Crotalus oreganus concolor: Envenomation Case with Venom Analysis and a Diagnostic Conundrum of Myoneurologic Symptoms

This is an accepted manuscript of an article published by Elsevier in Wilderness & Environmental Medicine on 12/03/2020, available online: https://doi.org/10.1016/j.wem.2019.12.007 The accepted version of the publication may differ from the final published version.A case of midget-faded rattlesnake (Crotalus oreganus concolor) envenomation of an adult male professional herpetologist occurred in a rural setting and resulted in an array of venom induced myoneurologic symptoms. The patient experienced blurry vision, total body paresthesia, dyspnea, chest tightness, and waves of spastic muscle movements of the hands and feet that resembled tetany. It was not apparent whether these symptoms were potentially venom induced or were related to stress-induced physiologic responses. Local envenomation effects were minimal, and coagulation parameters remained within normal limits. Antivenom was not administered per patient concerns related to a history of acute allergic reactions to antivenom. Venom was collected from the Crotalus oreganus concolor responsible for the bite, and analysis revealed the presence of high levels of myotoxins (SR calcium pump antagonists) and concolor toxin, a presynaptic neurotoxin that can have myotoxic effects and cause respiratory paralysis; several serine proteinases associated with coagulopathies were also present in the venom profile.Published versio

Quotients of incidence geometries

We develop a theory for quotients of geometries and obtain sufficient conditions for the quotient of a geometry to be a geometry. These conditions are compared with earlier work on quotients, in particular by Pasini and Tits. We also explore geometric properties such as connectivity, firmness and transitivity conditions to determine when they are preserved under the quotienting operation. We show that the class of coset pregeometries, which contains all flag-transitive geometries, is closed under an appropriate quotienting operation.Comment: 26 pages, 5 figure

Evidence for divergent patterns of local selection driving venom variation in Mojave Rattlesnakes (\u3ci\u3eCrotalus scutulatus\u3c/i\u3e)

Snake venoms represent an enriched system for investigating the evolutionary processes that lead to complex and dynamic trophic adaptations. It has long been hypothesized that natural selection may drive geographic variation in venom composition, yet previous studies have lacked the population genetic context to examine these patterns. We leverage range-wide sampling of Mojave Rattlesnakes (Crotalus scutulatus) and use a combination of venom, morphological, phylogenetic, population genetic, and environmental data to characterize the striking dichotomy of neurotoxic (Type A) and hemorrhagic (Type B) venoms throughout the range of this species. We find that three of the four previously identified major lineages within C. scutulatus possess a combination of Type A, Type B, and a ‘mixed’ Type A + B venom phenotypes, and that fixation of the two main venom phenotypes occurs on a more fine geographic scale than previously appreciated. We also find that Type A + B individuals occur in regions of inferred introgression, and that this mixed phenotype is comparatively rare. Our results support strong directional local selection leading to fixation of alternative venom phenotypes on a fine geographic scale, and are inconsistent with balancing selection to maintain both phenotypes within a single population. Our comparisons to biotic and abiotic factors further indicate that venom phenotype correlates with fang morphology and climatic variables. We hypothesize that links to fang morphology may be indicative of co-evolution of venom and other trophic adaptations, and that climatic variables may be linked to prey distributions and/or physiology, which in turn impose selection pressures on snake venoms

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia: Design of the ADvance Randomized Controlled Trial

Background: There are currently few available treatments and no cure for Alzheimer disease (AD), a growing public health burden. Animal models and an open-label human trial have indicated that deep brain stimulation (DBS) of memory circuits may improve symptoms and possibly slow disease progression. The ADvance trial was designed to examine DBS of the fornix as a treatment for mild AD. Methods: ADvance is a randomized, double-blind, placebo-controlled, delayed-start, multicenter clinical trial conducted at six sites in the US and one site in Canada. Eighty-five subjects initially consented to be screened for the trial. Of these, 42 subjects who met inclusion and exclusion criteria were implanted with DBS leads anterior to the columns of the fornix bilaterally. They were randomized 1:1 to DBS off or DBS on groups for the initial 12 months of follow-up. After 1 year, all subjects will have their devices turned on for the remainder of the study. Postimplantation, subjects will return for 13 follow-up visits over 48 months for cognitive and psychiatric assessments, brain imaging (up to 12 months), and safety monitoring. The primary outcome measures include Alzheimer\u27s Disease Assessment Scale -- cognitive component (ADAS-cog-13), Clinical Dementia Rating sum of boxes (CDR-SB), and cerebral glucose metabolism measured with positron emission tomography. This report details the study methods, baseline subject characteristics of screened and implanted participants, and screen-to-baseline test€“retest reliability of the cognitive outcomes. Results: Implanted subjects had a mean age of 68.2 years, were mostly male (55%), and had baseline mean ADAS-cog-13 and CDR-SB scores of 28.9 (SD, 5.2) and 3.9 (SD, 1.6), respectively. There were no significant differences between screened and implanted or nonimplanted subjects on most demographic or clinical assessments. Implanted subjects had significantly lower (better) ADAS-cog-11 (17.5 vs 21.1) scores, but did not differ on CDR-SB. Scores on the major outcome measures for the trial were consistent at screening and baseline. Conclusion: ADvance was successful in enrolling a substantial group of patients for this novel application of DBS, and the study design is strengthened by rigorous subject selection from seven sites, a double-blind placebo-controlled design, and extensive open-label follow-up

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Search for Low Scale Gravity Effects in e+e- Collisions at LEP

Recent theories propose that quantum gravity effects may be observable at LEP energies via gravitons that couple to Standard Model particles and propagate into extra spatial dimensions. The associated production of a graviton and a photon is searched for as well as the effects of virtual graviton exchange in the processes: e+e- -> gamma gamma, ZZ, WW, mu mu, tau tau, qq and ee No evidence for this new interaction is found in the data sample collected by the L3 detector at LEP at centre-of-mass energies up to 183 GeV. Limits close to 1 TeV on the scale of this new scenario of quantum gravity are set

Measurement of inclusive D*+- and associated dijet cross sections in photoproduction at HERA

Inclusive photoproduction of D*+- mesons has been measured for photon-proton centre-of-mass energies in the range 130 < W < 280 GeV and a photon virtuality Q^2 < 1 GeV^2. The data sample used corresponds to an integrated luminosity of 37 pb^-1. Total and differential cross sections as functions of the D* transverse momentum and pseudorapidity are presented in restricted kinematical regions and the data are compared with next-to-leading order (NLO) perturbative QCD calculations using the "massive charm" and "massless charm" schemes. The measured cross sections are generally above the NLO calculations, in particular in the forward (proton) direction. The large data sample also allows the study of dijet production associated with charm. A significant resolved as well as a direct photon component contribute to the cross section. Leading order QCD Monte Carlo calculations indicate that the resolved contribution arises from a significant charm component in the photon. A massive charm NLO parton level calculation yields lower cross sections compared to the measured results in a kinematic region where the resolved photon contribution is significant.Comment: 32 pages including 6 figure

Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference

Measurement of the diffractive structure function in deep inelastic scattering at HERA

This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in $ep$ interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of \xpom, the momentum fraction lost by the proton, of $\beta$, the momentum fraction of the struck quark with respect to \xpom, and of $Q^2$. The \xpom dependence is consistent with the form \xpoma where $a~=~1.30~\pm~0.08~(stat)~^{+~0.08}_{-~0.14}~(sys)$ in all bins of $\beta$ and $Q^2$. In the measured $Q^2$ range, the diffractive structure function approximately scales with $Q^2$ at fixed $\beta$. In an Ingelman-Schlein type model, where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil