153 research outputs found

    Prenatal exposure to fine particles and polycyclic aromatic hydrocarbons and birth outcomes : a two-pollutant approach

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    Background Previous epidemiologic studies have considered the effects of individual air pollutants on birth outcomes, whereas a multiple-pollutant approach is more relevant to public health policy. Objectives The present study compared the observed effect sizes of prenatal fine particulate matter ( PM2.5) and polycyclic aromatic hydrocarbons (PAH) (a component of PM2.5) exposures on birth outcome deficits, assessed by the single vs. two-pollutant approaches. Methods The study sample included 455 term infants born in Krakow to non-smoking mothers, among whom personal exposures to PM2.5 and PAH were monitored in the second trimester of pregnancy. The exposure effect estimates (unstandardized and standardized regression coefficients) on birth outcomes were determined using evant covariates. Results In the single-pollutant approach, each pollutant was inversely associated with all birth outcomes. The effect size of prenatal PAH exposure on birth weight and length was twice that of PM2.5, in terms of standardized coefficients. In the two-pollutant approach, the negative effect of PM2.5 on birth weight and length, adjusted for PAH exposure, lost its significance. The standardized effect of PAH on birth weight was 10-fold stronger (ÎČ\beta = -0.20, ρ\rho = 0.004) than that estimated for PM2.5 (ÎČ\beta = -0.02, ρ\rho = 0.757). Conclusion The results provide evidence that PAH had a greater impact on several measures of fetal development, especially birth weight, than PM2.5. Though in the singlepollutant models PM2.5 had a significant impact on birth outcomes, this effect appears to be mediated by PAH

    A new health care index predicts short term mortality for TB and HIV co-infected people

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    BACKGROUND: Using 2004–2007 TB:HIV Study data from Europe and Latin America, we previously generated a health care index (HCI) for TB and HIV co-infected people. With improvements in diagnostic and management practices, we have now updated the HCI with new data. METHODS: We evaluated nine aspects of health care in Cox proportional hazards models on time from TB diagnosis to death. Kaplan-Meier methods were used to estimate the probability of death by HCI quartile. RESULTS: Of 1396 eligible individuals (72% male, 59% from Eastern Europe), 269 died within 12 months. Use of rifamycin/isoniazid/pyrazinamide-based treatment (HR 0.67, 95% CI 0.50–0.89), TB drug susceptibility testing (DST) and number of active TB drugs (DST + <3 drugs (HR 1.09, 95% CI 0.80–1.48), DST + ≄3 drugs (HR 0.49, 95% CI 0.35–0.70) vs. no DST), recent HIV-RNA measurement (HR 0.64, 95% CI 0.50–0.82) and combination antiretroviral therapy use (HR 0.72, 95% CI 0.53–0.97) were associated with mortality. These factors contributed respectively 5, –1, 8, 5 and 4 to the HCI. Lower HCI was associated with an increased probability of death; 30% (95% CI 26–35) vs. 9% (95% CI 6–13) in the lowest vs. the highest quartile. CONCLUSION: We found five potentially modifiable health care components that were associated with mortality among TB-HIV positive individuals. Validation of our HCI in other TB cohorts could enhance our findings

    Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study

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    Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use. / Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort. / Methods: We compared individuals ≄18 years and starting combination antiretroviral therapy (ART, ≄3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed. / Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU). / Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs

    The influence of student gender on the assessment of undergraduate student work

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    The aim of this study was to investigate the influence of perceived student gender on the feedback given to undergraduate student work. Participants (n = 12) were lecturers in higher education and were required to mark two\ud undergraduate student essays. The first student essay that all participants marked was the control essay. Participants were informed that the control essay was written by Samuel Jones (a male student). Participants then marked the target essay. Although participants marked the same essay, half of the participants (n = 6) were informed that the student essay was written by Natasha Brown (a female student), while the remaining participants were informed that it was written by James Smith (a male student). In-text and end-of-text feedback were qualitatively analysed on six dimensions: academic style of writing; criticality; structure, fluency and cohesion; sources used; understanding/knowledge of the subject; and other. Analysis of feedback for both the control and target essay revealed no discernible differences in the number of comments (strengths of the essay, areas for improvement) made and the content and presentation of these comments between the two groups. Pedagogical implications pertaining to the potential impact of anonymous marking on feedback processes are discussed

    A conceptual framework for implementation fidelity

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    <p>Abstract</p> <p>Background</p> <p>Implementation fidelity refers to the degree to which an intervention or programme is delivered as intended. Only by understanding and measuring whether an intervention has been implemented with fidelity can researchers and practitioners gain a better understanding of how and why an intervention works, and the extent to which outcomes can be improved.</p> <p>Discussion</p> <p>The authors undertook a critical review of existing conceptualisations of implementation fidelity and developed a new conceptual framework for understanding and measuring the process. The resulting theoretical framework requires testing by empirical research.</p> <p>Summary</p> <p>Implementation fidelity is an important source of variation affecting the credibility and utility of research. The conceptual framework presented here offers a means for measuring this variable and understanding its place in the process of intervention implementation.</p

    Immigrant women’s experiences of maternity-care services in Canada: a systematic review using a narrative synthesis

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    Background: Canada’s diverse society and its statutory commitment to multiculturalism means that a synthesis of knowledge related to the healthcare experiences of immigrants is essential to realise the health potential for future Canadians. Although concerns about the maternity experiences of immigrants in Canada are relatively new, recent national guidelines explicitly call for the tailoring of services to user needs. We therefore assessed the experiences of immigrant women accessing maternity-care services in Canada. In particular, we investigated the experiences of immigrant women in Canada in accessing and navigating maternity and related healthcare services from conception to 6 months postpartum in Canada. Our focus was on (a) the accessibility and acceptability of maternity-care services for immigrant women and (b) the effects of the perceptions and experiences of these women on their birth and postnatal outcomes. Methods: We conducted a systematic review using a systematic search and narrative synthesis of peer-reviewed and non-peer-reviewed reports of empirical research, with the aim of providing stakeholders with perspectives on maternity-care services as experienced by immigrant women. We partnered with key stakeholders (‘integrated knowledge users’) to ensure the relevancy of topics and to tailor recommendations for effective translation into future policy, practice and programming. Two search phases and a three-stage selection process for published and grey literature were conducted prior to appraisal of literature quality and narrative synthesis of the findings. Results: Our knowledge synthesis of maternity care among immigrants to Canada provided a coherent evidence base for (a) eliciting a better understanding of the factors that generate disparities in accessibility, acceptability and outcomes during maternity care; and (b) improving culturally based competency in maternity care. Our synthesis also identified pertinent issues in multiple sectors that should be addressed to configure maternity services and programs appropriately. Conclusions: Although immigrant women in Canada are generally given the opportunity to obtain necessary services, they face many barriers in accessing and utilising these services. These barriers include lack of information about or awareness of the services, insufficient supports to access these services and discordant expectations between the women and their service providers. Systematic review registration: PROSPERO registration number: CRD42012002185

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

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    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
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