The role of computed tomography for identifying mechanical bowel obstruction in a Pakistani population

Objective: To retrospectively review our experience of CT scan in cases with a final diagnosis of surgically confirmed mechanical bowel obstruction. Methods: It is a retrospective analytical study, done from 2003 to 2008. All adult patients having undergone laparotomy in addition to a preoperative abdominal CT scan over a 5 year period were identified through the medical records and their case notes reviewed. Taking surgery to be the gold standard for diagnosing mechanical bowel obstruction, we compared results of the CT with operative findings to determine the sensitivity, specificity, positive and negative predictive values of CT scans. The data was analyzed using SPSS version 16.0. Results: A total of 271 patient records were reviewed. The mean age was 46 +/- 19 years and (64%) were men. Mechanical intestinal obstruction was found in 104 patients on laparotomy and CT scan had diagnosed 97 of these. The sensitivity and specificity was 93% respectively. CT scanning correctly identified the cause of the obstruction in 72 (74%) cases. The common reasons for bowel obstruction identified by surgery were adhesions 29 (40%), neoplasm 12 (17 %) and hernias 7 (10%). Conclusion: CT scans are reliable at diagnosing intestinal obstruction with a high sensitivity and specificity but they are not as accurate at defining the etiology of the obstruction

Effects of Liraglutide and Fenretinide treatments on the diabetic phenotype of neuronal human BACE1 knock-in mice

The authors would like to acknowledge University of Aberdeen PhD studentship to RD and Scottish Alzheimer’s Research UK Junior member research grant to RD to perform GLP-1 ELISA and Alzheimer’s Research UK grant to BP and MD (ARUK-PG2017B-11). We thank Dr Oliver Helk for advice concerning statistical analyses and Prof Gernot Riedel for kindly providing the PhenoTyper home cages and advice in behavioural studies.Peer reviewedPostprin

Effects of Liraglutide and Fenretinide treatments on the diabetic phenotype of neuronal human BACE1 knock-in mice

The authors would like to acknowledge University of Aberdeen PhD studentship to RD and Scottish Alzheimer’s Research UK Junior member research grant to RD to perform GLP-1 ELISA and Alzheimer’s Research UK grant to BP and MD (ARUK-PG2017B-11). We thank Dr Oliver Helk for advice concerning statistical analyses and Prof Gernot Riedel for kindly providing the PhenoTyper home cages and advice in behavioural studies.Peer reviewedPostprin

Permafrost Landscape History Shapes Fluvial Chemistry, Ecosystem Carbon Balance, and Potential Trajectories of Future Change

Intensifying permafrost thaw alters carbon cycling by mobilizing large amounts of terrestrial substrate into aquatic ecosystems. Yet, few studies have measured aquatic carbon fluxes and constrained drivers of ecosystem carbon balance across heterogeneous Arctic landscapes. Here, we characterized hydrochemical and landscape controls on fluvial carbon cycling, quantified fluvial carbon fluxes, and estimated fluvial contributions to ecosystem carbon balance across 33 watersheds in four ecoregions in the continuous permafrost zone of the western Canadian Arctic: unglaciated uplands, ice-rich moraine, and organic-rich lowlands and till plains. Major ions, stable isotopes, and carbon speciation and fluxes revealed patterns in carbon cycling across ecoregions defined by terrain relief and accumulation of organics. In previously unglaciated mountainous watersheds, bicarbonate dominated carbon export (70% of total) due to chemical weathering of bedrock. In lowland watersheds, where soil organic carbon stores were largest, lateral transport of dissolved organic carbon (50%) and efflux of biotic CO2 (25%) dominated. In watersheds affected by thaw-induced mass wasting, erosion of ice-rich tills enhanced chemical weathering and increased particulate carbon fluxes by two orders of magnitude. From an ecosystem carbon balance perspective, fluvial carbon export in watersheds not affected by thaw-induced wasting was, on average, equivalent to 6%–16% of estimated net ecosystem exchange (NEE). In watersheds affected by thaw-induced wasting, fluvial carbon export approached 60% of NEE. Because future intensification of thermokarst activity will amplify fluvial carbon export, determining the fate of carbon across diverse northern landscapes is a priority for constraining trajectories of permafrost region ecosystem carbon balance

Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial

Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds

Stream dissolved organic matter in permafrost regions shows surprising compositional similarities but negative priming and nutrient effects

Permafrost degradation is delivering bioavailable dissolved organic matter (DOM) and inorganic nutrients to surface water networks. While these permafrost subsidies represent a small portion of total fluvial DOM and nutrient fluxes, they could influence food webs and net ecosystem carbon balance via priming or nutrient effects that destabilize background DOM. We investigated how addition of biolabile carbon (acetate) and inorganic nutrients (nitrogen and phosphorus) affected DOM decomposition with 28-day incubations. We incubated late-summer stream water from 23 locations nested in seven northern or high-altitude regions in Asia, Europe, and North America. DOM loss ranged from 3% to 52%, showing a variety of longitudinal patterns within stream networks. DOM optical properties varied widely, but DOM showed compositional similarity based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis. Addition of acetate and nutrients decreased bulk DOM mineralization (i.e., negative priming), with more negative effects on biodegradable DOM but neutral or positive effects on stable DOM. Unexpectedly, acetate and nutrients triggered breakdown of colored DOM (CDOM), with median decreases of 1.6% in the control and 22% in the amended treatment. Additionally, the uptake of added acetate was strongly limited by nutrient availability across sites. These findings suggest that biolabile DOM and nutrients released from degrading permafrost may decrease background DOM mineralization but alter stoichiometry and light conditions in receiving waterbodies. We conclude that priming and nutrient effects are coupled in northern aquatic ecosystems and that quantifying two-way interactions between DOM properties and environmental conditions could resolve conflicting observations about the drivers of DOM in permafrost zone waterways

Establishment of porcine and human expanded potential stem cells.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine

Knowledge Priorities on Climate Change and Water in the Upper Indus Basin: A Horizon Scanning Exercise to Identify the Top 100 Research Questions in Social and Natural Sciences

River systems originating from the Upper Indus Basin (UIB) are dominated by runoff from snow and glacier melt and summer monsoonal rainfall. These water resources are highly stressed as huge populations of people living in this region depend on them, including for agriculture, domestic use, and energy production. Projections suggest that the UIB region will be affected by considerable (yet poorly quantified) changes to the seasonality and composition of runoff in the future, which are likely to have considerable impacts on these supplies. Given how directly and indirectly communities and ecosystems are dependent on these resources and the growing pressure on them due to ever-increasing demands, the impacts of climate change pose considerable adaptation challenges. The strong linkages between hydroclimate, cryosphere, water resources, and human activities within the UIB suggest that a multi- and inter-disciplinary research approach integrating the social and natural/environmental sciences is critical for successful adaptation to ongoing and future hydrological and climate change. Here we use a horizon scanning technique to identify the Top 100 questions related to the most pressing knowledge gaps and research priorities in social and natural sciences on climate change and water in the UIB. These questions are on the margins of current thinking and investigation and are clustered into 14 themes, covering three overarching topics of ‘governance, policy, and sustainable solutions’, ‘socioeconomic processes and livelihoods’, and ‘integrated Earth System processes’. Raising awareness of these cutting-edge knowledge gaps and opportunities will hopefully encourage researchers, funding bodies, practitioners, and policy makers to address them

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Low biodegradability of particulate organic carbon mobilized from thaw slumps on the Peel Plateau, NT, and possible chemosynthesis and sorption effects

Warming and wetting in the western Canadian Arctic are accelerating thaw-driven mass wasting by permafrost thaw slumps, increasing total organic carbon (TOC) delivery to headwater streams by orders of magnitude primarily due to increases in particulate organic carbon (POC). Upon thaw, permafrost carbon entering and transported within streams may be mineralized to CO2 or re-sequestered into sediments. The balance between these processes is an important uncertainty in the permafrost-carbon-climate feedback. Using aerobic incubations of TOC from streams affected by thaw slumps we find that slump-derived organic carbon undergoes minimal (g 1/4g 4g %) oxidation over a 1-month period, indicating that this material may be predominantly destined for sediment deposition. Simultaneous measurements of POC and dissolved organic carbon (DOC) suggest that mineralization of DOC accounted for most of the TOC loss. Our results indicate that mobilization of mineral-rich tills in this region may protect carbon from mineralization via adsorption to minerals and promote inorganic carbon sequestration via chemolithoautotrophic processes. With intensification of hillslope mass wasting across the northern permafrost zone, region-specific assessments of permafrost carbon fates and inquiries beyond organic carbon decomposition are needed to constrain drivers of carbon cycling and climate feedbacks within stream networks affected by permafrost thaw