668 research outputs found

    Help-seeking behaviours of university students in a Northern Ontario community

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    Prevalence rates for mental illness are high for Canadian youth 15-24 years old and for those living in northern and rural populations; however, a concerning portion of youth in need do not access mental health services. Although university student populations have higher prevalence rates than the general population, little is known about how Canadian university students seek help for mental health issues and the barriers they may face. This mixed-methods study examined the help-seeking attitudes, intentions, barriers-to-care, depressive symptomology, and help-seeking experiences of a sample of 61 undergraduate university students in the Northern Ontario community of Sudbury, Ontario. There was a total of 61 participants for this study. All participants completed a questionnaire package and seven of the participants volunteered to engage in an additional semi-structured interview. The overall sample had moderately positive attitudes toward help-seeking. Students who had accessed services were more likely to seek help from professional mental health services, had experienced more barriers-to-care, and had higher BDI-II scores than students who had not accessed services. Students not accessing care were more likely to seek help from their parents. There were no differences in the types of barriers faced between users vs. non-users of mental health services. Using thematic analysis, three primary themes were identified from the interview data: 1) Important factors in mental health care; 2) Experiences with mental health professionals and services; and 3) Barriers to accessing mental health care. The findings may help direct future research and endorse the need to further refine outreach interventions and available mental health services to promote student engagement with treatment at universities across Ontario.Master of Arts (MA) in Applied Psycholog

    Drop Test Release Mechanism

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    Many boxes for shipping undergo drop tests by the manufacturer to ensure their durability. Certain constraints are necessary to successfully carry out these tests such as not damaging the box prior to the drop and maintaining consistency throughout every drop. Our team has designed a Drop Test Release Mechanism that addresses these constraints. It provides repetitive drops for different objects that vary in shape and size such as small electronics or parts. This device utilizes a soft-clamping mechanism that can release an object with minimal force applied onto it prior to drop. A frame made of 80/20 was designed to provide rigidity to the soft-clamping mechanism. The soft clamping mechanism supports the object between it by utilizing foam and a friction pad to induce a high friction force. The clamp can be adjusted for multiple sized objects by use of sliding rails that allow it to widen or tighten. Our design focuses on just the release of the test object. A test stand to introduce varying heights must be designed for a fully functional drop test measurement process. The final prototype was tested to analyze the effectiveness of our design. The tests involved verifying the repeatability of the drop mechanism by testing the object to see if it fell in the same orientation and with the same impact each time. The drop mechanism passed these tests but failed at a usability test and an electronic test. The report goes into detail about the design and testing of the prototype

    Promoting ethical behaviour and preventing wrongdoing in organisations: A rapid evidence assessment

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    This Rapid Evidence Assessment (REA), based on 57 studies carried out in policing and other professions, aimed to identify interventions, mechanisms and levers that might encourage ethical behaviour and prevent wrongdoing in organisations. Taken together, the evidence raises a number of possibilities for organisations for action, though no readymade single solution was identified. The importance of strong and effective leadership – such as leaders being open, acting as role models, and also being ‘firm’ in terms of setting and enforcing standards – was highlighted as encouraging ethical behaviour, as well as being an essential ingredient for the successful implementation of interventions. Promising interventions tended to be broadly preventive or remedial in their approach, rather than focused on apprehending and disciplining those responsible for wrongdoing

    Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice

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    STUDY QUESTION: Does the Irinotecan metabolite 7-ethyl-10-hydroxycamptothecan (SN38) damage the gonads of male and female prepubertal mice? SUMMARY ANSWER: The Irinotecan metabolite SN38 reduces germ cell numbers within the seminiferous tubules of mouse testes at concentrations that are relevant to cancer patients, while in contrast it has little if any effect on the female germ cell population. WHAT IS KNOWN ALREADY: Little is known about the role of the chemotherapeutic agent Irinotecan on female fertility, with only one article to date reporting menopausal symptoms in perimenopausal women treated with Irinotecan, while no data are available either on adult male fertility or on the impact of Irinotecan on the subsequent fertility of prepubertal cancer patients, female or male. STUDY DESIGN SIZE, DURATION: Male and female gonads were obtained from postnatal day 5 C57BL/6 mice and exposed in vitro to a range of concentrations of the Irinotecan metabolite SN38: 0.002, 0.01, 0.05, 0.1 or 1 ”g ml(–1) for the testis and 0.1, 1, 2.5 or 5 ”g ml(–1) for the ovary, with treated gonads compared to control gonads not exposed to SN38. SN38 was dissolved in 0.5% dimethyl sulfoxide, with controls exposed to the same concentration of diluent. The number of testis fragments used for each analysis ranged between 3 and 9 per treatment group, while the number of ovaries used for each analysis ranged between 4 and 12 per treatment group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Neonatal mouse gonads were developed in vitro, with tissue analysed at the end of the 4–6 day culture period, following immunofluorescence or hematoxylin and eosin staining. Statistical analyses were performed using one-way ANOVA followed by Bonferroni post-hoc test for normally distributed data and Kruskal-Wallis test followed by Dunns post-test for non-parametric data. MAIN RESULTS AND THE ROLE OF CHANCE: Abnormal testis morphology was observed when tissues were exposed to SN38, with a smaller seminiferous tubule diameter at the highest concentration of SN38 (1 ”g ml(−1), p < 0.001 versus control) and increased number of Sertoli cell-only tubules at the two highest concentrations of SN38 (0.1 ”g ml(−1), p < 0.001; 1 ”g ml(−1), p < 0.0001, both versus control). Within seminiferous tubules, a dose response decrease was observed in both germ cell number (mouse vasa homologue (MVH)-positive cells) and in proliferating cell number (bromodeoxyuridine (BrdU)-positive cells), with significance reached at the two highest concentrations of SN38 (0.1 ”g ml(−1), p < 0.01 for both; 1 ”g ml(−1), p < 0.001-MVH, p < 0.01-BrdU; all versus control). No change was seen in protein expression of the apoptotic marker cleaved caspase 3. Double immunofluorescence showed that occasional proliferating germ cells were present in treated testes, even after exposure to the highest drug concentration. When prepubertal ovaries were treated with SN38, no effect was seen on germ cell number, apoptosis or cell proliferation, even after exposure to the highest drug concentrations. LIMITATIONS REASONS FOR CAUTION: As with any study using in vitro experiments with an experimental animal model, caution is required when extrapolating the present findings to humans. Differences between human and mouse spermatogonial development also need to be considered when assessing the effect of chemotherapeutic exposure. However, the prepubertal testes and ovaries used in the present studies contain germ cell populations that are representative of those found in prepubertal patients, and experimental tissues were exposed to drug concentrations within the range found in patient plasma. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate that the prepubertal mouse ovary is relatively insensitive to exposure to the Irinotecan metabolite SN38, while it induces a marked dose-dependent sensitivity in the testicular germ cell population. The study identifies the importance of further investigation to identify the risk of infertility in young male cancer patients treated with Irinotecan. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTEREST(S): Work supported by Medical Research Grant (MRC) grant G1002118 and Children with Cancer UK grant 15-198. The authors declare that there is no conflict of interest that could prejudice the impartiality of the present research

    An essential role for decorin in bladder cancer invasiveness

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    Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours.Fil: El Behi, Mohamed. Institute Curie; Francia. Centre de Recherche de I; Francia. Inserm; FranciaFil: Krumeich, Sophie. Institute Curie; Francia. Inserm; FranciaFil: Lodillinsky, Catalina. Institute Curie; Francia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kamoun, Aurélie. Institute Curie; FranciaFil: Tibaldi, Lorenzo. Institute Curie; Francia. Inserm; FranciaFil: Sugano, Gaël. Institute Curie; Francia. Inserm; FranciaFil: de Reynies, Aurélien. Ligue Nationale Contre le Cancer; FranciaFil: Chapeaublanc, Elodie. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Laplanche, AgnÚs. Centre National de la Recherche Scientifique; Francia. Institut de Cancérologie Gustave Roussy; FranciaFil: Lebret, Thierry. HÎpital Foch. Service d; Francia. Université de Versailles; FranciaFil: Allory, Yves. Inserm; FranciaFil: Radvanyi, François. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lantz, Olivier. Institute Curie; Francia. Inserm; FranciaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernard Pierrot, Isabelle. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Théery, Clotilde. Institute Curie; Francia. Inserm; Franci

    Pertussis immunisation strategies to optimise infant pertussis control : a narrative systematic review

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    Objective Countries routinely offering acellular pertussis vaccine, where long-term protection is not sustained, have the challenge of selecting an optimal schedule to minimise disease among young infants. We conducted a narrative systematic review and synthesis of information to evaluate different pertussis immunisation strategies at controlling pertussis disease, hospitalisation, deaths, and vaccine effectiveness among young infants. Methods We conducted a review of the literature on studies about the primary, booster, and/or maternal vaccination series and synthesised findings narratively. Countries offering the first three doses of vaccine within six-months of life and a booster on or before the second year or life were defined as accelerated primary and booster schedules, respectively. Countries offering primary and booster doses later were defined as extended primary and booster schedules. All search results were screened, and articles reviewed and reconciled, by two authors. The Risk of Bias in Non-randomised Studies of Intervention tool was used to evaluate the risk of bias. Findings A total of 98 studies were included in the analyses and the following recurring themes were described: timing of vaccination, vaccine coverage, waning immunity/vaccine effectiveness, direct and indirect effectiveness, switching from an accelerated to extended schedule, impact of changes in testing. The risk of bias was generally low to moderate for most studies. Conclusion Comparing schedules is challenging and there was insufficient evidence to that one schedule was superior to another. Countries must select a schedule that maintains high vaccine coverage and reduced the risk of delaying the delivery vaccines to protect infants

    Dual Mechanism of Interleukin-3 Receptor Blockade by an Anti-Cancer Antibody

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    SummaryInterleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor α chain (IL3Rα) in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, and IL-13 receptors, adopting unique “open” and classical “closed” conformations. Although extensive mutational analyses of the NTD epitope of CSL362 show minor overlap with the IL-3 binding site, CSL362 only inhibits IL-3 binding to the closed conformation, indicating alternative mechanisms for blocking IL-3 signaling. Significantly, whereas “open-like” IL3Rα mutants can simultaneously bind IL-3 and CSL362, CSL362 still prevents the assembly of a higher-order IL-3 receptor-signaling complex. The discovery of open forms of cytokine receptors provides the framework for development of potent antibodies that can achieve a “double hit” cytokine receptor blockade

    Marine ecosystem assessment for the Southern Ocean: birds and marine mammals in a changing climate

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    The massive number of seabirds (penguins and procellariiformes) and marine mammals (cetaceans and pinnipeds) – referred to here as top predators – is one of the most iconic components of the Antarctic and Southern Ocean. They play an important role as highly mobile consumers, structuring and connecting pelagic marine food webs and are widely studied relative to other taxa. Many birds and mammals establish dense breeding colonies or use haul-out sites, making them relatively easy to study. Cetaceans, however, spend their lives at sea and thus aspects of their life cycle are more complicated to monitor and study. Nevertheless, they all feed at sea and their reproductive success depends on the food availability in the marine environment, hence they are considered useful indicators of the state of the marine resources. In general, top predators have large body sizes that allow for instrumentation with miniature data-recording or transmitting devices to monitor their activities at sea. Development of scientific techniques to study reproduction and foraging of top predators has led to substantial scientific literature on their population trends, key biological parameters, migratory patterns, foraging and feeding ecology, and linkages with atmospheric or oceanographic dynamics, for a number of species and regions. We briefly summarize the vast literature on Southern Ocean top predators, focusing on the most recent syntheses. We also provide an overview on the key current and emerging pressures faced by these animals as a result of both natural and human causes. We recognize the overarching impact that environmental changes driven by climate change have on the ecology of these species. We also evaluate direct and indirect interactions between marine predators and other factors such as disease, pollution, land disturbance and the increasing pressure from global fisheries in the Southern Ocean. Where possible we consider the data availability for assessing the status and trends for each of these components, their capacity for resilience or recovery, effectiveness of management responses, risk likelihood of key impacts and future outlook

    Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?

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    Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014-September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable
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