Neurotoxins from Snake Venom

Found within snake venoms are a variety of toxic and nontoxic proteins. The effects of snake venoms depend on all of the components of that venom. However, the lethal effects are usually related to the most potent toxins found within the venom; the two most toxic proteins found in snake venom are neuro- and cardiotoxins. This article reviews a variety of neurotoxins found in snake venom. The range of neurotoxins present in snake venom is varied and includes: peripheral and noncentral, presynaptic, postsynaptic, potassium-channel inhibiting, muscarinic transmission inhibiting, and anticholinesterase types

Age-period-cohort analysis of trends in amyotrophic lateral sclerosis incidence

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with an unknown cause. Studies have reported that the incidence rate of ALS might be changing. As ALS is an age related disease, crude incidence could increase as population structure changes and overall life expectancy improves. Age-period-cohort (APC) models are frequently used to investigate trends in demographic rates such as incidence. Age-specific incidence rate for ALS from 1996 to 2014 were taken from a population-based ALS register in Ireland. To circumvent the well-known identifiability issue in APC models, we apply the method of Partial Least Squares Regression to separate the effects of Age, Period and Cohort on ALS incidence over time. This APC analysis shows no cohort effect and the initial signs of a period effect; increasing incidence of ALS in the most recently diagnosed group. As further years of data accrue to the Irish register it will become clear if this effect emerges as a strong trend in the incidence of ALS in Ireland and replication of these analyses in other populations will show if our findings on temporal patterns in ALS incidence are shared elsewhere

Surgical need among the ageing population of Uganda

Background: Uganda’s ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgi- cally-treatable conditions is unknown. Objectives: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. Methods: A cluster randomized sample representing the national population of Uganda was enumerated. The previously vali- dated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any sur- gically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation.   Results: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes.Conclusion: There is disproportionately high need for surgical care among the ageing population of Uganda with approximate- ly 700,000 consultations needed.Keywords: Surgical need, ageing population, Uganda

Optimizing Care for Ugandans with Untreated Abdominal Surgical Conditions

Background: Abdominal operations account for a majority of surgical volume in low-income countries, yet population-level prevalence data on surgically treatable abdominal conditions are scarce. Objective: In this study, our objective was to quantify the burden of surgically treatable abdominal conditions in Uganda. Methods: In 2014, we administered a two-stage cluster-randomized Surgeons OverSeas Assessment of Surgical Need survey to 4,248 individuals in 105 randomly selected clusters (representing the national population of Uganda). Findings: Of the 4,248 respondents, 185 reported at least one surgically treatable abdominal condition in their lifetime, giving an estimated lifetime prevalence of 3.7% (95% CI: 3.0 to 4.6%). Of those 185 respondents, 76 reported an untreated condition, giving an untreated prevalence of 1.7% (95% CI: 1.3 to 2.3%). Obstructed labor (52.9%) accounted for most of the 238 abdominal conditions reported and was untreated in only 5.6% of reported conditions. In contrast, 73.3% of reported abdominal masses were untreated. Conclusions: Individuals in Uganda with nonobstetric abdominal surgical conditions are disproportionately undertreated. Major health system investments in obstetric surgical capacity have been beneficial, but our data suggest that further investments should aim at matching overall surgical care capacity with surgical need, rather than focusing on a single operation for obstructed labor

Surgical need among the ageing population of Uganda

Background: Uganda\u2019s ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgically-treatable conditions is unknown. Objectives: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. Methods: A cluster randomized sample representing the national population of Uganda was enumerated. The previously validated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any surgically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation. Results: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes. Conclusion: There is disproportionately high need for surgical care among the ageing population of Uganda with approximately 700,000 consultations needed. DOI: https://dx.doi.org/10.4314/ahs.v19i1.54 Cite as: Tran TM, Fuller AT, Butler EK, Muhumuza C, Ssennono VF, Vissoci JR, et al. Surgical need among the ageing population of Uganda. Afri Health Sci. 2019;19(1). 1778-1788. https:// dx.doi. org/10.4314/ ahs. v19i1.5

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Negative Regulators of Insulin Signaling Revealed in a Genome-Wide Functional Screen

Type 2 diabetes develops due to a combination of insulin resistance and β-cell failure and current therapeutics aim at both of these underlying causes. Several negative regulators of insulin signaling are known and are the subject of drug discovery efforts. We sought to identify novel contributors to insulin resistance and hence potentially novel targets for therapeutic intervention.An arrayed cDNA library encoding 18,441 human transcripts was screened for inhibitors of insulin signaling and revealed known inhibitors and numerous potential novel regulators. The novel hits included proteins of various functional classes such as kinases, phosphatases, transcription factors, and GTPase associated proteins. A series of secondary assays confirmed the relevance of the primary screen hits to insulin signaling and provided further insight into their modes of action.Among the novel hits was PALD (KIAA1274, paladin), a previously uncharacterized protein that when overexpressed led to inhibition of insulin's ability to down regulate a FOXO1A-driven reporter gene, reduced upstream insulin-stimulated AKT phosphorylation, and decreased insulin receptor (IR) abundance. Conversely, knockdown of PALD gene expression resulted in increased IR abundance, enhanced insulin-stimulated AKT phosphorylation, and an improvement in insulin's ability to suppress FOXO1A-driven reporter gene activity. The present data demonstrate that the application of arrayed genome-wide screening technologies to insulin signaling is fruitful and is likely to reveal novel drug targets for insulin resistance and the metabolic syndrome

Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was supported by a Grant core funding from the Agency for Science Technology and Research (A*STAR, Singapore) and a Singapore Translational Research Investigator Award (NRMC/StaR/013/2012) to AB as well as NIHR Biomedical Centre, Oxford, WT 091663MA, NIAID1U19AI082630-01, Oxford Martin School funding and an NIHR Senior Investigator award to PK