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Taking a Closer Look at COVID-19's Effects on the Brain
Posted on January 14th, 2021 by Dr. Francis Collins
Caption: Magnetic resonance microscopy showing lower part of a COVID-19 patient's brain stem postmortem. Arrows point to light and dark spots indicative of blood vessel damage with no signs of infection by the coronavirus that causes COVID-19. Credit: National Institute of Neurological Disorders and Stroke, NIH
While primarily a respiratory disease, COVID-19 can also lead to neurological problems. The first of these symptoms might be the loss of smell and taste, while some people also may later battle headaches, debilitating fatigue, and trouble thinking clearly, sometimes referred to as "brain fog." All of these symptoms have researchers wondering how exactly the coronavirus that causes COVID-19, SARS-CoV-2, affects the human brain.
In search of clues, researchers at NIH's National Institute of Neurological Disorders and Stroke (NINDS) have now conducted the first in-depth examinations of human brain tissue samples from people who died after contracting COVID-19. Their findings, published in the New England Journal of Medicine, suggest that COVID-19's many neurological symptoms are likely explained by the body's widespread inflammatory response to infection and associated blood vessel injury—not by infection of the brain tissue itself [1].
The NIH team, led by Avindra Nath, used a high-powered magnetic resonance imaging (MRI) scanner (up to 10 times as sensitive as a typical MRI) to examine postmortem brain tissue from 19 patients. They ranged in age from 5 to 73, and some had preexisting conditions, such as diabetes, obesity, and cardiovascular disease.
The team focused on the brain's olfactory bulb that controls our ability to smell and the brainstem, which regulates breathing and heart rate. Based on earlier evidence, both areas are thought to be highly susceptible to COVID-19.
Indeed, the MRI images revealed in both regions an unusual number of bright spots, a sign of inflammation. They also showed dark spots, which indicate bleeding. A closer look at the bright spots showed that tiny blood vessels in those areas were thinner than normal and, in some cases, leaked blood proteins into the brain. This leakage appeared to trigger an immune reaction that included T cells from the blood and the brain's scavenging microglia. The dark spots showed a different pattern, with leaky vessels and clots but no evidence of an immune reaction.
While those findings are certainly interesting, perhaps equally noteworthy is what Nath and colleagues didn't see in those samples. They could find no evidence in the brain tissue samples that SARS-CoV-2 had invaded the brain tissue. In fact, several methods to detect genetic material or proteins from the virus all turned up empty.
The findings are especially intriguing because there has been some suggestion based on studies in mice that SARS-CoV-2 might cross the blood-brain barrier and invade the brain. Indeed, a recent report by NIH-funded researchers in Nature Neuroscience showed that the viral spike protein, when injected into mice, readily entered the brain along with many other organs [2].
Another recent report in the Journal of Experimental Medicine, which used mouse and human brain tissue, suggests that SARS-CoV-2 may indeed directly infect the central nervous system, including the brain [3]. In autopsies of three people who died from complications of COVID-19, the NIH-supported researchers detected signs of SARS-CoV-2 in neurons in the brain's cerebral cortex. This work was done using the microscopy-based technique of immunohistochemistry, which uses antibodies to bind to a target, in this case, the virus's spike protein. Also last month, in a study published in the journal Neurobiology of Disease, another NIH-supported team demonstrated in a series of experiments in cell culture that the SARS-CoV-2 spike protein could cross a 3D model of the blood-brain barrier and infect the endothelial cells that line blood vessels in the brain [4].
Clearly, more research is needed, and Nath and colleagues continue to explore how COVID-19 affects the brain and triggers the neurological symptoms often seen in people with COVID-19. As we learn more about the many ways COVID-19 wreaks havoc on the body, understanding the neurological symptoms will be critical in helping people, including the so-called Long Haulers bounce back from this terrible viral infection.
[1] Microvascular Injury in the Brains of Patients with Covid-19. Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. N Engl J Med. 2020 Dec 30.
[2] The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Rhea EM, Logsdon AF, Hansen KM, Williams LM, Reed MJ, Baumann KK, Holden SJ, Raber J, Banks WA, Erickson MA. Nat Neurosci. 2020 Dec 16.
[3] Neuroinvasion of SARS-CoV-2 in human and mouse brain. Song E, Zhang C, Israelow B, et al. J Exp Med (2021) 218 (3): e20202135.
[4] The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, Razmpour R, Hale JF, Galie PA, Potula R, Andrews AM, Ramirez SH. Neurobiol Dis. 2020 Dec;146:105131.
COVID-19 Research (NIH)
Avindra Nath (National Institute of Neurological Disorders and Stroke/NIH)
NIH Support: National Institute of Neurological Disorders and Stroke; National Institute on Aging; National Institute of General Medical Sciences; National Cancer Institute; National Institute of Mental Health
Tags: blood vessels, blood-brain barrier, brain, brain fog, brainstem, coronavirus, COVID-19, COVID-19 infections, COVID-19-inflammation, long COVID, long-haulers, microglia, neurology, novel coronavirus, olfactory bulb, pandemic, SARS-CoV-2, spike protein, T cells
What A Year It Was for Science Advances!
At the close of every year, editors and writers at the journal Science review the progress that's been made in all fields of science—from anthropology to zoology—to select the biggest advance of the past 12 months. In most cases, this Breakthrough of the Year is as tough to predict as the Oscar for Best Picture. Not in 2020. In a year filled with a multitude of challenges posed by the emergence of the deadly coronavirus disease 2019 (COVID-2019), the breakthrough was the development of the first vaccines to protect against this pandemic that's already claimed the lives of more than 360,000 Americans.
In keeping with its annual tradition, Science also selected nine runner-up breakthroughs. This impressive list includes at least three areas that involved efforts supported by NIH: therapeutic applications of gene editing, basic research understanding HIV, and scientists speaking up for diversity. Here's a quick rundown of all the pioneering advances in biomedical research, both NIH and non-NIH funded:
Shots of Hope. A lot of things happened in 2020 that were unprecedented. At the top of the list was the rapid development of COVID-19 vaccines. Public and private researchers accomplished in 10 months what normally takes about 8 years to produce two vaccines for public use, with more on the way in 2021. In my more than 25 years at NIH, I've never encountered such a willingness among researchers to set aside their other concerns and gather around the same table to get the job done fast, safely, and efficiently for the world.
It's also pretty amazing that the first two conditionally approved vaccines from Pfizer and Moderna were found to be more than 90 percent effective at protecting people from infection with SARS-CoV-2, the coronavirus that causes COVID-19. Both are innovative messenger RNA (mRNA) vaccines, a new approach to vaccination.
For this type of vaccine, the centerpiece is a small, non-infectious snippet of mRNA that encodes the instructions to make the spike protein that crowns the outer surface of SARS-CoV-2. When the mRNA is injected into a shoulder muscle, cells there will follow the encoded instructions and temporarily make copies of this signature viral protein. As the immune system detects these copies, it spurs the production of antibodies and helps the body remember how to fend off SARS-CoV-2 should the real thing be encountered.
It also can't be understated that both mRNA vaccines—one developed by Pfizer and the other by Moderna in conjunction with NIH's National Institute of Allergy and Infectious Diseases—were rigorously evaluated in clinical trials. Detailed data were posted online and discussed in all-day meetings of an FDA Advisory Committee, open to the public. In fact, given the high stakes, the level of review probably was more scientifically rigorous than ever.
First CRISPR Cures: One of the most promising areas of research now underway involves gene editing. These tools, still relatively new, hold the potential to fix gene misspellings—and potentially cure—a wide range of genetic diseases that were once to be out of reach. Much of the research focus has centered on CRISPR/Cas9. This highly precise gene-editing system relies on guide RNA molecules to direct a scissor-like Cas9 enzyme to just the right spot in the genome to cut out or correct a disease-causing misspelling.
In late 2020, a team of researchers in the United States and Europe succeeded for the first time in using CRISPR to treat 10 people with sickle cell disease and transfusion-dependent beta thalassemia. As published in the New England Journal of Medicine, several months after this non-heritable treatment, all patients no longer needed frequent blood transfusions and are living pain free [1].
The researchers tested a one-time treatment in which they removed bone marrow from each patient, modified the blood-forming hematopoietic stem cells outside the body using CRISPR, and then reinfused them into the body. To prepare for receiving the corrected cells, patients were given toxic bone marrow ablation therapy, in order to make room for the corrected cells. The result: the modified stem cells were reprogrammed to switch back to making ample amounts of a healthy form of hemoglobin that their bodies produced in the womb. While the treatment is still risky, complex, and prohibitively expensive, this work is an impressive start for more breakthroughs to come using gene editing technologies. NIH, including its Somatic Cell Genome Editing program, continues to push the technology to accelerate progress and make gene editing cures for many disorders simpler and less toxic.
Scientists Speak Up for Diversity: The year 2020 will be remembered not only for COVID-19, but also for the very public and inescapable evidence of the persistence of racial discrimination in the United States. Triggered by the killing of George Floyd and other similar events, Americans were forced to come to grips with the fact that our society does not provide equal opportunity and justice for all. And that applies to the scientific community as well.
Science thrives in safe, diverse, and inclusive research environments. It suffers when racism and bigotry find a home to stifle diversity—and community for all—in the sciences. For the nation's leading science institutions, there is a place and a calling to encourage diversity in the scientific workplace and provide the resources to let it flourish to everyone's benefit.
For those of us at NIH, last year's peaceful protests and hashtags were noticed and taken to heart. That's one of the many reasons why we will continue to strengthen our commitment to building a culturally diverse, inclusive workplace. For example, we have established the NIH Equity Committee. It allows for the systematic tracking and evaluation of diversity and inclusion metrics for the intramural research program for each NIH institute and center. There is also the recently founded Distinguished Scholars Program, which aims to increase the diversity of tenure track investigators at NIH. Recently, NIH also announced that it will provide support to institutions to recruit diverse groups or "cohorts" of early-stage research faculty and prepare them to thrive as NIH-funded researchers.
AI Disentangles Protein Folding: Proteins, which are the workhorses of the cell, are made up of long, interconnected strings of amino acids that fold into a wide variety of 3D shapes. Understanding the precise shape of a protein facilitates efforts to figure out its function, its potential role in a disease, and even how to target it with therapies. To gain such understanding, researchers often try to predict a protein's precise 3D chemical structure using basic principles of physics—including quantum mechanics. But while nature does this in real time zillions of times a day, computational approaches have not been able to do this—until now.
Of the roughly 170,000 proteins mapped so far, most have had their structures deciphered using powerful imaging techniques such as x-ray crystallography and cryo–electron microscopy (cryo-EM). But researchers estimate that there are at least 200 million proteins in nature, and, as amazing as these imaging techniques are, they are laborious, and it can take many months or years to solve 3D structure of a single protein. So, a breakthrough certainly was needed!
In 2020, researchers with the company Deep Mind, London, developed an artificial intelligence (AI) program that rapidly predicts most protein structures as accurately as x-ray crystallography and cryo-EM can map them [2]. The AI program, called AlphaFold, predicts a protein's structure by computationally modeling the amino acid interactions that govern its 3D shape.
Getting there wasn't easy. While a complete de novo calculation of protein structure still seemed out of reach, investigators reasoned that they could kick start the modeling if known structures were provided as a training set to the AI program. Utilizing a computer network built around 128 machine learning processors, the AlphaFold system was created by first focusing on the 170,000 proteins with known structures in a reiterative process called deep learning. The process, which is inspired by the way neural networks in the human brain process information, enables computers to look for patterns in large collections of data. In this case, AlphaFold learned to predict the underlying physical structure of a protein within a matter of days. This breakthrough has the potential to accelerate the fields of structural biology and protein research, fueling progress throughout the sciences.
How Elite Controllers Keep HIV at Bay: The term "elite controller" might make some people think of video game whizzes. But here, it refers to the less than 1 percent of people living with human immunodeficiency virus (HIV) who've somehow stayed healthy for years without taking antiretroviral drugs. In 2020, a team of NIH-supported researchers figured out why this is so.
In a study of 64 elite controllers, published in the journal Nature, the team discovered a link between their good health and where the virus has inserted itself in their genomes [3]. When a cell transcribes a gene where HIV has settled, this so-called "provirus," can produce more virus to infect other cells. But if it settles in a part of a chromosome that rarely gets transcribed, sometimes called a gene desert, the provirus is stuck with no way to replicate. Although this discovery won't cure HIV/AIDS, it points to a new direction for developing better treatment strategies.
In closing, 2020 presented more than its share of personal and social challenges. Among those challenges was a flood of misinformation about COVID-19 that confused and divided many communities and even families. That's why the editors and writers at Science singled out "a second pandemic of misinformation" as its Breakdown of the Year. This divisiveness should concern all of us greatly, as COVID-19 cases continue to soar around the country and our healthcare gets stretched to the breaking point. I hope and pray that we will all find a way to come together, both in science and in society, as we move forward in 2021.
[1] CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. Frangoul H et al. N Engl J Med. 2020 Dec 5.
[2] 'The game has changed.' AI triumphs at protein folding. Service RF. Science. 04 Dec 2020.
[3] Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Jiang C et al. Nature. 2020 Sep;585(7824):261-267.
2020 Science Breakthrough of the Year (American Association for the Advancement of Science, Washington, D.C)
Tags: AlphaFold, artificial intelligence, beta thalassemia, coronavirus, COVID-19, COVID-19 vaccine, CRISPR, CRISPR/Cas9, cryo-electron microscopy, cryo-EM, deep learning, Deep Mind, diversity, elite controllers, gene editing, George Floyd, HIV, imaging, misinformation, Moderna, mRNA vaccine, NIH Distinguished Scholars Program, NIH Equity Committee, novel coronavirus, pandemic, Pfizer, protein folding, SARS-CoV-2, Science Breakthroughs of the Year 2020, Science's Breakthroughs of the Year, Science's Top 10 Science Advances, sickle cell disease, Somatic Cell Genome Editing, spike protein, structural biology, transfusion-dependent beta thalassemia, x-ray crystallography
DNA Base Editing May Treat Progeria, Study in Mice Shows
Posted on January 7th, 2021 by Dr. Francis Collins
Credit: Progeria Research Foundation
My good friend Sam Berns was born with a rare genetic condition that causes rapid premature aging. Though Sam passed away in his teens from complications of this condition, called Hutchinson-Gilford progeria syndrome, he's remembered today for his truly positive outlook on life. Sam expressed it, in part, by his willingness to make adjustments that allowed him, in his words, to put things that he always wanted to do in the "can do" category.
In this same spirit on behalf of the several hundred kids worldwide with progeria and their families, a research collaboration, including my NIH lab, has now achieved a key technical advance to move non-heritable gene editing another step closer to the "can do" category to treat progeria. As published in the journal Nature, our team took advantage of new gene-editing tools to correct for the first time a single genetic misspelling responsible for progeria in a mouse model, with dramatically beneficial effects [1, 2]. This work also has implications for correcting similar single-base typos that cause other inherited genetic disorders.
The outcome of this work is incredibly gratifying for me. In 2003, my NIH lab discovered the DNA mutation that causes progeria. One seemingly small glitch—swapping a "T" in place of a "C" in a gene called lamin A (LMNA)—leads to the production of a toxic protein now known as progerin. Without treatment, children with progeria develop normally intellectually but age at an exceedingly rapid pace, usually dying prematurely from heart attacks or strokes in their early teens.
The discovery raised the possibility that correcting this single-letter typo might one day help or even cure children with progeria. But back then, we lacked the needed tools to edit DNA safely and precisely. To be honest, I didn't think that would be possible in my lifetime. Now, thanks to advances in basic genomic research, including work that led to the 2020 Nobel Prize in Chemistry, that's changed. In fact, there's been substantial progress toward using gene-editing technologies, such as the CRISPR editing system, for treating or even curing a wide range of devastating genetic conditions, such as sickle cell disease and muscular dystrophy
It turns out that the original CRISPR system, as powerful as it is, works better at knocking out genes than correcting them. That's what makes some more recently developed DNA editing agents and approaches so important. One of them, which was developed by David R. Liu, Broad Institute of MIT and Harvard, Cambridge, MA, and his lab members, is key to these latest findings on progeria, reported by a team including my lab in NIH's National Human Genome Research Institute and Jonathan Brown, Vanderbilt University Medical Center, Nashville, TN.
The relatively new gene-editing system moves beyond knock-outs to knock-ins [3,4]. Here's how it works: Instead of cutting DNA as CRISPR does, base editors directly convert one DNA letter to another by enzymatically changing one DNA base to become a different base. The result is much like the find-and-replace function used to fix a typo in a word processor. What's more, the gene editor does this without cutting the DNA.
Our three labs (Liu, Brown, and Collins) first teamed up with the Progeria Research Foundation, Peabody, MA, to obtain skin cells from kids with progeria. In lab studies, we found that base editors, targeted by an appropriate RNA guide, could successfully correct the LMNA gene in those connective tissue cells. The treatment converted the mutation back to the normal gene sequence in an impressive 90 percent of the cells.
But would it work in a living animal? To get the answer, we delivered a single injection of the DNA-editing apparatus into nearly a dozen mice either three or 14 days after birth, which corresponds in maturation level roughly to a 1-year-old or 5-year-old human. To ensure the findings in mice would be as relevant as possible to a future treatment for use in humans, we took advantage of a mouse model of progeria developed in my NIH lab in which the mice carry two copies of the human LMNA gene variant that causes the condition. Those mice develop nearly all of the features of the human illness
In the live mice, the base-editing treatment successfully edited in the gene's healthy DNA sequence in 20 to 60 percent of cells across many organs. Many cell types maintained the corrected DNA sequence for at least six months—in fact, the most vulnerable cells in large arteries actually showed an almost 100 percent correction at 6 months, apparently because the corrected cells had compensated for the uncorrected cells that had died out. What's more, the lifespan of the treated animals increased from seven to almost 18 months. In healthy mice, that's approximately the beginning of old age.
This is the second notable advance in therapeutics for progeria in just three months. Last November, based on preclinical work from my lab and clinical trials conducted by the Progeria Research Foundation in Boston, the Food and Drug Administration (FDA) approved the first treatment for the condition. It is a drug called Zokinvy, and works by reducing the accumulation of progerin [5]. With long-term treatment, the drug is capable of extending the life of kids with progeria by 2.5 years and sometimes more. But it is not a cure.
We are hopeful this gene editing work might eventually lead to a cure for progeria. But mice certainly aren't humans, and there are still important steps that need to be completed before such a gene-editing treatment could be tried safely in people. In the meantime, base editors and other gene editing approaches keep getting better—with potential application to thousands of genetic diseases where we know the exact gene misspelling. As we look ahead to 2021, the dream envisioned all those years ago about fixing the tiny DNA typo responsible for progeria is now within our grasp and getting closer to landing in the "can do" category.
[1] In vivo base editing rescues Hutchinson-Gilford Progeria Syndrome in mice. Koblan LW et al. Nature. 2021 Jan 6.
[2] Base editor repairs mutation found in the premature-ageing syndrome progeria. Vermeij WP, Hoeijmakers JHJ. Nature. 6 Jan 2021.
[3] Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Nature. 2016 May 19;533(7603):420-424.
[4] Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR. Nature. 2017 Nov 23;551(7681):464-471.
[5] FDA approves first treatment for Hutchinson-Gilford progeria syndrome and some progeroid laminopathies. Food and Drug Administration. 2020 Nov 20.
Progeria (Genetic and Rare Diseases Information Center/NIH)
What are Genome Editing and CRISPR-Cas9? (National Library of Medicine/NIH)
Somatic Cell Genome Editing Program (Common Fund/NIH)
David R. Liu (Harvard University, Cambridge, MA)
Collins Group (National Human Genome Research Institute/NIH)
Jonathan Brown (Vanderbilt University Medical Center, Nashville, TN)
NIH Support: National Human Genome Research Institute; National Center for Advancing Translational Sciences; National Institute of Biomedical Imaging and Bioengineering; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Common Fund
Tags: aging, base editors, CRISPR, DNA, gene editing, genetic diseases, genomics, Hutchinson-Gilford progeria syndrome, inherited disease, lamin-A, LMNA, LMNA gene variant, mouse model, mouse study, progeria, Progeria Research Foundation, progerin, rare disease, sam berns
The People's Picks for Best Posts
It's 2021—Happy New Year! Time sure flies in the blogosphere. It seems like just yesterday that I started the NIH Director's Blog to highlight recent advances in biology and medicine, many supported by NIH. Yet it turns out that more than eight years have passed since this blog got rolling and we are fast approaching my 1,000th post!
I'm pleased that millions of you have clicked on these posts to check out some very cool science and learn more about NIH and its mission. Thanks to the wonders of social media software, we've been able to tally up those views to determine each year's most-popular post. So, I thought it would be fun to ring in the New Year by looking back at a few of your favorites, sort of a geeky version of a top 10 countdown or the People's Choice Awards. It was interesting to see what topics generated the greatest interest. Spoiler alert: diet and exercise seemed to matter a lot! So, without further ado, I present the winners:
2013: Fighting Obesity: New Hopes from Brown Fat. Brown fat, one of several types of fat made by our bodies, was long thought to produce body heat rather than store energy. But Shingo Kajimura and his team at the University of California, San Francisco, showed in a study published in the journal Nature, that brown fat does more than that. They discovered a gene that acts as a molecular switch to produce brown fat, then linked mutations in this gene to obesity in humans.
What was also nice about this blog post is that it appeared just after Kajimura had started his own lab. In fact, this was one of the lab's first publications. One of my goals when starting the blog was to feature young researchers, and this work certainly deserved the attention it got from blog readers. Since highlighting this work, research on brown fat has continued to progress, with new evidence in humans suggesting that brown fat is an effective target to improve glucose homeostasis.
2014: In Memory of Sam Berns. I wrote this blog post as a tribute to someone who will always be very near and dear to me. Sam Berns was born with Hutchinson-Gilford progeria syndrome, one of the rarest of rare diseases. After receiving the sad news that this brave young man had passed away, I wrote: "Sam may have only lived 17 years, but in his short life he taught the rest of us a lot about how to live."
Affecting approximately 400 people worldwide, progeria causes premature aging. Without treatment, children with progeria, who have completely normal intellectual development, die of atherosclerotic cardiovascular disease, on average in their early teens.
From interactions with Sam and his parents in the early 2000s, I started to study progeria in my NIH lab, eventually identifying the gene responsible for the disorder. My group and others have learned a lot since then. So, it was heartening last November when the Food and Drug Administration approved the first treatment for progeria. It's an oral medication called Zokinvy (lonafarnib) that helps prevent the buildup of defective protein that has deadly consequences. In clinical trials, the drug increased the average survival time of those with progeria by more than two years. It's a good beginning, but we have much more work to do in the memory of Sam and to help others with progeria. Watch for more about new developments in applying gene editing to progeria in the next few days.
2015: Cytotoxic T Cells on Patrol. Readers absolutely loved this post. When the American Society of Cell Biology held its first annual video competition, called CellDance, my blog featured some of the winners. Among them was this captivating video from Alex Ritter, then working with cell biologist Jennifer Lippincott-Schwartz of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development. The video stars a roving, specialized component of our immune system called cytotoxic T cells. Their job is to seek out and destroy any foreign or detrimental cells. Here, these T cells literally convince a problem cell to commit suicide, a process that takes about 10 minutes from detection to death.
These cytotoxic T cells are critical players in cancer immunotherapy, in which a patient's own immune system is enlisted to control and, in some cases, even cure the cancer. Cancer immunotherapy remains a promising area of research that continues to progress, with a lot of attention now being focused on developing immunotherapies for common, solid tumors like breast cancer. Ritter is currently completing a postdoctoral fellowship in the laboratory of Ira Mellman, Genentech, South San Francisco. His focus has shifted to how cancer cells protect themselves from T cells. And video buffs—get this—Ritter says he's now created even cooler videos that than the one in this post.
2016: Exercise Releases Brain-Healthy Protein. The research literature is pretty clear: exercise is good for the brain. In this very popular post, researchers led by Hyo Youl Moon and Henriette van Praag of NIH's National Institute on Aging identified a protein secreted by skeletal muscle cells to help explore the muscle-brain connection. In a study in Cell Metabolism, Moon and his team showed that this protein called cathepsin B makes its way into the brain and after a good workout influences the development of new neural connections. This post is also memorable to me for the photo collage that accompanied the original post. Why? If you look closely at the bottom right, you'll see me exercising—part of my regular morning routine!
2017: Muscle Enzyme Explains Weight Gain in Middle Age. The struggle to maintain a healthy weight is a lifelong challenge for many of us. While several risk factors for weight gain, such as counting calories, are within our control, there's a major one that isn't: age. Jay Chung, a researcher with NIH's National Heart, Lung, and Blood Institute, and his team discovered that the normal aging process causes levels of an enzyme called DNA-PK to rise in animals as they approach middle age. While the enzyme is known for its role in DNA repair, their studies showed it also slows down metabolism, making it more difficult to burn fat.
Since publishing this paper in Cell Metabolism, Chung has been busy trying to understand how aging increases the activity of DNA-PK and its ability to suppress renewal of the cell's energy-producing mitochondria. Without renewal of damaged mitochondria, excess oxidants accumulate in cells that then activate DNA-PK, which contributed to the damage in the first place. Chung calls it a "vicious cycle" of aging and one that we'll be learning more about in the future.
2018: Has an Alternative to Table Sugar Contributed to the C. Diff. Epidemic? This impressive bit of microbial detective work had blog readers clicking and commenting for several weeks. So, it's no surprise that it was the runaway People's Choice of 2018.
Clostridium difficile (C. diff) is a common bacterium that lives harmlessly in the gut of most people. But taking antibiotics can upset the normal balance of healthy gut microbes, allowing C. diff. to multiply and produce toxins that cause inflammation and diarrhea.
In the 2000s, C. diff. infections became far more serious and common in American hospitals, and Robert Britton, a researcher at Baylor College of Medicine, Houston, wanted to know why. He and his team discovered that two subtypes of C. diff have adapted to feed on the sugar trehalose, which was approved as a food additive in the United States during the early 2000s. The team's findings, published in the journal Nature, suggested that hospitals and nursing homes battling C. diff. outbreaks may want to take a closer look at the effect of trehalose in the diet of their patients.
2019: Study Finds No Benefit for Dietary Supplements. This post that was another one that sparked a firestorm of comments from readers. A team of NIH-supported researchers, led by Fang Fang Zhang, Tufts University, Boston, found that people who reported taking dietary supplements had about the same risk of dying as those who got their nutrients through food. What's more, the mortality benefits associated with adequate intake of vitamin A, vitamin K, magnesium, zinc, and copper were limited to amounts that are available from food consumption. The researchers based their conclusion on an analysis of the well-known National Health and Nutrition Examination Survey (NHANES) between 1999-2000 and 2009-2010 survey data. The team, which reported its data in the Annals of Internal Medicine, also uncovered some evidence suggesting that certain supplements might even be harmful to health when taken in excess.
2020: Genes, Blood Type Tied to Risk of Severe COVID-19. Typically, my blog focuses on research involving many different diseases. That changed in 2020 due to the emergence of a formidable public health challenge: the coronavirus disease 2019 (COVID-19) pandemic. Since last March, the blog has featured 85 posts on COVID-19, covering all aspects of the research response and attracting more visitors than ever. And which post got the most views? It was one that highlighted a study, published last June in the New England Journal of Medicine, that suggested the clues to people's variable responses to COVID-19 may be found in our genes and our blood types.
The researchers found that gene variants in two regions of the human genome are associated with severe COVID-19 and correspondingly carry a greater risk of COVID-19-related death. The two stretches of DNA implicated as harboring risks for severe COVID-19 are known to carry some intriguing genes, including one that determines blood type and others that play various roles in the immune system.
In fact, the findings suggest that people with blood type A face a 50 percent greater risk of needing oxygen support or a ventilator should they become infected with the novel coronavirus. In contrast, people with blood type O appear to have about a 50 percent reduced risk of severe COVID-19.
That's it for the blog's year-by-year Top Hits. But wait! I'd also like to give shout outs to the People's Choice winners in two other important categories—history and cool science images.
Top History Post: HeLa Cells: A New Chapter in An Enduring Story. Published in August 2013, this post remains one of the blog's greatest hits with readers. The post highlights science's use of cancer cells taken in the 1950s from a young Black woman named Henrietta Lacks. These "HeLa" cells had an amazing property not seen before: they could be grown continuously in laboratory conditions. The "new chapter" featured in this post is an agreement with the Lacks family that gives researchers access to the HeLa genome data, while still protecting the family's privacy and recognizing their enormous contribution to medical research. And the acknowledgments rightfully keep coming from those who know this remarkable story, which has been chronicled in both book and film. Recently, the U.S. Senate and House of Representatives passed the Henrietta Lacks Enhancing Cancer Research Act to honor her extraordinary life and examine access to government-funded cancer clinical trials for traditionally underrepresented groups.
Top Snapshots of Life: A Close-up of COVID-19 in Lung Cells. My blog posts come in several categories. One that you may have noticed is "Snapshots of Life," which provides a showcase for cool images that appear in scientific journals and often dominate Science as Art contests. My blog has published dozens of these eye-catching images, representing a broad spectrum of the biomedical sciences. But the blog People's Choice goes to a very recent addition that reveals exactly what happens to cells in the human airway when they are infected with the coronavirus responsible for COVID-19. This vivid image, published in the New England Journal of Medicine, comes from the lab of pediatric pulmonologist Camille Ehre, University of North Carolina at Chapel Hill. This image squeezed in just ahead of another highly popular post from Steve Ramirez, Boston University, in 2019 that showed "What a Memory Looks Like."
As we look ahead to 2021, I want to thank each of my blog's readers for your views and comments over the last eight years. I love to hear from you, so keep on clicking! I'm confident that 2021 will generate a lot more amazing and bloggable science, including even more progress toward ending the COVID-19 pandemic that made our past year so very challenging.
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Tags: aging, blood type, brown fat, C. diff, cancer, cancer immunotherapy, cathepsin, cathepsin B, Clostridium difficile, coronavirus, COVID-19, cytotoxic T cells, diet, dietary supplements, DNA-PK, exercise, FDA, genes, HeLa cells, Henrietta Lacks, Henrietta Lacks Enhancing Cancer Research Act, Hutchinson-Gilford progeria syndrome, Ira Mellman, Jennifer Lippincott-Schwartz, lonafarnib, lung cells, memory, mitochondria, muscle, obesity, progeria, sam berns, T cells, trehalose, weight gain, Zokinvy
Accepting the COVID-19 Vaccine
Posted on December 22nd, 2020 by Dr. Francis Collins
I was thrilled to roll up my sleeve and get the Moderna COVID-19 vaccine today at the NIH Clinical Center. As NIH Director, I've followed closely the development of these first vaccines, and I know they have been rigorously tested and found to be safe and effective. I encourage everyone to accept the vaccines when offered to you. It's our best chance to turn the tide on the pandemic. Also receiving the vaccine today were Health and Human Services Secretary Alex Azar, Anthony Fauci, Director of NIH's National Institute of Allergy and Infectious Diseases; Colleen McGowan, Director of NIH's Office of Research Services; and six frontline healthcare workers at the NIH Clinical Center. Credit: NIH
Posted In: Director's Album - Photos
Tags: Alex Azar, Colleen McGowan, COVID-19, COVID-19 vaccine, Moderna, NIH Clinical Center, pandemic, SARS-CoV-2, Tony Fauci


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Posted inBody Cameras for Police, Featured, More headlines, News, Top
Ithaca's Council looks at police budget, cost of new cameras
by Jeff Stein October 20, 2015 January 31, 2023
This story was written by the Ithaca Voice's Mike Smith.
Ithaca, N.Y. — Ithaca's Common Council continues to work through the details of Mayor Svante Myrick's proposed budget, with much of a budget meeting last week dedicated to police spending.
[do_widget id= text-55 ]
The mayor's budget proposes an increase of a little over 1% to the IPD's $11.5 million operating budget.
Here are 3 takeaways from the meeting:
1 — New Programs Cost Money, Manpower
IPD is poised to roll out its body camera program in the the coming months. Official trainings are on the books for the end of October.
This technology comes at substantial cost – both in terms of both raw dollars and staffing requirements.
IPD Chief John Barber rolled out the figures: an initial investment of $74,200 was to purchase the cameras, followed by a yearly investment of $29,000 to cover the storage space and powerful software needed to utilize the cameras.
This new body camera protocol also raises concerns about an already understaffed police department. When footage from a camera is needed in a case, the process of preparing that footage is very labor intensive.
According to Barber, this may require the department to expand its administrative capabilities to keep up, so that officers aren't stuck behind desks reviewing film when they could be out making an impact in the community.
2 — Staffing Crisis Looms
Even without body cameras adding to the workload, the IPD is already stretched thin.
While the department is funded for up to 69 officers, only 62 are on staff – and 8 of those are on light duty, out on disability, awaiting additional training, or otherwise unable to work at full capacity. This leaves the number of active officers at just 54. In addition, a number of officers are up for retirement next year, many of them senior officers and investigators.
Even with 3 new recruits being sworn in soon, and a potential new batch of recruits soon to be taking their civil service tests in November, the IPD may be dealing with this staffing shortage for many months to come, according to officials.
Mayor Svante Myrick's proposed budget calls for a small increase to IPD
3 — Success Stories
Despite the ongoing manpower problem, IPD is still making strides forward. Chief Barber reported that crime rates are down and recent county-wide stings had made a substantial dent in Ithaca's illegal narcotics market.
Additionally, Ithaca seems poised to adopt something akin to Seattle's "LEAD" program – an alternative to jailing low-level drug offenders that seeks to get them in treatment instead of a cell. Mayor Myrick was quick to note, however, that implementing such a major program will require, you guessed it, more money and manpower.
The department has also maintained its focus on community outreach programs. Chief Barber pointed out that IPD has made over 100 community outreach efforts this year – like the upcoming Community – IPD Barbecue on Saturday.
Jeff Stein
Jeff Stein is the founder and former editor of the Ithaca Voice. More by Jeff Stein
Ithaca man convicted of assault, burglary in 2021 home invasion

redpajama_set_name: RedPajamaCommonCrawl


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Parents & Caregivers
The #MeToo Movement Gives Me Hope for a World Without Abuse
Neesha Arter
The year 2017 has been an uphill battle for women, and a year of liberation. Numerous people have asked me how I feel about the #MeToo movement being a person who could say, "me too." In 2015, I released my first book, CONTROLLED, a memoir which details my own sexual assault and its aftermath. Through my book I outline what occurred after my assault, a legal case I never wanted and a battle against anorexia to cope with PTSD.
Through the experience, I learned it is reported that 30% of people with eating disorders have been sexually abused, but I'd be willing to guess that 30% is nowhere near the real number of victims. There is a huge stigma surrounding sexual assault.
I don't think women, men, girls or boys have been so forthcoming and willing to remove that shame until the year 2017, which is one of the greatest changes I could ever hope to see. I could not be prouder of every single person who did, in my opinion, the bravest thing a person can do: put their shame aside for the greater cause.
The two years following the release of my book became a constant learning curve I never expected, for a variety of reasons. It could have been the sheer excess of emotions I was not prepared for, or the hundreds of people who reached out to share their stories. But in focusing on the year of 2017, most of the questions I received were surrounding the #MeToo movement and my reactions. Was I triggered? Was I upset? Or, was I empowered?
Actually, my first reaction was validation. For many years I felt like I was screaming in a crowded room and no one would even turn their head. I just wanted to get one person to listen to me, to be able share my story, to get people to care about this global issue. I have always been passionate about social advocacy and I've seen that sharing my story inspires others to know they are not alone and their trauma is not their fault.
Unfortunately, I feel that we live in a world where everyone's problems are boring until their problem becomes your problem. No one realizes just how bad this issue is, or how deep it goes.
As for the movement, it sometimes seems overwhelming, but that's the exact reason why it is also so empowering and far-reaching. For me, I've always known, through the writing of my book that began at age 18, that my sexual assault was never my fault.
However, not everyone does. Society continually blames the victims and even family and friends are unable to offer their support. It is impossible to cope with trauma from a sexual assault or rape by yourself. I tried to deal with it on my own, and that ended up in a battle of numbers and control. This battle over control took me years to get out of. It wasn't until I began writing my book that I was able to speak about my past and come to terms with it.
Control is a near impossible force to regain, once you have lost it. After I was sexually assaulted I felt like my body was not my own anymore. It felt like something that no longer belonged to me, and consequently had no worth. With extreme confusion on where I belonged in the world at fourteen, I didn't feel like a child anymore. I felt like my innocence was gone and began down a rabbit hole of trying to regain my childhood self by controlling how I looked and what I ate. In some twisted way, it made me feel safer. I was able to escape reality and live in a world of self-preservation, never facing my real problem: I had lost control.
For those who have experienced trauma, I don't need to tell you what it feels like to turn on survival mode. But for those who don't, I cannot express enough the importance of empathy. People forget how toxic shame is and how it keeps the struggle alive for those who have experienced sexual assault and eating disorders.
I look forward to living in a world without abuse. I have always been a skeptic on whether or not that world is possible, but the #MeToo movement has given me, and so many others, hope.
If you or someone you care about has been the victim of sexual assault, please act now to ensure that you get the help you need and deserve. Call RAINN's National Sexual Assault Hotline at 800-656-HOPE.
For recovery resources and treatment options, call the National Eating Disorders Association Helpline at 800-931-2237. In crisis situations, text "NEDA" to 741741 to be connected with a trained volunteer from Crisis Text Line.
Take action today! Channel your inner champion, face your fears, and raise money for a great cause through NEDA's Fearless Challenge! Is there that one thing you have always wanted to do but something has been holding you back? Maybe it's sharing your story in front of a crowd, attending a march or protest, or something as simple as posting an unedited selfie. Whatever that one thing is, now is your chance! Join the campaign by visiting myneda.org/fearless.
Neesha Arter is a journalist, author, and speaker in New York City. Her memoir, CONTROLLED, was published in August 2015. Her work has appeared in The New York Times, The Daily Beast, the New York Observer, New York Magazine, Interview, Teen Vogue, and others. Neesha is also an advocate, appearing in the UN's He for She Campaign, End Rape on Campus, Newsweek, The U.S. Office on Women's Health, Huffington Post, and more, sharing her story to promote sexual assault and eating disorder awareness.
World Mental Health Day 2018: Resource Round-Up
Eating Disorders and Complex Post Traumatic Stress Disorder
Sexual Assault, Anorexia Nervosa, and Recovery
You Are Not Alone: Self-Care Tips and Resources for Survivors of Sexual Assault
Contact the Helpline
You can call our confidential eating disorders Helpline Monday-Thursday from 11am to 9pm ET, and Friday from 11am to 5pm ET.
You can also chat with our Helpline! NEDA Helpline chat hours are Monday-Thursday from 9am to 9pm ET, and Friday from 9am to 5pm ET.
© Copyright 2022 National Eating Disorders Association Privacy Policy


Blackstone acquired Extended Stay in 2004, improved it, sold it at a big profit in 2007, and then helped reacquire with others in 2009 at a steep discount. Now Blackstone plans to pull in some cash for Extended Stay again; it's just the latest plot twist.
Extended Stay America, the mid-price lodging chain owned by Blackstone Group LP, Centerbridge Partners LP and Paulson & Co., made a regulatory filing for a U.S. initial public offering.
Extended Stay, based in Charlotte, North Carolina, hasn't decided how many shares will be sold or at what price, the company said in a statement today. The offering will consist of common stock of Extended Stay America and Class B common stock of its ESH Hospitality affiliate, which will be attached and trade together, according to the statement.
The Bloomberg REIT Hotel Index has gained 21 percent with dividends this year and is hovering around a five-year high set in May amid a recovery in the real estate market. Extended Stay is owned in equal thirds by its private-equity and hedge-fund shareholders.
The company filed a registration document with the Securities and Exchange Commission, according to the statement. Deutsche Bank Securities, Goldman Sachs & Co. and JPMorgan Chase & Co. were hired as joint book-running managers for the offering.


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MEC Seminar
Middle East Centre (231) Apply Middle East Centre filter
Latin American Centre (1) Apply Latin American Centre filter
(-) Remove MEC Seminar filter MEC Seminar
Last Chance The Middle East in the Balance
David Gardner, The Financial Times
3 November 2009 - 5:00pm
Middle East Centre, 68 Woodstock Road
Talks about the new book Last Chance The Middle East in the Balance (London: I.B. Tauris)
Is there an Iraqi refugee crisis?
Jarvis Doctorow, Junior Research Fellow in International Relations and Conflict Resolution in the Middle East, St Edmund Hall and the Department of Politics and International Relations, University of Oxford, Dr Shahira Samy
The Israeli Democracy: Human Rights and Minority Rights in Times of Peace and War
Justice Dalia Dorner, Justice (retired) of Israel's Supreme Court President of the Israeli Press Council
The Sultan's Armed Forces in Muscat & Oman, 1962-1964 Recollections by contemporaries of the time
David Gwynne-James, Allan Williams
An informal illustrated talk
On Mannequins and the Politics of Moral Imagination in Iran
16 June 2009 - 6:00pm
Viewing of Rough Cut A Documentary Film Written, Produced and Directed By Firouzeh Khosrovani Camera: Abbas Kowsari; Sound: Amir Hossein Ghasemi. Editors: Bijan Mirbagheri, Keyvan Jahanshahi; Music:... Read more
Oxford University Arab Cultural Society: Iraq's Democratic Moment: British Imperialism, Hashemite Kings and the National Democrats
Mr. Foulath Hadid (Honorary Fellow, St Antony's College, Oxford)
Youth political views in Lebanon amid a confessional political and educational system
Dr Maha Shuayb (Centre for Lebanese Studies Visiting Fellow)
When Law Prevents Justice: The Case of France and the Algerian War
Dr Stephanie Hare (Alistair Horne Fellow – St Antony's College)
British-French relations in the Middle East between the wars
James Barr St Antony's College
The Crisis of Islamic Civilization
Ali A. Allawi (St Antony's College)
8 May 2009 - 6:00pm
The New Israeli Government: Implications for U.S. Policy in the Middle East
Professor Shai Feldman (Director of the Crown Center for Middle East Studies at Brandeis University)
27 April 2009 - 2:00pm
Settler colonialism and public commemoration: Commemorating and negotiating conquest in colonial Algeria, 1840s - 1914
Jan Jansen (SOAS)
13 March 2009 - 1:00pm
'Under a Mushroom Cloud – Europe, Iran and the Bomb'
Dr Emanuele Ottolenghi (Director of the Translantic Institute in Brussels)
9 March 2009 - 12:45pm
A study of Iran's nuclear programme and what Europe can do
"Reflections on the American Intervention in Iraq"
Dr Ahmad Chalabi
Seminar: Foreign Aid to the Palestinians and Middle East Peacemaking
Dr Anne Le More (Associate Fellow, Middle East & North Africa Programme The Royal Institute of International Affairs Chatham House)


Perfect for birthdays for both adults and kids, this sweet illustrated card from The Grey Earl features the best of pals, Batboy and Robin.
A6 in size, and accompanied by a brown kraft envelope, this card is printed in the UK on recycled paper.
Perfect for birthdays for both adults and kids, this sweet illustrated card from The Grey Earl features the best of pals, Batboy and Robin. A6 in size, and accompanied by a brown kraft envelope, this card is printed in the UK on recycled paper.


People who drive manual transition cars use their clutch every time they drive. It is important that someone who races for a living considers a variety of clutches before they simply have one installed. Consider specialised components that have been manufactured specifically for race cars and super cars. In this article I will focus on the types of clutches suitable for race cars.
Combustion engines generally have low torque bands. Because of this the speed of the wheels need to be altered so that it is compatible with the speed. Changing transmissions helps to control the driving experience and the speed. If you want to change the flow of energy in a car, you would require a clutch to do so. That's why the clutch is so important. They are used to change the flow of speed and energy in a car without turning it off or causing it to lag.
Many clutches are available in sets called clutch kits. It contains all the components necessary for a properly functioning clutch. The material that the clutch is made of is quite important and must be taken into consideration. Some clutches are made of Kevlar. Kevlar is a material that was created to last for a long time and it has a smooth transition sequence. Although they may last for a long time, they often require a long break-in period up to a thousand miles. It's definitely a good choice if you're choosing to drive with an engine that may have been modified.
However, Kevlar isn't the only material to consider. A ceramic clutch will be very practical for those who plan on driving a race car. Your car is going to work hard and drive a lot. The transmissions are going to be continuously engaging and disengaging with the engines. This can cause a lot of heat. Fortunately, ceramic clutches can withstand a great amount of heat. Due to the high heat resistance that ceramic clutches offer, this is one of the best options out there.
All clutches, regardless of strength or what material they're made are eventually going to break down. At this stage clutch repairs are vital to anyone who wants to preserve their manual transmission race car. Race car clutches will need to be checked as often as possible to avoid delays and problems on the track. Every part has to be in optimum working condition if you want to win that next race.


Here are the poems about Gluttony on Commaful, including titles such as "Within the Kitchen's Stool."Click here to sign up and read more about Gluttony.
Gluttony doesn't have anything to say, but he has something to eat.


Having multiple streams of income means having more stable income. If any one of them changes, the others are still going smoothly. This is important, because this peace of mind allows you to calmly proceed towards making even more money … and makes you more likely to achieve it. ..


Home » Bedroom » Luxury Bed Sets » Luxury Bed Sets #2 Red Luxury Bedding Set Designer Bedspreads Cotton Silk Sheets Quilt Duvet Cover Bed In A Bag Linen Full Queen King Double Size Comforter Sets Bed Sets Duvet .
Luxury Bed Sets #2 Red Luxury Bedding Set Designer Bedspreads Cotton Silk Sheets Quilt Duvet Cover Bed In A Bag Linen Full Queen King Double Size Comforter Sets Bed Sets Duvet .
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The Puritan Dilemma
In The Puritan Dilemma we discover Edmund S. Morgan's views of what Puritanism is and how John Winthrop dealt with the dilemma of being a puritan. After receiving his Ph.D. from Harvard in 1942, Edmond S. Morgan taught at the University of Chicago (1945–46) and at Brown (1946–55) before becoming professor of history at Yale (1955). An expert on American colonial history, Morgan writes in a way that appeals to the general reading public while maintaining high scholarly standards. His many books include The Puritan Family, The Stamp Act Crisis, with his wife Helen, The Puritan Dilemma and biographies of Ezra Stiles and Roger Williams. Morgan's work, The Puritan Dilemma, fits into his body of works based on the common thread of history that many of his works shared.
Morgan traces how John Winthrop struggled with the dilemma,first internally, as he dealt with the question of whether traveling to the New World represented a selfish form of "separatism", the desire to separate himself from an impure England, or whether, as he eventually determined, it offered a unique opportunity to set an example for all men by establishing a purer Christian community in the Massachusetts Bay Colony. It seems to have been important to Winthrop and his fellow Puritans that they had the approval of the King and that though they were distancing themselves from the Church of England, they were not actually in turn renouncing it.
Three major themes of The Puritan Dilemma are a series of challenges that stem from the Puritan dilemma itself, which Winthrop describes as, "the paradox that required a man to live in the world without being of it." The overall theme of the book was how to deal with keeping one's own beliefs pure when faced with trials and tribulations.These themes include the question of how the colony was to be governed, the separatism that was occurring within the church, and the beli
The Massachusetts Puritans and their Covenant Government
The Puritan Reformation: Why Cromwell Fails


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Maybe It's a Trend
Last month we were happy to note the launch of PolitiFact.com, a joint project of the St. Petersburg Times of Florida and Congressional Quarterly of Washington, D.C. Today we welcome The Washington Post's new feature, "The Fact Checker," written by veteran journalist Michael Dobbs with the assistance of chief researcher Alice Crites.
The first four Fact Checker articles find fault with statements by Republican presidential candidates Fred Thompson and Sam Brownback,
Operation Iraqi Gloss-Over
President Bush played loose with the facts in his address to the nation Thursday night as he tried to convince the American public that the surge in U.S. troops in Iraq has made the country more stable.
He said "36 nations … have troops on the ground in Iraq." In fact, his own State Department puts the number at 25.
He said "ordinary life" was returning to Baghdad. Perhaps. In fact, news reports describe the city as starkly segregated with Shiites and Sunnis living in separate neighborhoods,
Richardson Flunks Two Subjects
Democratic presidential candidate Bill Richardson, governor of New Mexico, has claimed again and again U.S. students, from kindergarten through 12th grade, are ranked 29th in the world in math and science. He claims they used to be No. 1, too. But none of that is true.
The two leading international assessments of student achievement rank U.S. students better in all cases, and in most cases much better, than Richardson claims. Furthermore, neither of them even tries to cover all grades K through 12.
Twisting Facts in Spanglish
The Sunday night debate, complete with interpreters, produced a few flubs or fibs from the Democratic field, including these:
Rep. Dennis Kucinich gave a figure for health insurance company profits that was vastly overstated. He also made a much-disputed claim about NAFTA.
Former Sen. John Edwards made his health care plan seem cheaper than it would actually be. He assumed it was in effect right now, rather than the soonest it could possibly be implemented,
Some Old, Some New
The Republican candidates aired their views, claims and criticisms in yet another debate. We found a few mistakes and questionable pronouncements:
Rudy Giuliani said 2,000 illegal immigrants was the most the federal government deported from New York City during any of his years as mayor. That doesn't square with Department of Homeland Security figures. Giuliani also took a little too much credit for a drop in New York's welfare rolls.
Sen. Sam Brownback of Kansas tried to link gay marriage with an increase in children being born out of wedlock.
Overspiced Louisiana Gumbo
The Louisiana Democratic Party is serving up a hard-to-stomach mix of exaggeration, mischaracterization and falsehood against Republican candidate Bobby Jindal, who's running for governor in a contest that could be decided in October.
We found these items floating in the stew:
One ad falsely claims Jindal "supported raising the Medicare eligibility age." The proposal actually came from former Democratic Sen. John Breaux, not Jindal.
The same ad claims Jindal, a member of the House of Representatives,
We have company!
We're often asked if there are other sites like ours, trying in a nonpartisan way to help voters sort out fact from fiction. Now, there is.
The St. Petersburg Times of Florida and Congressional Quarterly of Washington, D.C. announced a new Web site called PolitiFact.com. The official launch date is Tuesday, Sept. 4th, but the site has been available to the public for several days.
The new site does something we don't. It offers a "truth-o-meter"
Clinton Wrong on Cancer Stat
Sen. Hillary Clinton used the wrong statistic in talking about cervical cancer today. She said that 500,000 women die from the disease worldwide each year. Actually, 250,000 do.
The Lance Armstrong Foundation hosted a presidential forum on cancer issues for the Democratic candidates Aug. 27 in Cedar Rapids, Iowa. Four of the candidates participated – Sen. Hillary Clinton, former Sen. John Edwards, New Mexico Gov. Bill Richardson and Rep.
Liberal Lobby Lacks Context
A liberal coalition calling itself Americans Against Escalation in Iraq is running a TV ad that says the U.S. will be in Iraq for a decade to come and that the military draft will be reinstated. But the ad supports those conclusions by twisting the words of two senior generals.
Richardson's Job Boast
Democratic presidential contender Bill Richardson boasts of creating 80,000 jobs since becoming governor of New Mexico. Not yet, he hasn't. The state has gained fewer than 76,000 payroll jobs since he took office, and official figures showed a mere 68,100 gain when he first started making his inflated boast last year. He bases his claim on a definition of "jobs" that includes unpaid workers in family businesses and freelancers who don't draw a paycheck.
Tweets from @factcheckdotorg/recommended-tweets


A wine that, due to the vinification technique, can be considered unique; produced from Groppello, Marzemino, Sangiovese and Barbera grapes. The colour is shiny pink, the taste is fresh and remarkably savoury with an aftertaste of almond sometimes, with particularly subtle fragrance of flowers.
Harvested by hand into boxes, maceration on the skins at a controlled temperature for a few hours (12-24 hours depending on the year), alcoholic fermentation via selected yeasts.
Alcoholic content 12,50% by volume; Total acidity 6,3 g/l; Residual sugars 5,0 g/l.
Brilliant pink colour, graceful and subtle on the nose with smell of rose and peach, fresh and distinctively delicious flavour with an almond aftertaste.
Pleasant summer aperitif, excellent with fish especially from the lake, fried bleaks, grilled sardines and spaghetti with white fish, and combined to white meats.


If you own a JPC, or one of any number of venerable PC designs, you may already be using QASM Vertical Connectors from Down Range Gear.
If you're not using them already, why would you need them?
Well, you may want to mount a chest rig on your PC. It's becoming more and more common: have a couple of 'placards' ready built, and if you use something like a Velocity Systems SCARAB Light, you're golden.
Even Crye put anchor points on its revamp of the JPC – the JPC 2.0 – so that a chest rig could be easily integrated.
And that's just one use. These connectors can be used for all sorts of kit fiddling. Reptile House contributor John, just rigged up a Mayflower Gen IV with a hydro pouch on the back, using QASMs.
Each pair of QASM connectors comes merchandised in a paper envelope.
Down Range Gear uses great quality ITW hard wear, attached to a webbing ribbon.
The webbing ribbon folds over and locks into the business end of the clip. It's basically a way of hanging a female Fastex clip off PALS webbing, or equivalent.
I've inserted QASMs into the bib's PALS webbing at the appropriate height to mount a chest rig.
I've then locked the webbing ribbon into the opposite end of the QASM.
Next, the chest rig's male Fastex clips are docked with the QASMs.


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Behavioral Boarding Schools in North Dakota
What are Behavioral Boarding Schools in North Dakota?
Behavioral boarding schools, also known as therapeutic boarding schools, are specialized facilities that provide both therapeutic intervention and a fully accredited academics program to troubled teens whose problematic behavior and academic standing is in need of major restoration. But while there are currently no behavioral boarding schools in North Dakota, parents from North Dakota have plenty of out-of-state treatment options, Like that of Elevations RTC, to consider.
For immediate assistance, Please call us at 1-855-290-9681.
Behavioral boarding schools for troubled teens are an academic institution that also provides intensive integrated therapies, typically offering treatment to teens ages 12-17 (Of course, this includes troubled teens from North Dakota ). These specialized boarding schools effectively treat troubled adolescents from North Dakota who require more intensive therapeutic treatment than that of traditional one-on-one therapy sessions.
Moreover, these therapeutic boarding schools provide treatment for adolescents who - due to behavioral and emotional immaturity - are not able to proactively function in a more traditional boarding school setting.
Elevations RTC: One of The Nation's Premier Behavioral Boarding Schools
As one of the nation's top-tier behavioral boarding schools, Elevations RTC knows a thing or two when it comes to addressing the complex psychological issues in troubled teens. It is our expertise in providing troubled teens with excellent, life-restoring care that makes our facility popular among parents from North Dakota.
Although Elevations may be located outside of North Dakota, Elevations accepts enrollments from struggling teenage boys and girls from all over the US. Also, it is beneficial to have troubled teen boys and girls receive assistance away from the harmful influence of their unsupportive peer group. We know from experience that relocating your teenager to an out-of-state, distraction-free setting has historically caused the greatest success.
We know teens—and more importantly, we know how to help them fight the battles that are disrupting their lives. Call (855) 290-9681
Our students are made up of highly gifted, albeit, misguided troubled teens who come from every part of the country (and beyond). While our rural and mountainous location in Utah may sound far from North Dakota, almost all of our students come from out of state, including teens from North Dakota.
At Elevations Behavioral Boarding School, we provide treatment for the following mental, emotional, and behavioral disorders in teens from North Dakota :
Bipolar disorder (bipolar I and II)
Attention Deficit Disorder (ADD)
Attention Deficit Hyperactivity Disorder (ADHD)
Generalized Anxiety Disorder (GAD)
Reactive Attachment Disorder (RAD)
Maladaptive Behavioral Disorder (MBD)
Self-harm (including hair-pulling, cutting, scratching, etc.)
Low self-image
Eating disorders (Bulimia, Anorexia, Binging, Etc.)
Our Behavioral Boarding Schools' Comprehensive Therapeutic Approach
At Elevations, we are committed to providing clinical excellence to troubled teens from North Dakota, (and beyond). Our comprehensive approach to providing leading anxiety, behavioral defiance, and depression treatment works like this:
8 hours of therapist-led interactions
13 hours of staff and peer-driven groups
Full-time psychiatrist
Outdoor and off-campus activities led by recreation therapists
Our holistic, community-based approach helps to recognize and better understand how the pieces in their lives (e.g. academics, home, social, free time) are connected to each other.
At Elevations RTC, we embrace a comprehensive, fully personalized and multifaceted approach to providing treatment to troubled teens who are in need of emotional, social, and behavioral restoration.
We also understand that not every student learns at the same pace. Instead of keeping our students in therapy sessions throughout the day, we provide students with a more personalized approach - one which philosophically grounded in holistic support and a peer-driven culture - that is specifically designed to treat their personally complex mental and emotional issues.
Elevations RTC's Coed Peer Culture Model
While most programs in North Dakota adhere to an authoritative culture model (wherein the authority figure is in complete charge of providing therapeutic feedback) we at Elevations choose to emphasize a strong peer-driven culture instead. We find that peer-given feedback and support is most effective in motivating disconnected teens who suffer from a low self-esteem and who would otherwise feel as though they have nothing to personally contribute.
Our co-educational peer setting gives our students the opportunity to normalize the experience of male and female interactions while noticing the differences between the two. Elevations is co-educational, which is a fairly unique aspect and contributes to Elevations as one of the leading depression treatments centers. As your child moves through the program they are provided with increased situations to enjoy co-educational recreational and social activities. Our students can get the clinical models of top therapeutic boarding schools in a residential treatment center environment.
If you are a parent from North Dakota in search of a top-tier behavioral boarding school, don't hesitate to call our child placement specialist at 1-855-290-9681.
Residential Treatment Centers for North Dakota Teenagers
We appreciate the common issues that troubled teens are being faced with every day. Here at Elevations RTC, we will help your child to deal with their emotional and learning-related problems in a healthful and productive way. Our accredited academics program will ensure that your teen can graduate on time. We help struggling teens and families from North Dakota. Call (855) 290-9681 to get more information about our fees and enrollment. We are a leading treatment program that assists the struggling teen to regain self-worth and confidence in the face of their future. We want to help your family!
"No matter what you're going through, there's a light at the end of the tunnel and it may seem hard to get to it but you can do it and just keep working towards it and you'll find the positive side of things." Demi Lovato
"If you have a positive attitude and constantly strive to give your best effort, eventually you will overcome your immediate problems and find you are ready for greater challenges." Pat Riley
Pick Your City in ND
Bismarck (ND)
Fargo (ND)
Minot (ND)
From the moment your child arrives at Elevations, it will feel like home.
Get The Help They Need
Call Elevations RTC Today!
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The to&from collection takes inspiration from Indian homeware, including the thali, a round serving platter, and the chakla, a flat kitchen board made of wood or marble.
Nine different stones from the Northern part of India were used, including green, white, Makrana and black marble, slate, gray and rainbow sandstone, Jaiselmer stone and black limestone. As a result no two pieces are the same, as each carries its own individual veining and colour formations.
The pieces, whose rounded edges appeal to the sense of touch, were designed to be versatile, beautiful and functional. They can be used as tableware, sharing platters or presentation dishes; in a bathroom or spa; or for decorating a mantle or coffee table. The solid forms and weight add gravitas and substance.
to&from worked with skilled artisans from the outskirts of Jaipur, Rajasthan and each piece is handmade.
Chakla is a fusion of two cultures. It is inspired by chakla & belan, the objects used to make flat bread in India, ours is an inverted version. The handle comes from a European wooden cheese board. Our Chakla is made from black slate. the top is slightly convex, revealing the layers of natural formation of the material.
Slate is a natural material which means that no two objects will be the same, every piece that you buy will be individual to you.
Hand wash only. Slate may stain with coloured foods.


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What Do I Do When Apple Removes an App I Bought from the App Store?
Adam Dachis
Dear Lifehacker,
I bought an app in the iTunes App Store and the next day Apple pulled it. Now I can't get updates and I'm worried my copy of the app is going to disappear. If it does, Apple doesn't even offer refunds. What can I do?
App Victim
Dear App Victim,
Apple's app approval process is far from perfect, as they often let in apps that their policies seem to prohibit and remove apps that are hardly in violation of anything with often no warning at all. But you know this, and you know it sucks, because when Apple screws up their approval process their users get screwed. Here's what you can do about it.
If You Want to Keep the App...
Back it up! Although Apple does have the power to remotely disable apps on your iDevice, it's not a power they've been known to exercise. If you have a copy of an app they've killed, you should be able to continue to use it. The problem arises, however, when you delete that app. Once it's gone, it's gone—they're not giving you another copy to download. You have to be responsible for backing up that app.
Apple Can Remotely Disable Apps Installed on Your iPhone
By now, we're well aware that Apple can make apps vanish without a trace (or explanation) from the…
IMPORTANT: We're assuming a copy of this app exists on your computer. If you purchased the app on your iDevice, make sure you sync with your computer and transfer your purchases so you have an actual app file available to you.
You probably understand how backing up works, as you're just making a duplicate of a file in this case, but this is a circumstance where incremental backups are very important. If you don't backup regularly and on a schedule, you may lose your app and find yourself unable to go back and get it. Fortunately, incremental backups are very easy to set up. In Mac OS X, you have Time Machine built into the operating system and can just turn it on. So long as you have a big external hard drive that it can use to store these backups, and Time Machine isn't instructed to ignore your iTunes folder (you have to do this manually so don't worry about it if you're not sure), you'll be in good shape. Windows users can use Windows Backup and Restore Center to set up a similar incremental backup situation. Alternatively, either platform can use Time Drive or backup iTunes with Dropbox and subscribe to Dropbox's pack rat feature ($39/year) to keep unlimited copies file versions and deleted files.
First Look at Windows 7's Backup and Restore Center
It may have been a while since you considered using Windows' built-in tools for backing up your…
If you'd prefer to manually backup the app, or need to find it when it's time to restore, you're going to need to know where iTunes keeps all the apps you download. This is pretty easy.
Windows 7: C: -> Users -> Username -> My Music -> iTunes -> iTunes Media -> Mobile Applications
Mac OS X: Macintosh HD -> Users -> yourusername -> Music -> iTunes -> Mobile Applications
Just locate that folder and you'll be able to find a copy of the app. If you're looking to back it up manually, just copy to another drive or burn it to a disc. If you're restoring this app from your backup you'll want to drag it onto iTunes instead so iTunes is aware it exists. Just dropping into the folder where iTunes stores apps won't actually tell iTunes it's there.
That's it! Now your app is about as secure as it's going to be. Some apps make it back into the iTunes App Store later on, once they've resolved whatever was troubling Apple, so if you hold tight you may end up with a sanctioned copy after all.
If You Want a Refund...
Apple doesn't give refunds for App Store purchases, which is frustrating when you buy an app and don't like it after using it for a few minutes. It's even more frustrating when you buy an app and Apple tells you that you can't have it, and you can't have your money either. While there's no miracle cure for this problem, you can actually get a refund if you employ some good old-fashioned arguing and persistance.
I've purchased a few apps there were removed from the iTunes App Store at some point in their lifespans and I somehow managed to lose one of them. Since I couldn't retrieve another copy of the app I contacted iTunes support and asked for a copy of the app. I believe this is a good place to start because then they have to tell you they can't provide you with the thing you paid for. That's when you can ask for a refund, which they'll deny, you'll argue, and eventually get what you want. The refund will come in the form of iTunes store credit, but that's better than nothing. If you still have an iDevice, chances are you'll find a way to use the few dollars credited back to you.
When Apple removes an app, it's really not a good situation for anybody. It's generally PR trouble for them, wasted effort on the part of the developer, and—as we've just detailed—a crappy experience for the users. You're not going to be able to magically turn a removed app into a regular, Apple-sanctioned one, but with a little diligence you can at least keep the copy you purchased or obtain a refund.


New Year's Eve Inversion Celebration!
This will be our 8th year of celebrating New Year's Eve with an Inversion Yoga Practice. Inversions are "any asana that places the head below the heart". They revitalize, rejuvenate and refresh your entire system, even if your feet remain firmly connected to the floor. In addition, inverted positions increase your capacity for growth and transformation by allowing you to see the world from a different perspective.
This workshop will include: bringing awareness to the power of breath, maintaining the integrity of your neck, strengthening of the abdominal muscles, energizing and awakening the legs, honoring concerns and fears when upside down.


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Arts Culture
See Romeo & Juliet and More at Hudson Valley Shakespeare Festival
Sabrina Sucato April 26, 2022
The cast of HVSF's 2021 production of The Tempest. Photo by T. Charles Erickson, courtesy of Hudson Valley Shakespeare Festival
After saying goodbye to Boscobel, Hudson Valley Shakespeare Festival is ready for a season like no other at its new home in Garrison.
The Bard is back in the Hudson Valley. At least, his spirit is. Thanks to Hudson Valley Shakespeare Festival, anyone can experience the poetic works of one of English literature's greatest icons.
Views from Hudson Valley Shakespeare Festival's new home. Photo by Amy Brown, courtesy of Hudson Valley Shakespeare Festival
After hosting its final season at its longtime home at Boscobel House and Gardens in 2021, Hudson Valley Shakespeare Festival (HVSF) is ready to welcome visitors to its new, permanent home in Garrison in 2022. (P.S. It's just down the road from Boscobel!) For those already familiar with HVSF, the theater tent will be a welcome sight, since the fest will continue to use its preexisting one while it works on plans for a permanent, open-air venue.
As for the season, which runs from July 7 to September 18, it will be one in which theatergoers can revel in the works of the Bard – and other talented playwrights – like never before. In anticipation of the opening, here's what to know about the shows:
July 7 – September 18
Arguably the most famous of all of Shakespeare's works, Romeo & Juliet tells the story of two star-crossed lovers in a refreshing new way this summer. The age-blind production is directed by Gaye Taylor Upchurch, who taps the talents of HVSF mainstay actors Kurt Rhoads and Nance Williamson as the main characters in the iconic, tragic tale. Head to the tent to lose yourself in the story of deep, powerful love as it fights to overcome family tensions that threaten it all.
Mr. Burns, a Post-Electric Play
Shakespeare isn't the only attraction under the tent this summer. For fans of The Simpsons and post-apocalyptic fiction, Mr. Burns, a Post-Electric Play is a must. The one-of-a-kind plot follows a group of survivors who band together following an event that nearly destroys society. The drama, which spans across decades, offers a unique celebration of the theater and the strength and resilience of humanity. Written by Anne Washburn, with music by Michael Friedman, Mr. Burns is directed by HVSF's artistic director, Davis McCallum.
Where We Belong
Open for a limited run, Where We Belong is a special collaboration between HVSF and the Woolly Mammoth Theatre Company in association with Folger Shakespeare Library. The show, which is a solo piece by Mohegan theater-maker Madeline Sayet, follows Sayet during her journey to England to study Shakespeare. Throughout the spectacle, Sayet and audiences dive into a journey of self-discovery that transcends geographic borders and explores culture, history, and the Bard himself.
For the full schedule of performances and to purchase tickets, visit Hudson Valley Shakespeare Festival's website or call 845.265.9575.
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My Uber ride pulls up in a black 2016 Hyundai Genesis with "TOOTEE" vanity plates. The 84-year-old driver, Richard Patterson, is dressed in a black suit and tie.
"It's a profession," he said. "You're giving service, so let's be serviceable."
Patterson loves his work and has no plans for slowing down, even though he's been driving professionally for 68 years. He said it keeps him young, and it must be working. He certainly doesn't look his years.
"I'm having fun, why would I want to quit having fun?" he said. "I'm being productive, I feel like I'm worth something, a purpose of being here."
This is a retirement job for Patterson, but not with retirement hours. He says he's on the road between 10 and 12 hours a day, nearly every day that he's not traveling or working on his "honey do" list at home.
His Uber app shows that in the past year, he's given 3,026 five-star-rated trips, with an average 4.91-star rating and a 100 percent pickup rate. He scrolls through his digital achievement badges earned for excellent service, great conversation and having a "cool car."
But passengers are a different type of cargo. They can listen to your stories and tell their own. For Patterson, driving for Uber is like sightseeing with strangers, all day long.
"I could be sitting at home watching a TV screen and getting bored with the commercials coming, or I got this TV screen here," he said, gesturing to the windshield. "No commercials in it, and I get to see a different view all the time."
Patterson grew up in Oregon and Washington and spent much of his childhood on a dairy farm in Molalla, where chores began at 5 a.m. and ended at 8 p.m.
"That was seven days a week, no sickness, no holidays," he said. "The cows had to be milked, every night and morning, every day, so I grew up with those kind of hours."
Before long, Patterson was driving his father's milk trucks. He hasn't stopped since, driving log trucks and local routes before moving to long-distance work.
"You learn the gratification of being productive at a young age, so it wasn't because of the money, it was that gratification of something being done at the end of the day," he said. "You could look back at your life and say yeah, I did something today that was productive for society."
On a Thursday morning, he starts in Southeast Portland, then makes his way to Milwaukie, back to town, out to the Beaverton transit station and to the Nike campus. By the time he drops someone off, another passenger is waiting for him nearby. It's non-stop. People are headed to work or to the doctor. We meet a French family on vacation, a young man headed to class at PCC.
The "TOOTEE" of Patterson's license plate is his late wife, Lucille, whom he met as a teenager on the family farm.
"The farmhand's wife had a new baby and her sister, who happened to be the same age as me, came out to the farm to help with that new baby," Patterson said. "And pretty good lookin'. So I grabbed ahold of her and held on to her for 62 years."
They married at 18 and raised four children. When the kids were grown, Patterson bought his own semi-truck cab and they traveled together on long-haul drives.
Lucille died in 2012 after a battle with bone cancer. Afterward, Patterson let the kids take what they wanted from the house, sold everything else and moved into his truck cab. He drove long distance for Interstate Distributors until he was 82.
"What my original game plan was when I started downsizing, I was getting ready to get out of here," he said. "I couldn't see a purpose for me here."
Slowly, it becomes clear what he means by "here."
"My purpose was gone," he said. "My wife was my purpose in life, doing for her. When you take that away, it leaves you feeling pretty, well, it just takes that away from ya."
Time passed and things began to get brighter.
"But I got connected up with this gal and kinda got a purpose for being awhile yet, so here I am, still doing it," he said.
This gal is his girlfriend, Maggie Conley, whom at age 80 he describes as his "young little thing." Conley is twice widowed, and her first husband was Lucille's younger brother. She's known Patterson most of her adult life.
"Three years after my wife died, she lost her second husband," Patterson said. "And because we were email buddies, our emails took on a different tone, and we come to the conclusion that we'll just get old together."
So Patterson retired from long-distance trucking and moved in with Conley two years ago. At the time, Conley had a small farm that he helped tend. But when she sold it more than a year ago, he got bored.
Last fall, Patterson saw a TV commercial seeking Uber drivers and signed up. He sold Lucille's 2004 Chrysler and bought himself a new car, though he kept her vanity plate – she spelled her nickname "Tootie" but "TOOTEE" was as close as he could get – and the little glass heart that hung on her rearview mirror.
It now hangs from his mirror, a bit of Tootie still with him.
"Well, I really don't need nothing to remind me," he said. "She's with me all the time."
That new Hyundai now has 66,000 miles on it, pretty much entirely racked up through Uber. About every four months, he said, he earns enough driving to take Conley on a cruise. They've traveled to Panama, French Polynesia and Belize. He's booked a three-week tour of Costa Rica for November, a trip to Orlando in February.
Patterson says driving gives him a purpose, a reason for being here.
But really, it's what he's driving for, what he comes home to, that keeps him going.