Showing papers by "Yale University published in 2010"
TL;DR: Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood and, as compared with patients receiving standard care, patients received less aggressive care at the end of life but longer survival.
Abstract: Background Patients with metastatic non–small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease. Methods We randomly assigned patients with newly diagnosed metastatic non–small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records. Results Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P = 0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P = 0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P = 0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P = 0.02). Conclusions Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival. (Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)
5,450 citations
TL;DR: A large effect size is found for rumination, medium to large for avoidance, problem solving, and suppression, and small to medium for reappraisal and acceptance in the relationship between each regulatory strategy and each of the four psychopathology groups.
4,471 citations
Ames Research Center1, University of California, Berkeley2, San Jose State University3, Las Cumbres Observatory Global Telescope Network4, Search for extraterrestrial intelligence5, York University6, Aarhus University7, University of Texas at Austin8, Lowell Observatory9, Harvard University10, California Institute of Technology11, Space Telescope Science Institute12, Lawrence Hall of Science13, Goddard Space Flight Center14, United States Department of the Navy15, Carnegie Institution for Science16, University of Washington17, University of Hawaii at Hilo18, University of California, Santa Cruz19, Massachusetts Institute of Technology20, Fermilab21, San Diego State University22, Southern Connecticut State University23, Planetary Science Institute24, Yale University25, Marshall Space Flight Center26, The Catholic University of America27, University of Idaho28, Villanova University29
TL;DR: The Kepler mission was designed to determine the frequency of Earth-sized planets in and near the habitable zone of Sun-like stars, which is the region where planetary temperatures are suitable for water to exist on a planet's surface.
Abstract: The Kepler mission was designed to determine the frequency of Earth-sized planets in and near the habitable zone of Sun-like stars. The habitable zone is the region where planetary temperatures are suitable for water to exist on a planet’s surface. During the first 6 weeks of observations, Kepler monitored 156,000 stars, and five new exoplanets with sizes between 0.37 and 1.6 Jupiter radii and orbital periods from 3.2 to 4.9 days were discovered. The density of the Neptune-sized Kepler-4b is similar to that of Neptune and GJ 436b, even though the irradiation level is 800,000 times higher. Kepler-7b is one of the lowest-density planets (~0.17 gram per cubic centimeter) yet detected. Kepler-5b, -6b, and -8b confirm the existence of planets with densities lower than those predicted for gas giant planets.
3,663 citations
TL;DR: The concepts of design and the scientific philosophy of Green Chemistry are covered with a set of illustrative examples and the challenge of using the Principles as a cohesive design system is discussed.
Abstract: Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).
2,942 citations
Rutgers University1, New York University2, University of Oxford3, Harvard University4, Bangor University5, University of Copenhagen6, National Institutes of Health7, Oregon Health & Science University8, Yale University9, Nathan Kline Institute for Psychiatric Research10, Medical College of Wisconsin11, University of Oulu12, Radboud University Nijmegen13, National Yang-Ming University14, Cleveland Clinic15, Duke University16, Max Planck Society17, Emory University18, University of Queensland19, University of Michigan20, Kennedy Krieger Institute21, Washington University in St. Louis22, Technische Universität München23, Leiden University24, University of Texas at Dallas25, Charité26, University of Pittsburgh27, Southeast University28, Otto-von-Guericke University Magdeburg29, Massachusetts Institute of Technology30, University of Western Ontario31, Medical University of Vienna32, Beijing Normal University33
TL;DR: The 1000 Functional Connectomes Project (Fcon_1000) as discussed by the authors is a large-scale collection of functional connectome data from 1,414 volunteers collected independently at 35 international centers.
Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
2,787 citations
University of Kiel1, Cedars-Sinai Medical Center2, Wellcome Trust Sanger Institute3, University of Pennsylvania4, QIMR Berghofer Medical Research Institute5, Peninsula College of Medicine and Dentistry6, University of Edinburgh7, University of Cambridge8, University of Otago9, University of Washington10, University of Groningen11, University of Liège12, Harvard University13, Casa Sollievo della Sofferenza14, King's College London15, University of Chicago16, Yale University17, Johns Hopkins University18, Ludwig Maximilian University of Munich19, Charité20, McGill University21, Lille University of Science and Technology22, Cincinnati Children's Hospital Medical Center23, Ghent University24, Torbay Hospital25, Mater Health Services26, Université libre de Bruxelles27, RWTH Aachen University28, University of Utah29, Örebro University30, Leiden University31, University of Paris32, Technion – Israel Institute of Technology33, University of Western Australia34, Tel Aviv University35, University of Dundee36, University of Manchester37, University of Pittsburgh38, Royal Hospital for Sick Children39, Katholieke Universiteit Leuven40, Guy's and St Thomas' NHS Foundation Trust41, University of Bern42, University of Toronto43, University of Amsterdam44, Karolinska Institutet45, University of Zurich46, Université de Montréal47, Emory University48, Newcastle University49
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
2,482 citations
TL;DR: The results demonstrate that the effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamines.
Abstract: The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.
2,345 citations
Emory University1, University of Iowa2, Wayne State University3, Brown University4, Case Western Reserve University5, University of Cincinnati6, University of Alabama at Birmingham7, University of Texas Health Science Center at Houston8, Indiana University9, University of California, San Diego10, Yale University11, University of Miami12, University of Texas Southwestern Medical Center13, Wake Forest University14, Duke University15, Stanford University16, University of Utah17, University of Rochester18, Tufts University19, University of New Mexico20, National Institutes of Health21
TL;DR: Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.
Abstract: OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified. CONCLUSION: Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.
2,277 citations
TL;DR: Questions are discussed including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune Recognition in host defense from infection and injury.
Abstract: Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.
1,998 citations
TL;DR: In this article, the role of social learning in the diffusion of a new agri cultural technology in Ghana is investigated, using unique data on farmers' communication patterns to define each individual's information neighborhood, finding evidence that farmers adjust their inputs to align with those of their information neighbors who were surpris ingly successful in previous periods.
Abstract: This paper investigates the role of social learning in the diffusion of a new agri cultural technology in Ghana. We use unique data on farmers' communication patterns to define each individual's information neighborhood. Conditional on many potentially confounding variables, we find evidence that farmers adjust their inputs to align with those of their information neighbors who were surpris ingly successful in previous periods. The relationship of these input adjustments to experience further indicates the presence of social learning. In addition, applying the same method to input choices for another crop, of known technol ogy, correctly indicates an absence of social learning effects. (JEL D83, 013, 033, Q16)
1,954 citations
TL;DR: The genome-wide characteristics of rare (<1% frequency) copy number variation in ASD are analysed using dense genotyping arrays to reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
TL;DR: The presence and spread of antibiotic resistance in non-agricultural, non-clinical environments is explored and the need for more intensive investigation on this subject is demonstrated.
Abstract: Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject
Pierre-and-Marie-Curie University1, Yale University2, University of British Columbia3, Bristol-Myers Squibb4, University of California, Los Angeles5, University of Virginia6, French Institute of Health and Medical Research7, University College London8, University of California, San Diego9, McGill University10, Goethe University Frankfurt11, University of Kentucky12, Tohoku University13, Newcastle University14, University of Lille Nord de France15, University of Nice Sophia Antipolis16, Brown University17, NewYork–Presbyterian Hospital18, VU University Amsterdam19, Maastricht University Medical Centre20
TL;DR: This paper aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities.
Abstract: Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.
TL;DR: A plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention, and implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
Abstract: Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
TL;DR: The structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity, and a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily are described, demonstrating that BRAF-mutant melanomas are highly dependent on B- RAF kinases activity.
Abstract: B-RAF is the most frequently mutated protein kinase in human cancers.1 The finding that oncogenic mutations in BRAF are common in melanoma2 followed by the demonstration that these tumors are dependent on the RAF/MEK/ERK pathway3 offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity. Preclinical experiments demonstrated that PLX4032 selectively blocked the RAF/MEK/ERK pathway in BRAF mutant cells and caused regression of BRAF mutant xenografts.4 Toxicology studies confirmed a wide safety margin consistent with the high degree of selectivity, enabling Phase 1 clinical trials using a crystalline formulation of PLX4032.5 In a subset of melanoma patients, pathway inhibition was monitored in paired biopsy specimens collected before treatment initiation and following two weeks of treatment. This analysis revealed substantial inhibition of ERK phosphorylation, yet clinical evaluation did not show tumor regressions. At higher drug exposures afforded by a new amorphous drug formulation,4,5 greater than 80% inhibition of ERK phosphorylation in the tumors of patients correlated with clinical response. Indeed, the Phase 1 clinical data revealed a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily.5 These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity.
TL;DR: In this paper, a pedagogical introduction to the physics of quantum noise and its connections to quantum measurement and quantum amplification is given, and the basics of weak continuous measurements are described.
Abstract: The topic of quantum noise has become extremely timely due to the rise of quantum information physics and the resulting interchange of ideas between the condensed matter and atomic, molecular, optical--quantum optics communities. This review gives a pedagogical introduction to the physics of quantum noise and its connections to quantum measurement and quantum amplification. After introducing quantum noise spectra and methods for their detection, the basics of weak continuous measurements are described. Particular attention is given to the treatment of the standard quantum limit on linear amplifiers and position detectors within a general linear-response framework. This approach is shown how it relates to the standard Haus-Caves quantum limit for a bosonic amplifier known in quantum optics and its application to the case of electrical circuits is illustrated, including mesoscopic detectors and resonant cavity detectors.
TL;DR: It is proposed that weight stigma is not a beneficial public health tool for reducing obesity, but rather, stigmatization of obese individuals threatens health, generates health disparities, and interferes with effective obesity intervention efforts.
Abstract: Stigma and discrimination toward obese persons are pervasive and pose numerous consequences for their psychological and physical health. Despite decades of science documenting weight stigma, its public health implications are widely ignored. Instead, obese persons are blamed for their weight, with common perceptions that weight stigmatization is justifiable and may motivate individuals to adopt healthier behaviors. We examine evidence to address these assumptions and discuss their public health implications. On the basis of current findings, we propose that weight stigma is not a beneficial public health tool for reducing obesity. Rather, stigmatization of obese individuals threatens health, generates health disparities, and interferes with effective obesity intervention efforts. These findings highlight weight stigma as both a social justice issue and a priority for public health.
TL;DR: The meaning of work literature is the product of a long tradition of rich inquiry spanning many disciplines as discussed by the authors, and the field lacks overarching structures that would facilitate greater integration, consistency, and understanding of this body of research.
TL;DR: Inflammation is an essential immune response that enables survival during infection or injury and maintains tissue homeostasis under a variety of noxious conditions but comes at the cost of a transient decline in tissue function, which can in turn contribute to the pathogenesis of diseases of alteredHomeostasis.
Brown University1, University of Florida2, University of Washington3, University of Maryland, Baltimore4, Yale University5, Veterans Health Administration6, University of New Mexico7, Massachusetts Institute of Technology8, Cornell University9, Duke University10, United States Environmental Protection Agency11
TL;DR: In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy.
Abstract: Background Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. Methods In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. Results At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], −0.23 to 4.58) and worse than ...
University of Pennsylvania1, Medical University of Vienna2, St Mary's Hospital3, Creighton University4, Georgetown University5, Harvard University6, University of California, Irvine7, Yale University8, Guy's and St Thomas' NHS Foundation Trust9, Netherlands Cancer Institute10, City of Hope National Medical Center11, Mayo Clinic12, University of Chicago13, NorthShore University HealthSystem14, University of California, Los Angeles15, Fox Chase Cancer Center16, University of Texas Health Science Center at San Antonio17, Duke University18, Baylor University Medical Center19
TL;DR: Among a cohort of women with BRCa1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer, first diagnosis of breastcancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer- specific mortality.
Abstract: Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.
TL;DR: The root-mean-square charge radius, rp, has been determined with an accuracy of 2 per cent by electron–proton scattering experiments, and the present most accurate value of rp (with an uncertainty of 1 per cent) is given by the CODATA compilation of physical constants.
Abstract: Considering that the proton is a basic subatomic component of all ordinary matter — as well as being ubiquitous in its solo role as the hydrogen ion H+ — there are some surprising gaps in our knowledge of its structure and behaviour. A collaborative project to determine the root-mean-square charge radius of the proton to better than the 1% accuracy of the current 'best' value suggests that those knowledge gaps may be greater than was thought. The new determination comes from a technically challenging spectroscopic experiment — the measurement of the Lamb shift (the energy difference between a specific pair of energy states) in 'muonic hydrogen', an exotic atom in which the electron is replaced by its heavier twin, the muon. The result is unexpected: a charge radius about 4% smaller than the previous value. The discrepancy remains unexplained. Possible implications are that the value of the most accurately determined fundamental constant, the Rydberg constant, will need to be revised — or that the validity of quantum electrodynamics theory is called into question. Here, a technically challenging spectroscopic experiment is described: the measurement of the muonic Lamb shift. The results lead to a new determination of the charge radius of the proton. The new value is 5.0 standard deviations smaller than the previous world average, a large discrepancy that remains unexplained. Possible implications of the new finding are that the value of the Rydberg constant will need to be revised, or that the validity of quantum electrodynamics theory is called into question. The proton is the primary building block of the visible Universe, but many of its properties—such as its charge radius and its anomalous magnetic moment—are not well understood. The root-mean-square charge radius, rp, has been determined with an accuracy of 2 per cent (at best) by electron–proton scattering experiments1,2. The present most accurate value of rp (with an uncertainty of 1 per cent) is given by the CODATA compilation of physical constants3. This value is based mainly on precision spectroscopy of atomic hydrogen4,5,6,7 and calculations of bound-state quantum electrodynamics (QED; refs 8, 9). The accuracy of rp as deduced from electron–proton scattering limits the testing of bound-state QED in atomic hydrogen as well as the determination of the Rydberg constant (currently the most accurately measured fundamental physical constant3). An attractive means to improve the accuracy in the measurement of rp is provided by muonic hydrogen (a proton orbited by a negative muon); its much smaller Bohr radius compared to ordinary atomic hydrogen causes enhancement of effects related to the finite size of the proton. In particular, the Lamb shift10 (the energy difference between the 2S1/2 and 2P1/2 states) is affected by as much as 2 per cent. Here we use pulsed laser spectroscopy to measure a muonic Lamb shift of 49,881.88(76) GHz. On the basis of present calculations11,12,13,14,15 of fine and hyperfine splittings and QED terms, we find rp = 0.84184(67) fm, which differs by 5.0 standard deviations from the CODATA value3 of 0.8768(69) fm. Our result implies that either the Rydberg constant has to be shifted by −110 kHz/c (4.9 standard deviations), or the calculations of the QED effects in atomic hydrogen or muonic hydrogen atoms are insufficient.
TL;DR: Evidence on behavior change and clinical outcomes was compiled from randomized or quasi-experimental controlled trials of text message interventions published in peer-reviewed journals by June 2009.
Abstract: Mobile phone text messaging is a potentially powerful tool for behavior change because it is widely available, inexpensive, and instant. This systematic review provides an overview of behavior change interventions for disease management and prevention delivered through text messaging. Evidence on behavior change and clinical outcomes was compiled from randomized or quasi-experimental controlled trials of text message interventions published in peer-reviewed journals by June 2009. Only those interventions using text message as the primary mode of communication were included. Study quality was assessed by using a standardized measure. Seventeen articles representing 12 studies (5 disease prevention and 7 disease management) were included. Intervention length ranged from 3 months to 12 months, none had long-term follow-up, and message frequency varied. Of 9 sufficiently powered studies, 8 found evidence to support text messaging as a tool for behavior change. Effects exist across age, minority status, and nationality. Nine countries are represented in this review, but it is problematic that only one is a developing country, given potential benefits of such a widely accessible, relatively inexpensive tool for health behavior change. Methodological issues and gaps in the literature are highlighted, and recommendations for future studies are provided.
TL;DR: In this article, the authors explore the mechanisms using a microbial-enzyme model to simulate the responses of soil carbon to warming by 5'∘C. They find that declines in microbial biomass and degradative enzymes can explain the observed attenuation of soil-carbon emissions in response to warming.
Abstract: The loss of carbon dioxide from soils increases initially under climate warming, but tends to decline to control levels within a few years. Simulations of the soil-carbon response to warming with a microbial-enzyme model show that a decline in both microbial biomass and the production of degrading enzymes can explain this attenuation response. Most ecosystem models predict that climate warming will stimulate microbial decomposition of soil carbon, producing a positive feedback to rising global temperatures1,2. Although field experiments document an initial increase in the loss of CO2 from soils in response to warming, in line with these predictions, the carbon dioxide loss from soils tends to decline to control levels within a few years3,4,5. This attenuation response could result from changes in microbial physiological properties with increasing temperature, such as a decline in the fraction of assimilated carbon that is allocated to growth, termed carbon-use efficiency6. Here we explore these mechanisms using a microbial-enzyme model to simulate the responses of soil carbon to warming by 5 ∘C. We find that declines in microbial biomass and degradative enzymes can explain the observed attenuation of soil-carbon emissions in response to warming. Specifically, reduced carbon-use efficiency limits the biomass of microbial decomposers and mitigates the loss of soil carbon. However, microbial adaptation or a change in microbial communities could lead to an upward adjustment of the efficiency of carbon use, counteracting the decline in microbial biomass and accelerating soil-carbon loss. We conclude that the soil-carbon response to climate warming depends on the efficiency of soil microbes in using carbon.
TL;DR: Among patients recently hospitalized for heart failure, telemonitoring did not improve outcomes, and the results indicate the importance of a thorough, independent evaluation of disease-management strategies before their adoption.
Abstract: Methods We randomly assigned 1653 patients who had recently been hospitalized for heart failure to undergo either telemonitoring (826 patients) or usual care (827 patients). Telemonitoring was accomplished by means of a telephone-based interactive voiceresponse system that collected daily information about symptoms and weight that was reviewed by the patients’ clinicians. The primary end point was readmission for any reason or death from any cause within 180 days after enrollment. Secondary end points included hospitalization for heart failure, number of days in the hospital, and number of hospitalizations. Results The median age of the patients was 61 years; 42.0% were female, and 39.0% were black. The telemonitoring group and the usual-care group did not differ significantly with respect to the primary end point, which occurred in 52.3% and 51.5% of patients, respectively (difference, 0.8 percentage points; 95% confidence interval [CI], −4.0 to 5.6; P = 0.75 by the chi-square test). Readmission for any reason occurred in 49.3% of patients in the telemonitoring group and 47.4% of patients in the usualcare group (difference, 1.9 percentage points; 95% CI, −3.0 to 6.7; P = 0.45 by the chi-square test). Death occurred in 11.1% of the telemonitoring group and 11.4% of the usual care group (difference, −0.2 percentage points; 95% CI, −3.3 to 2.8; P = 0.88 by the chi-square test). There were no significant differences between the two groups with respect to the secondary end points or the time to the primary end point or its components. No adverse events were reported. Conclusions Among patients recently hospitalized for heart failure, telemonitoring did not improve outcomes. The results indicate the importance of a thorough, independent evaluation of disease-management strategies before their adoption. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00303212.)
TL;DR: Treating lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix suggests that repopulation of lung matrix is a viable strategy for lung regeneration.
Abstract: Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 minutes) the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
TL;DR: Two major patterns emerged: coastal species showed maximum diversity in the Western Pacific, whereas oceanic groups consistently peaked across broad mid-latitudinal bands in all oceans, and changes in ocean temperature, in conjunction with other human impacts, may ultimately rearrange the global distribution of life in the ocean.
Abstract: Using large-scale data sets, these authors present a new assessment of global marine species diversity and its correlation with environmental and spatial parameters.
TL;DR: Current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies are described.
Abstract: Type 1 diabetes is an autoimmune disorder afflicting millions of people worldwide. Once diagnosed, patients require lifelong insulin treatment and can experience numerous disease-associated complications. The last decade has seen tremendous advances in elucidating the causes and treatment of the disease based on extensive research both in rodent models of spontaneous diabetes and in humans. Integrating these advances has led to the recognition that the balance between regulatory and effector T cells determines disease risk, timing of disease activation, and disease tempo. Here we describe current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies.
American Foundation for Suicide Prevention1, San Francisco State University2, University of California, Los Angeles3, Pennsylvania State University4, University of Colorado Denver5, Columbia University6, University of Illinois at Chicago7, City University of New York8, University of Arizona9, University of California, San Francisco10, Drexel University11, University of Minnesota12, Fenway Health13, Yale University14, University of Pennsylvania15, Ben-Gurion University of the Negev16, University of Pittsburgh17, Howard Brown Health Center18, Kaiser Permanente19
TL;DR: This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes.
Abstract: Despite strong indications of elevated risk of suicidal behavior in lesbian, gay, bisexual, and transgender people, limited attention has been given to research, interventions or suicide prevention programs targeting these populations. This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes. This article summarizes existing research findings, and makes recommendations for addressing knowledge gaps and applying current knowledge to relevant areas of suicide prevention practice.