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17 Years Later, I'm Still Coming Out
Two years ago, I wrote I'm not a boy, but I'm not a girl either. Because it's National Coming Out Day. Because coming out matters. Because telling my story makes room for kids to tell their stories. For allies to hear the stories that make us human. And believing that we're human, that we matter, is what keeps us safe. It keeps people from voting against us. It helps people stand up for us. Or at least that's the hope I like to hold on to.
I've been coming out for 17 years. I thought it would get easier, but it doesn't. For all the voices of support, there are the louder ones that echo. That I'm not enough. That I'm too complicated. That I'm a burden. That I just want attention.
And being a gender nonconforming trans person, I get a lot of attention. I get invasive body searches at airports that leave me hysterical, gasping for breath through tears. I get stared at and questioned in public. I get yelled at and followed and misgendered and embarrassed. I get so much attention.
I don't want attention. I just want some room.
You get to grow and change and are encouraged to be yourself. You're told you can be anything you want. You can follow your dreams. You get to think hard and talk so much about who you are and what you want to be. It's not political. It's life. It's some kind of journey. What about my journey?
I'm coming out of the struggle to fit in a gender binary that didn't have enough room for me. I'm coming out of the restrictions of language and expectations. I'm coming out of something that never worked and felt like trash and oh my god I'm finally free. I wish you could celebrate with me instead of debating the grammatical rules of the pronouns I use. I wish you would celebrate with me instead of questioning why I need to make it so difficult.
I'm coming out because this gender binary cannot work for everyone. Just like good and bad has a whole lot in the middle. And that middle place? That's where the beauty is. It's always in the middle. Right between right and wrong and light and dark and this and that.
I'm coming out because it's hard to be misgendered. Because if you're a woman and I call you a man, you'd be horrified. But you can call me whatever you want, because of convenience. Because it's too complicated to use a different pronoun or different words for me. Even though you use singular they all the time for people you don't even know (listen to the way to you yell at strangers in traffic for an example, "they didn't even use a blinker!" is a good place to start). Because you'd rather argue grammar or make it my problem for complicating your vocabulary than see that this is something I need. This isn't asking too much.
I'm coming out with some kind of gender math of this body and weekly shots of testosterone and how together it somehow equals neither this nor that and goodness it's been exhausting running from this body. This isn't a transition from one to another but more of a settling in to right here. Where you are is where you are.
I'm coming out because trans kids are in trouble. Suicide rates are too high. Trans kids are scared and hurting and we have a responsibility to keep them not just alive but happy and fulfilled and everything every kid deserves.
I'm coming out because the evangelicals are waging a war against trans people and we need help. Trans rights are truly human rights and shouldn't be up for a vote or some kind of political bargain. We are human beings. It shouldn't be this hard.
I'm coming out because kids like me need to know we're not a burden. We're not too complicated. We're not in this for some kind of attention. I'm coming out because there's nothing wrong with us. We're okay. I'm coming out because I'm done with expectations that none of us are really any good at.
I'm coming out because my parents taught me that I could do anything and be anything. I'm choosing to be me.
Listen Up, It's Story Time
Me: Riley, do you like screen time?
Roozle: Kind of. When I do have screens I like it because I get to watch my YouTube videos and I like crafts but when I don't have screens I like it because I get to hang out with you and read my books and I get to have more time with my family.
Me: Do you think that screens make you not have time with your family?
Roozle: When you're like working and you're in the other room while I'm watching screens, it feels like I'm far away from you and I'm alone, but when I don't have screens, I feel more close to you.
Me: What things do you like to do together?
Roozle: I like to go to JP Licks for ice cream, I like to play games with you, I like to go swimming, and I like to eat dinner with you.
Me: Do you know what I like to do with you?
Roozle: No.
Me: I like to listen to stories. Do you like to listen to stories?
Roozle: Yeah!
Me: What did you think about the story we listened to last week about the man who felt a little bit squished in his house?
Roozle: I liked the story, even though I had already heard it before. I liked to listen to the story with you.
Me: I liked that too, that it was another way for us to spend some time together. I really liked the voices and the way they told the story. It was interesting even for this boring grown up. And I like that sometimes we know the stories, but that they're told in a different way. Like with fairy tales.
Roozle: Yeah, I like that too. I love fairy tales.
Me: So right now, we're about to listen to this week's story which is about a dragon, I think. Are you excited?
Roozle: I am excited because I've never heard this story before and I want to know what happens.
Me: Do you think it's going to be scary?
Roozle: I think Stella is a nice name so it won't be scary and this is a story for children.
Me: Well, in case it gets scary, I'm glad we're listening together. Is this something you want to do every week?
Roozle: YEAH! Because I like to listen to stories!
Me: Yeah, me too. And I like to have a routine during the week so we know what to expect each day. Like, on Tuesdays, we go swimming. On Wednesdays, we go to the library.
Roozle: And now on Tuesdays, we listen to stories!
You can listen to Circle Round episodes here and on Apple Podcasts, or wherever you get your podcasts. You can also find Circle Round on Facebook and Twitter.
SPOILER ALERT WE LISTENED TO THE STORY AND TALKED ABOUT IT. Note: the stories come with questions after to initiate conversation, but it was bedtime and we were tired so we went with "What was your favorite part?" which is also my trick question to see how much she was listening.
Me: What was your favorite part of the story?
Roozle: My favorite part was when Stella said that was so powerful and that she could lift the boulder. But she actually couldn't so she tricked the dragon by saying that if she threw the boulder it might hit the moon and then she said that maybe all the pieces would come flying straight for them and the dragon got scared. And then the dragon told her not to throw it because he was scared.
Me: Was that a surprise that the scary dragon was the scared one?
Roozle: Yeah!
Me: I was surprised by that too.
Me: Are you excited about next week?
Roozle: I'm excited about next week because I had never heard that story before and I'm excited to find out what the story is!
Me: Until next Tuesday, Roozle.
Roozle: Until next Tuesday, Apa!
New stories come out every Tuesday, and we're way too excited to wait, so we've picked Tuesdays as our Circle Round days, but subscribing to the podcast means you can listen whenever you want. The stories are from 5-20 minutes and include all kinds of famous people my kid totally doesn't care about, but OMG I DO. And since we're trying to listen to them together, that matters a lot. And bonus points? THEY HAVEN'T USED ANY GENDERED PARENT LANGUAGE SO FAR! WE ARE VERY EXCITED.
This post is sponsored by WBUR's new podcast Circle Round for kids and their grownups, where "story time happens all the time." Opinions are mine, and Roozle's. We have so many opinions. You're never too old or young for a good story.
Parenting Is Better With Friends
I started talking with my kid about alcohol responsibility a long time ago. She was little. It was easy. Because we started with the basics. What is alcohol? What does it do? What are the rules? And then she got older. Now, this new third grader has different questions. Now sometimes these conversations are a bit more complicated. Sometimes she pushes back and the things that were so easy feel like some kind of stand off (the kind with fancy high tops, the best kind, really).
Now she has the ability to see herself a bit beyond where she is now and wonders what kinds of decisions she will make as a teenager or a college student. And sometimes our conversations are better with a little guidance from friends who have been there done that. Just like learning how to wash cloth diapers or figure out the best lunch box to buy for tiny kindergarten fingers to open.
So I asked my friends. Do you drink in front of your kids? And no surprise here, my friends had a lot of good stuff to say.
And what about the times we get it wrong? What about talking with older kids? Do we tell them when we've made a mistake? Do we point out when those around us get it wrong?
Thankfully, we don't have to get this all right on our own. We get to learn from our friends. We get to teach our kids from our own mistakes. We get to do better next time. We get to keep learning what responsibility looks like from all the different angles. And always, we get to keep talking. Talk about the easy things, talk about the hard things. Keep talking, keep listening. Talk with your friends, talk with your kids, all the talking all the time.
This post is sponsored by Responsibility.org. Thank you to all my lovely friends for your willingness to tell your stories to my phone camera.
We're So Complicated: Adventures In Meal Planning
Meal planning is hard. Even on the best weeks. And around here? We don't have many of those. My kid eats early to get to bed early, she's a vegetarian. My partner often works events in the evenings, she's a vegetarian. I've recently started eating meat again, but gave up dairy. We're a mess.
We've tried meal kits, and failed. We've tried fancy bullet journal meal planning, and failed. We've tried to not get take out too much, and failed. But we don't want take out, we want to eat together when we can, we want to shop sales, we want to do better. We just couldn't figure it out.
So when The Dinner Daily asked if we wanted to try it out, I said yes! With enthusiasm! Let's add another plan to our failure list! Except, this one didn't fail. Maybe because we tried harder? Nah, we didn't. Maybe because our schedule was easy this week? Nope, with the first week of school, my kid off to the Cape to visit my parents, my partner away last weekend with friends, a holiday, late nights at work, and even an event, this week was literally the worst week for us to start any kind of meal plan. OMG THIS WEEK THOUGH. Without The Daily Dinner, we would've eaten take out way too much. This post would've been a sobbing Facebook post about how I blew my budget in the first week of the month. Instead, we went out once. Budget saved!
Connected to our local grocery store, we chose our menu, ordered the groceries, and Roche Bros. DELIVERED THEM TO THE HOUSE. Bonus: Roche Bros. even delivers beer, so yes, I would like to add that fancy 12 pack of fall beers to my order! For us, we decided to set our defaults on The Dinner Daily to all dairy free (because it's easy to add dairy to half the recipe and hard to take it out), 5 vegetarian meals (it's easy to add meat), 1 meat meal (for the nights I'm on my own), and 1 seafood meal (for nights when Riley it's here). I told you we're complicated. They don't even mind!
The Dinner Daily works with what's on sale at your chosen store and builds your menu accordingly. Because you're buying the groceries, you're buying the full size of what is included in the recipe allowing for leftovers and super easy modifications. Like how the fajita night turned into quesadilla and guacamole night instead without wasting food. Later in the week, we made veggie tacos with the tortillas and what was left from the fajita ingredients.
Friday night curry on the couch in front of the tv? Yes please. Note: this was supposed to have tofu in it, but the tofu they had us make for it was so good, I ate it all while waiting for the curry to cook. No regrets.
There *was* @TheDinnerDaily's tofu on this plate but it was so good I ate it all while the curry simmered. Regrets. Or success? Can't tell. pic.twitter.com/pJaRiycLhU
— Casey Brown (@lifewithRoozle) September 9, 2017
"If I knew what to make, I'd make it," is my whole life. I never know what to make and never know what to buy to actually make the thing I don't know what to make. What a life! The Dinner Daily helps that. Now I have the groceries for 7 dinners and the plans to follow if I can. And if I run out of time for the recipe, it doesn't mean those tiny little meal kit bags rot and end up in the trash. I can just modify and continue on. SO IT ACTUALLY WORKS.
This post is sponsored by The Dinner Daily and Roche Bros. and all opinions are my own. Opinions are my favorite.
Headaches Are The Worst
Me at every check up, "I get headaches a lot."
My doctor, "How much is a lot?"
Me, "I don't really know, maybe a few a month?"
My doctor, "How long do they last? How do you treat them?"
Me, "I'm not really sure. Sometimes a little while, sometimes a day. I take over the counter pain medicine and caffeine and sleep."
It's really no wonder that my doctor hasn't really been able to help me with my headaches. They're nasty and often and I never track them enough to know how much how bad how long to help her help me. I've tried to watch for what causes them. I've given up drinking beer and wine a few times, thinking maybe that was it. It wasn't. I've gotten more sleep. Sometimes it helps, sometimes it doesn't. I've treated my every-season allergies more consistently. That seemed to help at first, then didn't. I tried a prescription migraine medicine, but only took it once because my pill aversion is stronger than my headaches. So I just keep getting headaches. They ruin weekends. They ruin trips. They ruin mornings and evenings. They sometimes linger. Headaches are the worst.
And yet I keep ending up at the doctor's office with nothing to say.
Because what do I think? In those 15 minutes, I will remember all the headache details? I won't. I never do. Ask me about my kid's scratch on her face, though, and I can tell you a story with full detail. Ask me about her baby milestones and that 18 month appointment where they asked about her communication. Spoiler alert: Roozle had a lot to say.
I kept notes for her, though. I searched what was expected at each appointment and made lists of the milestones she was meeting and the ones she wasn't. I wrote down my concerns and questions. And I brought it all with me. Because as a new parent, you make those 15 minutes with a pediatrician cover an hour's worth of child health and wellness and all the things in between.
Last week, Roozle and I were at her latest wellness visit (pro tip: if you get lazy about scheduling your April child's wellness visit, you'll end up with yearly visits in the summer and she won't ever have to miss school), and her beloved pediatrician told us she's moving. OH NO. This one was Riley's THIRD pediatrician in 8 years and goodness I don't want to do this again.
Then I realized that my own new doctor sees kids! So I moved her. And now I have no excuse. Because when I walk in with 14 pages printed from Doctor Google for my kid's appointments, you know that same doctor will expect me to be as prepared for my own. I'm done treating my own health as somehow less important than my kid's.
I'm starting with these headaches. According to the neurologists Dr. Robert G. Kaniecki and Dr. Stewart J. Tepper, the most important focus of headache tracking is threefold: time, symptoms, and impact. This is where I go terribly wrong, as I spend nearly all my headache focus on triggers—trying to just prevent them—and I consistently fail. And apparently, all headaches aren't the same. Untreated migraines last 4 to 72 hours. Migraines are accompanied by nausea and/or light/sound sensitivity. And for migraines to be considered chronic, headache symptoms of any kind need to show up 15 or more days a month. In order to know any of that, you have to keep track. And sometimes wrap your noggin in a blanket and sleep for a day. Because headaches are the worst.
Time, symptoms, and impact. That's it. If I can keep track of that in a note in my phone, I can let my doctor do the rest.
If you suffer from horrific headaches like I do, learn how to tell your story and take this survey to be entered to win up to $1,000 in prizes because prizes make everything better.
This post is sponsored by Med-IQ and supported by an educational grant by Teva Pharmaceuticals. All opinions are mine, and Roozle's. She has so many opinions.
Mornings Are Hard
Mornings are hard for grownups. Mornings are hard for kids. Mornings are the worst, really. And I need the smallest person in the house to brush her teeth and get herself dressed and omg why do I have to say these things over and over and over every morning. SOS.
"How many times do I have to tell you…"
"Ooooh Apa you hate it when people say that to youuuuu."
Mornings with a kid were making me into the person I don't want to be. So I started leaving her notes.
Everyone loves notes.
The notes were great. The notes worked. But then I had to write notes every morning. Because if I didn't, the kid would be reading for an hour and not dressed and would never ever eat a single morning thing.
The notes got an upgrade to something more permanent. Because mornings are always the worst, but we don't have to ALSO be fighting about the regular stuff in between.
I might need to make myself a fancy list. Maybe then I'd eat something more than a gallon of coffee. Maybe.
There's No Such Thing As "What a boy looks like," Lessons From My 8-year-old On Gender Identity
"Can you always tell when someone is queer?" She hesitated, and nearly not finishing the question. We sat at a window seat for dinner overlooking the busy street. Provincetown on Memorial Day is what queer looks like, I wanted to reply, as we were surrounded by drag queens and rainbows and poodles in tutus. It was her first time there, and she was starting to understand. And along with that understanding, she was beginning to piece together the stereotypes that go with all of it, and the problematic erasure that comes along for the ride.
I'm not going to tell my kid this time
I'm not going to tell my kid about the bombing, this time. And yes it's the privilege of being unaffected enough to not have to, I know. After the Boston Marathon bombings here, I know the other side of that, too.
I know all the reasons to tell her. I've written some of them here before, but this time feels different. Too close to her childhood, maybe. Too close to her understanding that those were kids just like her. Too close to why is everything so terrifying.
I'm scared a lot of the time. She will be too, soon enough, I imagine. But she doesn't need to be yet.
I don't want to tell her. And if she finds out and asks more? This time, I'm keeping it simple. Vague even. Maybe for her. Maybe for me. This time is too many times. This time is too much. This time shouldn't be again.
I've turned off the radio. I bought a subway pass for the week and left the car at home. I don't want to hear about it. Let's go to the playground. Let's take the way too old dog for a way too long walk. Because being a part of something bigger sometimes starts in the neighborhood.
This time, I don't need to know every detail. I'm not going to solve the world's problems by scrolling through Twitter. I don't need to process or wonder or hear any of it to know that this, again, is devastating. I don't need to tell my kid and I don't need anyone to tell me. Not this time. I can't do it this time. This time is just too many times. There's nothing left to say.


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Fergie And Josh Duhamel Are Expecting A…. (VIDEO)
Subscribe to My 103.5 FM on
I love Josh Duhamel. He's from North Dakota and does a lot to give back to his home state. He is married to Fergie from The Black Eyed Peas and they are expecting a baby. Josh was on Live with Kelly & Michael and he revealed the sex of the baby! Watch the video to see what gender they will be having soon!

subset: commoncrawl


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Garen Humor Guide by khlex
Not Updated For Current Season
This guide has not yet been updated for the current season. Please keep this in mind while reading. You can see the most recently updated guides on the browse guides page.
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Garen Build
Ability Sequence
Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Hey and welcome to my first mobafire build featuring Garen, as you probably can see(if you don't have problems with your eyes or something, but then you can not read this either).
For runes,
I take 22 Greater Marks of Potency for an early game advantage.
I take 3 Greater Seals of Intellect for an extra mana boost.
I take 2 Greater Glyphs of Potency also for an early game advantage.
I take 11 Greater Quintessence of Force for an late game advantage.
Take the masteries I have if you have a brain. They give you everything you need, Ability Power and Mana. It can't be better!!
I actually think you should pick these items, anything else is stupid.
Well, you could change one Archangel's Staff for an Dorans Ring if you are looking after extra survivability, though I think you already have enough. Also, you can get an Augment: Death if you want to.
Skill Sequence
As you can see, I'm picking Demacian Justice in lvl 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and 18 as this is the best skill sequence.
This will give you a high damage output. You will kill everything with 100%hp and up.
Summoner Spells
I am using Clarity and Clarity, you are in need of loads of mana and then this is your best choice. You should never pick anything else. NEVER!
Ranked Play
If you want to play ranked with Garen, follow this build exactly. You have a 102% chance to win!
Pros / Cons
If you follow this build, you will certainly win
High damage
Not very squishy
Team Work
Team work!? That is for *******! Go alone, overextend and then whine at your team when you die. THAT is how a real player plays.
Unique Skills
Garens Unique skill is that he can make swords fall down from the sky, take this to your advantage and kill your enemies from the skies.
Farm 24/7. This will make you afford your items faster and do more damage. If an AD carry tells you he is supposed to get all the minion kills cuz you are a tank, whine in all-chat and report him.
Veigar can be a big threat sometimes, therefore you should make a big sword fall down in his head and knock him out.
Morgana and Lux can be really annoying sometimes with their snares, therefore you should make big swords fall down in their heads too.
Jarvan IV only came in fourth place, therefore he is mad and wants to kill you(It can be because of you raped his doughter during the race, but I don't think so). You should make a sword fall down on him to survive yourself.
Watch out for Master Yi's CC's, they are really fu*king annoying.
Garen is a real fu*king OP champ, but only if you play him AD. That is why you are supposed to play him AP, no one will call you a noob then.
If an AD Garen kills you, just start whining and report him after the game.


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De Niro calls Trump's political bid 'crazy'
Trump is seriously contemplating challenging current U.S. leader Barack Obama for the White House next year (12) and his potential presidential run has been a regular topic in the headlines over the last few weeks.
The property mogul has been vocal about his disapproval of the current president and has raised doubts over whether Obama was born in the U.S., and his comments prompted comedian Jerry Seinfeld to pull out of a planned appearance at a charity event linked to Trump.
De Niro has now become the latest star to remark on Trump's political challenge, telling NBC News' Brian Williams, "How did we get to this point?… This is crazy. I won't mention names, but certain people in the news the last couple (of) weeks, just, what are they doing? It's crazy. They're making statements about people that they don't even back up. Go get the facts before you start saying things about people."
The Oscar-winner refused to name Trump, but when Williams asked whether the person he was talking about had a TV show on NBC – referring to Trump's Celebrity Apprentice – De Niro replied, "Yes. It's like a big hustle. It's like being a car salesman. Don't go out there and say things unless you can back them up. How dare you? It's awful. Just go out there and speak and say these terrible things? It's crazy."


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|Home | About | Journals | Submit | Contact Us | Français
Rare mitochondrial mutations cause neurologic disease including ischemic stroke and MRI white matter changes. We investigated whether common mitochondrial genetic variants influence risk of sporadic ischemic stroke and, in patients with stroke, the volume of white matter hyperintensity (WMHV).
In this multicenter, mitochondrial genome-wide association study (GWAS), 2284 ischemic stroke cases and 1728 controls from the International Stroke Genetics Consortium were genotyped for 64 mitochondrial single nucleotide polymorphisms (SNPs). Imputation resulted in 144 SNPs, which were tested in each cohort and in meta-analysis for ischemic stroke association. A genetic score of all mitochondrial variants was also tested in association with ischemic stroke.
No individual SNP reached adjusted significance in meta-analysis. A genetic score comprised of the summation of contributions from individual variants across the mitochondrial genome showed association with ischemic stroke in meta-analysis (OR = 1.13, p < 0.0001) with minimal heterogeneity (I2 = 0.00). This ischemic stroke score was robust to permutation, and was also associated with WMHV in 792 nested case individuals with ischemic stroke (p = 0.037).
In this mitochondrial GWAS of ischemic stroke, a genetic score comprised of the sum of all common variants in the mitochondrial genome showed association with ischemic stroke. In an independent analysis of a related trait, this same score correlated with WMHV in stroke cases. Despite this aggregate association, no individual variant reached significance. Substantially larger studies will be required to identify precise sequence variants influencing cerebrovascular disease.
Rare diseases caused by gene mutations encoding mitochondrial proteins often result in neurologic manifestations, including seizures, optic atrophy, white matter MRI abnormalities, and ischemic stroke [1,2]. Because mitochondrial proteins are encoded within both the nuclear and mitochondrial genomes, mutations within either can result in mitochondrial disease, with resultant differences in inheritance patterns. Neurons are highly susceptible to such mutations because of their sensitivity to impaired mitochondrial energy metabolism [3].
Ischemic stroke is a heritable disease [4], and recent data suggest there may be a maternal inheritance pattern – the hallmark of a disorder related to mitochondrial DNA [5]. Traditional genome-wide association study (GWAS) approaches, which have focused on the nuclear genome, have included only limited coverage of sequence variation in the mitochondrial genome. Genome-wide coverage of common variation within the mitochondrial genome requires custom genotyping because the current generation of whole genome arrays does not provide complete coverage of common variation in the mitochondrial genome. While recent GWAS have identified promising loci where common autosomal genetic variants may alter the risk of ischemic stroke [6], no study has yet identified an association between individual common mitochondrial variants and ischemic stroke.
The mitochondrial genome predominantly encodes proteins functioning in the oxidative respiratory chain, thereby impacting energy metabolism [7]. Due to the high energy requirements of endothelial and neurologic tissues, we hypothesized that common variants in the mitochondrial genome may play a role in ischemic stroke, and that any variants that emerge may also influence the burden of white matter hyperintensity volume (WMHV), an established determinant of risk of stroke recurrence and degree of recovery from stroke [8,9].
To explore this hypothesis, we performed a multi-center mitochondrial GWAS (mtGWAS) of ischemic stroke with a panel of single nucleotide polymorphisms (SNPs) covering all common variation in the mitochondrial genome. Four centers within in the International Stroke Genetics Consortium (ISGC, http://www.strokegenetics.org) participated. Association testing was performed for all-cause ischemic stroke. A genetic score-based approach was used to combine effects of all mitochondrial SNPs in analysis, to assess the cumulative impact of multiple mitochondrial variants on respiratory chain function. This genetic score was further applied to WMHV as a biological extension to a related phenotype.
Samples were contributed by the Massachusetts General Hospital Ischemic Stroke GWAS (MGH) (n = 1236) [10], the University of Cincinnati Greater Cincinnati and Northern Kentucky Stroke Study (GCNKSS) (n = 749) [11], the Jagiellonian University (Krakow, Poland) Stroke Study (JUSS) (n = 981) [12], and investigators participating in either the Ischemic Stroke Genetics Study or the Siblings With Ischemic Stroke Study (ISGS/SWISS) (n = 1046) [13,14] [Table 1]. All of these participating studies utilized a prospectively enrolled hospital-based case-control study design. Analysis of WMHV was restricted to ischemic stroke cases from individuals in the MGH and ISGS/SWISS datasets (n = 792). Individuals with T2-FLAIR sequences of sufficient quality for quantification on cranial MRIs obtained < 72 hours after admission for stroke were included in the WMHV analysis. All Institutional Review Boards approved the study, and all participants gave informed consent for data collection, genotyping, and analysis of genetic data.
Case and control recruitment and phenotype ascertainment were performed in each cohort as described previously [10–14]. Cases were all consenting adults presenting to the emergency department of each participating institution for evaluation of acute stroke. For the purposes of this study, individuals were defined as ischemic stroke cases in the presence of (1) a radiographically proven infarct associated with an appropriate clinical syndrome, or (2) a fixed neurologic deficit persisting > 24 hours, consistent with a vascular event, without evidence of demyelination or non-vascular disease. All samples within the ISGS/SWISS, GCNKSS, and MGH datasets were assessed and Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes [15] were assigned by a neurologist. As in the original classification, infarct area, but not white matter burden, was considered in assigning TOAST subtype diagnosis. All controls were recruited from the same populations as the cases, and were confirmed to be free of stroke symptoms by interview and review of medical records. All clinical information, demographics, and comorbidities were abstracted prospectively by patient or proxy interview, and/or supplemented through medical chart review.
Common mitochondrial variants were genotyped according to a validated protocol, with selection of 144 SNPs capturing 100% of variants with MAF > 0.01 in Europeans [16]. A total of 64 tagging SNPs were selected to capture all common variation outside the hyper-variable D-loop, and genotyping was performed with use of a Sequenom platform (San Diego, CA, USA). Haplotype-based imputation was used to capture the remaining 80 variants (all r2 ≥ 0.8 with directly-genotyped SNPs). . All genetic analysis was performed using PLINK v1.07 [17].
Quality control of genotyped individuals included filters for missingness by individual > 0.1, missingness by SNP > 0.1, and minor allele frequency (MAF) < 0.005 [Supplementary Figure S1]. The MAF filter was set after empiric assessment of MAF in the current study population and in previously published data [16].
European haplogroups (H1, H2, I, J, K, T, U, pre-HV, and W/X) were assigned according to previously published methods [18]. A total of 1074 complete sequences from the 10 most common European haplogroups were downloaded from mtDB (http://www.genpat.uu.se/mtDB/). From these sequences, the genotypes at tagging SNP loci were determined and used as predictors in a linear discriminant function analysis in R v2.10.0. The accuracy of prediction of haplogroup was determined using a bootstrap cross-validation approach, and determined to be >98.5%.
Only individuals of European ancestry were analyzed. Principal component analysis (PCA) has been identified as a robust means to control confounding by population stratification [19,20]. Population structure was assessed by performing PCA on all SNPs passing quality control. PCA was performed using the EIGENSOFT v3.0 software package [19] and confirmed using Multidimensional Scaling in PLINK v1.07. Principal components (PCs) 1 – 10 were extracted for each individual, and PCs were added until no additional reduction in mitochondrial genomic inflation factor (mtGIF) could be achieved (PC1–5 for all analyses) [Figure S2].
We determined statistical power for identification of association between analyzed variants and ischemic stroke at α = 0.00035 (144 independent tests). Power calculations specific to mitochondrial analysis were performed using a simulation-based method published in a prior study [18]. Power estimates were by Monte Carlo simulation, with power differences averaged over the observed distribution of MAF. Power was calculated for effect sizes of 1.2, using a haploid model with MAF 0.05, and disease prevalence of 0.03 [21]. Post-hoc power calculations were performed similarly, using assumptions of MAF and effect size based on data from meta-analysis results. Power estimation for the haplogroup-based meta-analysis was performed according to published methods using Monte Carlo permutation testing [22]. Because each haplogroup represents a variable proportion of the study population, detectable odds ratios at power 0.80 were assigned independently for each haplogroup, assuming α = 0.05.
Genotype data were analyzed using an allele-based model, with odds ratio (OR) expressing the effect of the reference allele. All analyses included age, sex, and PC1–5 as covariates. Statistical significance was defined as Bonferroni-adjusted p-value for 144 independent tests. Association tests by study were combined in meta-analysis with a conservative, random-effects pooling method (DerSimonian-Laird), using R v2.10.0. SNPs that did not pass quality control filters in at least 3 studies were excluded, leaving 121 SNPs. Reference alleles were checked to ensure concordance, and MAFs were inspected by cohort.
European haplogroups were tested in a case-control logistic regression for ischemic stroke, using age and sex as covariates. Pooled results from each study were then used in a random-effects meta-analysis accounting for site. For this haplogroup-based analysis only, an additional cohort of 481 cases and 537 controls of European ancestry from the University of Maryland Genetics of Early Onset Stroke (GEOS) study were incorporated into the meta-analysis. These individuals had sufficient genotyping for haplogroup assignment, but lacked the comprehensive mitochondrial genotyping needed for the remainder of the study.
Combined effects of all mitochondrial SNPs were evaluated using a score-based method previously used to assess the cumulative effect of loci affecting lipid levels, risk for myocardial infarction, blood pressure, and schizophrenia [23–26]. Briefly, meta-analysis results were extracted for SNPs passing quality control filters in all 4 cohorts, resulting in 90 SNPs available across all 4 studies. The stroke risk conferred by each SNP (expressed as a beta coefficient) was then applied to each individual in the dataset, with the sum of all SNP beta coefficients resulting in the "score" for each individual [Figure 1]. This genetic score was then divided into quintiles and used as the dependent variable in a logistic regression for ischemic stroke, with age, sex, site, and PC1-PC5 used as covariates. Because only one test was performed in this analysis, Bonferroni correction was not necessary. Results from each cohort were meta-analyzed using the meta library for R v. 2.10.0. Power estimation for association with the genetic score was performed using R (http://www.r-project.org), v2.10.0, assuming an effect size of 1.20 (per risk score quintile) for ischemic stroke, and explanation of 1% of variance for WMHV.
To test the results of the genetic score analysis against the null hypothesis and limit the possibility of false positive association, two forms of permutation were employed using R v2.10.0. In the first method, case and control assignment was randomized in 10,000 permutations, betas and scores were re-calculated, and tests for association with the permuted case/control status were performed.
In the second method, the beta coefficients used to generate the score were assigned randomly to different SNPs in 10,000 iterations, scores were re-calculated, and these scores were then tested against the original case/control status. For both methods, the empiric p-value reported is defined as the number of times the observed test-statistic in permutation was superior to the test-statistic of the original dataset, divided by the number of permutations (10,000).
MRI scans performed within 72 hours of stroke onset were converted from DICOM to Analyze format using MRIcro software (University of Nottingham School of Psychology, Nottingham, UK, www.mricro.com) for computer-assisted determination of WMHV. All WMHV measurements were performed at MGH. Using MRIcro, a region-of-interest map of supratentorial WMHV was created by signal intensity thresholding followed by manual editing as necessary [27,28]. Axial T2 fluid attenuated inversion recovery (FLAIR) sequences were used to create the WMH maps. Areas of signal change from previous infarctions were not considered WMH and the corresponding brain regions were masked. In order to correct WMHV for head size we used the sagittal midline cross-sectional intracranial area (ICA) as a surrogate measure of the intracranial volume, according to a previously validated method [29]. The intracranial cavity was manually outlined on the two most mid-sagittal T1-weighted slices using MRIcro software, and the areas were averaged. All MRI measurements were performed centrally by readers blinded to clinical data, including functional outcome and TOAST subtype assignment.
The genetic score for each individual developed using the ischemic stroke phenotype was divided into quintiles to improve normality of distribution, and applied as a dependent variable in linear regression of WMHV. Additional covariates included age, sex, site, and PC1–5. Results were reported as a coefficient and p-value for association between the ischemic stroke genetic score and WMHV.
We performed permutation testing of the association between the ischemic stroke mitochondrial genetic score and WMHV through 10,000 permutations with randomization of the WMHV phenotype. Permutation testing was performed in R v2.10.0. Permutation empiric p-value is reported as the number of times the observed test-statistic in permutation was superior to the test-statistic of the original dataset, divided by the number of permutations (10,000).
5,912 individuals from the four cohorts had mitochondrial genotype information available. After quality control filtering, 2284 cases and 1728 controls remained for analysis of ischemic stroke. Filtering of mtGWAS data was applied to the initial pool of 64 SNPs, and after imputation, 109 – 132 SNPs remained for analysis within the four cohorts [Supplementary Figure S1]. Of these, 121 SNPs were common to at least 3 cohorts, and 90 SNPs were common to all four cohorts [Supplementary Table S1]. Population stratification was assessed by calculating the mtGIF for each study after incorporation of PCs [Supplementary Figure S2]. In pooled analysis of the 90 shared SNPs, the mtGIF was 1.00 after correction for PC1-PC5.
Given our sample size, our study had power of 0.99 to detect an effect size of 2.0, given an expected MAF of 0.05 and disease prevalence of 0.03. Our power fell to 0.04 to detect effect sizes of 1.2. To achieve power of 0.8 to detect effect sizes of 1.2 at this MAF would require 13,638 cases with matching controls. For association between individual haplogroups and ischemic stroke, detectable odds ratios at power 0.80 varied from 1.18 for haplogroup H to 2.80 for haplogroup I as risk alleles, and 0.84 for haplogroup H to 0.36 to haplogroup I as protective alleles [Supplementary Table S2]. For analysis of WMHV, our genetic score analysis had 0.85 power to explain 1% of the variance in WMHV, assuming for WMHV α = 0.05.
No individual SNP in any cohort met the pre-specified significance threshold of p < 0.00035. In meta-analysis of all cohorts, again no individual variant reached statistical significance [Table 2]. While there was significant heterogeneity (I2 > 40%) for a minority of SNPs (n = 14), none of the leading association results showed significant heterogeneity (all I2 < 40%). Accordingly, MAF concordance between cohorts was excellent (average Spearman correlation coefficient: 0.92, range 0.90 – 0.95, all p < 0.0001).
We tested all European haplogroups in meta-analysis (MGH, ISGS/SWISS, GCNKSS, JUSS, and GEOS cohorts) for association with ischemic stroke. No significant link between any particular haplogroup and ischemic stroke was identified [Table 3]. In particular, using our larger cohort and rigorous control for population stratification [20], we failed to replicate the findings of association with H1 and pre-HV haplogroups [30] and K haplogroup [31] as previously published. Using our power calculations [Supplementary Table S2], we had power > 0.99 to detect these associations at the effect sizes reported [30,31].
In examination of all SNPs in meta-analysis, the median MAF was 0.032, with average effect sizes of 1.09 for risk alleles and 0.92 for protective alleles. We recalculated study power under these assumptions, both for risk and protective variants. Average study power for risk alleles was found to be 0.002, while power for protective alleles was 0.0017. To achieve power of 0.80 with this MAF and effect size would require over 80,000 cases with matching controls.
We performed a genetic score-based analysis in order to assess the possible effects of multiple mitochondrial variants acting in concert to influence respiratory chain function. Using the effect sizes generated in meta-analysis for SNPs passing quality control filters in all cohorts [Supplementary Table S1], we computed genetic score values for all individuals [Figure 1]. These values were then used in logistic regression for association with ischemic stroke, both in each cohort as well as in meta-analysis of all cohorts [Figure 2, Table 4]. This genetic score analysis had power of 0.99 to detect an effect size of 1.20 for ischemic stroke per risk score quintile. Our mitochondrial genetic score was strongly associated with ischemic stroke in meta-analysis (OR 1.13, 95% confidence interval 1.06 – 1.20, p < 0.0001), and showed very little between-study heterogeneity (I2 = 0%). The odds ratios shown in Table 4 represent the risk of ischemic stroke for each quintile increase of the mitochondrial genetic score. This result was robust to permutation by both case-control switching (p = 0.0012) and beta randomization (p = 0.0023).
Using 792 ischemic stroke cases from the MGH and ISGS/SWISS cohorts, we determined whether the mitochondrial genetic score for ischemic stroke correlated with increasing WMHV. This independent case-only analysis demonstrated a significant (p = 0.037) association between the aggregated risk SNPs for ischemic stroke, and the quantity of WMHV, with a coefficient of 0.0665 (SE = 0.032). This coefficient represents the log-transformed WMHV attributable to each quintile of the mitochondrial ischemic stroke genetic score. Other predictors of WHMV in the regression included age (p < 0.001), and site (p < 0.001). To investigate the role of the site in the determination of WMHV, we inserted all TOAST subtype classifications into the regression model. None of the TOAST subtypes demonstrated a strong association (all p = NS), but the inclusion of these subtypes in the regression model reduced the significance of site in the association with WMHV, decreasing the p-value from < 0.001 to 0.02 with an effective halving of the effect size. The association between the ischemic stroke mitochondrial genetic score and WMHV was also robust to permutation via phenotype randomization, with p = 0.009.
Although our analysis was underpowered to detect associations for individual mitochondrial variants, our data provide evidence for an aggregate effect of common mitochondrial variation on risk of ischemic stroke. The score-based approach used to demonstrate this effect has been applied successfully to resolve genetic associations for lipid profiles, myocardial infarction, and blood pressure, as well as other complex traits [20–22]. While in these conditions the score was comprised of SNPs with genome-wide significance, in schizophrenia a score built from multiple non-significant SNPs with small effect sizes has been validated in multiple independent cohorts [26]. Our approach parallels that taken by the schizophrenia researchers, although we are not able to present replication in an independent data set. Our results were derived from meta-analysis of four independent cohorts, the results of which were all quite consistent with one another and without significant heterogeneity. Although this does not constitute formal replication, the correspondence in effect size and lack of between-study heterogeneity in these independent cohorts is suggestive of generalizability. In addition, the genetic score derived from these cohorts was also robust to two different forms of permutation, in which our results were tested repeatedly against the null hypothesis. Finally, we have applied our ischemic stroke genetic score to WMHV in an independent case-only sample, showing that this score comprised of mitochondrial variants that influence stroke risk also has an effect on the burden of white matter disease in individuals with ischemic stroke. This biologic extension to a related phenotype of ischemic stroke further strengthens the robustness of our findings.
We did not identify any SNP of large effect (OR > 2), despite sufficient power to detect such variants. Our analysis was underpowered to detect variants of small or moderate effects. Because we have not identified an association between ischemic stroke and any specific common variants, mitochondrial genetic testing for common alleles is not warranted at this time. Additionally, because our haplogroup-based analysis does not demonstrate a robust association between individual haplogroups and ischemic stroke, our results do not support haplogroup assignment for clinical prediction. However, future DNA sequencing studies building on our demonstration that common variants have an aggregate influence on risk of ischemic stroke may lead to discovery of individual rare variants with clinical implications for risk stratification in stroke.
This analysis provides concrete examples of the challenges particular to GWAS of mitochondrial variants. Autosomal GWAS studies often assume MAFs > 0.05 for common variants, while our observed median mitochondrial MAF was 0.032, with some variants displaying MAF as low as 0.005. These low observed MAFs greatly limit power to detect differences between groups, because larger sample sizes must be assembled to recruit rarer risk alleles. Furthermore, the mitochondrial genome is haploid, making it impossible for homozygous risk alleles to contribute additional signal in an additive genetic model. Finally, the low effect sizes seen in meta-analysis also limit power to detect novel SNP associations. These constraints altered our power estimates greatly in post hoc analysis.
The majority of the known genes in the mitochondrial genome subserve respiratory chain functions [7]. It has been demonstrated that multiple rare mitochondrial variants can work in concert to cause disease [32], possibly through collective impairment of the respiratory chain [33]. This provides a strong biologic rationale for the application of a genetic-score approach, as this technique allows assessment of the aggregate effect of all mitochondrial SNPs. Under the genetic score paradigm, SNPs that do not contribute to disease association only introduce random associations to the model, favoring the null hypothesis. For this reason, and because our genetic score was robust to two independent forms of permutation, our data provide strong support for a role of common mitochondrial variants in ischemic stroke. Of note, our genetic score was comprised of all available genetic variants, and was therefore an unbiased approach to disease association. The selection of individual candidates for inclusion in a genetic score could introduce biases that limit replicability.
Our mtGWAS was performed using an exhaustive panel of SNPs, encompassing all variation with MAF > 1% in individuals of European ancestry. While mitochondrial SNPs are available on commercially-available genotyping platforms, they do not capture all known common variation. Even with imputation, these platforms cannot achieve full coverage of all common variants, limiting the utility of pooling data from the exhaustive mitochondrial panel and standard GWAS platforms for analysis. Future mitochondrial association studies will require continued use of targeted exhaustive panels [16] to minimize risk of false negative results due to insufficient mitochondrial genome coverage.
Our study has limitations. Despite amassing a large, multi-center cohort of ischemic stroke cases and controls, we did not have power to detect individual SNP associations for the effect sizes and MAF observed in meta-analysis. To be adequately powered to identify associations with individual SNPs would require a cohort in excess of 80,000 cases with matching controls. Even introducing additional controls to our study to reach a 4:1 (control:case) ratio would only increase our power from 0.002 to 0.004. Our results cannot exclude a stroke subtype-specific effect for mitochondrial variants. Restricting sample size in sub-analysis of stroke subtypes would further erode power, decreasing the probability of detecting positive associations even for substantial subtype specificity. This study focused solely on inherited common variation in SNPs outside the D-loop. Mutations within the D-loop or insertion/deletion mutations would require a different study design to detect. We did not model heteroplasmy in our analysis, but this phenomenon would theoretically only erode power to detect associations for common inherited variants. Most importantly, we do not have an additional cohort of individuals in which to replicate our findings, and only after replication can our results be considered robust. While the fact that our results are robust to permutation supports our conclusions, our analysis is still based on a single data-set. However, the observation that the genetic score derived from ischemic stroke is also associated with WMHV in a nested case-only cohort represents a biologic extension of our results in what must be considered an independent phenotype assessed only in stroke cases. It is important to note that this result is insufficient to constitute a demonstration of an effect of specific common mitochondrial variants on WMHV. Rather, it shows that the common variants that increase the risk of ischemic stroke seem to also play some as-yet undefined role in the genetics of WMHV. Further research will be needed to independently assess the role of common mitochondrial variants in the phenotype of WMHV.
This large, multi-center mitochondrial GWAS of ischemic stroke was underpowered to detect individual variants. However, we have shown that some association does exist between common mitochondrial variants and stroke risk. Further studies are necessary to replicate our findings, and substantially larger sample sizes will be required to identify specific variants. It is possible that common variants in the mitochondrial genome conferring a small increase in stroke risk are in linkage with rare variants conferring much larger risk. Detection of these rare variants, through sequencing of the mitochondrial genome, may yield important new information on the role of mitochondria on ischemic stroke and other neurologic diseases.
The authors would like to acknowledge the many study coordinators and technologists at all sites that assisted in the collection and analysis of samples for the current study. The Deane Institute for Integrative Study of Atrial Fibrillation and Stroke, Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine, Marriott Mitochondrial Fund, the Greater Cincinnati Foundation Grant, and the Myron and Jane Hanley Award in Stroke Research also contributed funding for this study. We would additionally like to acknowledge the GENEVA Consortium, including the CIDR Genotyping and Data Coordinating Center at the University of Washington, Seattle, for their support of the University of Maryland GEOS Study.
American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke, Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine, Marriott Mitochondrial Fund, National Institute for Neurologic Disorders and Stroke (R01NS059727, R01NS42733, P50NS051343-04, K23NS064052, K24NS056207, R01NS042147, U54NS057405, R01NS039987, R01NS36695, R01NS30678), Greater Cincinnati Foundation Grant, Myron and Jane Hanley Award in Stroke Research, Fulbright Foundation, American Association of University Women, and the State Committee for Scientific Research (Poland) (2 PO5 CO1226).
Reprints: None Requested
Manuscript Preparation: Christopher D. Anderson (co-leader), Alessandro Biffi (co-leader), Jonathan Rosand. Data Acquisition: Rosanna Rahman, Natalia Rost, Yu-Ching Cheng, Lynelle Cortellini. Manuscript Revision: Rosanna Rahman, Lynelle Cortellini, Natalia Rost, Paul I.W. de Bakker, Daniel Woo, Owen A. Ross, Bradford B. Worrall, Robert D. Brown, Jr, Thomas G. Brott, Agnieszka Slowik, Jeremiasz M. Jagiella, Braxton D. Mitchell, John W. Cole, Steven J. Kittner, James F. Meschia, Joseph P. Broderick, Karen L. Furie, Steven M. Greenberg, Richa Saxena. Data Analysis: Christopher D. Anderson (co-leader), Alessandro Biffi (co-leader), Rosanna Rahman, Paul I.W. de Bakker, Yu-Ching Cheng, Richa Saxena. Study Management: Jonathan Rosand, Karen L. Furie, Joseph P. Broderick, Daniel Woo, Agnieszka Slowik, Bradford B. Worrall, Robert D. Brown, Jr, Thomas G. Brott, Braxton D. Mitchell, John W. Cole, Steven J. Kittner, James F. Meschia, Owen Ross.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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What is it about working in the public sector?
No, we're not bashing government workers - most of them are, in fact, dedicated public servants. But today's issue is the number of lawsuits that are filed against municipalities, school boards and other governmental bodies by disgruntled current or former employees.
Are public-sector supervisors so inept that they are constantly doing things for which they can be sued? Apparently.
In the past two months, Galloway Township has twice paid out $250,000 to settle lawsuits. The Northfield Board of Education recently settled a disgruntled employee's lawsuit by agreeing to pay her $437,500.
The public officials who agree to pay these settlements invariably say the same thing: The settlement is not an admission of wrongdoing, and the town's or the school board's insurer felt that it would be cheaper to settle rather than go to trial.
Neither of which makes taxpayers feel any better about these settlements, which one way or another come out of their pockets.
Lisa Tilton, Galloway Township's former clerk, got her $250,000 settlement after alleging sexual harassment and other illegal actions. And perhaps even more amazing, although the dollar figure is much lower, Tilton is also receiving a $35,000 settlement from Middle Township. She said officials there unfairly discriminated against her by suggesting she should not be hired because of her litigation in Galloway. Really? That's actionable?
In Northfield, Carol Ferguson is receiving a $437,500 settlement after alleging that she was demoted from a school supervisor position for filing an ethics complaint - which ultimately was dismissed by the state Department of Education's School Ethics Commission - against three school board members and the current superintendent.
These kinds of settlements simply do not appear to occur with such frequency in the private sector.
And one obvious reason may be that a business owner is going to more fiercely protect his or her money. Public officials are playing - and paying - with other people's money - yours.
Certainly, people who have been wronged are entitled to seek redress in the courts. And none of this is a commentary on the particular merits of the lawsuits cited above.
But why are such suits so prevalent? Do public-sector supervisors need better training? It would certainly seem so. Indeed, Galloway's department heads are now undergoing training in the hope that the township will be less likely to be exposed to such suits in the future.
Do public bodies settle too soon because - again - it is other people's money that is at stake? Atlantic City, a hotbed of such suits, recently adopted a more aggressive strategy and is fighting many more lawsuits in court. Settlements and judgments against the city have declined as a result.
And finally, are some public employees just waiting for the slightest opportunity to sue, knowing that no matter how groundless their complaint, they are likely to get a lucrative settlement? Probably.
At the very least, governmental agencies must stop making it so easy for these plaintiffs in waiting.


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I'm interested to know the following from the Flob people:
1) On bringing up cross-strait politics in the workplace:Never? Only to certain co-workers? Only when the time and the place is right?
2) When you are back in your own home country:Do you feel compelled to stand up for your position on cross-strait relations? Do you feel compelled to "educate" your fellow compatriots more about Taiwan and cross-strait relations?
3) On disagreements:You meet somebody who sits on the opposite side of the table on these contentious political issues. How far do you go? Or do you simply just let it go?
As a foreigner in Taiwan, I only discuss politics when someone else brings it up first. I figure I have more to learn from them on the topic than they do from me.
In the US, I educate about Taiwan to people who are interested in knowing more about it.
I don't really meet many pro-Beijing people in either Taiwan or the US, so I haven't had any contentious discussions.
1) I've often discussed this with Taiwanese co-workers as well as Chinese who live here and it has never felt like a taboo argument.
2) Only if people ask me about it, or if I ear/read something completely wrong.
3) In nearly every discussion about micro/macro economics and political systems, there are usually 2 sides of the coin (sometimes more, like a cube-coin or whatever) and the "right" one is always based on personal views and interests rather than clear facts. Occasionally there will be someone who supports system X because he doesn't know all the facts*, and a discussion with that kind of person can be very very important, in order to give him/her a chance to make corrections. In general, an argument shouldn't necessarily be about enforcing your point of view and making the other person change his/her mind. Explaining your train of thought and giving the reasons why you believe in a certain thing is the start, and if the other person thinks your point of view is better then he/she gets the chance to change.
If I bring up politics, it's from a bust-the-frame angle. Scott Adams talks about this a lot. Facts and logic don't matter per se in forming opinions. Weaken the worldview that the opinions emerge from. Throw shade on the hidden assumptions.
Actually, facts do matter sometimes - but never in conjunction with logic. Use facts to surprise and discombobulate. Pray the mindset apart at the cognitive dissonance fault lines.
And don't talk politics at work if you need that job. In fact, don't talk facts and logic at work if you need the job.


text:
Bio & Info
Amanda Barnes is a British freelance writer and editor who specializes in wine and travel writing, as well as dabbling in food, the arts, environment issues, profiling people and (unless she can avoid it) politics. Resume/CV link Awards & Scholarships: Born Digital Wine Awards 2016, Winner. Best Tourism Content with a Focus on Wine. Amanda won the award for best wine travel piece in … Continue reading Bio & Info


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The hotel is offering an outdoor diamond shape pool with a view of the beach, and a fitness center. (0802:KL) The hotel is a modern high-rise white stone building. The hotel is offering a restaurant, and a cocktail lounge. The lobby is medium size with marble floors and a seating area. There is a styling salon, memorabilia store and a souvenirs store in the lobby. The rooms are large and modern. There are white color tiles on the floor, tan color furniture and a wall-to-wall mirror. The rooms are offering beautiful views of the sandy beach, the ocean and the pool. The hotel is located directly on the beach. It is 9.5 kilometers form the Hollywood Art Deco District, 9.5 kilometers from the Port Everglades and 3.2 kilometers from the Sun Cruz Casino Cruises. It is also within 12.5 kilometers from Ft. Lauderdale/Hollywood International airport and 40.32 kilometers from the Miami International airport.
101 North Ocean Drive ,Hollywood,Estados Unidos
Teléfono:No especificadoFax:No especificado


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|21 Jan 2014
windows 7 black 64 bit
OS running slowly
just reinstalled my os and for some reason its very slow im running a dell inspiron 17R 5720 im running 6 gigs of ram 500 gig hd all updates and drivers are done what else can i do
|My System Specs
|21 Jan 2014
Windows 7 ultimate 64-bit
get rid of all the bloatware that comes with the dell system(bloatware is extra programs you know you wont need). Just uninstall those and then use the revo uninstaller to completely uninstall those programs. below is the link to the revo uninstaller:
|My System Specs
|23 Jan 2014
Windows 7 Pro x64 Windows 10 Pro x64
Do a clean install, again
Maybe it`s the version of Windows you`re running, what is windows 7 Black ?
Anti-virus None ??????
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text: This page is under construction.Please excuse its informal appearance while it is being worked on. We hope to complete it as soon as possible! This is the nerd's article, don't edit without his permission at all! Got that, <insert your name here>? My Games Koopalings Universe, Koopalings Z Super Smash Bros. Origin is a movie by LegendaryIce/PhoenixFire, and it is a movie based off of The Super Smash Bros. Series, and explains the origin of Super Smash Bros Super Smash Bros. Origin Studio(s) Phoenix Fire Budget 40.7 million dollars This page is a stubIt should be expanded by users with permission to edit it. Retrieved from "http://fantendo.wikia.com/wiki/Super_Smash_Bros._Origin?oldid=2040990" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Articles under Construction Films Stubs Super Smash Bros. (series) Fan Films


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The Westwood LargeCap Value Equity strategy:
- Is actively managed, utilizing a fundamental bottom-up security selection process.
- Typically invests in approximately 40-60 companies with attractive valuations.
- Identifies high quality companies with prospects for future profitability that are significantly stronger than what is reflected in the current stock price.
- Seeks companies with ample free cash flow and low debt.
- Controls risk by limiting the target weight of each holding, imposing maximum position sizes, and limiting sector weightings. The beta of the portfolio is typically less than that of the market.
(As of 9/30/2017)
|Inception date
|1 yr
|3 yr
|5 yr
|10 yr
|Since Inception
|LargeCap Value Gross of Fees
|LargeCap Value Net of Fees
|Russell 1000 Value Index
Investment Team
Westwood believes that team management creates a sense of ownership, accountability and consistency in the investment process. Our LargeCap Value team is supported by a fundamental research team where analysts have cross capitalization responsibilities in specific sectors.
Within our process, Research Analysts generate investment ideas, while the Portfolio Team is responsible for portfolio construction. Each of our Research Analysts is also on a Portfolio Team, which leads to a very collaborative environment where we fully utilize the expertise of all investment team members.
Portfolio Team
Matthew R. Lockridge
Portfolio Manager/Research Analyst
Lisa Dong, CFA
Portfolio Manager/Research Analyst
Mark R. Freeman, CFA
Chief Investment Officer
Scott D. Lawson, CFA
Portfolio Manager/Research Analyst
Varun V. Singh, PhD, CFA
Portfolio Manager/Research Analyst
For purposes of compliance with the GIPS standards, the firm ("Westwood" or the "Firm") is defined as the assets of Westwood Management Corp. and Westwood International Advisors Inc. Westwood Management Corp. is an SEC registered investment adviser under the Investment Advisers Act of 1940 that provides investment supervisory services, managing equity and fixed income portfolios. Westwood International Advisors Inc. is a registered portfolio manager with the Ontario Securities Commission and the Autorité des marchés financiers in Quebec that provides investment supervisory services for global and emerging markets equity portfolios. Westwood Management Corp. and Westwood International Advisors Inc. are wholly owned subsidiaries of Westwood Holdings Group, Inc. (NYSE: WHG). Policies for valuing portfolios, calculating performance, and preparing compliant presentations are available upon request, as is a complete list and description of the Firm's composites, by contacting email@example.com.
Westwood Management Corp. claims compliance with the Global Investment Performance Standards (GIPS®). Unless otherwise stated, performance shown is in U.S. Dollars.
The LargeCap Value composite, previously known as the LargeCap Value Equity Composite, includes all taxable and tax-exempt, fee-paying fully discretionary accounts invested primarily in equity securities with market capitalizations above $5 billion and having comparable objectives. The minimum portfolio size for inclusion in the LargeCap Value Composite is $5 million beginning January 1, 2006. Portfolio returns reflect the reinvestment of dividend and interest income. The LargeCap Value Composite is benchmarked against the Russell 1000 Value Index. The Russell 1000 Value Index is an unmanaged market index that measures the performance of those Russell 1000 Index companies with lower price-to-book ratios and lower expected growth values. The Russell 1000 Value Index contains those Russell 1000 companies that have higher book-to-price ratios, and thus a less-than-average growth orientation, than the remaining companies in the Russell 1000 Index that encompass the Russell 1000 Growth Index. The comparative index returns include reinvestment of income but do not include transaction costs or management fees.


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NachlamSie (813) Denver, Colorado | May 20, 2016
This place seems to sell a lot of pizza. It feels welcoming and spacious inside, very restaurant-focused. The bar is tiny with only four seats. Service was friendly and efficient. They had three of their own beers along with about four quality guest taps. I thought the blonde and amber ales were a little rough around the edges. Didn't eat on this visit, but it seems like a really good place to grab pizza.
3fourths (1569) Boulder, Colorado | October 14, 2011| Updated October 15, 2011
more popular to townsfolk as a pizzeria than a brewery. small bar up front, 5-6 beer on tap, 1-2 seasonals/specials. busy at lunchtime on a friday. didn't eat. drank a double ipa next to some locals with moustaches.
soul11man (54) Portland, Oregon | August 18, 2011
Great pizza and beer joint. Fun atmosphere, great beers with a decent house selection. Nice experimental varieties like the Green Chile Ale. If you are hanging out or passing through Salida this is a great stop.
performula (28) Heart of the Rockies, Colorado | July 13, 2011
The pizzas are great and the beers are very good. Service has always been superb. Prices don't break the bank either.
bleeng (168) Seattle still not near Beersel., Washington | August 20, 2010
Located downtown in a surprisingly vibrant area. Very busy when we were there mid-week in August 2010. Like a few before me noted, the ordering/seating process is a bit confusing but once you get the hang of it you're ok. Large pizza list and 6-8 house beers. The pizza was very good and the IPA and oaked/smoked porter were solid. Purchased a chili beer to go-yet to have it. Overall a good experience and the service was good once seated. Recommended.
bblack99 (30) Kansas City, Missouri | August 12, 2010
Busy little funky joint in the small town of Salida, nested between the Sawatch and Sangre de Cristo Ranges of Colorado. A little chaotic when you first walk in, as there's a strange system of getting your seat, then returning to the entrance to place you order. Other than that, service was perfectly fine and everyone was friendly. Beer selection is limited to just the house's own brews, but there were 6 or 7 different styles on tap when I stopped in. Great beers, everything available in a growler for just over $11. Starting to bottle their beers, but tonight only the green chile was available in a bomber. Expanded bottling and distribution would be awesome! Back on point -- food is as good as just about any you'll find in a brewpub, where beer should be the star. Goat cheese wood-fired pizza in rural(ish) Colorado? Sweet! A little pricey, but good quality stuff costs a bit more when you get away from the big city. If you're ever in Salida, whether hiking or just passing through, be sure to eat and drink at Amicas!
Alerider (42) Charleston, South Carolina | September 13, 2009
Fun place in this small town. Good beers, great food and service.
jb43 (47) Colorado Springs, Colorado | May 31, 2009
Small local brewpub. Good selection of beer on tap (7 brews). Food was very good. Value and service were decent. Bartenders and waitstaff were busy but attentive and friendly. Didn't really like the set-up of ordering before you sat down though. Green Chile beer and Headwaters IPA were very good.
Crosling (70) Fort Collins, Colorado | March 27, 2008
Really enjoyed my stop here this past summer. Solid ales. Cool atmosphere, friendly service. I was there when they opened and a large line formed behind me. The locals obviously love this place, I would to. Amicas is an impressive establishment.
BeerandBlues2 (1056) Escondido, California | November 2, 2007
Quaint, nearly upscale brewery and eatery tucked in a sleepy little town. The interior is very nicely decorated with local artwork. Nice selection of 7 house beers on draught along with a wonderful wood-oven baked pizza. This is a nice watering hole stuck in central Colorado.


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Lack of symptoms
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January 23rd, 2012, 10:08 PM
Join Date: Oct 2011
Location: Northeastern Pennsylvania
Posts: 312
Haha that is funny, I am hoping it's a girl again bc it would make things so much easier for us right now if it were.
Oh another symptom I have been having I keep forgetting it's even a symptom is extreme Irritability. Everything sets me off anymore.
Thanks, I never smoked much to begin with, was a casual smoker. If there wasn't extra money I never bought them, if I did I would. Also a pack would last me a week because I would only have 1-2 before and after work. Never smoked when I I'm home. I Quit fully with DD up until I was 5 months pregnant. Then my father passed away and that was it. I started up again until DD was born. I felt bad for doing it but it was my stress reliever but I still only had the 1-4 a day depending on how I felt. But it's been like that off and on since I had her. But this time I'm determined to be done for good. I hated it because it's such a bad habit. But it was the only one I ever had and I didn't do it often I didn't think it was so bad. But I'm tired of sneaking around too bc DF never knew I did it while pregnant with DD or even after, he thought when I quit I did for good because I just hid it from him. I'm doing good right now, haven't had any major cravings yet, I hope I don't either lol
Hope you can do it this time around. I know it's hard and its easier to do it when your ready.
DD1 BreastFed for.
DD2 Breasfed so far.
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Discussion in 'Irrigation' started by FIMCO-MEISTER, Jun 30, 2010.
The dude clearly has a problem... none of those skanks he was with were worth that! Nevermind the fact that he has/had a smoking hot wife at home....
Skanks or not seems like home was not where his heart was. After all is said and done the wife did amazingly well. I am guessing they had a troubling relationship without the extramarital affairs.
Does she pay for his window broken out of the SUV?
i hope he gets the dogs
this time he took it in the rear.
750 million, thats about one days pay for old tiger. He will make out just fine.
Sure as hell beats my $540K divorce.
Maybe it would have cost me more if she broke the window out of one of my trucks - but sadly all she did was shoot at me.
On an upbeat note - at least I got the dog.
I like a-1s advice. Go broke first then divorce.
i got into one helluva nasty custody battle in mine. I got my daughter though. My theory was if my ex was going to cut me out of her life I was going to make sure when my daughter got older she knew her Dad put up one expensive fight to prevent it. I got custody because I gave my ex plenty of rope..... I cook better anyway.
Best way to prevent a costly divorce....... don't get married.
I would probably still need to go through some kind of divorce proceedings if W and I broke up. The state considers us married after 20 years.
tell the judge your watch stopped


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on September 23rd 2016 (Originally Published May 27th 2008)
Buy on Amazon
Finley Gallagher has a business to run, a sexy-as-sin neighbor to avoid and no time for everyone's fascination with the city's mysterious vigilante who's putting criminals in their place—until she's attacked. With no one else to turn to, she's forced to rely on the two men she'd rather not have anything to do with. One hides who he is, unleashing her deepest fantasies from the shadows, while the other slowly disarms her with one devastating smile after another.
Trace Fairbanks is determined to do whatever it takes to keep the streets safe, even if it means leading a double life. He's wanted Finley for months, and now that he knows she's more into his alter ego than he ever realized, he's willing to blur the line between fantasy and reality to prove he's the only hero she'll ever need. But getting the girl might not be as hard as keeping her alive if he can't trust her with the truth before it's too late.
I just love Sydney Somers writing. It's so wonderful. It keeps me engaged and devouring the book. I mean, have you read her Pendragon Gargoyles series?? I blew through them very quickly, they are that good!
Okay. Now that I've gone on a little rant, let's carry on to the review. 🙂
I can say I have never read a book with the trope of the hero being a vigilante or super hero with a super power like in comic books. For this alone, I knew the book was going to be good. Finley was great to read, but she was out-shown by Trace. I mean, who can beat out a FREAKING SUPER HOT VIGILANTE?? Some scenes were lighting up my kindle with the sparks flying between the characters. I enjoyed the depth we were able to see in the two. It added a wonderful nugget to the story.
My only complaint is that I wish it was slightly longer. Of course, I can also see if I beg her enough she'll cave and write another book, turning this into a series! *wink, wink* *nudge, nudge*


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Often times, I will be walking down the street when random passers-by will approach me and inquire, "Barry, how is it that you are so successful? What is the secret that makes women weep and men tremble at your approach?"1
I usually modestly brush them off, but I've thought recently that perhaps I should share the secret of my success with you, my closest friends on the Internet.
How did I become such a towering figure of renown and fame? How did I come to bestride the world like unto a Colossus? I shall tell you, and the telling you shall be now.
That's right: Oatmeal.
Since the very earliest days of my career, I have eaten oatmeal for breakfast pretty much every single day. Exceptions are made when I'm at a breakfast meeting or when my wife gives me that look that says, I cannot abide watching you eat oatmeal again, so we are going out for brunch.
But easily 300+ days a year, I eat oatmeal for breakfast. I'm a creature of habit and routine.2
And you're thinking Oatmeal, and I say, Have you been listening? Yes. Oatmeal.
Perhaps you are skeptical. Perhaps you scoff. Perhaps you think there can be no connection between oatmeal and success. But I can tell you this: I've breakfasted3 with M.T. Anderson and do you want to know what he ordered?
That's right, punk: Oatmeal.
If it's good enough for YA's own personal Jesus, why isn't it good enough for you?
Now, realize that when I say I eat oatmeal, I speak not of a simple grayish bowl of mush, as you might see in a production of Oliver! or on a small child's high-chair tray. Oh, no. I have an elite, special recipe that I will now bequeath unto you, so that you, too, may achieve your dreams. Here we go:
Uncle Barry's Success! Oatmeal Recipe
- 1/2 cup Quaker Quick Oats
- 1/2 cup H2O ("water")
- 1/2 cup vanilla almond milk, unsweetened
- 1 Tbsp honey
- 1 palmful blueberries, rinsed
- 1/2 banana, sliced evenly
- 1 handful chopped walnuts
- Combine the oats, "water," and milk in a microwave-safe bowl. Nuke the combination for one minute and forty-five seconds. No longer, no shorter. Tamper not with the timing.
- Add the honey and stir until evenly distributed.
- In the following order and only in the following order, add the remaining ingredients: First blueberries, then banana, and finally walnuts.
- Stir.
- Enjoy your oatmeal and your success. They are both delicious.
You may be tempted to substitute blueberries with, say, blackberries, or a similar fruit. You may be tempted to use the whole banana, or even to replace the walnuts with almonds. DO NOT DO THIS! STRAY NOT FROM THE RECIPE, OR ONLY DOOM AWAITS YOU!
There you go: Now just do that every day for several years in a row and you, too, will walk on water.


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Jesse C.
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