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Background Despite accumulating evidence of the important health benefits of bariatric surgery in morbidly obese patients in general, bariatric surgery outcomes are less clear in higher-risk, high-priority populations of patients with BMI ≥ 50 kg/m 2 . To help the Department of Veterans Affairs (VA) Health Services Research & Development Service (HSR&D) develop a research agenda, we conducted a rapid evidence review to better understand bariatric surgery outcomes in adults with BMI ≥ 50 kg/m 2 . Methods We searched MEDLINE ® , the Cochrane Database of Systematic Reviews, the Cochrane Central Registry of Controlled Trials, and ClinicalTrials.gov through June 2016. We included trials and observational studies. We used pre-specified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO registration number CRD42015025348). All decisions were completed by one reviewer and checked by another. Results Among 1892 citations, we included 23 studies in this rapid review. Compared with usual care, one large retrospective VA study provided limited evidence that bariatric surgery can lead to increased mortality in the first year, but decreased mortality long-term among super obese veterans. Studies that compared different bariatric surgical approaches suggested some differences in weight loss and complications. Laparoscopic gastric bypass generally resulted in greater short-term proportion of excess weight loss than did other procedures. Duodenal switch led to greater long-term weight loss than did gastric bypass, but with more complications. Conclusions The published literature that separates the super obese is insufficient for determining the precise balance of benefits and harms of bariatric surgery in this high-risk subgroup. Future studies should evaluate a more complete set of key outcomes with longer follow-up in larger samples of more broadly representative adults.

Assessing fish assemblages in subtidal and intertidal habitats is challenging due to the structural complexity of many of these systems. Trapping and collecting are regarded as optimal ways to sample these assemblages, but this method is costly and destructive, so researchers also use video techniques. Underwater visual census and baited remote underwater video stations are commonly used to characterise fish communities in these systems. More passive techniques such as remote underwater video (RUV) may be more appropriate for behavioural studies, or for comparing proximal habitats where the broad attraction caused by bait plumes could be an issue. However, data processing for RUVs can be time consuming and create processing bottlenecks. Here, we identified the optimal subsampling method to assess fish assemblages on intertidal oyster reefs using RUV footage and bootstrapping techniques. We quantified how video subsampling effort and method (systematic random) affect the accuracy and precision of three different fish assemblage metrics; species richness and two proxies for the total abundance of fish, MaxN and MeanCount , which have not been evaluated previously for complex intertidal habitats. Results suggest that MaxN and species richness should be recorded in real time, whereas optimal sampling for MeanCount is every 60 s. Systematic sampling proved to be more accurate and precise than random sampling. This study provides valuable methodology recommendations which are relevant for the use of RUV to assess fish assemblages in a variety of shallow intertidal habitats.

Habitat interactions play key roles in regulating biodiversity and ecosystem functions. This is particularly important in aquatic ecosystems, where the flow of water facilitates exchanges of energy and matter. Oyster reefs, a highly degraded habitat globally and a key focus for restoration efforts, can reduce water movement and facilitate the deposition of particles around them, affecting nutrient cycling in surrounding sediments. The effects of these reefs on sediment infauna taxonomic and functional biodiversity, however, remain unknown. We sampled sediments at increasing distances from reefs at three estuaries to evaluate the relationships between proximity to oyster reefs and composition and functionality of infaunal communities and explored the potential mechanisms behind those relationships. Sediments close to oyster reefs had consistently greater amounts of labile organic matter, which in turn was positively related to the number of taxa and total abundance of infauna. Also, the functional traits of infauna, such as bioturbation and feeding modes, were related to proximity to reefs, but they were variable between estuaries indicating the importance of background estuarine environmental conditions. These results suggest that habitat linkages between oyster reefs and sediments are important in regulating taxonomic biodiversity, while functional biodiversity seems to be driven by processes operating at larger scales. Given burgeoning restoration initiatives worldwide, particularly those of oyster reefs, incorporating seascape interactions can help inform recovery of biodiversity and functions beyond the target habitat at the seascape level, which is often overlooked.

The worldwide prevalence of obesity has lead to increased efforts to find therapies to treat obesity-related pathologies. Ceramide is a well-established mediator of several health problems that arise from adipose tissue expansion. The purpose of this study was to determine whether AICAR, an AMPK-activating drug, selectively reduces skeletal muscle ceramide synthesis. Murine myotubes and rats were challenged with palmitate and high-fat diet, respectively, to induce ceramide accrual, in the absence or presence of AICAR. Transcript levels of the rate-limiting enzyme in ceramide biosynthesis, serine palmitoyltransferase 2 (SPT2) were measured, in addition to lipid analysis. Student's t-test and ANOVA were used to assess the association between outcomes and groups. Palmitate alone induced an increase in serine palmitoyltransferase 2 (SPT2) expression and an elevation of ceramide levels in myotubes. Co-incubation with palmitate and AICAR prevented both effects. However, ceramide and SPT2 increased with the addition of compound C, an AMPK inhibitor. In rats fed a high-fat diet (HFD), soleus SPT2 expression increased compared with normal chow-fed littermates. Moreover, rats on HFD that received daily AICAR injections had lower SPT2 levels and reduced muscle ceramide content compared with those on HFD only. These results suggest that AICAR reduces ceramide synthesis by targeting SPT2 transcription, likely via AMPK activation as AMPK inhibition prevented the AICAR-induced improvements. Given the role of skeletal muscle ceramide in insulin resistance, it is tempting to speculate that interventions that activate AMPK may lead to long-term ceramide reduction and improved metabolic function.

The Uganda Martyrs have grown to become one of the country's most persistent national symbols throughout the last 130 years. They maintain a commanding presence in everyday life to this day, both as a symbol of the Christian faith and of Ugandan perseverance and character amidst hardship. This thesis seeks to examine the legacy of these martyrs as they took on an increasingly pivotal role in public discourse in the early years of Ugandan independence, as promoted and transmitted by the Roman Catholic Church (RCC). Specifically, it tracks the lively and enthusiastic co-opting of the Martyrs' story into the workings of the Second Vatican Council, and in the RCC's concentrated post-Conciliar activity in the developing world in two critical moments: the canonization of the Martyrs during a session of the Council in 1964, and Paul VI's subsequent visit to Uganda to bless the new shrines to the martyrs being built there in 1969. Both of these events provided ideal outlets for the RCC to display a new approach to Christianity in the developing world based on the liturgical reforms of the Second Vatican Council, which had concluded in 1965. This thesis utilises a novel combination of visual and written source material, bringing together work on the Second Vatican Council, Ugandan postcolonialism, and modernist architectural theory. It seeks to combine written material, in the form of official RCC documents and European press coverage, with a variety of visual media. It relies on extended fieldwork and site visits conducted in the greater Kampala area in addition to European archival material. Ultimately, the story of the Uganda Martyrs provides a unique insight into the interaction point between the global RCC and the local Ugandan Christian community.

[...]the Los Angeles-based artist treats the entire studio as her canvas, using organic, sustainable materials on location to make new site-specific installations. Initially the idea was I'm going to transition from using traditional art materials, which is like oil paint on stretched linen, and then it turned into me incorporating materials which reflected environments I was looking at...

Mice were fed cholesterol or various other sterols for 26 hr, after which the amount of hepatic cholesterol synthesis was measured in a cell-free system. The following sterols were as effective as cholesterol itself in depressing the conversion of acetate into sterol: pregn-5-en-3β -ol, which lacks an isohexyl group on C-20; (E)-17(20)-dehydrocholesterol, in which the isohexyl group is fixed to the right; (E)-17(20)-dehydrocholesterol, in which C-23 is oriented away from the nucleus; and 20-epicholesterol. Moreover, when the isohexyl group was fixed to the left in (Z)-17(20)-dehydrocholesterol, this dietary sterol, identified in the liver, caused not only a depression in the conversion of acetate into sterols but also a depression in the conversion of both mevalonate and squalene into sterols. The incorporation of acetate into fatty acids was not depressed, nor did the (Z)-sterol appear to have a generalized effect on membranous enzymes, because the activity of glucose-6-phosphatase was unaffected. Thus, feedback inhibition was retained when the stereochemistry of cholesterol's side chain was drastically changed and even after the nearly complete removal of the side chain. This implies that the side chain is only minimally recognized by the mechanisms involved in feedback inhibition.

We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system . 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 , 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 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly . 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.