Development of a new scale to measure ambiguity tolerance in veterinary students

The ability to cope with ambiguity and feelings of uncertainty is an essential element of professional practice. Research with physicians has identified that intolerance of ambiguity or uncertainty is linked to stress and some authors have hypothesised that there could be an association between intolerance of ambiguity and burnout (e.g. Cooke et al 2013). We describe the adaptation of the TAMSAD (Tolerance of Ambiguity in Medical Students and Doctors) scale for use with veterinary students. Exploratory factor analysis supports a unidimensional structure for the Ambiguity tolerance construct. Although internal reliability of the 29 item TAMSAD scale is reasonable (α = 0.50), an alternative 27 item scale (drawn from the original 41 items used to develop TAMSAD) shows higher internal reliability for veterinary students (α = 0.67). We conclude that there is good evidence to support the validity of this latter TAVS (Tolerance of Ambiguity in Veterinary students) scale to study ambiguity tolerance in veterinary students

Canadian packaged gluten-free foods are less nutritious than their regular gluten-containing counterparts

Background A strict gluten-free (GF) diet is required for the management of celiac disease (CD). The nutritional adequacy of this diet has been questioned due to the elimination of wheat, an important vehicle for micronutrient fortification and source of fibre. While novel and/or reformulated packaged GF products have rapidly entered the marketplace, providing alternatives to wheat-based staples, it is unknown whether these new products are nutritionally comparable. Methods From a database of 3,851 foods collected across 21 grocery stores in Eastern Canada, we compared the nutrient content of 398 unique GF items with 445 gluten-containing (GC) equivalents. Wilcoxon rank tests were conducted on listed nutrient content (g, mg, µg) per 100 g of product and the nutrient contribution of iron, folate and fibre were evaluated using Health Canada’s nutrient claim regulations. Results GF staples (cereals, breads, flours, pastas) contained 1.3 times more fat and less iron (by 55%), folate (by 44%) and protein (by 36%), than GC counterparts (P < 0.0001). On average, GF pastas had only 37% of the fibre in GC pastas (P < 0.0001). Notably, GF and GC flours were equivalent in nutrient content. Despite GF and GC flours having similar nutritional content, the vast majority of the processed GF foods fell short in key nutrients. Discussion Packaged GF foods in Canada are generally less nutritious than their GC counterparts, suggesting that GF diets should not be promoted to those who do not require it. The use of nutrient-dense GF flours in homemade foods may improve nutrient intakes on the GF diet

Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

&lt;b&gt;Background&lt;/b&gt; Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p &lt; .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.&lt;p&gt;&lt;/p&gt

Development of a Personalized Tumor Neoantigen Based Vaccine Formulation (FRAME-001) for Use in a Phase II Trial for the Treatment of Advanced Non-Small Cell Lung Cancer

Stage III-IV non-small cell lung cancer (NSCLC) is a devastating disease characterized by a poor prognosis. NSCLC tumors carry genetic mutations, which can lead to the expression of altered protein sequences. Peptides originating from mutated proteins and bound to MHC molecules on the tumor cell surface are referred to as neoantigens, as they are tumor-specific and not expressed in normal cells. Due to their tumor specificity, neoantigens have a strong potential to induce an anti-tumor immune response and have been investigated for development of personalized therapeutic cancer vaccines. The current study describes the development of a clinical grade neoantigen vaccine formulation (FRAME-001) intended as immunotherapy in advanced NSCLC in combination with the immune checkpoint inhibitor pembrolizumab. The detection of aberrant tumor-specific transcripts as well as an algorithm to select immunogenic neoantigen peptides are described. Subsequently, selected neoantigen peptides were synthesized with a high throughput synthesis platform and aseptically formulated under good manufacturing practice (GMP) conditions into four aqueous peptides mixtures that each contained six neoantigen peptides. A validated stability-indicating analytical method was developed in which we considered the personalized nature of the formulation. An extensive stability study performed either at -25 degrees C or -80 degrees C showed that the formulation was stable for up to 32 weeks. The formulation was mixed with the vaccine adjuvant Montanide ISA 51 VG, which yielded the final vaccine emulsion. The stability of the vaccine emulsion was demonstrated using microscopic examination, differential light scattering, and the water-drop test. The presented data show that FRAME-001 is a feasible personalized vaccine formulation for the treatment of stage III-IV NSCLC. The presented data may give guidance in the development of novel personalized therapeutic vaccines since this formulation strategy could be used for any cancer indication

Hydrothermal Chimney Distribution on the Endeavour Segment, Juan de Fuca Ridge

The Endeavour Segment of the Juan de Fuca Ridge is well known for its abundance of hydrothermal vents and chimneys. One‐meter scale multibeam mapping data collected by an autonomous undersea vehicle revealed 572 chimneys along the central 14 km of the segment, although only 47 are named and known to be active. Hydrothermal deposits are restricted to the axial graben and the near‐rims of the graben above a seismically mapped axial magma lens. The sparse eruptive activity on the segment during the last 4,300 years has not buried inactive chimneys, as occurs at more magmatically robust mid‐ocean ridges

Hydrothermal Chimney Distribution on the Endeavour Segment, Juan de Fuca Ridge

The Endeavour Segment of the Juan de Fuca Ridge is well known for its abundance of hydrothermal vents and chimneys. One-meter scale multibeam mapping data collected by an autonomous undersea vehicle revealed 572 chimneys along the central 14 km of the segment, although only 47 are named and known to be active. Hydrothermal deposits are restricted to the axial graben and the near-rims of the graben above a seismically mapped axial magma lens. The sparse eruptive activity on the segment during the last 4,300 years has not buried inactive chimneys, as occurs at more magmatically robust mid-ocean ridges

Advanced EFL learners' beliefs about language learning and teaching: a comparison between grammar, pronunciation, and vocabulary

This paper reports on the results of a study exploring learners’ beliefs on the learning and teaching of English grammar, pronunciation and vocabulary at tertiary level. While the importance of learners’ beliefs on the acquisition process is generally recognized, few studies have focussed on and compared learners’ views on different components of the language system. A questionnaire containing semantic scale and Likert scale items probing learners’ views on grammar, pronunciation and vocabulary was designed and completed by 117 native speakers of Dutch in Flanders, who were studying English at university. The analysis of the responses revealed that (i) vocabulary was considered to be different from grammar and pronunciation, both in the extent to which an incorrect use could lead to communication breakdown and with respect to the learners’ language learning strategies, (ii) learners believed in the feasibility of achieving a native-like proficiency in all three components, and (iii) in-class grammar, pronunciation and vocabulary exercises were considered to be useful, even at tertiary level. The results are discussed in light of pedagogical approaches to language teaching

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Exploring the work–life challenges and dilemmas faced by managers and professionals who live alone

This article aims to question the dominant understanding of work–life balance or conflict as primarily a ‘work–family’ issue. It does this by exploring the experiences of managers and professionals who live alone and do not have children – a group of employees traditionally overlooked in work–life policy and research but, significantly, a group on the rise within the working age population. Semi-structured interviews with 36 solo-living managers and professionals were carried out in the UK, spanning a range of occupations. In addition to previously identified work–life issues, four themes emerged that were pressing for and specific to solo-living managers and professionals. These are articulated here as challenges and dilemmas relating to: assumptions about work and non-work time; the legitimacy of their work–life balance; lack of support connected to financial and emotional well-being; and work-based vulnerabilities

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis