APOE* *ɛ*3 and *APOE* *ɛ*4 carriers) \[[@ref003]\]. Studies of older individuals have found that the frequency of *APOE* *ɛ*4 is lower and *APOE* *ɛ*2 is higher than in the general population \[[@ref004]\]. Many studies have examined the associations between *APOE* genotype and mortality with often conflicting findings. Genome-wide association studies have linked *APOE* with longevity \[[@ref005]\]. It has been reported that carriers of the *APOE* *ɛ*4 allele die earlier than expected \[[@ref006]\], whereas other studies find earlier age at death only in those with the *APOE* *ɛ*4/*ɛ*4 genotype \[[@ref007]\]. A study looking at three independent cohorts from Italy, Spain, and Japan concluded that longevity was negatively associated with the *ɛ*4 allele and positively associated with the *ɛ*2 allele \[[@ref008]\]. Similarly, another study reported that extreme longevity was negatively associated with *APOE* *ɛ*4/*ɛ*4, *ɛ*3/*ɛ*4, and *ɛ*2/*ɛ*4 genotypes whereas there was a positive association between longevity and the *APOE* *ɛ*2/*ɛ*3 genotype \[[@ref009]\]. However, associations between age at death and *APOE* *ɛ*4 allele(s) were not found in other studies based on individuals over the age of 85 \[[@ref010]\], nor were they found when attempting to correlate *APOE* isoforms, age, and levels of blood cholesterol \[[@ref012]\]. In the present study, we have investigated relationships between *APOE* genotype and age at death in both cognitively normal and cognitively impaired individuals recruited in the Manchester arm of the Brains for Dementia Research (BDR) programme and University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UMLCHA). We focused principally on those individuals with AD pathology (without concomitant or secondary pathologies) and those with pathology considered normal for age. The main aims of the study were to assess the interactions between *APOE* genotype and age group at death (79 years and under, 80--89 years, and 90 years and over) and investigate the impact of cognitive impairment on any associations found. MATERIALS AND METHODS {#sec0010} ===================== The present study combines the UMLCHA and the Manchester arm of the BDR cohorts. Details concerning clinical characteristics and neuropathological features of these cohorts have been presented by the authors elsewhere \[[@ref013]\]. The study was approved by Manchester Brain Bank Management Committee (REC reference 19/NE/0242). Under conditions agreed with the Research Ethics Committee, The Manchester Brain Bank can supply data to researchers, without any requirement for researchers to apply individually to the REC for approval. For BDR, participants underwent cognitive assessments either via telephone interview or via a visit to the participant's home. Details of cognitive assessments have been previously described \[[@ref012]\]. For UMLCHA, cognitive status at death was assigned using a combination of last modified Telephone Instrument for Cognitive Status (TICSm) score, patient notes obtained via the participants' general practitioner, cause of death as recorded on the death certificate and information gained from the Brain Bank Coordinator (PT). Neuropathological assessment {#sec0015} ---------------------------- Postmortem assessment of the individuals in these cohorts has been previously described \[[@ref014]\]. Consensus criteria were used to establish the presence and stage of neurodegenerative diseases and cerebrovascular pathology. For the purpose of this study, we excluded all cases where the primary neuropathological diagnosis was not AD and also excluded AD cases where there was any concomitant or secondary pathology (other than cerebral amyloid angiopathy or small vessel disease). We included cases of primary age-related tauopathy, aging-related tau astrogliopathy, and limbic-predominant age-related TDP-43 encephalopathy due to the fact that they are relatively common age-related pathologies. The two ongoing cohorts currently comprise 290 subjects. After applying the above exclusion criteria, a total of 182 participants (84 BDR and 98 UMLCHA) were considered eligible for the present study ([Supplementary Table 1](#S1){ref-type="supplementary-material"}). These were then stratified into groups based on age at death: 79 years and under, 80--89 years, and 90 years and over. APOE genotyping {#sec0020} --------------- DNA was extracted from frozen brain tissue using REDExtract-N-Amp™ Tissue PCR Kit (Sigma) or from blood (UMLCHA --3 cases). The *APOE* genotype was determined using routine polymerase chain reaction (PCR) methods \[[@ref016]\]. Statistical analysis {#sec0025} -------------------- Pearson's Chi-squared test was used to compare demographic features. This test was also used to analyze whether there were differences between proportions of *APOE* *ɛ*4 and *APOE* *ɛ*2 carriers in the various age at death groups. *T*-test was used to distinguish between differences in mean age at death for *APOE* genotypes both overall and stratified by cognitive status. A *p* value of \<0.05 was considered significant for all tests. RESULTS {#sec0030} ======= Demographics {#sec0035} ------------ Demographic information, stratified by age group at death, can be found in [Table 1](#adr-4-adr200203-t001){ref-type="table"}. There were differences in sex ratio when comparing those 79 years and under with those 80--89 years (*χ*^2^ = 4.25; *p* = 0.039) and with those 90 years and over (*χ*^2^ = 4.78; *p* = 0.029) with males appearing more frequently in the 79 years and under group and females over represented in the 80--89 years and 90 years and over groups. However, there were no differences in the sex ratio between those 80--89 years and those 90 years and over (*χ*^2^ = 0.03; *p* = 0.869). ###### Basic demographics of the 182 eligible participants split by age group at death Age group at death ------------------ -------------------- ------ ---- ------ ---- ------ Sex Male 23 56.1 26 36.1 24 34.8 Female 18 43.9 46 63.9 45 65.2 Cognitive status Normal 16 39.0 37 51.4 45 65.2 Impaired 25 61.0 35 48.6 24 34.8 The proportion of cognitively impaired individuals was lower in the 90 years and over age group when compared with the 79 years and under age group (*χ*^2^ = 7.14; *p* = 0.008). No other differences in cognitive status were apparent between the age groups. APOE genotype distribution {#sec0040} -------------------------- The frequency and distribution of *APOE* genotype, stratified by cognitive status, can be found in [Table 2](#adr-4-adr200203-t002){ref-type="table"}. The most common *APOE* genotype was 3/3 (53.2%) and the least common was 2/2 (1.1%). When analyzing all eligible participants, regardless of cognitive status, we found that those with *APOE* 2/3 genotype had a later age at death compared to those with *APOE* 3/4 genotype (*p* = 0.004) and *APOE* 4/4 (*p* \< 0.001). Mean age at death was also significantly later in those with *APOE* 2/4 genotype when compared with those with *APOE* 3/4 genotype (*p* = 0.026). Similarly, those with *APOE* 3/3 genotype died at a later age compared to those with *APOE* 4/4 genotype (*p* = 0.008). When stratifying the participants based on cognitive status, there were no differences in mean age at death when comparing cognitively normal and cognitively impaired individuals of the same genotype. ###### Mean (±SD) age at death for each *APOE* genotype stratified by cognitive status *APOE genotype* *N* Age at death (Mean±SD) ----------------- ----- ------------------------ ----------- 2/2 2 81.0±4.2 n/a 2/3 17 90.5±6.2 86.7±3.2 2/4 4 79.0±14.1 73.0±19.8 3/3 97 86.8±9.1 86.1±8.6 3/4 50 85.2±11.1 82.8±9.1 4/4 12 n/a 79.3±7.2 Effects of APOE *ɛ*4 and APOE *ɛ*2 alleles on age at death {#sec0045} ---------------------------------------------------------- The proportion of cases exhibiting one or more *APOE* *ɛ*4 and *APOE* *ɛ*2 allele(s) and allele frequencies of *APOE* *ɛ*4 and *APOE* *ɛ*2 alleles are shown in [Fig. 1](#adr-4-adr200203-g001){ref-type="fig"}A and B. {#adr-4-adr200203-g001} When analyzing all eligible participants, regardless of cognitive status, we found a significantly greater proportion of *APOE* *ɛ*4 carriers in the 79 years and under age group compared with those in the 80--89 years group (*χ*^2^ = 6.791; *p* = 0.009) and also the 90 years and over age group (*χ*^2^ = 11.472; *p* = 0.001). In addition, the *APOE* *ɛ*4 appeared more frequently in the 79 years and under age group when compared with the 80--89 years age group (*χ*^2^ = 11.133; *p* = 0.001) and the 90 years and over age group (*χ*^2^ = 18.425; *p* \< 0.001). Although there was a trend for those who carry *APOE* *ɛ*2 to be found in the older age groups, and for the frequency of the *APOE* *ɛ*2 allele to be greater in the older age groups, these were not statistically significantly different. Similar analyses were conducted after stratifying cases by cognitive status ([Fig. 1](#adr-4-adr200203-g001){ref-type="fig"}C, D). In cognitively normal individuals, frequencies for *APOE* *ɛ*4 and *APOE* *ɛ*2 alleles were not found to be statistically different between the age groups. However, in those considered cognitively impaired at death, the frequency of *APOE* *ɛ*4 allele was greater in the 79 and under age group when compared with the 80--89 years age group (*χ*^2^ = 6.773; *p* = 0.009) and the 90 years and over age group (*χ*^2^ = 8.814; *p* = 0.003). No such differences were found between the 80--89 years and 90 years and over age groups or in *APOE* *ɛ*2 allele frequency for any of the age groups. Investigation into relationships between severity of small vessel disease in the basal ganglia and presence of *APOE* *ɛ*4 allele(s), *APOE* *ɛ*2 allele(s), age group at death and cognitive impairment at death yielded no significant associations. DISCUSSION {#sec0050} ========== The importance of *APOE* genotype in AD and longevity has long been known but remains to be clearly understood. Here, using a carefully selected group of individuals with autopsy confirmed AD and also those considered (both cognitively and neuropathologically) normal for their age we found that an individual carrying *APOE* *ɛ*4 has a reduced chance of reaching 80+ years while avoiding cognitive impairment. Thus, it can be concluded that the effects of *APOE* *ɛ*4 on reducing longevity are strongest when cognitive impairment is also present. In contrast, there was a (non-significant) trend that suggested that carrying *APOE* *ɛ*2 increases the chances of living longer and avoiding cognitive impairment (unless an individual is *APOE* *ɛ*2/*ɛ*4). The lack of statistical significance could be due to the low numbers of *APOE* *ɛ*2 carriers in the study. Although a large number of previous studies have found similar results \[[@ref005]\], a smaller proportion of studies have shown conflicting findings \[[@ref010]\]. A large, recent review of 12 cohorts \[[@ref017]\] sought to use meta-analyses to assist in deducing the influence of *APOE* on longevity. Here, they concluded that, when compared to the *ɛ*3 allele, the *ɛ*4 allele was associated with a shorter lifespan and the *ɛ*2 allele was associated with a longer lifespan. Other meta-analyses have come to similar conclusions \[[@ref018]\] as have studies examining the effects of *APOE* on the longevity of those with Down syndrome (where AD pathology is almost ubiquitous in aged cases) \[[@ref019]\] leading to the assumption that our findings are in line with what has previously been found. A main strength of the present study is that it uses autopsy verified cases of AD and also confirms no (or little) pathology in the cognitively normal individuals. Many prior studies have used other methods of deducing disease state at death, such as death certification, which can lead to errors in assigning cognitive status as under-reporting of dementia in clinical practice is a known phenomenon \[[@ref020]\]. Alongside the robust neuropathological work-up, the study uses clinical information regarding cognitive impairment from a number of varied sources rather than simply relying on one measure of dementia (e.g., Mini-Mental State Examination). This ensures that the cognitive status of the individuals is as accurate as possible. A general limitation of the study is that the recruitment strategies for both BDR and UMLCHA could introduce bias. They are both self-selecting and only cover specific geographical areas in the UK. Future studies might perhaps include the whole BDR cohort which may better reflect society in the UK. Another possible limitation is that the study combined two cohorts which had different methods of collecting data. However, previous studies on these cohorts have shown that, although different in their approach, they both provide a robust clinical diagnosis which matches well to the neuropathological diagnosis \[[@ref015]\]. In conclusion, our data show that carrying the *APOE* *ɛ*4 allele leads to an increased chance of cognitive impairment and an early death. Conversely, carrying the *APOE* *ɛ*2 allele may lead to a longer life and better odds of remaining cognitively normal. These findings provide further evidence that *APOE* genotype is associated with mortality, especially in those who find themselves to be cognitively impaired. CONFLICT OF INTEREST {#sec0055} ==================== The authors have no conflict of interest to report. Supplementary Material ====================== ###### Supplementary Material ###### Click here for additional data file. University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age was funded by Medical Research Council, Economic and Social Research Council, The Wellcome Trust (grant reference number 003889) and Unilever PLC. The work of Manchester Brain Bank is supported by Alzheimer's Research UK and Alzheimer's Society through the Brains for Dementia Research (BDR) Programme. We also thank Daniel du Plessis and Piyali Pal for their help and assistance with neuropathology. The supplementary material is available in the electronic version of this article: <https://dx.doi.org/10.3233/ADR-200203>. [^1]: These authors contributed equally to this work. | High | [
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10 a factor of 6/q + 158/13? False Is 84 a factor of 1509/9 - ((-40)/(-24) + -2)? True Suppose k + 2 = 3. Let g(p) = 26*p**2 + 1. Let s be g(k). Suppose 32*b - s*b - 150 = 0. Does 15 divide b? True Let s = -228 + 158. Let x = 100 + s. Is x a multiple of 15? True Let o be 8/(-2) - (4 + -4). Let w be (-4)/(-24)*o*-3. Suppose -w*x + x + 38 = 0. Does 16 divide x? False Let h = -1818 + 3438. Is h a multiple of 20? True Let x(a) = a**2 - 4*a - 8. Let o(r) = -2*r**2 + 4*r + 8. Let p(b) = -2*o(b) - 3*x(b). Is 16 a factor of p(-9)? False Let n be (9/(-21))/((-3)/21) - -1063. Is 1/(-4) - n/(-8) a multiple of 19? True Is (328/(-4))/((-23)/828) a multiple of 12? True Suppose 3*k - 18 = 3*r - 6*r, 10 = 5*r - 5*k. Suppose 0 = -p + d - 110 + 269, -755 = -5*p - 5*d. Suppose -v - r*v = -p. Does 11 divide v? False Let m(y) = -y**2 + 2*y + 28. Let q be m(-16). Let a = 395 + q. Suppose 0 = -0*b + 5*b - a. Is 27 a factor of b? True Let p be 605/4 + 9/12. Suppose 0*i + 192 = 3*i. Let s = p - i. Is 24 a factor of s? False Let o be (((-132)/3)/(-2))/2. Let b = -12 + o. Let q = b + 5. Does 2 divide q? True Suppose 0 = b - 61 - 3. Suppose 2*t = -0*t + 2*r + b, -3*t + r = -98. Let n = t - 9. Is n a multiple of 12? True Suppose 34*a = 31*a + 840. Does 28 divide a? True Let w = -67 + 159. Is 3 a factor of w? False Let m = 71 - 58. Let o = -28 + 20. Let q = m + o. Is q a multiple of 5? True Does 11 divide (297/(-2))/9*(-480)/18? True Let a(j) = -5*j**3 - 3*j**2 - 4*j + 5. Let f be a(1). Let z be (-2 + -1)*(-2)/(-3). Is 15 a factor of 1/z*546/f? False Suppose -14*p - 2295 = -31*p. Does 3 divide p? True Let q(c) = 26*c + 231. Is 22 a factor of q(-7)? False Suppose 382 + 274 = -8*i. Let x = i + 299. Does 44 divide x? False Suppose 0*t - 2 = t. Is -2 - (t - -143)/(-3) a multiple of 25? False Suppose -5*b = -0*i + 2*i - 223, 4*b + 5*i - 175 = 0. Suppose 41 = 3*c - 5*z - 25, 0 = 2*c - z - 37. Let j = b - c. Is 9 a factor of j? False Let d(v) be the first derivative of 7*v**3/3 - 2*v**2 - 6*v - 2. Is 5 a factor of d(3)? True Let w(h) = -4*h**2 + 10*h - 8. Suppose 0*x - 10 = 5*x. Let r(n) = 21*n**2 - 50*n + 39. Let b(q) = x*r(q) - 11*w(q). Does 11 divide b(6)? True Let q(i) = -i + 12. Let m(t) = -3*t + 24. Let g(p) = 3*m(p) - 5*q(p). Does 8 divide g(-19)? True Is 34 a factor of (-3)/((-9)/511)*(84 + -81)? False Let k(d) = 49*d**2 - 8*d - 17. Is k(-4) a multiple of 47? True Let n = 5 - 3. Suppose i - 17*l = -13*l + 205, -417 = -n*i + l. Is i a multiple of 27? False Suppose 3*j = 6*j - 30. Let f(s) = -s**2 + 8*s + 8. Let o be f(j). Let n = 0 - o. Is n a multiple of 3? True Let l(d) = 58*d - 8. Suppose u + 8 = 4*b, 10 = 2*b + 3*b + u. Is 8 a factor of l(b)? False Let d be 12/16*(4 + -8). Does 20 divide (-7 - d)/4*114/(-2)? False Suppose 44 + 63 = q. Is q a multiple of 55? False Let s = -785 - -3161. Is 30 a factor of s? False Suppose i = 3, 2*k + 5*i = 610 + 245. Is 6 a factor of k? True Let j be 1/(-2) - 33/(-6). Suppose u - 56 = -2*m + 49, -2*u = -5*m - 228. Suppose -b - 4*b - 4*n = -u, j*b - 5*n = 145. Is 10 a factor of b? False Let q(b) = 9*b**2 + 41*b + 34. Let y(f) = 6*f**2 + 27*f + 23. Let j(i) = 5*q(i) - 7*y(i). Let c = 768 + -775. Is j(c) a multiple of 11? True Suppose 4*t - 56 - 48 = 0. Does 42 divide (t/4)/((-3)/(-78)) - 1? True Let p = -12 - -16. Let o be -2*p/(-8) + 8. Suppose 92 = 13*x - o*x. Is 7 a factor of x? False Let h(j) = j**2 + 2*j - 11. Suppose q - 45 = -50. Let v be h(q). Suppose 21 - 61 = -v*t. Is t a multiple of 5? True Let z = 956 - 654. Is 32 a factor of z? False Suppose -5*w - 6*j + 2*j = -10, -j = 3*w + 1. Let y be 4 + -9 - w - -348. Suppose -3*d = 2*d + l - y, -4*d = -4*l - 252. Is d a multiple of 14? False Suppose -6*i + 17 = -7. Does 8 divide (i + (-10)/(-2))*(-16)/(-6)? True Let f = 15 - 10. Let w be (-4)/10 - 28/f. Let n = 39 - w. Is n a multiple of 15? True Let s = -140 + 321. Let v = 47 + s. Is v a multiple of 12? True Suppose -3*w + 5*q + 156 = 0, -2*q + 115 = 2*w - 5. Is w even? False Suppose 0 = -2*c + 2 - 4, -f + 424 = -2*c. Does 12 divide f? False Suppose 5*r = -1 - 9, 5*r + 4864 = 3*d. Is 64 a factor of d? False Let u(x) = -71*x**3 + 7*x + 8. Is 18 a factor of u(-1)? True Suppose -47 + 128 = 3*z. Suppose -4*t = 3*x + 29, 3*t - x = -5*x - z. Let b(c) = -4*c + 2. Is 7 a factor of b(t)? False Let d = 716 - 472. Is 2 a factor of d? True Let v = -97 - -221. Does 18 divide v? False Let g(v) = -v**3 + 5*v**2 + 8*v. Let a = -8 - -13. Is 20 a factor of g(a)? True Let m(s) = -13*s - 238. Is 19 a factor of m(-62)? False Let q(i) = 2*i**2 + 11*i - 11. Does 2 divide q(1)? True Let w(m) = -m**2 + 1. Let a(r) = r**3 + 10*r**2 + 4*r - 7. Let k(u) = -a(u) - 5*w(u). Let d be k(-4). Is 1/d*168/4 a multiple of 15? False Let r(j) = -j**2 + 4*j + 5. Let b be r(4). Let p(l) = -l**3 + 7*l**2 - 4*l - 6. Is p(b) a multiple of 5? False Let w = 294 - -2196. Is 23 a factor of (w/(-12))/(-5)*2/1? False Let o(w) = 2*w**3 - 3*w + 2. Let t be o(-2). Does 37 divide (-1032)/(-14) - t/28? True Suppose -12*r = -11*r - 10. Suppose -r*v + 32 = -6*v + 4*c, -c = -2*v + 13. Does 2 divide v? False Let n be (168/(-15))/(1/20). Let t = n + 580. Is 17 a factor of t? False Is (-5*(-9)/15)/1 + 188 a multiple of 29? False Suppose -18 = 4*d - 146. Let k = 72 - d. Is 10 a factor of k? True Let r(p) = -p**3 - 16*p**2 + 11*p - 17. Suppose -3*h + 6*n = 11*n + 31, h - 2*n + 25 = 0. Is 17 a factor of r(h)? True Suppose -3*s + 39 - 12 = 0. Let w = 39 - s. Is 15 a factor of w? True Let h(l) = -182*l**3 + 2*l**2 - 21*l - 21. Does 8 divide h(-1)? True Let g be -1*(3 + -3)*(-1)/2. Is 3/6*((0 - g) + 178) a multiple of 19? False Suppose -4*d + 9 = -3*h, -5*h + 8 = d - 0*h. Let j be 32/12 + d/9. Suppose 0 = j*y - 7*y + 180. Is y a multiple of 15? True Let q be ((-8)/(-10))/((-4)/1220). Let l = -88 - q. Is 12 a factor of l? True Let h(z) = -435*z + 398. Does 16 divide h(-6)? True Suppose -5*v + 0*v = -100. Suppose 0*x = 4*x - 4*h - v, h = 5. Does 5 divide 4 + (x - (-3 + 2))? True Let q(u) = -14*u**2 + 7*u + 59. Let i(j) = -j + 6*j**2 - 18 - 2 - j**2 - j. Let w(h) = 17*i(h) + 6*q(h). Is w(-13) a multiple of 23? False Suppose -7*b = 4*r - 2*b - 2699, -2*b = -3*r + 2007. Does 11 divide r? True Let a be (-5)/2*(-27 - -25). Suppose -5*m = a*k - 1005, -13*k - 5*m = -16*k + 627. Is 34 a factor of k? True Suppose -3*o = 3 - 24. Suppose 4 = -3*u + o*u. Is 21 a factor of u*47 - (-9 + 9)? False Let s be (6 - 0)*(-9)/(-45)*-5. Does 24 divide s/(-27) + (-2 - (-709)/9)? False Let u(p) = -3*p + 1. Let x be u(1). Let w(o) = -18*o + 49. Let n be w(0). Is 27 a factor of n - (-3)/(-6)*x? False Does 4 divide ((-728)/(-12))/(14/42)? False Let y = -1883 - -4798. Does 23 divide y? False Suppose -3 - 4 = i. Let h(b) = b**2 - 14*b - 17. Let u be h(16). Let r = i + u. Does 2 divide r? True Suppose c + 4*c = -2075. Let g = -108 - c. Is g a multiple of 26? False Let f(q) = -q + 3. Let l be f(1). Suppose -3*n = l*u - 117 + 13, 0 = -u - 3*n + 46. Does 10 divide u? False Does 14 divide ((-2)/2)/((-4)/9596)? False Suppose 3*g + 104 = 7*g. Is (-10)/(((-4)/g)/1) a multiple of 8? False Let b be 52*(25/10 - 2). Is 1348/b - 12/(-78) a multiple of 26? True Let g(j) be the first derivative of j**7/840 - j**6/60 + j**5/20 + 5*j**4/24 + 2*j**3/3 - 3. Let m(s) be the third derivative of g(s). Is m(6) a multiple of 14? False Let m(h) be the first derivative of -h**2/2 + 7*h - 18. Is 2 a factor of m(4)? False Let a(i) = -1013*i**3 + 6*i**2 + 2*i - 5. Is a(-1) a multiple of 74? False Let z(p) = 8*p**2 - 7*p - 2. Suppose 17 = -4*n + 9. Does 5 divide z(n)? False Let p(n) = n**2 + 5*n - 8. Let a be p(-6). Let t be 2/(-4)*a + 19. Suppose -f = 5*o - 3*f - t, 0 = -o - 2*f + 16. Is o a multiple of 3? True Suppose 38 = 3*i + t, -13 - 15 = -2*i + 2*t. Let d be (-8)/28 + 74/14. Let v = i + d. Does 3 divide v? True Let x(l) = l - 1 + 4*l + 7*l - 4*l. Let i be x(5). Let g = 60 - i. Is g a multiple of 9? False Is 68 a factor of (2/4)/((-60)/(-46680))? False Let f = -7 - -9. Let n(c) = 108*c - 4. Let x be n(f). Let m = x + -137. Is 23 a factor of m? False Let u = 19 + -15. Let o = 10 + u. Suppose 4*f = 3*f + o. Is 14 a factor of f? True Suppose -195 = -3*w - 4*v, 8*w - 232 = 4*w + 4*v. Is 5 a factor of w? False Let p(r) = 73*r**2 + r. Let w be p(3). Suppose | Low | [
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Q: How to give a default value to a textfield when using bloc framework I've written some simple flutter apps which use stateful widgets / forms / textformfields to enter and manage data. Now I'm trying to understand how to use BLoCs and streambuilders to do similar work. But I can't work out how to set initial values for my fields. I've tried to create the simplest example I could come up with of a tiny app using a bloc. This just takes a name that is entered into a TextField and echos it onto the next line. import 'package:flutter/material.dart'; import 'package:rxdart/rxdart.dart'; void main() => runApp(MyApp()); class MyApp extends StatelessWidget { @override Widget build(BuildContext context) { return MaterialApp( title: 'Bloc Example', home: MyHomePage(), ); } } class MyHomePage extends StatelessWidget { MyHomePage(); String initialData = 'Fred'; @override Widget build(BuildContext context) { TextEditingController _controller = new TextEditingController(); return Scaffold( appBar: AppBar(title: Text('Bloc Example')), body: Center( child: Column( children: <Widget>[ StreamBuilder( initialData: initialData, stream: bloc.nameStream, builder: (context, snapshot) { if ( snapshot.connectionState == ConnectionState.waiting) _controller.text = snapshot.data; return TextField( controller: _controller, onChanged: bloc.nameChangedStream, decoration: InputDecoration(labelText: 'Enter name' ), ); } ), StreamBuilder( initialData: initialData, stream: bloc.nameStream, // builder: (context, snapshot) { return Text('Name is ${snapshot.hasData ? snapshot.data : 'unknown'}'); } ), ], ), ), ); } } class Bloc { final nameStreamController = BehaviorSubject<String>(); Stream<String> get nameStream => nameStreamController.stream; Function(String) get nameChangedStream => nameStreamController.sink.add ; } final Bloc bloc = new Bloc(); I can't work out how to specify an initial value to my name field. I must admit, coming from an old style programming background, it's taking me a while to get my mind into reactive programming - but onwards and upwards! EDIT - thanks to the comments given - updated the code to use a combination of TextEditingController and StreamBuilder initialData and seems to be working ok. Happy to take further comments if there's a better solution :) A: You can give your behaviorSubject a seed value that will be used as its initial value by doing this. final nameStreamController = BehaviorSubject<String>.seeded('InitialName'); for older versions of rxDart, use final nameStreamController = BehaviorSubject<String>(seedValue:'InitialName'); A: Without knowing what you want to do with the name field, there are a few routes you can go. You could supply a hintText to the InputDecoration (InputDecoration(hintText: 'name')). You could set an initial value on the StreamBuilder: StreamBuilder( stream: bloc.nameStream, initialData: 'Initial Name', builder: (context, snapshot) { return TextField( onChanged: bloc.nameChangedStream, decoration: InputDecoration(labelText: 'Enter name' ), ); } ), Though, that won't persist that value in the stream, so if the user doesn't change the text field, 'Initial Name' won't be in your nameStreamController's stream. As @nonybrighto mentioned, you can seed your nameStreamController with the initial value. If you cannot use a seeded value, you could also add an initial value to your stream during the bloc's init: class Bloc { final nameStreamController = BehaviorSubject<String>(); Stream<String> get nameStream => nameStreamController.stream; Function(String) get nameChangedStream => nameStreamController.sink.add; Bloc() { String initialValue = _getInitialValue(); nameStreamController.add(initialValue); } } Here's a more full, real-world example: we found this authentication and login BLoC example in which we followed a lot of the stuff laid out here: Didier Boelens BloC Example. It shows you how can use BLoC, reactive programming, and streams to set up a registration form and auth. | Mid | [
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Q: Extreme drop in framerate when playing Dragon Age: Origins for PS3 I'm playing Dragon Age: Origins Ultimate Edition for PS3 with the 1.01 patch installed. Whenever I'm exploring and enter into combat, the game pauses/freezes/the framerate drops to near zero. After a second or two, it begins to refresh again, but the framerate continues to lag for several seconds after that. Eventually, after five seconds or so, framerate picks back up to interactive levels. Is this a known issue? It makes playing the game a chore, especially when entering areas with lots of mobs. A: If software is ruled out (by updates), the cause most-likely resides in the hardware. While this doesn't necessarily help your problem, the cause is likely a combination of wear and tear on your PS3 (namely the video processing unit) in culmination with high demands from the game on a potentially older PS3 model. Not much can be done if the developers ignored older model architecture restrictions besides waiting for a software update to address them. Try to get your hands on some other games made by the same company and some released around the same time period to see if the problem comes up. | Mid | [
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An affluent suburban Kansas City woman who admitted last year shoplifting truckloads of clothing from area retailers has been arrested again, this time on suspicion of stealing bras. The Kansas City Star reports 47-year-old Kelli Bauer of Overland Park, Kansas, is accused of stealing an unknown number of bras from a Kohl's store on Nov. 15. Police searched Bauer's $900,000 home in an exclusive Johnson County neighborhood in April 2015 and found more than 1,000 stolen items, some of which she was trying to sell. She was scheduled to be sentenced on Wednesday on a felony theft conviction, but that was pushed back to January after Johnson County prosecutors filed a motion seeking to be released from her plea bargain. | Low | [
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1. Introduction {#sec1-pathogens-09-00241} =============== Prion diseases are lethal neurodegenerative disorders that can affect both humans and animals. The pathogenesis of prion diseases requires the conversion of normal cellular prion protein (PrPC) to its disease-associated isoform (PrPSc) and is accompanied by its accumulation in the brains of affected organisms. \[[@B1-pathogens-09-00241]\]. The presence of PrPSc correlates with infectivity \[[@B2-pathogens-09-00241]\], and hence, it is believed to be the main agent of prion diseases. PrPSc exhibits partial proteolytic resistance against proteinase K (PK), and proteinase-resistant PrPSc (PrPres) has been considered a surrogate marker for prion infection. Several studies have shown that prion infectivity does not always correlate well with PrPres levels \[[@B3-pathogens-09-00241]\]. In previous temporal correlative studies on infectious titers and PrPres levels in prion-infected animals, a continuous increase in PrPres levels was observed even after the infectious titer reached a plateau \[[@B4-pathogens-09-00241],[@B5-pathogens-09-00241],[@B6-pathogens-09-00241],[@B7-pathogens-09-00241]\]. In addition, high levels of infectivity with undetectable or extremely low PrPres were observed in transgenic mice expressing murine PrP P101L (Tg 101LL) with Gerstmann--Sträussler--Scheinker syndrome \[[@B8-pathogens-09-00241],[@B9-pathogens-09-00241]\] or 263K scrapie \[[@B10-pathogens-09-00241]\]. Real-time quaking-induced conversion (RT-QuIC) is one of the novel in vitro amplification assays that was developed based on the prion-seeded conversion of recombinant prion proteins (recPrP) to the amyloid fibrillar form by shaking \[[@B11-pathogens-09-00241],[@B12-pathogens-09-00241]\] rather than the sonication used in its original assay \[[@B13-pathogens-09-00241]\]. There is a strong correlation between RT-QuIC positivity and prion infection. The RT-QuIC assay has been shown to detect prion seeding activity in tissues and body fluids of animals and humans with prion diseases, with sensitivities higher than those of animal bioassays \[[@B11-pathogens-09-00241]\]. Thus, RT-QuIC can act as a possible antemortem test for prion disease \[[@B12-pathogens-09-00241]\], an evaluation tool for decontamination methods \[[@B14-pathogens-09-00241]\], and a risk assessment tools for iatrogenic prion transmission via tissues \[[@B15-pathogens-09-00241]\]. Considering the aforementioned discrepancies between PrPres and prion infectivity, it is important to establish the relationship between prion seeding activity and infectivity. A previous study reported a closer correlation of prion seeding activity with infectivity than with PrPres levels, as judged by the similar seeding activities in the brains of 139A or 263K scrapie-affected Tg 101LL mice containing equivalent infectious titers but discrepant PrPres levels \[[@B16-pathogens-09-00241]\]. On the other hand, it has also been reported that prion infectivity is eliminated by a disinfectant without altering seeding activity \[[@B17-pathogens-09-00241]\]. Hence, the controversial relationship between seeding activity and infectivity remains to be elucidated. Although time-course prion seeding activity in scrapie-infected hamsters has been described \[[@B18-pathogens-09-00241]\], the temporal relationship between prion seeding dose and infectious titer has not yet been determined. In our previous temporal study on mouse-adopted classical bovine spongiform encephalopathy (mBSE) prion, we reported that the infectious titer reached a plateau at 100 days postinfection (dpi) whereas PrPres levels were continuously elevated towards the end of the incubation period, suggesting the uncoupling of prion titer and PrPres levels \[[@B19-pathogens-09-00241]\]. In this study, we attempted to determine the kinetics of prion seeding activity in the brains of these mice. We applied endpoint dilution RT-QuIC on brain homogenates to obtain a detailed measurement of seeding activities at defined intervals during the incubation period in mice and assessed the temporal relationships among seeding dose, PrPres levels, and prion titer. In addition, we investigated the alterations in seeding doses associated with the reduction of PrPres levels after high-speed centrifugation of brain homogenates. 2. Results {#sec2-pathogens-09-00241} ========== 2.1. RT-QuIC Detection of mBSE BH-Derived Seeding Activity {#sec2dot1-pathogens-09-00241} ---------------------------------------------------------- A previous study indicated that RT-QuIC using N-terminally truncated hamster recombinant PrP residues 90--231 (recPrP) could detect a mouse-adopted scrapie RML strain in wild-type mice \[[@B20-pathogens-09-00241]\]. To determine if prion seeding activity derived from mBSE in CD-1 mice can be detected, we performed RT-QuIC using hamster recPrP. Quintuplicate RT-QuIC reactions were seeded with serial dilutions of the brain homogenates (BHs) of terminally ill mice with mBSE (from a 10^−2^ to 10^−9^ dilution of a 10% weight per volume BH). We used 96-well plates from three lot numbers for the four analyses. In parallel, we assessed the effect of rinsing the 96-well plates with an acetone-ethanol 1/9 (v/v) mixture, as Hoover and colleagues demonstrated that the inhibitory effect of brain lipids on prion amyloid formation can be abrogated using an alcohol-based extraction technique \[[@B21-pathogens-09-00241]\]. With the mBSE strain, seeding activity was detected using RT-QuIC and hamster recPrP. The amyloid formation rate, which is represented by the inverse of the time (h) for the thioflavin T fluorescence signals to exceed the threshold for each replicate seeded with serially-diluted brain tissues, is shown in [Figure 1](#pathogens-09-00241-f001){ref-type="fig"}a. The amyloid formation rate, which was measured using non-treated 96-wells plates, had a linear detection range from 200 ng (dilutions of 1 × 10^−3^) to 20 pg (dilutions of 1 × 10^−7^) ([Figure 1](#pathogens-09-00241-f001){ref-type="fig"}b). The number of the positive replicates started to decrease at 200 pg seeded, and the mean ± SD of Spearman--Käber estimates of the SD~50~ per unit tissue was 10.15 ± 0.06 log SD~50~ per gram of brain ([Figure 1](#pathogens-09-00241-f001){ref-type="fig"}c). After rinsing the 96-well plates with the acetone-ethanol mixture, we observed significantly higher rates of amyloid formation from 10^−3^ to 10^−7^ dilutions than those measured using the non-treated 96-well plates. The amyloid formation rates that were measured in the acetone-ethanol mixture rinsed 96-well plates displayed a linear detection range from 200 ng (dilutions of 1 × 10^−3^) to 2 pg (dilutions of 1 × 10^−8^). In addition, the SD~50~ per unit of the same tissue was 11.15 ± 0.06 log SD~50~ per gram of brain, indicating that rinsing the 96-well plates with an acetone-ethanol mixture improved the RT-QuIC detection limit by an order of magnitude without increasing the false positive rate. Similar improvements in the RT-QuIC detection limit and amyloid formation after rinsing the 96-well plates were also observed for chronic wasting disease (CWD)-affected elk BH ([Figure S2](#app1-pathogens-09-00241){ref-type="app"}). Hence, we used 96-well plates rinsed with the acetone-ethanol mixture for subsequent RT-QUIC analyses. For mechanistic insight, we assessed the adsorption of recPrP to the 96-well plates rinsed with or without the acetone-ethanol mixture; however, bicinchoninic acid assays showed no significant difference in the surface adsorption of recPrP (data not shown). Investigations on the precise effect of organic solvents in improving prion amyloid formation might possibly provide clues regarding the mechanistic details of amyloid assembly. 2.2. Correlation among Seeding Activity, Infectivity, and PrPres Levels {#sec2dot2-pathogens-09-00241} ----------------------------------------------------------------------- To determine the amplification characteristics of mBSE prion seeding activity, we performed end-point dilution RT-QuIC on BH stocks at multiple defined time points and calculated the SD~50~ ([Figure 2](#pathogens-09-00241-f002){ref-type="fig"}a). The LD~50~ of the same BH had previously been estimated using a mouse bioassay \[[@B19-pathogens-09-00241]\]. In addition, to semi-quantify the levels of PrPres, we reprocessed the same BH stocks for ELISA using the Seprion ligand \[[@B22-pathogens-09-00241]\]. Seeding doses did not increase during the first \~30 days after inoculation. However, there was a progressive increase in seeding activity (30 to 125 days) after this lag phase. A similar trend was observed for PrPres levels, whereas the infectious titer increased exponentially without any lag phase until 100 days and then reached a plateau phase. The estimated infectious titer at 100 days was 7.9 log LD~50~ per gram, which was indistinguishable from that at 140 days. These data suggested that the kinetics of infectious titer did not correlate with those of the seeding dose and PrPres levels in mBSE prion mouse models, especially in the first 30 days and from 100 to 140 days. The exponential phase of the seeding dose, infectious titer, and PrPres levels from 40 to 100 days was used to calculate each doubling time as PrPres was undetectable or barely detectable until 40 days \[[@B19-pathogens-09-00241]\], and the infectious titer reached a plateau by 100 days. The best fit exponential curve showed the relationships with seeding doses as 3,541,353\* e\^(0.085361\*days), infectious units as 296,647\* e\^(0.056066\* days), and PrPres (arbitrary light units) as 19.2724\* e\^(0.083569\* days). These curves showed correlation coefficients of 0.906, 0.971, and 0.972, respectively. According to a previous study \[[@B6-pathogens-09-00241]\], the doubling times of seeding dose, infectious titer, and PrPres levels were calculated as 8.1 days, 12.4 days, and 8.3 days, respectively, from 40 to 100 days. We observed a similar doubling time of seeding activity and PrPres accumulation. Notably, at end-stage disease, an uncoupling of seeding doses and PrPres levels was observed. The seeding doses seemed to reach a plateau level by 125 dpi, whereas PrPres levels were still elevated. A significant increase in PrPres after 125 dpi was also confirmed by western blot analysis ([Figure 2](#pathogens-09-00241-f002){ref-type="fig"}b). It is conceivable that PrPSc that accumulated at late-stage disease formed larger aggregates ([Figure 2](#pathogens-09-00241-f002){ref-type="fig"}c), which might have little contribution to the increase in seeding activities. To investigate this possibility, we sonicated the BHs from an mBSE-affected mouse with terminal disease and compared the seeding doses of those with or without sonication. No major differences in seeding dose were identified in comparisons of sonicated BH and untreated BH (data not shown). 2.3. Seeding Activity and PrPres Levels in BHs After Centrifugation {#sec2dot3-pathogens-09-00241} ------------------------------------------------------------------- We previously reported that, after the centrifugation (20,000× *g* for 10 min) of crude brain homogenates of mBSE-affected mice, most PrPres was precipitated as a pellet (20K-ppt), whereas the supernatant (20K-sup) still contained almost similar levels of infectivity as those in crude BHs \[[@B19-pathogens-09-00241]\]. To further elucidate the relationship between seeding activity and PrPres, we performed end-point dilution RT-QuIC on the supernatant (20K-sup) and pellet (20K-ppt) obtained after the centrifugation of crude BHs from three mBSE-infected mice. Semiquantitative densitometric analysis of PrPres after western blotting indicated that the 20K-sup contained \~22 and \~29-fold lower PrPres levels than the 20K-ppt and crude BHs, respectively ([Figure 3](#pathogens-09-00241-f003){ref-type="fig"}a). Consistent with the western blotting results, we observed lower seeding activity for the 20K-sup (9.20 ± 0.20 log SD~50~/g) than for the 20K-ppt and crude homogenates (10.33 ± 0.32 and 10.45 ± 0.20 log SD~50~/g, respectively; [Figure 3](#pathogens-09-00241-f003){ref-type="fig"}b). As the 20K-sup and crude BHs were reported to harbor similar infectivity, these results suggest potential discrepancy between RT-QuIC seeding activity and prion infectivity. 2.4. PK-Resistance of Seeding Activities with mBSE BHs {#sec2dot4-pathogens-09-00241} ------------------------------------------------------ To examine the possibility that PK-sensitive PrPSc contributes to seeding activity, mBSE BHs were pretreated with triton X-100 and treated with or without PK prior to end-point dilution RT-QuIC. The PrPres was clearly detected, and intact PrPSc signal was not detected from the digested samples ([Figure 4](#pathogens-09-00241-f004){ref-type="fig"}a). No significant effect of PK treatment on the mean SD~50~/g brain was seen with mBSE BH ([Figure 4](#pathogens-09-00241-f004){ref-type="fig"}b). 3. Discussion {#sec3-pathogens-09-00241} ============= In the present study, we used the modified RT-QuIC method to assess prion amyloid formation and established the time course of seeding doses in the brains of mBSE-affected wild-type mice. Although the time course of seeding doses in scrapie-infected hamsters has been described \[[@B18-pathogens-09-00241]\], the temporal relationship between seeding dose and infectious titer has not yet been determined. Our temporal correlative study revealed that seeding activity correlated more tightly with a PrPres subset than prion infectivity in this model. We observed that rinsing the 96-well plates with an acetone-ethanol mixture improved the RT-QuIC detection limit and the amyloid formation of mBSE and CWD prions. However, the precise role of organic solvents remains unclear. Possibly, the acetone-ethanol mixture might remove inhibitory factors from the surface of 96-well plates. Alternatively, a study has shown that the inhibitory effect of brain lipids on prion amyloid formation can be abrogated by alcohol-based extraction \[[@B21-pathogens-09-00241]\]. Thus, it is plausible that rinsing with the acetone-ethanol mixture might change the surface properties of 96-well plates and allows them to absorb more lipids from the samples, which would inhibit prion amyloid formation in vitro. Our results demonstrated that there is a close relationship between prion seeding activity and PrPres levels, except for in late-stage disease, in an mBSE-affected wild-type mouse model. We followed prion seeding activity after mBSE prion infection using end-point dilution RT-QuIC. At the early stage, the lag phases were followed by an exponential phase of seeding dose as well as PrPres amplification whereas no lag phase in prion titer was observed. In the exponential phase (from 40 to 100 days), the calculated doubling time of 8.1 days for seeding dose was closer to that of 8.3 days for PrPres levels than to that of 12.4 days for infectious titer. In addition, by 100 days, the prion titer reached a plateau whereas the seeding dose and PrPres levels remained elevated. Furthermore, our RT-QuIC analysis of supernatants and pellets obtained by high-speed centrifugation of BHs suggested potential discrepancy between seeding activity and prion infectivity. These characteristics of temporal changes in seeding dose, infectious titer, and PrPres levels led us to conclude that RT-QuIC seeding activity correlates more closely with PrPres levels than with prion infectivity. Nonetheless, at end-stage disease, an uncoupling of seeding doses and PrPres levels was observed. One possible explanation is that PrPSc that accumulated at late-stage disease might contribute little to the increase in seeding activities. Hughson and colleagues reported that a disinfectant neutralizes prion infectivity without eliminating seeding activity, implying that infectious PrPSc comprises only a subset of PrP particles with RT-QuIC activity \[[@B17-pathogens-09-00241]\]. Considering our present data together with this previous finding, it is likely that PrPSc with RT-QuIC seeding activity has a substantial but not complete overlap with proteinase-resistant PrPSc rather than infectious PrPSc. Since it is plausible that the formation of large PrPSc aggregates at late-stage disease might affect seeding activity, BH was processed by RT-QuIC with or without sonication. Contrary to our expectations, the seeding doses of the sonicated BHs were not significantly altered compared to those of the untreated BHs, suggesting that the extent of PrPSc aggregation might exert little influence on RT-QuIC seeding activity. Although the partial fragmentation of PrPSc aggregates after the sonication of BHs was confirmed by sucrose density gradient centrifugation, we cannot exclude the possibility that our sonication treatments were insufficient to collapse the PrPSc aggregate to enhance seeding activities. Alternatively, since it is known that amyloid fibril growth begins with binding of monomers to the growing ends \[[@B23-pathogens-09-00241]\], at late-stage disease, larger aggregates of PrPSc might be mainly formed by amorphous aggregates with PK resistance which have less growing ends rather than amyloid fibrils. Including the involvement of proteinase-sensitive PrPSc and the effect of the hamster recPrP as RT-QuIC substrate, the precise mechanisms underlying an uncoupling of seeding doses and PrPres levels for PrPSc are yet to be determined. Our present findings appear to be inconsistent with the data reported for 139A or 263K scrapie-affected Tg101LL mice, where an equivalent prion seeding dose and infectious titer but discrepant PrPres levels were observed, indicating a close correlation between prion seeding activity and infectivity \[[@B16-pathogens-09-00241]\]. One possible reason for this discrepancy might be the differences in the mice analyzed in these studies. It is plausible that, unlike PrPres in wild-type mice, only a small population of PrPres in Tg101LL mice might be responsible for seeding activity. In other words, although substantial amounts of PrPres are present in Tg 101LL mice inoculated with 139A scrapie, most of the PrPres might not be relevant for amyloid formation. Alternatively, the PrPres that accumulated in Tg101LL mice affected by 263K possibly possess higher amyloid-formation abilities than in those affected by 139A, resulting in a similar seeding activity, albeit with low amounts of detectable PrPres. To address this discrepancy, it might be necessary to conduct temporal correlative studies on seeding dose, infectious titer, and PrPres levels in Tg101LL mice affected by 139A and 263K scrapie strains. More detailed temporal correlative studies of various prion strains are required to elucidate the relationship among prion seeding activity, infectivity, and PrPres levels. We performed a temporal correlative study with only one prion strain using wild-type mice, and thus, we cannot exclude the possibility that another prion strain in other host species might show a different correlative relationship between seeding dose and infectious titer. Indeed, in a scrapie-affected hamster model where a continuous increase in both PrPSc levels and infectious titer to the end of disease is observed \[[@B24-pathogens-09-00241]\], the seeding dose also increased toward the end of the incubation period with no plateau phase \[[@B18-pathogens-09-00241]\]. To the best of our knowledge, we believe that this is the first correlative study on the kinetics of prion seeding dose, infectious titer, and PrPres levels in parallel. We demonstrated that amyloidogenic PrPSc substantially but not completely overlaps with PrPres, as compared to infectious PrPSc, in this model. Further studies will be required to clarify the relationship among different types of PrPSc based on various prion strains in another host species. 4. Materials and Methods {#sec4-pathogens-09-00241} ======================== 4.1. Mouse-Adapted Classical BSE Brain Homogenates {#sec4dot1-pathogens-09-00241} -------------------------------------------------- Mouse-adapted classical BSE prions were propagated first in RIII mice and then sequentially in 3-week-old specific pathogen-free female CD-1 mice 14 times. In our previous study \[[@B19-pathogens-09-00241]\], 20 µL of mBSE brain homogenates (BHs), which contained 10^5.9^ LD~50~ of mBSE prion, was intracerebrally inoculated into CD-1 mice. Three recipient mice were sacrificed at designated time points (5, 30, 40, 60, 70, 90, 100, 125, and 140 days postinfection), and the brains were collected. The brains at each time point were homogenized in phosphate buffered saline (PBS) and stored at −80 °C until further use. In the current study, we used these BHs for the kinetic analysis of seeding dose, infectious titer, and PrPres levels. The data regarding infectious titers which were estimated by incubation-time assay using four to six CD-1 mice were obtained from our previous report \[[@B19-pathogens-09-00241]\] with the permission of its authors including the corresponding author. 4.2. Recombinant Prion Protein {#sec4dot2-pathogens-09-00241} ------------------------------ Recombinant Syrian hamster prion protein (recPrP; amino acids 90--231) constructs were expressed in *Escherichia coli* strain BL21-CodonPlus (DE3)-RIPL (Stratagene, La Jolla, CA, USA) and purified as previously described with slight modifications \[[@B25-pathogens-09-00241]\]. The solubilized inclusion body containing recPrP was applied to an Ni-NTA Superflow resin (Qiagen, Venlo, Netherland) and loaded onto a XK16-20 column (GE Healthcare, Buckinghamshire, England) connected to an AKTA~FPLC~ system. The elution peak was pooled and dialyzed in dialysis buffer containing 100 mM NaCl in 10 mM NaPO~4~, pH 5.5, overnight at 4 °C. Concentrations of recPrP were estimated by its absorbance at 280 nm. Aliquots of proteins were stored at −80 °C until further use. After thawing, aliquots of proteins were centrifuged at 20,000× *g* for 30 min at 4 °C and the soluble recPrP was used. 4.3. Rinsing of 96-Well Plate {#sec4dot3-pathogens-09-00241} ----------------------------- Optical-bottom black 96-well plates (\#265301, Thermo Fisher Scientific, Waltham, MA, USA) were rinsed with an acetone-ethanol 1/9 (v/v) mixture. Each well was filled with 320 μL of acetone--ethanol mixture and aspirated completely. The rinsed 96-well plate was dried in a safety cabinet for at least 15 min before use. 4.4. Real-Time QUIC {#sec4dot4-pathogens-09-00241} ------------------- Real-time QuIC (RT-QuIC) assays were performed as reported previously with slight modifications \[[@B25-pathogens-09-00241]\]. Briefly, 98 µL of the RT-QuIC reaction substrate mixture containing 0.1 mg/mL Syrian hamster recPrP (aa 90--231), 320 mM NaCl, 1 mM ethylenediaminetetraacetic acid (EDTA), and 10 µM thioflavin T (Th T) in 100 mM phosphate (pH 7.4) was loaded into an optical-bottom black 96-well plate. The reaction substrate mixtures were seeded with 2 μL of BH 10-fold serially diluted with 0.075% sodium dodecyl sulfate (SDS) in PBS. The seeded brain tissue equivalents from an mBSE-inoculated mouse were diluted to 2 µg to 200 fg (10^−2^ to 10^−9^ dilutions of 10% weight per volume of the BH), and those from a normal mouse were diluted to 20 ng. Each brain homogenate was assayed in quadruplicate wells at least three times using independent reaction substrate mixtures. The plates were sealed and incubated in a BMG FLUOstar Omega plate reader (BMG LABTECH, Ortenberg, Germany) at 37 °C with 1 min of shaking (1100 r.p.m., double-orbital) and 1 min of rest for 62 h. ThT fluorescent readings (450-nm excitation and 480-nm emission, bottom-read, 20 flashes per well, gain of 1500) were recorded every 15 min. The threshold for positivity of each BH was calculated as four-fold greater than the average of the initial fluorescence of all samples. The lag phase (h) was defined as the reaction time required to exceed the threshold. Amyloid formation rate (AFR; 1/h), which is the inverse of lag phase, was used as an indicator of amyloid seeding activity. RT-QuIC conditions such as the concentration of SDS, reaction temperature, and shaking speed were optimized to minimize the false positive rate without a loss of sensitivity. 4.5. Calculation of Seeding Dose {#sec4dot5-pathogens-09-00241} -------------------------------- Seeding doses of 50% (SD~50~) were determined using end-point dilution RT-QuIC. The log-dose of the dilution yielding 50% positive replicates per gram wet weight equivalent (indicated as log SD~50~ per gram) was calculated using the Spearman--Kärber method, with 10-fold dilutions of each of the positive and negative seeding activity ratios. 4.6. Enzyme-Linked Immunosorbent Assay (ELISA) {#sec4dot6-pathogens-09-00241} ---------------------------------------------- The BHs were processed for ELISA using the Seprion ligand (Microsens Biotechnologies, London, UK) to semi-quantify the levels of PrPres \[[@B22-pathogens-09-00241]\]. The Seprion ligand is a group of polymeric compounds with specificity for PrPSc and can be immobilized directly on the wells of a microplate as a substitute for capturing antibodies. Briefly, the BHs were lysed in capture buffer (1% N-lauroyl sarcosine, 1% triton X-100, 1% bovine serum albumin, and 0.5% trypsin in 50 mM tris--HCl, pH 8.3) and applied to a 96-well microplate (FluorNunc Black, Thermo Fisher Scientific) coated with the Seprion ligand. After incubation for 2 h, PrPres captured on the well was denatured with 4 M guanidine thiocyanate in 20% polyethylene glycol 8000 (Fisher Scientific, Hampton, NH, USA) and detected using anti-PrP mAb T2 conjugated with horse radish peroxidase (HRP) \[[@B26-pathogens-09-00241]\]. The plates were developed using a chemiluminescence solution (Supersignal West Dura Extended Duration Substrate; Pierce Biotechnology, Rockford, IL, USA), and the signal was determined using an ARVO SX 1420 multilabel counter (Wallac, Turku, Finland). Four-fold serial dilutions of the BH from a terminally ill mouse with mBSE were subjected to ELISA to confirm its linear dynamic range ([Figure S1](#app1-pathogens-09-00241){ref-type="app"}). 4.7. Western Blot Analysis {#sec4dot7-pathogens-09-00241} -------------------------- The 10% (w/v) BHs of mBSE-affected mice were centrifuged at 20,000× *g* for 10 min at 4 °C. After collecting the supernatant (20K-sup), the pellet was reconstituted with the same volume of PBS with brief sonication (20K-ppt). Each sample was diluted 20-fold with lysis buffer containing 10 mM tris-HCl (pH 7.4), 150 mM NaCl, 1 mM EDTA, 0.5% triton X-100, and 0.5% sodium deoxycholate. For PrPres detection, each sample was treated with 40 µg proteinase K (PK) for 30 min at 37 °C. For proteinase-sensitive PrPSc analyses, the 10% (w/v) BHs of mBSE-affected mice were pretreated with 0.5% triton X-100 (final concentration) and digested with 0, 5, and 40 µg/mL of PK for 30 min at 37 °C. PK digestion was terminated by adding Pefabloc (Roche Diagnostics, Mannheim, Germany) at a final concentration of 4 mM. All samples were suspended in three times their volumes of 4 × lithium dodecyl sulfate sample loading buffer (Thermo Fisher Scientific) and boiled. The samples were electrophoresed on 12% NOVEX pre-cast gels (Thermo Fisher Scientific) and electrotransferred onto Durapore (Merck Millipore, Burlington, MA, USA) polyvinylidene fluoride membranes. The blots were probed with HRP-conjugated PrP-specific antibody T2. Chemilumi One Super (Nakarai Chemical, Kyoto, Japan) was used for immunodetection. The blots were visualized with a Fluorchem (Alpha Innotech, San Leandro, CA, USA) and analyzed using image reader software (AlphaEaseFC; Alpha Innotech) according to the manufacturer's instructions. 4.8. Immunohistochemistry {#sec4dot8-pathogens-09-00241} ------------------------- Formalin-fixed left hemispheres were embedded in paraffin wax following immersion in 98% formic acid to decrease infectivity. After epitope retrieval, PrPSc immunocytochemistry was performed using the anti-PrP monoclonal antibody SAF84. As the secondary antibody, the anti-mouse universal immunoperoxidase polymer (Nichirei Histofine Simple Stain MAX-PO (M); Nichirei, Tokyo, Japan) was used. PrPSc was visualized with 3,3′-diaminobenzedine tetrachloride as the chromogen. 4.9. Statistical Analysis {#sec4dot9-pathogens-09-00241} ------------------------- Values in the text are expressed as means ± SD. To determine statistical significance, a Student's *t* test for paired samples was used. Statistical analysis of the data was performed using Excel and R software programs. We are grateful to Naoko Tabeta, Junko Yamada, and Naomi Furuya for their technical assistance. The following are available online at <https://www.mdpi.com/2076-0817/9/3/241/s1>, Figure S1: Detection of PrPres accumulation in the brain of mouse-adopted bovine spongiform encephalopathy (mBSE)-affected mice using ELISA with the Seprion ligand, Figure S2: RT-QuIC detection of prion seeding activity in the brains of elk affected by chronic wasting disease. ###### Click here for additional data file. Conceptualization, Y.I.; resources, K.M.; data curation, Y.I. and K.M.; writing---original draft preparation, Y.I.; writing---review and editing, Y.I., Y.M., and K.M.; software, Y.M. All authors have read and agreed to the published version of the manuscript. This study was conducted under the research project on "Development of the Management Technologies for the Risk of Introduction of Livestock Infectious Diseases and Their Wildlife-borne Spreads in Japan", funded by the Ministry of Agriculture, Forestry, and Fisheries of Japan (FY2018-2022). The authors declare no conflict of interest. {ref-type="fig"}a. The mean ± SD of the AFR is displayed for each dilution. Significant differences at *p* \< 0.05 (\*) between AFR measured in rinsed and non-rinsed 96-well plates are indicated. (**c**) Each box represents Spearman--Käber estimates of the SD~50~ per unit per gram of brain tissue measured in a 96-well plate rinsed with (pale red) or without (grey) the acetone-ethanol mixture. Data are derived from quintuplicate wells of four experiments for each brain tissue dilution.](pathogens-09-00241-g001){#pathogens-09-00241-f001} {#pathogens-09-00241-f002} {#pathogens-09-00241-f003} {#pathogens-09-00241-f004} [^1]: These authors contributed equally to this study. | Mid | [
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HIAL will engage youths from multiple Himalayan countries in Research & Development to tackle the issues faced by mountain people, especially in the domains of education, culture, and the environment. Like SECMOL, the university aims to break the rigid boxes of conventional thinking, be relevant to people's lives, and encourage learning via practical application of knowledge. | High | [
0.7156726768377251,
32.25,
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The Korean magazine Hangyeoreh 21 is launching a game design contest in collaboration with Kakao Story Funding and Korea Boardgames. It’s about answering a simple question: “Would you like to receive a basic monthly income of 1.35 million won – or about $1200US?” Game designers are well-suited to explore issues surrounding the universal basic income. You’ll be tasked with designing a game about a society that guarantees fixed income to anyone. By letting us experience the reality of basic income, can such a game influence how we feel about equal opportunities? Could this income be a new hope for Hell Joseon? We are counting on you to turn the imagination into reality. The contest will be conducted and evaluated by the representatives of Korea Boardgames. The first prize winner will be published and commercialized by the company (if no game has enough potential for publishing, there will no 1st prize winner). If the game is published, it will be the first board game based on basic income in the world! Contest Information Assignment Design a tabletop game based on basic income, with a playtime under one hour. Outline Submitted games will go through two evaluation phases. Jury will evaluate rules and entry form sent by each contestant and select finalists for 2nd phase. Jury will evaluate prototypes sent by contestants selected in the previous phase, and select winners. Submission [email protected] Korea Boardgames (3F, Contest), 10 Yopung-gil, Tanhyeon-myeon, Paju-si, Gyeonggi-do 413-841, Korea. Submission Requirements Game description (no longer than single A4 page) Complete rules (only .pdf, .doc or .ppt accepted) 1-2 pictures of gameplay Author information form Signature must be handwritten. When submitting your project by mail, please print the form to sign and scan it (or take a clear picture of the form) to send it to the Jury. Deadline The submission deadline is February 1st, 2017 (submissions sent by post stamped on that date are taken into account). Schedule Announcement of 1st phase finalists: February 13th February 13th 2nd phase prototype sent to Jury: from February 14th to March 10th from February 14th to March 10th Announcement of winners: March 31th Prizes 1st place: 1,000,000 won (~$850US at time of publication) 2nd place: 400,000 won (~$350US at time of publication) 3rd place: 200,000 won (~$170US at time of publication) Please be aware that under the Articles 21 and 33 of Korea’s Corporation & Income Tax Law, prizes are subject to taxes. Additional rules | High | [
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Nick Clegg was right to acknowledge on Wednesday that phone hacking is the symptom of a wider problem: the cosy, corrupt relationship between the power elites. He didn't, however, identify the root cause of this corruption – the secretive system of information patronage. I was amazed, having been a reporter in the US, to discover that all the public records we used routinely to conduct basic verification and investigation were off limits in the UK. Records such as criminal convictions, arrest logs, full court documents and land ownership documents were either illegal or very difficult and expensive to obtain. Even the detailed financial accounts of public bodies were unavailable. When I tried to investigate parliamentary expenses, all the records I'd normally access in the US were secret. A five-year legal battle to access official information was ultimately ineffective, as parliament tried to retrospectively change the law so the Freedom of Information Act didn't apply. At that point, someone on the inside sold the full database to the Daily Telegraph. This puts journalists wanting to do serious public interest investigations legitimately at a severe disadvantage. The fact is, all information is vulnerable to release – it is simply a matter of the resources someone wants to devote to obtaining it. In Britain information is not equally accessible to all, rather its release depends on one's wealth, power or privilege. Only the richest and most powerful media organisations have a shot at access and they, in turn, only want to expend their resources on investigations they believe will guarantee a story and a big audience – thus the focus is on sex, scandal and celebrity. When journalism is treated as just another widget in a commercial enterprise, the focus isn't on truth, verification or public good, but productivity and output. Spending years on a story, whether to investigate MPs' expenses or phone hacking, doesn't make business sense. If we are serious about wanting this type of journalism, we have to make it easier and more cost-effective to access information legitimately. Instead, journalism in Britain is a patronage system – just like politics. It is rare to get good, timely information through merit (eg by trawling through public records); instead it's about knowing the right people, exchanging favours. In America reporters are not allowed to accept any hospitality. In Britain, taking people out to lunch is de rigueur. It's where information is traded. But in this setting, information comes at a price. This is why there is collusion between the elites of the police, politicians and the press. It is a cartel of information. The press only get information by playing the game. There is a reason none of the main political reporters investigated MPs' expenses – because to do so would have meant falling out with those who control access to important civic information. The press – like the public – have little statutory right to information with no strings attached. Inside parliament the lobby system is an exercise in client journalism that serves primarily the interests of the powerful. Freedom of information laws bust open the cartel. They give everyone an equal right to access information. You don't have to take anyone out to lunch. You don't have to pay anyone or suppress a damaging story to maintain a flow of information. You simply ask, with the full power of the law behind you. The way to stop this black-market trade in official information isn't to further criminalise valuable civic data, but to legitimise those records necessary for good reporting. By doing so we remove the patronage power of the elite and open the door to a new form of civic journalism. | Mid | [
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Kidneys from uncontrolled donors after cardiac death: which kidneys do worse? Kidneys from uncontrolled donors after cardiac death (DCD) expand the donor pool, but are associated with more primary nonfunction (PNF) and delayed graft function (DGF) compared with more conventional donor kidneys. It remains unclear, which factors influence outcome of uncontrolled donation. Therefore, we studied which donor, graft, and recipient characteristics are associated with PNF in a large cohort study. The association between different characteristics and short-term graft function was analyzed for kidneys procured in the Maastricht region from 1 January 1981 to 1 July 2009. Patients were followed until 7 January 2010. A total of 135 uncontrolled donor kidneys were included in this study. The incidence of PNF and DGF was 22% and 61%, respectively. Increasing donor age is an independent risk factor for graft failure in a univariate analysis (OR 1.035, 95% CI 1.004-1.068, P = 0.028). Donor age remains strongly associated with PNF in a multivariate analysis (OR 1.064, 95% CI 1.013-1.118, P = 0.014). However, the predictive value of donor age alone is poor (AURC 0.640, 95% CI 0.553-0.721). Increasing donor age of uncontrolled DCD donors is a major risk factor for PNF. Other clinically relevant variables were not associated with PNF. Donor age is strongly associated with PNF and remains an important parameter in donor selection. | High | [
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Gaming juggernaut Ubisoft and Montreal agency Revolver 3 have put together this series of entertaining viral videos for the upcoming launch of Rayman: Raving Rabbis Rabbids. One part cute, one part fun and one part disturbing. Watch. | Low | [
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Q: std::vector error C2582: 'operator =' function is unavailable in im using simple vector push_back to object of Type A and getting this error , this is my code : class A { public: A(int a,int b,int c); }; #include "A.h" .... .... .... .... std::vector<A>* vec_objects = new std::vector<A>(); while(....some condition ...) { A a(1,2,3) vec_objects->push_back(a); } getting this error: c:\program files\microsoft visual studio 9.0\vc\include\xutility(3159) : error C2582: 'operator =' function is unavailable in 'A' 1> c:\program files\microsoft visual studio 9.0\vc\include\xutility(3187) : see reference to function template instantiation 'void std::_Fill<A*,_Ty>(_FwdIt,_FwdIt,const _Ty &)' being compiled 1> with 1> [ 1> _Ty=A, 1> _FwdIt=A * 1> ] 1> c:\program files\microsoft visual studio 9.0\vc\include\vector(1231) : see reference to function template instantiation 'void std::fill<A*,_Ty>(_FwdIt,_FwdIt,const _Ty &)' being compiled 1> with 1> [ 1> _Ty=A, 1> _FwdIt=A * 1> ] 1> c:\program files\microsoft visual studio 9.0\vc\include\vector(1153) : while compiling class template member function 'void std::vector<_Ty>::_Insert_n(std::_Vector_const_iterator<_Ty,_Alloc>,unsigned int,const _Ty &)' 1> with 1> [ 1> _Ty=A, 1> _Alloc=std::allocator<A> 1> ] 1> what i did wrong ? A: An element of vector must be: Copyable, i.e., have a constructor compatible with T(const T&). Assignable, i.e., have an operator= compatible with operator=(const T&). Default-constructible, i.e., have a constructor compatible with T(). While the error indicates the assignable requirement is violated, the code suggests otherwise. Every class gets a compiler-generated copy constructor and assignment operator unless they are defined manually, so your class actually should be assignable. However default constructor is only generated implicitly if there are no other constructors defined. You have a constructor, therefore also have to define a default constructor. As Mike noted, the requirements were reduced to only moveable in C++11, but you would need a compiler that already supports respective C++11 features and would have to have those features enabled. However the paths in the errors indicate Visual Studio 9.0, a.k.a Visual Studio 2008, which predates C++11, so the restriction applies. The copyable and assignable are satisfied by default unless you broke them. The specification says, In 12.8.4: If the class definition does not explicitly declare a copy constructor, one is declared implicitly. In 12.8.10: If the class definition does not explicitly declare a copy assignment operator, one is declared implicitly. In both cases it is only defined if all base classes and all members have accessible and non-ambiguous corresponding copy constructor respectively copy assignment operator. A: There's nothing wrong with the code you've posted. It sounds like your real class (or a base class) declares a non-public assignment operator. This means that the class is not assignable, and so there are restrictions on how it can be used in standard containers. You will also have problems if it's not copyable - that is, if a non-public copy constructor is declared. In C++03, it can't be used at all. You will need to make it copy-constructible and assignable to use it in any standard container. In C++11, it can be stored in a vector as long as it's movable. push_back might not work if it's also uncopyable, in which case you can use emplace_back(1,2,3) or push_back(std::move(a)). A: You need to add operator= and copy-constructor to class A class A { public: A(int a,int b,int c); A(const A& element); A& operator=(const A& element); //which needs definition }; | Low | [
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It is something every restaurateur and hotel owner knows: good reviews boost takings while terrible ones can close you down. And, in an age when everyone can be an online critic, ratings have never been more important. But until now no one could be sure just how important the online star ratings system employed by sites such as Toptable and Tripadvisor could be for a business's fortunes. Work by two economists at the University of California, Berkeley, Professors Michael Anderson and Jeremy Magruder, published in this month's edition of the Economic Journal, represents the first attempt to gauge the relationship between online star ratings and customers' purchasing decisions. The pair focused on the effects of positive online ratings on 300 San Francisco restaurants that were then collated to form a star system on Yelp.com, a popular US ratings site. They found that a restaurant with a rating improved by just half a star – on a scale of 1 to 5 – was much more likely to be full at peak dining times. Indeed, an extra half-star rating caused a restaurant's 7pm bookings to sell out on from 30% to 49% of the evenings it was open for business. Significantly, the two economists found that the increase in trade happened without any change in prices or the quality of food and service, confirming that it was the reviews that brought in the new customers. The economists write: "The findings of this study demonstrate that – although social media sites and forums may not generate the financial returns for which investors yearn – they play an increasingly important role in how consumers judge the quality of goods and services." The economists conceded that, while restaurants with strong reviews on the site did better business than poorly reviewed restaurants, establishing cause and effect was difficult. "After all, restaurants that get good reviews are those that appeal to consumers and they would probably do well even in the absence of any reviews," the pair write. However, they are confident the research is robust. They note that, when Yelp.com computes a business's average rating (which ranges from 1 to 5 stars), it rounds off to the nearest half-star. So, two restaurants that have similar average ratings can actually appear to be of very different quality to online viewers. For example, a restaurant with an average rating of 3.74 displays a 3.5-star average rating, while a restaurant with an average rating of 3.76 displays a 4-star average rating. This, the economists claim, allows them to make important comparisons between restaurants that have different ratings – for example, 4 stars versus 3.5 stars – but are of nearly identical quality (for example, a 3.76 average versus a 3.74 average). Their conclusion? That half a star makes all the difference. The economists write: "Differences in customer flows between such restaurants can therefore be attributed to the ratings themselves rather than differences in the quality of food or service." The study collected reviews and daily reservation availability for 328 restaurants in San Francisco. It found that moving from 3 stars to 3.5 stars increased a restaurant's chance of selling out during prime dining times from 13% to 34%. Moving from 3.5 stars to 4 stars increased the chance of selling out during prime dining times by 19 percentage points. The pair conclude that changes in consumer preferences "occur even though restaurant quality is held constant. This study demonstrates that these reviews have become a salient factor in consumer decisions." Significantly, they found that the effect was even more profound when alternative information was hard to come by, opening up the possibility that invented reviews could boost fortunes. The pair write: "These returns suggest that restaurateurs face incentives to leave fake reviews, but a rich set of robustness checks confirm that restaurants do not manipulate ratings in a confounding, discontinuous manner." Concerns that retailers and restaurant owners are seeking to manipulate the online ratings system are becoming a key issue for the internet. "Everyone's trying to do something to make themselves look better," Linchi Kwok, an assistant professor at Syracuse University in New York who is researching social media and the hospitality industry, told the New York Times last month. "Some of them, if they cannot generate authentic reviews, may hire somebody to do it." Tripadvisor places a "red flag" against the names of hotels that it suspects have planted enthusiastic reviews on its website. | High | [
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What's the easiest way to tell Myth to shut down after a specified period of time has passed? It would be nice if I could change the sleep function within the Internal Player's menu to shut down the computer rather than just returning to the main menu if possible. Also, if the recording I'm watching has already ended, I still want it to turn off. For example, if I set the timer to 30 minutes and the recording I'm watching is only 22 minutes long, I still want it to turn off in 30 minutes. What I've tried so far is to add a custom menu option to the main menu, but I haven't been able to get it to work for whatever reason. I did something similar to adding this <button> <type>SHUTDOWN</type> <text>Sleep</text> <action>EXEC sudo shutdown -h +30</action> </button> to the main menu. If I launch Myth by double clicking the front-end icon from Gnome, it doesn't work at all. I'm not sure why myth doesn't respond to the command in this case. If I start the frontend by typing in "mythfrontend" into the command line, then it works, but it "freezes" myth because myth waits for the process to end before regaining control. So I tried to fix that by doing: <button> <type>SHUTDOWN</type> <text>Sleep</text> <action>EXEC sudo shutdown -h now &</action> </button> But that still causes problems, myth doesn't seem to like the ampersand. So the point is: whats the best way to do this? If possible it would be nice to just be able to change the command for the built in sleep function on the internal player, but I don't know if that's easy to change or if it will work if the recording I'm watching has ended. Otherwise, a new menu option is fine with me, but how can I get the above to work so that myth will still listen to the command when I launch the front end by double clicking the icon and so it won't "freeze"? Thanks, -Matt _________________________________________________________________ Earn cashback on your purchases with Live Search - the search that pays you back! http://search.live.com/cashback/?&pkw=form=MIJAAF/publ=HMTGL/crea=earncashback -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mythtv.org/pipermail/mythtv-users/attachments/20080624/0d808ffc/attachment.htm | Mid | [
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Nefazodone in community use: the results of prescription-event monitoring. This study was a pharmacovigilance exercise which aimed to determine the post-marketing event profile of nefazodone, a newly marketed antidepressant, in community use. Information was collected on patients included in a non-interventional observational cohort study conducted by means of Prescription-Event Monitoring in England. Incidence densities were calculated for all reported events. Information was obtained for 11 834 patients. Nausea and dizziness were the most frequent adverse events that led to stopping nefazodone and the most frequently reported events during the first month of treatment. Unsteadiness and falls were reported more frequently in the elderly. Hepatic events, involuntary movements, thrombocytopenia, hallucinations and withdrawal reactions were reported rarely but were possibly associated with nefazodone. Eight overdoses involving nefazodone alone were reported with no serious clinical sequelae. Two premature births, one low birth weight term baby and two babies with renal abnormalities were outcomes in 38 pregnancies exposed in the first trimester to nefazodone. One death in a woman aged 71 years followed an illness with serotonergic features. Event data are presented for patients dispensed nefazodone in the community. The findings are discussed. | High | [
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Q: Can anyone explain what a dominant scale is? I wanted to sign up for some guitar lessons, the prerequisites for joining it are in the image attached. I know and understand most of the things mentioned except for the "dominant" scale mentioned. I was hoping if anyone here can explain what it is and provide a link to a lesson about it A: There isn't one "dominant scale", but they do exist. Dominant scales are an interesting phenomena in music because they almost always have other names and the requirements are simple: be able to build a dominant 7th chord off the tonic so the scale needs to have a Major 3rd, Perfect 5th, and minor 7th in it. The most popular dominant scale is the Phrygian dominant scale as it is a mode of the harmonic minor scale, but there are others such as the Aeolian dominant scale,Mixolydian mode which can be looked at as a dominant scale, and Lydian Dominant. | Mid | [
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A-League History W-League History Archie 'looking a million dollars' Coming off his least interrupted pre-season in four seasons, Archie Thompson is fitter than ever, according to Melbourne coach Ernie Merrick and ready to fire when Hyundai A-League season five kicks off against the Central Coast Mariners on August 6 at Etihad Stadium. Coming off his least interrupted pre-season in four seasons, Archie Thompson is fitter than ever, according to Melbourne coach Ernie Merrick and ready to fire when Hyundai A-League season five kicks off against the Central Coast Mariners on August 6 at Etihad Stadium. Thompson's pre-season build-ups have been hampered by both his international commitments and injury in the past three seasons, making it difficult for him to be at his peak for the first match. In 2006, Thompson was involved in Australia's World Cup campaign, while in 2007 it was the Asian Cup which took his focus ahead of the season. Last year it was the Beijing Olympics for the mercurial striker, ruling him out of the first two games. But according to Merrick, there are no excuses this season and that his marquee man is looking fit and fabulous. "Archie is looking fantastic. I've never seen Archie looking slimmer," Merrick said. "He's got to run around in the shower now to get wet. He's looking a million dollars, Archie and every game he's played, he's been great." Thompson and Danny Allsopp have forged the most successful strike partnership in the Hyundai A-League over the past four seasons and with both players in the midst of a strong pre-season, Merrick predicts their best could be yet to come. "He and Dan are combining better than ever," he said. "It's a great competition between the two. Then you have Tommy Pondeljak, and Nick Ward, settling in so well." When you combine those names with newly-re-signed midfielder Carlos Hernandez, Merrick could not be more pleased with his attacking options. "To re-sign Carlos (Hernandez), who has only had two weeks training with us and has some more work to do, is great. He's back, he's signed on for three years, he's happy as ever, smiling every time he trains. He's looking good. But he knows he has to work to do as he is behind the rest of the boys." The one striker who has had trouble with injuries in the off-season, Ney Fabiano, is making steady progress from an ankle injury suffered on the recent tour of China. "He's looking very fit, and he's training harder than ever even though he can-t weight bear to much," Merrick said. "We don't want to rush that, because he's split the fibula and tibia at the bottom there. You can't rush him back." With Jose Luis Lopez returning to his Costa Rican club last week, Merrick confirmed that Victory, which has two spaces left on its roster, is looking for a replacement, most likely a defender. "It hasn't changed from that priority of finding a centre back. The first option is to find a centre back within Victoria or within Australia. The second option is to, if we can afford, look overseas now that we have a visa vacancy," he said. Melbourne's next pre-season match is against Wellington Phoenix in the South Island tourist town of Queenstown on Saturday. | Mid | [
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26 B.R. 576 (1983) In re E.C. ERNST, INC., E.C. Ernst Midwest, Inc., E.C. Ernst International Corp., Debtors. E.C. ERNST, INC., Plaintiff, v. GRUMMAN ECOSYSTEMS CORPORATION, Defendant. Arrangement No. 79 B 2139-41. United States Bankruptcy Court, S.D. New York. January 24, 1983. Shea & Gould, Friedman & Gass, New York City, for debtors. Layton & Sherman, New York City, for defendant Grumman Ecosystems Corp. DECISION AND ORDER ON MOTION TO IMPOSE DISCOVERY SANCTIONS EDWARD J. RYAN, Bankruptcy Judge. On December 1, 1978 E.C. Ernst, Inc. ("Ernst") filed a Chapter XI petition in this court pursuant to the Bankruptcy Act of 1898. Ernst was thereafter continued in business. On September 15, 1982, Ernst instituted the instant adversary proceeding against Grumman Ecosystems Corporation ("Grumman") alleging the willful failure to comply with discovery requirements. The relief requested was the expungement of Grumman's claim in the Ernst reorganization pursuant to Rule 37 of the Federal Rules of Civil Procedure ("FRCP") made applicable to adversary proceedings in the bankruptcy court by Bankruptcy Rule 737. The facts of the dispute are as follows: On or about December 1, 1977 Grumman and Ernst entered into a contract ("the Subcontract") whereby Ernst agreed to perform the electrical construction work on the Hampton Roads, Virginia, Army Base Wastewater Treatment Plant, Phase II Improvements ("the Project"). Grumman was the general contractor on the Project. In November, 1979 Grumman contracted with Perini Corporation ("Perini") for Perini to serve as Grumman's construction manager for the Project. In December, 1979 Grumman terminated Ernst from the Project and engaged Manzi Electrical Company ("Manzi") to complete the work left unperformed by Ernst. On April 24, 1981 Grumman filed a proof of an administrative claim against Ernst in *577 its reorganization proceeding for $693,720.41. That claim represented the damages suffered by Grumman as a result of Ernst's alleged breach of the Subcontract. On July 10, 1981 Ernst instituted an adversary proceeding in this court alleging that it was Grumman who had breached the Subcontract. Ernst requested this court to (a) expunge Grumman's administrative claim, or in the alternative, permit rejection of the Subcontract and adjudicate that any claim proved by Grumman be allowed only as a general unsecured claim; and (b) enter a judgment against Grumman for $158,368 which represents unpaid sums due Ernst upon the Subcontract. On July 24, 1981 Grumman answered seeking dismissal of the complaint and counterclaiming for its administrative expense claim. Discovery began shortly thereafter. In September, 1981 each party served the other with extensive document requests. Grumman delivered to Ernst voluminous documents pursuant to such request including copies of the invoices assembled by Manzi and Perini representing costs incurred by Grumman in securing completion of the unperformed portion of the Subcontract. Ernst has also taken numerous depositions. Ernst has examined the following employees of Grumman: George Brown (on March 23, 1982); Dean Cassell (on March 24, 1982), Alex Wasyl (on June 23, 1982); and Jay Witte (on March 31, 1982, September 23, 1982 and October 18, 1982). Ernst has also deposed Warren Found of Manzi (on September 29, 1982) and Eugene Dragon of Perini (on March 31, 1982). On June 20, 1982 Ernst served Grumman with written interrogatories seeking, inter alia, the component parts of Grumman's claim in the Ernst reorganization proceeding; identification of the documents supporting the claim; identification of the persons who calculated the claim; when and where such claim was calculated; and information relating to the completion of the Project. During the third week of July, counsel to Grumman requested and received from counsel to Ernst an extension until August 20, 1982 of the time by which Grumman would be required to respond to the Ernst interrogatories. However, on that date the interrogatories were not delivered due to "mechanical difficulties and missed deliveries." On September 14, 1982 Ernst instituted the instant proceeding requesting discovery sanctions be imposed against Grumman for willful failure to comply with discovery. Although responses to the interrogatories were served on September 17, 1982 and Supplemental Responses served on October 18, 1982 Ernst continues to seek the imposition of sanctions against Grumman. Ernst maintains that the responses to the interrogatories and the deposition testimony are so unresponsive, vague and incomplete that the Grumman claim remains totally unexplained. The sanctions requested are: the dismissal of Grumman's claim, the striking of Grumman's answer to Ernst's complaint and direction of judgment in favor of Ernst for $158,362. Whether a court has the power to dismiss a claim for a failure of discovery depends exclusively upon FRCP 37 and not upon any inherent equity powers of a Federal court. Societe Internationale pour Participations Industrielles et Commerciales, SA v. Rogers, 357 U.S. 197, 207, 78 S.Ct. 1087, 1093, 2 L.Ed.2d 1255 (1958). Dismissal for a failure to cooperate in pretrial discovery, pursuant to FRCP 37 is a draconian sanction which should be used only in extreme circumstances. See Israel Aircraft Ltd. v. Standard Precision, 559 F.2d 203, 208 (2d Cir.1977). Courts must exercise restraint because such a dismissal may operate to deprive a person of property without due process of law in contravention of the Fifth Amendment. See Societe Internationale, supra 357 U.S. at 209, 78 S.Ct. at 1094; Notes of Advisory Committee on Rules, Rule 37, 28 U.S.C.A. (1975 Supp.) page 53. Therefore, there is a strong policy favoring a trial on the merits and against depriving a party of his day in court because of misconduct during discovery. *578 See Fox v. Studebaker-Worthington, Inc., 516 F.2d 989, 996 (8th Cir.1975); Pioche Mines Consolidated, Inc. v. Dolman, 333 F.2d 257, 270 (9th Cir.1964) cert. denied 380 U.S. 956, 85 S.Ct. 1082, 13 L.Ed.2d 972 (1965); Gill v. Stolow, 240 F.2d 669, 670 (2d Cir.1957). FRCP 37(b)(2) and (d) authorizes a court to impose discovery sanctions. Rule 37(b)(2) is inapplicable in the instant case as dismissal pursuant to this subsection must be preceded by an order compelling discovery. Kropp v. Ziebarth, 557 F.2d 142, 146 n. 7 (8th Cir.1977); Israel Aircraft Ind., Ltd. v. Standard Precision, 559 F.2d 203, 208 (2d Cir.1977). No such order has been issued here. Dismissal pursuant to Rule 37(d) is a proper remedy only when there has been a total failure of discovery. Id. See also Al Barnett & Son, Inc. v. Outboard Marine Corp., 611 F.2d 32, 35 (3d Cir.1979); Flaks v. Koegel, 504 F.2d 702, 706 n. 2 (2d Cir. 1974). Ernst maintains that there has been a failure of discovery here as insufficient information has been supplied to enable it to ascertain the basis for Grumman's claim. However, this high standard has not been approached as Grumman's claim is substantially explained and documented. Grumman's claim was computed by Jay A. Witte, its Manager of Contracts. The claim was computed by calculating the actual cost to Grumman of the supplies and services within the scope of the Subcontract (the "Actual Cost") and subtracting from that figure the amount it would have cost Grumman had Ernst performed its obligation under the Subcontract. The Actual Cost has two components. The first is payments made by Grumman to Ernst's account prior to the termination of Ernst from the Project. This figure is based upon accounting records prepared and maintained by Grumman. The second component is payments made to secure completion of the Subcontract after Ernst's termination. This was computed using a document entitled the "Manzi Cost Narrative Analysis," which document was prepared by Warren Found of Manzi and John Julian of Perini to document for Grumman the costs incurred in completing the Subcontract. (Ernst has deposed Mr. Found but has failed to depose Mr. Julian). Mr. Witte made his calculation of the claim by hand on a copy of the Manzi Cost Narrative Analysis, a copy of which has been provided to Ernst. Ernst has also been provided with all invoices paid by Grumman in connection with the completion of the Subcontract. On April 16, 1981 Grumman transmitted a copy of the computation of the claim to counsel, who filed it with this court on April 24, 1981. The amount of the claim filed was identical to the figure calculated by Mr. Witte. Clearly, there has been no total failure of discovery. Therefore, the expungement of Grumman's claim would be inappropriate. Ernst's motion is denied. It is so ordered. | Low | [
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Q: Cocoa Programming on Windows Is there a way to develop windows applications using cocoa and objective-c in general A: To be clear, Objective-C is to Cocoa as C# is to .NET, or even as the Java language is to the Java platform — it's the primary way of doing things. Objective-C can be used wherever the compiler supports it, but the Cocoa frameworks are really the most valuable part of the equation. One should also note that (os OS X) Safari is a Cocoa app, but iTunes is not yet (it still uses the legacy Carbon APIs) so I'm not sure how it is on Windows. Apple has ported some significant parts of Cocoa to Windows DLL's to port Safari, but to my knowledge, that code is not available for public consumption. (One can imagine that Apple doesn't really want to make it easy to create robust apps for a competing OS, they have only published two key apps to further their own goals, like adoption of iPod/iTunes and the WebKit browser core.) Don't expect to see these Cococa-Windows libraries become widely available; if they do, it will be a surprise to many of us. As @Gregory mentioned, GNUStep and Cocotron are plausible options to explore, but I'd suggest thinking long and hard about whether you really should do what you're asking. By and large, Microsoft's tools have much better support for Windows, you'll run into fewer undocumented limitations, and their native apps will tend to "feel right" to Windows users. I learned some time back that although I love Objective-C/Cocoa, if I ever had to write a Windows program, I would do it with the C#/.NET platform. A: Well, Cocoa is specific to Mac OSX. But you might have a look at Cocotron. For Objective-C, you might want to have a look at GNUStep. | Low | [
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In low- and middle-income countries, perinatal depression is a major public health problem, affecting up to a quarter of all pregnant women in rural Pakistan.^[@R1]--[@R3]^ In addition to its effects on the mother's well-being, perinatal depression is associated with adverse outcomes of pregnancy^[@R4]^ and adverse effects on the infant including delayed growth^[@R5]^ and poor health and development.^[@R6]^ Relevant effective interventions are being developed^[@R1],[@R7]^ but their effectiveness in low- and middle-income countries may be limited by factors that maintain persistent depression, such as poverty, lack of social support and women's lack of financial independence from their husbands.^[@R8],[@R9]^ Poverty and mental ill health interact in a negative cycle and this is relevant to postnatal depression in low- and middle-income countries.^[@R8],[@R10]^ Poverty alleviation interventions do not appear to improve mental health but mental health interventions may be associated with improved economic outcomes, although more high-quality research is needed.^[@R11]^ The identification of moderators can specify for whom, or under what conditions, the treatment works, to guide the design of future randomised controlled trials (RCTs) and to advance our understanding of the nature of clinical disorders. To date the moderators of treatment of postnatal depression have been studied little.^[@R12]^ In particular, it is not known whether psychological interventions can reduce depression in women who are very poor and financially dependent on their husbands, or whether these factors limit the effectiveness of the intervention.^[@R9]^ In a recent RCT (trial registration: ISRCTN65316374) we tested an intervention, 'The Thinking Healthy Programme', which was based on culturally adapted cognitive--behavioural therapy (CBT) principles but also involved the husband and family in supporting the woman with depression during therapy.^[@R1]^ The intervention was delivered by local community health workers; these workers were women who were influential and resourceful, and could help the women with depression and their families to mobilise community resources to overcome psychosocial difficulties through problem-solving.^[@R13]^ Qualitative evaluations demonstrated that the problem-solving approach in the hands of these resourceful women was useful in addressing some of the socioeconomic risk factors at a practical level, for example, assisting women in obtaining small loans from government microcredit schemes. Through an agenda of effective child-rearing, the intervention also gently challenged gender stereotype and encouraged fathers to play an active role in supporting the mother in child care and interaction. The trial was effective in treating depression (effect size 0.66) but had additional benefits on maternal support, family relationships and infants' health.^[@R1]^ These benefits are compatible with the underlying theory of our approach, which regards the child as the centre of the intervention with the mother and father working together with the 'lady health worker' (LHW) to achieve child health. The present study was aimed at identifying the moderators of treatment outcome, on the basis that if a treatment has its effects by influencing a particular process this finding establishes the importance of the process in maintaining the disorder and may lead to further refinements of the intervention in a future trial. Specifically, we wished to determine whether poverty, debt or any of the other social variables associated with persistent depression (lack of financial empowerment, lack of social support) moderated the effect of treatment. We wished also to assess whether the intervention reduced the proportion of women with household debt and increased the proportion who were financially empowered. Method {#S1} ====== Study area, participants and sampling {#S2} ------------------------------------- This study used data from a cluster, randomised, community-based trial of a psychological intervention for perinatal depression in two rural subdistricts (Gujar Khan and Kallar Syedan) of Rawalpindi, Pakistan, between 2004 and 2007. The details of the methods and the main results of this trial have been reported elsewhere.^[@R1]^ In a cluster randomised trial ([Fig. 1](#F1){ref-type="fig"}), 40 union councils (an administrative unit consisting of 5--10 villages and a population of about 20 000) were randomised into an equal number of treatment and control clusters. A total of 3898 women in their third trimester of pregnancy were identified by obtaining official lists from 250 government-employed LHWs, who routinely collect data on new pregnancies. All married women aged 17--40 years in their third trimester of pregnancy, who had depression, were considered for inclusion in the study ([Fig. 1](#F1){ref-type="fig"}). Women with a diagnosed medical condition, pregnancy-related illness, significant physical or intellectual disability, postpartum or other form of psychosis and severe depression were excluded. We obtained informed verbal and written consent from the participants. Ethical approval for the study was granted by committees of the University of Manchester, UK, and the Institute of Psychiatry, Rawalpindi. Data ascertainment {#S3} ------------------ ### Psychiatric disorder and depression severity {#S4} Assessments were carried out at all time points by two trained and experienced clinicians (A.M. and S.S.) using a structured clinical instrument for DSM-IV diagnosis of major depressive episode (SCID)^[@R14]^ and the Hamilton Rating Scale for Depression (HRSD)^[@R15]^ to assess severity. The former was used to assess the inclusion criteria for the study and whether depressive disorder was still present at follow-up.^[@R1]^ The HRSD was used to assess the severity of depression at these times. Both of these semi-structured interviews have been used repeatedly in cross-cultural, epidemiological and treatment studies of pre- and postnatal depression. All interviews were carried out in Urdu after translation, back-translation and cultural adaptation of the interview schedule using an established procedure.^[@R16]^ Interrater reliability was established prior to the study when both interviewers independently assessed 20 women (10 had clinical depression) and agreed on the diagnosis of 9 (κ = 0.90). The interviewers were masked to the allocation status of the union councils and, therefore, the arm of the trial to which each of the women had been randomised. This masking was maintained because the interviewers had no contact with the team that did the randomisation, and throughout the duration of the study they had no contact with the LHWs or any other health personnel in the study area. Mothers were asked not to tell the interviewers anything about their meetings with the LHWs. The HRSD has a maximum score of 57; the mean baseline score in this sample was 14.6 (s.d. = 14.1). {#F1} ### Others potential moderators of treatment effect {#S5} Social support. This was measured with the Multidimensional Scale of Perceived Social Support (MSPSS),^[@R17]^ a brief instrument that addresses subjective assessment of social support. The scale consists of 12 items; each is scored on a seven-point scale. Four questions each ask about the source of social support: family, friends, significant other. Thus, for the family support scale the scores range from 4 to 28, with higher scores indicating greater support; the mean score in this sample was 16.3 (s.d. = 6.8). The MSPSS has been locally validated and shown to have satisfactory internal reliability, factorial validity, and test and retest reliability.^[@R18]^ In addition, we assessed whether intense social support from family members for 40 days after the birth (*chilla*) was satisfactory. **Sociodemographic variables.** Age, education, employment, family structure and composition were assessed at baseline by the same interviewers using a specially designed Personal Information Questionnaire. Education was categorised into no formal education, 1--6 years, 7--10 years and 11 or more years of formal education. Family structure was categorised into nuclear family (parents and children only) or extended family (three generations living in the same home). **Mothers' nutritional status**. Maternal body mass index (BMI) was measured as an indicator of nutritional status. **Socioeconomic status**. Our study used several sources of information to determine the socioeconomic status of our participants because of the difficulty of measuring this variable in south Asia.^[@R19]^ At baseline we asked LHWs, who lived in the same locality and had intimate knowledge of the families participating in our study, to rate the household on a five-point Likert scale ranging from 1 (least poor) to 5 (poorest). Participants were asked whether their family was in debt and this was verified by asking the LHW, who was generally aware of the nature of the loan, for example, to buy a tractor or to purchase healthcare for a family member. This assessment was repeated at 1-year follow-up. We also asked the participants about the family's monthly income at baseline only. **Financial empowerment**. Maternal financial empowerment within the household was measured at baseline by asking the women whether they were given a lump-sum amount of money for day-to-day household expenses, and whether they could take independent decisions about its use. Mothers who answered 'yes' to both questions were classified as financially empowered within the household. Called '*kharcha*', this is a culturally valid concept indicating a degree of empowerment within the household even if the women were not earning. This assessment was repeated at 6 months after baseline. Statistical analysis {#S6} -------------------- All analyses were carried out with SPSS for Windows, version 16. The first analysis (data not shown) included all the participants in the trial for whom complete data were available at 1-year follow-up (*n* = 791). These initial univariable analyses were performed to identify baseline variables associated with HRSD scores at follow-up and used *t*-test, analysis of variance (ANOVA) or correlation as appropriate. We then performed multiple regression analyses with follow-up HRSD score as the dependent variable. The independent variables were: baseline HRSD, arm of trial (intervention or control), the participant's age, BMI, duration of formal education, family structure (nuclear or joint), socioeconomic status rated by the LHW, empowerment (whether the woman was empowered to manage household finances or not), and debt (yes/no). In further regression analyses we entered in turn each of the following interaction terms: arm × age, arm × BMI, arm × debt (at baseline) and arm × empowerment (at baseline) to identify which of these interaction terms were significant predictors of follow-up HRSD score. We used two-way analysis of covariance (ANCOVAR) to test for the effects of treatment arm, being in debt or not, and the interaction term arm × debt on the follow-up HRSD score. We adjusted for baseline HRSD, mother's age, BMI, years of education, family structure, and socioeconomic status rated by the LHW. This analysis was repeated for financial empowerment instead of debt. We performed further analyses to examine how debt and financial empowerment fit into the more established risk factors for depression in this population (poverty, having numerous children, an uneducated husband and lack of a confidant or friend). In order to examine the predictors of empowerment and freedom from debt at follow-up we performed logistic regression analysis with each of these variables as the dependent variable. The following variables were included as independent variables in model 1, which included only baseline variables: mother's age, BMI, duration of formal education, arm of trial, HRSD score, family support (MSPSS family score), financial empowerment and debt. In model 2 of the analysis with debt at 12 months follow-up as the dependent variable, the following measures made at 6 months were included: HRSD score, family support (MSPSS family score), reported relationship with husband and financial empowerment. For the analysis with financial empowerment at follow-up as the dependent variable, being in debt at 6 months was included instead of financial empowerment as an independent variable. Results {#S7} ======= The recruitment to the trial has been described in detail elsewhere.^[@R1]^ Out of 3898 women in the last trimester of pregnancy, 3518 consented to baseline screening with the SCID and 903 eligible women had a DSM-IV major depressive episode and consented to join the trial. These women received the intervention or enhanced routine care according to the union council in which they lived and they were followed up for 1 year postnatally. This study is concerned with 791 women who completed the 1-year follow-up with complete data; details of the sample are shown in [Table 1](#T1){ref-type="table"}. ###### Description of the sample: sociodemographic data ---------------------------------------------------- Participants\ (*n* = 791) ------------------------------------ --------------- Age, years: mean (s.d.) 26.8 (4.9) Trial arm, *n* (%) Intervention arm 407 (51.5) Control arm 384 (48.5) Financially empowered, *n* (%) 415 (2.5) Family size, *n* (%) Prima gravida 136 (17.2) One child only 173 (21.9) Two or more children 482 (60.9) Education, *n* (%) No formal education 325 (41.1) 1--6 years 242 (30.6) 7--10 years 199 (25.2) \>11 years 25 (3.2) Extended family structure, *n* (%) 461 (58.3) SES rated by lady health worker Poorest 172 (21.7) Poor 233 (29.5) Intermediate 308 (38.9) Relatively well-off 78 (9.9) In debt, *n* (%) 441 (55.8) ---------------------------------------------------- SES, socioeconomic status. All women were married and living with their husbands; only 2.6% were employed outside the home. Just over half (52.5%) were empowered to manage household finances. The mean family monthly income for the four socioeconomic groups shown in [Table 1](#T1){ref-type="table"}, were 4690 rupees (s.d. = 8272), 2421 (s.d. = 4651), 1506 (s.d. = 2747) and 985 (s.d. = 2096) for the relatively well-off, intermediate, poor and poorest categories respectively. These approximate to US\$470, 242, 150 and 98 per month. Just over half (55%) of participants stated that their family were in debt and the proportions were: 9.9%, 38.9%, 29.5% and 21.7% for the relatively well-off, intermediate, poor and poorest categories respectively. Depression at follow-up {#S8} ----------------------- At follow-up, 111/407 (27.3%) participants in the intervention arm remained depressed compared with 226/384 (58.9%) of those in the control arm.^[@R1]^ Mean follow-up HRSD scores, adjusted for baseline values, were 5.4 (95% CI 4.7--6.1) in the intervention arm and 10.8 (95% CI 10.1--11.5) in the control arm (*P*\<0.001, effect size 0.72). Mean follow-up HRSD scores, adjusted for baseline values, were 8.9 (95% CI 8.2--9.6) and 6.9 (95% CI 6.1--7.7) for women with and without household debt respectively (*P*\<0.001). Corresponding results for women not financially empowered and empowered were 9.4 (95% CI 8.6--10.2) and 6.7 (95% CI 6.0--7.4) (*P*\<0.001). Multivariate analysis {#S9} --------------------- In multiple regression with follow-up HRSD score as the dependent variable, and adjusting for treatment arm, the following baseline variables predicted a high follow-up score: high baseline HRSD score, low BMI, older age, woman not empowered financially, and presence of household debt ([Table 2](#T2){ref-type="table"}). The MSPSS score (indicating low support) was omitted from these analyses as it was so highly correlated with financial empowerment (MSPSS score for empowered women 51.3 (95% CI 49.9--52.8) and not empowered 38.8 (95% CI 37.3--40.3)). ###### Multiple regression analysis with the Hamilton Rating Scale for Depression score at follow-up as dependent variable (*n* = 791) including arm × debt interaction term as an independent variable in model 2 Model 1 Model 2 ------------------------------------------------------ --------- --------- --------- --------- ------- --------- Baseline Hamilton Rating Scale for Depression score 0.296 0.061 \<0.001 0.297 0.061 \<0.001 Arm of trial --5.33 0.493 \<0.001 --5.193 0.495 \<0.001 Financially empowered --2.519 0.503 \<0.001 --2.482 0.501 \<0.001 Body mass index --0.155 0.062 0.012 --0.168 0.062 0.007 Age 0.164 0.054 0.002 0.164 0.054 0.002 Years education --0.116 0.295 0.69 --0.173 0.295 0.56 Extended family structure --0.658 0.534 0.22 --0.629 0.532 0.24 Low socioeconomic status rated by lady health worker 0.400 0.244 0.10 0.375 0.243 0.12 In debt 1.610 0.526 0.002 1.647 0.525 0.002 Arm × debt --0.592 0.248 0.017 The addition to the multiple regression analysis of possible moderator variables showed that the interaction terms arm × age (*P* = 0.52) and arm × BMI (*P* = 0.34) and arm × socioeconomic status (*P* = 0.54) were not significant predictors. However, the interaction terms for debt and mother empowered financially were significant (*P* = 0.017 and *P* = 0.045 respectively). ### ANCOVAR analyses for the moderators, debt and empowerment {#S10} [Figure 2](#F2){ref-type="fig"} shows that the reduction of HRSD score was very similar in the intervention arm for those women with and without household debt at baseline (mean adjusted HRSD scores at follow-up 5.8 (95% CI 4.9--6.7) and 5.1 (95% CI 4.1--6.2) respectively). For the control arm, however, the women without household debt had a lower mean adjusted HRSD scores at follow-up (9.0, 95% CI 7.9--10.0) than those with household debt (12.1, 95% CI 11.2--13.1). The effect sizes for the intervention for women with and without household debt were 0.80 and 0.55 respectively. [Figure 3](#F3){ref-type="fig"} shows that the reduction of HRSD score was similar in the intervention arm for those women who were and were not financially empowered at baseline (mean adjusted HRSD scores at follow-up 4.68 (95% CI 3.7--5.6) and 6.35 (95% CI 5.4--7.3) respectively). For the control arm the women who were financially empowered had a lower mean follow-up HRSD score (mean 9.0, 95% CI 8.0--9.9) than those who were not empowered (mean 12.67, 95% CI 11.64--13.7). The effect sizes for women not empowered and empowered were 0.81 and 0.61 respectively. For 235 women who were both in debt at baseline and not empowered financially, the follow-up HRSD score, adjusted for baseline value, was 13.6 (SEM = 0.68) in the control group and 6.9 (SEM = 0.64) in the intervention arm. The effect size was 0.936. For 347 women with either household debt or not financially empowered (not both) the effect size was 0.808. For 209 women empowered and not in debt the effect size was 0.50. Changes in debt and empowerment {#S11} ------------------------------- Of the 441 women who were in debt at baseline, a significantly higher proportion in the intervention group --79/233 (33.9%) --were no longer in debt at follow-up compared with 49/208 (23.6%) of the control group (*P* = 0.017). Of the 387 women who reported not being financially empowered at baseline, 40.3% (81/201) in the intervention group and 29.0% (54/186) in the control group reported being financially empowered at 6 months (*P* = 0.020). Inclusion of these change scores in the multiple regression made no difference to the statistical significance of the arm of the trial indicating that changes in debt or empowerment did not mediate the effect of the intervention ([Table 3](#T3){ref-type="table"}). {#F2} {#F3} ###### Multiple regression analysis with Hamilton Rating Scale for Depression score at follow-up as dependent variable (*n* =791) including change in debt and change in financial empowerment as independent variables B s.e. *P* ------------------------------------------------------ --------- ------- --------- Baseline Hamilton Rating Scale for Depression score 0.296 0.061 \<0.001 Arm of trial --4.915 0.497 \<0.001 Financially empowered --0.416 0.631 0.510 Body mass index --0.116 0.062 0.064 Age 0.159 0.054 0.003 Years of education --0.049 0.066 0.456 Extended family structure --0.766 0.530 0.149 Low socioeconomic status rated by lady health worker 0.279 0.243 0.251 In debt --0.945 0.943 0.316 Change in debt 0.583 0.182 0.001 Change in empowerment --0.875 0.183 \<0.001 Debt, financial empowerment and outcome of the intervention {#S12} ----------------------------------------------------------- In addition to the variables shown in [Table 2](#T2){ref-type="table"} as predictors of higher depression score at follow-up (older age, being in debt, not being empowered financially and high BMI), MSPSS score indicating low family support and unsatisfactory *chilla* (intense social support from family members for 40 days after the birth) were additional predictors. Number of young children, a husband with very little formal education, socioeconomic status assessed by the LHW and social support from outside of the family were not predictors of depression score at follow-up when included in this multiple regression analysis. In logistic regression analyses adjusting for age, years of education, BMI, depression score and family support (model 1 in [Table 4](#T4){ref-type="table"}) the intervention arm of the trial was associated directly with a reduced likelihood of being in debt at follow-up (B = 0.73, 95% CI 0.53--0.99). The arm of the trial was also associated with an increased likelihood of the woman being financially empowered (B = 1.93, 95% CI 1.40--2.66) (model 1 in [Table 5](#T5){ref-type="table"}). Neither of these results could be explained by baseline depression severity, support from family or duration of education (model 1 in Tables [4](#T4){ref-type="table"} and [5](#T5){ref-type="table"}). When 6-month follow-up assessments were added to the logistic regression (model 2) it is clear that debt at follow-up was associated with baseline debt, few years of education, BMI, HRSD score at 6 months and mother not financially empowered at 6 months ([Table 4](#T4){ref-type="table"}). ###### Logistic regression analysis with debt at 12 months follow-up as dependent variable (*n* = 784)[^a^](#TFN2){ref-type="fn"} Model 1 Model 2 ------------------------------------------------------------------------ --------- --------- --------- --------- ------- --------- Age 0.025 0.017 0.127 0.024 0.017 0.160 Arm of trial --0.314 0.159 0.049 --0.019 0.173 0.912 Baseline Hamilton Rating Scale for Depression score --0.009 0.020 0.630 --0.032 0.021 0.123 Body mass index --0.056 0.020 0.005 --0.050 0.021 0.014 Years of education --0.054 0.021 0.009 --0.048 0.021 0.023 Multidimensional Scale of Perceived Social Support, family baseline --0.002 0.013 0.876 0.008 0.014 0.535 Financially empowered --0.154 0.175 0.380 0.102 0.192 0.596 In debt 1.616 0.163 \<0.001 1.593 0.167 \<0.001 Hamilton Rating Scale for Depression score at 6 months 0.050 0.015 0.001 Financially empowered at 6 months --0.494 0.192 0.010 Multidimensional Scale of Perceived Social Support, family at 6 months --0.016 0.017 0.337 Relationship with husband 0.009 0.091 0.920 Model 1 includes baseline variables only. Model 2 includes variables also measured at 6 months. Corresponding analysis for financial empowerment at follow-up (model 2 in [Table 5](#T5){ref-type="table"}) showed that this was associated with financial empowerment at baseline, low 6-month HRSD score, high family support scores at 6 months and good relationship with husband. Physical violence from the husband was associated with a lack of empowerment at follow-up but this did not add significantly to the model when the relationship with the husband was included. The same applied to the relationship with the mother-in-law (details available from the authors on request). We conclude from these analyses that the intervention had a greater direct effect on empowerment than on debt reduction. Furthermore, the beneficial effect of the intervention on empowerment and debt reduction were part of a range of improvements, which also included depression reduction and increased social support. Discussion {#S13} ========== Main findings {#S14} ------------- The main new finding of this study indicates that our intervention, based on CBT principles but involving the family and using LHWs as 'agents of change', was effective even for women who reported being in debt and/or not empowered financially. The latter two variables were moderators of treatment and the effect sizes show that improvement in depression was greater for those women who reported household debt and/or not being financially empowered. Second, the intervention was associated with a reduction of households in debt and an increase in women reporting that they were financially empowered but neither of these factors mediated the effect of the intervention on depression. ###### Logistic regression analysis with mother financially empowered at follow-up as dependent variable (*n* = 784)[^a^](#TFN3){ref-type="fn"} Model 1 Model 2 ------------------------------------------------------------------------ --------- --------- --------- --------- ------- --------- Age 0.024 0.017 0.171 0.035 0.019 0.059 Arm of trial 0.657 0.165 \<0.001 0.207 0.185 0.263 Baseline Hamilton Rating Scale for Depression score --0.034 0.020 0.086 0.004 0.022 0.845 Body mass index 0.024 0.021 0.235 0.018 0.022 0.401 Years of education 0.036 0.021 0.098 0.023 0.023 0.326 Multidimensional Scale of Perceived Social Support, family baseline 0.031 0.013 0.018 0.013 0.014 0.379 Financially empowered 1.594 0.175 \<0.001 1.662 0.190 \<0.001 In debt --0.215 0.167 0.197 0.054 0.196 0.783 Hamilton Rating Scale for Depression score at 6 months --0.061 0.015 \<0.001 In debt at 6 months --0.333 0.196 0.090 Multidimensional Scale of Perceived Social Support, family at 6 months 0.081 0.017 \<0.001 Relationship with husband 0.255 0.095 0.007 Model 1 includes baseline variables only and Model 2 includes variables also measured at 6 months. Strengths and limitations {#S15} ------------------------- Before considering the results further it is necessary to recognise the strengths and limitations of the study. The results come from data collected in a large RCT, which was based on a population-based sample of women with clinical depression during the last trimester of pregnancy. The intervention and control groups were similar on a wide range of sociodemographic characteristics and the intervention was effective in reducing depression.^[@R1]^ The findings of the current study must be regarded as exploratory, however, as we did not have an *a priori* hypothesis with regard to moderators,^[@R20],[@R21]^ although our study was based on the predictors of persistent depression arising from our previous study in a similar sample.^[@R8]^ In our analysis we did us a specific test of the interaction between baseline factors and interventions.^[@R21]^ We did not, however, have any test of reliability and validity for our measures of debt and empowerment. Our assessment instruments have been validated in this population.^[@R22]^ It has been suggested that identification of moderators should be undertaken whenever possible as this can specify for whom, or under what conditions, the treatment works, to guide the design of future RCTs and to advance our understanding of the nature of clinical disorders.^[@R20],[@R23]^ Kraemer *et al* stated that 'if a treatment has its effects by influencing a particular process this finding establishes the importance of the process in maintaining the disorder'.^[@R20]^ Our finding that reducing household debt and increasing the financial empowerment of women are associated with improved depression demonstrates the importance of these factors in maintaining depression. Moreover, we found that these factors, together with low family support and unsatisfactory *chilla*, were more strongly associated with follow-up depression score than those in our previous study (number of young children, a husband with very little formal education, low socioeconomic status and general social support), emphasising the importance of identifying these crucial aspects of the women's environment (debt, empowerment, family support) when treating their depression. The data presented here focus on the moderating effect of household debt and financial empowerment, as the other variables we considered as possible mediators did not fulfilled the requirements of mediators.^[@R20]^ Implications {#S16} ------------ The main findings are important as nearly all studies of depression in low-income countries find debt or poverty to be associated with depression so it has been suggested that depression and poverty can interact in a vicious circle.^[@R24]^ More recently it has been observed in a qualitative study of women in India that women's financial empowerment and mental health are 'inextricably linked'.^[@R9]^ Our intervention appears to be a way of breaking the vicious circle of depression with debt or lack of empowerment. It is noteworthy that, although low socioeconomic status was associated with a high depression scores at follow-up, it was debt that was a moderator of outcome, hence debt may be more amenable to change than poverty. Although only having a few years of formal education predicted debt at follow-up, this was not so for empowerment, which is a strength of the approach taken by the LHWs in the intervention arm. Our intervention, the 'Thinking Healthy Programme', was developed to provide a culturally appropriate, feasible and evidence-based psychological intervention for women living in very poor communities in rural Pakistan. It was delivered by ordinary female community health workers to overcome the lack of trained specialist therapists in low-income settings. We believe the community health workers were effective as therapists partly because they could readily engage with the local women, but also because they understood fully their social stressors. This meant they could use problem-solving effectively as part of the therapy to address these stressors. The improvement in financial empowerment can be seen as a direct effect of the intervention, even though it was not a specific focus of the intervention. The intervention focused on the mother's care of herself, including her diet and appearance; it aimed to boost self-esteem. Another specific focus was the modification of family behaviour where it was important for child healthcare. This involved engaging the father as well as the mother. These aspects of the intervention might well have encouraged empowerment of the women, even though this was not a specific aim. Reduction of debt was rather less directly associated with the intervention. It probably arose as a result of the LHWs' freedom to seek solutions to the problems faced by many families as part of a child-focused agenda. Thus, debt would have been highlighted as a major problem in approximately half of the families and this could have led to the LHW gently encouraging mothers and families to take small steps to better themselves financially. Future interventions for depression in women in low- and middle-income countries might usefully incorporate this element of problem-solving in addition to the cognitive and behavioural aspects of a CBT-like intervention. The fact that the intervention was associated with the household coming out of debt is immensely important in a low-income setting such as rural Pakistan, where debt can have disastrous effects on a family. In this setting household debt may result from a catastrophic health problem in a family member^[@R25]^ but the intervention was associated also with infants having fewer episodes of diarrhoeal illness and higher rates of immunisation so the benefits of our intervention go beyond improvement in the mothers' mental health. An intervention targeting maternal mental health may have economic benefits for the household. We strongly advocate the case for including mental health interventions, especially those targeting women and children, in programmes of poverty alleviation. Similarly, the use of local non-specialist workers to deliver therapies may be a very effective strategy to deliver psychological interventions in poor communities. We would like to thank the Human Development Research Foundation, Islamabad, for logistic assistance; the Ministry of Health, Government of Punjab, for their permission to do this study; Fareed Minhas at Rawalpindi for his unflinching support and encouragement; and Zaeem Haq for assistance with the development of training materials and supervision of the lady health workers. **Declaration of interest** None. **Funding** The study was funded by the Wellcome Trust, UK, through a career development fellowship in tropical medicine awarded to A.R. The fellowship was awarded through the Wellcome Trust Tropical Centre at the Liverpool School of Tropical Medicine and hosted by the University of Manchester and the Institute of Psychiatry, Rawalpindi. | High | [
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FIFA’s ethics committee is investigating the awarding of the world cups in 2018 to Russia and in 2022 to Qatar after allegations of bribery and corruption. The committee is to issue a report to the adjudicatory chamber mid-July. Nasser Al Khater, Qatar 2022 communications director, told Qatari news channel Al Jazeera Tuesday that they are confident the World Cup will take place in Qatar. Qatar’s direct World Cup spending is estimated at $16bn, or 7.5% of GDP, according to the report. The ancillary infrastructure spending, however, is much larger. The five-year projected government capital expenditure is $100bn. The report expects that if Qatar loses its hosting right of the World Cup, the infrastructure spending will lose execution focus and face potential delays. The nominal effect of the World Cup cancellation is credit positive, as capital spending would be lower and more efficient, according to the bank. | Low | [
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357 F.2d 517 Glenn D. BARTLE, Trustee of Markson Bros., Inc. now known as M B H, Inc., Plaintiff-Appellant,v.Asher S. MARKSON, Defendant-Appellee. No. 68. Docket 29803. United States Court of Appeals Second Circuit. Argued October 20, 1965. Decided February 14, 1966. COPYRIGHT MATERIAL OMITTED Laurence Sovik, Syracuse, N. Y. (Smith, Sovik, Terry, Kendrick, McAuliffe & Schwarzer, Syracuse, N. Y.), for appellant. William J. Mackay, Syracuse, N. Y. (Mackay & Caswell, Syracuse, N. Y.), for appellee. Before WATERMAN, MOORE and FRIENDLY, Circuit Judges. FRIENDLY, Circuit Judge: 1 Judge Medina's opinion in Bartle, Receiver v. Markson, 340 F.2d 30, 31-33 (2 Cir. 1965), so well describes the tangled background of the proceeding now before us that a summary statement will suffice at this point. On March 31, 1961, Markson Bros., Inc., a large retailer of furniture and house furnishings in New York, filed a petition for arrangement under Chapter XI of the Bankruptcy Act in the District Court for the Northern District of New York. Following a complicated series of challenges by creditors, the bankruptcy hearings were terminated on October 28, 1963, by a Referee's order confirming the transfer of all the debtor's assets and reserving to the unsecured creditors all causes of action against its officers, directors and stockholders. Banruptcy Act § 4(b). At that time a suit against Asher S. Markson, one of the officers and directors, had been instituted in the New York courts on behalf of all creditors; another class action was commenced shortly thereafter. When Markson subsequently challenged the use of the class action device and contended that each creditor must establish his individual claim, creditors petitioned the district court to reopen the bankruptcy hearing for the purpose of appointing a receiver or trustee to appear in the New York proceedings. On March 3, 1964, Judge Brennan reopened the estate and appointed a receiver. After the receiver's motion to intervene in the state court was denied without prejudice, he commenced a suit against Markson in the District Court for the Northern District of New York. Judge Brennan dismissed the complaint and on appeal this court concluded that when all the debtor's assets had been transferred and all causes of action against its officers and directors had been reserved to the creditors, no basis remained to support prosecution of creditors' claims by a receiver appointed under Chapter XI of the Bankruptcy Act, and that such a suit was "an improper method of gaining admission to the federal courts." 340 F.2d at 33. Observing that the question had not been presented, the court did not deem the occasion appropriate to consider "whether some alternative procedure might render a federal forum available for the prosecution of these claims." 340 F.2d at 33. That issue now comes before us. 2 Shortly after our decision, a special meeting of creditors of Markson Bros. was held on due notice, and Bartle was elected trustee. He immediately renewed the attack by bringing this action against Markson in the District Court. Markson moved for summary judgment dismissing the complaint both for failure to state a claim upon which relief could be granted and for lack of capacity to sue; the contention was that all claims against him had been reserved to the individual creditors, who were pursuing their remedies in an action in the New York courts, and that the re-opening of the estate and the appointment of a trustee did not vest the latter with the claims thus transferred. Judge Brennan expressed doubts as to federal jurisdiction, but since the point had not been briefed or argued,1 thought it more practical to act upon the contentions urged in the moving papers. So doing, he dismissed the complaint on the ground that "plaintiff has no capacity to sue since he has no ownership or control of the asserted claim for relief and is therefore not the real party in interest." From this judgment the trustee appeals. I. 3 Despite the attractiveness of the course followed by the district judge, we think the question of federal jurisdiction should be faced in limine before reaching the issue of the trustee's capacity to sue, see Arrowsmith v. United Press International, 320 F.2d 219, 221 (2 Cir. 1963). It is true that Arrowsmith was concerned with jurisdiction over the person, in the absence of which any judgment would be void, whereas lack of federal jurisdiction would not usually afford ground for collateral attack. Restatement, Judgments § 7, comment c (1942). However, a federal court which has noted a possible lack of federal jurisdiction must generally decline to proceed further until it has favorably resolved the doubt, Mitchell v. Maurer, 293 U.S. 237, 55 S. Ct. 162, 79 L.Ed. 338 (1934), and, despite the special considerations outlined in the margin that might justify departure from that practice in this case,2 we shall first examine the jurisdictional issue. 4 The complaint, as Judge Brennan noted, failed to comply with the command of F.R.Civ.P. 8(a) (1) that it contain "a short and plain statement of the grounds upon which the court's jurisdiction depends." This must be spelled out from the rather obscure factual allegations. Defendant Markson and his relatives owned all the stock of Markson Bros., the bankrupt. For many years preceding the filing of its Chapter XI petition on March 31, 1961, he was in active charge of its affairs, and, except for an interval from November 6 to December 30, 1959, was its president and a director. In August 1959, he negotiated the sale of the Markson Bros. stock for $1,350,000 to Son-Mark Industries, Inc., a corporation organized by the purchasers. Son-Mark borrowed $1,350,000 from Markson Bros. The latter, with the knowledge and consent of Markson, parted with various sound assets in order to make the loan, for which it received subordinated debentures of Son-Mark having "no market value and no readily saleable value."3 Although the public was informed of the purchase of the stock by Son-Mark, there was no disclosure that $1,350,000 of Markson Bros. assets had been liquidated and used to facilitate the purchase. The depletion of these assets on November 6, 1959, rendered Markson Bros. insolvent, and it remained so. In addition, with Markson's knowledge and consent, between January 1960 and February 1961, $1,329,039.42 was withdrawn from Markson Bros. bank accounts and paid over to Son-Mark, nearly half being appropriated to the latter's use; other sums were paid by Markson Bros. to Son-Mark without consideration; in February 1961 Markson Bros. acquired the assets of a company from Son-Mark for cash, but thereafter paid over to Son-Mark the receipts from its operation; on March 28, 1960, Markson Bros. assigned accounts receivable to Redisco, Inc., for a loan of $985,464, of which $639,000 was used to pay the balance of the Walter E. Heller & Co. loan to Son-Mark for the purchase of Markson Bros. stock; and advances under this agreement with Redisco increased to $1,970,320 by February 7, 1961. The various transactions were alleged to violate Article 10 of the New York Debtor and Creditor Law, McKinney's Consol.Laws, c. 12, § 60 of the General Corporation Law, McKinney's Consol.Laws, c. 23, §§ 15 and 58 of the Stock Corporation Law, McKinney's Consol. Laws, c. 59, and § 67 of the Bankruptcy Act. 5 Federal jurisdiction over such a suit by a trustee is controlled by § 23 of the Bankruptcy Act:4 6 § 23. Jurisdiction of United States and State Courts. a. The United States district courts shall have jurisdiction of all controversies at law and in equity, as distinguished from proceedings under this Act, between receivers and trustees as such and adverse claimants, concerning the property acquired or claimed by the receivers or trustees, in the same manner and to the same extent as though such proceedings had not been instituted and such controversies had been between the bankrupts and such adverse claimants. 7 b. Suits by the receiver and the trustee shall be brought or prosecuted only in the courts where the bankrupt might have brought or prosecuted them if proceedings under this Act had not been instituted, unless by consent of the defendant, except as provided in sections 60, 67, and 70 of this Act. 8 The District Court was justified in assuming that Markson is a resident of New York and thus in concluding that the debtor, a New York corporation, could not have sued him in federal court. Markson has not yet consented to such a suit, and it seems unlikely that he will, see fn. 2. Absent such a consent, federal jurisdiction does not exist unless the suit falls within the provisions of §§ 60, 67 or 70 of the Bankruptcy Act — applicable in Chapter XI proceedings by virtue of §§ 302, 342 and 352 — which confer federal jurisdiction over certain plenary actions to recover property. On the other hand a fair reading of § 23 sustains federal jurisdiction in any such case even though this may not precisely square with every letter; despite the disturbing redundancy and contradictions in the statute, which badly needs overhaul,5 it seems fairly plain that Congress intended a trustee to be able to prosecute a plenary suit in federal court if, although only if, one of the enumerated conditions was satisfied. See MacLachlan, Bankruptcy § 219 (1956); 1 Moore, Federal Practice ¶ 0.60 [8. -6], at 654-656 (2d ed. 1964). 9 The complaint, lacking any allegation of a debtor-creditor relationship between Markson Bros. and Son-Mark, does not sufficiently charge a preference avoidable under § 60. Section 67, to which the complaint refers, is a rather slender reed since most of the transactions alleged, even if within the definition of fraudulent conveyances, did not occur within a year prior to the filing of the petition, as § 67 requires. A much stronger and, in our view, sufficient basis for jurisdiction can be found in § 70e, which declares that the trustee can avoid any transfer of property that is fraudulent or voidable "under any Federal or State law applicable thereto." 10 The complaint, when read with appropriate charity, does allege conveyances condemned as fraudulent by §§ 273-276 of the New York Debtor and Creditor Law, and transfers of corporate property violating § 15 of the Stock Corporation Law. If the action were against Son-Mark to set aside the transfer of November 1959, the applicability of § 70e (1) and consequent federal jurisdiction would be too clear for discussion. We see no reason for taking a different view because the action is solely against Markson, who, along with the other stockholders of Markson Bros., was alleged to be the ultimate recipient of the proceeds of the company's assets that were transferred to Son-Mark to pay the purchase price of the stock; as to the initial transfer of $1,350,000 from Markson Bros., Son-Mark is claimed to have been simply a vessel wherein these sums, exchanged for unmarketable subordinated debentures, were mingled with the loan from Heller before the payment to the stockholders. To the extent that Markson has received the benefit of a conveyance allegedly fraudulent against creditors, he is the proper defendant in a suit to avoid the transfer and § 70e is applicable even on the most literal reading. Cf. Lytle v. Andrews, 34 F.2d 252 (8 Cir. 1929); Eisenrod v. Utley, 211 F.2d 678 (9 Cir. 1954). 11 The other transactions challenged in the complaint, where Markson's liability is for having caused or consented to a fraudulent transfer, cf. New York General Corporation Law § 60, subd. 2, rather than for having received its fruits, may not fit so neatly under § 70e. Compare Glenn, Fraudulent Conveyances and Preferences §§ 56, 605 (1940). But, assuming arguendo that the claims are not within that section, we see no reason why federal jurisdiction to hear them should not attach under the principle of Hurn v. Oursler, 289 U.S. 238, 53 S.Ct. 586, 77 L.Ed. 1148 (1933), since the alleged fraudulent conveyance of Markson Bros. assets to Son-Mark and thence to Markson and other stockholders was the source from which all else flowed. To be sure, these other transactions may not constitute "different grounds asserted in support of the same cause of action," 289 U.S. at 247, 53 S.Ct. at 590; Strachman v. Palmer, 177 F.2d 427, 12 A.L.R.2d 687 (1 Cir. 1949), and recovery for them may not rest upon facts that are substantially identical, see Musher Foundation, Inc. v. Alba Trading Co., 127 F.2d 9, 10 (2 Cir.), cert. denied, 317 U.S. 641, 63 S.Ct. 33, 87 L.Ed. 517 (1942); Zalkind v. Scheinman, 139 F.2d 895, 900 (2 Cir. 1943), cert. denied, 322 U.S. 738, 64 S.Ct. 1055, 88 L. Ed. 1572 (1944). But the formulation of the standard for recognizing pendent jurisdiction in the Hurn case, prior to Erie R. R. v. Tompkins, 304 U.S. 64, 58 S.Ct. 817, 82 L.Ed. 1188 (1938), was made at a time when federal adjudication of state-created rights offered greater danger of a result incongruent with state law, cf. Maternally Yours, Inc. v. Your Maternity Shop, Inc., 234 F.2d 538, 540 n. 1 (2 Cir. 1956); and the narrow view that would limit pendent jurisdiction to situations within that formulation has not been universally adopted. Compare United Lens Corp. v. Doray Lamp Co., 93 F.2d 969 (7 Cir. 1937); Musher Foundation, Inc. v. Alba Trading Co., supra, 127 F.2d at 11 (Clark, J., dissenting); Manosky v. Bethlehem-Hingham Shipyard, Inc., 177 F.2d 529, 534 (1 Cir. 1949); Errion v. Connell, 236 F.2d 447, 454 (9 Cir. 1956); Wechsler, Federal Jurisdiction and the Revision of the Judicial Code, 13 Law & Contemp.Prob. 216, 232-233 (1943); ALI, Study of the Division of Jurisdiction between State and Federal Courts, Tent. Draft No. 3, pp. 9, 54-58 (1965); cf. Maternally Yours, Inc. v. Your Maternity Shop, Inc., supra, 234 F.2d at 544. The proper balance between the evils of piecemeal litigation in different courts and undesirable federal handling of state law claims depends upon the nature of the state claim to be adjudicated and its relationship to the cause of action on which federal jurisdiction is based. See Wechsler, supra, at 232. Here the claims which we are assuming not to come within the grant of federal jurisdiction, advanced by a trustee in bankruptcy to gather assets of the estate, are simply the second act of a play in which the claim within federal jurisdiction (state-created but federally adopted) is the first; in a state court action on this second group of claims, the trustee would have to reconstruct proof already presented in the federal suit. The argument in favor of recognizing pendent jurisdiction, thereby avoiding fragmentation of the trustee's case, seems particularly strong since Congress could "throw into the bankruptcy courts all litigation to which receivers or trustees in bankruptcy properly become parties," MacLachlan, Bankruptcy § 219, at 245 (1956); Taubel-Scott-Kitzmiller Co. v. Fox, 264 U.S. 426, 430-431, 44 S.Ct. 396, 68 L.Ed. 770 (1924), and determination of the state claims thus represents no extension of federal judicial power into areas constitutionally prohibited in the absence of diversity.6 II. 12 Having established the existence of federal jurisdiction independent of any consent by Markson, we turn to the question of the trustee's capacity to sue in this case. When the Referee terminated the Chapter XI proceeding, while expressly reserving to the creditors all claims against officers, directors and stockholders, everyone expected these claims to be vindicated in suits on behalf of all creditors in the state courts. So they doubtless would have been had Markson not "sought to prevent the use of the class action device, and to require each creditor to appear individually and demonstrate the validity and amount of his claim." 340 F.2d at 32. The potential frustration of creditors' rights, threatened by the procedural obstacles thrown up by Markson,7 afforded ample justification for reopening the estate. Section 2a(8), which had previously authorized a bankruptcy court to reopen estates "whenever it appears they were closed before being fully administered," was broadened by the Chandler Act to permit reopening "for cause shown." See 1 Collier, Bankruptcy ¶¶ 2.47, 2.49 (14th ed. 1964). "What constitutes `cause' is not defined and lies primarily within the discretion of the district judge; only for plain abuse of discretion should his decision be reversed." In re Perlman, 116 F.2d 49, 50 (2 Cir. 1940). Discovery that the claims of creditors might not be susceptible of effective prosecution in the manner initially contemplated is a wholly appropriate basis for affirmative exercise of the court's discretion. We perceive scant equity in an attack on this from the defendant whose challenge to the attempted class action created the occasion for the reopening. 13 The district judge, having thus soundly exercised his discretion to reopen and appoint a trustee, was mistaken in later concluding that the trustee lacked capacity because the claims had passed to the creditors beyond recall. The order of October 28, 1963, cannot reasonably be read as an instrument of conveyance to the several hundred creditors. The claims against Markson had been assertable by the creditors before the filing of the Chapter XI petition, but thereupon became subject to prosecution by the debtor in possession by virtue of §§ 70a, 302, 342, and 352. See 8 Collier, Bankruptcy ¶ 6.32[1]and [2]. Although the termination of the Chapter XI proceeding returned to the creditors the initiative they had held before its beginning, the reopening renewed the status that had existed during its pendency, save only that a trustee was substituted for the debtor in possession. And a trustee, unlike a receiver in bankruptcy whose primary function "is to preserve the debtor's property," see 340 F.2d at 33, is normally empowered to act as the representative of the creditors. 14 The final argument against maintenance of the suit is that, however the matter might stand in other types of reopening, a trustee cannot be appointed in a proceeding begun by an original petition for arrangement under Chapter XI, § 322. While § 44a provides that the creditors of a bankrupt "shall, at the first meeting of creditors after the adjudication, or after a vacancy has occurred in the office of trustee, or after an estate has been reopened, appoint a trustee or three trustees of such estate," Markson says that § 44a cannot apply in an arrangement proceeding under § 322 because it is inconsistent and in conflict with the provisions of Chapter XI, see § 302; 8 Collier, Bankruptcy ¶ 5.49[3]. The argument is that where a debtor's petition is filed under § 322 (or presumably when such a petition is filed under § 321 and no prior adjudication has occurred), there is no adjudication, no "first meeting of creditors after the adjudication" and no bankruptcy administration in the ordinary sense. Moreover, §§ 338 and 378(2) of Chapter XI provide for the creditors' "nomination" of a trustee who shall be appointed by the court only in the event that an order is entered directing a bankruptcy proceeding to administer the debtor's estate; where no such proceeding is pending or contemplated, any appointment of a trustee by creditors under § 44(a) is said to be inconsistent with these provisions. 15 We have no quarrel with this analysis in general; we agree that Chapter XI contemplates that in proceedings under § 322 the debtor's possession shall remain undisturbed. But the argument fails to take account of the special situation where such an estate is reopened, not for any reconsideration of the arrangement or management of the debtor's business, which has been completely liquidated, but for the limited purpose of insuring effective prosecution of creditors' claims. Under these circumstances, a court may properly look to § 44(a) with its authorization of a trustee's appointment at a meeting of creditors "after an estate has been reopened." Where the reopening is for the sole purpose of prosecuting claims, and especially claims against officers or directors of the debtor, which are the debtor's only remaining asset, we see nothing inconsistent with the scheme of Chapter XI in the court's appointing a trustee rather than following the tortuous path of having the creditors require the debtor in possession to sue its own officers or directors — very likely with special counsel appointed to insure independence, cf. In re Martin Custom Made Tires Corp., 108 F.2d 172 (2 Cir. 1939); In re National Pub.Serv. Corp., 68 F.2d 859, 862-863 (2 Cir.), cert. denied Utilities Power & Light Corp. v. Irving Trust Co., 292 U.S. 641, 54 S.Ct. 773, 78 L.Ed. 1492 (1934); Weintraub & Levin, Practical Guide to Bankruptcy and Debtor Relief 201 (1964). 16 The order dismissing the complaint is reversed. Notes: 1 The point had not been urged in the proceedings relating to the receiver's suit 2 What might set the instant case apart is that, as will appear below, the governing statute presents the rare situation where federal jurisdiction can be conferred by the defendant's consent. Although it would be unrealistic to find a "consent" by Markson simply because he failed to challenge federal jurisdiction in his motion to dismiss, we would take a different view if he should go to trial without raising the issue, see Wymard v. McCloskey & Co., 342 F.2d 495, 498 (3 Cir. 1965), and cases cited therein. Although that is conceivable, it is hard to suppose that Markson, who has not exactly welcomed this action, would not press the point on a remand now that it has been sharply brought to his attention, and, if a motion to dismiss were to be granted, we would have still another appeal. Under these circumstances we deem it best to determine at the outset whether there is a basis for federal jurisdiction independent of any consent 3 Son-Mark became the subject of a bankruptcy proceeding in the Eastern District of Pennsylvania, see Bartle v. Markson Bros., Inc., 314 F.2d 303, 306 (2 Cir. 1963) 4 28 U.S.C. § 1334, giving the district courts exclusive jurisdiction "of all matters and proceedings in bankruptcy," is inapplicable to what was necessarily a plenary suit. See 2 Collier, Bankruptcy ¶ 23.02 (14th ed. 1964) 5 For example, subdivision (a) uses the phrase "adverse claimants" which subdivision (b) does not, and does not contain the two exceptions which subdivision (b) does. This contrariety is doubtless due to the fact that the two subdivisions originally served different purposes. See Schumacher v. Beeler, 293 U.S. 367, 55 S.Ct. 230, 79 L.Ed. 433 (1934) and 2 Collier, Bankruptcy ¶ 23.13, at 593 n. 9 (14th ed. 1964). There is the still more basic question whether the grant of federal jurisdiction comes from § 23, see MacLachlan, Bankruptcy § 219, or from § 2a(7) with § 23 as a limitation, see 2 Collier, Bankruptcy ¶ 23.12, at 590-91 — an issue put in doubt by Williams v. Austrian, 331 U.S. 642, 67 S.Ct. 1443, 91 L.Ed. 1718 (1947). And there is the further anomaly, which gave rise to that decision, that, because of § 102, § 23 does not apply in proceedings for corporate reorganization under Ch. X, although it does in proceedings for railroad reorganization under § 77 and for arrangements under Ch. XI 6 This court's decision in Lowenstein v. Reikes, 60 F.2d 933 (2 Cir. 1932), cert. denied, 287 U.S. 669, 53 S.Ct. 315, 77 L.Ed. 577 (1933), need not be read as taking a contrary view since the two transactions joined in the complaint were not so closely related as here. Moreover, that decision was rendered while this court was taking a position as to pendent jurisdiction which the Supreme Court later held too narrow, see Hurn v. Oursler, 289 U.S. 238, 53 S.Ct. 586, 77 L. Ed. 1148 (1933), reversing 61 F.2d 1031 (2 Cir. 1932) 7 The petition for reopening alleged that there were 432 creditors, scattered throughout the country, with total claims of $655,297 | Low | [
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Electrochemical cells comprising polymer electrolyte membranes (PEMs) may be operated as fuel cells wherein a fuel and an oxidant are electrochemically converted at the cell electrodes to produce electrical power, or as electrolyzers wherein an external electrical current is passed between the cell electrodes, typically through water, resulting in generation of hydrogen and oxygen at the respective electrodes of the cell. FIG. 1 illustrates a typical design of a conventional electrochemical cell comprising a PEM, and a stack of such cells. Each cell comprises a membrane electrode assembly (MEA) 5 such as that illustrated in an exploded view in FIG. 1a. MEA 5 comprises an ion-conducting PEM layer 2 interposed between two electrode layers 1,3 which are typically porous and electrically conductive, and comprise an electrocatalyst at the interface with the adjacent PEM layer 2 for promoting the desired electrochemical reaction. The electrocatalyst generally defines the electrochemically active area of the cell. The MEA is typically consolidated as a bonded laminated assembly. In an individual cell 10, illustrated in an exploded view in FIG. 1b, an MEA is interposed between a pair of separator plates 11, 12, which are typically fluid impermeable and electrically conductive. The cell separator plates are typically manufactured from non-metals such as graphite or from metals, such as certain grades of steel or surface treated metals, or from electrically conductive plastic composite materials. Fluid flow spaces, such as passages or chambers, are provided between the plate and the adjacent electrode to facilitate access of reactants to the electrodes and removal of products. Such spaces may, for example, be provided by means of spacers between separator plates 11, 12 and corresponding electrodes 1, 3, or by provision of a mesh or porous fluid flow layer between separator plates 11, 12 and corresponding electrodes 1, 3. More commonly channels (not shown) are formed in the face of the separator plate facing the electrode. Separator plates comprising such channels are commonly referred to as fluid flow field plates. In conventional PEM cells, resilient gaskets or seals are typically provided between the faces of the MEA 5 and each separator plate 11, 12 around the perimeter to prevent leakage of fluid reactant and product streams. Electrochemical cells with a ion-conductive PEM layer, hereinafter called PEM cells, are advantageously stacked to form a stack 100 (see FIG. 1d) comprising a plurality of cells disposed between a pair of end plates 17, 18. A compression mechanism (not shown) is typically employed to hold the cells tightly together, maintain good electrical contact between components and to compress the seals. In the embodiment illustrated in FIG. 1c, each cell 10 comprises a pair of separator plates 11, 12 in a configuration with two separator plates per MEA. Cooling spaces or layers may be provided between some or all of the adjacent pairs of separator plates in the stack assembly. An alternative configuration has a single separator plate or "bipolar plate" interposed between pairs of MEAs, contacting the cathode of one cell and the anode of the adjacent cell, thus resulting in only one separator plate per MEA in the stack (except for the end cell). The stack may comprises a cooling layer interposed between every few cells of the stack, rather than between each adjacent pair of cells. The cell elements described have openings 30 formed therein which, in the stacked assembly, align to form fluid manifolds for supply and exhaust of reactants and products and, if cooling spaces are provided, for a cooling medium. Again, resilient gaskets or seals are typically provided between the faces of the MEA 5 and each separator plate 11, 12 around the perimeter of these fluid manifold openings to prevent leakage and intermixing of fluid streams in the operating stack. In the future it is anticipated that a major area of application for PEM fuel cells, will be for electrical power generation in stationary power plants and portable power generation systems, and for propulsion in motor vehicles. For these applications, a PEM fuel cell service life of at least 10 years is desirable. Production costs are important and will play a central role in the successful commercialization of PEM fuel cells for these applications. Other important considerations when designing a PEM cell are simplicity and cost-effectiveness of maintenance and repair. The present invention relates to improved sealing and construction of individual PEM cells and stacks of such cells. Conventional PEM cell sealing mechanisms generally employ resilient gaskets made of elastomeric materials, which are typically disposed in grooves in the separator plates or MEAs, for example, as described in U.S. Pat. Nos. 5,176,966 and 5,284,718. Over the course of an electrochemical cell's service life the elastomeric gaskets are subjected to prolonged deformation and sometimes a harsh operating environment. Over time such gaskets tend to decrease in resilience, for example due to compression set and chemical degradation, and may become permanently deformed. This impacts negatively on the sealing function and can ultimately lead to an increased incidence of leaks. With such gasketed plates, the plastic deformation of the plates increases as the full force of pressure on the sealing area of the plate is continuously applied. Moreover, an uneven gasket pressure force distribution along the length of the stack, with a minimum in the center, can be observed in stacks using such a sealing mechanism. Thus, the sealing elements of the cells are typically exposed to higher pressure in the end plate areas in order to guarantee adequate sealing performance in the center cells of the stack. Increased sealing pressure applied to the cells in the end plate areas may then lead to increased plastic deformations and a shorter time to gasket failure. The assembly of a PEM cell stack which comprises a plurality of PEM cells each having many separate gaskets which must be fitted to or formed on the various components is labor-intensive, costly and generally unsuited to high-volume manufacture due to the multitude of parts and assembly steps required. Further, in the design and manufacture of PEM cells, in order to achieve the desired specifications, such as increased power density, there is a desire to make the individual cell elements thinner. Accordingly, there will be finer dimensional tolerances required for such thin cell elements and it will become more difficult to design gaskets which will maintain high dimensional tolerances, despite the use of highly elastic materials, as even highly elastic materials have a limited elastic deformation range. With conventional PEM cell designs, it is sometimes difficult to remove and repair an individual cell or to identify or test which cells in a stack may require repair. Furthermore, disassembly of a stack consisting of multiple cells each comprising separate cell components can be very costly as in many instances, after the removal of one cell, the gaskets of all the remaining cells may need to be replaced before the stack can be reassembled and reused. Another disadvantage of conventional PEM cells arises because the PEM typically projects beyond the edges of the electrodes and cell separator plates around the perimeter and around manifold openings. The projecting portion of the PEM may serve to avoid short circuits between plates, and it typically contacts and cooperates with the gaskets to form the fluid seal between the MEA and separator plates. However, such designs tend to leave the PEM edge exposed to air and/or reactant or coolant streams. Exposure to air or other dry gas streams can cause drying of the PEM beginning from the edge and moving towards the center. Drying of the membrane can lead to permanent damage to the membrane, reduced cell performance and ultimately malfunction of the PEM cells. Exposure of the PEM edge to some coolants and other streams can result in physical and/or chemical damage to the membrane or electrodes. German printed patent application number DE 44 42 285 describes a PEM cell stack where individual components of the stack are mechanically pressed together with a frame element or clamp of U-shaped cross-section. Specifically, the edge portions of two separator plates are pressed against the membrane, which is disposed between them, to form a gas-tight seal. The European published application EP 0 331 128 and related U.S. Pat. No. 4,786,568 disclose a liquid electrolyte fuel cell with a porous electrode substrate which has a sealant material injected into a marginal edge portion thereof. EP 0 122 150 describes a fuel cell stack with liquid, fixed electrolytes. In this stack array, two adjacent, porous and gas-bearing plates are bonded or glued together across their entire surface, in a face-to-face bond. The purpose of this arrangement is to keep the gases in the two gas-bearing plates separated from one another. In the EP 0 083 937 and related U.S. Pat. No. 4,397,917, individual components of a fuel cell stack are glued together with an adhesive material. The purpose of this arrangement is to solidly join the components to form a stack, and not to reliably seal the gas spaces. DE 19 64 811 discloses a fuel cell stack where the electrodes are attached inside a sectional plastic frame, respectively, and where the sectional frames are glued together in a gas and liquid-tight manner. An improved electrochemical PEM cell uses an adhesive bonding agent between individual PEM cell components and/or between adjacent PEM cells in a stack. The present approach provides a simplified PEM cell and stack design with a reduced part count, and associated manufacturing and cost benefits. Sealing is generally more reliable with this approach, and embodiments of the present construction may permit easier stack disassembly, testing, repair and maintenance. | Mid | [
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This story is part of a special series that explores the global water crisis. For more clean water news, photos, and information, visit National Geographic's Freshwater Web site. Your shampoo may seem harmless, but it could be contributing to the formation of a mysterious, cancer-causing substance, a new study says. New research reveals that common household products such as shampoo can interact with disinfectants at U.S. wastewater treatment plants to form a little-studied class of cancer-causing substances. These substances, called nitrosamines, can end up in drinking water, experts say. Several nitrosamines, including the chemical NDMA, a focus of the new Yale study, are classified by the U.S. Environmental Protection Agency (EPA) as probable human carcinogens. Nitrosamines form in small amounts when exposed to chloramine, the disinfectant of choice at the nation's wastewater treatment plants. The chemical—a combination of chlorine and ammonia—has been used increasingly in drinking water disinfection since the EPA set limits for better-known toxic substances that can arise from the use of chlorine, the traditional disinfectant. Though inconclusive, the study suggests "it's entirely possible that we're producing more problems—and maybe even worse problems—with chloramines," said David Reckhow, an environmental engineer at the University of Massachusetts in Amherst who was not involved in the new study. Cost of Beauty? Nitrosamines are found in a wide variety of sources, including processed meats and tobacco smoke, but what sparks their formation in drinking water has long baffled scientists. Past studies with cosmetics have hinted that substances called quaternary amines, which are also ingredients in household cleaning agents, may play a role in creating nitrosamines. Other work has shown the drug ranitidine, a stomach acid reducer also known as Zantac, can be transformed into NDMA. But those chemicals occur in trace concentrations in wastewater, and "ranitidine itself has not been detected as far as I know," said study co-author William Mitch, a chemical engineer at Yale University. "We started to think about chemicals that are used in high concentrations in consumer products." In search of more sources of nitrosamines, Mitch and his colleagues tested water at three treatment plants in Connecticut. The team then analyzed the relative amounts of quaternary amines and nitrosamines before and after treatment with chloramine. They also tested four common household products, chosen at random, for chemicals that readily form nitrosamines: Suave and Pantene shampoos, Dawn dishwashing soap, and Cheer laundry detergent. Mixed Results The researchers found that although sewage treatment plants remove some of the quaternary amines that form NDMA, quaternary amines are used in such large quantities that some may make it through the treatment process. For example, if 80 percent of people in an area served by a treatment plant used a typical amount of Suave shampoo daily, that amount of shampoo would account for up to 3 percent of nitrosamines in the treated wastewater, the authors wrote. Dawn detergent created 26 times more NDMA than Suave, according to the study in the January 19 edition of the journal Environmental Science & Technology. Some products, such as Cheer laundry detergent and Pantene shampoo, did not form nitrosamines. And the highly preliminary results do not indicate whether other brands of household products would. Mitch said that while some quaternary amines might be removed during wastewater treatment, others might be biologically transformed into tertiary amines, which yield even higher amounts of nitrosamines. "The problem is that we don't know because many of these materials are polymeric, and current analytical techniques are not geared to measure polymer concentrations," he said. Polymers are molecules made up of chains of simple, repeated units. "So at this point, it's a suggestion, because we cannot measure polymeric quaternary amines to demonstrate a link." Don't Pee in the Pool? Mitch said the combination of disinfectants and quaternary amines can occur in places other than treatment plants—when different household cleaners are combined, for instance, or in swimming pools. "In fact, we measured nitrosamine concentrations in swimming pools, and the precursors are either consumer products or human waste," he said, referring to the fact that people sometimes urinate in pools. Those results were published in 2008 in the journal Environmental Science & Technology. Yet no regulations exist so far in the United States—the University of Massachusetts' Reckhow said it's not unusual for regulations to lag behind scientific discovery. "There’s no way of getting around that, end even the science isn’t really sure" about the consequences of combining chloramination at treatment plants with household products, he said. Still, the work represents an important step, said Susan Richardson, a research chemist with the National Exposure Research Laboratory in Athens, Georgia, who was not involved in the research. | Mid | [
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This is the latest installment of PBT’s series of “What your team should do when the lockout ends.” Up next is the Miami Heat. You can also check out our thoughts on other NBA teams here as we work our way through all 30 squads. Last Season: Honestly, it could have been a lot worse. I understand that’s going to come as no consolation to Raptors fans who had to sit through a season with no defense yet again, where the team’s biggest star is the fans’ least favorite (Andrea Bargnani), and who never capitalized on the space gained from Chris Bosh’s rapid departure. But really, it could have been much worse. The Raptors were simply a non-factor last season, and it wasn’t really anything surprising. You knew they would be bad defensively, and they were. Primarily, the players caught the heat for that. At no point was the blame directed at Jay Triano, despite the fact that system has more of an effect on NBA defense than personnel nearly every time. But there was a lot to hate about this team. Bargnani struggled with double teams and continued to be horrid defensively, at least as a help defender. (Research shows Bargnani’s actually pretty decent at man defense, but don’t tell Raptors fans, they’ll throw things at you.) Jose Calderon was overpaid still even if he contributed as much as he could. Amir Johnson was Amir Johnson and not the revelation many hoped he would be. Johnson was better at the things he’s bad at but not much better at the things he’s good at. Jerryd Bayless provided a spark but got lost in the mass and perhaps the most promising player was DeMar DeRozan. Since we last saw the Raptors: Well, they hired an NBA champion assistant coach, for starters. Triano was lifted from the head coaching position and into a consultant role by Bryan Colangelo, while Dwane Casey was brought in. Casey is expected to bring in the defense he helped oversee in Dallas and focus on changing the culture of the Raptors. Speaking of Colangelo, the big guy was given an extension which almost no one understood as he has seemingly perpetuated the problems in Toronto with personnel and strategic decision making. The Raptors drafted Jonas Valanciunas who is expected to be the big tough center Bargnani never was, and there’s talk of Bargnani moving to power forward, since moving him is nearly impossible with the extension granted to him in 2010. Valanciunas won’t be available until the 2012-2013 season, however, due to his overseas contract. The Raptors clear a ton of cap space this season, and a possible amnesty clause could have dramatic effects for them. Leandro Barbosa exercised his option before the lockout and is owed $8 million. But the Raptors will be clearing a lot of excess. When the lockout ends, the Raptors need to: Make sure there’s an amnesty clause. The Raptors aren’t in the worst shape financially. But an amnesty clause could do wonders for them. You’ll find a good discussion of their options for the amnesty clause here. Most notably, and this is tough for me to say, they need to find a way to rid themselves of Andrea Bargnani. I’m a Bargnani guy. I think guys that can score from the 4-5 spot are rare in this league, and despite his terrible tendencies defensively, I don’t see a player beyond hope. I think with Dwane Casey working with him and beside Valanciunas, he could redeem himself for years of apparent apathy and laziness. But the Raptors fans I hear from are simply done with him. They want nothing more to do with him, they don’t want him to be the face of the franchise, and he is, by any and all measure, drastically overpaid. If it’s the amnesty, it’s probably going to Calderon. But Calderon will be movable in 2012. So will Amir Johnson. Barbosa might even be dumpable in a sign-and-release deal at the deadline. But Bargnani is anchored to Toronto due to his contract. He deserves a fresh start somewhere and Raptors fans deserve a reprieve from their frustrations with him. From there, it’s just about building up. DeMar DeRozan has to make the leap this season. Not start to, he’s got to make it. Otherwise, the Raptors need to move him and aim for a draft pick in this year’s insanely good draft to nab a premier wing. Ed Davis showed a lot of promise, and the Raptors need to determine what they have with him. Casey needs to be supported in his efforts to bring in defensive personnel to reshape the identity of the team and the Raptors need to get to work on forgetting who they’ve been and trying to be something wholly different. | Mid | [
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Q: How exactly does InsertAllOnSubmit works in Linq I have two tables Products and Order for some reason I just want a few records to come and sit in Orders table I have the following code public ActionResult Order() { List<Product> products=TempData["products"] as List<Product>; List<Order> orders = new List<Order>(); Order order = new Order(); foreach (var item in products) { order.Customer_Id = 1; order.Product_Name = item.Model_Name; order.Amount = item.Price; order.Order_Date = DateTime.Now.ToLocalTime(); orders.Add(order); } db.Orders.InsertAllOnSubmit(orders); db.SaveChanges(); return View(products); } I just want to know how does it work found some stuff online but couldn't understand how really it works. Can anyone could tell how it works nad how to apply it in the above code A: I have no idea why it doesn't compile, according to the discussion under your question you possibly paste some other code, however this should definitely work: public ActionResult Order() { List<Product> products=TempData["products"] as List<Product>; foreach (var item in products) { Order order = new Order(); order.Customer_Id = 1; order.Product_Name = item.Model_Name; order.Amount = item.Price; order.Order_Date = DateTime.Now.ToLocalTime(); db.Orders.Add(order); } db.SaveChanges(); return View(products); } Edit: note that since you are calling SaveChanges rather than SubmitChanges Then most probably you are not using linq2sql but rather, the Entity Framework and you are just confusing these two! The InsertAllOnSubmit is not implemented in EF, you just use the code I suggest above. | Mid | [
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You are here Dixon Gets 35 Year Prison Sentence in Double Murder The man charged with the fatal shooting of two men at a residence on Tommy Harrell Street in Smithville almost sixteen months ago may spend the rest of his life in prison. 45 year old David Howard Dixon, who was indicted on two counts of first degree murder in November 2012, pleaded guilty Monday in DeKalb County Criminal Court under a negotiated settlement to two counts of second degree murder in the August 7, 2012 deaths of 55 year old Ervin Raymon Beacham and Jose Sagahon Ticante. Judge David Patterson sentenced Dixon to 35 years in each case to run concurrently with each other for a total of 35 years. The term is also to run concurrently with a sentence he is serving for violation of probation. Dixon, who has been incarcerated since the day of the murders, has been given jail credit for those sixteen months behind bars. After being arrested in the case, Dixon was initially held in the DeKalb County Jail without bond for violation of probation and for failure to appear. He was later transferred to the Henderson County Jail. State prosecutors called only one witness Monday to testify as to the proof in the case, TBI Special Agent Dan Friel. Dixon was represented by Allison West, assistant District Public Defender. After being alerted to the shooting, the Smithville Police Department responded to Beacham's residence at 311 Tommy Harrell Street on August 7, 2012 and discovered Beacham shot to death on the couch in his home. Ticante was also found murdered and his body hidden under a tarp and some lumber in the backyard of the residence. TBI investigated the murders with the Smithville Police Department, DeKalb County Sheriff's Office and the 13th Judicial District Attorney General's Office. "He (Dixon) shot Mr. Beacham twice in the chest with a 22 caliber pistol," said Assistant District Attorney General Greg Strong in an interview with WJLE on Monday. "He (Dixon) then shot Mr. Ticante once in the chest with a pistol. After the shooting, he (Dixon) pulled Ticante's body from the house and put it in the back yard underneath a stack of lumber. Dixon later sold a pistol and offered a bill of sale with the pistol with his name on it. TBI, the Smithville Police Department, and the DeKalb County Sheriff's Department investigated the case and quickly identified Dixon as a suspect. Dixon was picked up and interviewed. He confessed on three different occasions to shooting these two men. The bodies were examined by the medical examiner's office and found to have been shot with a small caliber weapon in the torso area," he said. Although Dixon confessed to the killings, Strong said he gave no reason to investigators as to why he committed the murders. "We didn't establish a motive. That's all kind of speculation. We wouldn't want to say what we think (the motive was) because we don't know that," he said. Months after being indicted and arraigned for the double murder, Dixon underwent an evaluation by a Clinical Psychologist at Plateau Mental Health Center in Cookeville to determine his competency to stand trial. In a letter to the court, Dr. Sandra DeMott Phillips, the Clinical Psychologist who conducted the evaluation, wrote that Dixon "has sufficient present ability to consult with his lawyer with a reasonable degree of rational understanding and a rational as well as a factual understanding of the proceedings against him". Dr. Phillips further wrote "After completion of the evaluation, it is my opinion that at the time of the commission of the acts constituting the alleged offenses, severe mental disease or defect did not prevent the defendant (Dixon) from appreciating the nature or wrongfulness of the alleged acts." In July, a December 2 trial date was set for Dixon. Had he gone to trial and been convicted on the original charges of first degree murder, Dixon could have been facing life with or without parole. The range of punishment for second degree murder is 30-50 years but under this plea agreement, Dixon is getting a total sentence of 35 years of which he must serve at least 85% or 29 years and nine months before his release eligibility date. Dixon has a lengthy criminal history in DeKalb County including charges for possession of a handgun while under the influence, manufacture and delivery of a schedule IV controlled substance, assault, public intoxication, violation of an order of protection, aggravated assault, theft, domestic assault, and simple possession. | Low | [
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Q: File storage microservice design Problem overview: I'm creating a spring application just for learning purposes. I would like to create a microservice just for files, which: at the beginning would have only two basic endpoints upload/download a file (used by other microservices, not by a user directly) create db only for that microservice with thefile table. At least at the beginning. store files in a cloud (f.e. Amazon S3) store meta-information about the file in the file table. By meta I mean: Url to file in the cloud Name Size Type (a directory or a file) Extension Example flow: a microservice A sends an image: user_attachment.jpg to the files microservice upload endpoint. server does validation, secuirty check etc. sends the file to a cloud storage f.e. Amazon S3 saves meta-info about that file in a local table called file. F.e. it adds: INSERT INTO file (url, name, size, type, extension) VALUES ("http://aws.amazon.com/testapp/pictures/2018-09/picutre.jpg", "picture", 34233, "FILE", "JPG") send meta-info back to the microservice A that initialized upload operation. Uploading to cloud would be in a different thread, asynchronously and maybe even with a messagebroker help. Questions: Is it a clean/good-design-patterns-compliant approach ? What is good/bad about that approach? How could I do that in a better way ? (don't want to store files (content) on the machine where application is running [locally] ) Misc: This example is simple. I believe in commercial/big projects design might have similar assumptions/foundations. Thus let's assume that there is multiple tables in the file microservice, and both their structure and microservice logic are advanced. How does file-management-microservice in commercial application might look like according to good design-pattern rules ? A: A goal of a service in SOA is to perform some logic which, otherwise, would have to be duplicated among other services. That logic is, in turn, the reason for the service to exist. In your case, you add no value through the service. Any other service could easily access S3 directly, given that S3 is itself a service (it is not your service, but that is irrelevant here). Not only there is no added value to the intermediary service, but its cost is rather prohibitive. You may imagine that you can draft one in a few hours, which is true. However, in order to have something that works reliably and handles all the edge cases, you have to deal with caching, redundancy, interrupted uploads and recovery, large files, timeouts, brute force and DDOS, special characters in parameters, permissions and IAM, and dozens of other pretty things. Therefore, you're about to spend two or three weeks of development and possibly one week of debugging (YMMV; I don't know your experience in HTTP, SOA and the technology you want to use to create your service, but even if you're highly experienced, you shouldn't expect spending less than two weeks on that, which is a lot). I just wanted to know how it's done in commercial/big projects. Companies pay on average $700/day for a highly experienced developer, so given my estimate of two weeks, you're at $7,000 for a task. Commercial projects are about money; when there is an opportunity to save an amount even as small as $7,000, they'll do it. Additional to this direct cost, there is a cost in terms of hosting and code maintenance. This service will have to be maintained for years, adding to the bill much more than the original price. Again, all this money wasted without the clear understanding of what could such service save to the company. It doesn't save bandwidth, nor other resources. It doesn't reduce the amount one will pay to Amazon, so... This is not all. The cost of maintenance of all the projects which depend on the intermediary service will also increase. If a service: Has to be patched and the patch requires an interface change, Has to be moved to another location, with a change in its URL, Is down, requiring to have a circuit breaker to ensure the client service doesn't go down in turn, Is deprecated, requiring to migrate the client to something else, the immediate and unforeseen maintenance is required and is usually costly as well. Now, it is much more likely that those four things happen to your service than to Amazon's S3. Not because you are a bad developer, no. But because Amazon's scale is slightly different than the scale of your service, which means that they have much more workforce to pay to ensure the clients can rely on S3. Finally, many developers have prior experience with Amazon AWS (and possibly S3). This means that when you hire a new guy, he can easily understand how a service is storing files if it uses S3 directly. If you add a level of indirection, this benefit is lost. And, more importantly, every time someone has a problem with the storage, he would need to ask himself if the problem comes from the client service, from your intermediary or from S3. This adds to the debugging time. So: Is it a clean/good-design-patterns-compliant approach ? No. Add services when they add value. Don't make things more complex than they need to be (KISS) and, specifically, don't add layers which bring no benefits. What is good/bad about that approach? What is good: the fact that you provide an interface which is much simpler compared to S3. For developers unfamiliar with AWS, S3 can be quite complex. What is bad: already told it above. How could I do that in a better way ? (don't want to store files (content) on the machine where application is running [locally] ) By calling directly S3. | Low | [
0.463529411764705,
24.625,
28.5
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'use strict'; const test = require('ava'); const bashParser = require('../src'); const utils = require('./_utils'); /* eslint-disable camelcase */ test('parse if elif else', t => { const cmd = `if true; then echo 1; elif false; then echo 3; else echo 2; fi `; const result = bashParser(cmd, {insertLOC: true}); // utils.logResults(result) const expected = { type: 'If', clause: { type: 'CompoundList', commands: [ { type: 'Command', name: { text: 'true', type: 'Word', loc: { start: { col: 4, row: 1, char: 3 }, end: { col: 7, row: 1, char: 6 } } }, loc: { start: { col: 4, row: 1, char: 3 }, end: { col: 7, row: 1, char: 6 } } } ], loc: { start: { col: 4, row: 1, char: 3 }, end: { col: 7, row: 1, char: 6 } } }, then: { type: 'CompoundList', commands: [ { type: 'Command', name: { text: 'echo', type: 'Word', loc: { start: { col: 2, row: 2, char: 15 }, end: { col: 5, row: 2, char: 18 } } }, loc: { start: { col: 2, row: 2, char: 15 }, end: { col: 7, row: 2, char: 20 } }, suffix: [ { text: '1', type: 'Word', loc: { start: { col: 7, row: 2, char: 20 }, end: { col: 7, row: 2, char: 20 } } } ] } ], loc: { start: { col: 2, row: 2, char: 15 }, end: { col: 7, row: 2, char: 20 } } }, else: { type: 'If', clause: { type: 'CompoundList', commands: [ { type: 'Command', name: { text: 'false', type: 'Word', loc: { start: { col: 6, row: 3, char: 28 }, end: { col: 10, row: 3, char: 32 } } }, loc: { start: { col: 6, row: 3, char: 28 }, end: { col: 10, row: 3, char: 32 } } } ], loc: { start: { col: 6, row: 3, char: 28 }, end: { col: 10, row: 3, char: 32 } } }, then: { type: 'CompoundList', commands: [ { type: 'Command', name: { text: 'echo', type: 'Word', loc: { start: { col: 2, row: 4, char: 41 }, end: { col: 5, row: 4, char: 44 } } }, loc: { start: { col: 2, row: 4, char: 41 }, end: { col: 7, row: 4, char: 46 } }, suffix: [ { text: '3', type: 'Word', loc: { start: { col: 7, row: 4, char: 46 }, end: { col: 7, row: 4, char: 46 } } } ] } ], loc: { start: { col: 2, row: 4, char: 41 }, end: { col: 7, row: 4, char: 46 } } }, else: { type: 'CompoundList', commands: [ { type: 'Command', name: { text: 'echo', type: 'Word', loc: { start: { col: 2, row: 6, char: 55 }, end: { col: 5, row: 6, char: 58 } } }, loc: { start: { col: 2, row: 6, char: 55 }, end: { col: 7, row: 6, char: 60 } }, suffix: [ { text: '2', type: 'Word', loc: { start: { col: 7, row: 6, char: 60 }, end: { col: 7, row: 6, char: 60 } } } ] } ], loc: { start: { col: 1, row: 5, char: 49 }, end: { col: 7, row: 6, char: 60 } } }, loc: { start: { col: 1, row: 3, char: 23 }, end: { col: 7, row: 6, char: 60 } } }, loc: { start: { col: 1, row: 1, char: 0 }, end: { col: 2, row: 7, char: 64 } } }; // console.log(diff(result.commands[0].left.commands[0], expected)); utils.checkResults(t, result.commands[0], expected); }); | Mid | [
0.5456852791878171,
26.875,
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An explosive device was found on Monday at the New York home of billionaire George Soros. Bedform police said the department received a phone call from the Soros residence in Westchester County about a suspicious package. An employee that works at the home found the package and opened it, revealing what appeared to be an explosive device, according to a press release from the Bedford Police Department. The employee then placed the package in a wooded area until authorities arrived. The department told Fox News that a suspicious package was found in a mailbox. The package contained bomb components, police said. Police referred Fox News to the F.B.I's New York office, which did not confirm the report. Soros was not home at the time of the incident, according to the New York Times. The bomb squad deactivated the device, and authorities have said there is no further threat to the area. The investigation has been turned over to the Joint Terrorism Task Force Division of the FBI. The wealthy liberal donor started his philanthropic efforts in 1979, but his contributions have not always been welcomed. Campaigns against Soros emerged in Romania, where the billionaire was accused of financing "evil" as well as in Macedonia, Serbia and Slovakia – and have escalated to some extent since President Donald Trump took office. Soros, who made his fortune in hedge funds, has donated heavily to liberal causes and is vilified on the right. He is also the subject of many unfounded conspiracy theories. Recently, conservative critics have, without evidence, accused him of secretly financing a caravan of Central American migrants to make their way north toward Mexico and the U.S. Others have falsely accused him of being a Nazi collaborator during World War II, when he was a child in Hungary. Activists frequently post the addresses of homes he owns in Westchester County, north of New York City, on social media sometimes accompanied by ill wishes. The 88-year-old has focused his efforts as of late on the midterm elections in the U.S., and has funneled upwards of $15 million to Democrats as they push to regain control of Congress. Soros told the Times in July that for every Trump supporter "there is more than one Trump enemy who will be more intent, more determined." In October, Soros was linked to a non-profit group called the Center for Popular Democracy (CPD), which rose to prominence for organizing civil disobedience actions and confronting several Republican lawmakers during the contentious hearings for then-Supreme Court nominee Brett Kavanaugh. Soros’ organization has donated to the CPD over the years, giving $1.5 million to the non-profit in 2016 and 2017 through his Open Society Foundations, the records show. He also donated in the past two years another $1.2 million to the nonprofit’s sister organization Center for Popular Democracy Action. The Associated Press contributed to this report. | Low | [
0.5020408163265301,
30.75,
30.5
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Clinical symptoms of schizophrenia affect reference-independent measures of task-induced EEG alpha asymmetry. Differential patterns of EEG alpha asymmetry during verbal and spatial cognitive activity are commonly described and are thought to reflect predominance of left- vs. right-sided cortical activation. Although these patterns have been difficult to elicit reliably in schizophrenics, the authors have previously suggested that clinical status may have confounded results. Therefore, EEG data from 17 additional schizophrenic patients, 16 mood disorder patient controls, and 17 normal controls were used to examine the relationship between severity of schizophrenic symptoms and task induced alpha asymmetry. Subjects performed verbal and spatial tasks during recording of 16-channel EEG. After transformation to the average reference, log alpha power from central and temporal leads was analyzed by MANOVA and MANCOVA. The expected task-side interaction (P < 0.02) was present for the total sample and for each control group when analyzed alone. However, it was only present in schizophrenics when the BPRS score was entered as a covariable. Patterns of correlations between BPRS scores, left temporal alpha power, right/left temporal alpha ratios, and task differences in ratios suggested that higher symptom levels were associated with excessive left-sided activation during spatial activity. This is consistent with other evidence of left hemisphere overactivity in schizophrenics. | Mid | [
0.635294117647058,
33.75,
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/* mpc_sub -- Subtract two complex numbers. Copyright (C) 2002, 2009, 2011 INRIA This file is part of GNU MPC. GNU MPC is free software; you can redistribute it and/or modify it under the terms of the GNU Lesser General Public License as published by the Free Software Foundation; either version 3 of the License, or (at your option) any later version. GNU MPC is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Lesser General Public License for more details. You should have received a copy of the GNU Lesser General Public License along with this program. If not, see http://www.gnu.org/licenses/ . */ #include "mpc-impl.h" int mpc_sub (mpc_ptr a, mpc_srcptr b, mpc_srcptr c, mpc_rnd_t rnd) { int inex_re, inex_im; inex_re = mpfr_sub (mpc_realref(a), mpc_realref(b), mpc_realref(c), MPC_RND_RE(rnd)); inex_im = mpfr_sub (mpc_imagref(a), mpc_imagref(b), mpc_imagref(c), MPC_RND_IM(rnd)); return MPC_INEX(inex_re, inex_im); } | Mid | [
0.594488188976378,
37.75,
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Q: Unsure of best way to handle a task in SQL I have items in a table that need to have a history associated with them. The history will have information about where a part is / has been. So, Part A was received, then put in a machine, then taken out, then tested, then put into a new machine. I need to store each of those events and associate them with the part. originally my thought was to simply add a column each time a new event happened. so PartA would have a column Hist1 = receivedID, Hist2 = usedID .. and so on. With each column pointing to an ID that identifies the event. But this doesn't feel like a clean solution at all, With parts sometimes moving around a lot, the amount of columns could get unnecessarily big for some, and would be left empty for others. Would anyone with more experience have an Idea as to how best handle this? A: You need to have a EVENTS table. In that EVENT row, you will associate the corresponding part with the event itself. Something like this: create table parts(part_id numeric(10) primary key, ... more parts columns); create table part_events( event_id numeric(10) primary key, part_id numeric(10) references parts(part_id), event_number numeric(2) not null, event_type varchar(24) not null, -- event type tstamp timestamp not null, -- date/time of the event ... ); | High | [
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29,
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go with friends like most do, or at least with friends that support what your doing. Im 26 yrs old,I am a solo skater in elk city Oklahoma and the skate community is small, but we have a park , but in the smaller community skaters clique up I didn’t grow up here so I’m left out. I learn a I can online and practice little bit s out of the day when I have time from both jobs I work, I just don’t get a lot of beef cause I ignore them and do my own thing , but I’ve noticed my tricks that I land alone fairly easy they get difficult in the presence of others for some reason Being standoffish and skate with a lil aggression you’ll be alright, just don’t give up man at all costs do not give up. EXPERIENCED SKATER! This board is amazing for the price! (notice i said FOR THE PRICE) At the time of this review, the board was $44.40 and for that price the board i got was phenomenal. It is a 7-ply deck with aluminum trucks (havent figured out the bearings but they definitely feel like the abec 5 they claim to be). The trucks arent the best quality out there and the board can be a little thinner (maybe 5-ply) but the overall board is amazing. There are only two complaints. The hole in the wheels is a tiny TINY TIIINYYY bit off center, but nothing that cant be fixed with a new set. I can see what another review said by it not coming assembled, as a couple of the bolts on the wheels are a little loose, but the board does come assembled. The Rimable Complete 22″ Skateboard is the most compact street board that are ready-to-use. It is best for exercise and fun, and very portable. There are five colors that you can choose from Black, Blue, White, Purple, and Green. It has high-quality construction, with a high-density plastic deck. It features extremely smooth 59mm wheels along with ABEC7 bearings and solid aluminum trucks. It measures 22″ long and 6″ wide and weighs 4 pounds. It has the best rating of 4.3 on Amazon. Regardless of your skating ability or style, CCS is the definitive place for the best skateboard decks around. With hundreds in stock, take your pick from some of the sickest decks available! Alien Workshop, Baker, Deathwish, Element, enjoi, Girl, Welcome. WKND, Santa Cruz, Primitive, and Real are among the most popular offered. Additionally, notable brands such as Almost, DGK, Flip, Krooked, Alien Workshop, Skate Mental, Zero, Creature, and Chocolate are available for all your skating needs. The skater can gain greater clearance from the ground by jumping higher, popping faster, sliding the front foot farther forwards (starting the jump with the front foot farther back), and pulling the legs higher into the chest to raise the feet higher. Skaters attempting record-setting ollies even contort the legs so that board and feet are not directly below them, allowing the board to rise at or just below the level of the pelvis. From cheap skateboards to high end, custom complete skateboard decks, we have boards for riders of every skill level and tax bracket - we get it, we put skateboarding before everything else first. If you can’t always afford a new board, but go through decks like toilet paper, consider a CCS Skateboard - they cost less, but are manufactured in the same factories as other brands we carry. CCS Skateboards are held to the same standards as every skateboard we sell, but we can sell them for less. The wheels of your skateboard can greatly affect your ride in numerous ways, such as the speed, your ability to take control of the skateboard’s movements, and what you feel while riding the board. The good news is that they come in various sizes, levels of durability, and colors, allowing you to pick one that suits your skateboard preference and style. Ollie 180: an Ollie where the skateboarder and the skateboard spins 180 degrees after leaving the ground. Both the skateboarder and the skateboard rotate in the same direction (Frontside or Backside) with the skateboarder's feet sticking to the skateboard. This trick is usually referred to as a frontside or backside 180, or less frequently and more popular with older skateboarders and/or when performed on a bank/quarterpipe, a frontside / backside ollie The Powell Golden Dragon 2 Skateboard is an affordable and complete skateboard for the beginners and also for the advanced skaters. It has high-rebound, hand-cast polyurethane wheels to give you a great roll and grip. It measures 7.5 inches wide with a colorful screen-printed bottom. It is made in China and has an average rating of 4.2 on Amazon. Pull your knees up into your chest – How far you actually want to pull your legs up is totally up to you, but the higher your feet go, the higher your board will go too. By the way, the highest recorded preferred stance ollie-pop is 45 inches, done by Aldrin Garcia, and the highest switch stance ollie-pop is 40.125 inches, by Gavin Caperton. And if you’re going for endurance rather than height, the record for most consecutive hops is held by Rob Dyrdek, who did 215 of them in a row on his TV show Rob and Big. So those give you something to shoot for. This was a simple purchase. No issues at all and the skateboards are really nice! Some people have said it comes unassembled, that's not the case. I ordered 2 different boards and both came assembled and ready to roll.. The boards are topped with grip tape and trucks and wheels were assembled perfectly. If I had a need to get another board I would run straight back to this kit, they are great! When looking at skateboarding’s history, the only thing that’s stayed the same is the overall structure: every board consists of four skateboard wheels, two skateboard trucks, and a riding surface of some kind. And while we’ve come a long way from the days of metal and clay wheels, some aspects of skateboarding - like the brands manufacturing some of the most trusted products - haven’t changed at all. Independent Trucks has been designing trucks since 1978. Powell Peralta, the company responsible for Powell Skateboards, Bones Wheels, Bones Bearings, and the Bones Brigade also started in 1978. NHS, Inc., the company that produces Santa Cruz Skateboards, Independent Trucks, Bronson Speed Bearings, Krux trucks, Flip Skateboards, Ricta Wheels, Mob Grip, and OJ Wheels started in 1973. It’s no wonder these brands are still doing so well - they’ve been with skateboarding since the beginning. Since the day skateboarding went from something surfers did when the waves were flat to its own sport that involves technique, practice, and careful consideration, a small handful companies have been there to help skateboarding become what it is today. A skateboard is moved by pushing with one foot while the other remains on the board, or by pumping one's legs in structures such as a bowl or half pipe. A skateboard can also be used by simply standing on the deck while on a downward slope and allowing gravity to propel the board and rider. If the rider's leading foot is their right foot, they are said to ride "goofy;" if the rider's leading foot is their left foot, they are said to ride "regular." If the rider is normally regular but chooses to ride goofy, they are said to be riding in "switch," and vice versa. A skater is typically more comfortable pushing with their back foot; choosing to push with the front foot is commonly referred to as riding "mongo", and has negative connotations of style and effectiveness in the skateboarding community. Almost no one lands an ollie on their first try. Repetition is the most important part of learning how to ollie. Once you learn how to do an ollie, you can try doing them while rolling. Learning is one of the funnest parts of skateboarding. After you learn ollies, you can move onto 180s, Pop Shove-Its, and flips. Soon a whole world of tricks will open up. GREAT board. Great design graphics. The boards deck has a real POP to it that makes it GREAT for tricks and a AWESOME beginner board. Only problem is It's super slow and requires a lot of work to maintain speed or to pick up speed period. A simple $20 wheel barring upgrade will fix that and BOOM PERFECT board, PERFECT caved in deck. Only 4 stars because of the lack of speed. I prefer my boards ready out of the box already pre-upgraded, but for the price, no point in complaining. Like almost all new boards, u have to ajust the wheels and the flex of the board to customize it to your liking. You won't regret it. But order it with some "Lucky" or "Red bearings" and your set. | Mid | [
0.5462012320328541,
33.25,
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LORD, HELP ME ACCEPT WHAT'I CANNOT HANDLE' For every single one of us in this room and for every single person outside this room, there is at least one thing (and likely many things) that we just cannot handle. Whatever that thing is, we are "handled" by it instead of "handling" it. For some, that thing is money. For others, it is credit. For others, it is power. For others, it is control. For others, it is popularity. For others, it is pleasure. For everyone, it is knowledge. May I anticipate the response of many people? "David, that is absolutely ridiculous! Knowledge is basic to existence! Knowledge is highly valued in this culture! We seek to educate all our children because knowledge is important. We stress knowledge on our jobs and careers. We even have Bible classes because we want children and adults to have Bible knowledge." I definitely agree that knowledge is basic to existence. I understand the value of an education. I realize how essential knowledge is on jobs and in careers. I totally endorse the pursuit of knowledge in seeking to be a godly person. Listen to me carefully. I did not say knowledge was unimportant. I said people cannot handle possessing knowledge. The most ungodly problems each of us have are created by what we know. I challenge you to think about that truth. When are you powerfully tempted to feel superior to someone? Is it not when you know something they do not know? When are you powerfully tempted to "look down" on another person? Is it not when you regard them to be incredibly ignorant? More than money, more than power, more than control, more than popularity, knowledge creates an arrogance that makes self big and important and makes others small and insignificant. Consider a specific illustration. All I ask you to do is be honest with yourself as you answer to you silently. Do you personally "look down on" many people in the Middle East? If you do, why do you? See if any of these statements sound familiar. "I do not understand how anyone could be a suicide bomber!" "I do not understand how people can hate people so intensely just because of their nationality." "I do not understand how people can attack jeeps and guns by throwing stones!" You do not understand those things? "NO!" Why do you not understand those things? "Bottom line, those are stupid acts!" Would you do any of those things? "NO!" Why? "I know better!" So, what you know makes you superior? Please pray with me: "God, teach us how to have minds and hearts filled with the love that comes from you. In our love for You and others, never let us use our knowledge to destroy those for whom You sacrificed the Jesus." Both Christianity and Judaism traces the root of all our personal problems and all the world's problems to humanity's inability to handle knowledge. The first book in the Bible makes two bold declarations. The first temptation was based on the human inability to handle knowledge. The first act of evil was based on the human inability to handle knowledge. Read with me from Genesis 3:1-10. Now the serpent was more crafty than any beast of the field which the Lord God had made. And he said to the woman, "Indeed, has God said, 'You shall not eat from any tree of the garden'?" The woman said to the serpent, "From the fruit of the trees of the garden we may eat; but from the fruit of the tree which is in the middle of the garden, God has said, 'You shall not eat from it or touch it, or you will die.' " The serpent said to the woman, "You surely will not die! For God knows that in the day you eat from it your eyes will be opened, and you will be like God, knowing good and evil." When the woman saw that the tree was good for food, and that it was a delight to the eyes, and that the tree was desirable to make one wise, she took from its fruit and ate; and she gave also to her husband with her, and he ate. Then the eyes of both of them were opened, and they knew that they were naked; and they sewed fig leaves together and made themselves loin coverings. They heard the sound of the Lord God walking in the garden in the cool of the day, and the man and his wife hid themselves from the presence of the Lord God among the trees of the garden. Then the Lord God called to the man, and said to him, "Where are you?" He said, "I heard the sound of You in the garden, and I was afraid because I was naked; so I hid myself." We could spend a lot of time focusing on talking snakes and eating a fruit that provides knowledge--but if we did, I fear we would miss the lessons. "What lessons?" In contrast to God, humanity has never been able to "handle" the knowledge of evil. In contrast to God, the knowledge of evil deceives us--not God, but us. In contrast to God, the knowledge of evil tempts us--not God, but us. God can handle the knowledge of evil because He cannot be deceived (Galatians 6:7) or tempted (James 1:13). Before humanity had the knowledge of evil, there were some basic problems we did not have. It was the knowledge of evil that produced shame. It was the knowledge of evil that produced a sense of guilt. It was the knowledge of evil that produced fear. How different would your life be if you never felt shame, never knew guilt, and were never afraid? Nothing good resulted from the human knowledge of evil. Why? We could not handle knowing what evil was! Evil deceives; God does not; and we are easy prey for skillful deception! The highest form of deception is an addiction. I am speaking of any form of addiction: to alcohol, to drugs, to sex, to power, to money, to control, to pleasure. Either an addict denies an addiction, or an addict abandons himself or herself to an addiction. Basically an addiction is any form of destructive escape--the attempt to flee rather than face or endure. The addict often becomes a powerful advocate for his or her addiction. He or she often does so with the words, "If you only knew. . ." If as a Christian you really doubt the fact that humans cannot handle knowledge, I ask you to consider a couple of statements. In 1 Corinthians 13, Paul discussed the most important and enduring qualities of human existence. He named three: faith, hope, and love. He declared that the greatest of the three is love, which he discussed in detail. Would you please note that knowledge was not one of the three. Please read with me as we look at 1 Corinthians 8:1-13. Now concerning things sacrificed to idols, we know that we all have knowledge. Knowledge makes arrogant, but love edifies. If anyone supposes that he knows anything, he has not yet known as he ought to know; but if anyone loves God, he is known by Him. Therefore concerning the eating of things sacrificed to idols, we know that there is no such thing as an idol in the world, and that there is no God but one. For even if there are so-called gods whether in heaven or on earth, as indeed there are many gods and many lords, yet for us there is but one God, the Father, from whom are all things and we exist for Him; and one Lord, Jesus Christ, by whom are all things, and we exist through Him. However not all men have this knowledge; but some, being accustomed to the idol until now, eat food as if it were sacrificed to an idol; and their conscience being weak is defiled. But food will not commend us to God; we are neither the worse if we do not eat, nor the better if we do eat. But take care that this liberty of yours does not somehow become a stumbling block to the weak. For if someone sees you, who have knowledge, dining in an idol's temple, will not his conscience, if he is weak, be strengthened to eat things sacrificed to idols? For through your knowledge he who is weak is ruined, the brother for whose sake Christ died. And so, by sinning against the brethren and wounding their conscience when it is weak, you sin against Christ. Therefore, if food causes my brother to stumble, I will never eat meat again, so that I will not cause my brother to stumble. For us, nothing is more black and white than idolatry--there is only one God or there is not, and there are no ifs, ands, or buts about it. Those who had knowledge and were quite correct in their knowledge knew there was only one God. They knew that an idol did not represent an existing, living god, and they were correct in their knowledge. They knew that a sacrifice offered to an idol was offered to nothing, and they were correct in their knowledge. And Paul said that correct knowledge was the foundation of arrogance. Knowledge was the foundation of arrogance. Love built people up. Paul said if you are going to know something, know the importance of love. Then Paul said something else that was most strange to the people to whom he wrote and is incredibly strange to us. Not every Christian knows there is just one God and idols are nothing. Some Christians know that, but all Christians do not know that. So Paul said that he would not wound their consciences by eating a food given in sacrifice to a nonexistent god. "Why, Paul? If you have correct knowledge and they are the victims of ignorance, why would you let their ignorance control your behavior?" Bottom line: he understood how much God paid in Jesus' blood for their salvation, and he would not allow knowledge to destroy the saving work of God by destroying someone for whom Christ died. Love is the ultimate, in God, and in those who follow God. I want to share a couple of things with you and I have a very specific purpose in my sharing: I want your thoughts to penetrate to the inner core of your being. I want to begin by stating that I take confidences very seriously. Unless I have permission from the person, I do not even share confidences with my wife. The first thing I want to share with you I have permission to share. When I returned from vacation, a lady I deeply respect told me that while I was gone she acquired a specific set of knowledge. I have worked with, encouraged, and tried to help people for decades. I can assure you that the knowledge she learned would have devastated most Christians. The knowledge she acquired had the potential of bringing major devastation to her life. There was zero question about the authenticity of her knowledge. Her new knowledge was based on unquestionable fact. But in her situation, her love is greater than her knowledge. So instead of her new knowledge bringing devastation, Her love is growing in spite of that knowledge. The greatest challenge that we Christians have is allowing God's love to become the most powerful influence in our lives. It is extremely challenging to let God's love teach us how to love. In no situation or in no relationship will any of us be as forgiving just one time as God already has forgiven each of us in Christ. Never will being compassionate to others cost us as much as God's compassion toward us cost Him--it cost Him the life of his only son WHEN HE COULD HAVE STOPPED IT! Please do not let this happen to you on judgment day. Us: "Lord, that Christian who was baptized into Christ was doing something the wrong way--so I stopped him!" God: "You do realize that I gave Jesus to die for him. Did you love him as much as I do, or did you destroy someone that I sent Jesus to die for?" 1 Corinthians 8:11,12 For through your knowledge he who is weak is ruined, the brother for whose sake Christ died. | Mid | [
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Chinese President Xi Jinping visited Panama on Monday to sign a range of cooperation agreements and extend China's influence in Central America. China only opened diplomatic ties with the nation last year, and with the new deals, Panama became the first Latin American country to sign on to Beijing's vast "Belt and Road" investment initiative. What they agreed upon President Xi and his Panamanian counterpart Juan Carlos Varela signed 19 deals, including: An extradition treaty An arrangement where China will provide a non-specified amount of non-reimbursable aid to carry out various projects. Memoranda of understanding on commercial, tourist, educational matters. Other deals on trade, infrastructure and banking. Read more: China's ambitious foreign policy agenda Watch video 26:00 Share Quadriga - The New Silk Road: China’s Route to Europe? Send Facebook google+ Whatsapp Tumblr linkedin stumble Digg reddit Newsvine Permalink https://p.dw.com/p/2yGXE Quadriga - The New Silk Road: China’s Route to Europe? Connecting two oceans Varela thanked Xi for his visit, and recalled that Xi once told him China's economy was an ocean. "I want to complement those words by saying Panama connects two oceans, and his visit consolidates our country as China's commercial arm and gateway to Latin America," Varela said. Xi said: "Our bilateral relations have had a strong start after only a year and a half." He wrote in a local paper that the two countries must become "cooperative partners of mutual benefit and shared profits." Read more: Dominican Republic opens diplomatic ties with China, drops Taiwan Why is Panama important: China has particular interest in Panama due to its strategic location and its eponymous canal. It is also highly attractive for its political stability, growing economy and financial networks. Beijing hopes to use Panama as a logistics hub to help expand its trade in Latin America and the Caribbean. Usurping US power: Beijing's growing role in Latin America has drawn the attention of the US, sparking fears it is losing influence in its backyard. A series of Latin American countries have made moves to strengthen ties with China, initially by disavowing their recognition of Taiwan. That loss is only being accelarated by the bluster of President Donald Trump against Latin American migrants. Nonetheless, experts have warned Panama faces possible reprisals from the US, the primary user of the Panama Canal, if it gets in the middle of a dispute between the two powers. Further ties: The 19 deals are the start of growing ties. Panama and China are in the midst of negotiating a free trade deal. aw/rt (AFP, Reuters, dpa) Every evening at 1830 UTC, DW's editors send out a selection of the day's hard news and quality feature journalism. You can sign up to receive it directly here. | Mid | [
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That is until Tanzania is fully satisfied that the industrial sugar used to manufacture the sweet, biscuits, chocolates et al from Kenya is not zero-rated in terms of import duty, as Tanzania alleges. According to Tanzania’s Commissioner for Customs and Excise Ben Usaje, a report that was prepared by the East African Community (EAC), that was supposed to shed light on Kenya’s denial of Tanzania’s tax-cheating allegations, is not conclusive and now Tanzania wants the EAC experts that inspected Kenyan firms that manufacture confectioneries to repeat the whole inspection again. "I can tell you for a fact that we know Kenya was not telling the truth on the duty free industrial sugar that was used to manufacture these sweets,”Mr Usaje told the Standard at an interview in Dar es Salaam. “We will keeping charging the Kenyan manufacturers the 25 per cent levy until we are satisfied that EAC experts are thorough in their inspection,” he added. While making the stern statements emphasising why Tanzania will keep charging Kenya the levy, Usaje produced a copy of the EAC inspection team report that Tanzania rejected and pointed out at the conclusions the team made, which Tanzania considers vague and indecipherable. The concussions read in part: “products manufactured using industrial sugar when transferred to the EAC qualify for preferential treatment provided they meet the criteria set under EAC rules of Origin 2015 and any other conditions set under the EACCMA 2004.” A conclusion that Usaje claims gave no pointer on whether Kenyan confectioneries specifically used the sugar under scrutiny or not. | Mid | [
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If a national catastrophe isn’t bad enough, make it worse. That appears to be the thinking behind a decision by New York City officials this week that sent the number of dead attributed to the coronavirus outbreak in the city soaring to more than 10,000 — a 57 percent increase over the previous count. And these are numbers Americans are supposed to trust forevermore. Unfortunately, in a United States where the mainstream media daily shows itself to be ever more corrupt, trust is in short supply. According to The New York Times, New York City’s death count attributed to COVID-19, the disease caused by the coronavirus, was a disastrous 6,589 on Tuesday, before NYC officials announced a decision that increased the death toll by more than half. TRENDING: McConnell Makes His Decision, Announces Senate Will Hold a Vote on Any Nominee Trump Puts Forward To Replace RBG A number of fatalities more than double the deaths that took place in the 9/11 attacks is bad, but clearly not bad enough for the regime of leftist Democrat Mayor Bill de Blasio, which decided to add more than 3,700 deaths that might have been caused by the coronavirus, though no tests could prove it. The added deaths — 3,778, according to Bloomberg — not only increased the number in New York City, of course. They also sent the national death toll to more than 26,000, an increase of 17 percent, The Times reported. Now, there’s no doubt at least some of those deaths could be attributed to COVID-19 since, as Bloomberg reported, the deceased showed symptoms including coughing, shortness of breath and fever, hallmarks of the deadly infection. That doesn’t mean all of them should be counted that way. Does NYC artificially raising the death rate from Covid-19 seem fishy? Yes No Completing this poll entitles you to our news updates free of charge. You may opt out at anytime. You also agree to our Privacy Policy and Terms of Use. You're logged in to Facebook. Click here to log out. 98% (134 Votes) 2% (3 Votes) It’s an artificial number, serving a need that’s very real to Democrats and the mainstream media. In a nutshell, there’s no doubt that inflated COVID-19 numbers will end up being used as a weapon against President Donald Trump in the 2020 presidential election. As distasteful as the idea is, it wouldn’t be the first time magically inflated death counts from a national tragedy will have been used by the president’s opponents in the Democratic Party and the mainstream media (at the risk of redundancy) to attack the Trump administration. As The Times article itself noted, New York Health Commissioner Dr. Oxiris Barbot recalled a somewhat similar count revision related to the deaths caused by Hurricane Maria’s strike on the island of Puerto Rico in September 2017. In that case, the death toll went from 64, a figure that was accepted for almost a year, to almost 3,000, according to an estimate accepted by the Puerto Rican government in August 2018. The reason? Studies had determined that “excess deaths” on Puerto Rico in the four months after the hurricane struck should be attributed to conditions on the island caused by the storm, according to CBS News. Hence, a death toll that was tragic, but small, became a death toll to rival 9/11. Again, it’s possible that some of the 2,975 deaths attributed to Maria were actually caused by the storm, at least indirectly. But it’s more than possible that certain political and media institutions that are inextricably allied had a reason to push the higher number. And it just happened to be right before the 2018 midterm elections when Democrats wanted every weapon they could get to try to take control of the House of Representatives and launch the impeachment proceedings their base had been dreaming of since November 2016. With Trump himself on the ballot in 2020, that Democratic drive to get out the vote is only going to be stronger — and if that means conjuring up thousands of corpses caused by the coronavirus, Nancy Pelosi & Co. are not above playing games like that. That’s not to mention the amount of federal aid that will be coming to affected cities — money that will no doubt be increased with the size of the tragedy affecting individual locations. Again, it’s distasteful, it’s crass, but it’s a fact — the worse off a city can look, the better it can do. And that’s just in New York. As the incomparable Andrew McCarthy pointed out at National Review on Wednesday, it could happen everywhere else in the country where the coronavirus has exacted a heavy toll. “And if the Big Apple is going to cook the books this way, what is to stop Newark, New Orleans, Philadelphia, Boston, Chicago, Detroit, Los Angeles, and the rest?” McCarthy wrote. The feds have basically encouraged this but…”if the Big Apple is going to cook the books this way, what is to stop Newark, New Orleans, Philadelphia, Boston, Chicago, Detroit, Los Angeles, and the rest?” https://t.co/Sk7ZCiTOLf — Brit Hume (@brithume) April 15, 2020 McCarthy didn’t point it out, and his post didn’t dwell on the politics or financial aide side of it all, but all of the cities he cited are deep-blue Democratic strongholds. Social media users noticed it though, and knew what that meant. Cooking the books = scare tactics and fraud rolled into one! Is there no decency left? — liliana murray (@MurrayLiliana) April 15, 2020 Dems chest at everything… even deaths! Monitor and investigate!!! — Peggy Campbell (@pcampbell88) April 15, 2020 It’s “science” this virus has exposed the total manipulation of science — Hayden (@cantwellland) April 15, 2020 That last one hit it right on the head. Democrats claim to be the party of “science,” but what matters is the progressive political agenda. The same desire for power that drives climate change “models” drives estimations of tragedies like Hurricane Maria on a local scale to COVID-19 on a national scale. These are the numbers that are going to be turned into political attacks on Trump and his supporters by the Democratic Party, and they’re going to be echoing through the mainstream media all the way to November and beyond. As bad a catastrophe as the coronavirus has been, Democrats are dying to make it worse. This article appeared originally on The Western Journal. | Low | [
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Prebiotic effects of cassava fibre as an ingredient in cracker-like products. Cassava fibre, a waste product formed in starch production, was incorporated into wheat to give composite flours at ratios of 80/20, 70/30, 60/40 and 50/50, respectively. A cracker-like biscuit was produced from the preferred ratios (60/40 and 50/50). The effects of these on diets as a prebiotic were evaluated in a rat assay. Determinations of the proximate composition and haematological parameters were made as well as microbiological analysis. The protein content of the cracker-like product based on the 50/50 and 60/40 (fibre/wheat flour) ratios were 15.0% and 10.0%, respectively. Crude fibre ranged from 14.1-17.1% while ash ranged from 3.0 and 5.0%. Low cholesterol levels of 28.75 mg dL(-1) and 18.75 mg dL(-1) were recorded for the 50/50 and 60/40 composite ratios, respectively. The result of liver function test showed that the rats that were fed the fibre-based cracker product had an average value of 44.00 IU L(-1) of aspartate amino transferase (AST), which is lower than the 67.75 IU L(-1) recorded for the control. There was a significant increase in the packed cell volume (PCV) of the rats fed a fibre-based diet, relative to those fed "Ogi" (fermented maize). Haemoglobin was significantly higher in the control sample than all others, while no significant difference was observed in the white blood cell (WBC) count, with average of 11.75 mm(3). Data obtained from the faecal analysis showed that the rats fed with the composite ratios and other diets had an increased Lactobacillus count. However, by increasing the number of days that the rats were fed the fibre-based diet, the E. coli count in the rat faeces reduced significantly. The data obtained shows that cassava fibre-based crackers have good nutraceutic effects, with reduction in the E. coli count found in the rat faeces and healthy performances in terms of weight gain. | Mid | [
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Shoebot 1.0b ! Shoebot 1.0b ! Hi list! So Libre Graphics Meeting 2014 is ongoing, and for the first time there was a Shoebot developer meeting :-) Stuart and I hosted a workshop/hackathon yesterday, which resulted in a packed room of hackers doing beautiful new examples for inclusion in Shoebot. It was also a great moment to see Stuart's exciting work in the livecoding branch, and get some precious feedback from real-world usage(tm). After discussing next moves, we decided it was well time to follow Inkscape's example and move to a 1.0 release ASAP, since 0.x necessarily convey a state of non-maturity. Shoebot has been continuously improved for 7 years (yeah!), and we decided to ride the post-workshop excitement and move things forward. Some new things here: * New Github hosted website; maintenance of the previous site was hampering efforts to make it better, so we just rebooted it on Github's platform. * More examples! * Small and not so small fixes. See the commit list for the poor-man's changelog. * The Sphinx docs are being improved and we'll hopefully have good news in the next few weeks as I document what's not yet there. So yes, Shoebot is alive and well :-) Let us know if you have any issue you think should be looked at before we move to a 1.0 release + announcement. Re: Shoebot 1.0b ! > Hi list! > > So Libre Graphics Meeting 2014 is ongoing, and for the first time there > was a Shoebot developer meeting :-) > > Stuart and I hosted a workshop/hackathon yesterday, which resulted in a > packed room of hackers doing beautiful new examples for inclusion in > Shoebot. It was also a great moment to see Stuart's exciting work in the > livecoding branch, and get some precious feedback from real-world usage(tm). > > After discussing next moves, we decided it was well time to follow > Inkscape's example and move to a 1.0 release ASAP, since 0.x necessarily > convey a state of non-maturity. Shoebot has been continuously improved > for 7 years (yeah!), and we decided to ride the post-workshop excitement > and move things forward. > > Some new things here: > > * New Github hosted website; maintenance of the previous site was > hampering efforts to make it better, so we just rebooted it on Github's > platform. > > * More examples! > > * Small and not so small fixes. See the commit list for the poor-man's > changelog. > > * The Sphinx docs are being improved and we'll hopefully have good news > in the next few weeks as I document what's not yet there. > > So yes, Shoebot is alive and well :-) Let us know if you have any issue > you think should be looked at before we move to a 1.0 release + > announcement. > > Cheers, > :r > _______________________________________________ > Shoebot-devel mailing list > [hidden email]> http://lists.tinkerhouse.net/listinfo.cgi/shoebot-devel-tinkerhouse.net> For this, you would only need to move the 'gh-pages' branch from the 'shoebot' named repo to a 'shoebot.github.io' named repo. This would maybe also simplify updates to the website and separate it from the main shoebot dev. > Hi list! > > So Libre Graphics Meeting 2014 is ongoing, and for the first time there > was a Shoebot developer meeting :-) > > Stuart and I hosted a workshop/hackathon yesterday, which resulted in a > packed room of hackers doing beautiful new examples for inclusion in > Shoebot. It was also a great moment to see Stuart's exciting work in the > livecoding branch, and get some precious feedback from real-world usage(tm). > > After discussing next moves, we decided it was well time to follow > Inkscape's example and move to a 1.0 release ASAP, since 0.x necessarily > convey a state of non-maturity. Shoebot has been continuously improved > for 7 years (yeah!), and we decided to ride the post-workshop excitement > and move things forward. > > Some new things here: > > * New Github hosted website; maintenance of the previous site was > hampering efforts to make it better, so we just rebooted it on Github's > platform. > > * More examples! > > * Small and not so small fixes. See the commit list for the poor-man's > changelog. > > * The Sphinx docs are being improved and we'll hopefully have good news > in the next few weeks as I document what's not yet there. > > So yes, Shoebot is alive and well :-) Let us know if you have any issue > you think should be looked at before we move to a 1.0 release + > announcement. > > Cheers, > :r > _______________________________________________ > Shoebot-devel mailing list > [hidden email]> http://lists.tinkerhouse.net/listinfo.cgi/shoebot-devel-tinkerhouse.net > Hi list!> > So Libre Graphics Meeting 2014 is ongoing, and for the first time there> was a Shoebot developer meeting :-)> > Stuart and I hosted a workshop/hackathon yesterday, which resulted in a> packed room of hackers doing beautiful new examples for inclusion in> Shoebot. It was also a great moment to see Stuart's exciting work in the> livecoding branch, and get some precious feedback from real-world usage(tm).> > After discussing next moves, we decided it was well time to follow> Inkscape's example and move to a 1.0 release ASAP, since 0.x necessarily> convey a state of non-maturity. Shoebot has been continuously improved> for 7 years (yeah!), and we decided to ride the post-workshop excitement> and move things forward.> > Some new things here:> > * New Github hosted website; maintenance of the previous site was> hampering efforts to make it better, so we just rebooted it on Github's> platform.> > * More examples!> > * Small and not so small fixes. See the commit list for the poor-man's> changelog.> > * The Sphinx docs are being improved and we'll hopefully have good news> in the next few weeks as I document what's not yet there.> > So yes, Shoebot is alive and well :-) Let us know if you have any issue> you think should be looked at before we move to a 1.0 release +> announcement.> > Cheers,> :r> _______________________________________________> Shoebot-devel mailing list> [hidden email]> http://lists.tinkerhouse.net/listinfo.cgi/shoebot-devel-tinkerhouse.net Re: Shoebot 1.0b ! Thank you so much for the easy explanation. I had used the auto-generator in GitHub since 1. I haven't used GitHub pages before and 2. wanted to get something out as quickly as possible. It's now up in a nicer URL: The site is still plain HTML, which is what GitHub generates. I want to change it to proper Jekyll Markdown so that it's easier to edit, as well as customising the theme, but for now the current site is miles ahead of the old shoebot.net. I now realise that meeting up or working in parallel via IRC are great ways to move things forward. Wondering if we could consider an online hackathon in the near future? Perhaps even consider a physical meetup? > Hello Ricardo and shoebot list > > Congrats on the workshop yesterday. It was awesome. > >> * New Github hosted website; maintenance of the previous site was >> hampering efforts to make it better, so we just rebooted it on Github's >> platform. > > About the site. If I may suggest. I think the > http://shoebot.github.io/shoebot/ is a bit too long and could be > simplified to http://shoebot.github.io (with now returns 404) > > For this, you would only need to move the 'gh-pages' branch from the > 'shoebot' named repo to a 'shoebot.github.io' named repo. This would > maybe also simplify updates to the website and separate it from the > main shoebot dev. > > What do you think? > > Julien > _______________________________________________ > Shoebot-devel mailing list > [hidden email]> http://lists.tinkerhouse.net/listinfo.cgi/shoebot-devel-tinkerhouse.net> Re: Shoebot 1.0b ! Hello Ricardo and the list On 05/04/14 15:15, Ricardo Lafuente wrote: > I now realise that meeting up or working in parallel via IRC are great > ways to move things forward. Wondering if we could consider an online > hackathon in the near future? Perhaps even consider a physical meetup? Sorry to write after such a delay. I think setting up IRC meetings for parallel working might be a good idea. I'm in favor of trying that and giving you a little help here and there. On 05/04/14 15:15, Ricardo Lafuente wrote:> I now realise that meeting up or working in parallel via IRC are great> ways to move things forward. Wondering if we could consider an online> hackathon in the near future? Perhaps even consider a physical meetup? Sorry to write after such a delay. I think setting up IRC meetings forparallel working might be a good idea. I'm in favor of trying that andgiving you a little help here and there. On 05/04/14 15:15, Ricardo Lafuente wrote:> I now realise that meeting up or working in parallel via IRC are great> ways to move things forward. Wondering if we could consider an online> hackathon in the near future? Perhaps even consider a physical meetup? Sorry to write after such a delay. I think setting up IRC meetings forparallel working might be a good idea. I'm in favor of trying that andgiving you a little help here and there. Re: Shoebot 1.0b ! On 22/04/14 17:50, Stuart Axon wrote: > Hi, > It looks like I should be able to free up some time this weekend for shoebot, so will be on IRC if there is any interest in shoebot hackery... > > S Hey Stuart. Sorry to reply now. Just seeing your mail today. Was busy all this weekend. I won't be available before next week for any work. When are you (and others? Ricardo?) mostly free to chat/work on this? On 22/04/14 17:50, Stuart Axon wrote:> Hi,> It looks like I should be able to free up some time this weekend for shoebot, so will be on IRC if there is any interest in shoebot hackery...> > SHey Stuart.Sorry to reply now. Just seeing your mail today.Was busy all this weekend. I won't be available before next week for any work.When are you (and others? Ricardo?) mostly free to chat/work on this? | Mid | [
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The invention relates to an electrical system for vehicles for vehicles having a combustion engine, a generator, a starter motor that can be manually activated, a starter battery and a breaker, controlled by a crash sensor and arranged in a starter circuit which includes the starter battery and the starter motor. Electrical systems for vehicles are designed to prevent overheating and overload of wires caused by electrical short circuits in the event of a crash. For this purpose, most circuits are protected from short circuits by use of fuses and/or circuit breakers, except for the starter cable, i.e., the connection between the positive pole of the battery and the starter motor. Because of the high current of the starter motor, there is no suitable fuse for this cable. EP 0 825 068, discloses a starter circuit which includes a breaker that interrupts the flow of current in response to a signal from a crash sensor, wherein the breaker immediately interrupts power to the starter cable in the event of a crash. The breaker may be constructed as a pyrotechnic device which triggers an explosion that interrupts the main path of the current. DE 196 06 448 and DE 44 02 994 respectively show a breaker of this type in the form of a battery terminal which is ordinarily actuated with the assistance of a pyrotechnical blasting cap in cooperation with an air bag sensor. For this purpose, the breaker is provided with two contact pieces whose contacting surfaces normally lie on top of each other and which may be separated from each other by pyrotechnical means, more specifically in the form of a propellant charge, when the vehicle undergoes an abnormally high acceleration. According to DE 44 25 307, the propellant charge may constitute a structural part of a battery terminal. All of the prior approaches result in a permanent interruption of the starter circuit when a crash occurs. As a result, the vehicle cannot be started after the crash sensor has been triggered. This is particularly disadvantageous when the air bag sensor is triggered on account of a failure, or in a minor accident, when the driver would like to at least drive the car to the garage. In such a case, the vehicle can no longer be moved without repair. An electrical system for vehicles is described in DE 40 28 242 wherein there is provided a second battery for supplying electrical accessories, in addition to a starter battery. The two batteries are connected together when the voltage of the electrical system battery is higher than the voltage of the starter battery. Conversely, when the voltage of the electrical system battery has dropped relative to the voltage of the starter battery, the two batteries are separated from each other. Accordingly, the generator is capable of recharging both batteries. In this solution, the second electrical accessory battery and the starter battery are permanently connected in parallel and the starter battery alone may be disconnected by a starter battery breaker in the starter circuit. A diagram of connections for achieving an appropriate function in connection with the above mentioned reference is described in DE 38 41 769. WO 96133078 describes a battery terminal cooperating with a switch in the line leading to the battery, the switch being provided with monitoring means for controlling the switch in accordance with the signals received at its monitoring inputs. It is the object of the present invention to make it possible to restart vehicles having a starter circuit breaker after response of the crash sensor and the irreversible interruption of the starter circuit in response thereto. According to the invention, there is provided a bypass electrical switch which may be actuated by a control circuit, that is used in to detect whether there is a short circuit in the starter circuit, such that, after interruption of the starter circuit on account of a activation of a breaker, an electrical connection may be re-established between the starter and a battery in the starter circuit by the bypass switch, when the starter circuit is free from any short circuit. A feature of the preferred embodiment of the invention is that a bypass-switch is arranged to re-connect the starter circuit when the control circuit senses that the starter circuit is free from any short circuit. Thus, the engine may be re-started when the mechanical damage occasioned by the crash is not so severe as to destroy the functionality of the starter. The energy source which is connected by the bypass switch to the starter circuit may be any available battery within the electrical system. The solution according to the invention is independent of the position of the breaker, which may also, e.g. be located in the ground cable of the starter battery. According to a preferred embodiment of the invention, the bypass switch is preferably arranged parallel to the breaker, to thereby restore an electrical connection between the starter and the starter battery. The starter battery is therefore used for restarting the vehicle after the crash (as far as it has not been destroyed). The safety relevant function of the breaker is preserved in that the response of the breaker to the crash sensor prevents overload of the wires in the event of an accident, and on the other hand, the vehicle can be restarted when it is in running order. The electronics of the control circuit senses whether there is any short circuit in the starter wire and triggers the connection means when there is none. In an alternative embodiment of the invention for electrical systems having a second battery, the bypass switch makes an electrical connection between the starter circuit and the second battery of the electrical system in the event the response of the breaker permanently interrupts the starter circuit. The energy source use for the starter thereby is the second battery of the electrical system, which ordinarily is not damaged in a frontal collision, as it may be located in the rear part of the vehicle. In this arrangement, the commutator that is already provided in such vehicles can function as the bypass switch when it is provided with a suitable control circuit for sensing short circuits in the starter circuit. The invention will be more fully explained hereinafter with reference to two exemplary embodiments that are illustrated in the Figures. | Low | [
0.533916849015317,
30.5,
26.625
] |
The definition of panic attacks, Part I. Phenomenological data are presented for panic attacks and non-panic anxiety in 159 patients. Anxiety episodes of sudden onset tend to have greater severity, more symptoms, and shorter duration and some distinctive cognitive features. This cluster of features emerged from the analysis as characteristic of the panic attack. There were no differences between situational and spontaneous attacks nor are attacks occurring in depressed patients different from those in-patients who suffered from anxiety disorders. The ideas characteristic of normal anxiety are directed towards ordeals in the future. It is the immediacy of the anxious cognitions of imminent death, collapse or becoming insane that are characteristic of panic attacks. A definition of panic attacks is suggested. | High | [
0.67612293144208,
35.75,
17.125
] |
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