text:
Oxford study finds digital screen time has little effect on teen mental health
By Rich Haridy
A new study found that wearing glasses has a greater negative impact on a teenager's well-being that digital technology use
monkeybusiness/Depositphotos
A new study from researchers at the University of Oxford has tracked data from several hundred thousand subjects finding digital technology use accounts for less than half a percent of a young person's negative mental health. The research suggests everything from wearing glasses to not getting enough sleep have bigger negative effects on adolescent well-being than digital screen use.
The effects of digital screen time on children's well-being and development is a source of huge debate at the moment. While concerns over the effects of these new devices on childhood development are not unwarranted, scientists have not been able to reach a clear consensus on the topic.
The latest study is one of the largest and most definitive to date, examining data from over 350,000 subjects in the UK and US. The first challenge the researchers faced with this study was trying to overcome the selection bias that can plague this type of technology research.
"Of the three datasets we analyzed for this study, we found over 600 million possible ways to analyze the data," explains Amy Orban, an author on the new research. "We calculated a large sample of these and found that – if you wanted – you could come up with a large range of positive or negative associations between technology and wellbeing, or no effect at all."
The new study used a method called Specification Curve Analysis (SCA) to dig through the data and find meaningful associations. The method essentially attempts to analyze the data using as many justifiable specifications as possible. After calculating as many variables as the data would allow the researchers are then able to compare the effects of digital technology use on well-being against a vast array of other factors.
The results were stark and convincing with digital technology use accounting for just 0.4 percent of a young person's overall negative well-being. Binge-drinking and marijuana use were noted as having significantly larger negative effects on a young person's well being. Bullying, for example, was found to have four times larger the negative effect on well-being than digital screen use.
On the positive end of the spectrum, things like eating a good breakfast and getting enough sleep were much more statistically relevant in affecting well-being than the effects of technology use.
"Our findings demonstrate that screen use itself has at most a tiny association with youth mental health," says Andrew Przybylski, lead researcher on the study. "The 0.4% contribution of screen use on young people's mental health needs to be put in context for parents and policymakers. Within the same dataset, we were able to demonstrate that including potatoes in your diet showed a similar association with adolescent wellbeing. Wearing corrective lenses had an even worse association."
Although this study is relatively robust it isn't without limitations, perhaps the most significant of these being how all digital technology use is rolled into one homogenous entity. Ben Carter, a researcher from King's College London who did not work on this new study, suggests the lack of specificity surrounding digital technology use is important when trying to interpret what this research means moving forward.
"This study was only able to look at the duration of use and not the way in which the technology was being used (the content and time it was being used) which could possibly provide a better indicator of well-being," says Carter. "For example, is the technology use of a twelve-year-old spending a few hours on a computer doing school work during the day the same as if it was say, 10pm at night and scrolling through social media posts for the same length of time? Therefore, the way in which technology is used by young people and the impact of social media specifically is something we need to look at in future studies."
Przybylski would perhaps be the first to agree with Carter's suggestion that more granular research is needed to ascertain specific and contextual consequences of digital technology use. Last year Przybylski published a study suggesting general digital screen time does not disrupt children's sleep. At the time Przybylski said, "Focusing on bedtime routines and regular patterns of sleep, such as consistent wake-up times, are much more effective strategies for helping young people sleep than thinking screens themselves play a significant role."
The general implication here is that screen time, in and of itself, is not a harmful causal agent. Max Davie, from the Royal College of Pediatrics and Child Health (RCPCH) in the UK, recently published new screen time guidelines suggesting general age-appropriate time limits for children are nearly impossible to quantify. The new RCPCH guidelines instead focus on positive activities such as socializing, exercise and sleep, noting that it is only when screen time displaces these activities that there is a risk to a child's well-being.
"This study supports the findings of our recent review of the evidence base on screen time, that while there are some negative associations between screen time and poor mental health, we cannot be sure that these links are causal, or if other factors are causing both negative health outcomes and higher screen time," says Davie.
Przybylski's research is working hard to overcome the big problem facing this kind of observational research into the effects of technology. It's a classic causation versus correlation dilemma, and in the field of technology research, individual bias cannot help but seep in. Kevin McConway, a professor in applied statistics from Open University, suggests the vast majority of modern screen time research suffers from this shortcoming.
"So if young people who report more screen use are also more likely to be depressed, that could be because screen use tends to cause depression, or it could be because young people who are depressed anyway tend to spend more time using screens," says McConway.
McConway's solution backs up the recommendations from Davie and the RCPCH affirming the best guidance is towards better general parenting principles rather than trying to determine an ideal hour-per-day amount of screen time that is appropriate for all children.
"The nuanced pictureprovided by these results is in line with previous psychological andepidemiological research suggesting that the associations betweendigital screen-time and child outcomes are not as simple as manymight think," Przybylski and his team conclude in the recently published study.
It is becoming increasingly clear that there is no simple answer to the screen time debate. Not all screen time is created equal and parents looking for a straightforward answer regarding how much time they should allow their child to have with screens may begin to realize they are asking the wrong question.
The new study was published in the journal Nature Human Behavior.
Source: University of Oxford
ScienceDigital MediaDigitalScreensChildrenNew Atlas Audio
Rich Haridy
Rich has written for a number of online and print publications over the last decade while also acting as film critic for several radio broadcasters and podcasts. His interests focus on psychedelic science, new media, and science oddities. Rich completed his Masters degree in the Arts back in 2013 before joining New Atlas in 2016.
fb36 January 14, 2019 05:44 PM
How about checking Screen Time VS Unable to Focus (on any subject) for long?
How about checking Social Media Time VS Unhealthy Social Life, etc?
Instead, they just look at "is screen time make teenagers crazy or not?"!!!
Anybody could tell that the answer they would find would be no! Because if screen time made people crazy then there would be no computer office jobs!
How about checking/testing/answering more important/relevant questions next time!!!
Sharky67 January 15, 2019 06:39 PM
By the very nature of their own comment, this study is flawed.
In fact, this entire exercise reminds me of Douglas Adams' Deep Thought computer. "I think the problem with your answer, is you didn't entirely understand what the question was."
Admitting in one breath you can interpret data in a myriad of ways, and produce negative or positive results accordingly, but then to go on and choose your own way to blanket analyse such a large data set seems entirely counter-intuitive to discovering the needles in the haystack
Nobody January 16, 2019 12:53 PM
Since everything is now digital, the kids can not get away from it. As an older person I am more concerned about how dependent young people are getting. Most young people are losing their ability to do simple math. They also feel that they need to be entertained constantly. Everything is instant gratification. They also don't think that they need to know anything because they can Google it if any question comes up. My daughter in law made a profound observation. Her children would rather just sit and watch other children play on youtube. How damaging will this be. Time will tell and it won't be good. We have become too civilized to survive. Believe me, Nobody knows what will happen.


My experiences with Mother Sai.
I had some problem and decided to ask baba a question and tried the question and answers book. When I asked baba, I got an answer 'I will save you from death. Have firm faith'. I didn't understand at that time, as I asked some other question. But I got it later. The next day I got up early and read paper for sometime, as it was too early I again went to sleep. I was slowly falling asleep and was about to get the same kind of dream, which I described in my earlier post. It started in the same way and that too at the same time. In the dream I heard someone's words saying not to tell this to my mother. And calling me repeatedly to come. I was following the words and thought I was going somewhere. And all of the sudden my sister slipped something and it made a loud sound that I got up startled and broke that stupid dream. This is how baba saved me from that bad dream or rather a bad experience. Baba's words that he would save me, made me believe that baba is obviously involved in breaking that dreaming and help me come to my senses. om sai ram.
That night I continuously sang the bhajan 'sai reham nazar….' and begged baba about my wish. I like that bhajan very much and that bhajan revolves in my mind day and night. It's not only about my wish but I sing that bhajan non stop for all our sai devotees. That night I got a dream in which I was in a temple of so many lords. There was a small cute idol of our dear deva. When I saw that idol, I said 'baba' as if I have seen and known that idol for long time. No sooner did I called baba and forwarded my palms like a beggar, that idol began to move and gave me 1rp i.e. one 50np and two 25nps totaling 1rp. And without any shock in seeing that idol moving, I too took the money and kept inside my bag. As usual my stupid brain didn't get the meaning what baba was trying to say but I was happy with the dream. One thing I knew for sure is baba used to distribute money if he is happy with that person. Hence I felt very happy to learn that baba is along with me. Thank you so much baba. om sai ram.
I too saw Sai Baba in my dream few days back.
This picture i had got from the temple a few months back.
I am happy that Sai baba gave me Darshan.
I got a dream few days back, where I saw baba in live. The dream is as follows: I went back to my childhood days; it was the first day of my school. Very strange, but I really saw myself as a kid again. There my teacher was none other than our dear deva. He was sitting in the teacher's chair, with the same dress. The good thing is he didn't have any stick in his hands. While baba is my teacher, being the first day of the school I was very busy with my friends talking to them. I just saw baba and again turned back to my friends. I didn't say anything to him, didn't even offer my namaskaras. But baba was just smiling. After few minutes, we heard an emergency alarm. All of the sudden, everyone began to run away from the class hearing the siren, fearing for their lives. All my friends were already gone and now the class is empty. I also started packing my school bag and was ready to run away from my class. As soon as I got up from my place, a sudden light flashed me saying 'what about baba?' then I remembered him and thought, 'how can I be so stupid to leave baba alone and run away for my life' and when I turned back I still saw baba on that chair with the usual sweet smile on his face. There ends my dream. After coming to my senses, I felt very happy and proud of my heart and my mind that they think about him even in my dreams and give him the first preference. May baba bless everyone. Om sai ram.
WONDERFUL EXPERIENCES. YOU ARE INDEED BLESSED BY BABA.
I am sure that Baba is always with you, even in your dreams.
Do you get the scary dream now?
I feel It is just one of Baba's unbelievable Leelas.
thank you so much for your wishes. May baba bless you always and fullfill all your wishes.
By baba's grace i got a thread which is tied to our wrists. I was not planning about it and always believed that baba is there to take care of me. But I got a signal from baba to accept that thread and believe me from the day when I tied it to my wrist, all my bad dreams stopped. And it also increased my confidence level. Now i get dreams only about baba and no one else may baba bless every one and be with them all the time. om sai ram.
Yesterday I got a dream where I went to shirdi along with my parents. It's really strange that shirdi was located up on the hills like the balaji hills, in my dream. My father said we will go directly there and stay there for 1 or 2 days. Then we were standing in the queue for the darshan. The masjid did not resemble the general shirdi one. It was totally different. The queue was on road and the masjid was very small. We just have to have the darshan and continue passing thats it. No samadhi too and the line was very crowded. Baba was inside the temple and everyone were supposed to have the darshan from outside, no one is allowed inside. As I couldn't see baba clearly I was disappointed. I just cried 'BABA' and the idol disappeared from the temple and appeared beside the temple where I can see very clearly. I couldn't believe my eyes. It was as if he vanished from inside and gave a darshan outside. At last I saw him clearly and got a wonderful darshan of him. Baba's idol was not the usual marble one, it was painted with rich and different colours. He was smiling like always. There ended my dream. And when I got the dream I was half asleep. Just thought of sleeping few more minutes and by the time I completely got to my senses, I got this beautiful dream. It was like within 10 minutes of gap. Baba bless everyone and fulfill their wishes soooooooooon. Love you my sai . Please forgive me for all my mistakes. om sai ram.
i read your posting and your experiences. i admire the love and devotion that you have in your heart for Baba and pray to Baba to keep it growing. You are truly blessed, i think your devotion for Baba is like that of an inocent child's love for it's mother, just pure love.
May Baba be with you in all walks of life and always keep you away from all troubles.
Thank you for your encouraging words and blessings. Yes baba is always there with me, not only with me, he protects all his children with his powers. No one can harm baba's kids. He cries, laughs along with us. What we know about his leelas and miracles are very less we may not know what he is doing to us wihtout our knowledge. He might be doing something more than what we see. Baba bless you. om sai ram.
I was feeling low yesterday with full of fear and anxiety. Begged baba not to leave me alone. Cried and cried and finally asked him to come in my dreams if he is there with me. I never thought baba would come into my dreams as soon as I call him because till now he never appeared when I called him. Went to bed early and here comes my dream. In my dream I was totally sad, disappointed, unhappy and completely lost. I went to a friend's birth day party and returned from there soon. Don't want any of them to notice me going away like that. Hence went downstairs, took my vehicle slowly and escaped from there. It was very dark by the time I left that place. After going a few kms, I was still crying. Couldn't see the road and what's coming in the opposite direction, because of the tears. I was continuously crying and told baba 'I couldn't take this anymore'. As soon as I opened the eyes, it was like hell. Darkness everywhere. Completely dark, couldn't see the road, no street lights nothing. Was scared to death. Sweating all over, I thought I am dead now. My mind was completely blank. Don't know what to do. Then I heard a voice. But I didn't get scared of that voice. It was giving me some advice. Boosting me up. It said 'do not panic. Follow the reverse way. Do not let others know that you are scared'. I followed the voice. Took a turn and went back through the way which I came. Couldn't see anything but still I was able to ride my vehicle without any light. Slowly I saw one street light and another car coming in the opposite direction. The voice again said 'don't care about that car, just ignore it' after few minutes I can see the hi-way and it was such a relief but never wondered what that voice was. As soon as I was out a bus passed me where I saw a huge baba's face with abhaya mudra. The whole picture was on the glass of the bus. Immediately I understood whose voice it was. The voice was like the one who gives commentary in discovery channel. It was mature and very powerful. As soon as I got my hi-way it was like a path to the heaven. End of my dream and my body was full of sweat as soon as I got up. Another example of the words 'why fear when baba is here'. Baba bless everyone. om sai ram.
I don't remember that much about this dream as it happened few months back. I wanted to pen it down soon but postponed it. Now I got the chance. All I could remember is only baba. The dream goes like this. I was standing in the masjid getting ready for the aarti which was about to start in few minutes. There was a lady behind me, talking to me continuously. I was not listening to her but was just watching baba. She was going on talking even though I wasn't interested about it. All of the sudden baba became live and took a plate which was near his feet and moved it aside. I was shocked and couldn't believe my eyes. No sooner did I realize that it wasn't any dream I felt at his feet and holded them. I just cried 'baba baba' then he gave me ashirwad by putting his hand on my head. I can actually feel his hand over my head and got up from sleep. I still couldn't forget that heaviness over my head. He is the only one who always thinks about us. Luv u nanna.
You are truly blessed by Baba.May Baba shower his divine blessings on u always.
Page created in 0.647 seconds with 69 queries.


WELLINGTON, New Zealand, October 15, 2013 (LifeSiteNews.com) – In a newly released report, a coroner in Wellington, New Zealand has urged politicians to address the issue of euthanasia.
The call by coroner Ian Smith comes after he investigated the death of Edna Gluyas, 85, who was found dead on her bed by her daughter on August 3, 2011. Gluyas' death was brought about by the use of a home-made contraption which suffocated her.
It was initially thought Gluyas was aided in her death, as she suffered from arthritis and the contraption seemed awkward for her to use without help. However the inquiry found that she acted alone.
He said her death "raises the vexed issue of euthanasia." "This process simply will not go away, and it will be necessary for Parliament to address this matter yet again," he added.
Labour MP Maryan Street recently withdrew her End of Life Choice Bill from the ballot as it was feared that discussion of such an emotional topic during an election year would be a negative distraction.
It is possible for another Member of Parliament to submit a private member's bill on the issue.
Despite seemingly high approval of legalising euthanasia and assisted suicide in New Zealand, opposition does still exist.
The national director of Family Life International NZ, Dame Colleen Bayer, explained that her organisation would "continue to educate society on the value and dignity of the human person, especially in moments of great suffering." However, she also noted that education was not enough. "We must be there, offering a hand of friendship to those who are most vulnerable to euthanasia practices – the elderly, the sick and the disabled," she said.


text:
The Wikipedia for Spies—And Where It Goes From Here
Nicholas Rigg/Getty Images
Major General Dale Meyerrose jokes that he doesn't think much of millennials. But he does largely credit that generation with fundamentally changing the way the US intelligence community collaborates.
In 2005, when Meyerrose worked as the Associate Director of National Intelligence, he was tasked with figuring out how to get 16 different spy agencies—all accustomed to decades of siloed secrecy—to talk to each other. In the end, one of his most lasting accomplishments was championing a small grassroots effort led by young analysts that resulted in what would become Intellipedia.
Think of Intellipedia as a Wikipedia for spies. It works the same, except that there's no anonymity for contributors, and nothing can ever be unsourced. Its contents range from Unclassified to Top Secret, though it's the lowest rung of Top Secret. Anyone in the executive branch—which includes the intelligence community—has enough clearance to access it. According to one intelligence official who asked to remain anonymous because he was not authorized to speak publicly on behalf of the community, the Intellipedia that exists today is part wiki, part bulletin board, part internal newspaper. "It's a great place to come in and see what's happening in the community as a whole," the official says.
That's helpful, but it's not the game-changing collaboration tool National Geospatial Intelligence-Agency analyst Chris Rasmussen, who was one of Intellipedia's earliest and most ardent users, had hoped for. Back in 2006, he and his fellow Intellipedians, as they called themselves, imagined full crowd-sourced intelligence reports, those official documents that land on the desks of high-level government officials and shape foreign and domestic policy. It's fallen well short. Intellipedia helped the intelligence community catch up to Web 2.0, but still has far to go before it lives up to its original promise.
In the days after 9/11, intelligence operatives learned that their aversion to sharing information had allowed warnings about the attack to go unheeded. The spy agencies were operating as they had since the Cold War, when their main enemy was the Soviet Union, a monolith they understood and, more importantly, could predict. Now, not only was the enemy more broadly distributed, there was more information than ever, and no single place to organize and share it.
The idea for Intellipedia first caught on after D. Calvin Andrus, an Innovation Officer at the CIA, wrote an essay in 2005 that suggested the same power of Wikipedia and blogs to aggregate and share information could also support the high-stakes world of spying. The essay spread, and before long, Meyerrose gave the all-clear to set up a server to try it out. "It was truly a grassroots effort, bottom up in the analyst community," he says.
What wasn't obvious to the powers-that-be back then, before the iPhone or Facebook existed, was that anyone would use it. "Nobody thought it would catch on," Meyerrose says. "Looking back on it, I'm absolutely certain of all the senior officials I told 'Oh, this is a good idea,' most of them thought that it would die of its own weight."
It didn't. Rasmussen and the other young analysts just kept writing articles and submitting them to the growing Intellipedia library. There was cachet in getting your contributions accepted. When people contested facts in the discussion section, things got hairy. "This is tribal warfare," Meyerrose says. By 2008, when he retired, he couldn't go into any field office and not see a shortcut to Intellipedia on every computer screen.
Spying Staple
Over a decade since its inception, Intellipedia has grown into a standard part of the intelligence community's workday. It has a homepage with featured and developing articles, help pages, and requests for collaboration. You can find tips on tradecraft in its pages, and primers on conflicts in certain parts of the world. After news broke Tuesday of a leak of CIA hacking data, you can bet there's a page explaining what's known about that. It runs on Intelink, the internal classified intranet network that links all the agencies and is operated by a team overseen by DNI.
It's the spying world's office water cooler.
The New York Times reported last week that Obama aides had scrambled to get as much information about the investigation into Russia's meddling with the 2016 election onto Intellipedia as they could, knowing that would mean a broad range of analysts across multiple agencies would see it. Which makes sense. Intellipedia can help spark conversation. It's the spying world's office water cooler.
Rasmussen always wanted it to be more, though. His dream was that eventually analysts could use Intellipedia—or something like it—to streamline the process of creating National Intelligence Estimates. But when Intellipedians tried to write NIEs on Intellipedia in 2006, 2007, bureaucracy got in the way. Every agency has a slightly different process for writing reports, and getting people to deviate from that for something so radically crowd-sourced proved impossible.
Realizing Intellipedia wasn't ever going to be accepted as an official voice of the intel community, Rasmussen tried to create a more official version of it after-the-fact. He called it the Living Intelligence System, and you can watch his YouTube video pitch about the specifics of how it worked here. Though it won accolades from the community, and became a real opt-in program, Living Intelligence never caught on.
"Everyone agreed that the tech was better, most people agreed that the process benefits were better, but they just couldn't make the pivot," Rasmussen says.
Something Entirely New
But Rasmussen is tenacious. He fervently believes that the intelligence community would benefit from streamlined collaboration. To find a place for it, he just needed a part of the process that wasn't already mired in bureaucracy.
He found it by focusing on a specific chunk of most intelligence reports. Any given report will be roughly 20-percent classified info–"the spooky stuff," Rasmussen calls it—and 80-percent unclassified context and background that someone reading the spooky stuff needs to know to understand why the hell it matters. It's less sensitive. It represents an opportunity.
For the past few years, Rasmussen has led a team working to create an entirely new way to crowdsource that 80 percent. It still won't live up to that original dream of fully crowdsourced reporting—but it could get the community most of the way. It'll even, because this is 2017, have an app.
As Meyerrose would say, the millennials will love that.
#spies

redpajama_set_name: RedPajamaCommonCrawl


Clearly, the most expensive parts of Lucknow are those across the river towards the East - Indira Nagar, Gomti Nagar - as well as Hazratganj and Mall Avenue. These are precisely the areas where few Muslims live. But the map also shows that the old city (delimited by the thick black line) is not cheap either; while average property prices in the trans-Gomti area reach 8748 Rs/sqm, they stand at 6564 Rs/sqm in the old city, which is still more than in the rest of Lucknow, including the newest developments in the South (6222 Rs/sqm). This is at least a tentative hint that Muslim poverty (which is hard to measure in the first place, more on this, perhaps, in a few weeks time) is an insufficient explanation for residential pattern: with the exception of the abovementioned hot spots across the river, houses in new Lucknow are not necessarily more expensive than those in the old city, where most Muslims tend to live.
What about discrimination then, the second prominent explanation? Using the namematching algorithm that I developed, I classified each seller and buyer as Muslim or non-Muslim. I then ran a regression of standardized house prices1 on the religion of buyer and seller and part of town, controlling for approximate size of property2 and date of registration. Without going into statistical details (if you are interested in those, email me), the regression shows that Muslim sellers achieve higher prices in the old city while the inverse is true in other parts of town, and particularly in the trans-Gomti area.
If you compare this map to the one of Muslim population distribution, you see that Muslims have an advantage in areas where many Muslims live: in the old city, the areas east thereof, a small corridor towards the South and, interestingly the Cantonment. They have a harder time in Mall Avenue and the trans-Gomti area, where they achieve lower prices because of their religious identity - which on first view seems to confirm allegations of discrimination in these parts of Lucknow (while the same affects non-Muslims in the old city in turn). Jagah!


At Elevian, we develop new medicines to restore regenerative capacity, with the potential to prevent and treat many age-related diseases.
Our mission is to help people age, unburdened by the diseases of aging.
Groundbreaking research at our labs and others has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs. The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. Elevian's scientific founders identified specific circulating factors that may be responsible for these effects.
One example, a naturally occurring molecule known as "growth differentiation factor 11" ("GDF11"), when injected into aged mice, reproduces many of the regenerative effects of young blood. GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism. Our founder's discoveries are published in leading journals and were recognized by Science as a global top 10 scientific breakthrough of 2014.
Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors, in order to restore our body's natural regenerative capacity, which we believe address a root cause of age-associated diseases.
Elevian has acquired exclusive worldwide license rights under a portfolio of multiple patent families from Harvard University, based on the research activities of our scientific founders who lead labs at Harvard, and on the research activities of others as well.
The following contains links to research from our team (in bold) and others, using websites owned and operated by third parties.
Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle.
Sinha M,...,Lee RT, Wagers AJ. Science, 2014.
Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors.
Katsimpardi L,...,Lee RT, Wagers AJ, Rubin LL. Science, 2014.
Biochemistry and Biology of GDF11 and Myostatin Similarities, Differences, and Questions for Future Investigation.
Walker RG,...,Rubin LL, Wagers AJ, Lee RT. Circulation Research, 2016.
Structural basis for potency differences between GDF8 and GDF11.
Walker RG,...,Wagers AJ, Lee RT et al. BMC Biology, 2017.
Molecular characterization of latent GDF8 reveals mechanisms of activation.
Walker RG,...,Lee RT et al. PNAS, 2018.
Growth Differentiation Factor 11 treatment leads to neuronal and vascular improvements in the hippocampus of aged mice.
Ozek C,…, Rubin LL. Scientific Reports, 2018.
Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans.
Olson KA et al. European Heart Journal, 2015.
Decrease in an anti-aging factor, growth differentiation factor 11, in chronic obstructive pulmonary disease.
Onodera K et al. Thorax, 2017.
GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet β-Cell Function and Survival.
Li et al. Diabetes, 2017.
Lifelong exercise, but not short-term high-intensity interval training, increases GDF11.
Elliott BT et al. Physiological Reports, 2017.
GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer's Disease.
Zhang et al. Journal of Alzheimer's Disease, 2018.
Potential strategic partner? Email info@elevian.com to explore a collaboration.
Elevian Co-Founder; xPrize, Singularity U, Celularity, Human Longevity, Inc.
Jul. 15, 2017 - Might that be true for people, too?
Jan. 22, 2015 - By splicing animals together, scientists have shown that young blood rejuvenates old tissues. Now, they are testing whether it works for humans.
Dec. 18, 2014 - In work with profound implications for aging, researchers showed that blood from a young mouse can rejuvenate an old mouse's muscles and brain.
May 4, 2014 - After combining the blood circulations of two mice by conjoining them — one old, the other young — researchers found dramatic improvements in the older mouse's muscle and brain. After four weeks, stem cells in both those areas got a boost of activity and were better able to produce neurons and muscle tissue.


"Nike has retained pricing power"
The "Halftime Report" traders discuss what to expect from Nike ahead of its earnings report today after the bell.
Jon Najarian is a buyer. He needs a Hail Mary for his Halftime Portfolio, and he thinks Nike--along with Foot Locker--may just be the ticket.
Stephanie Link comments on the ripple effect in the athletic space. If Nike beats, it will also boost Under Armour and Foot Locker.
Josh Brown is bullish on the athletic space, but is looking at Under Armour over Nike.


text:
Q: How to find generalized Eigen vectors of a matrix with Eigen vectors already on diagonal? I have a matrix
A= \begin{bmatrix}
    1 & -1 & 0 & 0  \\
    1 & 1 & 0 & 0 \\
    0 & 0 & 1 & -1\\
    0 & 0 & 1 & 1
  \end{bmatrix}
This matrix has eigen values $\lambda = 1+i, 1-i$ where each have multiplicity 2.
Notice this matrix is also already is the form:
$A= diag(\begin{bmatrix}
    a_j & -b_j   \\
    b_j & a_j
  \end{bmatrix})
$
Where $\lambda = a_j + ib_j$ for $\lambda_1 = 1+i$.
In other words, this matrix already is diagonalized with the eigen values on the diagonal.
For the problem, I am trying to find the eigen vectors and corresponding generalized eigen vectors for the eigen values to make a basis of $\mathbb{R}^4$, by using the real and imaginary parts of the eigen vector and generalized eigen vector for $\lambda_1 = 1+i$.
I have found the eigen vector for $\lambda_1 = 1+i$ to be $ v_1 = \begin{bmatrix}
    i \\
    1  \\
    i\\
    1
  \end{bmatrix}$.
But when I then try to find the generalized eigen vector for this eigen value by solving the system:
$(A-\lambda_1I)^2v_2 = {0}$
The system row reduces to the same system that gave me $v_1$, and I again get $v_1$ as my generalized eigen vector, which does not provided me with a new linearly independent vector to use for my basis. I think this has to do with the matrix A already having the eigen values on the diagonal but I am not sure.
Ref. pg 36 and 38 #3e of Lawrence Perko's, Differential Equations and Dynamical Systems.

A: Since the matrix is block diagonal, an eigenvalue and the corresponding eigenvector provided by one block becomes the eigenvalue of the whole matrix, and the block eigenvector, stacked with $0$ to complete the dimension, will become the eigenvector of the whole matrix.
So in your case, to the eigenvalue $1+i$, for instance corresponds the eigenvectors $(i,1,0,0)$ and $(0,0,i,1)$.

redpajama_set_name: RedPajamaStackExchange


The term sciatica means that the sciatic nerve is being compressed somewhere along its pathway. This is used to describe a group of symptoms. There are many possible causes of sciatica, some of the most common are due to a bulging or prolapsed disc.
The disc can cause mechanical compression directly on the sciatic nerve or the inflammation caused by the damaged disc can lead to irritation of the sciatic nerve. This pinched nerve can lead to very painful symptoms. Severe pain shooting down the leg is most common. This is often accompanied by altered sensation and even muscle weakness. If this weakness gets worse, consult your doctor. Any alteration in bladder or bowel function (i.e. loss of sensation when going to the toilet) means urgent medical care is needed. Acute back pain is also common due to damage to the disc.
People often describe this as a slipped disc. This is a misleading description. What actually happens is that the pulpy contents of the disc bulge out, pressing on one of the spinal nerves. The bulge itself can be painful and cause localised back pain. This is often referred to as discogenic pain. If it presses on a spinal nerve as it exits the spinal canal, pain can be felt in a more distant area such as the arm, leg, hand or foot.
Arthritis can cause sciatic type symptoms as little bony growths can cause compression on the nerve. This can be due to previous injuries or just the normal process of ageing. Symptoms gradually get worse over longer periods of time and after being in certain positions for prolonged periods.
However, it does not have to be as serious as a slipped disc or arthritis to cause sciatica. Minor muscle tightness can press on the sciatic nerve which can cause severe pain down the leg. Reasons for this can range from sitting in a chair with poor support to compensation due to pain in the knee or ankle.
Treatment is totally dependent on what the underlying problem is. If the cause is a muscle then it is normally very straightforward to treat and recovery time is quick. If the sciatica is due to disc damage, treatment initially has to be fairly conservative. Emphasis is placed on restoring some movement within the spine and reduce pain. This is a very important stage as studies have found getting moving sooner is better for long term recovery. Your osteopath can aid your movements in many ways but not necessarily by working the affected area. Working higher up in the back and through the hips can help your body to compensate and adapt. Advice regarding your posture and, gradually, stretches and rehabilitation exercises will be introduced.


text:
Giambattista Valli discusses his much-anticipated M.A.C collab
The princess-pink hue of Rihanna's 2015 Grammy gown (you know the one) is now available in lipstick form.
by : Victoria DiPlacido- Jun 16th, 2015
Giambattista Valli has teamed up with long-time collaborator M.A.C Cosmetics to produce five limited-edition matte lipsticks and a pot of high-shine gloss that will hit stores in July.
"The first thing I thought of when designing this collection was the idea of dressing your lips with Giambattista Valli," the designer told us at his New York showroom. "This Valli girl, she's a passionate kind of woman. She laughs, she kisses, she talks—she's very alive." How she wears the collection—matte lipstick worn solo or layered with gloss, gloss used as a highlighter on cheekbones—is entirely up to her, says Valli, who counts Amal Clooney and Diane Kruger as clients. "I always need the support of the woman. Even though I created these lipstick shades, it's the woman who gives them life."
From left: Lipstick in Bianca B, Charlotte, Margherita, Eugenie and Tats ($21 each)
Below, read more of our interview with the designer.
How was designing a makeup collection different from your normal design process?
"You know what, I've worked with M.A.C the last ten years, starting with my first collection. So there is this very natural relation between fashion and beauty, something we built it up – this image of this woman with M.A.C. The moment we knew it was going to be 10 years for this collaboration, we said let's do something to [mark] it. I think [these] colours are one of the signature things of Giambattista Valli. It's feminine. It's a label for women. I love the idea of radically changing your look with a different colour on the lips – we had this idea to match the inside colour with the outside so it's practical – when you have it in your bag, you can find it right away without checking [the colour inside the tube]."
What keeps you creative?
"I'm curious about everything… it can be anything. Everywhere in every single moment. Some things call me and others I don't even look at. There are things that come to me and I look at them and hold it in my mind. And the day that it comes out of my mind I put it in a lipstick or a book or garment."
Is there a specific time period that you look back to for inspiration?
"Right now is a very inspiring moment [in time], I can say."
What are you currently reading and/or watching?
"I don't have a TV. I don't watch TV at all. But I read a lot of books."
Fiction? Non-fiction?
"I love biographies a lot. I'm reading a philosophy book but the title is in Italian: The Utility of the Useless. So what we think is useless, how useful it is. Flowers can be [seen as] useless, but are useful."
And is music a source of inspiration for you as well? Because the music on your website…
…it's very particular.
"It's the soundtrack of life sometimes, no? Some music reminds you of a specific moment of your life. Tracy Chapman reminds me of when I was 18 or 19 years old in London…and then Sade remind me like when I was in New York. "Diamonds" by Rihanna reminds me about partying in New York." [Laughs]
Is there something you always bring with you when you travel?
"My music, toothbrush, my pillow."
You bring your own pillow?
"Of course, always. I have a very specific pillow."
Do you have a favourite beauty look on a woman?
"Beauty is a mental position. You have to feel beautiful to be beautiful. It's not a physical thing."
What are some stand-out moments from the past ten years of Giambattista Valli?
"There's so many. Probably the best part of these ten years is all the risks that I took and I'm still taking. So that's something that keeps me alive and young….Or it's like, if I think of this dress [Rihanna's 2015 Grammy gown] I think of Rihanna wearing it, or if I think of that dress I think of Amal wearing it, or when I look at another one I think of Diane Kruger being beautiful. But I always need the support of the woman to be alive and to be represented."
My favourite things: Urban Decay's Wende Zomnir
4 ways to fake supernatural skin
Naomi Campbell's 8 best beauty looks on Instagram
CHANEL Launches 'Le Lion' Fragrance, Inspired by Gabrielle Chanel's Totem Animal
Le Lion joins the Les Exclusifs de CHANEL collection as the newest scent in the fragrance franchise.
by : Nancy Pierri- Jan 20th, 2021
Academy Award Winner Viola Davis Has Done the Work to Reach Her Truth
It was a long road to reach that point, though.
by : Lesa Hannah- Jan 14th, 2021
The Best Black Friday & Cyber Monday Beauty Deals
The Best Skin & Hair Gift Sets This Season
10 Beauty Products We're Coveting For December
The 20 Best Beauty Products of 2020
Shine on This Season With a Legendary Beauty Product


Shears that actually work! After buying several pairs of totally useless shears this is a revelation. A joy to use - I'm even looking forward to the hedge growing so I can use them again. Well worth the extra expense.
So much easier to use than the ones I had for years. The effort required is strikingly minimal,and there is hardly a sound with them. A pleasurable experience clipping away with these!
Having worked with these shears for years, I was pleased that the quality hasn't deteriorated.
Robust, easy action, providing a perfect cut.
A little heavy for a weak feeble woman! Nice, clean cut.
You can calculate your postage charge for Bahco P51 Professional Hedge Shears before you checkout.


text:
Follo og Nordre Østfold District Court () is a district court located in Innlandet county, Norway. This court is based at two different courthouses which are located in Ski and Mysen. The court serves the eastern part of the county which includes cases from nine municipalities. The court in Ski accepts cases from the municipalities of Enebakk, Frogn, Nesodden, Nordre Follo, Vestby, and Ås. The court in Mysen accepts cases from the municipalities of Indre Østfold, Marker, and Skiptvet. The court is subordinate to the Eidsivating Court of Appeal.

The court is led by a chief judge () and several other judges. The court is a court of first instance. Its judicial duties are mainly to settle criminal cases and to resolve civil litigation as well as bankruptcy. The administration and registration tasks of the court include death registration, issuing certain certificates, performing duties of a notary public, and officiating civil wedding ceremonies. Cases from this court are heard by a combination of professional judges and lay judges.

History
This court was established on 26 April 2021 after the old Follo District Court and Heggen og Frøland District Court were merged into one court. The new district court system continues to use the courthouses from the predecessor courts. When the court was created, the Storting also approved moving these areas from the Borgarting Court of Appeal to the Eidsivating Court of Appeal. This change was not carried out immediately, however, but on 1 March 2022 the change was officially enacted.

References

District courts of Norway
2021 establishments in Norway
Organisations based in Mysen

redpajama_set_name: RedPajamaWikipedia


The Star of Australia No. 200 It's about how good of a man you want to be.
fraternal organization that promotes proper and righteous conduct and personal advancement.
of New South Wales and the Australian Capital Territories. Our mission is guided by the enduring tenets of our fraternity - Brotherly Love, Relief and Truth. Our value includes Ethics, which our lives are based on moral principles. Honesty, trust and compassion are important to us. Tolerance, we value ethnic, social, cultural, and religious differences and respect the opinion of others and Philanthropy, we believed we can make a difference in our communities through charitable giving and community service. Freemasonry is a place where you will find an unlimited opportunity to acquire leadership experience, self-development, and personal growth..
Early in the year 1891, twenty Italian Brethren, led by W Bro. Harry Passmore, a Past Master of Lodge Wentworth No.89, petitioned the United Grand Lodge of New South Wales to form a new Lodge, to be called Lodge La Stella d' Italia (The Star of Italy). The petition was approved and a dispensation Warrant was issued empowering the Brethren named in the petition to meet as a regular Lodge and perform all the functions of Freemasonry in conformity with the laws and regulations of The United Grand Lodge of New South Wales, founded three years earlier in 1888. The new Lodge first met in September 1891. During the early years of the Lodge, it was customary to obligate Italian candidates in Italian, whilst English-speaking candidates were obligated in English. Gradually, the number of native English speaking Brethren increased. In 1904 the Lodge made application to The United Grand Lodge of New South Wales for the name of the Lodge to be changed to Lodge The Star of Australia. The request was granted and became effective in May 1904. Following the change of name, all candidates joining the Lodge were obligated in English. When the call to arms resounded in 1914 and 1939, the Brethren readily responded and many joined the armed services, but the Lodge carried on in great strength with numerous regular and emergent meetings. Dispensation from Grand Lodge was granted to enable Brethren to attend Lodge without having to wear dark clothing during war years. Candidates were so plentiful in those days that initiations were handled in regular and emergent meetings, but then, like recently, had to be passed on to other Lodges for their further progress in freemasonry. Following the Second World War, there blossomed for Masonry that many now see as the Golden Years of Freemasonry during which Lodge The Star of Australia was getting an average of two hundred and eighty Brethren at its Installations and one hundred and twenty in its regular meetings. Following the demolition of the old Grand Lodge building in Sydney, the Lodge moved to Hunters Hill in 1971 but sadly prior to the move, attendances at Lodge meetings were down and there were fewer candidates at Hunters Hill, attendance was down to as few as fifteen to twenty members. In August 1982, the Lodge moved to Hurlstone Park Masonic Centre where it has been our home for 32 years. Due to the closure of Hurlstone Park Masonic Centre on September 2014, the members temporarily hold their meeting at the Royal Arch Masonic Centre in Petersham. On the 23rd of May 2015, The Lodge was officially housed at the Castle Hill Masonic Centre in Castle Hill, under Masonic Region 2, District 25A.
Freemasonry is one of the world's oldest and largest non-political. non- religious fraternal organization that promotes proper and righteous conduct and personal advancement. It not only binds us together as fraternal brothers, but also as a citizens and members of a greater society. The Star of Australia No. 200 is a masonic lodge warranted by the United Grand Lodge of New South Wales and The Australian Capital Territories. Our mission is guided by the enduring tenets of our fraternity - Brotherly Love, Relief and Truth. Our Value include Ethics, which our lives are based on moral principles, Honesty, trust and compassion are important to us, Tolerance, we value ethnic, social, cultural and religious differences and respect the opinion of others, Philanthropy, we believe we can make a difference in our communities through charitable giving and community service. Freemasonry is a place where you will find unlimited opportunity to acquire leadership experience, self-development, and personal growth..


Milwaukee might not come to mind when you're thinking of romantic couples' vacations along the lakefront, but this big city offers plenty when it comes to beautiful views and exciting attractions. Check out these tips to find romantic Milwaukee vacation rentals, and enjoy a Midwestern getaway.
Wander the shores of Milwaukee along Bradford Beach's soft sand and sparkling lake waters. With the city looming behind you, Bradford Beach offers an exciting view of the towering skyscrapers from your beach chair or your water float. Check out Summerfest and enjoy music all along the lakefront with dozens of festivals that draw tourists from all around the world. Wander the Historic Third Ward for a glimpse of Milwaukee's vibrant art scene, plenty of interesting boutiques and galleries that highlight the beauty of the Midwest.
From June until September, the summer season in Milwaukee provides visitors with tons of activities, lovely lakefront restaurants and vacation rentals and a battle for the best lodging. However, plan to skip the summer there if you want to find more options when it comes to romantic lakeside vacation rentals. Keep in mind that the water cools quickly in the fall, making it chilly for swimming but ideal for sunset views. Late spring and early fall offer a break in the vacation crowds, making it easier to obtain the top couples' vacation homes and rentals by the lake.
Lake Michigan's waterfront bordering the city of Milwaukee is loaded with places to stay that offer romantic sunsets and access to fun attractions. Pick a house with views of the bay just a few miles from Summerfest in Downtown Bay View. Overlooking the lake and offering a pretty covered patio, homes along this area of the lake provide an ideal space for couples to fall in love with each other and Milwaukee.
Enjoy a gorgeous home or condo in the Historic Third Ward area of Milwaukee and enjoy some of the best dining in the city. A small peninsula juts into Lake Michigan and offers space for condos, apartments and homes with lovely lake views. Pick out a River Place loft, or explore a lovely Victorian home that provides space for a romantic vacation getaway.
Not all Milwaukee vacation rentals are created alike, and finding your favorite amenities makes it easy to create a romantic getaway. Look for hot tubs, private balconies with views of the lake and gourmet kitchens to create some romantic ambience during your stay. Rentals within walking distance of great restaurants, boat tours of the city and shopping opportunities also provide you with fun things to do when you're exploring the city.


text:
High school baseball: Mentor loses to St. Ignatius
By Eddie Dwyer Correspondent.com and Eddie Dwyer |
PUBLISHED: April 19, 2010 at 9:26 a.m. | UPDATED: July 16, 2021 at 12:48 p.m.
When Mentor was run-ruled by Saint Ignatius in last season's Strongsville Dugout Club Tournament, the Cardinals, by their own admission, were a team in transition that was learning on the job. A year later and Mentor's players learned that when it comes to St. Ignatius' offensive capabilities, some things never change. The Wildcats, ringing the aluminum loud and clear, jumped on Cardinals pitching in the top of the first inning and rode strong third and fourth innings to a 13-3 victory in Sunday's final round of the Dugout Club Tournament at Strongsville High School. The game was called after six innings because of the 10-run mercy rule. St. Ignatius, which was riding the emotion of Saturday's 8-6 second-round victory over defending Division II state champion Notre Dame-Cathedral Latin, an effort that snapped the Lions' 14-game winning streak, led, 3-0, after the top of the first. Mentor would answer in the bottom of the first. Cardinals junior shortstop Joe Kasper, who made a highlight-reel 6-3 defensive play in the top of the first, led off with an infield hit, stole second base and advanced to third on a fielder's choice. He came home on a hit by sophomore first baseman Justin Fritts. Mentor then cut the deficit to 3-2 entering the second inning on a two-out error by the Wildcats. After Ignatius senior left fielder Kevin Hopkins delivered his second double in as many at-bats, the Wildcats led, 4-2. Senior right-hander Dave Gallagher (2-0) struck out two in blanking the Cardinals in the bottom of the second and, at that point, things began to look all too familiar for the Mentor players and their coaching staff. St. Ignatius (11-1), which is seeking its fourth consecutive appearance in the Division I state final four and its 11th overall, combined hits by senior designated hitter Mike Burke and Gallagher, a double steal, a two-run double by junior right fielder Neal Jacobs, a bunt for a hit by senior shortstop Zach Seybert and three wild pitches into an 8-2 lead in the top of the third. The Cardinals scored their final run on an RBI double by sophomore relief pitcher Anthony Gallo in the bottom of the third, but the Wildcats came right back with three runs in the top of the fourth, including a majestic two-out, two-run home run by Jacobs that soared over the fence in left field. Jacobs, who now has four home runs on the season, completed his seven-RBI day by saying goodbye to Mr. Rawlings again with a two-run rope that darted over the fence in right-center in the top of the sixth.
Eddie Dwyer Correspondent.com
Eddie Dwyer


Coyote is an unincorporated community in Lincoln County, New Mexico, United States. Coyote is located near U.S. Route 54, 12.2 miles (19.6 km) north-northeast of Carrizozo.
^ a b "Coyote, New Mexico". Geographic Names Information System. United States Geological Survey.
This page was last edited on 14 January 2018, at 21:45 (UTC).


text:
Join Insider for Free
KSAT Investigates
Vote 2023
Behind the Kitchen Door
Get News App
Thermometer Thursday
Science with Sarah
Weather History
KSAT Connect
Get Weather App
Big Game Coverage
BGC Streams
KSAT Pigskin Classic
Scholar Athletes
Spurs Newsletter
Spurs Stats
BGC Newsletter
Get BGC App
KSAT Plus
Texas Crime Stories
KSAT News Now
9 at Night
KSAT Explains
Texas Eats
9 @ 9
Leading SA
21 Taken
Necessary Evil
Get Streaming App
SA Live
As Seen On SA Live
Happy Space
Meet The Cast
KSAT Kids
KSAT Deals
Educator of the Month
KSAT Experts
Great Grads
San Antonio Business Journal
Live from the Southside
KSAT Community
Daily Forecast Email
Texas Crime Stories Newsletter
Outdoors Newsletter
Texas Eats Newsletter
Open Court Newsletter
KSAT Explains Newsletter
KSAT Kids Newsletter
Big Game Coverage Newsletter
Crime Report Newsletter
KSAT Insider
BOBBY SCOTT
Black pastors group holds vigil for Walmart shooting victims
Five days have passed since Lorenzo Gamble was killed in a mass shooting at a Walmart in Chesapeake, Virginia.
After cancellation, Dems look to reduce future student debt
House Democrats are proposing new legislation that would increase federal student aid, lower interest rates on loans and take other steps to make college more affordable.
Building on President Joe Biden's student debt cancellation plan, House Democrats on Thursday proposed new legislation that would increase federal student aid, lower interest rates on loans and take other steps to make college more affordable. The bill is being pushed as a complement to Biden's plan, which promises to wipe away student debt for millions of Americans but does little to help future students avoid heavy levels of debt. Democrats say their plan would tackle the root causes behind America's $1.6 trillion in federal student debt.
Student loan crisis awaits new generation despite Biden plan
President Joe Biden's student loan cancellation offers a life-changing financial break for millions of Americans.
The U.S. student population is more diverse, but schools are still highly segregated
A new report from the U.S. Government Accountability Office finds that public schools remain highly segregated along racial, ethnic and socioeconomic lines. One reason: school district secession.
US education chief seeks action to prevent school shootings
Education Secretary Miguel Cardona says he's ashamed the United States is "becoming desensitized to the murder of children" and he's calling for action to prevent more lives from being lost in school shootings like the one in Uvalde, Texas.
Feds: Thousands may have student debt that should be erased
A new federal report finds that record-keeping failures by the Education Department may have left thousands of Americans stuck with student debt that should have been forgiven.
Exclusive: How the student loan safety net has failed low-income borrowers
Income-driven repayment plans were intended to help low-income student loan borrowers, and eventually cancel their debt. New documents paint a breathtaking picture of the program's failure.
McAuliffe's backslapping political brand put to test in 2021
Terry McAuliffe won Virginia's 2013 governor's race by embracing his own brand of personal politics that rely on decades-old friendships, backslapping charisma and tell-it-like-it-is authenticity.
Flush with COVID-19 aid, schools steer funding to sports
A growing number of school districts in the U.S. are using federal pandemic funding on athletics projects.
Black colleges' funding hopes dim amid federal budget battle
Officials at historically Black colleges thought they might finally have a pipeline for long-term funding from the federal government after the Biden administration included at least $45 billion for them in its multitrillion dollar economic package.
Roughly 40% of Americans don't understand 401(k) fees, government watchdog finds
A report by the Government Accountability Office, a congressional watchdog, found many Americans do not understand fees for their 401(k) retirement plans.
Some governors use federal virus aid to expand school choice
Some Republican governors are using federal pandemic assistance to promote school choice programs, including charter schools and vouchers for private schools.
Republicans seek apology for yell of 'racist' during critical race theory questioning
House Republicans are demanding an apology after a Democrat yelled, "Racist," at a colleague who was quizzing Education Secretary Miguel Cardona about critical race theory during a committee hearing Thursday.
Biden admin extends protections to transgender students
The U.S. Education Department on Wednesday expanded its interpretation of federal sex protections to include transgender and gay students.
LETTER: Congress should pass bill to lower drug costs
LETTER TO THE EDITOR:
fredericksburg.com
Democratic leaders criticize Biden administration's "outmoded" guidance on aerosol COVID-19 spread
A group of House Democratic leaders are questioning the basis for the Biden administration's guidance on aerosol transmission of COVID-19, which they say relies on "outmoded" science. A dozen doctors and experts detailed their concerns in a letter in mid-February to the Biden administration. Congressman Bobby Scott, the chairman of the House education and labor committee, is leading the advocacy effort for greater workplace protections and regulations regarding COVID-19 safety. Experts told CBS News the lack of specificity from the CDC could be an impediment for OSHA. The White House, CDC and Labor Department did not immediately respond to a request for comment.
Dems attempt to push through school funding, wage increase
The plan faces opposition from Republicans who want to tie new school funding to reopening. Biden's plan for $130 billion in school funding is in addition to more than $8 billion from previous relief packages. Stop ruining their futures and stop playing games."Scott countered that schools can't make changes needed to reopen safely unless they get the funding in Biden's plan. AdRepublicans also signaled a fight over standardized testing, backing a proposed change to prevent relief funding from being used on academic assessments. The $350 billion portion of the bill before the committee also includes Biden's plan to raise the minimum wage from $7.25, where is has been since 2009.
Dems propose $1,400 payments as part of Biden virus relief
Less than three weeks into his presidency, Biden has declared that vanquishing the virus and resuscitating the economy are his top priorities. AdHouse Education and Labor Committee Democrats also previewed their plans Monday. Couples who make up to $150,000 would be entitled to $2,800 relief payments, which would gradually diminish and fully disappear for those earning $200,000. Biden has said he will not allow the per-person payments to fall below $1,400 but has indicated flexibility on the income thresholds. A federal law known as COBRA already allows them to temporarily keep their old employer's health plan, but they typically have to pay prohibitively high premiums.
Democrats reintroduce labor rights bill as Covid puts spotlight on workplace safety
Democrats are reintroducing a sweeping labor rights bill on Thursday, touting it as a means to create safer workplaces and boost employee benefits during the coronavirus pandemic. Even so, the bill highlights Democrats' push to strengthen labor unions after years of eroding membership. "The COVID-19 pandemic has demonstrated the urgent need for Congress to protect and strengthen workers' rights," he said in a statement Thursday. The reintroduction of the bill underscores the party's renewed focus on using unified control of Congress and the White House to boost labor rights. During her introduction of Walsh, committee Chair Sen. Patty Murray of Washington touted the PRO Act as one of the policies she aims to pursue.
Trump eases rules for religious social service providers
It also removes a rule telling religious groups to give clients written notice about their rights, including that they can't be forced to participate in religious activities. Trump also vowed to protect prayer in public schools and bolster the rights of religious groups on college campuses. Civil rights group blasted the new changes, saying the previous rules were meant to protect LGBTQ people, religious minorities and others who may face discrimination from religious groups. American Atheists, a civil rights group, said the previous rules were created with support from religious and civil rights groups alike. Religious groups applauded the changes, while civil rights groups said they opened the door for discrimination.
Trump, DeVos raise school choice in appeal to vexed parents
DeVos and President Donald Trump have repeatedly invoked school choice as the solution to parents' woes. And in fact, we are."In nearly every public appearance she has made during the pandemic, DeVos has used the spotlight to draw attention to school choice. Her focus on school choice has drawn sharp opposition from Democrats and public school leaders. And supporters of school choice say DeVos is right to press for the issue now. "I'm focused on students, not on school buildings, school systems or any word that comes before school," DeVos said.
US Sen. Stabenow urges USDA to extend food program waivers
The U.S. Department of Agriculture will not continue to provide food program waivers that have ensured students are fed while schools are closed during the coronavirus pandemic unless Congress acts, U.S. Sen. Debbie Stabenow of Michigan warned Tuesday. Some children get their only meals at school. Should Congress choose to go in this direction, USDA stands ready to provide technical assistance.The USDA did not return a request for further comment Tuesday. She said she hoped it was not coming from the Trump administrations push to put students back in schools for in-person instruction. Report for America is a nonprofit national service program that places journalists in local newsrooms to report on undercovered issues.
Democrats say White House blocking CDC head from testifying
Director of the Centers for Disease Control and Prevention Robert Redfield, speaks during a White House Coronavirus Task Force briefing at the Department of Education July 8, 2020, in Washington. (AP Photo/Manuel Balce Ceneta)WASHINGTON House Democrats are criticizing the White House for blocking the head of the Centers for Disease Control and Prevention from testifying at a public hearing on safely reopening the nation's schools. Democrats said they invited CDC officials, including director Robert Redfield, to testify at a hearing next Thursday but were rebuffed by the White House. A committee spokesperson said the panel asked for any CDC official to testify but was rejected. A White House spokesperson said Friday that Dr. Redfield has testified on Capitol Hill at least four times over the last three months.
DeVos defends policy boosting virus aid for private schools
The policy has drawn backlash from Democrats and state education leaders who say it reroutes money from needy public schools to wealthier private ones. The legislation tells states to divide the funding among public schools based on the number and share of low-income students they teach. It also tells public schools to use a portion of the money to provide services, such as busing or tutoring, to students who attend local private schools. On April 30, however, DeVos issued new guidance telling public schools to divide the coronavirus aid based on the total number of students at local private schools, not just low-income ones. In the state's Orleans Parish, at least 77% of its relief allotment would end up going to private schools.
Half million students could lose free meals due to food stamp changes
Andrew Burton/Getty ImagesWASHINGTON, D.C. - Rep. Bobby Scott says the US Department of Agriculture concealed data showing that its recent proposed changes to the food stamp program could result in more than 500,000 low-income students losing free meals. Scott writes that "the proposed rule will impact not only SNAP eligibility, but will also affect children's eligibility for school meal programs." The program, Scott noted, "allows schools to provide free meals to all students in high-poverty communities." The proposed rule, released last week, could end up stripping more than 3 million people of their food stamp benefits. It would curtail so-called broad-based categorical eligibility, which makes it easier for Americans with somewhat higher incomes and more savings to participate in the food stamp program.
House passes bill to hike the federal minimum wage to $15 per hour
The House passed a bill Thursday to hike the federal minimum wage to $15 per hour in a win for liberal activists who have long pushed to give low-wage workers a raise. Congress last raised the federal minimum wage to $7.25 per hour about a decade ago. Now, 29 states and Washington, D.C., have higher pay floors than the U.S., while seven states have approved $15 per hour minimum wages. An amendment adopted Thursday, proposed by Rep. Tom O'Halleran, requires a Government Accountability Office report on the effects of minimum wage increases. Activists such as Fight for $15, a movement started by striking fast-food workers, helped to spur $15 per hour minimum wage laws around the country.
The House just voted to give 33 million workers a raisehere's what has to happen to make it a reality
The Raise the Wage Act would also create an equal minimum wage for Americans with disabilities. Many Republicans cited concerns that a $15 federal minimum wage may cause significant job loss. Why advocates say minimum wage needs to increaseIt's been 10 years since Congress set the current federal minimum wage at $7.25. In recent years, some cities and states have taken steps to increase local minimum wage statutes, but there are still 21 states where the minimum wage remains frozen at $7.25. Nicholson, 28, makes $8.60 an hour, $1.35 more than the federal minimum wage, thanks to a recent state increase.
$15 minimum wage would boost pay for 17 million but 1.3 million would lose their jobs, CBO says
People gather together to ask the McDonalds corporation to raise workers wages to a $15 minimum wage as well as demanding the right to a union on May 23, 2019 in Fort Lauderdale, Florida. Hiking the U.S. minimum wage to $15 per hour would give millions of Americans a raise but put a smaller share of people out of work, according to projections released Monday. Raising the pay floor to $15 per hour by 2025 would boost wages for 17 million workers, the nonpartisan Congressional Budget Office estimated. Earlier this year, House Democrats led by Rep. Bobby Scott, D-Va., introduced a bill to gradually raise the federal minimum wage to $15 per hour by 2024. Opponents of hiking the pay floor to that level more than twice the current U.S. minimum wage of $7.25 that took effect in 2009 argue it would cut positions for minimum wage workers amid higher costs.
KSAT Internships
Subscribe to KSAT RSS Feeds
Careers at KSAT
Copyright © 2023 KSAT.com is managed by Graham Digital and published by Graham Media Group, a division of Graham Holdings.


text:
/* $Header: rdc.c,v 2.2 84/07/20 11:19:31 sater Stab $ */
/*
 * (c) copyright 1983 by the Vrije Universiteit, Amsterdam, The Netherlands.
 *
 *          This product is part of the Amsterdam Compiler Kit.
 *
 * Permission to use, sell, duplicate or disclose this software must be
 * obtained in writing. Requests for such permissions may be sent to
 *
 *      Dr. Andrew S. Tanenbaum
 *      Wiskundig Seminarium
 *      Vrije Universiteit
 *      Postbox 7161
 *      1007 MC Amsterdam
 *      The Netherlands
 *
 */

#include	<pc_file.h>

extern		_rf();
extern		_incpt();

int _rdc(f) struct file *f; {
	int c;

	_rf(f);
	c = *f->ptr;
	_incpt(f);
	return(c);
}

redpajama_set_name: RedPajamaGithub


text:
//
// "$Id: Fl_Menu_.H 11801 2016-07-09 17:06:46Z AlbrechtS $"
//
// Menu base class header file for the Fast Light Tool Kit (FLTK).
//
// Copyright 1998-2016 by Bill Spitzak and others.
//
// This library is free software. Distribution and use rights are outlined in
// the file "COPYING" which should have been included with this file.  If this
// file is missing or damaged, see the license at:
//
//     http://www.fltk.org/COPYING.php
//
// Please report all bugs and problems on the following page:
//
//     http://www.fltk.org/str.php
//

/* \file
   Fl_Menu_ widget . */

#ifndef Fl_Menu__H
#define Fl_Menu__H

#ifndef Fl_Widget_H
#include "Fl_Widget.H"
#endif
#include "Fl_Menu_Item.H"

/**
  Base class of all widgets that have a menu in FLTK.

  Currently FLTK provides you with Fl_Menu_Button, Fl_Menu_Bar, and Fl_Choice.

  The class contains a pointer to an array of structures of type Fl_Menu_Item.
  The array may either be supplied directly by the user program, or it may
  be "private": a dynamically allocated array managed by the Fl_Menu_.

  When the user clicks a menu item, value() is set to that item
  and then:

    - If the Fl_Menu_Item has a callback set, that callback
      is invoked with any userdata configured for it.
      (The Fl_Menu_ widget's callback is NOT invoked.)

    - For any Fl_Menu_Items that \b don't have a callback set,
      the Fl_Menu_ widget's callback is invoked with any userdata
      configured for it. The callback can determine which item
      was picked using value(), mvalue(), item_pathname(), etc.
*/
class FL_EXPORT Fl_Menu_ : public Fl_Widget {

  Fl_Menu_Item *menu_;
  const Fl_Menu_Item *value_;

protected:

  uchar alloc;			// flag indicates if menu_ is a dynamic copy (=1) or not (=0)
  uchar down_box_;
  Fl_Font textfont_;
  Fl_Fontsize textsize_;
  Fl_Color textcolor_;

  int item_pathname_(char *name, int namelen, const Fl_Menu_Item *finditem,
                     const Fl_Menu_Item *menu=0) const;
public:
  Fl_Menu_(int,int,int,int,const char * =0);
  ~Fl_Menu_();

  int item_pathname(char *name, int namelen, const Fl_Menu_Item *finditem=0) const;
  const Fl_Menu_Item* picked(const Fl_Menu_Item*);
  const Fl_Menu_Item* find_item(const char *name);
  const Fl_Menu_Item* find_item(Fl_Callback*);
  int find_index(const char *name) const;
  int find_index(const Fl_Menu_Item *item) const;
  int find_index(Fl_Callback *cb) const;

  /**
    Returns the menu item with the entered shortcut (key value).

    This searches the complete menu() for a shortcut that matches the
    entered key value.  It must be called for a FL_KEYBOARD or FL_SHORTCUT
    event.

    If a match is found, the menu's callback will be called.

    \return matched Fl_Menu_Item or NULL.
  */
  const Fl_Menu_Item* test_shortcut() {return picked(menu()->test_shortcut());}
  void global();

  /**
    Returns a pointer to the array of Fl_Menu_Items.  This will either be
    the value passed to menu(value) or the private copy.
    \sa size() -- returns the size of the Fl_Menu_Item array.

    \b Example: How to walk the array:
    \code
    for ( int t=0; t<menubar->size(); t++ ) {                // walk array of items
        const Fl_Menu_Item &item = menubar->menu()[t];       // get each item
        fprintf(stderr, "item #%d -- label=%s, value=%s type=%s\n",
            t,
            item.label() ? item.label() : "(Null)",          // menu terminators have NULL labels
            (item.flags & FL_MENU_VALUE) ? "set" : "clear",  // value of toggle or radio items
            (item.flags & FL_SUBMENU) ? "Submenu" : "Item"); // see if item is a submenu or actual item
    }
    \endcode

  */
  const Fl_Menu_Item *menu() const {return menu_;}
  void menu(const Fl_Menu_Item *m);
  void copy(const Fl_Menu_Item *m, void* user_data = 0);
  int insert(int index, const char*, int shortcut, Fl_Callback*, void* = 0, int = 0);
  int  add(const char*, int shortcut, Fl_Callback*, void* = 0, int = 0); // see src/Fl_Menu_add.cxx
  /** See int Fl_Menu_::add(const char* label, int shortcut, Fl_Callback*, void *user_data=0, int flags=0) */
  int  add(const char* a, const char* b, Fl_Callback* c, void* d = 0, int e = 0) {
      return add(a,fl_old_shortcut(b),c,d,e);
  }
  /** See int Fl_Menu_::insert(const char* label, int shortcut, Fl_Callback*, void *user_data=0, int flags=0) */
  int insert(int index, const char* a, const char* b, Fl_Callback* c, void* d = 0, int e = 0) {
      return insert(index,a,fl_old_shortcut(b),c,d,e);
  }
  int  add(const char *);
  int  size() const ;
  void size(int W, int H) { Fl_Widget::size(W, H); }
  void clear();
  int clear_submenu(int index);
  void replace(int,const char *);
  void remove(int);
  /** Changes the shortcut of item \p i to \p s. */
  void shortcut(int i, int s) {menu_[i].shortcut(s);}
  /** Sets the flags of item i.  For a list of the flags, see Fl_Menu_Item.  */
  void mode(int i,int fl) {menu_[i].flags = fl;}
  /** Gets the flags of item i.  For a list of the flags, see Fl_Menu_Item.  */
  int  mode(int i) const {return menu_[i].flags;}

  /** Returns a pointer to the last menu item that was picked.  */
  const Fl_Menu_Item *mvalue() const {return value_;}
  /** Returns the index into menu() of the last item chosen by the user.  It is zero initially. */
  int value() const {return value_ ? (int)(value_-menu_) : -1;}
  int value(const Fl_Menu_Item*);
  /**
    The value is the index into menu() of the last item chosen by
    the user.  It is zero initially.  You can set it as an integer, or set
    it with a pointer to a menu item.  The set routines return non-zero if
    the new value is different than the old one.
  */
  int value(int i) {return value(menu_+i);}
  /** Returns the title of the last item chosen.  */
  const char *text() const {return value_ ? value_->text : 0;}
  /** Returns the title of item i.  */
  const char *text(int i) const {return menu_[i].text;}

  /** Gets the current font of menu item labels.  */
  Fl_Font textfont() const {return textfont_;}
  /**  Sets the current font of menu item labels.  */
  void textfont(Fl_Font c) {textfont_=c;}
  /**  Gets the font size of menu item labels.  */
  Fl_Fontsize textsize() const {return textsize_;}
  /**  Sets the font size of menu item labels.  */
  void textsize(Fl_Fontsize c) {textsize_=c;}
  /** Get the current color of menu item labels.  */
  Fl_Color textcolor() const {return textcolor_;}
  /** Sets the current color of menu item labels. */
  void textcolor(Fl_Color c) {textcolor_=c;}

  /**
    This box type is used to surround the currently-selected items in the
    menus.  If this is FL_NO_BOX then it acts like
    FL_THIN_UP_BOX and selection_color() acts like
    FL_WHITE, for back compatibility.
  */
  Fl_Boxtype down_box() const {return (Fl_Boxtype)down_box_;}
  /**    See Fl_Boxtype Fl_Menu_::down_box() const   */
  void down_box(Fl_Boxtype b) {down_box_ = b;}

  /** For back compatibility, same as selection_color() */
  Fl_Color down_color() const {return selection_color();}
  /** For back compatibility, same as selection_color() */
  void down_color(unsigned c) {selection_color(c);}
  void setonly(Fl_Menu_Item* item);
};

#endif

//
// End of "$Id: Fl_Menu_.H 11801 2016-07-09 17:06:46Z AlbrechtS $".
//


text:
"Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile"
N Engl J Med. 2013 Jan 31;368(5):407-15. [free full text]
Clostridioides (formerly Clostridium) difficile infection (CDI) is a common, increasingly prevalent, and increasingly recurrent disease. As discussed in the 2017-2018 Academic Year Week 43 post, the IDSA/SHEA guidelines published March 2018 now list vancomycin PO as first line treatment for initial, non-severe CDI. These guidelines also list fecal microbiota transplantation (FMT) as an option for treatment of a second or subsequent recurrence of CDI. FMT received a rating of "Strong [recommendation] / Moderate [level of evidence]" for this indication thanks to this 2013 trial by van Nood et al. – the first prospective RCT to compare antibiotic therapy to FMT in recurrent CDI.
This single-academic-center (Netherlands), open-label, randomized controlled trial compared three regimens for the treatment of recurrent CDI. One treatment arm received vancomycin 500mg PO QID x4-5 days followed by bowel lavage and then infusion of donor feces through nasoduodenal tube, another treatment arm received a standard 14-day vancomycin 500mg PO QID regimen, and the final treatment arm received a standard 14-day vancomycin regimen with additional bowel lavage on day 4 or 5. The primary endpoint was cure without relapse by 10 weeks.
43 patients were randomized prior to the termination of the trial due to the markedly higher rates of recurrent CDI among patients who did not receive FMT. Regarding the primary outcome, 13 (81%) of the FMT group were cured after the first infusion (and remained so) at 10 weeks, whereas resolution of CDI occurred in only 4 (31%) of the vancomycin-alone group and in only 3 (23%) of the vancomycin + bowel lavage group (p < 0.001 for both pairwise comparisons vs. FMT).
In this randomized controlled trial, fecal microbiota transplantation was superior to both vancomycin and vancomycin plus bowel lavage in the cure of recurrent Clostridium difficile infection. Although this trial was small, its effect was enormous. As mentioned above, FMT is now recommended by guidelines for the treatment of multiply-recurrent CDI. FMT has been the subject of numerous published and ongoing trials, including this notable 2017 study by Kao et al. that demonstrated noninferiority of FMT delivered via oral capsules versus "conventional" colonoscopic delivery.
3. 2017 Update to IDSA/SHEA Clinical Practice Guidelines for Clostridium difficile Infection
4. Kao et. al, "Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection." JAMA. 2017;318(20):1985-1993.
5. IDSA, "Fecal Microbiota Transplantation"
6. Food and Drug Administration, "Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies"
Image Credit: CDC/ Lois S. Wiggs (PHIL #6260), Public Domain, via Wikimedia Commons
Author Duncan MoorePosted on June 26, 2019 Categories GastroenterologyLeave a comment on Week 52 – Donor-Feces Infusion for Recurrent C. difficile
Week 51 – Rifaximin Treatment in Hepatic Encephalopathy
"Rifaximin Treatment in Hepatic Encephalopathy"
N Engl J Med. 2010 Mar25;362(12):1071-81. [free full text]
As we are well aware at Georgetown, hepatic encephalopathy (HE) is highly prevalent among patients with cirrhosis, and admissions for recurrent HE place a significant burden on the medical system. The authors of this study note that HE is thought to result from "the systemic accumulation of gut-derived neurotoxins, especially ammonia, in patients with impaired liver function and portosystemic shunting." Lactulose is considered the standard of care for the prevention of HE. It is thought to decrease the absorption of ammonia in the gut lumen through its cathartic effects and by alteration of colonic pH. The minimally absorbable oral antibiotic rifaximin is thought to further reduce ammonia production through direct antibacterial effects within the gut lumen. Thus the authors of this pivotal 2010 study sought to determine the additive effect of daily rifaximin prophylaxis in the prevention of HE.
The study enrolled adults with cirrhosis and 2+ episodes of overt HE during the past 6 months and randomized them to treatment with either rifaximin 550mg PO BID x6 months or placebo 550mg PO BID x6 months. The primary outcome was time to first breakthrough episode of HE (West Haven Score of 2+ or West Haven Score 0 –> 1 with worsening asterixis). Secondary outcomes included time to first hospitalization involving HE and adverse events, including those "possibly related to infection."
299 patients were randomized. 140 and 159 patients were assigned to rifaximin and placebo, respectively. Baseline characteristics were similar among the two groups. Lactulose use prior to and during the study was similar in both groups at approximately 91%. Breakthrough HE occurred in 31 (22.1%) of the rifaximin patients and 73 (45.9%) of the placebo patients [HR 0.42, 95% CI 0.28-0.64, p<0.001, absolute risk reduction 23.7%, NNT = 4.2]. This result was consistent within all tested subgroups, except patients with MELD score 19-24 and patients who were not using lactulose at baseline. (See Figure 3.) Hospitalization involving HE occurred in 19 (13.6%) of the rifaximin patients and 36 (22.6%) of the placebo patients [HR 0.50, 95% CI 0.29-0.87, p = 0.01, absolute risk reduction 9.1%, NNT = 11.0]. There were no differences in adverse events among the two treatment groups.
Thus, prophylactic rifaximin reduced the incidence of recurrent HE and its resultant hospitalizations. This landmark trial showed a clear treatment benefit with implied savings in healthcare utilization costs associated with HE recurrences and hospitalizations. This marked effect was demonstrated even in the setting of relatively good (91%) lactulose adherence in both treatment arms prior to and throughout the trial. On the day this trial was published in 2010, the FDA approved rifaximin for "reduction in risk of overt hepatic encephalopathy recurrence" in adults.
Because rifaximin is not generic and remains quite expensive, its financial utility is limited from an insurance company's perspective. There is no other comparable nonabsorbable antibiotic for this indication. UpToDate suggests starting with lactulose therapy and then adding a nonabsorbable antibiotic, such as rifaximin, both for the treatment of overt HE and for the prevention of recurrent HE. In practice, most insurance companies will require a prior authorization for outpatient rifaximin treatment, but in my recent experience, this process has been perfunctory and easy.
1. ClinicalTrials.gov, NCT00298038
2. FDA, NDA approval letter for Xifaxan (rifaximin)
3. UpToDate, "Hepatic encephalopathy in adults: Treatment"
Author Duncan MoorePosted on June 20, 2019 Categories GastroenterologyLeave a comment on Week 51 – Rifaximin Treatment in Hepatic Encephalopathy
The trial enrolled post-menopausal women with either 2 or more vertebral fractures per radiography or 1 vertebral fracture with decreased lumbar spine bone mineral density. Patients were randomized to the treatment arm (risedronate 2.5mg PO daily or risedronate 5mg PO daily) to the daily PO placebo control arm. Measured outcomes included: 1) the prevalence of new vertebral fracture at 3 years follow-up, per annual imaging, 2) the prevalence of new non-vertebral fracture at 3 years follow-up, per annual imaging, and 3) change in bone mineral density, per DEXA q6 months.
Oral risedronate reduces the risk of vertebral and non-vertebral fractures in patients with osteoporosis while increasing bone mineral density. Overall, this was a large, well-designed RCT that demonstrated a concrete treatment benefit. As a result, oral bisphosphonate therapy has become the standard of care both for treatment and prevention of osteoporosis. This study, as well as others, demonstrated that such therapies are well-tolerated with relatively few side effects. A notable strength of this study is that it did not exclude patients with GI comorbidities. One weakness is the modification of the trial protocol to eliminate the risedronate 2.5mg treatment arm after 1 year of study. Although this arm demonstrated a reduction in vertebral fracture at 1 year relative to placebo (p = 0.02), its elimination raises suspicion that the pre-specified analyses were not yielding the anticipated results during the interim analysis and thus the less-impressive treatment arm was discarded.
1. Weekly alendronate vs. weekly risedronate [https://www.ncbi.nlm.nih.gov/pubmed/15619680]
2. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review (2014) [https://www.ncbi.nlm.nih.gov/pubmed/25199883]
Image Credit: Nick Smith, CC BY-SA 3.0, via Wikimedia Commons
Author Duncan MoorePosted on June 11, 2019 Categories Endocrinology, non-NEJM, OutpatientLeave a comment on Week 50 – VERT
"Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure"
N Engl J Med. 2014 Sep 11;371(11):993-1004. [free full text]
Thanks to the CONSENSUS and SOLVD trials, angiotensin-converting enzyme (ACE) inhibitors have been a cornerstone of the treatment of heart failure with reduced ejection fraction (HFrEF) for years. Neprilysin is a neutral endopeptidase that degrades several peptides, including natriuretic peptides, bradykinin, and adrenomedullin. Inhibiting neprilysin increases levels of these substances and thus counteracts the neurohormonal overactivation of heart failure (which would otherwise lead to vasoconstriction, sodium retention, and maladaptive remodeling). Prior experimental data has demonstrated that, in terms of cardiovascular outcomes, neprilysin inhibition with an ARB is superior to ARB monotherapy. However, a clinical trial of concurrent neprilysin-inhibitor and ACE inhibitor therapy resulted in unacceptably high rates of serious angioedema. This study sought to show improved cardiac and mortality outcomes with neprilysin inhibition plus an ARB when compared to enalapril alone.
The study enrolled adults with NYHA class II, III, or IV heart failure, LVEF ≤ 35%, and BNP ≥ 150 or NT-proBNP ≥600. Pertinent exclusion criteria included symptomatic hypotension, SBP < 100mmHg at screening or 95mmHg at randomization, eGFR < 30 or decrease in eGFR by 25% between screening and randomization, K+ > 5.2, or history of angioedema/side effects to ACE inhibition or ARBs. Patients were randomized to treatment with either sacubitril/valsartan 200mg BID or to enalapril 10mg BID. (Screened patients were initially given sacubitril/valsartan followed by enalapril in single blinded run-in phases in order to ensure similar tolerance of the drugs prior to randomization.) The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. Selected secondary outcomes included: 1) change from baseline in the clinical summary score of the Kansas City Cardiomyopathy Questionnaire (KCCQ), 2) time to new-onset atrial fibrillation, and 3) time to first occurrence of decline in renal function.
4187 patients were randomized to the sacubitril/valsartan group, and 4212 were randomized to the enalapril group.
The primary endpoint (composite death due to cardiovascular causes or first hospitalization for HF) occurred in 914 patients (21.8%) in the sacubitril/valsartan group and 1117 patients (26.5%) in the enalapril group (p < 0.001; NNT = 21). Death due to cardiovascular causes occurred 558 times in the sacubitril/valsartan group and 693 times in the enalapril group (13.3% vs. 16.5%, p < 0.001; NNT = 31). Hospitalization for heart failure occurred (at least once) 537 times in the sacubitril/valsartan group and 658 times in the enalapril group (12.8% vs. 15.6%, p < 0.001; NNT = 36).
Regarding secondary outcomes, the mean change in KCCQ score was a reduction of 2.99 points (i.e. a worsening of symptoms) in the sacubitril/valsartan group versus a reduction of 4.63 points in the enalapril group (p = 0.001). There was no significant group difference in time to new-onset atrial fibrillation or time to diminished renal function.
Regarding safety outcomes, patients in the sacubitril/valsartan group were more likely to have symptomatic hypotension compared to patients in the enalapril group (14.0% vs. 9.2%; p < 0.001; NNH = 21). However, patients in the enalapril group were more likely to have cough, serum creatinine ≥ 2.5, or potassium ≥6.0 compared to sacubitril/valsartan (p value varies, all significant). There was no group difference in rates of angioedema (p = 0.13).
In patients with HFrEF, inhibition of both angiotensin II and neprilysin with sacubitril/valsartan significantly reduced the risk of cardiovascular death or hospitalization for heart failure when compared to treatment with enalapril alone.
This study had several strengths. The treatment with sacubitril/valsartan was compared to treatment with a dose of enalapril that had previously been shown to reduce mortality when compared with placebo. Furthermore, the study used a run-in phase to ensure that patients could tolerate an enalapril dose that had previously been shown to reduce mortality. Finally, more patients in the enalapril group than in the sacubitril/valsartan group stopped the study drug due to adverse effects (12.3% vs. 10.7%, p = 0.03).
This study ushered in a new era in heart failure management and added a new medication class – Angiotensin Receptor-Neprilysin Inhibitors or ARNIs – to the arsenal of available heart failure drugs. Entresto (sacubitril/valsartan), the ARNI posterchild, has been advertised widely over the past several years. However, clinical use so far has been lower than expected (see http://www.cardiobrief.org/2017/12/05/after-slow-start-entresto-is-poised-for-takeoff/). Novartis, Entresto's drug maker, is currently sponsoring PARAGON-HF, a trial of Entresto in patients with heart failure with preserved ejection fraction (HFpEF).
The 2017 ACC/AHA update to the guidelines for management of symptomatic HFrEF states that primary inhibition of the renin-angiotensin system with an ARNI in conjunction with evidence-based beta blockade and aldosterone antagonism is a Class I recommendation (Level B evidence). However, it does not favor this regimen over the Level-A-evidence regimens of an ARB or ACE inhibitor substituted for the ARNI. Yet the new guidelines also state that patients who have chronic symptomatic HFrEF of NYHA class II or III and tolerate an ACE inhibitor or ARB should substitute an ARNI for the ACE inhibitor or ARB in order to further reduce morbidity and mortality (Class I recommendation, level B evidence). See pages 15 and 17 here to read the details.
Among patients with symptomatic HFrEF, treatment with an ARNI reduces cardiovascular mortality and HF hospitalizations when compared to treatment with enalapril. Due to this study's impact, the use of ARNIs is now a Class I recommendation by the 2017 ACC/AHA guidelines for the treatment of HFrEF. Despite its higher cost, the use of sacubitril/valsartan appears to be cost-effective in terms of QALYs gained.
1. PARADIGM-HF @ Wiki Journal Club
2. PARADIGM-HF @ 2 Minute Medicine
3. ACC/AHA 2017 Focused Update for Guideline Management of Heart Failure
4. CardioBrief, "After Slow Start Entresto Is Poised For Takeoff."
5. PARAGON-HF @ ClinicalTrials.gov
6. McMurray et al., "Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction." Heart, 2017.
Summary by Patrick Miller, MD
Author Patrick MillerPosted on June 8, 2019 June 8, 2019 Categories CardiologyLeave a comment on Week 49 – PARADIGM-HF
N Engl J Med. 2014 Apr 10;370(15):1393-401 [free full text]
Approximately 10% of patients with hypertension have resistant hypertension (SBP > 140 despite adherence to three maximally tolerated doses of antihypertensives, including a diuretic). Evidence suggests that the sympathetic nervous system plays a large role in such cases, so catheter-based radiofrequency ablation of the renal arteries (renal denervation therapy) was developed as a potential treatment for resistant HTN. The 2010 SYMPLICITY HTN-2 trial was a small (n=106), non-blinded, randomized trial of renal denervation vs. continued care with oral antihypertensives that demonstrated a remarkable 30-mmHg greater decrease in SBP with renal denervation. Thus the 2014 SYMPLICITY HTN-3 trial was designed to evaluate the efficacy of renal denervation in a single-blinded trial with a sham-procedure control group.
Currently, there is no role for renal denervation therapy in the treatment of HTN (resistant or otherwise). However, despite the results of SYMPLICITY HTN-3, other companies and research groups are assessing the role of different radioablation catheters in patients with low-risk essential HTN and with resistant HTN. (For example, see https://www.ncbi.nlm.nih.gov/pubmed/29224639.)
Author Duncan MoorePosted on June 1, 2019 Categories Nephrology, OutpatientLeave a comment on Week 48 – SYMPLICITY HTN-3


Whether it be an evening out in the club or an evening at an elegant wedding ceremony; wobbling around in a pair of tight-fitting, toe-squeezing stiletto high heel sandals has decided to turn your dancing experience in a nightmare! The perfect couple of heels that does not only look sophisticated and elegant, however that also permit you to move around easily could make a big difference on earth.
Balancing your body and the balance is often a prerequisite for beautiful movements, be they simple or complex. Our women's high heel sandals influence and effect our spine and pelvis, knees, ankles along with the feet, but all of the sparkling heels available, how can we determine what shoe is perfect for us? These guidelines are primarily for ladies, because high heel shoes create particular challenges, but a majority of in the advice may also be necessary to men.
SELECT DESIGN: If you would like maximum support, opt for the fully enclosed heel cage. The shoe strap need to keep the shoe securely (and comfortably) in your foot, despite each of the dynamic flexion of your respective foot whilst you dance. Flex and point your ankles to check the fit.
SELECT HEEL HEIGHT: Go without your shoes, ascend to your tiptoes and walk around for a time. Once you're more comfortable with walking, let's check how high your heels are raised higher than the floor; here is the ideal heel height for you. If you want, you can contribute in regards to a 1/4", since heels provide slightly better support compared to walking on tiptoes. Avoid taking it to the maximum - it's easier to focus on the lower sizes and train your muscle mass gradually towards higher heels, in the event the latter is utterly needed for unknown reasons.
SELECT WIDTH: For optimum stability if you dance, your toes have to work! You should be able to stretch them long and open them wide, almost as should you be barefoot.
Keep in mind that suede and leather material stretch over the sneakers designed to use satin or patent leather.
SELECT LENGTH: Your toes need protection from minor brushes together with your partner's shoe. That is why the sole should extend slightly after dark length of your extended toes.
More info about giay cao got nu please visit web page: read.