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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.

Clinical datasets are commonly limited in size, thus restraining applications of Machine Learning (ML) techniques for predictive modelling in clinical research and organ transplantation. We explored the potential of Decision Tree (DT) and Random Forest (RF) classification models, in the context of small dataset of 80 samples, for outcome prediction in high-risk kidney transplantation. The DT and RF models identified the key risk factors associated with acute rejection: the levels of the donor specific IgG antibodies, the levels of IgG4 subclass and the number of human leucocyte antigen mismatches between the donor and recipient. Furthermore, the DT model determined dangerous levels of donor-specific IgG subclass antibodies, thus demonstrating the potential of discovering new properties in the data when traditional statistical tools are unable to capture them. The DT and RF classifiers developed in this work predicted early transplant rejection with accuracy of 85%, thus offering an accurate decision support tool for doctors tasked with predicting outcomes of kidney transplantation in advance of the clinical intervention.

"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.

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 ...

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 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.

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.

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.

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.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

Introduction: This small scale qualitative research study investigated the perceptions by both academic tutors and clinical placement educators of integrating the research-informed teaching experience (RiTe) within an undergraduate radiography curriculum to support the learning and practice of image quality and dose optimization.\ud \ud \ud Method: A purposeful sampling approach was used to recruit participants and two asynchronous online focus groups (OFG) were used for data collection. An inductive thematic approach was taken to analyse both sets of OFG data.\ud \ud \ud Results and discussion: Five academic tutors and four clinical placement educators participated in the research. Three overarching themes common to both sets of OFG data were identified. Findings confirmed that both OFGs felt that the RiTe supported student learning of image quality and dose optimization as well as the development of research skills. However, the clinical placement educators did identify that students may find it difficult to transfer and apply this knowledge into practice (theory-practice gap).\ud \ud \ud Conclusion: Results from both OFGs suppor tRiT ewith regard tot he teaching and practice of image quality and dose optimization.However, greater involvement by clinical placement educators may help to overcome issues with the translation of RiTe by students into the clinical environment (theory-practice gap) and support its continued development within the curriculum. It was also identified that RiTe could be developed for qualified staff for continued professional development.

Aim To explore the experiences of students and tutors who participated in a residential multi-cultural and multi-professional 3 week summer school event (OPTIMAX). Method A grounded theory approach was adopted. Two semi-structured focus group interviews (student and tutor) were conducted to explore participant experiences. Both focus groups were audio recorded and then transcribed and coded to identify the main themes and draw conclusions. Results Inductive coding defined categories and sub-categories to explore the relationships within and between the two sets of focus group data. Discussion OPTIMAX was seen a positive experience by both students and tutors and provided an opportunity to undertake team learning with peers from different countries or professional backgrounds. However, consideration needs to be given to team size and tutor leadership. Summary By participating with international collaborative projects such as this, there is an opportunity to develop learning and explore current practices within radiography.

Summary A diagnosis of transmural ileal ganglioneuromatosis was made in a 15-day-old goat that was found dead following a period of diarrhoea and inappetence. Grossly, the entire length of the wall of the ileum was pale and firm with a variably segmental to transmural thickening. Microscopically, the ileal transmural thickening was due to a diffuse proliferation of both ganglionic and glial cells forming cell nests or packets that infiltrated the wall and into the mesentery surrounding a mesenteric lymph node. The neoplastic ganglionic cells were immunoreactive for S100, synaptophysin and triple neurofilament, while the glial spindle cells were immunoreactive with glial fibrillary acidic protein, S100 and laminin confirming their Schwann cell identity. Nerve fibres expressing neurofilament protein 200 and phosphorylated neurofilament (SMI-31) were observed rarely. Ganglioneuromatosis is defined as diffuse exuberant proliferation of all components of the intestinal ganglionic plexuses. In man, the transmural form has more grave clinical consequences than a focal pattern and is commonly associated with germline mutations in the RET proto-oncogene. Whether there is any comparable molecular genetic abnormality in animals remains unknown; however, ganglioneuromatosis needs to be included in the differential diagnosis of tumours of the autonomic enteric nervous system.

Aim Previously we reported on focus group research which explored the level 4 (year 1) student experience of the Research-informed Teaching experience (RiTe). This article discusses follow up research with a new student cohort. Method An online questionnaire was used to explore the level 4 student cohort experience of RiTe. A Multi-method approach was taken to analyse the data, identify themes and link questionnaire findings with those from the focus group research. Results A 54% (27/50) response rate was achieved. Students found RiTe to be a positive experience and there was strong agreement that it had increased their knowledge of research methods and understanding of key areas of practice. Conclusions Results from the questionnaire supported the focus group findings. One of the key factors in the success of RiTe was that of collaborative learning. This was achieved by the students undertaking an inquiry and situated approach to learning within small groups.

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

This article discusses the piloting and evaluation of the Research-informed Teaching experience (RiTe) project. The aim of RiTe was to link teaching and learning with research within an undergraduate diagnostic radiography curriculum. A preliminary pilot study of RiTe was undertaken with a group of level 4 (year 1) volunteer BSc (Hons) diagnostic radiography students to evaluate their experiences. The students undertook a weeklong set of activities to facilitate their understanding of the effects of X-ray exposure factor settings on image quality and patient radiation dose. A mixed methods approach using a group interview with the students in conjunction with a student evaluation form was used to assess their experiences. Analysis of both sets of data revealed a positive student learning experience, although the student perception of the purpose of RiTe needed to be more explicit. RiTe has now become integrated into the level 4 curriculum. Further work is planned to better examine the student holistic exp...

Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues.To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders.A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders.A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD.The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.

Aim This article discusses the level 4 (year 1) diagnostic radiography student holistic experience of the Research-informed Teaching experience (RiTe) at the University of Salford, UK. The purpose of RiTe is to expose undergraduate radiography students to more formal research, as part of their normal teaching and learning experience. Method A grounded theory approach was adopted and a focus group with eight level 4 students was used to explore and evaluate the student experience and perception of RiTe. Results Open coding defined categories and sub-categories, with axial and selective coding used to interrogate and explore the relationships between the focus group data. A number of insights were gained into the student holistic experience of RiTe. The issue of leadership for level 4 students was also identified. Discussion The focus group participants found RiTe to be an extremely positive learning experience. RiTe also facilitated their translation of learnt theory into clinical skills knowledge alongside their understanding of and desire to participate in more research as undergraduates. The article also highlights areas for future research.

Highlights? Mathematical models to describe antibody (IgG, IgA and IgM) in vivo kinetics. ? Method to predict the immune response and treatment effectiveness. ? Apheresis modality should be chosen to target specific antibody classes. When any foreign object is found in the human body antibodies are generated that mark it for removal by the immune system. In most cases these are natural and healthy responses; however, when considering organ transplants the immune response to the implanted organ must be kept to a minimum to avoid host rejection. To reduce the host's immune response to the implant, clinicians are able to manipulate the antibody dynamics through drug therapy, to minimise the antibody synthesis (immunosuppression), and by the removal of antibodies directly from the patients' blood, a process known as apheresis. In this paper models are presented that describe the in vivo kinetics of three immune complexes which are routinely measured pre- and post-operatively in implant patients, namely IgA, IgG and IgM. These models are then used to analyse the effective clearance rates of different apheresis methods (plasmapheresis, plasma absorption or plasma exchange) and to quantify the impact immune-suppression drugs have on the underlying antibody synthesis. It is hoped that the simplicity of the mathematical models, and associated implementation, will allow the translation of knowledge gained of the process dynamics to positively impact future patient diagnosis and treatment.

Primary and secondary nervous system involvement occurs in 4% and 5%–12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes. In this study, we studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary (n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16; 43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12 lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic study identified 6 different anatomically based histologically defined patterns of lymphoma infiltration in the nervous system of dogs. Different and distinct combinations of anatomical patterns correlated with specific lymphoma subtypes. Lymphoma infiltration within the meningeal, perivascular, and periventricular compartments were characteristic of DLBCL, whereas peripheral nerve involvement was a frequent feature of PTCL. Similarly cell counts above 64 cells/μL in cerebrospinal samples correlated best with marked meningeal and periventricular lymphoma infiltration histologically. Prospective studies are needed in order to confirm the hypothesis that these combinations of histological neuroanatomic patterns reflect targeting of receptors specific for the lymphoma subtypes at these various sites.

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options. This position paper was written on behalf of the Descartes Working Group and ERBP, which are both official bodies of the ERA-EDTA. Both Descartes and ERBP are financially supported by ERA-EDTA. Ionuţ Nistor is a fellow of ERBP, amember of the Methods Support Team of ERBP, and supported by a grant of the ERA-EDTA.

Background Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting young horses of various breeds that resembles ataxia with vitamin E deficiency in humans, an inherited disorder caused by mutations in the alpha-tocopherol transfer protein gene (TTPA). To evaluate variants found upon sequencing TTPA in the horse, the mode of inheritance for NAD/EDM had to be established. Hypothesis NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in TTPA. Animals 88 clinically phenotyped (35 affected [ataxia score ≥2], 53 unaffected) QHs with a diagnosis of NAD/EDM with 6 affected and 4 unaffected cases confirmed at postmortem examination. Procedures Pedigrees and genotypes across 54,000 single nucleotide polymorphism (SNP) markers were assessed to determine heritability and mode of inheritance of NAD/EDM. TTPA sequence of exon/intron boundaries was evaluated in 2 affected and 2 control horses. An association analysis was performed by 71 SNPs surrounding TTPA and 8 SNPs within TTPA that were discovered by sequencing. RT-PCR for TTPA was performed on mRNA from the liver of 4 affected and 4 control horses. Results Equine NAD/EDM appears to be inherited as a polygenic trait and, within this family of QHs, demonstrates high heritability. Sequencing of TTPA identified 12 variants. No significant association was found using the 79 available variants in and surrounding TTPA. RT-PCR yielded PCR products of equivalent sizes between affected cases and controls. Conclusions and Clinical Importance NAD/EDM demonstrates heritability in this family of QHs. Variants in TTPA are not responsible for NAD/EDM in this study population.

Adenovirus-associated enteritis was diagnosed by histopathology of small intestine in a 2-year-old alpaca ( Vicugna pacos). Electron microscopy confirmed intracytoplasmic and intranuclear adenoviral particles within enterocytes. Nucleic acid was extracted from paraffin-embedded tissue sections, and a pan-adenovirus nested polymerase chain reaction (PCR) assay was employed to target a partial sequence of the polymerase gene. The PCR product (321 bp) was cloned and sequenced. Comparison of the nucleotide sequence against the National Center for Biotechnology Information (NCBI) nucleotide database demonstrated 68% identity with the isolates Canine adenovirus 1 and Bovine adenovirus 3. Comparison of the predicted amino acid sequence against the NCBI database demonstrated 75% identity with Bovine adenovirus 3. Phylogenetic analysis supported the relatively close relationship of this isolate to Bovine adenovirus 3, but the alpaca isolate was sufficiently distant to be considered a potentially novel adenovirus for this species.

Background: The role of the complement system in antibody-mediated rejection has been investigated in relation to circulating complement interacting with renal microvascular endothelium, resulting in the formation of peritubular capillary C4d. However, the possible importance of local complement synthesis is less clear. The aim of this study was to determine whether human vascular endothelium could produce C4 in response to stimulation in vitro. METHODS: Human microvascular endothelial cells and glomerular endothelial cells were stimulated with endotoxins, cytokines, and human leukocyte antigen-specific antibodies. Synthesis of complement was investigated using western blotting and indirect immunofluorescence. De novo C4 synthesis was confirmed by using C4 small interfering RNA. RESULTS: Glomerular and microvascular endothelium, both produce C3 and C4 complement protein. Complement synthesis was stimulant-specific-C3 was produced mainly after stimulation with lipopolysaccharide whereas C4 synthesis occurred on treatment with gamma interferon. Culture with human leukocyte antigen-specific antibodies resulted in a significant increase of C4 protein synthesis by both cell lines. CONCLUSIONS: We have shown for the first time that human microvascular endothelium can be stimulated to synthesize C4 in vitro. The implications of this for clinical transplantation, especially in the context of antibody-mediated rejection, its histological interpretation and as a potential target for therapy would have to be determined by further studies. © 2012 Lippincott Williams & Wilkins.

Blood group (ABO) incompatible transplants carry an increased risk of rejection. This risk could be dramatically reduced by the removal and suppression of the antibody types that would attack the donor organ. A prerequisite for this removal is an experimental procedure that can estimate the binding affinities of multiple antibodies from patient blood samples. This paper presents the usage of surface plasmon resonance (SPR) experiments with a pre existing mathematical model and a recently created expanded version of it that can estimate multiple antibody binding affinities from parallel experiments. SPR experiments were conducted on purified patient antibody samples of the IgG and IgA isotype, as well as mixed antibody from the other isotypes. The result of these experiments was analyzed with both mathematical models, and the expanded model was demonstrated to give a vastly improved fit. Estimates of antibody binding affinity were compared between samples and the non IgG/IgA protein sample was seen to have the highest binding affinity.

Background. Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes. Methods. Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant. Results. Mean follow-up posttransplantation was 39.6 (range 2-91) months. Patient survival after the first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was 97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years in the CDC+ve than in the CDC-ve/DSA+ve group at 45.6% and 88.6%, respectively (P < 0.03). Five-year graft survival in the DSA+ve group was 82.1%. Rejection occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the DSA+ve patients (P < 0.003). Conclusions. HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

Cryofiltration is a technique in which plasma is separated from blood and chilled, leading to the formation of "cryogel", a composite of heparin, fibronectin, fibrinogen, immunoglobulins, and other proteins. This is retained by further filtration and plasma is returned to the patient. There may be a role for cryofiltration in the treatment of cryoglobulinemia or where the application of other forms of plasmapheresis or immunoadsorption is limited. Five patients received six courses of cryofiltration. Two patients had cryoglobulinemia and three were treated before HLA antibody-incompatible renal transplantation. The treatment was associated with few adverse effects, and it was possible to treat up to 120 mL/kg plasma per session. There was a good clinical response in four patients. One patient was switched back to double filtration plasmapheresis (DFPP) because cryofiltration seemed to remove HLA antibodies less effectively, but the other two transplants have excellent function. In the cryoglobulinemia patients there was excellent clearance of cryoglobulins during each treatment (mean decrease of 78.2 (SD 14.1)% per treatment). Compared with DFPP, fewer immunoglobulins were removed and the mean percentage reductions in immunoglobulin G per treatment were 36.0 (4.0)% for cryoglobulinemia and 59.2 (2.5)% for DFPP (P < 0.01), with respective mean plasma volumes of 64.2 (10.3) and 71.1 (6.8) mL/kg treated. Cryofiltration offers a treatment choice in patients with cryoglobulinemia and in those who may not be able to tolerate high-volume DFPP. The technique used in the patients described here was less effective than DFPP; however, use of an alternative fractionator and treatment of higher plasma volumes may enhance the efficiency of cryofiltration.

Although histologic examination following stereotactic or surgical brain biopsy is required for definitive antemortem diagnosis of intracranial neoplasms, these tumors are often associated with magnetic resonance (MR) imaging features that warrant a presumptive or prioritized differential diagnosis. The MR imaging features of common canine central nervous system (CNS), adenohypophyseal, and metastatic intracranial neoplasms are reviewed. Characterization of neoplasms by histologic type and biological grade is based on the 2007 World Health Organization classification system for CNS tumors in humans.

Antibody incompatible transplantation (AiT) is on the rise. This is because of advances in detection of donor specific antibodies, even at very low levels. In spite of this there is an increased risk of acute antibody mediated rejection. There are multiple protocols to prevent and treat antibody mediated rejection. Though they are reasonably successful in reversing acute rejection, graft loss still occurs due to ongoing chronic antibody mediated rejection.