Showing papers by "Boston University published in 2009"
TL;DR: In this paper, the basic theoretical aspects of graphene, a one-atom-thick allotrope of carbon, with unusual two-dimensional Dirac-like electronic excitations, are discussed.
Abstract: This article reviews the basic theoretical aspects of graphene, a one-atom-thick allotrope of carbon, with unusual two-dimensional Dirac-like electronic excitations. The Dirac electrons can be controlled by application of external electric and magnetic fields, or by altering sample geometry and/or topology. The Dirac electrons behave in unusual ways in tunneling, confinement, and the integer quantum Hall effect. The electronic properties of graphene stacks are discussed and vary with stacking order and number of layers. Edge (surface) states in graphene depend on the edge termination (zigzag or armchair) and affect the physical properties of nanoribbons. Different types of disorder modify the Dirac equation leading to unusual spectroscopic and transport properties. The effects of electron-electron and electron-phonon interactions in single layer and multilayer graphene are also presented.
20,824 citations
University of Colorado Boulder1, Harvard University2, Mayo Clinic3, Boston University4, University of Pennsylvania5, University of Pittsburgh6, University of Siena7, University Health Network8, Institut Gustave Roussy9, Oregon Health & Science University10, University of Texas MD Anderson Cancer Center11, Duke University12, University of Cincinnati13, Memorial Sloan Kettering Cancer Center14, MedStar Washington Hospital Center15
TL;DR: Evidence-based recommendations are developed to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer and represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...
10,501 citations
Johns Hopkins University1, University of Michigan2, University of Colorado Denver3, Ohio State University4, Boston University5, University of Pennsylvania6, University of Florida7, Mayo Clinic8, University of Siena9, Institut Gustave Roussy10, University of Cincinnati11, Memorial Sloan Kettering Cancer Center12
TL;DR: Evidence-based recommendations in response to the appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...
7,525 citations
TL;DR: In this article, a field is emerging that leverages the capacity to collect and analyze data at a scale that may reveal patterns of individual and group behaviors at a large scale, such as behavior patterns.
Abstract: A field is emerging that leverages the capacity to collect and analyze data at a scale that may reveal patterns of individual and group behaviors.
2,619 citations
Boston University1, Saint Louis University2, Northwestern University3, University of Texas MD Anderson Cancer Center4, University of North Carolina at Chapel Hill5, Mashantucket Pequot Tribal Nation6, Columbia University7, University of California, San Francisco8, National Institutes of Health9, Yale Cancer Center10, University of Texas Health Science Center at Houston11
TL;DR: The diverse types of feasibility studies conducted in the field of cancer prevention, using a group of recently funded grants from the National Cancer Institute are described.
2,189 citations
TL;DR: This work reviews 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professionalathletes, 1 football player and 2 boxers.
Abstract: Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
2,049 citations
TL;DR: A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA(2)R, indicating that PLA( 2)R is a major antigen in this disease.
Abstract: BACKGROUND Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. METHODS We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. RESULTS Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in nonreduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A 2 receptor (PLA 2 R). Reactive serum specimens recognized recombinant PLA 2 R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA 2 R antibody. Anti-PLA 2 R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA 2 R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA 2 R. CONCLUSIONS A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA 2 R. PLA 2 R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA 2 R is a major antigen in this disease.
1,643 citations
Harvard University1, Brigham and Women's Hospital2, University of California, San Francisco3, Yale University4, St Christopher's Hospice5, Cedars-Sinai Medical Center6, University of California, Los Angeles7, University of Western Sydney8, University of Missouri–St. Louis9, Stony Brook University10, University of Memphis11, Columbia University12, Memorial Sloan Kettering Cancer Center13, Utrecht University14, University of Zurich15, Veterans Health Administration16, Boston University17
TL;DR: The psychometric validity of criteria for prolonged grief disorder (PGD) is tested to enhance the detection and care of bereaved individuals at heightened risk of persistent distress and dysfunction.
Abstract: Background: Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction. Methods and Findings: A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12– 24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment. Conclusions: The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for the Editors’ Summary.
1,437 citations
TL;DR: In this article, a randomized controlled trial was conducted to evaluate the clinical effect of implementing RED among patients admitted to a general medical service and found that a nurse discharge advocate and clinical pharmacist working together to coordinate hospital discharge, educate patients, and reconcile medications led to fewer follow-up emergency visits and rehospitalizations than usual care alone.
Abstract: One in 5 hospitalizations is complicated by postdischarge adverse events (1, 2), some of which may lead to preventable emergency department visits or readmissions. Despite this finding, hospital discharge procedures have not been standardized (3). In addition, the declining presence of primary care providers (PCPs) in hospitals has not been adequately accompanied by systems to ensure that patient data are transferred to subsequent caregivers (4, 5). For example, discharge summaries frequently lack critical data and are not sent to the PCP in a timely fashion (6, 7), resulting in outpatient clinicians being unaware of test results that were pending at discharge (8) and evaluations that were scheduled to be done after discharge not being completed (9). Similarly, patients are often left unprepared at discharge; many do not understand their discharge medications and cannot recall their chief diagnoses (10). With more than 32 million adult discharges in the United States each year (11), these deficiencies in the transition of care increase illness, unnecessary hospital utilization, and cost.
Some peridischarge interventions have shown a reduction in hospital readmission rates and cost (12-14), emergency department visits (15), and postdischarge adverse events (16), whereas some have shown little or no effect (17-20). Peridischarge interventions have also shown improved PCP follow-up and outpatient work-ups (21) and higher patient satisfaction (15). Most of these studies have focused on specific diagnoses (14, 22, 23) or highly selected populations, such as geriatric adults (12, 13, 19, 24). Some have focused on specific aspects of the discharge, such as increasing access to primary care follow-up (25), connecting with transitional nursing services (26), or improving patients′ ability to advocate for themselves after discharge (12). To date, no study has evaluated a standardized discharge intervention that includes patient education, comprehensive discharge planning, and postdischarge telephone reinforcement in a general medical population.
Context
Emergency department visits and rehospitalizations are common after hospital discharge.
Contribution
This trial demonstrated that a nurse discharge advocate and clinical pharmacist working together to coordinate hospital discharge, educate patients, and reconcile medications led to fewer follow-up emergency visits and rehospitalizations than usual care alone.
Caution
The trial was conducted at a single center, and not all eligible patients were enrolled.
Implication
A systematic approach to hospital discharges can reduce unnecessary health service use.
—The Editors
In 2004, we began an in-depth examination of hospital discharge, for which we designed a package of services to minimize discharge failures—a process called reengineered discharge (RED) (Table 1) (3, 27). We did a randomized, controlled trial to evaluate the clinical effect of implementing RED among patients admitted to a general medical service.
Table 1
Components of Reengineered Hospital Discharge
1,382 citations
Massachusetts Institute of Technology1, Boston University2, Harvard University3, University of Michigan4, Merck & Co.5, University of Oxford6, National Institutes of Health7, French Institute of Health and Medical Research8, University of Eastern Finland9, University of Southern California10, National Institute for Health and Welfare11, Imperial College London12, Lund University13, University of Helsinki14, Wellcome Trust Sanger Institute15, Tufts University16, University of North Carolina at Chapel Hill17
TL;DR: The results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
Abstract: Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
1,358 citations
National Institutes of Health1, University of Geneva2, Johns Hopkins University3, University of Washington4, Erasmus University Rotterdam5, University of Texas Health Science Center at Houston6, University of Iceland7, Boston University8, Cedars-Sinai Medical Center9, Harvard University10, Group Health Cooperative11
TL;DR: A genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium identifies 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10−7.
Abstract: Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
TL;DR: Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation, which increased with advancing age and were higher in women than in men.
Abstract: Results During the study period, 655,613 enrollees (68.8%) underwent at least one imaging procedure associated with radiation exposure. The mean (±SD) cumulative effective dose from imaging procedures was 2.4±6.0 mSv per enrollee per year; however, a wide distribution was noted, with a median effective dose of 0.1 mSv per enrollee per year (interquartile range, 0.0 to 1.7). Overall, moderate effective doses of radiation were incurred in 193.8 enrollees per 1000 per year, whereas high and very high doses were incurred in 18.6 and 1.9 enrollees per 1000 per year, respectively. In general, cumulative effective doses of radiation from imaging procedures increased with advancing age and were higher in women than in men. Computed tomographic and nuclear imaging accounted for 75.4% of the cumulative effective dose, with 81.8% of the total administered in outpatient settings. Conclusions Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation.
TL;DR: In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Abstract: Background: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: ,5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: $30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80– 1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleepdisordered breathing showed a pattern of association similar to all-cause mortality. Conclusions: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors’ Summary.
TL;DR: It is demonstrated that cortical volume measures combine at least 2 distinct sources of genetic influences, and using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
Abstract: Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
TL;DR: In this article, the effect of tensional strain in the electronic structure of graphene was analyzed and it was shown that strain-induced anisotropy and local deformations can be used as a means to affect transport characteristics and pinch off current flow in graphene devices.
Abstract: We analyze the effect of tensional strain in the electronic structure of graphene. In the absence of electron-electron interactions, within linear elasticity theory, and a tight-binding approach, we observe that strain can generate a bulk spectral gap. However, this gap is critical, requiring threshold deformations in excess of 20% and only along preferred directions with respect to the underlying lattice. The gapless Dirac spectrum is robust for small and moderate deformations and the gap appears as a consequence of the merging of the two inequivalent Dirac points only under considerable deformations of the lattice. We discuss how strain-induced anisotropy and local deformations can be used as a means to affect transport characteristics and pinch off current flow in graphene devices.
Harvard University1, Broad Institute2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, McMaster University4, McGill University5, University of Leicester6, University of Lübeck7, University of Pennsylvania8, Vanderbilt University9, University of Missouri–Kansas City10, University of Münster11, University of Verona12, Queen's University Belfast13, University of Washington14, Boston University15, University of Helsinki16, National Institute for Health and Welfare17, Lund University18, University of Cambridge19, Vita-Salute San Raffaele University20, University of Ferrara21, University of Turin22, Hebrew University of Jerusalem23, University of Girona24, University of Milan25, University of Leeds26, University of Regensburg27, Ludwig Maximilian University of Munich28, University of Kiel29, Wellcome Trust Sanger Institute30, University of Paris31, MedStar Washington Hospital Center32, deCODE genetics33, University of Iceland34
TL;DR: SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with my Cardiovascular Infarction risk.
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk
TL;DR: This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature and the regulation of PRP by antidoping agencies is discussed.
Abstract: Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.
TL;DR: In the case of a video game system, the intermediary is the console producer, while the two sets of agents are consumers and video game developers as mentioned in this paper, and neither consumers nor game developers will be interested in the PlayStation if the other party is not.
Abstract: At a local Best Buy, a child places a new Sony PlayStation 3 on the cashier’s counter while the parents dig out their Visa card. The gaming system and the payment card may appear to have little connection other than this purchase. However, these two items share an important characteristic that is generating a series of economic insights and has important implications for strategic decision making and economic policymaking. Both video game systems and payment cards are examples of two-sided markets. Broadly speaking, a two-sided market is one in which 1) two sets of agents interact through an intermediary or platform, and 2) the decisions of each set of agents affects the outcomes of the other set of agents, typically through an externality. In the case of a video game system, the intermediary is the console producer—Sony in the scenario above—while the two sets of agents are consumers and video game developers. Neither consumers nor game developers will be interested in the PlayStation if the other party is not. Similarly, a successful payment card requires both consumer usage and merchant acceptance, where both consumers and merchants value each others’ participation. Many more products fit into this paradigm, such as search engines, newspapers, and almost any advertisersupported media (examples in which consumers often negatively value, rather than positively value, the participation of the other side), as well as most software or title-based operating systems and consumer electronics. Malls which seek retailers and consumers, convention organizers which seek buyers and sellers, dating services which seek men and women, and The Journal of Economic Perspectives which seeks content and readership, all experience the economics of two-sided markets. The multi-sided nature of many Internet and high-technology markets, as well as
TL;DR: A growing body of data suggests that ED crowding is associated both with objective clinical endpoints, such as mortality, as well as clinically important processes of care,such as time to treatment for patients with time-sensitive conditions such as pneumonia.
Abstract: Background: An Institute of Medicine (IOM) report defines six domains of quality of care: safety, patient-centeredness, timeliness, efficiency, effectiveness, and equity. The effect of emergency department (ED) crowding on these domains of quality has not been comprehensively evaluated.
Objectives: The objective was to review the medical literature addressing the effects of ED crowding on clinically oriented outcomes (COOs).
Methods: We reviewed the English-language literature for the years 1989–2007 for case series, cohort studies, and clinical trials addressing crowding’s effects on COOs. Keywords searched included “ED crowding,”“ED overcrowding,”“mortality,”“time to treatment,”“patient satisfaction,”“quality of care,” and others.
Results: A total of 369 articles were identified, of which 41 were kept for inclusion. Study quality was modest; most articles reflected observational work performed at a single institution. There were no randomized controlled trials. ED crowding is associated with an increased risk of in-hospital mortality, longer times to treatment for patients with pneumonia or acute pain, and a higher probability of leaving the ED against medical advice or without being seen. Crowding is not associated with delays in reperfusion for patients with ST-elevation myocardial infarction. Insufficient data were available to draw conclusions on crowding’s effects on patient satisfaction and other quality endpoints.
Conclusions: A growing body of data suggests that ED crowding is associated both with objective clinical endpoints, such as mortality, as well as clinically important processes of care, such as time to treatment for patients with time-sensitive conditions such as pneumonia. At least two domains of quality of care, safety and timeliness, are compromised by ED crowding.
TL;DR: The results suggest that the strong effect of weight on bone mineral density is due to load on weight‐bearing bones in both sexes, and the sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.
Abstract: We evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight-bearing and non-weight-bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988–1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dual-photon absorptiometry (DPA) and radius bone mass assessed by single-photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9–19.8% of total variance, all p < 0.01) and for only weight-bearing sites (femur and spine) in men (2.8–6.9% of total variance, all p < 0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for < 1% of variance in men (p NS). Weight change since biennial examination 1 (1948–1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight-bearing bones in both sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in women after menopause.
University College Dublin1, Massachusetts Institute of Technology2, Broad Institute3, University of Aveiro4, University of Aberdeen5, Boston University6, University of Minnesota7, Duke University8, Imperial College London9, Stanford University10, University of Exeter11, Leibniz Association12, University of Amsterdam13, Wellcome Trust Sanger Institute14, University of Illinois at Urbana–Champaign15, Stony Brook University16, Newcastle University17, University of Iowa18, University of Sheffield19, University of Texas Health Science Center at Houston20
TL;DR: There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence in Candida albicans species.
Abstract: Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
TL;DR: It is shown that strain can be easily tailored to generate electron beam collimation, 1D channels, surface states, and confinement, which can be seen as basic elements for all-graphene electronics which, by suitable engineering of local strain profiles, could be integrated on a single graphene sheet.
Abstract: We explore the influence of local strain on the electronic structure of graphene We show that strain can be easily tailored to generate electron beam collimation, 1D channels, surface states, and confinement These can be seen as basic elements for all-graphene electronics which, by suitable engineering of local strain profiles, could be integrated on a single graphene sheet In addition this proposal has the advantage that patterning can be made on substrates rather than on graphene, thereby protecting the integrity of the latter
TL;DR: Evidence is provided that PRT is an effective intervention for improving physical functioning in older people, including improving strength and the performance of some simple and complex activities, and some caution is needed with transferring these exercises for use with clinical populations.
Abstract: Background
Muscle weakness in old age is associated with physical function decline. Progressive resistance strength training (PRT) exercises are designed to increase strength.
Objectives
To assess the effects of PRT on older people and identify adverse events.
Search methods
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 01, 2008), EMBASE (1980 to February 06 2007), CINAHL (1982 to July 01 2007) and two other electronic databases. We also searched reference lists of articles, reviewed conference abstracts and contacted authors.
Selection criteria
Randomised controlled trials reporting physical outcomes of PRT for older people were included.
Data collection and analysis
Two review authors independently selected trials, assessed trial quality and extracted data. Data were pooled where appropriate.
Main results
One hundred and twenty one trials with 6700 participants were included. In most trials, PRT was performed two to three times per week and at a high intensity. PRT resulted in a small but significant improvement in physical ability (33 trials, 2172 participants; SMD 0.14, 95% CI 0.05 to 0.22). Functional limitation measures also showed improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179 participants, MD 0.08 m/s, 95% CI 0.04 to 0.12); and a moderate to large effect for getting out of a chair (11 trials, 384 participants, SMD -0.94, 95% CI -1.49 to -0.38). PRT had a large positive effect on muscle strength (73 trials, 3059 participants, SMD 0.84, 95% CI 0.67 to 1.00). Participants with osteoarthritis reported a reduction in pain following PRT(6 trials, 503 participants, SMD -0.30, 95% CI -0.48 to -0.13). There was no evidence from 10 other trials (587 participants) that PRT had an effect on bodily pain. Adverse events were poorly recorded but adverse events related to musculoskeletal complaints, such as joint pain and muscle soreness, were reported in many of the studies that prospectively defined and monitored these events. Serious adverse events were rare, and no serious events were reported to be directly related to the exercise programme.
Authors' conclusions
This review provides evidence that PRT is an effective intervention for improving physical functioning in older people, including improving strength and the performance of some simple and complex activities. However, some caution is needed with transferring these exercises for use with clinical populations because adverse events are not adequately reported.
TL;DR: In this article, a single layer of electrically controlled metamaterial was used to achieve active control of the phase of terahertz waves and demonstrated high-speed broadband modulation.
Abstract: Using a single layer of electrically controlled metamaterial, researchers have achieved active control of the phase of terahertz waves and demonstrated high-speed broadband modulation.
TL;DR: From clinical factors readily accessible in primary care, the risk score could help to identify risk of atrial fibrillation for individuals in the community, assess technologies or markers for improvement of risk prediction, and target high-risk individuals for preventive measures.
University of Oxford1, University of Paris2, University of Barcelona3, Southend University Hospital NHS Foundation Trust4, University of Zurich5, University of Groningen6, Boston University7, Norfolk and Norwich University Hospital8, Lund University9, Food and Drug Administration10, Istanbul University11
TL;DR: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
TL;DR: The results indicate that high-throughput yeast two-hybrid interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome.
Abstract: Several attempts have been made to systematically map protein-protein interaction, or 'interactome', networks. However, it remains difficult to assess the quality and coverage of existing data sets. Here we describe a framework that uses an empirically-based approach to rigorously dissect quality parameters of currently available human interactome maps. Our results indicate that high-throughput yeast two-hybrid (HT-Y2H) interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome. We estimate that the human interactome contains approximately 130,000 binary interactions, most of which remain to be mapped. Similar to estimates of DNA sequence data quality and genome size early in the Human Genome Project, estimates of protein interaction data quality and interactome size are crucial to establish the magnitude of the task of comprehensive human interactome mapping and to elucidate a path toward this goal.
International Agency for Research on Cancer1, Catholic University of the Sacred Heart2, Fred Hutchinson Cancer Research Center3, Universidade Federal do Rio Grande do Sul4, University of São Paulo5, National Institutes of Health6, Brown University7, Harvard University8, Oswaldo Cruz Foundation9, University of Milan10, Pennsylvania State University11, University of Lausanne12, University of Buenos Aires13, Universidade Federal de Pelotas14, Boston University15, University of North Carolina at Chapel Hill16, University of Iowa17, University of Texas MD Anderson Cancer Center18, Nofer Institute of Occupational Medicine19, Russian Academy20, Medical University of Warsaw21, University of California, Los Angeles22
TL;DR: It is confirmed that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk, however, a substantial proportion of head and head cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head andneck cancer among women and among young-onset cases.
Abstract: Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter ( ψ ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk ( ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)
TL;DR: Evidence is provided that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities, and six combinations whose selective synergy depends on multitarget drug activity are highlighted.
Abstract: Drug combinations are a promising strategy to overcome the compensatory mechanisms and unwanted off-target effects that limit the utility of many potential drugs. However, enthusiasm for this approach is tempered by concerns that the therapeutic synergy of a combination will be accompanied by synergistic side effects. Using large scale simulations of bacterial metabolism and 94,110 multi-dose experiments relevant to diverse diseases, we provide evidence that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities. We highlight six combinations whose selective synergy depends on multitarget drug activity. For one anti-inflammatory example, we show how such selectivity is achieved through differential expression of the drugs' targets in cell types associated with therapeutic, but not toxic, effects and validate its therapeutic relevance in a rat model of asthma. The context specificity of synergistic combinations creates many opportunities for therapeutically relevant selectivity and enables improved control of complex biological systems.
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TL;DR: In this paper, the authors propose a conceptual model that explains how CSR provides individual stakeholders with numerous benefits (functional, psychosocial, and values) and how the type and extent to which a stakeholder derives these benefits from CSR initiatives influences the quality of the relationship between the stakeholder and the company.
Abstract: Corporate social responsibility (CSR) continues to gain attention atop the corporate agenda and is by now an important component of the dialogue between companies and their stakeholders. Nevertheless, there is still little guidance as to how companies can implement CSR activity in order to maximize returns to CSR investment. Theorists have identified many company-favoring outcomes of CSR; yet there is a dearth of research on the psychological mechanisms that drive stakeholder responses to CSR activity. Borrowing from the literatures on means-end chains and relationship marketing, we propose a conceptual model that explains how CSR provides individual stakeholders with numerous benefits (functional, psychosocial, and values) and how the type and extent to which a stakeholder derives these benefits from CSR initiatives influences the quality of the relationship between the stakeholder and the company. The paper discusses the implications of these insights and highlights a number of areas for future research.