The effect of hypothermia on influx of leukocytes in the digital lamellae of horses with oligofructose-induced laminitis

Sepsis-related laminitis (SRL) is a common complication in the septic/endotoxemic critically-ill equine patient, in which lamellar injury and failure commonly lead to crippling distal displacement of the distal phalanx. Similar to organ injury in human sepsis, lamellar injury in SRL has been associated with inflammatory events, including the influx of leukocytes into the lamellar tissue and markedly increased expression of a wide array of inflammatory mediators at the onset of Obel grade 1 (OG1) laminitis. The only treatment reported both clinically and experimentally to protect the lamellae in SRL, local hypothermia (“cryotherapy”), has been demonstrated to effectively inhibit lamellar expression of multiple inflammatory mediators when initiated at the time of administration of a carbohydrate overload in experimental models of SRL. However, the effect of hypothermia on leukocyte influx into affected tissue has not been assessed. We hypothesized that cryotherapy inhibits leukocyte emigration into the digital lamellae in SRL. Immunohistochemical staining using leukocyte markers MAC387 (marker of neutrophils, activated monocytes) and CD163 (monocyte/macrophage-specific marker) was performed on archived lamellar tissue samples from an experimental model of SRL in which one forelimb was maintained at ambient temperature (AMB) and one forelimb was immersed in ice water (ICE) immediately following enteral oligofructose administration (10\ua0g/kg, n\ua0=\ua014 horses). Lamellae were harvested at 24\ua0h post-oligofructose administration (DEV, n\ua0=\ua07) or at the onset of OG1 laminitis (OG1, n\ua0=\ua07). Both MAC387-positive and CD163-positive cells were counted by a single blinded investigator on images [n\ua0=\ua010 (40× fields/digit for MAC387 and 20\ua0x fields/digit for CD163)] obtained using Aperio microscopy imaging analysis software. Data were assessed for normality and analyzed with a paired t-test and one-way ANOVA with significance set at p\ua

Detecting the start of an influenza outbreak using exponentially weighted moving average charts

Background. Influenza viruses cause seasonal outbreaks in temperate climates, usually during winter and early spring, and are endemic in tropical climates. The severity and length of influenza outbreaks vary from year to year. Quick and reliable detection of the start of an outbreak is needed to promote public health measures. Methods. We propose the use of an exponentially weighted moving average (EWMA) control chart of laboratory confirmed influenza counts to detect the start and end of influenza outbreaks. Results. The chart is shown to provide timely signals in an example application with seven years of data from Victoria, Australia. Conclusions. The EWMA control chart could be applied in other applications to quickly detect influenza outbreaks

A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex.

Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes

The impact of the Great Exhibition of 1851 on the development of technical education during the second half of the nineteenth century

This paper examines the contribution made by the mechanics’ institute movement in Britain just prior to, and following, the opening of the Great Exhibition of 1851 in London. It argues that far from making little contribution to education, as often portrayed by historians, the movement was ideally positioned to respond to the findings of the Exhibition, which were that foreign goods on display were often more advanced than those produced in Britain. The paper highlights, through a regional study, how well suited mechanics’ institutes were in organising their own exhibitions, providing the idea of this first international exhibition. Subsequently, many offered nationally recognised technical subject examinations through relevant education as well as informing government commissions, prior to the passing of the Technical Instruction Acts in 1889 and the Local Taxation Act of 1890. These acts effectively put mechanics’ institutes into state ownership as the first step in developing further education for all in Britai

Identifying challenges to implementation of clinical practice guidelines for sentinel lymph node biopsy in patients with melanoma in Australia: Protocol paper for a mixed methods study

Introduction Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1mm in thickness (or >0.8mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAFdirected molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. Methods and analysis This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis.This work was funded by the Melanoma Centre of Research Excellence grant (1135285) from the Australian National Health and Medical Research Council (NHMRC). RLM received funding from an NHMRC Translating Research into Practice Fellowship (1150989). AEC received an NHMRC Career Development Fellowship (1147843) and Cancer Institute NSW Career Development Fellowship (15/CDF/1-14)

Health-related quality of life and a cost-utility simulation of adults in the UK with osteogenesis imperfecta, X-linked hypophosphatemia and fibrous dysplasia.

BACKGROUND: Health-related quality of life of adults with osteogenesis imperfecta (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly described. The aim of this study was to describe the HRQoL of adults with osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and perform a cost-utility simulation to calculate the maximum cost that a health care system would be willing to pay for a hypothetical treatment of a rare bone disease. RESULTS: Participants completed the EQ-5D-5 L questionnaire between September 2014 and March 2016. For the economic simulation, we considered a hypothetical treatment that would be applied to OI participants in the lower tertile of the health utility score. A total of 109 study participants fully completed the EQ-5D-5 L questionnaire (response rate 63%). Pain/discomfort was the most problematic domain for participants with all three diseases (FD 31%, XLH 25%, OI 16%). The economic simulation identified an expected treatment impact of +2.5 QALYs gained per person during the 10-year period, which led to a willing to pay of £14,355 annually for a health care system willing to pay up to £50,000 for each additional QALY gained by an intervention. CONCLUSIONS: This is the first study to quantitatively measure and compare the HRQoL of adults with OI, FD and XLH and the first to use such data to conduct an economic simulation leading to healthcare system willingness-to-pay estimates for treatment of musculoskeletal rare diseases at various cost-effectiveness thresholds

Measurement of the WW Boson Mass

A measurement of the mass of the $W$ boson is presented based on a sample of 5982 $W \rightarrow e \nu$ decays observed in $p\overline{p}$ collisions at $\sqrt{s}$ = 1.8~TeV with the D\O\ detector during the 1992--1993 run. From a fit to the transverse mass spectrum, combined with measurements of the $Z$ boson mass, the $W$ boson mass is measured to be $M_W = 80.350 \pm 0.140 (stat.) \pm 0.165 (syst.) \pm 0.160 (scale) GeV/c^2$.Comment: 12 pages, LaTex, style Revtex, including 3 postscript figures (submitted to PRL

Search for First Generation Scalar Leptoquark Pairs in ppbar Collisions at sqrt(s)=1.8 TeV

We have searched for first generation scalar leptoquark (LQ) pairs in the enu+jets channel using ppbar collider data (integrated luminosity= 115 pb^-1) collected by the DZero experiment at the Fermilab Tevatron during 1992-96. The analysis yields no candidate events. We combine the results with those from the ee+jets and nunu+jets channels to obtain 95% confidence level (CL) upper limits on the LQ pair production cross section as a function of mass and of beta, the branching fraction to a charged lepton. Comparing with the next-to-leading order theory, we set 95% CL lower limits on the LQ mass of 225, 204, and 79 GeV/c^2 for beta=1, 1/2, and 0, respectively.Comment: 14 pages, 4 figures, submitted to Physical Review Letters Replaced to correct visitor addresse

Measurement of the Top Quark Mass Using Dilepton Events

The D0 collaboration has performed a measurement of the top quark mass based on six candidate events for the process t tbar -> b W+ bbar W-, where the W bosons decay to e nu or mu nu. This sample was collected during an exposure of the D0 detector to an integrated luminosity of 125 pb^-1 of sqrt(s)=1.8 TeV p-pbar collisions. We obtain mt = 168.4 +- 12.3 (stat) +- 3.7 (sys) GeV/c^2, consistent with the measurement obtained using single-lepton events. Combination of the single-lepton and dilepton results yields mt = 172.0 +- 7.5 GeV/c^2.Comment: 12 pages, 3 figure

Search for Top Squark Pair Production in the Dielectron Channel

This report describes the first search for top squark pair production in the channel stop_1 stopbar_1 -> b bbar chargino_1 chargino_1 -> ee+jets+MEt using 74.9 +- 8.9 pb^-1 of data collected using the D0 detector. A 95% confidence level upper limit on sigma*B is presented. The limit is above the theoretical expectation for sigma*B for this process, but does show the sensitivity of the current D0 data set to a particular topology for new physics.Comment: Five pages, including three figures, submitted to PRD Brief Report