Showing papers by "University of Miami published in 2016"

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine

Abstract: Importance Since publication of the report by the Panel on Cost-Effectiveness in Health and Medicine in 1996, researchers have advanced the methods of cost-effectiveness analysis, and policy makers have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years. Objective To review the state of the field and provide recommendations to improve the quality of cost-effectiveness analyses. The intended audiences include researchers, government policy makers, public health officials, health care administrators, payers, businesses, clinicians, patients, and consumers. Design In 2012, the Second Panel on Cost-Effectiveness in Health and Medicine was formed and included 2 co-chairs, 13 members, and 3 additional members of a leadership group. These members were selected on the basis of their experience in the field to provide broad expertise in the design, conduct, and use of cost-effectiveness analyses. Over the next 3.5 years, the panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process. Findings The concept of a “reference case” and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability are recommended. All cost-effectiveness analyses should report 2 reference case analyses: one based on a health care sector perspective and another based on a societal perspective. The use of an “impact inventory,” which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the 2 reference case analyses is also recommended. This special communication reviews these recommendations and others concerning the estimation of the consequences of interventions, the valuation of health outcomes, and the reporting of cost-effectiveness analyses. Conclusions and Relevance The Second Panel reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations. Major changes include the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences.

Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Global Carbon Budget 2016

Abstract: . Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates and consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models. We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2006–2015), EFF was 9.3 ± 0.5 GtC yr−1, ELUC 1.0 ± 0.5 GtC yr−1, GATM 4.5 ± 0.1 GtC yr−1, SOCEAN 2.6 ± 0.5 GtC yr−1, and SLAND 3.1 ± 0.9 GtC yr−1. For year 2015 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr−1, showing a slowdown in growth of these emissions compared to the average growth of 1.8 % yr−1 that took place during 2006–2015. Also, for 2015, ELUC was 1.3 ± 0.5 GtC yr−1, GATM was 6.3 ± 0.2 GtC yr−1, SOCEAN was 3.0 ± 0.5 GtC yr−1, and SLAND was 1.9 ± 0.9 GtC yr−1. GATM was higher in 2015 compared to the past decade (2006–2015), reflecting a smaller SLAND for that year. The global atmospheric CO2 concentration reached 399.4 ± 0.1 ppm averaged over 2015. For 2016, preliminary data indicate the continuation of low growth in EFF with +0.2 % (range of −1.0 to +1.8 %) based on national emissions projections for China and USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. In spite of the low growth of EFF in 2016, the growth rate in atmospheric CO2 concentration is expected to be relatively high because of the persistence of the smaller residual terrestrial sink (SLAND) in response to El Nino conditions of 2015–2016. From this projection of EFF and assumed constant ELUC for 2016, cumulative emissions of CO2 will reach 565 ± 55 GtC (2075 ± 205 GtCO2) for 1870–2016, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015b, a, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center ( doi:10.3334/CDIAC/GCP_2016 ).

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Guidelines of care for the management of acne vulgaris

Abstract: Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection

Abstract: Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype) into four (TNBCtype-4) tumor-specific subtypes (BL1, BL2, M and LAR) and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50) or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively). Collectively, we provide pre-clinical data that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.

American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline

Abstract: The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for Clinicians and Journal of Clinical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Cancer Society or the American Society of Clinical Oncology.

The Economics of Disclosure and Financial Reporting Regulation: Evidence and Suggestions for Future Research

Abstract: This paper discusses the empirical literature on the economic consequences of disclosure and financial reporting regulation, drawing on U.S. and international evidence. Given the policy relevance of research on regulation, we highlight the challenges with (1) quantifying regulatory costs and benefits, (2) measuring disclosure and reporting outcomes, and (3) drawing causal inferences from regulatory studies. Next, we discuss empirical studies that link disclosure and reporting activities to firm-specific and market-wide economic outcomes. Understanding these links is important when evaluating regulation. We then synthesize the empirical evidence on the economic effects of disclosure regulation and reporting standards, including the evidence on International Financial Reporting Standards (IFRS) adoption. Several important conclusions emerge. We generally lack evidence on market-wide effects and externalities from regulation, yet such evidence is central to the economic justification of regulation. Moreover, evidence on causal effects of disclosure and reporting regulation is still relatively rare. We also lack evidence on the real effects of such regulation. These limitations provide many research opportunities. We conclude with several specific suggestions for future research.

A Transdisciplinary Framework for SLA in a Multilingual World

Abstract: THE PHENOMENON OF MULTILINGUALISM is as old as humanity, but multilingualism has been catapulted to a new world order in the 21st century. Social relations, knowledge structures, and webs of power are experienced bymany people as highly mobile and interconnected—for good and for bad—as a result of broad sociopolitical events and global markets. As a consequence, today’s multilingualism is enmeshed in globalization, technologization, and mobility. Communication and meaning-making are often felt as deterritorialized, that is, lived as something “which does not belong to one locality but which organizes translocal trajectories and wider spaces” (Blommaert, 2010, p. 46), while language use and learning are seen as emergent, dynamic, unpredictable, open ended, and intersubjectively negotiated. In this context, increasingly numerous and more diverse populations of adults and youth become multilingual and transcultural later in life, either by elective choice or by forced circumstances, or for a mixture of reasons. They must learn to negotiate complex demands and opportunities for varied, emergent competencies across their languages. Understanding such learning requires the integrative consideration of learners’ mental and neurobiological processing, remembering and categorizing patterns, and momentto-moment use of language in conjunction with a variety of socioemotional, sociocultural, sociopolitical, and ideological factors. The field of second language acquisition (SLA) seeks (a) to understand the processes by which school-aged children, adolescents, and adults learn and use, at any point in life, an additional language, including second, foreign,

A randomized trial of focused ultrasound thalamotomy for essential tremor

Abstract: BackgroundUncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. MethodsWe enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label exte...

Agency Costs of Free Cash Flow

Abstract: Free Cash Flow (FCF) agency conflicts exist when managers divert cash flow for private benefits. We identify the impact of unobservable FCF conflicts on firm policy using a structural approach. Measurement equations are constructed based on observable managerial choices: payout policy changes and personal portfolio decisions around exogenous tax rate changes. We find that FCF agency conflicts cause (i) under-leverage, leading to higher corporate taxes and (ii) under-investment in PP&E, leading to slower firm growth. Capital markets recognize FCF conflicts and discount such firms. Finally, firms with (i) large institutional holdings or (ii) better-aligned executive compensation, suffer less from FCF agency conflicts.

International consensus guidance for management of myasthenia gravis: Executive summary

Abstract: Objective: To develop formal consensus-based guidance for the management of myasthenia gravis (MG). Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input. Results: Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy. Conclusion: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide.

Preexposure Prophylaxis for HIV Infection Integrated With Municipal- and Community-Based Sexual Health Services

Abstract: Importance Several randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM). Objective To assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States. Design, Setting, and Participants Demonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015. Interventions A combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring. Main Outcomes and Measures Concentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition. Results Overall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P P = .02) and those reporting at least 2 condomless anal sex partners in the past 3 months (88.6%; P = .01) were more likely to have protective levels. The mean number of anal sex partners declined during follow-up from 10.9 to 9.3, whereas the proportion engaging in condomless receptive anal sex remained stable at 65.5% to 65.6%. Overall STI incidence was high (90 per 100 person-years) but did not increase over time. Two individuals became HIV infected during follow-up (HIV incidence, 0.43 [95% CI, 0.05-1.54] infections per 100 person-years); both had tenofovir diphosphate levels consistent with fewer than 2 doses/wk at seroconversion. Conclusions and Relevance The incidence of HIV acquisition was extremely low despite a high incidence of STIs in a large US PrEP demonstration project. Adherence was higher among those participants who reported more risk behaviors. Interventions that address racial and geographic disparities and housing instability may increase the impact of PrEP.

Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis

Abstract: BackgroundIn the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during 4 years of follow-up. We now extend the results to 10 years. MethodsAmong patients with carotid-artery stenosis who had been randomly assigned to stenting or endarterectomy, we evaluated outcomes every 6 months for up to 10 years at 117 centers. In addition to assessing the primary composite end point, we assessed the primary end point for the long-term extension study, which was ipsilateral stroke after the periprocedural period. ResultsAmong 2502 patients, there was no significant difference in the rate of the primary composite end point between the stenting group (11.8%; 95% confidence interval [CI], 9.1 to 14.8) and the endarterectomy group (9.9%; 95% CI, 7.9 to 12.2)...

Quantifying the evolution of individual scientific impact

Abstract: Are there quantifiable patterns behind a successful scientific career? Sinatra et al. analyzed the publications of 2887 physicists, as well as data on scientists publishing in a variety of fields. When productivity (which is usually greatest early in the scientist's professional life) is accounted for, the paper with the greatest impact occurs randomly in a scientist's career. However, the process of generating a high-impact paper is not an entirely random one. The authors developed a quantitative model of impact, based on an element of randomness, productivity, and a factor Q that is particular to each scientist and remains constant during the scientist's career. Science , this issue p. [596][1] [1]: http://www.sciencemag.org/content/354/6312/aaf5239.full

The quiescent intracluster medium in the core of the Perseus cluster

Abstract: The Hitomi collaboration reports X-ray observations of the core of the Perseus cluster of galaxies the brightest X-ray-emitting cluster in the sky. Such clusters typically consist of tens to thousands of galaxies bound together by gravity and are studied as models of both small-scale cosmology and large-scale astrophysical processes. The data reveal a remarkably quiescent atmosphere, where gas velocities are quite low, with a line-of-sight velocity dispersion of about 164 kilometres per second at a distance of 3060 kiloparsecs from the central nucleus.

Effectiveness of Remote Patient Monitoring After Discharge of Hospitalized Patients With Heart Failure: The Better Effectiveness After Transition–Heart Failure (BEAT-HF) Randomized Clinical Trial

Abstract: Importance It remains unclear whether telemonitoring approaches provide benefits for patients with heart failure (HF) after hospitalization. Objective To evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF. Design, Setting, and Participants We randomized 1437 patients hospitalized for HF between October 12, 2011, and September 30, 2013, to the intervention arm (715 patients) or to the usual care arm (722 patients) of the Better Effectiveness After Transition–Heart Failure (BEAT-HF) study and observed them for 180 days. The dates of our study analysis were March 30, 2014, to October 1, 2015. The setting was 6 academic medical centers in California. Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF. Interventions The intervention combined health coaching telephone calls and telemonitoring. Telemonitoring used electronic equipment that collected daily information about blood pressure, heart rate, symptoms, and weight. Centralized registered nurses conducted telemonitoring reviews, protocolized actions, and telephone calls. Main Outcomes and Measures The primary outcome was readmission for any cause within 180 days after discharge. Secondary outcomes were all-cause readmission within 30 days, all-cause mortality at 30 and 180 days, and quality of life at 30 and 180 days. Results Among 1437 participants, the median age was 73 years. Overall, 46.2% (664 of 1437) were female, and 22.0% (316 of 1437) were African American. The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge, which occurred in 50.8% (363 of 715) and 49.2% (355 of 722) of patients, respectively (adjusted hazard ratio, 1.03; 95% CI, 0.88-1.20; P = .74). In secondary analyses, there were no significant differences in 30-day readmission or 180-day mortality, but there was a significant difference in 180-day quality of life between the intervention and usual care groups. No adverse events were reported. Conclusions and Relevance Among patients hospitalized for HF, combined health coaching telephone calls and telemonitoring did not reduce 180-day readmissions. Trial Registration clinicaltrials.gov Identifier:NCT01360203

Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia

Abstract: OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50–80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA 1c RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year, and by 71% at 2 years. The median HbA 1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores ( P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

Epithelial-mesenchymal transition in tissue repair and fibrosis.

Abstract: The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

A multi-decade record of high-quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

Abstract: . The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) "living data" publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770 . The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID .

Altering the course of schizophrenia: progress and perspectives

Abstract: Despite a lack of recent progress in the treatment of schizophrenia, our understanding of its genetic and environmental causes has considerably improved, and their relationship to aberrant patterns of neurodevelopment has become clearer. This raises the possibility that 'disease-modifying' strategies could alter the course to — and of — this debilitating disorder, rather than simply alleviating symptoms. A promising window for course-altering intervention is around the time of the first episode of psychosis, especially in young people at risk of transition to schizophrenia. Indeed, studies performed in both individuals at risk of developing schizophrenia and rodent models for schizophrenia suggest that pre-diagnostic pharmacotherapy and psychosocial or cognitive-behavioural interventions can delay or moderate the emergence of psychosis. Of particular interest are 'hybrid' strategies that both relieve presenting symptoms and reduce the risk of transition to schizophrenia or another psychiatric disorder. This Review aims to provide a broad-based consideration of the challenges and opportunities inherent in efforts to alter the course of schizophrenia.

American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

Abstract: Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.