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Three dimensional morphometric methods are a powerful tool for comparative analysis of shape. However, morphological shape is often represented using landmarks selected by the user to describe features of perceived importance, and this may lead to over confident prediction of form-function relationships in subsequent analyses. We used Generalized Procrustes Analysis (GPA) of 13 homologous 3D landmarks and spherical harmonics (SPHARM) analysis, a homology-free method that describes the entire shape of a closed surface, to quantify the shape of the calcaneus, a landmark poor structure that is important in hind-limb mechanics, for 111 carnivoran species spanning 12 of 13 terrestrial families. Both approaches document qualitatively similar patterns of shape variation, including a dominant continuum from short/stout to long/narrow calcanea. However, while phylogenetic generalized linear models indicate that locomotor mode best explains shape from the GPA, the same analyses find that shape described by SPHARM is best predicted by foot posture and body mass without a role for locomotor mode, though effect sizes for all are small. User choices regarding morphometric methods can dramatically impact macroevolutionary interpretations of shape change in a single structure, an outcome that is likely exacerbated when readily landmarkable features are few.

OurStats ( https://www.cbrc.net/ourstats ) is a data visualization dashboard developed by the Community-Based Research Centre (CBRC) to increase access to data from the Sex Now surveys—Canada’s largest community-based surveillance study of gay and bisexual men. An evaluation of the OurStats dashboard was conducted using an online survey distributed through the CBRC and Advance Alliance—an alliance of Canada’s leading HIV and queer men’s health organizations. Since being launched in November 2019 (through December 2019), 350 unique visitors used the OurStats Dashboard (5.8 per day). Based on responses from 10 community partners, all respondents said they would probably/definitely use OurStats again and would probably/definitely recommend it to colleagues; nine felt it was much/somewhat better than traditional academic outputs (e.g., poster presentations, journal articles); and seven felt it was much/somewhat better than traditional knowledge translation outputs (e.g., fliers, posters, and social media posts). Respondents said they would use OurStats to identify needs of gay and bisexual men (n = 9), prepare grant/funding applications (n = 9), prepare presentations about Sex Now data (n = 7), and evaluate the impact of local programs (n = 4). Overall, half felt that OurStats was somewhat/extremely easy to use and half felt that it was somewhat difficult to use. The most commonly identified requested improvement was to provide help documentation that explained how each of the display settings changed the visualizations. From these findings, we conclude that dynamic visualizations for community-based survey data are highly feasible and acceptable, provided appropriate support is available to help community partners use these tools.

Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft outcomes. Complement activation by donor-specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross-match-positive). We explored the role of C3d-positive DSAs in sub-stratification of cross-match-positive cases and relate to the graft outcomes. We investigated 139 cross-match-positive living-donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post-transplant. C3d-positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post-transplant. Median follow-up of patients was 48 months (IQR 20.47–77.57). In the multivariable analysis, pretreatment C3d-positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37–7.86). The relative risk of death-censored five-year graft failure was 2.83 (95% CI 1.56–5.13). Patients with both pretreatment and Day 14 C3d-positive DSAs had the worst five-year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d-negative DSA patients with the relative risk of death-censored five-year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub-stratify the risk of poor graft outcome in cross-match-positive living-donor renal transplantation.

BACKGROUND: Integrated cardiothoracic surgery residencies began 2006 to address workforce shortages in cardiothoracic surgery. As more attention has been given to racial and gender disparities, our goal was to examine trends in diversity among integrated cardiothoracic residents. METHODS: All US accredited integrated cardiothoracic programs that had accepted residents through 2020 were included. A resident list was collected through online websites and direct institutional contact. Gender, race, and year of entry were recorded. Linear regression models were used to evaluate racial and gender trends over time. RESULTS: From 2006 through 2020, 321 residents were accepted into integrated cardiothoracic training programs. Men comprised 72% (232/321) of the cohort. The racial distribution was 66.4% White (213/321), 26.2% Asian (84/321), 5.3% Hispanic (17/321), and 2.2% African American (7/321). Over the study period the time slope for Whites was −2.95 (P < .01), indicating an approximately 3% decrease each year. The time slope for Asians was 1.60 (P < .01), whereas the time slope did not change significantly for African Americans (0.10, P = .94) or Hispanics (0.13, P = .91). Adjusting for the number of integrated programs each year as a covariate did not change trends for any race. The time slope did not change significantly over the time period for men (−0.25, P = .71). CONCLUSIONS: Gender and racial diversity have not improved over time in integrated cardiothoracic residencies. Institutions should strive to recruit medical students from underrepresented backgrounds and increase their focus on gender diversity.

Background. \ud HLA incompatible renal transplantation still remains one of best therapeutic options for a subgroup of patients who are highly sensitized and difficult to match but not much is known about its long-term graft and patient survival.\ud \ud Methods. \ud One hundred thirty-four HLA incompatible renal transplantation patients from 2003 to 2018 with a median follow of 6.93 y were analyzed retrospectively to estimate patient and graft survivals. Outcomes were compared with groups defined by baseline crossmatch status and the type and timings of rejection episodes.\ud \ud Results. \ud The overall patient survival was 95%, 90%, and 81%; and graft survival was 95%, 85%, and 70% at 1, 5, and 10 y, respectively. This was similar to the first-time deceased donor transplant cohort. The graft survival for pretreatment cytotoxic-dependent crossmatch (CDC) positive crossmatch group was significantly low at 83%, 64%, and 40% at 1, 5, and 10 y, respectively, compared with other groups (Bead/CDC, P = 0.007; CDC/Flow, P = 0.001; and microbead assay/flow cytometry crossmatch, P = 0.837), although those with a low CDC titer (

Introduction\ud As part of the BSc (Hons) Diagnostic Radiography programme students learn and undertake research relevant to their development as first post radiographers (dose optimisation and image quality) within the Research-Informed Teaching experience (RiTe). Due to the COVID-19 pandemic, the delivery of RiTe to our year 2 students was moved to an online format using Microsoft Teams and Blackboard Collaborate and focused on a key area of current practice - COVID-19 and chest X-ray imaging. Within RiTe students are placed into collaborative enquiry-based learning (CEBL) groups to share tasks, but to also support and learn from one another.\ud \ud Methods\ud An online survey was used to explore the year 2 student cohort task value and self-efficacy of this online version of RiTe.\ud \ud Results\ud A 73% (32/44) response rate was achieved. Students found the online version of RiTe to be a positive learning and development experience. There was strong agreement that they not only found it relevant to their area of practice (task-value), but also strongly agreed that they understood and could master the skills taught (self-efficacy).\ud \ud Conclusion\ud This online version of RiTe was effectively structured to help scaffold student learning and development of research data analysis skills despite the lack of face-to-face teaching. The students also valued the topic area (COVID-19 and chest X-ray imaging). A blended learning approach with RiTe will be used next year with a combination of collaborative online teaching and physical data collection and analysis in the university-based X-ray imaging laboratory. Further evaluation and data collection will also be undertaken.\ud \ud Implications for practice\ud University-based empirical work in groups to learn about research can be replaced by an online mechanism whilst still maintaining task-value and acceptable self-efficacy.

"U = U" is the principle that HIV is untransmittable from people living with an undetectable HIV viral-load. Wide-spread knowledge about U = U is believed to produce public health benefit by reducing HIV-related stigma - promoting wellbeing for people living with HIV. Therefore, we examined the diffusion of U = U with respect to the social position of sexual and gender minority men (SGMM). Participants were SGMM recruited from 16 LGBTQ2S+ pride festivals across Canada. Social position was measured using an index assessing whether participants were (a) trans, (b) a person of colour, (c) Indigenous, (d) born abroad, (e) bisexual or straight, (f) not out, (g) struggling with money, (h) not college educated, (i) and not participating in LGBTQ2S+ Organizations, Queer Pop-ups, or HIV advocacy organizations. Multivariable logistic regression tested whether Index Scores were associated with knowledge about U = U. Among 2681 participants, 72.6% knew about U = U. For HIV-negative/unknown status SGMM, each 1-point increase in Social Positionality Index Scores was associated with a 21% reduction in the odds that they knew about U = U (aOR: 0.79 [0.73, 0.85], per 1-point increase). Results indicate that social marginalization harms the diffusion of HIV-related biomedical knowledge, independent of risk-taking behaviour and other factors.

Antibodies specific for the blood group ABO system antigens are of clinical significance and immunological interest. Routine clinical methods typically employ direct or indirect haemagglutination methods to measure IgM and IgG, respectively. We have developed a simple, single tube method to quantify IgM, IgG, and IgA specific for A and B antigens in order to improve accuracy and reproducibility, and to investigate the relationships between ABO group antibody type, and antibody level. Plasma samples from 300 healthy blood donors were studied. Levels of IgM and IgG binding to reagent group A and B red cells were measure by agglutination (HA) and multi-colour flow cytometry (MC-FC). IgA was also measured by MC-FC. Our FC method was found to be significantly more reproducible than HA for the measurement of blood group A and B specific antibodies. We found statistically significant correlations between antibodies measured by GC-HA and MC-FC, but sufficient differences to indicate that these methods are not equivalent. By MC-FC, IgM, IgG and IgA levels and isotope profiles were found to be dependent on both the donor ABO type and the specificity of the antibody. This study demonstrated heterogeneity in the immunoglobulin class profiles of ABO-blood group specific antibodies within the healthy population. Differences in isotype profiles of ABO-blood group specific antibodies may indicate fundamental differences in the immune mechanisms that generate these antibodies. This is likely to be relevant to the clinical situations where management or diagnosis depend on ABO-specific antibody detection and measurement.

Introduction\ud \ud With the introduction of digital radiography, the feedback between image quality and over-exposure has been partly lost which in some cases has led to a steady increase in dose. Over the years the introduction of exposure index (EI) has been used to resolve this phenomenon referred to as ‘dose creep’. Even though EI is often vendor specific it is always a related of the radiation exposure to the detector. Due to the nature of this relationship EI can also be used as a patient dose indicator, however this is not widely investigated in literature.\ud \ud Methods\ud \ud A total of 420 dose-area-product (DAP) and EI measurements were taken whilst varying kVp, mAs and body habitus on two different anthropomorphic phantoms (pelvis and chest). Using linear regression, the correlation between EI and DAP were examined. Additionally, two separate region of interest (ROI) placements/per phantom where examined in order to research any effect on EI.\ud \ud Results\ud \ud When dividing the data into subsets, a strong correlation between EI and DAP was shown with all R-squared values > 0.987. Comparison between the ROI placements showed a significant difference between EIs for both placements.\ud \ud Conclusion\ud \ud This research shows a clear relationship between EI and radiation dose which is dependent on a wide variety of factors such as ROI placement, body habitus. In addition, pathology and manufacturer specific EI’s are likely to be of influence as well.\ud \ud Implications for practice\ud \ud The combination of DAP and EI might be used as a patient dose indicator. However, the influencing factors as mentioned in the conclusion should be considered and examined before implementation.

Author(s): Toyoda, Izumi; Vernau, William; Sturges, Beverly K; Vernau, Karen M; Rossmeisl, John; Zimmerman, Kurt; Crowe, Chelsea M; Woolard, Kevin; Giuffrida, Michelle; Higgins, Robert J; Dickinson, Peter J | Abstract: BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P l.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P l .001), but overall prognosis was poor.Conclusions and clinical importanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities.

We observe photocatalyst-based regioselectivity distinctions in Diels–Alder reactions using an electron-poor dienophile. We find that one complex, [Cr(Ph2phen)3](BF4)3, offers significantly higher ...

Introduction: Smart glasses can be adapted to display radiographic images to allow clinician’s gaze not to be directionally fixed or predetermined by computer monitor location. This study presents an analysis of eye lens dose during interventional fluoroscopy guided procedures, comparing fixed monitor positions against the use of smart glasses.\ud \ud Methods: Using a head phantom (simulating the clinician), thermoluminescent dosimeters and lead shielded glasses, the dose to the eye was measured for different head ‘rotations and tilts’ for: gaze directed towards the main scattering source (patient / primary beam) to represent potential gaze direction if smart glasses are used; gaze directed to a range of potential computer monitor positions. An anthropomorphic pelvis phantom was utilised to simulate the patient. Accumulated dose rates (µGy.sˉ¹) from five 10-second exposures at 75 kV 25.2 mAs were recorded. \ud \ud Results: An average DAP reading of 758.84 cGy.cm2 was measured during each 10 second exposure. Whilst wearing lead shielded glasses a 6.10 – fold reduction in dose rate to the lens is possible (p\ud \ud Conclusion: If the clinician’s gaze is directed towards the main scattering source a potential exists for reducing eye lens dose compared with fixed location computer monitors. Introduction of lead lined smart glasses into interventional radiology may lead to improvements in patient care, reducing the need for the clinician to look away from the patient to observe a radiographic image.

Background Qualitative studies suggest that substance use is central to the identities and cultures of many gay and bisexual men (gbMSM) – and a salient factor in how they manage HIV risk. To quantitatively assess this, we examined patterns of substance use and associations with awareness, interest, and uptake of key prevention strategies. Methods Canadian gbMSM were recruited online and asked to report their frequency of substance use. Latent class analysis identified patterns in use. Demographic-adjusted multivariable multinomial logistic regression models, stratified by HIV-status, assessed associations with key prevention strategies (TasP awareness, PrEP interest, HIV-testing). Results Among 669 HIV-positive and 7,184 HIV-negative men, six substance use classes were characterized: ‘limited’ (46.0%; i.e., infrequent/low use of most drugs), ‘conventional’ (25.9%; i.e., alcohol, marijuana, and tobacco), ‘club’ (9.5%; i.e., alcohol, cocaine, and psychedelics), ‘sex’ (11.4%; i.e., alcohol, crystal meth, GHB, poppers, and erectile dysfunction drugs), ‘prescription’ (12.1%; i.e., alcohol and prescription drugs), and ‘assorted’ (4.5%; i.e., most drugs) use. Limited use was selected as the referent class in all analyses. Other HIV-positive men were no more likely to have detectable viral-loads, nor were they less likely to know about the preventative benefits of TasP. HIV-negative men in the prescription (aOR:1.37,95%CI:1.15–1.63) and sex (aOR:1.58,95%CI:1.21–2.06) drug use classes were more likely to know about TasP. HIV-negative men in the prescription (aOR:1.6, 95%CI:1.34–1.91), conventional (aOR:1.30,95%CI:1.16–1.45), club (aOR:1.44,95%CI:1.15–1.81), sex (aOR:3.94,95%CI:2.92–5.33), and assorted (aOR:3.06,95%CI:1.64–5.72) use classes were more likely to report interest in taking PrEP. Membership in these classes was associated with higher odds of HIV-testing. Conclusion Among HIV-positive men, we observed high levels of viral-load undetectability and TasP awareness, independent of substance use. Among HIV-negative men, multiple patterns of substance use traditionally associated with heightened risk for acquiring HIV were associated with awareness, interest, and uptake of HIV risk management strategies, contravening stereotypes that link substance use to risk-indifferent attitudes. Disclosure No significant relationships.

Unconscious (or implicit) biases are learned stereotypes that are automatic, unintentional, deeply engrained, universal, and able to influence behavior. Several studies have documented the effects of provider biases on patient care and outcomes. This article provides a framework for exploring the implications for unconscious bias in surgical education and highlights best practices toward minimizing its impact. Presented is the background related to some of the more common unconscious biases and effects on medical students, resident trainees, and academic faculty. Finally, targeted strategies are highlighted for individuals and institutions for identification of biases and the means to address them.

The geographical origins of the Negroes in the Western Hemisphere have always been known, but the exact route between Africa and the present United States has never been clearly defined. Widespread Negro slavery was first introduced into the British Empire in the islands of the Caribbean. Negro slaves were among the earliest people to settle within the territory given by Charles II to the lords proprietors of Carolina. One of the reasons for the establishment of Carolina by the British was the need for a march between Virginia and the Spanish settlements in Florida and the French in the lower Mississippi region. The introduction of an alien element into the English culture within South Carolina necessitated some type of regulation. The slave trade passing through the ports of South Carolina had a far greater impact upon the future United States than its limited and immediate effect on Carolina.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

Background A glass ceiling effect exists for women in male-dominated professions. Recent studies also show a glass-cliff effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty. This study investigated gender and the perception of adverse clinical incidents in transplantation. Methods Prospective randomised web-based survey involving five clinical scenarios presenting two versions of episodes with errors or mistakes, with either a male or female as a randomly named protagonist (Set1 and Set2). To address unconscious bias, the study was described as examining actions following clinical adverse incidents in transplantation. Each scenario was followed by 2 closed questions: (1) clinical performance rating and (2) selection of action required. Reasoning was invited (open-text comments). Responses were analyzed using quantitative and qualitative methods. Results One hundred ninety-one invitees responded; 134 completed questionnaires. There were no statistically significant differences (P > 0.05) in responses between sets for performance ratings or recommended actions. However, for "first solo laparoscopic surgery" scenario, there was some indication that "No Action" was more likely if surgeon was male (P = 0.056). Male responses rated female performance as significantly worse (P = 0.035) for the laboratory-based scenario. One hundred two participants provided open-text comments. Thematic analysis identified 7 themes. Acceptable levels of risk theme demonstrated engendered leadership beliefs, that is, when clinical judgment proved incorrect, males described as forceful but females as needing support. In cases where things went wrong, respondents were more likely to comment females should not have decided to proceed. Conclusions While gender may no longer be an overt issue in perceived performance of senior staff in transplantation, respondents' use of language and their choice of words display elements of unconscious (covert) engendered views.

One-day Workshop delivered to academics and clinical tutors as part of the International student conference in health sciences "Health in our Hands" held at Tartu Healthcare College, Estonia.

Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine learning. This review examines key aspects of this work, performed by us and others.

Background Travelers’ diarrhea (TD) is a leading threat to military readiness. Most trials of rifaximin chemoprophylaxis involve civilians or short-duration travel, whereas military travelers are exposed for longer periods at austere locations and are often physically taxed. We sought to assess efficacy of two regimens among military personnel deployed overseas. Methods This was a multi-site, double-blind, placebo-controlled trial of deployed military, randomized to placebo, rifaximin 550 mg daily, or rifaximin 550 mg twice-daily, for up to 42 days (1:1:1; 6 randomizations/block). Diaries were reviewed with subjects on return. Primary endpoint was time to first unformed stool (TFUS) in a TD episode. Other endpoints were assessed by intention to treat (ITT) and subgroups included incidence of any loose stool, meeting criteria for TD, safety, efficacy, adherence and impact to activity endpoints. Results 343 subjects were included in the ITT population. All UK travelers deployed to a single-site in Kenya; US travelers mostly deployed to various Asia-Pacific locations. Of 73 (21.2%) subjects reporting diarrhea, 42 (57.5%) met TD criteria. Among rifaximin-treated subjects, 15.9% (n=17) reported diarrhea in the twice-daily arm, 20.7% (n=25) in the daily arm, vs. 27.0% (n=31) of placebo recipients; p=.04 and 0.26 respectively. TD was reported by 10.3% (n=11) and 10.7% (n=13) in the daily and twice-daily arms, vs. 15.7% (n=18) among placebo recipients; p=0.24 vs. 0.26 respectively. Among UK personnel, a twice-daily regimen vs. placebo resulted in significantly fewer TD episodes (1.6% vs. 11.9%; p=0.03). Adverse events were similar between groups. Table 1: Demographics, endpoints, and adverse events (Comparisons are across placebo vs. each dosing regimen. Intent-to-treat [ITT] population defined as subjects enrolled into the study, randomized, travelled and had follow-up. p-values calculated from chi-square or Fisher’s exact test [categorical variables] and Wilcoxon-Mann-Whitney test [continuous variables]. Analyses performed on SAS v9.4. BID: twice-daily) Conclusion This is the first trial comparing two high-dose regimens of rifaximin prophylaxis in deployed personnel. Unlike prior reports, neither regimen was associated with an overall significant decrease in TD, potentially due to low overall TD incidence. However, the twice-daily regimen was associated with a numerically lower incidence of diarrheal stool, and in the UK subject group, there was a significant decrease of both TD and diarrheal stool. The impact of variability in regional TD risk, pathogen distribution and adherence in austere deployment environments on efficacy will be reviewed. Disclosures All Authors: No reported disclosures

Choroid plexus tumors (CPTs) occur spontaneously in humans and dogs providing an opportunity for comparative cross species analysis of common tumor mechanisms. Large scale chromosomal copy number alterations are the hallmark of human CPTs and identification of driver genes within these regions is problematic. Copy number alterations in 12 spontaneous dog CPTs were defined using an Illumina 170 K single nucleotide polymorphism array and were characterized by highly recurrent whole chromosomal losses in up to 100% of cases with few chromosome wide gains. Loss of canine chromosomes 2, 5, 8, and 20 were seen in 90%-100% of cases and included regions syntenic to loci within commonly reported whole chromosome losses in human choroid plexus tumors. These regions included previously defined tumor suppressor clusters on chromosome 3p and 17p as well as genes associated with chromosomal instability such as TP53 and VHL. This karyotypic signature is similar to a previously defined hypodiploid subgroup of human choroid plexus carcinomas. The nonrandom, highly recurrent alterations in dog CPTs suggest specific selection pressures and oncogenic mechanisms are present. More extensive analysis of this spontaneous tumor model is warranted and may provide key insights into driver mechanisms common to both species.

HLA specific antibodies vary in their pathogenicity and this is likely to be the net effect of constant chain usage, quantity, specificity, and affinity. Here we have measured the affinity of human monoclonal antibodies for a range of HLA proteins. Purified antibodies and ligands allowed dynamic interactions to be measured directly by surface plasmon resonance. Physiochemical differences between pairs of ligands were quantified using electrostatic mismatch and hydrophobic mismatch scores. \ud \ud All antibodies were characterized by fast on-rates and slow off rates but with a wide range of association rates (kon, 3.63-24.25 × 10(5) per mol per second) and dissociation rates (koff, 0.99-10.93 × 10(-3) per second). Dissociation constants (KD) ranged from 5.9 × 10(-10) M to 3.0 × 10(-8) M. SN320G6 has approximately a twenty-fold greater affinity for HLA A2 compared with SN607D8, but has a similar affinity for HLA-A2 and B57. In contrast, SN607D8 has greater than a twofold greater affinity for HLA-A2 compared with A68. Similarly, WK1D12 has about a threefold greater affinity for HLA-B27 compared with B7. The higher affinity interactions correlate with the specificity of stimulating antigen. This is the first study to directly measure the binding kinetics and affinity constants for human alloantibodies against HLA.

Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) (p0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI1000, peak level was1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others (p0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.

In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.

The 3rd International Transplant Conference took place on 31st October and 1st November 2014 at the University of Warwick, Coventry, UK. Key focal points of the meeting were the exploration of the molecular basis of antibody–antigen interactions and their relation to clinical practice and to share experiences and knowledge regarding strategies to transplant the ‘high-risk’ patient. In addition, lively debate sessions were hosted where controversial clinical and immunological themes were discussed by leading experts in the field.

Falls in the serum levels of donor specific HLA antibodies (DSA) after kidney transplantation are of great clinical interest, as they are associated with resolution of rejection and good long term outcomes in patients at high risk of graft loss. A data-driven model in the form of third order differential equation has been developed to describe the dynamics of the falls in DSA after renal transplantation. The model characterises the post transplant DSA behaviour for two groups of renal transplant recipients: those who experienced acute antibody mediated rejection (AMR) in the first days after operation and those who did not. A variational Bayesian inference method was employed to find the form of the model, infer the system parameters and extract the information of the recognisable patterns and the common features in DSA post transplant dynamics. Three models of different order have been investigated, and the third order linear model with four parameters outperformed the models of lower orders. The inferred deterministic parameters were found to be significantly different between the two groups of people with and without AMR. The eigenvalues for each DSA time series have been calculated and compared between the groups. A higher frequency of oscillation and a faster dissipation rate of antibodies have been found in the AMR group, which demonstrate a potential for intelligent laboratory interrogation of the underlying immunological mechanisms, which at present are entirely opaque.

Acute bacterial septicemia is commonly diagnosed in brook trout Salvelinus fontinalis of Quebec, Canada. The agents most commonly isolated include Aeromonas salmonicida (furunculosis), Aeromonas hydrophila (motile aeromonad septicemia), and Pseudomonas species. Septicemia in brook trout caused by the gram-negative bacterium Edwardsiella tarda was diagnosed for the first time in the province of Quebec from two different fish farms producing stock for fee fishing establishments. Affected fish displayed nonspecific lesions associated with bacterial septicemia including hemorrhages on the gills and viscera and exophthalmia. Stress-associated immunosuppression due to an increase in summer water temperatures and lack of precipitation were considered as primary causes of these disease outbreaks.

BACKGROUND Patients with advanced chronic kidney disease (CKD) experience complex functional and structural changes of the cardiopulmonary and musculoskeletal system. This results in reduced exercise tolerance, quality of life and ultimately premature death. We investigated the relationship between subjective measures of health related quality of life and objective, standardised functional measures for cardiovascular and pulmonary health. METHODS Between April 2010 and January 2013, 143 CKD stage-5 or CKD5d patients (age 46.0±1.1y, 62.2% male), were recruited prospectively. A control group of 83 healthy individuals treated for essential hypertension (HTN; age 53.2±0.9y, 48.22% male) were recruited at random. All patients completed the SF-36 health survey questionnaire, echocardiography, vascular tonometry and cardiopulmonary exercise testing. RESULTS Patients with CKD had significantly lower SF-36 scores than the HTN group; for physical component score (PCS; 45.0 vs 53.9, p