text:
FELODIPINE
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 18 December 2020
FELODIPINE- felodipine tablet, extended release
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.
Felodipine is a calcium antagonist (calcium channel blocker). Felodipine is a dihydropyridine derivative that is chemically described as ± ethyl methyl 4-(2, 3-dichlorophenyl)-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylate. Its empirical formula is C18 H19 Cl2 NO4 and its structural formula is:
Felodipine, USP is a light yellow to yellow, crystalline powder with a molecular weight of 384.26. It is insoluble in water and is freely soluble in acetone and in methanol; very slightly soluble in heptane. Felodipine is a racemic mixture.
Felodipine extended-release tablets, USP provide extended release of felodipine. They are available as tablets containing 2.5 mg, 5 mg or 10 mg of felodipine, USP for oral administration. Inactive ingredients are: polyoxyl 40 hydrogenated castor oil, magnesium aluminum silicate, hypromellose 2208, lactose monohydrate, hydroxypropyl cellulose, sodium stearyl fumarate, hypromellose 2910 5cP, titanium dioxide and PEG 400. The 2.5 mg tablet strength also contains Iron oxide yellow, D&C yellow #10 aluminum lake and the 5 mg tablet strength also contains Iron oxide yellow.
USP dissolution test pending.
Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers). It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites, blocks voltage-dependent Ca++ currents in vascular smooth muscle and cultured rabbit atrial cells, and blocks potassium-induced contracture of the rat portal vein.
In vitro studies show that the effects of felodipine on contractile processes are selective, with greater effects on vascular smooth muscle than cardiac muscle. Negative inotropic effects can be detected in vitro , but such effects have not been seen in intact animals.
The effect of felodipine on blood pressure is principally a consequence of a dose related decrease of peripheral vascular resistance in man, with a modest reflex increase in heart rate (see Cardiovascular Effects ). With the exception of a mild diuretic effect seen in several animal species and man, the effects of felodipine are accounted for by its effects on peripheral vascular resistance.
Following oral administration, felodipine is almost completely absorbed and undergoes extensive first-pass metabolism. The systemic bioavailability of felodipine is approximately 20%. Mean peak concentrations following the administration of felodipine extended-release tablets are reached in 2.5 to 5 hours. Both peak plasma concentration and the area under the plasma concentration time curve (AUC) increase linearly with doses up to 20 mg. Felodipine is greater than 99% bound to plasma proteins.
Following intravenous administration, the plasma concentration of felodipine declined triexponentially with mean disposition half-lives of 4.8 minutes, 1.5 hours, and 9.1 hours. The mean contributions of the three individual phases to the overall AUC were 15, 40 and 45%, respectively, in the order of increasing t1/2 .
Following oral administration of the immediate-release formulation, the plasma level of felodipine also declined polyexponentially with a mean terminal t1/2 of 11 to 16 hours. The mean peak and trough steady-state plasma concentrations achieved after 10 mg of the immediate-release formulation given once a day to normal volunteers, were 20 and 0.5 nmol/L, respectively. The trough plasma concentration of felodipine in most individuals was substantially below the concentration needed to effect a half-maximal decline in blood pressure (EC50 ) [4 — 6 nmol/L for felodipine], thus precluding once-a-day dosing with the immediate-release formulation.
Following administration of a 10-mg dose of felodipine, the extended-release formulation, to young, healthy volunteers, mean peak and trough steady-state plasma concentrations of felodipine were 7 and 2 nmol/L, respectively. Corresponding values in hypertensive patients (mean age 64) after a 20-mg dose of felodipine extended-release tablets were 23 and 7 nmol/L. Since the EC50 for felodipine is 4 to 6 nmol/L, a 5 mg to 10 mg dose of felodipine extended-release tablets in some patients, and a 20 mg dose in others, would be expected to provide an antihypertensive effect that persists for 24 hours (see Cardiovascular Effects below and DOSAGE AND ADMINISTRATION).
The systemic plasma clearance of felodipine in young healthy subjects is about 0.8 L/min, and the apparent volume of distribution is about 10 L/kg.
Following an oral or intravenous dose of 14 C-labeled felodipine in man, about 70% of the dose of radioactivity was recovered in urine and 10% in the feces. A negligible amount of intact felodipine is recovered in the urine and feces (< 0.5%). Six metabolites, which account for 23% of the oral dose, have been identified; none has significant vasodilating activity.
Following administration of felodipine extended-release tablets to hypertensive patients, mean peak plasma concentrations at steady state are about 20% higher than after a single dose. Blood pressure response is correlated with plasma concentrations of felodipine.
The bioavailability of felodipine extended-release tablets are influenced by the presence of food. When administered either with a high fat or carbohydrate diet, Cmax is increased by approximately 60%; AUC is unchanged. When felodipine extended-release tablets were administered after a light meal (orange juice, toast, and cereal), however, there is no effect on felodipine's pharmacokinetics. The bioavailability of felodipine was increased approximately two-fold when taken with grapefruit juice. Orange juice does not appear to modify the kinetics of felodipine extended-release tablets. A similar finding has been seen with other dihydropyridine calcium antagonists, but to a lesser extent than that seen with felodipine.
Geriatric Use — Plasma concentrations of felodipine, after a single dose and at steady state, increase with age. Mean clearance of felodipine in elderly hypertensives (mean age 74) was only 45% of that of young volunteers (mean age 26). At steady state mean AUC for young patients was 39% of that for the elderly. Data for intermediate age ranges suggest that the AUCs fall between the extremes of the young and the elderly.
Hepatic Dysfunction — In patients with hepatic disease, the clearance of felodipine was reduced to about 60% of that seen in normal young volunteers.
Renal impairment does not alter the plasma concentration profile of felodipine; although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive.
Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
Cardiovascular Effects
Following administration of felodipine extended-release tablets, a reduction in blood pressure generally occurs within 2 to 5 hours. During chronic administration, substantial blood pressure control lasts for 24 hours, with trough reductions in diastolic blood pressure approximately 40 — 50% of peak reductions. The antihypertensive effect is dose dependent and correlates with the plasma concentration of felodipine.
A reflex increase in heart rate frequently occurs during the first week of therapy; this increase attenuates over time. Heart rate increases of 5 — 10 beats per minute may be seen during chronic dosing. The increase is inhibited by beta-blocking agents.
The P-R interval of the ECG is not affected by felodipine when administered alone or in combination with a beta-blocking agent. Felodipine alone or in combination with a beta-blocking agent has been shown, in clinical and electrophysiologic studies, to have no significant effect on cardiac conduction (P-R, P-Q, and H-V intervals).
In clinical trials in hypertensive patients without clinical evidence of left ventricular dysfunction, no symptoms suggestive of a negative inotropic effect were noted; however, none would be expected in this population (see PRECAUTIONS).
Renal/Endocrine Effects
Renal vascular resistance is decreased by felodipine while glomerular filtration rate remains unchanged. Mild diuresis, natriuresis, and kaliuresis have been observed during the first week of therapy. No significant effects on serum electrolytes were observed during short- and long-term therapy.
In clinical trials in patients with hypertension, increases in plasma noradrenaline levels have been observed.
Felodipine produces dose-related decreases in systolic and diastolic blood pressure as demonstrated in six placebo-controlled, dose response studies using either immediate-release or extended-release dosage forms. These studies enrolled over 800 patients on active treatment, at total daily doses ranging from 2.5 mg to 20 mg. In those studies felodipine was administered either as monotherapy or was added to beta blockers. The results of the 2 studies with felodipine extended-release tablets given once daily as monotherapy are shown in the table below:
MEAN REDUCTIONS IN BLOOD PRESSURE (mmHg)*
Placebo response subtracted.
Different number of patients available for peak and trough measurements.
Dose N Systolic/Diastolic Mean Peak Response Mean Trough Response Trough/Peak Ratios (%S )
Study 1 (8 weeks)
2.5 mg 68 9.4/4.7 2.7/2.5 29/53
5 mg 69 9.5/6.3 2.4/3.7 25/59
10 mg 67 18.0/10.8 10.0/6.0 56/56
10 mg 50 5.3/7.2 1.5/3.2 33/40†
50 11.3/10.2 4.5/3.2 43/34†
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Brand names beginning with the letter 'F' (FELODIPINE).
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Medication information from December 2020, newest first or December 2020, earliest first.
https://medlibrary.org/lib/rx/meds/felodipine-5/


Olia Lialina: Jennifer, you didn't say anything about yourself on the pages of Hollywood/Theater/5049/. Would you prefer to stay anonymous for this interview? Otherwise can you say some words about who you are and where you are from?
Jennifer Pursley: I am from the east coast of the United States. I'm living in a larger city now than I was at the time I made my website. I am a nurse practitioner, which is basically an advanced practice nurse that can diagnose illnesses, prescribe medications, and other treatments as part of a medical team. I am finishing up a doctorate now. I do not have much of an online presence anymore.
OL: How old were you when you started Star Wars vs. Titanic?
JP: I believe I was 15 or 16.
OL: The first capture on the Internet Archive is from February 1999, but the copyright is 1998, the content also suggests that it was not the first iteration of the web site. Do you remember when exactly you started?
JP: I remember Titanic came out in December 1997 and I believe I would have made it probably January or February after that. So that was 1998, January or February, that was when Titanic was kind of at its height of popularity. I don't know if you remember when it came out in the theaters. There were lots of people, everyone in school, going to see it, like three times, five times. It was a romance story and everyone loved it.
OL: And we cried the rest of the night and, if not for other obligations, we would probably come to the idea to make a Leo fan page ourselves.
JP: This film and fandom just really annoyed me for some reason. Despite the fact, I went to see it too, of course, which is kind of funny when you think about it. But the previous year – I don't know how much do you know about Star Wars – Star Wars had had their 20th anniversary and they had re-released the original Star Wars movies in the theaters. So if you were someone at my age, you had never seen Star Wars in the theater before. So we got very, very excited about that. So we were all hyped up about that from the beginning of the year (1997)… and then Titanic came out. There were lots of people at my school that kept saying, oh, Titanic, is so much better than Star Wars. I said, you know what? No, it's not, and I'm going to tell you why!
OL: Was it your first ever web page or did you have another one before ?
JP: That was my first time. Where I lived Internet was relatively uncommon for anyone to use it outside of, maybe school or in the library. Most people didn't have a computer at home and my community, even in 1998.
OL: Did you have any page after that or is it your one and only web site?
JP: Believe it or not, that is the one and only web page I had. Later at university we had to do a really basic kind of website for a class.
JP: Well, number one reason for a high school student: because it was free. And I also had seen other GeoCities websites. I liked how they looked. I liked the design and it seemed like a pretty friendly community too. There were lots of other people that looked like they were doing websites about things that they were a fan of and it just seemed like the right place.
OL: Do you remember the moment when you chose the neighborhood?
JP: Yes. Hollywood neighborhood and Theater suburb. I chose them because I was doing my site about Hollywood movies that were in the theater at that time. I do remember selecting it and then I remember looking at my neighbors' web pages too. The ones that were just right around me. It was lots of little rectangles and you could click one that was empty to move in.
OL: I had a chance to talk to David Bohnett recently, he was referring to this interface as a street map.
JP: I remember I wanted to pick the block that had some nice neighbors around it.
OL: Were you deciding because of the neighbors?
JP: Exactly. It was like moving into a home.
OL: The comment on the top of your index.html source suggests that your web site was <!–Created by GeoCities Home Page Generator–> But the code itself doesn't look like you were actually using this generator.
JP: I don't remember how I made the page initially, but there were some communities that showed you how to build a website. And I think my initial layout I did copy from where they were describing how to make it. And then I would go in and tweak things inside of that.
I was pretty clueless on how to make a website. A lot of people were doing frames then and that was a little confusing to me, since I didn't really have the knowledge. My dad had a book called HTML for Dummies that I used as a reference quite a lot when I was typing things.
I remember it being a free type. There were actually many GeoCities sites that had code on there to show you how to do it. And you could get some ideas from them.
And they had some examples of code that you can use. And I think I got it from there, and the comment you mention was may be a part of that.
OL: I guess every image you used on your site came from other web pages or free collections. Am I right? Did you make any graphic yourself?
OL: Can you say some words about your choice of elements?
JP: Making any graphic was beyond my skill level. Most of the graphics I used were pretty popular at the time on other sites. I found free collections on other GeoCities web pages and on website builder pages. I picked things that I liked. I really liked the fire graphic a lot!
The only thing I slightly made myself obviously was the anti-Titanic webring logo. I went in MS Paint and pasted NO sign on top of the official poster I took from the official Titanic website, I believe. Yes. I think that's the only thing that I actually made.
OL: Let's talk about your webring! According to the meta data The Anti-Titanic Webring registration page was last updated on the 16th of April 1998. Can it be that is also the date of the webring's birth?
JP: Yes. I think that was probably when the webring was made. I noticed that there were some other anti-Titanic websites. There wasn't really a good way then to get more views on your website, which was absolutely what everyone wanted. I had seen web rings before, so I thought, oh, we should make one. There were lots and lots of Titanic webrings. They had lots of different ones that said they were "official." So I decided to make the official anti-Titanic webring.
OL: How many web sites joined your ring?
JP: I think approximately 30. I actually did a Google search last night just to see if I could find any, and there's actually a few that still have my graphic. If you Google anti-Titanic webring the link doesn't go anywhere, but there are some Angelfire or Tripod sites that still had the ring navigation code at the bottom: Operation P.A.T.H, Titanic the 1997 film: FILTH.
I remember they were a lot of fun because they got tons of hate mail too.
Okay. He's Not A Hack. But He's No Genius Either!, SINK THE TITANIC, A.T.S. (Anti-Titanic Society) .
JP: I don't remember the A.T.S one, but I like the form for guests to leave comments. This reminds me of all the funny emails I would receive.
JP: It made me feel important.
OL: What were your ringmaster's duties?
JP: People would send me their websites for review. So I would get a lot more websites sent to me than I actually let in because I wanted it to only be websites that had anti-Titanic content within it. And I only would send them back the link of how to be added to it if I added them to the webring.
So at least once a week, I would go through websites. And I would try to respond to people that I didn't add, to tell them why I didn't add them. Because some people would get pretty upset that I didn't allow them to be in because "I mean, it's just a webring on GeoCities." and "Why are you not letting me in this exclusive club?" So I would try to let them know what kind of alterations they can make up so I would accept them.
OL: One person, a Nirvana fan, got a really special treatment from you!
OL: You made a page Salute to Ian, where you published your emails to each other. Can you say some words about it?
JP: We were 16, we thought it was very funny. Later, I thought, oh, we were being pretty mean. So yes, that was one particular guy and he kept emailing us over and over and over that he wanted to be in the webring. And I started off pretty polite answering back to him. And he just kept asking and asking to be in the webring and I told him that was impossible. And then the tone got nastier and nastier and he was using his father's personal email to email me, which happened a lot when you were using your dad's AOL account. It had his full name on there and you could see where he was from. So we said, okay, we went to a map site and sent him a screenshot of the map of his address and said, stop bothering us or… we know where you live. That was one of my friends and I were just, having fun on Friday night… we thought it was funny, of course.
OL: Why do you think he wanted to be in the anti-Titanic webring?
JP: I really don't know. I think there are lots of Nirvana rings he could have fed in. I really probably should have let him in because he sincerely hated Titanic enough to send about 10 emails about it. I'm not sure why he didn't just add something to his page to get accepted.
OL: You have a loooong list of people in your acknowledgement section. Who are these people?
JP: Yeah. Almost every single person on that page is a friend from school or someone I knew from school, either real name or a nickname that they had. And it was essentially that they had not ever seen their name on a web page before, and they asked me to put it on there. So in the beginning I said, I can't really do that because that's not what the page is about. It's not about school and my friends. But I solved the problem by just making an acknowledgement page. And a lot of the people, most of the people actually, specifically asked to be there. And some of the other people were just friends. I was involved in a student-government thing, and some of those were people I knew from student-government who wanted to be on the web page too. I don't think, it would be that novel now, but at the time, it was.
OL: But none of the names is linked. Were you the only webmaster in your school? Did you think about yourself as a web master at that time, did you use this word?
JP: I don't think I did at the time. But I think I was. And yes I was the only kid who knew how to make a web page. But I remember everyone was very interested in it. We had our own viral marketing campaign for my website. We made flyers about my website and gave them to people. We made buttons, anti-Titanic buttons that you could wear on your backpack.
OL: Is there anything left? Any button?
JP: I probably still have some… We made a poster one time. I probably have it somewhere at my parents' house.
OL: A poster for your web page, right?!
OL: This is how it should be! I hope you can find it and will share a photo with me!
JP: I will look for it. (Unfortunately Jennifer couldn't find the poster, but she send to me a photo of herself in 1998, which you can see on the top — OL) We were trying to figure out what you could do to get more interest in your webpage. It was hard back then.
OL: But you did succeed.
JP: I would say the website was really popular, whenever Titanic was in the theater, and Titanic stayed in the theater for a very long time. And then I did notice there was a resurgence in people looking at my page around the time—I believe it was May of 1999—when the new Star Wars movies came out. It was when episode one came out. And a lot of people, I think were searching for Star Wars on sites and found mine. So in the beginning, I got a lot of interest for people who liked Titanic. Later on, I got a lot of interests from people who liked Star Wars. So it was an interesting dichotomy.
JP: It had its moments that I was very surprised by how popular it was. The counter at the bottom… there were a few days where the Titanic searchers, it was getting several hundred hits a day, which to me at the time, as a personal website, that was really surprising.
OL: I didn't know these numbers, but the updates and your tone made me think that you were in constant and very intense communication with a lot of people.
JP: I got a lot of email. I was getting hundreds of emails a day from people, sometimes from repeat people, but usually from different people. Later on, I would maybe not check it for a little while. And then whenever I went back in to check, I would have like 300 or 400 new emails from just people around the world. I mean it was crazy, the amount of email I got. Either saying they liked my page or telling me that I could go and die because Titanic is the best movie ever.
Sometimes I would respond, sometimes I wouldn't, it just depended. I got a lot of just one line sort of things. But again, I had several friends that just would come over to my house and we would just read my email together. We would just have a great time reading the email. It was a lot of entertainment for living in a small town. There wasn't really anything to do there.
OL: I saw a lot of Titanic fan sites in the Geocities archive. Some of them are Titanic, some of them are Leonardo DiCaprio fan sites.
Preparing for the interview I looked through them again and thought that 1998 was probably the moment when this fan base stole outer space wallpapers from fans of Star Wars and from NASA scientists. Before these backgrounds were used for outer space and cyberspace and suddenly, it became the sky over Jack and Rose… you remember, the famous scene when they are "flying" and the final one in the water. I suppose you saw a lot of these sites. Would you say that your website was a parody of such fan websites? Or were you only targeting the film itself?
JP: Yes. It was definitely a parody of the fan sites as well. Maybe, initially I didn't realize it was going to be, but I did like to put my own brand of humor in it at the time. Lots of the websites were very fanatical about how no movie can compare to this one. And so I decided to make mine equally as fanatical, showing you the reasons—even if they didn't make any sense—that Star Wars was actually better than Titanic.
OL: There are two pages that really made me laugh: Do you love my page? and Do you hate my page? There you used all the website clichés of that time. You know if today somebody would want to imitate a 1996 website, this is what they would do.
JP: Exactly. Obviously, I had seen all kinds of of websites, where they were either welcoming comments or telling you they didn't want comments. So I did take a little of the verbiage of every single website and just put it all on there in one big mess.
OL: The "Do you love my page?" section is like a lady's website. Something what you would rather find in the Heartland neighborhood at that time. Was it on purpose?
JP: Yes. And that was absolutely the intention.
OL: Speaking of mimicking the style, have you seen the Captain Marvel official movie site? People keep sending me this link knowing my interest in amateur aesthetics, but I would like to ask your opinion.
JP: Oh wow. I like it. Yes. It looks authentic.
OL: Does it look like 16 year old made it in 1998?
JP: Yeah. Maybe a little nicer than what I could have made, but yeah, I like that. I like the music in the background too!
OL: Why your page didn't have music in background?
JP: My connection was very, very slow dial-up connection. So I didn't want to have a lot of extras because it slowed the web page down for me.
OL: What was your connection at that time?
JP: It was just a regular dial-up. Sometimes I was lucky to have like 28kb/s. It was very, very slow. I remember it would take websites several minutes to load. My parents got an extra phone line one day. So you could be on the Internet [constantly] because when we first got the Internet, you couldn't make any phone calls [and be online at the same time]. I remember my parents would get really frustrated if they tried to call home and the line was always busy because I was on the Internet.
OL: One thing about your site is a mystery for me. Everything is 100% early web style, classic GeoCities 1996 website, but you have only one external link! And it goes to the Star Wars drinking game, that I couldn't find.
JP: I thought I saw it the other day. Here!
OL: Why did you link to it? And more importantly, why didn't you link to more web sites?
JP: The reason that I did not link to other websites… that's a really good question. I think I wanted to just write everything myself and since my page was so specific, since it was Star Wars versus Titanic, I didn't see a lot of websites that I wanted to link to. But for some reason, the drinking game I thought was very funny, and I think that probably had something to do with the United States, you can't drink at my age here.
What are these things? Or was it just a teaser?
JP: I really don't know! I saw that yesterday too and I thought, what? What did I compare? Because I don't remember this and it looks like I did not follow through.
OL: Were you still in high school in '99?
JP: Yes. I finished high school in May of 2000 and I started college in August of 2000.
OL: As it seems next time you returned to your page only in April 2001, to add a quite huge message: "This Webpage Just Got Updated! Hell is Freezing Over!" You left your page unattended for two years and then you came back with the strong intention to make something, right?
JP: Yup. I can tell you exactly why. That was because that was when episode two of Star Wars came out and everyone started searching for Star Wars again. And I started getting emails again about the website, so I decided to put something else on it. I was in college, in university at the time, and I just decided it would be fun again. And it wasn't so fun the second time around, so I didn't keep it updated after that. I thought I would add some more content to it, but again, my follow through wasn't great and I didn't do it. I think I added a little bit, but it wasn't much.
OL: Around that time, did you think that you page was outdated or looked outdated? Did you plan to make it more modern, more 21st century?
JP: No, it was like a time capsule for me. I don't think I had really considered changing it to make it more contemporary just because, I did almost like the nostalgia factor that reminded me of high school. It reminded me of my friends. So there were many, much nicer looking websites by that time, even in just a few years. But no, I didn't really think about changing it. I kind of liked the clunky nature of it then.
OL: From what I know, earlier that year GeoCities discontinued FTP, which would mean you had to use Yahoo's editor and file managers or pay for the Premium . I also saw a lot of people leaving because they were said that they have to pay for the traffic….
JP: May be. Another reason I know that I left was LiveJournal had gotten popular, and a lot of my friends had made LiveJournal sites. And I made a LiveJournal site around that time. So that was another reason.
OL: Are you still on LiveJournal?
JP: I still have a LiveJournal. I don't update it anymore, but it exists.
OL: Are you on Facebook?
JP: I have Facebook, but I don't actually like it. I have it because people send event invites that way and it's a good way to network. But I really do not actively use Facebook. I have it to look at other Facebook pages rather, but I don't update it myself very often. I don't really have a niche for an online presence right now. I have Twitter, but it's mainly to read other people's tweets. So that's kind of sad, maybe I need to get active on something.
OL: I tried to reach you at boycotttitanic@hotmail.com, but my message bounced back. Did you kill this mailbox or you just forgot about it?
JP: I don't know. I think I must have forgotten about it, probably around 2002 or whenever I left, and I didn't check it again. I guess Microsoft deleted it.
OL: Did your fans and haters notice that you left in 2002?
JP: I never checked my email again, so I do not know. That is a really a sad end! Maybe they will see your project and reach out to me again.
OL: Btw, on the 28th of February 2019 the screen shot was posted on One Terabyte of Kilobyte Age Tumblr and didn't go unnoticed!
JP: I do have one question for you. What made you try to find me?
OL: I always wanted to talk to a Ringmaster!!
But seriously I was intrigued by the simplicity and the energy, and authenticity of your site… I think I should try to explain it properly in the introduction.
Thank you Jennifer, For your time and your thoughts!
And to all the readers out there, if you would like to talk about your home page, contact me at olia@profolia.org!


text:
Appeals Criminal Securities
SAC Capital Appeal Tests Insider-Trading Law
May 9, 2017 January 3, 2018 ADAM KLASFELD
banking, insider trading, Second Circuit
MANHATTAN (CN) — Fighting Tuesday to clear the name of the man once depicted as the face of Wall Street greed, a defense attorney painted the conviction of former SAC Capital executive Mathew Martoma as part of a pattern of overzealous federal prosecution.
"The government has literally gone 0-for-3 by swinging for the fences," Kirkland & Ellis attorney Paul Clement told the Second Circuit this morning.
Martoma's case had been a high-water mark in the insider-trading crusade of former U.S. Attorney Preet Bharara. Though the Manhattan federal prosecutor had busted multiple multibillion-dollar hedge funds before President Donald Trump sacked him this year, Stamford-based SAC Capital had been one of Bharara's biggest quarries.
Bharara dubbed Martoma's $276 million profit as the "most lucrative" example of insider trading in history, and he scored a $1.8 billion settlement against SAC's billionaire president Steven Cohen, whom the Securities and Exchange Commission briefly banned from managing money.
Martoma had been the 79th securities fraud conviction under Bharara's belt, receiving a nine-year prison sentence. How many of those convictions will hold, however, could depend on the Second Circuit's interpretation of three key decisions: Dirks v. SEC, United States v. Newman and United States v. Salman.
All three cases involved inside tips being passed on to relatives, friends or other people in a personal relationship, and appellate courts have made clear that a conviction must rest on proof of a benefit in the transaction.
Martoma received his tips from Dr. Sidney Gilman, a consultant who fed the executive information about clinical trials of an Alzheimer's drug.
Prosecutors say that the financial gain was clear: Gilman received $1,000 per hour for each of the 43 consultations where he traded inside trips, and Martoma's valuable information netted him a $9 million bonus from a powerful hedge fund.
"It was a pecuniary case, and that was how the jury decided it," Assistant U.S. Attorney Robert Allen told the Second Circuit on Tuesday.
But Gilman, whose own son died under tragic circumstances, also testified that he thought of Martoma as his child.
Martoma's attorneys hope to prove that the prosecution failed to prove whether money or friendship inspired Gilman's tips.
"That's what you cannot do in a post-Newman world," Clement argued, referring to the Second Circuit ruling loosening securities fraud laws.
The Newman precedent forced prosecutors to drop charges against Martoma's former colleague Michael Steinberg, an ex-portfolio manager at SAC Capital.
The U.S. Supreme Court later restored insider-trading law to some of its former strength, however, in the case of Bassem Salman, a grocery wholesaler who made $2 million on information from his investment banker brother-in-law.
Both the Newman and Salman cases interpret a far earlier precedent: the Dirk decision from 1983.
Attempting to thread the needle of this judicial trio, a three-judge panel today struggled to define when a personal relationship implicates securities laws.
"What does a 'meaningfully close' relationship mean?" Chief U.S. Circuit Judge Robert Katzmann asked. "How do we put teeth into that?"
Drawing a hypothetical, Katzmann asked both parties whether a tip of inside information to the doorman of an apartment in lieu of money would qualify.
"A gift to a doorman is just as impermissible as a gift to a brother or sister," Allen, the prosecutor, replied.
U.S. Circuit Judge Denny Chin appeared skeptical that the government needed to show anything more than the financial motive.
"Why isn't what the government pointed to enough?" Chin asked.
Today marks the second time that the Second Circuit has heard Martoma's appeal. The court called for a new round of hearings in light of evolving precedent.
The last time around, U.S. Circuit Judge Rosemary Pooler noted, prosecutors argued that it was logically impossible for the jury to have convicted on what it called the "pure friendship theory."
Clement, a onetime U.S. solicitor general, took the opportunity to land a dig at his former colleagues in government. "They may have said that," Clement said, "but they may not know what 'logically' and 'possible' mean."
The judges reserved decision on the appeal, leaving another cliffhanger in the securities-fraud saga.
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redpajama_set_name: RedPajamaCommonCrawl


What is the Affective Filter and How does it Impact Students?
The Affective Filter (AF) Hypothesis states that a students' emotional state can impede their ability to receive comprehensible input, aka understand what is being taught to them. For example, test anxiety is said to lower otherwise high-performing students' test scores. The AF theory applies that logic to all learning in the classroom. For example, if a student is so worried or anxious that they might be called on unexpectedly and/or embarrassed of their pronunciation or speaking skills, they could experience tunnel vision; staring intently on only one word on the page in front of them to seem as though they are paying attention… all the while mentally praying they are not called on. All possible learning is being blocked out by their extreme fear of being called on. It is impossible to know the inner-workings of each student's mind or who maybe be having this experience if the student does not discuss it with you. However, it is possible to employ some general teaching practices that can hopefully alleviate or at least help to mitigate the effects of some of the negative emotions students experience in the classroom.
Students like to feel heard. They like to know that they have a voice and that that voice is valued by their teacher. Be open for communication and feedback. Ask your students what works for them and what doesn't? Most programs provide end of course evaluation forms for students to complete. Go one step further. At the halfway point of your course ask your students to anonymously answer two questions: What do you like about this course so far? What could your teacher do differently/more of? Asking these questions at the halfway mark still leaves you time to address them head-on and create a more meaningful learning experience for your students.
One of the easiest ways to lessen student anxiety in your classroom is to have clear expectations. For example, you are going to be covering a selected reading in class today. Students will be asked to discuss comprehension and critical thinking questions related to the reading aloud. Setting this expectation before the reading, and also previewing the exact questions they will be asked, gives an anxious student time to mentally prepare for being called upon, and also lets them know exactly the information they should be on the lookout for during the reading. In short, you are eliminating the chance for surprises, something that arguably has no place in the classroom anyway –unless it's the unexpected and always pleasant cancelled class on a beautiful spring day.
Just as students like to feel heard, they like to feel valued. Some educators are choosing to have students complete a questionnaire at the beginning of the course asking what their interests, hobbies, and/or fields of interest are. Choosing to incorporate this information about your students not only makes them feel valued, but also makes the content infinitely more engaging. This can be done in a full classroom with many students, but is probably better suited to small group classes and/or tutoring. For example, when tutoring a student in grammar, who was a dermatologist in her home country before moving to the U.S., you could provide her with example sentences and activities revolving around the field of dermatology.
Why are your students here? Do they need academic English skills to get into a university program? Do they need survival English because they are refugees in a new country surrounded by a new language they don't understand? Do they need professional English skills for their jobs or trade? Understanding your students' goals, and helping them achieve them, is a sure fire way to make them feel comfortable in your classroom.
Your students had a life before your class. They continue that life when they leave your doors every day. Perhaps they're parents or grandparents, employees or employers, or even someone who hasn't been fortunate enough to ever receive a formal education before. Perhaps they've lived in refugee settlements, travelled the world, or even had to be evacuated due to natural or man0mad disasters in their country. Whatever their individual stories may be, the one thing they all have in common is that there is definitely a story for each of them. Acknowledging these life experiences or prior knowledge is yet another way to make them feel comfortable in your classroom. One way to do this is to ask open ended questions. Give your students the chance to share their story in relation to class materials. You may find that these experiences change not only the classroom culture, but also the course of your lesson –and sometimes that's OK!
The Affective Filter Hypothesis posits that the emotional state of your students has a direct impact on their ability to learn. While you cannot be a mind reader, you can try your best to build an environment that is conducive to learning by making your students comfortable in your classroom. This can be done from a variety of ways: being open to communication and feedback from your students, having clear expectations, incorporating their skills/hobbies/interests, including their goals into your instructional design, and finally by acknowledging their life experiences and prior knowledge. All of these methods are sure to build a strong rapport with your students.


1 long ride. Saddle time is sorely lacking. Bonked after hour 3 on first ride. I need to be able to do 8 hours without a thought because that's probably where Butte really gets started.
Haven't had time to just ride. In complete survival mode for Butte. I'll be fit by fall though.
I want a bowling ball.


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Active Club begins at 8:00am every morning, rain or shine. Parents who start work early are able to drop their children off to be active and have fun with friends in a safe and stimulating environment. With an abundance of resources and activities available, it allows the children who attend the club to interact with each other, get creative and be prepared for the rest of their school day. Children who attend Active Club have a special bond with each other and it is a fantastic way for children from Reception to Year 6 to play and learn together – developing new friendships along the way. For more information, call the school office or contact us via parentmail.
What The Students Say…
"It's really fun and I enjoy playing with the footballs." Jacob
"I love making dens with my friends." Riley
" I like playing with all my friends." Lex
"It's a fun experience and you get to play and chat with your mates." Ellie
"My mum goes to work so she drops me and my sister off. We can do almost anything. Building dens and going on the iPads are my favourite." Lyirah
"I like building dens and playing dodgeball and trying to hit the grown ups."
What Activities Are Available?
Playing with friends
Bench ball
Dolls and monster feet
What The Teachers Say…
"I love seeing their smiley faces on a morning and how well they interact from different year groups."
"It's a real privilege to support Active Club on a morning (apart from having to constantly dodge footballs and shuttlecocks). The children put smiles on our faces with their enthusiasm and ability to create their own games and activities using the resources available. It's a great start to our day!"
Mrs Friend and Mr Robins


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Poland in favour of lifting EU sanctions on Belarus
Polish Foreign Minister Witold Waszczykowski said on Monday that Warsaw supports the lifting of EU financial sanctions and visa restrictions on Belarus.
Polish Foreign Minister Witold Waszczykowski. Photo: EPA/ANDREAS GEBERT
Waszczykowski also said he plans to visit Belarus in the near future.
Speaking to reporters in Brussels ahead of a meeting of EU foreign ministers, Waszczykowski said that easing sanctions against Belarus would be an "experiment".
"We, as neighbors, are happy with that, because it will improve our relations, I hope," he added.
Waszczykowski told reporters: "I'm also planning a trip to Belarus in the near future, to see if there has been any progress and whether the goal of Belarus is the desire and determination to cooperate with the EU and, above all, to cooperate with us, with Poland."
EU foreign ministers are expected later on Monday to allow most of the bloc's sanctions against Belarus to expire.
Brussels imposed sanctions targeting the authorities in Minsk, including President Alexander Lukashenko, after flawed presidential elections and a crackdown against the Belarusian opposition. The sanctions included asset freezes and visa bans.
In October, the EU suspended for four months sanctions against 170 individuals in response to the release of political prisoners by Minsk and a thaw in relations between Brussels and Belarus. (pk/rg)
Source: PAP/IAR
tags: EU, Polish-Belarusian relations


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Free Digital Marketing Ebooks. Read a FREE SEO Book, FREE Web Analytics Book, FREE Social media marketing book and more – www.emarketinginstitute.org.


Welcome to The Cottage which offers luxury holiday accommodation for 4 people and is situated in the grounds of Carr Mount Estate, Whitby offering a tranquil setting for a special holiday or event.
This open plan area offers a sociable atmosphere with comfortable seating for 4 around the glass topped dining table looking out through the patio doors onto a private patio and lawn. The kitchen and dining area are extremely well equipped for your self catering needs. The kitchen boasts a dishwasher, fridge/freezer, an electric range with induction hob, microwave and plenty of high quality crockery and cutlery. Perfect for your self catering needs.
Between the two bedrooms there is a large built in cupboard which offers that all important extra storage for holiday clothes and cases.
The master bed room has a luxury 5ft bed, walk in wardrobe, built in bedside tables and dressing table area. The en suite shower/ wet room comprises of a modern white suite with walk in shower with seat and tiled to the same high standard as all the rest of the properties.
The twin room does not disappoint offering comfort and quality. With 2 3ft twin beds, plenty of storage, a built in wardrobe and adjoining dressing table this room is both tranquil and relaxing.
The first floor bathroom is a generous size, comprising of a white suite, separate walk in shower and echo's the same high quality décor as the rest of the property. It can be used as an ensuite to the twin room or as the house bathroom. The bathroom also comes with under floor heating.
The lawn and patio area are south facing and has the sun (weather permitting) for the majority of the day where you can relax either for early morning coffee or unwind with a glass of wine at the end of the day on comfortable outdoor seating.
Should, due to technical reasons, live availability or pricing not be available we do apologise. In this event please contact Carole on 07789934816 who will be pleased to help.
If you would like to find out if any of our properties are currently available and the cost for your stay you can either complete out the form below and one of our friendly staff will get back to you with more information or you can call Carole on 07789934816.
The Byre Cottage is not suitable for young children children, please contact Carole on 07789934816 to discuss.
Please request any extras in the comments field when making your payment or phone / email us after your transaction is complete.
The Barn and The Cottage can be booked together and used as one property for larger groups / events — as they use the same entrance hall.
To view availability for both properties together, please visit our Rates & Booking Info page and select 'The Barn Cottage' from the dropdown menu.


I was talking with Dr. Arturo V. Estuita, MD, a Filipino internist and chelationist, the other day, December 17,2012. He administers infusion chelation therapy for my heart disease (myocardial ischemia). He told me of his friendly visit and shop talk with a fellow chelationist in Quebec, Canada.
"In the three days that I was with him, we talked of nothing but stem cell," he said.
The latest in stem cell is oral stem cell therapy. You would think it is less effective than the infusion stem cell therapy. However, this oral stem cell has a role hitherto unsuspected. The dose of stem cell, small it may be, serves as a signal. It is a signal that activates stem cells stored in the body.
The assumption is that the body, having developed from a single stem cell, has reserves of stem cells that renew themselves. As the body grew and matured they might have lost their initiative to differentiate. Or their expression has been suppressed by some genes. Or that their potential to differentiate might have been disturbed by some factors. Candidate factors are free radicals and their derivatives called reactive oxygen species.
There are some free radicals that serve as signal, however. One is the nitric oxide (NO) whose production is catalyzed by endothelium nitric oxidase (iNOS). This signals the inner wall of the artery to dilate and allow more blood flow. Dilation prevents or alleviates angina and heart attack.
There is a NO that has an unintended adverse effect. Its production is catalyzed by the enzyme inducible nitric oxidase (iNOS). This NO/iNOS is mediated by the macrophage, a component of the immune system. The macrophage uses it to shoot the bacteria (Streptococcus pyogenes) that attacks muscles, including valves of the heart. NO/iNOS kills the bacteria but also inflicts damage on healthy cells in the vicinity of infected cells. Hit cells sustain scars that graduate into stenosis in heart valves resulting in valve insufficiency or defective closure. These allow backflow of blood.There, you have rheumatic heart disease.
The belief that neurons, brain and cardiovascular cells do not renew themselves appears not to be true. This is according to Prof. Jill Helms, a stem cell researcher at the Stanford Medical School, Stanford University in California, USA. End of editing.
I heard my conventional cardiologist tell a patient who had scars in his heart and who got well without medication that his heart healed. EPC might have done the healing.
Today, stem cells are collected from the blood and grown in culture to get more concentrated stem cells. These then will be used for stem cell therapy.
The start is conception (fertilization). "One month, your baby is an embryo consisting of two layers of cells from which all her organs and body parts will develop. Two months, your baby is now about the size of a kidney bean and is constantly moving. He has distinct, slightly webbed fingers" (Fetal development. Internet. Dec. 19.2012). This fetal development up until the ninth month shows differentiation.
Adult stem cells are in "different levels of multipotency and unipotency" like brain cells, bone morrow cells, digestive system cells and more (Bellomo, M. The Stem Cell Divide. 2006:39).
A newborn or an adult human being has stem cells, to repeat the obvious.
At the start of intensive stem cell research, it was believed that the only source of stem cell for use in research was the embryo. There arose an ethical issue over the use of embryo in research that is tantamount to killing the embryo.
Hubber AliciaC mentions that Sir John Gurdon and Shinya Yamanata succeeded in reprogramming adult cells into pluripotent stem cells for which they were awarded the Nobel Prize.
Later on stem cells from the cord blood were found to be alternative materials in research. In fact, cord blood is now being used in stem cell therapy in curing leukemia, for example. Methods in research has progressed until it was discovered that even adult cells can be used in stem cell research. All the better because it implies that adult cells can be grown to replace damaged cells. That is now being done.
Yamanaka reprogrammed adult skin cells. He took a small part of adult skin cell, grew it in dish and added four factors, Oct4, Sox2, Klf4 and c-Myc. The adult cells grew embryonic stem cells. Now, there is no more need for embryonic stem cells that came from the fertilization of the egg by the sperm for use in research and stem cell therapy. End of editing.
The above is the context of the use of oral stem cell therapy. The oral dose serves as a signal that triggers multipotent or unipotent cells to differentiate and replace damaged cells. If an earlobe had been torn, stem cells will regrow the earlobe. If a mitral valve had been damaged unintentionally by free radicals in an effort to kill bacteria, stem cells can regrow the mitral valve. If heart muscles had been damaged (myocardial atrophy), stem cells will regrow the heart. If the kidney had been damaged (kidney atrophy) stem cells will regrow the kidney. If the liver had been afflicted with cirrhosis, stem cells will regrow the liver.
However, organs cannot be grown in dish then grafted on the body. The stem cell feeders in dish do not contain the right growth factors and it lacks blood supply.
It's like the lizard. When its tail had been cut off that tail will regrow. We can say that the stem cells of the lizard are always active. In the case of the adult human being, his/her stem cells must be given a signal to regrow worn off, torn off, and diseased body parts.
The stem cell of the person who needs stem cell therapy can be used. Therefore, there is no rejection. The stem cell to use must be free of damage inflicted by free radicals or reactive oxygen species, according to Doug Wallace, director of the Center for Molecular and Mitochondrial Medicine and Genetics (Same source as above, page 184).
You can see the promise of stem cell therapy. In fact, it is no longer just a promise. Dr. Estuita, MD says that his clinic now administers stem cell therapy in addition to infusion chelation therapy for the heart, for the treatment of hepatitis B, C, D, and prevention of cirrhosis and cancer of the liver.
Dr. Robert Willix, MD, a cardiac surgeon who wrote that he had turned his back on surgery, has a book "3 Minutes In a Day To A Life Span of 120 Years" (published in 1995). He claims that by controlling free radicals, a fellow can attain that life span.
"With oral stem cell therapy I may live longer than that," Dr. Estuita said.
The United States is only starting with stem cell research. It is already in the trial stage. There are at least four stages in the development of protocol or procedure or drug. So, the West is behind in stem cell research and therapy.
The East, like Philippines, Thailand and China are now administering stem cell therapy. They have bypassed the trial stage and has gone ahead in therapy. Some people have been willing to try this new therapy consenting to take the risks. For example, an ailing heart is injected directly with stem cells. This heart is suffering from cardiomyopathy (atrophy) owing to severe bronchitis that it could pump only 25% of blood.
It is highly probable that Superman, Christopher Reeves, an American, could have survived and been revived had he been given stem cell therapy. His neck was broken when he was thrown off by his racehorse that suddenly stopped at an equestrian hurdle. He advocated stem cell research (Bellomo, M. Stem Cell Divide. 2006) He died before he could benefit from stem cell therapy in the United States. Some Americans had gone to Thailand and China for stem cell therapy.
One American went to China for stem cell therapy to heal his spinal cord. He met an accident and he was paralyzed from the chest down. He could not move his arms and legs. At the time a documentary film was taken on him, he can move about in the streets riding on a wheelchair with his arms rolling the wheels, could dismount from it and fold it in a pedestrian lane.
Thanks for stopping by. In the body, damage not inflicted by microbes are inflicted by free radicals and derivatives that are continuously produced or acquired from the environment. These must be controlled as well so that the regrown heart valve will not suffer another atrophy. In motor neuron disease that is caused by a derivative (hydroxyl radical) and is now being treated with stem cell therapy, chelation therapy must be added to take care of the "rusts."
This early the cost of stem cell therapy may be high but as soon as more convenient methods of application are developed the cost will go down. Of course competition will also come into play.
I have not come across any formal theory of stem cell therapy yet. It is like the Salk killed polio virus vaccine. Dr. Salk and his team came up with this vaccine without elaborating a theory. I have proposed one in my Hub on how the size and shape of killed poliovirus incite immunization. A theory will confer more confidence on the reliability of stem cell therapy.
It is amazing how far science has come. These new processes can help save many live. Great information!


How much are Middletown to Bridgeport train tickets?
How to find cheap train tickets from Middletown to Bridgeport ?
The most surefire way to find the lowest-priced train tickets from Middletown to Bridgeport is to plan ahead and book your train travel earlier. In the past 30 days, the cheapest average price users have found for trains from Middletown to Bridgeport was $75.50. If your travel date is still a number of days out, by booking your trip 21 days before you plan to travel, you could save an average of $30.00 compared to a typical last-minute fare. Trying to save on a last-minute fare and have a bit of flexibility on what day to travel? Take a look at midweek schedules, as these tend to be less busy and are often cheaper than buying tickets to travel on Friday, or a weekend departure.
How long is the train journey from Middletown to Bridgeport ? How far is Middletown to Bridgeport ?
The distance between Middletown to Bridgeport is 197.48 miles or 317.73 km. A train trip from Middletown to Bridgeport typically takes 6 hours, If you are looking to get to Bridgeport faster, the fastest advertised duration is offered by Amtrak. The fastest train trip covers the distance in 5 hours and 20 minutes to get from Middletown to Bridgeport.
Going from Middletown to Bridgeport by train takes over 6 hours to reach your destination. For a lengthy train journey we recommend you pack a great book, or download a few movies to have them available offline just in case you are outside of a service coverage area. Don't forget to bring some water and a battery pack to keep all of your electronics charged.
On Saturday trains from Middletown to Bridgeport are the busiest. If you are looking for a great deal on your train tickets or to have extra room to stretch out, you might consider traveling on Wednesday instead, as that tends to be the least traveled day of the week.
Typically there are 4 schedules to compare for your trip to Bridgeport. One train carrier operates regular service on the Middletown to Bridgeport route. Amtrak offers the most scheduled departures between Middletown to Bridgeport, usually offering 4 trips per day. On this route there are no direct schedules. This means that along your journey from Middletown to Bridgeport, you will need to disembark from the first train and board a connecting train. Depending on the carrier's policy, you may be responsible for transferring your own checked luggage, but you will definitely need to bring your hand luggage.
From Middletown to Bridgeport train travel on Amtrak takes 5 hours and 48 minutes. If you are looking to get to Bridgeport faster, Amtrak offers more express schedule options with a travel time of 5 hours and 0 minutes.
There is one train station from which trains depart Middletown on their way to Bridgeport. The busiest departure station in Middletown serving this route is Union Street and Mill Street.
There is one train station where trains arrive in Bridgeport from Middletown., The busiest departure station in Middletown serving this route is 525 Water St.


Winger, MinnesotaPhotos, maps and news from Winger, Minnesota.Updated December 21, 2018.
Winger is a city in Polk County, Minnesota, United States. It is part of the Grand Forks, ND-MN Metropolitan Statistical Area. The population was 220 at the 2010 census.
Guide to Winger Minnesota. ... US Post Office, Winger Minnesota.
Guide to Winger Minnesota. ... Winger City Hall, Winger Minnesota.
Guide to Winger Minnesota. Winger Minnesota Population Sign.
Winger, Minnesota - Wikipedia. .
Winger, Minnesota (MN 56592) profile: population, maps, real estate .... Winger, Minnesota map.
Guide to Winger Minnesota. ... Calvary Lutheran Church, Winger Minnesota.
Guide to Winger Minnesota. Minnesota State Highway Map of the Winger Minnesota area.
Welcome to the City of Winger!. header.
Winger Minnesota Gallery. Street scene, Winger Minnesota, 2008.
Guide to Winger Minnesota. ... Winger Implement Inc, Winger Minnesota.
Winger Minnesota Gallery. Winger Community Center, Winger Minnesota, 2008.
Guide to Winger Minnesota. ... Winger Fire Department, Winger Minnesota.
Minnesota history: The kid who won America's greatest honor 100 .... The entrance marker for Elim Cemetery outside Winger, Minnesota..
Minnesota history: The kid who won America's greatest honor 100 .... The marker placed on the grave of Nels Wold in Winger, Minnesota, in 1921.
Strong Sunday Night Storms Cause Damage In Northern Minnesota - KVRR .... Fosston's City Owned Cable TV System Took A Hit.
Winger, Minnesota (MN 56592) profile: population, maps, real estate .... Winger, MN map.
Winger, Minnesota (MN) ~ population data, races, housing & economy. Cities & Towns nearby Winger.
Winger Minnesota Gallery. Water Tower, Winger Minnesota, 2008.
Erskine, Minnesota - Wikipedia. .
WINGER Archives - KVRR Local News. WINGER.
Five Questions Salon Edition with Phil Winger of Urban Boatbuilders .... Phil Winger of Urban Boatbuilders.


Change is rarely easy. Often times the more challenging the hurdles, the more rewarding are the results. Such may be the case with implementing pharmacogenomics, the practice of prescribing medications matched to your genetic makeup — medications that are most likely to work and have the fewest side effects. Mayo Clinic Center for Individualized Medicine has developed a successful model for all health care providers that want to apply the latest advancements to improving clinical care.
Who pays for genetic testing if insurance won't?
Once you have patients' genetic test results, how do you develop a standard process for interpreting, storing and accessing the data?
It's so new, where is the evidence of clinical utility?
How do busy clinicians keep on top of all the latest discoveries?
How do you address any ethical or legal concerns?
"Leveraging health information technology, including clinical decision support (CDS) tools and electronic health records (EHRs), will be essential to overcoming many of the barriers associated with the translation of (pharmacogenomics) guidelines into clinical practice," writes Dr. Caraballo.
Organizational silos can sink the cross-departmental efforts that are needed to implement pharmacogenomics into patient care. Success depends on gaining cross- institutional leadership support at the highest levels in order to break down the silos and work together. At Mayo Clinic, top leadership supports pharmacogenomics as an investment in good patient care and in the future of medicine.
Mayo Clinic has formed a pharmacogenomics task force made up of experts from all areas involved in implementation: genomic medicine, primary and specialty care clinics, pharmacy, laboratory, education, research, informatics, information technology and administration. This task force is a catalyst for coordinating processes and resources needed to apply pharmacogenomics to patient care across Mayo Clinic.
Identify the champions of integrating pharmacogenomics into practice within your organization. Mayo's model has shown their feedback on use of pharmacogenomics and impact on patient care can influence clinical adoption.
One key challenge is coordinating standard definitions for different genotypes and phenotypes among different laboratories in order to deliver structured test results into the electronic health record (EHR). Mayo's model recommends implementing electronic interfaces between lab systems and the EHR, when possible. Because genetic results are most helpful at the time of prescribing medications, Mayo recommends proactive pharmacogenomics testing.
"Just in time" education is important for physicians and pharmacists who often don't have time on a daily basis to study the latest discoveries in drug-gene interactions. For example, Mayo Clinic offers learning that its clinicians can tap into at the point of care through the AskMayoExpert* online tool. The site is continually monitored and updated with the latest developments that can be applied immediately to patient care and prescribing habits.
Mayo uses CPIC as the main source of clinical guideline addressing specific drug-gene interactions. CPIC guidelines follow a standard format and are designed to help clinicians understand how available genetic test results should be used to optimize drug therapy. To complement that, we also use clinical guidelines published by medical societies and other professional groups.
Mayo Clinic has integrated provider alerts into its EHRs. When a patient has a genetic variation that could lead to an adverse drug-gene interaction, a pop-up alert will trigger, advising prescribing physicians to consider alternative therapies. This system has generated some 10,000 drug-gene interaction alerts at Mayo Clinic since 2012.
For the most effective pharmacogenomics practice, develop a long-term strategy for maintaining and updating drug-gene rules, pop up alerts and integrating genetic test results into patients' electronic health record.
The implementation model described in this study ran from August 2012 through June 2015 and evaluated 21 drug-gene interactions able to produce harmful reactions to drugs. Nineteen of those drug-gene interactions have been integrated into the EHR at Mayo Clinic by using several clinical decision support interventions. Eleven educational resources were developed to complement drug-gene interactions. Five online competency-based modules were developed specifically to aid pharmacists.
"Our aim was to develop a generalizable implementation model consisting of core components for initial use at Mayo Clinic but also applicable and transferable to other institutions regardless of size or available infrastructure," says Dr. Caraballo.
A. Keith Stewart, M.B., Ch.B.
*AskMayoExpert is an online tool available to Mayo Clinic and Mayo Clinic Care Network physicians.


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G For Games
Home Gambling The Worst Mistakes to Do When Choosing an Online Casino
The Worst Mistakes to Do When Choosing an Online Casino
Nina Smith
Source: wales247.co.uk
With this huge abundance of online casinos out there most of us think that it's an easy task to select the best one. But is it indeed? Although it's impossible for someone – whether a newbie or an experienced player in the field – to be unable to register in a brand new operator within 10 minutes after opening his smartphone, the final choice is actually not always optimal.
We have tracked several wrong tendencies in the modern audience's mechanism of selecting an online casino. It seems that about 60% of the users follow the same wrong approaches. Then, among them, we have sorted out the worst mistakes that can be made while choosing an online casino. Let's discuss them below, so you will never appear in their trap anymore.
Registering only because of the new customer bonus
Not caring about the available payment methods
Counting on an old-school desktop practice
No priority lists, no good choices
It's like an unwritten rule for today's gambling companies to on mandatory reward their newly registered players with a gift. The first account promotion is something you will find in 90% of the modern internet platforms for slots and table games.
Then why sign up in the first met operator just because it has a welcome bonus? They will all provide you with a bonus code, a new deposit promo or anything else to receive you as an honorable guest.
Source: bestuscasinos.org
Gambling is about two things – having fun and earning cash. Although we strongly recommend everyone seek entertainment rather than the money factor in casino activity, payments are tasks you cannot avoid.
Whether it's about your initial investment in your newly opened account or your monthly withdrawal, you will eventually deal with e-wallets, transactions, etc. What can be quite annoying is finding a decent website, registering on it, and when the moment for a deposit comes, figuring out that there are no payment methods that actually suit your needs. You can avoid such regret by checking out the deposit and withdrawal options in advance.
Although it's hard to believe, there are still gambling companies that don't care about the mobile era revolution. They keep on gathering their customers only on a desktop platform.
This is quite tricky because in many cases a player makes a registration on a PC or laptop believing that later he can switch to the mobile-friendly casino activity. It's a huge and not pleasant at all surprising for them to find out that there are no mobile options at all. The situation is when the operator has a mobile website version, but no mobile apps are similar. Yet, at least it offers some form of gambling on the go.
Source: godisageek.com
Players in most cases are the only ones to blame for not being satisfied by some casinos, their assortment of services, or a concrete product. The thing is that many customers start their search for a new operator without any preliminary preparation. They don't know what they want.
They are unaware of what games are appropriate for them. They underestimate the significance behind factors such as SSL encryption systems, licenses, and so on. What we are trying to tell you is that before you make your choice, know what's best, especially for you.
We are now in the 2023rd year – another year that is definitely promising for the online casino industry growth. We live in times when the options are out there and the best selection is possible to be done. Just avoid the mistakes we've listed above and you will do it, too.
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What are the requirements to become a crane operator?
You'd usually start with a crane operation apprenticeship. It's also frequent to start as a construction labourer, and from there, move on to becoming a crane operator after a period of apprenticeship or training.
Have you any idea how to go about the apprenticeship? I wouldn't know where to start.
I advise you to look at the ukdrivers page, I think it's very useful.


"My self-esteem was really low and I just didn't think I would be able to get a job. They just told me, 'You have a purpose and you need to do it for your children.' And the support that I found here with all of the girls has been phenomenal."
"I've been there. I've been one of those people who was embarrassed to ask anybody for anything. I felt like your private stuff should stay private. To feel so welcome and be able to just let it out, it felt so good."


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Q: What should I update in my PHP setup when I change my MySQL databases to UTF-8 encoding? I currently operate a website on a PHP 5 and MySQL backbone.  The MySQL databases uses cp1252 West Europe ( latin1 ) encoding, and latin1_swedish_cp collation.
I'd like to switch the MySQL databases to UTF-8 encoding and utf8_general_ci. I don't need help converting the content within MySQL as I'm processing that as it goes in and redoing all the content on the site.  Assume I'm doing that correctly for this conversation ( even though I'm probably not ).
I know there are settings in php.ini like default_charset that default to iso-8859-1.  I also know that many of PHP's string manipulation functions like strlen(), as well as regexes, will not work correctly if I'm dealing with strings that contain multi-byte UTF-8 characters, which I realize is not all characters in the UTF-8 set.
What do I need to do to PHP server side and within my webapp to deal with UTF-8 coming out of my database?  What does it all do?

A: You will have to set-up your DB connection with :
mysql_query("SET NAMES 'utf8'");

And then replace your "regular" string functions with those from the mbstring module :
http://php.net/manual/en/book.mbstring.php
like mb_strlen, mb_substr, etc.
As well as specify UTF-8 encoding where needed, for instance in the htmlentities function :
echo htmlentities($str, ENT_QUOTES, "UTF-8");

A: See this function.
Also, you should save all your files with utf-8 encoding (preferably without BOM).

redpajama_set_name: RedPajamaStackExchange


Brand new tune titled 'BACK', the highly Anticipated single from extremely talented and versatile OBAKONSO.
Obakonso move on with his Music Career after he has released his two single "Ire" and "Money (Owo)" that is already trending online and in the street now..
The melodious Song is Fi you all ladies is now here and I bet you'll all love to hear this sound and keep it on Repeat on your playlist. Enjoy!!
Back was produce by magicboi, mixed and mastered by Obakonso.


International Day against Drug Abuse and Illicit Trafficking: Calendar, History, Tweets, Facts, Quotes & Activities.
The International Day Against Drug Abuse and Illicit Trafficking serves to draw awareness to the need for action and cooperation in order to achieve a drug-free world. Illicit drugs and their trafficking pose a large health threat to humanity. Drug problems and dependencies put a great deal of pressure on health care systems and constitute a threat to the safety and well-being of humans all around the globe. Long-term drug abuse has been linked to poor general health, contraction of diseases through needle sharing, trouble with the law, poor self-hygiene and alienation from loved ones, psychological illnesses and death from overdose.
In December 1987, the International Day Against Drug Abuse and Illicit Trafficking was designated by the United Nations. It is celebrated annually on June 26, a symbolic day that commemorates the dismantling of the opium trade in Guangdong. The day also serves as an opportunity for Member Nations to reaffirm their support for UN Conventions that attempt to control the world's drug supply.
Deaths caused by drug overdose rose faster than ever in 2016, and were likely to continue to worsen in 2017, as reported by the New York Times.
Approximately 51 billion dollars is spent on the war on drugs in the US every year.
40% of all violent crimes occur under the influence of alcohol.
No one is immune from addiction; it afflicts people of all ages, races, classes, and professions. – Patrick J. Kennedy, American democratic politician and former US representative for Rhode Island.
Donate to one of the many addiction and substance abuse recovery charities and safe injection sites in your neighborhood. All proceeds are used to help treat addicts who are looking to recover from drug addiction and return to society and safe needle programs help reduce the spread of HIV/AIDS and other diseases.
Watch a movie on the perils of the war on drugs on society, government and the citizens involved. Some suggestions are: Dallas Buyers Club (2013), Sicario (2015), Requiem for a Dream (2000), Christiane F (1981) and Blow (2001).
Attend the World Drug Report 2016, which is organized by the United Nations Office on Drugs and Crime, by watching the webcast online.
Spread awareness by using the hashtags #WorldDrugDay, #saynotodrugs and #warondrugs on social media.
Read a book on the dangers of drug use and the problems with the war on drugs. Some suggestions are: Smoke and Mirrors , Chasing the Scream , and Drug Wars .


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Dollarama in Leduc opening hours
Leduc is one of the shops of Dollarama that have a place at 6102 50th Street, T9E 7L2. Our website provides detailed information about the opening and closing hours today, the address, services and more. The shop serves customers landing from neighbouring areas, for example,
Subway in Leduc - about 0.2 miles away,
KFC in Leduc - about 0.3 miles away,
McDonalds in Leduc - about 0.3 miles away,
Dollarama in Leduc is typically open on Monday: 09:00-21:00, Tuesday: 09:00-21:00, Wednesday: 09:00-21:00, Thursday: 09:00-21:00, Friday: 09:00-21:00, Saturday: 09:00-18:00. Its Sunday opening hours are: 10:00-17:00. The store provides services including:
T9E 7L2
Sorry, we don't have enough information.
You can send us more info about Dollarama, Leduc on T9E 7L2, 6102 50th Street using the link 'Report incorrect information' bellow.
Starbucks in Leduc - about 0.1 miles away,
Tim Hortons in Leduc - about 0.4 miles away,
Scotiabank in Leduc - about 0.4 miles away,
Canada Post in Leduc - about 0.6 miles away,
Royal Bank of Canada,RBC in Leduc - about 0.7 miles away,
Bank of Montreal,BMO in Leduc - about 0.7 miles away,
TD Canada Trust in Leduc - about 0.8 miles away,
Select ratingGive Dollarama 1/5Give Dollarama 2/5Give Dollarama 3/5Give Dollarama 4/5Give Dollarama 5/5
Nearest stores of Dollarama
Dollarama in Leduc, 5309 Discovery Way (1.0 miles)
Dollarama in Beaumont, 100A-5700 50th Street (8.0 miles)
Dollarama in Edmonton, 5015 111 St. NW (14.4 miles)
Dollarama in Edmonton, 10455 80th Ave. NW (16.7 miles)
Dollarama in Edmonton, 8882 170th St. Un M102 (17.3 miles)
Dollarama in Wetaskiwin, 3725 56th Street (23.1 miles)
Dollarama in St-Albert, 140 St. Albert Rd. (24.0 miles)
Dollarama in Spruce Grove, 187 Highway 16A (24.2 miles)
Dollarama in Fort Saskatchewan, 8802 100th Street (32.5 miles)


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See You All in Hell
From JoCopedia
Thing a Week One
Redux entry
{{#song:See+You+All+in+Hell }}
"See You All in Hell" is a song on Jonathan Coulton's fourth album Thing a Week One. It is both the opening track of the album and of the Thing a Week experiment. The vocals are done by Jonathan Coulton's Mac.
"See You All in Hell" was released as the first Thing a Week on September 16th, 2005. According to Jonathan, "The lyrics are taken from a text message that a TV producer sent while having a difficult time on some sort of aquatic shoot, somewhere far away where it's probably hot and dusty and hard to get around."
Live performance[edit]
"See You All in Hell" is believed to have never been played at a Jonathan Coulton concert. Given the sampled nature of the song, it is unlikely that it will be performed.
Availability[edit]
Downloads[edit]
"See You All in Hell" is available for purchase in the Jonathan Coulton MP3 Store as an individual track or as part of Thing a Week I. Of course, this song is also included as part of the "Everything" playlist.
Downloadable FLAC versions of the above are available in the Jonathan Coulton FLAC Store
CD[edit]
"Thing a Week I" is available for purchase as a CD here.
Themes[edit]
Thing-a-Week One
1. See You All in Hell · 2. My Monkey · 3. W's Duty · 4. Shop Vac · 5. Baby Got Back · 6. Someone Is Crazy · 7. Brand New Sucker · 8. Sibling Rivalry · 9. The Town Crotch · (*) When I'm 25 or 64 · 10. Podsafe Christmas Song · 11. Furry Old Lobster · 12. Drive
Retrieved from "https://wiki.jonathancoulton.com/index.php?title=See_You_All_in_Hell&oldid=26484"


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The Status of House Business provides cumulative information on the status of business before the House during a session. The document is updated after each sitting.
This section contains bills sponsored by private Members which concern matters of a particular interest or benefit to a person or persons. Bills in this section which originated in the House of Commons are numbered in sequence, starting with C-1001, while those which originated in the Senate have an ``S'' preceding the number of the Bill.
S-18 -- Mr. Godfrey (Don Valley West) -- An Act respecting the Alliance of Manufacturers and Exporters Canada
Message received from the Senate; Bill deemed read the first time; placed on the order of precedence; deemed designated as a votable item -- May 5, 1999
Petition for Private Bill filed with the Clerk of the House -- May 5, 1999
Report of the Clerk of Petitions -- May 6, 1999
Report of the Examiner of Petitions for Private Bills -- May 7, 1999
Read the second time and referred to a Committee of the Whole; considered in Committee of the Whole; reported without amendment; concurred in at report stage; read the third time and passed -- May 31, 1999
Royal Assent -- June 17, 1999
S-20 -- Mrs. Redman (Ketchener Centre) -- An Act to amend the Act of incorporation of the Roman Catholic Episcopal Corporation of Mackenzie
Petition for Private Bill filed with the Clerk of the House -- December 9, 1998
Report of the Clerk of Petitions; report of the Examiner of Petitions for Private Bills -- December 10, 1998
Message received from the Senate; Bill deemed read the first time; placed on the order of precedence; deemed designated as a votable item -- December 10, 1998
Debated at second reading; read the second time and referred to a Committee of the Whole; considered in Committee of the Whole; reported without amendment; concurred in at report stage; read the third time and passed -- March 18, 1999
Royal Assent -- March 25, 1999
S-25 -- Ms. Catterall (Ottawa West -- Nepean) -- An Act respecting the Certified General Accountants Association of Canada
Message received from the Senate; Bill deemed read the first time; placed on the order of precedence; deemed designated as a votable item -- April 23, 1999
Petition for Private Bill filed with the Clerk of the House -- April 26, 1999
Report of the Clerk of Petitions; report of the Examiner of Petitions for Private Bills -- April 27, 1999
Read the second time and referred to a Committee of the Whole; considered in Committee of the Whole; reported without amendment; concurred in at report stage; read the third time and passed -- April 28, 1999
Royal Assent -- April 29, 1999


Can you believe it? There's only a few more days left in the year. Time sure does fly by when you're having fun. The Mailjet team's spent the last week looking back on all that we've accomplished the past year – the projects we've completed, the products we've pushed, the places and people we've met.


Hiroshima has announced its "Spirit of the Season" holiday show schedule.
Inaugurated over 10 years ago in partnership with the Japanese American Cultural and Community Center to build community spirit in Little Tokyo, the program will feature Christmas favorites done the Hiroshima way and songs from the band's latest CD, "Departure," a follow-up to their 2010 Grammy-nominated "Legacy" CD.
Special guest stars include former Hiroshima vocalist Terry Steele and harmonica virtuoso Tetsuya "Tex" Nakamura, a former member of War.
Artists will be available to autograph CDs after the concert.
CDs are available online at www.hiroshimamusic.com (member discounts available for those who join the Hiroshima community); in Little Tokyo at Rafu Bussan and the Japanese American National Museum; and in Gardena at Cherrystones Grill & Grotto.
• Saturday, Dec. 1, at 8 p.m. and Sunday, Dec. 2, at 11 a.m. (brunch) and 7 p.m. at Spaghettini, 3005 Old Ranch Parkway, Seal Beach; (562) 596-2199, www.spaghettini.com. Buy tickets at http://spaghettini.tix.com/.
• Friday, Dec. 14, at 8 p.m. at Lewis Family Playhouse, Victoria Gardens Cultural Center, 12505 Cultural Center Drive, Rancho Cucamonga; www.lewisfamilyplayhouse.com. Box office: (909) 477-2752.
• Sunday, Dec. 23, at 7:30 and 9:30 p.m. at Anthology, 1337 India St., San Diego. Tickets: (619) 595-0300, www.anthologysd.com.


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VW GTI Clubsport S debuts, breaks 'Ring record for FWD cars
Volkswagen's GTI is 40 this year and we can think of few better ways to celebrate than the setting of a Nürburgring lap record.
Well, that's exactly what VW has done using the new GTI Clubsport S.
The Clubsport S was revealed today at the annual Wörthersee Tour GTI tuning fest in Austria, where it was also confirmed the car had lapped the Nürburgring in a time of 7:49.21. Doing the driving was German racer Benny Leuchter.
This was enough to nudge Honda's Civic Type R and its 7:50.63 lap time off the top pedestal. Of course, there's a new Civic Type R just around the corner and we're sure Honda will use it to reclaim the record. Note, this record is front-wheel drive cars. The record for all production cars still stands at 6:57 as set by the Porsche 918 Spyder in 2013.
But today it's all about the Clubsport S. The car is the most powerful Golf in production with its peak output coming in at 306 horsepower and 280 pound-feet of torque. The engine is a turbocharged 2.0-liter 4-cylinder like the one in the regular GTI and Golf R but benefits from specific ECU tuning, a new fuel pump, a less restrictive exhaust and added boost pressure.
Drive is to the front wheels only via a 6-speeed manual transmission. The transmission choice, along with the selection of the Golf's 3-door body, was chosen to keep weight at minimum. We're told the car tips the scales at less than 3,000 lb and will sprint from 0-62 mph in 5.8 seconds. The top speed is 162 mph.
Other key modifications include an aero kit, Michelin Sport Cup 2 tires and uprated brakes. Engineers also tweaked the GTI's electronic chassis control system by adding a setting fine-tuned to suit the unique conditions of the Nürburgring (the track is renowned for its sharp corners combined with numerous bumpers and dramatic elevation changes).
The GTI Clubsport S is an evolution of the tamer GTI Clubsport we saw last year. Production will be limited to just 400 units worldwide and sadly we hear none are earmarked for the United States. To make matters worse, we hear the car's development has come at the cost of a much more extreme model based on 2014's Golf R 400 concept.
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The deadly Chicago apartment on the weekend claimed its ninth victim.
Cesar Contreras, 14, died Monday night in one Hospital, while another boy of the same age remains in critical condition, said the Cook County Medical Examiner's Office.
The fire that took place in a three-story complex on Sunday at four in the morning Chicago's small village quarter broke out, killing seven children and two adults. Investigators found no functioning smoke detectors in the house.
The coroner's office gave The identity of three of the children released as three-month-old Amaya Almaraz, ten-year-old Giovanni Monarrez and 16-year-old Victor Mendoza. All three were listed as residents of the block where the fire happened.
Although one exact cause still needs to be determined, Langford said that children had firecrackers on the lobby in the past, and it was also a place where people smoked cigarettes. He said the investigators had ruled out problems with the building's electrical system as a cause and did not believe that it had done so on purpose. Langford pointed out that the victims, if there were smoke detectors, could have survived alive.
"Because where it started (on the back porch of a back house), if they had at least one smoke detector, you would have woken up and gone out the front door," said Langford, "they could all have grabbed a staircase and outside (because ) they had a clear chance on the front door. "
The Chicago Sun-Times reports that the city's building department says the owner of the apartment building is due to court next month after being cited for two electrical violations.  The fire is Chicago's deadliest since at least 2000, and possibly since 1993, when 19 people died in a blaze devouring a single-occupancy residential hotel.