PeerWise - The Marmite of Veterinary Student Learning

PeerWise is a free online student-centred collaborative learning tool with which students anonymously author, answer, and evaluate multiple choice questions (MCQs). Features such as commenting on questions, rating questions and comments, and appearing on leaderboards, can encourage healthy competition, engage students in reflection and debate, and enhance their communication skills. PeerWise has been used in diverse subject areas but never previously in Veterinary Medicine. The Veterinary undergraduates at the University of Glasgow are a distinct cohort; academically gifted and often highly strategic in their learning due to time pressures and volume of course material. In 2010-11 we introduced PeerWise into 1st year Veterinary Biomolecular Sciences in the Glasgow Bachelor of Veterinary Medicine and Surgery programme. To scaffold PeerWise use, a short interactive session introduced students to the tool and to the basic principles of good MCQ authorship. Students were asked to author four and answer forty MCQs throughout the academic year. Participation was encouraged by an allocation of up to 5% of the final year mark and inclusion of studentauthored questions in the first summative examination. Our analysis focuses on engagement of the class with the\ud tool and their perceptions of its use. All 141 students in the class engaged with PeerWise and the majority contributed beyond that which was stipulated. Student engagement with PeerWise prior to a summative exam was positively correlated to exam score, yielding a relationship that was highly significant (p<0.001). Student perceptions of PeerWise were predominantly positive with explicit recognition of its value as a learning and revision tool, and more than two thirds of the class in agreement that question authoring and answering reinforced their learning. There was clear polarisation of views, however, and those students who did not like PeerWise were vociferous in their dislike, the biggest criticism being lack of moderation by staff

The Characterisation of Specific EHV-4 Genes

Equine herpesvirus 4 (EHV-1) is an alphaherpesvirus primarily associated with respiratory disease. The genome of this virus has been characterised (strain 1942) and a BamHI library prepared (Cullinane et al. , 1988). This dissertation reports the localisation of five intact EHV-4 genes within the U1 component of the genome . Homologues of HSV-1 genes UL22 (gH), UL23 (thymidine kinase), UL24, and UL44 (gC) were identified. An additional EHV-4 mapped to the left of the gC gene homologue has no apparent HSV-1 homologue. Partial nucleotide sequences were determined for EHV-4 homologues of HSV-1 genes UL21, and UL43. The map positions, nucleotide sequence, and predicited amino acid sequence of the products of these genes are detailed. The EHV-4 polypeptides are compared to their counterparts in other herpesviruses. Sequence analysis revealed a region of direct repeats and a putative origin of DNA replication proximal to the 3' end of the gH gene. Five peptides derived from the predicted amino acid sequences of the EHV-4 gpl3 (gC) and gH polypeptides were tested for their immunogenicity in a hamster model. The implications of these data are discussed in reference to the relatedness of EHV-4 to other herpesviruses in terms of sequence conservation (at the amino acid level) and in genome organisation. Finally, possible applications of the data to the development of novel EHV vaccines and diagnostic tests are outlined

What is the association between childhood adversity and subsequent chronic pain in adulthood? A systematic review

Funding: NHS Education for Scotland. KN was academic fellow from 2018 to 2022. SEEM was funded through an academic clinical fellowship from the Scottish Government's Chief Scientist Office (CSO grant number CAF_17_06). DS is a fellow on the Multimorbidity Doctoral Training Programme for Health Professionals, which is supported by the Wellcome Trust [grant number 223499/Z/21/Z].Background Adverse childhood experiences and chronic pain are complex problems affecting millions of people worldwide, and result in significant healthcare utilisation. Our review aimed to determine known associations between adversity in childhood and chronic pain in adulthood. Methods We performed a prospectively registered systematic review (PROSPERO ID: 135625). Six electronic databases (Pubmed, Medline, Cochrane, Scopus, APA PsycNet, Web of Science) were searched from January 1, 2009 until May 30, 2022. Titles and abstracts were screened, and all original research studies examining associations between adverse childhood experiences and chronic pain in adulthood were considered for inclusion. Full texts were reviewed, and a narrative synthesis was used to identify themes from extracted data. Ten percent of studies were dual reviewed to assess inter-rater reliability. Quality assessment of study methodology was undertaken using recognised tools. Results Sixty-eight eligible studies describing 196 130 participants were included. Studies covered 15 different types of childhood adversity and 10 different chronic pain diagnoses. Dual reviewed papers had a Cohen's kappa reliability rating of 0.71. Most studies were of retrospective nature and of good quality. There were consistent associations between adverse childhood experiences and chronic pain in adulthood, with a ‘dose’-dependent relationship. Poor mental health was found to mediate the detrimental connection between adverse childhood experiences and chronic pain. Conclusion A strong association was found between adverse childhood experiences and chronic pain in adulthood. Adverse childhood experiences should be considered in patient assessment, and early intervention to prevent adverse childhood experiences may help reduce the genesis of chronic pain. Further research into assessment and interventions to address adverse childhood experiences is needed.Publisher PDFPeer reviewe

Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates

The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease the results of this assay may be used to support a diagnosis of non-effusive FIP

Risk Factors for Mobility Decline in Community-Dwelling Older Adults: A Systematic Literature Review

Mobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate-high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application

The clinical effectiveness of a physiotherapy delivered physical and psychological group intervention for older adults with neurogenic claudication: the BOOST randomised controlled trial.

This is the final version. Available from Oxford University Press via the DOI in this record. BACKGROUND: Neurogenic claudication (NC) is a debilitating spinal condition affecting older adults' mobility and quality of life. METHODS: A randomised controlled trial of 438 participants evaluated the effectiveness of a physical and psychological group intervention (BOOST programme) compared to physiotherapy assessment and tailored advice (best practice advice [BPA]) for older adults with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records and randomised 2:1 to the BOOST programme or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data was also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT) and falls. The primary analysis was intention-to-treat. RESULTS: The average age of participants was 74.9 years (SD 6.0) and 57% (246/435) were female. There was no significant difference in ODI scores between treatment groups at 12 months (adjusted mean difference (MD): -1.4 [95% Confidence Intervals (CI) -4.03, 1.17]), but, at 6 months, ODI scores favoured the BOOST programme (adjusted MD: -3.7 [95% CI -6.27, -1.06]). At 12 months, the BOOST programme resulted in greater improvements in walking capacity (6MWT MD 21.7m [95% CI 5.96, 37.38]) and ODI walking item (MD -0.2 [95% CI -0.45, -0.01]) and reduced falls risk (odds ratio 0.6 [95% CI 0.40, 0.98]) compared to BPA. No serious adverse events were related to either treatment. CONCLUSIONS: The BOOST programme substantially improved mobility for older adults with NC. Future iterations of the programme will consider ways to improve long-term pain related disability.National Institute for Health Research (NIHR

The Clinical Effectiveness of a Physiotherapy Delivered Physical and Psychological Group Intervention for Older Adults With Neurogenic Claudication: The BOOST Randomized Controlled Trial

Background Neurogenic claudication (NC) is a debilitating spinal condition affecting older adults’ mobility and quality of life. Methods A randomized controlled trial of 438 participants evaluated the effectiveness of a physical and psychological group intervention (BOOST program) compared to physiotherapy assessment and tailored advice (best practice advice [BPA]) for older adults with NC. Participants were identified from spinal clinics (community and secondary care) and general practice records and randomized 2:1 to the BOOST program or BPA. The primary outcome was the Oswestry Disability Index (ODI) at 12 months. Data were also collected at 6 months. Other outcomes included ODI walking item, 6-minute walk test (6MWT), and falls. The primary analysis was intention-to-treat. Results The average age of participants was 74.9 years (standard deviation [SD] 6.0) and 57% (246/435) were female. There was no significant difference in ODI scores between treatment groups at 12 months (adjusted mean difference [MD]: −1.4 [95% confidence intervals (CI) −4.03, 1.17]), but, at 6 months, ODI scores favored the BOOST program (adjusted MD: −3.7 [95% CI −6.27, −1.06]). At 12 months, the BOOST program resulted in greater improvements in walking capacity (6MWT MD: 21.7m [95% CI 5.96, 37.38]) and ODI walking item (MD: −0.2 [95% CI −0.45, −0.01]) and reduced falls risk (odds ratio: 0.6 [95% CI 0.40, 0.98]) compared to BPA. No serious adverse events were related to either treatment. Conclusions The BOOST program substantially improved mobility for older adults with NC. Future iterations of the program will consider ways to improve long-term pain-related disability. Clinical Trials Registration Number: ISRCTN1269867

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology