Virtual peer mentoring: A partnership between two UK Medical Schools

The first-year student experience in Higher Education (HE) is complex due to the multiple life changing events occurring within this period. It is therefore important that universities embed accessible welfare support for students transitioning into HE. With near-peer support receiving recent credit for its benefit to medical students, the University of Nottingham (UoN) Medical School established a peer mentoring scheme where second-year students act as mentors to their first-year peers. The establishment of the Lincoln Medical School (LMS) in 2018, formed from a partnership between UoN and University of Lincoln (UoL), led to the inception of the Virtual Peer Mentoring (VPM) scheme. With the acknowledgement that there was a lack of near-peer support for the LMS students, VPMs were recruited from a pool of students who had been peer mentors at the UoN Medical School, with the responsibility of offering support to this cohort of students virtually, given the separate locations of the two campuses. As a novel concept between two UK Medical Schools, an evaluation of the VPM scheme revealed a positive experience for the VPMs. However, challenges identified by the peer mentees included the lack of face-to-face interactions, limited insight into the geographical and local knowledge of Lincoln and the limited use of technology to aid the virtual relationship. In acknowledging these limitations, with adjustments, there is scope to refine and enhance the VPM scheme, especially within the current climate of the coronavirus pandemic and beyond

Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype

Histopathology, clinical chemistry, hematology and gene expression data were collected from the rat liver and blood after treatment with eight known hepatotoxins

High Natality Rates of Endangered Steller Sea Lions in Kenai Fjords, Alaska and Perceptions of Population Status in the Gulf of Alaska

Steller sea lions experienced a dramatic population collapse of more than 80% in the late 1970s through the 1990s across their western range in Alaska. One of several competing hypotheses about the cause holds that reduced female reproductive rates (natality) substantively contributed to the decline and continue to limit recovery in the Gulf of Alaska despite the fact that there have been very few attempts to directly measure natality in this species. We conducted a longitudinal study of natality among individual Steller sea lions (n = 151) at a rookery and nearby haulouts in Kenai Fjords, Gulf of Alaska during 2003–2009. Multi-state models were built and tested in Program MARK to estimate survival, resighting, and state transition probabilities dependent on whether or not a female gave birth in the previous year. The models that most closely fit the data suggested that females which gave birth had a higher probability of surviving and giving birth in the following year compared to females that did not give birth, indicating some females are more fit than others. Natality, estimated at 69%, was similar to natality for Steller sea lions in the Gulf of Alaska prior to their decline (67%) and much greater than the published estimate for the 2000s (43%) which was hypothesized from an inferential population dynamic model. Reasons for the disparity are discussed, and could be resolved by additional longitudinal estimates of natality at this and other rookeries over changing ocean climate regimes. Such estimates would provide an appropriate assessment of a key parameter of population dynamics in this endangered species which has heretofore been lacking. Without support for depressed natality as the explanation for a lack of recovery of Steller sea lions in the Gulf of Alaska, alternative hypotheses must be more seriously considered

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message.</p> <p>Methods/design</p> <p>The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with <b><it>informed</it></b>, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension.</p> <p>For each of the three replicates there will be three intervention groups. The first group will receive <b><it>informed </it></b>with an attached postcard-sized, short, directive "outsert." The second intervention group will receive <b><it>informed </it></b>with a two-page explanatory "insert" on the same topic. The third intervention group will receive <b><it>informed</it></b>, with both the above-mentioned outsert and insert. The control group will receive <b><it>informed </it></b>only, without either an outsert or insert.</p> <p>Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours.</p> <p>A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling.</p> <p>Trial registration number</p> <p>Current controlled trial ISRCTN72772651.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival