Showing papers by "Yale University published in 2006"
TL;DR: The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC, believing this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
14,724 citations
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
Abstract: MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer
5,693 citations
TL;DR: The authors examine the effect of consumer reviews on relative sales of books at Amazon.com and Barnesandnoble.com, and find that reviews are overwhelmingly positive at both sites, but there are more reviews and longer reviews at Amazon and that an improvement in a book's reviews leads to an increase in relative sales.
Abstract: The authors examine the effect of consumer reviews on relative sales of books at Amazon.com and Barnesandnoble.com. The authors find that (1) reviews are overwhelmingly positive at both sites, but there are more reviews and longer reviews at Amazon.com; (2) an improvement in a book's reviews leads to an increase in relative sales at that site; (3) for most samples in the study, the impact of one-star reviews is greater than the impact of five-star reviews; and (4) evidence from review-length data suggests that customers read review text rather than relying only on summary statistics.
4,180 citations
TL;DR: Analysis of preclinical cellular and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies, are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation ofBDNF plays a role in the actions of antidepressant treatment.
2,999 citations
TL;DR: T tandem affinity purification was used to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae to identify protein–protein interactions, which will help future studies on individual proteins as well as functional genomics and systems biology.
Abstract: Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.
2,975 citations
University of Pittsburgh1, Cedars-Sinai Medical Center2, Johns Hopkins University School of Medicine3, Johns Hopkins University4, Broad Institute5, Université de Montréal6, University of Toronto7, Harvard University8, University of Chicago9, McGill University10, North Shore-LIJ Health System11, Yale University12
TL;DR: A highly significant association is found between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23, which prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
Abstract: The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
2,937 citations
TL;DR: Survivors of childhood cancer have a high rate of illness owing to chronic health conditions, including severe, disabling, or life-threatening conditions or death due to a chronic condition.
Abstract: Background Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. Methods The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. Results Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. Conclusions Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.
2,897 citations
TL;DR: Inositol phospholipids mediate acute responses, but also act as constitutive signals that help define organelle identity, and play a fundamental part in controlling membrane–cytosol interfaces.
Abstract: Inositol phospholipids have long been known to have an important regulatory role in cell physiology. The repertoire of cellular processes known to be directly or indirectly controlled by this class of lipids has now dramatically expanded. Through interactions mediated by their headgroups, which can be reversibly phosphorylated to generate seven species, phosphoinositides play a fundamental part in controlling membrane-cytosol interfaces. These lipids mediate acute responses, but also act as constitutive signals that help define organelle identity. Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the permeability and transport functions of membranes.
2,528 citations
TL;DR: The natural history of cirrhosis is outlined, the model for end stage liver disease (MELD) has replaced the Child–Pugh score in the United States for prioritizing liver donor allocation and a systematic review of the literature regarding predictors of mortality in cirrhotic patients is reported on.
2,427 citations
TL;DR: Short-term exposure to PM2.5 increases the risk for hospital admission for cardiovascular and respiratory diseases and was higher in counties located in the Eastern region of the United States, which included the Northeast, the Southeast, the Midwest, and the South.
Abstract: Context Evidence on the health risks associated with short-term exposure to fine particles (particulate matter 2.5 µm in aerodynamic diameter [PM2.5]) is limited. Results from the new national monitoring network for PM2.5 make possible systematic research on health risks at national and regional scales. Objectives To estimate risks of cardiovascular and respiratory hospital admissions associated with short-term exposure to PM2.5 for Medicare enrollees and to explore heterogeneity of the variation of risks across regions. Design, Setting, and Participants A national database comprising daily timeseries data daily for 1999 through 2002 on hospital admission rates (constructed from the Medicare National Claims History Files) for cardiovascular and respiratory outcomes and injuries, ambient PM2.5 levels, and temperature and dew-point temperature for 204 US urban counties (population 200000) with 11.5 million Medicare enrollees (aged 65 years) living an average of 5.9 miles from a PM2.5 monitor. Main Outcome Measures Daily counts of county-wide hospital admissions for primary diagnosis of cerebrovascular, peripheral, and ischemic heart diseases, heart rhythm, heart failure, chronic obstructive pulmonary disease, and respiratory infection, and injuries as a control outcome. Results There was a short-term increase in hospital admission rates associated with PM2.5 for all of the health outcomes except injuries. The largest association was for heart failure, which had a 1.28% (95% confidence interval, 0.78%-1.78%) increase in risk per 10-µg/m 3
2,357 citations
TL;DR: In this paper, the state-of-the-art of the physical principles and applications of forward osmosis as well as their strengths and limitations are presented, along with a review of the current state of the art.
Brookhaven National Laboratory1, University of Minnesota2, Boston University3, University of Illinois at Urbana–Champaign4, Yale University5, Budker Institute of Nuclear Physics6, Heidelberg University7, Tokyo Institute of Technology8, University of Groningen9, Tokyo University of Science10, Cornell University11, Fairfield University12
TL;DR: In this article, the authors presented the final report from a series of precision measurements of the muon anomalous magnetic moment, a(mu)=(g-2)/2.54 ppm, which represents a 14-fold improvement compared to previous measurements at CERN.
Abstract: We present the final report from a series of precision measurements of the muon anomalous magnetic moment, a(mu)=(g-2)/2. The details of the experimental method, apparatus, data taking, and analysis are summarized. Data obtained at Brookhaven National Laboratory, using nearly equal samples of positive and negative muons, were used to deduce a(mu)(Expt)=11659208.0(5.4)(3.3)x10(-10), where the statistical and systematic uncertainties are given, respectively. The combined uncertainty of 0.54 ppm represents a 14-fold improvement compared to previous measurements at CERN. The standard model value for a(mu) includes contributions from virtual QED, weak, and hadronic processes. While the QED processes account for most of the anomaly, the largest theoretical uncertainty, approximate to 0.55 ppm, is associated with first-order hadronic vacuum polarization. Present standard model evaluations, based on e(+)e(-) hadronic cross sections, lie 2.2-2.7 standard deviations below the experimental result.
TL;DR: This review highlights the findings that have advanced the understanding of TGF-beta in the immune system and in disease.
Abstract: Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-beta is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-beta inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease.
TL;DR: A model has been constructed that integrates all quantitative data and includes structural models of abundant proteins and, with the exception of the V-ATPase, contains numerous copies of proteins essential for membrane traffic and neurotransmitter uptake.
Food and Drug Administration1, GE Healthcare2, Thermo Fisher Scientific3, Illumina4, Agilent Technologies5, National Institutes of Health6, Applied Biosystems7, University of Toledo8, Stratagene9, United States Environmental Protection Agency10, University of Massachusetts Boston11, Clinical Data, Inc12, University of California, Los Angeles13, SAS Institute14, Biogen Idec15, Yale University16, Cold Spring Harbor Laboratory17, Discovery Institute18, Stanford University19, Harvard University20, Vanderbilt University21, University of Texas at Dallas22, University of Oslo23, Novartis24, University of Texas MD Anderson Cancer Center25, Luminex Corporation26, Wake Forest University27, University of Illinois at Urbana–Champaign28
TL;DR: This study describes the experimental design and probe mapping efforts behind the MicroArray Quality Control project and shows intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed.
Abstract: Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.
TL;DR: It is shown that viral-mediated, mesolimbic dopamine pathway–specific knockdown of brain-derived neurotrophic factor is required for the development of experience-dependent social aversion in mice experiencing repeated aggression.
Abstract: Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
TL;DR: Using TRPA1-deficient mice, it is shown that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain.
TL;DR: MDR tuberculosis is more prevalent than previously realised in a rural area in KwaZulu Natal, South Africa and has been transmitted to HIV co-infected patients and is associated with high mortality.
Medical University of South Carolina1, Yale University2, Boston University3, University of Wisconsin–Milwaukee4, University of North Carolina at Chapel Hill5, University of Washington6, Harvard University7, University of Texas at San Antonio8, Brown University9, University of Miami10, National Institutes of Health11, University of New Mexico12, University of Pennsylvania13
TL;DR: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI.
Abstract: ContextAlcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.ObjectivesTo evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.Design, Setting, and ParticipantsRandomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.InterventionsEight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.Main Outcome MeasuresPercent days abstinent from alcohol and time to first heavy drinking day.ResultsAll groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.ConclusionsPatients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.Trial Registrationclinicaltrials.gov Identifier: NCT00006206
TL;DR: The primary aim of this review is to summarize the latest developments in the understanding of the different Ubl-protein modification systems, including the shared and unique features of these related pathways.
Abstract: Following the discovery of protein modification by the small, highly conserved ubiquitin polypeptide, a number of distinct ubiquitin-like proteins (Ubls) have been found to function as protein modifiers as well These Ubls, which include SUMO, ISG15, Nedd8, and Atg8, function as critical regulators of many cellular processes, including transcription, DNA repair, signal transduction, autophagy, and cell-cycle control A growing body of data also implicates the dysregulation of Ubl-substrate modification and mutations in the Ublconjugation machinery in the etiology and progression of a number of human diseases The primary aim of this review is to summarize the latest developments in our understanding of the different Ubl-protein modification systems, including the shared and unique features of these related pathways
Journal Article•
TL;DR: The GLOBOCAN 2002 database was first made available in September 2005 and presented estimates for 2002, based on the most recent incidence, mortality, and survival data available at IARC, but more recent figures may be available directly from local sources.
Abstract: Cancer is a major burden of disease worldwide. Each year, tens of millions of people are diagnosed with cancer around the world, and more than half of the patients eventually die from it. In many countries, cancer ranks the second most common cause of death following cardiovascular diseases. With significant improvement in treatment and prevention of cardiovascular diseases, cancer has or will soon become the number one killer in many parts of the world. As elderly people are most susceptible to cancer and population aging continues in many countries, cancer will remain a major health problem around the globe.
In this review, we summarized published data to describe the severity of the burden. We also analyzed the GLOBOCAN 2002 database to evaluate the morbidity and mortality of cancer in various geographic regions around the world. The GLOBOCAN 2002 database was put together using the huge amount of data available in the Descriptive Epidemiology Group of the International Agency of Research on Cancer (IARC), a World Health Organization agency in Lyon, France [1]. Incidence data are available from cancer registries. They cover either entire national populations or samples of such populations from selected regions. Cancer registries also provide statistics on cancer survival. Mortality data by cause are available for many countries through the registration of vital events.
Cancer data are always collected and compiled sometime after the events to which they relate, so the most recent statistics available are always “late.” GLOBOCAN 2002 was first made available in September 2005 and presented estimates for 2002. These estimates are based on the most recent incidence, mortality, and survival data available at IARC, but more recent figures may be available directly from local sources. The Age-Standardized Rate (ASR, world standard) is calculated using the five age groups of 0 to 14, 15 to 44, 45 to 54, 55 to 64, and ≥ 65 years. The weights of the world standard population for the five age groups were 0.31, 0.43, 0.11, 0.08, and 0.07, respectively.
TL;DR: Recent reports describe the removal of aggregates from the cytosol; reveal mechanisms for protein quality control in the endoplasmic reticulum; and provide new insight into two classes of molecular chaperones, the Hsp70 system and the AAA+ (Hsp100) unfoldases.
TL;DR: In this article, the authors introduce the construct of "leader inclusiveness", words and deeds exhibited by leaders that invite and appreciate others' contributions, and suggest that leader inclusivity helps cross-disciplinary teams overcome the inhibiting effects of status differences, allowing members to collaborate in process improvement.
Abstract: This chapter introduces the construct of “leader inclusiveness” – words and deeds exhibited by leaders that invite and appreciate others’ contributions. We propose that leader inclusiveness helps cross-disciplinary teams overcome the inhibiting effects of status differences, allowing members to collaborate in process improvement. The existence of a professional hierarchy in medicine and the differential status accorded to those in different disciplines are well established in the health care literature, as is the need for quality improvement. We build on this foundation to suggest that profession-derived status is positively associated with psychological safety (H1) – a key antecedent of speaking up and learning behaviour – in health care teams. We hypothesise that this effect varies across teams (H2), and furthermore, that leader inclusiveness predicts psychological safety (H3) and moderates the relationship between status and psychological safety (H4). Finally, we suggest psychological safety predicts “engagement in quality improvement work” (H5) and mediates the relationship between leader inclusiveness and engagement (H6). Survey data collected in 23 neonatal intensive care units involved in quality improvement projects support our hypotheses. These results provide insight into antecedents of and strategies for fostering improvement efforts in health care and other sectors in which cross-disciplinary teams engage in collaborative learning to improve products or services.
TL;DR: The study of explanation, while related to intuitive theories, concepts, and mental models, offers important new perspectives on high-level thought and particularly adept at using situational support to build explanations on the fly in real time.
Abstract: The study of explanation, while related to intuitive theories, concepts, and mental models, offers important new perspectives on high-level thought. Explanations sort themselves into several distinct types corresponding to patterns of causation, content domains, and explanatory stances, all of which have cognitive consequences. Although explanations are necessarily incomplete—often dramatically so in laypeople—those gaps are difficult to discern. Despite such gaps and the failure to recognize them fully, people do have skeletal explanatory senses, often implicit, of the causal structure of the world. They further leverage those skeletal understandings by knowing how to access additional explanatory knowledge in other minds and by being particularly adept at using situational support to build explanations on the fly in real time. Across development and cultures, there are differences in preferred explanatory schemes, but rarely are any kinds of schemes completely unavailable to a group.
TL;DR: Life on earth is almost entirely solar-powered, with carbohydrate acting as a source of high-energy electrons and dioxygen providing a lower-energy destination for these electrons.
Abstract: Life on earth is almost entirely solar-powered. We can get some idea of the enormous quantity of energy received from the sun by noting that during daylight hours, the sun provides several thousand times more power to the surface of the U.S.A. than is produced by all of the nation’s electrical power stations. 1,2 Around 50% of the radiation that reaches the earth’s surface, roughly the visible region, is of a frequency useful to photosynthetic organisms. Oxygenic photosynthetic organisms convert this radiation into chemical energy, in the form of carbohydrate and dioxygen, at an optimal efficiency of something like 25%. 3 These products together sustain the rest of aerobic life, with carbohydrate acting as a source of high-energy electrons and dioxygen providing a lower-energy destination for these electrons. The overall equation of oxygenic photosynthesis is given in eq 1, where (CH2O) represents carbohydrate:
TL;DR: In this article, the physics of the 21 cm transition were reviewed, focusing on processes relevant at high redshifts, and the insights to be gained from such observations were described.
TL;DR: It is clear that the authors do not know enough about bat biology; they are doing too little in terms of bat conservation; and there remain a multitude of questions regarding the role of bats in disease emergence.
Abstract: Bats (order Chiroptera, suborders Megachiroptera and Microchiroptera) are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviors, ability to echolocate, virus susceptibility) make them exquisitely suitable hosts of viruses and other disease agents. Bats of certain species are well recognized as being capable of transmitting rabies virus, but recent observations of outbreaks and epidemics of newly recognized human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. This paper summarizes information regarding chiropteran characteristics and information regarding 66 viruses that have been isolated from bats. From these summaries, it is clear that we do not know enough about bat biology, that we are doing too little in terms of bat conservation, and that there remain a multitude of questions regarding the role of bats in disease emergence.
TL;DR: For example, this paper showed that the vast majority of attempts to hit the ball would result in "making an out" and thus pose a potential threat to the player's sense of personal worth and social regard.
Abstract: In major league baseball, a hitter could have a long and productive career by maintaining a .300 average, that is, by getting a base hit 30% of the time. A great deal of money could be earned and fame accrued. Yet the other 70% of the time, this player would have failed. The vast majority of attempts to hit the ball would result in ‘‘making an out’’ and thus pose a potential threat to the player’s sense of personal worth and social regard. Like major league baseball players, people in contemporary society face innumerable failures and self‐threats. These include substandard performance on the job or in class, frustrated goals or aspirations, information challenging the validity of long‐held beliefs, illness, the defeat of one’s political party in an election or of one’s favorite sports team in a playoV, scientific evidence suggesting that one is engaging in risky health behavior, negative feedback at work or in school, rejection in a romantic relationship, real and perceived social slights, interpersonal and intergroup conflict, the misbehavior of one’s child, the loss of a loved one, and so on. In the course of a given day, the potential number of events that could threaten people’s ‘‘moral and adaptive adequacy’’—their sense of themselves as good, virtuous, successful, and able to control important life outcomes (Steele, 1988)—seems limitless and likely to exceed the small number of events that aYrm it. A major undertaking for most people is to sustain self‐integrity when faced with the inevitable setbacks and disappointments of daily life—the 70% of the time 183
Book•
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TL;DR: Covering details of NEURON's inner workings, and practical considerations specifying anatomical and biophysical properties to be represented in models, this book uses a problem-solving approach that includes many examples to challenge readers.
Abstract: Assuming no previous knowledge of computer programming or numerical methods, The NEURON Book provides practical advice on how to get the most out of the NEURON software program. Although written primarily for neuroscientists, teachers and students, readers with a background in the physical sciences or mathematics and some knowledge about brain cells and circuits, will also find it helpful. Covering details of NEURON's inner workings, and practical considerations specifying anatomical and biophysical properties to be represented in models, this book uses a problem-solving approach that includes many examples to challenge readers.
TL;DR: The development of new classes of blood glucose–lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the treatment options for type 2 diabetes.
Abstract: The epidemic of type 2 diabetes in the latter part of the 20th and in the early 21st century, and the recognition that achieving specific glycemic goals can substantially reduce morbidity, have made the effective treatment of hyperglycemia a top priority (1–3). While the management of hyperglycemia, the hallmark metabolic abnormality associated with type 2 diabetes, has historically had center stage in the treatment of diabetes, therapies directed at other coincident features, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy. Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial impact on diabetes-specific complications, including retinopathy, nephropathy, and neuropathy in the setting of type 1 diabetes (4,5); in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce complications (6–8). Intensive glycemic management resulting in lower HbA1c (A1C) levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes (9,10); however, the role of intensive diabetes therapy on CVD in type 2 diabetes remains under active investigation (11,12). Some therapies directed at lowering glucose levels have additional benefits with regard to CVD risk factors, while others lower glucose without additional benefits.
The development of new classes of blood glucose–lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the treatment options for type 2 diabetes. Whether used alone or in combination with other blood glucose–lowering interventions, the availability of the newer agents has provided an increased number of choices for practitioners and patients and heightened uncertainty regarding the most appropriate means of treating this widespread disease. Although numerous reviews on the …