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Purpose To assess the incidence, prognostic factors, and clinical outcomes of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. Materials and Methods In this single-institution retrospective study, 191 patients (m:f = 114:77, median age 54 years, median Model for End-Stage Liver Disease or MELD score 14) who underwent TIPS creation between 1999 and 2013 were studied. Medical record review was used to identify demographic characteristics, liver disease, procedure, and outcome data. Post-TIPS HE within 30 days was defined by new mental status changes and was graded according to the West Haven classification system. The influence of data parameters on HE occurrence and 90-day mortality was assessed using binary logistic regression. Results TIPS was successfully created with hemodynamic success in 99 % of cases. Median final PSG was 7 mmHg. HE incidence within 30 days was 42 % (81/191; 22 % de novo, 12 % stable, and 8 % worsening). Degrees of HE included grade 1 (46 %), grade 2 (29 %), grade 3 (18 %), and grade 4 (7 %). Medical therapy typically addressed HE, and shunt reduction was necessary in only three cases. MELD score ( P  = 0.020) and age ( P  = 0.009) were significantly associated with HE development on multivariate analysis. Occurrence of de novo HE post-TIPS did not associate with 90-day mortality ( P  = 0.400), in contrast to worsening HE ( P  < 0.001). Conclusions The incidence of post-TIPS HE is non-trivial, but symptoms are typically mild and medically managed. HE rates are higher in older patients and those with worse liver function and should be contemplated when counseling on expected TIPS outcomes and post-procedure course.

A survey study of 136, self identified, homosexual men, examined the relationship between the constructs of hardiness and internalized homophobia. Hardiness was measured using the Personal Views Survey III Revised (PVS-III-R). Internalized homophobia was measured using the Internalized Homonegativity Inventory (IHNI). Groups were established based on participant's internalized homophobia score using a median split. The data supported the hypothesis that individuals higher in hardiness would have significantly lower internalized homophobia scores than individuals low in hardiness.Subscales of the PVS-III-R were also examined. The commitment and challenge subscales were consistent with overall hardiness scores. Both subscales showed significantly that higher levels of commitment and challenge are negatively related to internalized homophobia. No significant difference could be found between the two groups on the subscale of control. The mean scores for both groups were in the high range of the scoring scale. This suggests that the hardiness attitude of control might be strongly related to openly identifying as a homosexual male.

Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two, and the overall management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide, despite substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar discusses the important topics of the pathophysiology, epidemiological trends, and modern management of acute myocardial infarction, focusing on the recent advances in reperfusion strategies and pharmacological treatment approaches.

A large fraction of heroin users now report that they formerly used prescription opioids nonmedically, a finding that has led to restrictions on opioid prescribing. Nevertheless, only a small fraction of prescription-opioid users move on to heroin use. The nonmedical use of prescription opioids is a major public health issue in the United States, both because of the overall high prevalence and because of marked increases in associated morbidity and mortality. 1 In 2014, a total of 10.3 million persons reported using prescription opioids nonmedically (i.e., using medications that were not prescribed for them or were taken only for the experience or feeling that they caused). 2 Emergency department visits involving misuse or abuse of prescription opioids increased 153% between 2004 and 2011, and admissions to substance-abuse treatment programs linked to prescription opioids more than quadrupled between 2002 and 2012. . . .

Anthropogenic global change compromises forest resilience, with profound impacts to ecosystem functions and services. This synthesis paper reflects on the current understanding of forest resilience and potential tipping points under environmental change and explores challenges to assessing responses using experiments, observations and models. Forests are changing over a wide range of spatio‐temporal scales, but it is often unclear whether these changes reduce resilience or represent a tipping point. Tipping points may arise from interactions across scales, as processes such as climate change, land‐use change, invasive species or deforestation gradually erode resilience and increase vulnerability to extreme events. Studies covering interactions across different spatio‐temporal scales are needed to further our understanding. Combinations of experiments, observations and process‐based models could improve our ability to project forest resilience and tipping points under global change. We discuss uncertainties in changing CO₂concentration and quantifying tree mortality as examples. Synthesis. As forests change at various scales, it is increasingly important to understand whether and how such changes lead to reduced resilience and potential tipping points. Understanding the mechanisms underlying forest resilience and tipping points would help in assessing risks to ecosystems and presents opportunities for ecosystem restoration and sustainable forest management.

Oligodendroglia ensheath axons in the brain with myelin, which provides the insulation that speeds up transmission of neuronal electrical impulses. The process of myelination in the human brain goes on for decades, concurrent with all manner of brain development and cognitive activity. Gibson et al. (p. 10.1126/science.1252304 , published online 10 April; see the Perspective by Bechler and ffrench-Constant ) used optogenetics to study myelination in response to neural activity. Electrical activity in the motor cortex of the brain of awake mice led to proliferation and differentiation of oligodendrocytes and consequently increased myelination and alterations in motor response. Optogenetic stimulation of the mouse motor cortex incites proliferation of myelin-producing cells and axonal myelination. [Also see Perspective by Bechler and ffrench-Constant ] Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity–regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

Orthopedic procedures represent a large expense to the Medicare program, and costs of implantable medical devices account for a large proportion of those procedures' costs. Physicians have been encouraged to consider cost in the selection of devices, but several factors make acquiring cost information difficult. To assess physicians' levels of knowledge about costs, we asked orthopedic attending physicians and residents at seven academic medical centers to estimate the costs of thirteen commonly used orthopedic devices between December 2012 and March 2013. The actual cost of each device was determined at each institution; estimates within 20 percent of the actual cost were considered correct. Among the 503 physicians who completed our survey, attending physicians correctly estimated the cost of the device 21 percent of the time, and residents did so 17 percent of the time. Thirty-six percent of physicians and 75 percent of residents rated their knowledge of device costs \"below average\" or \"poor.\" However, more than 80 percent of all respondents indicated that cost should be \"moderately,\" \"very,\" or \"extremely' important in the device selection process. Surgeons need increased access to information on the relative prices of devices and should be incentivized to participate in cost containment efforts. [PUBLICATION ABSTRACT]

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells 2 , providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 10 6 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly 3 . Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG. A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

Background Enhanced Recovery After Surgery (ERAS) protocols reduce length of stay, complications and costs for a large number of elective surgical procedures. A similar, structured approach appears to improve outcomes, including mortality, for patients undergoing high-risk emergency general surgery, and specifically emergency laparotomy. These are the first consensus guidelines for optimal care of these patients using an ERAS approach. Methods Experts in aspects of management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. Pubmed, Cochrane, Embase, and MEDLINE database searches on English language publications were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized controlled trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on non-emergency patients when appropriate. The Delphi method was used to validate final recommendations. The guideline has been divided into two parts: Part 1—Preoperative Care and Part 2—Intraoperative and Postoperative management. This paper provides guidelines for Part 1. Results Twelve components of preoperative care were considered. Consensus was reached after three rounds. Conclusions These guidelines are based on the best available evidence for an ERAS approach to patients undergoing emergency laparotomy. Initial management is particularly important for patients with sepsis and physiological derangement. These guidelines should be used to improve outcomes for these high-risk patients.

Malaria remains a major cause of death globally, especially in sub-Saharan Africa. Trends in malaria-associated mortality over the last 25 years are reported across sub-Saharan Africa. Measuring the burden of malaria according to age and geographic area and over time is important for malaria-control programs and health care providers for planning, implementing, monitoring, and evaluating control and elimination efforts. 1 , 2 The Malaria Atlas Project has produced high-spatial-resolution (5-km 2 ) estimates of the prevalence of malaria infection (parasite rate) and clinical incidence rates in sub-Saharan Africa from 2000 through 2015. 3 In parallel, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), also known as the Global Burden of Disease Study, has produced national-level estimates of morbidity and mortality from malaria on an annual basis since . . .