257 research outputs found

    Widespread sex differences in gene expression and splicing in the adult human brain

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    There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

    A survey of Sub-Saharan African medical schools

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    <p>Abstract</p> <p>Background</p> <p>Sub-Saharan Africa suffers a disproportionate share of the world's burden of disease while having some of the world's greatest health care workforce shortages. Doctors are an important component of any high functioning health care system. However, efforts to strengthen the doctor workforce in the region have been limited by a small number of medical schools with limited enrolments, international migration of graduates, poor geographic distribution of doctors, and insufficient data on medical schools. The goal of the Sub-Saharan African Medical Schools Study (SAMSS) is to increase the level of understanding and expand the baseline data on medical schools in the region.</p> <p>Methods</p> <p>The SAMSS survey is a descriptive survey study of Sub-Saharan African medical schools. The survey instrument included quantitative and qualitative questions focused on institutional characteristics, student profiles, curricula, post-graduate medical education, teaching staff, resources, barriers to capacity expansion, educational innovations, and external relationships with government and non-governmental organizations. Surveys were sent via e-mail to medical school deans or officials designated by the dean. Analysis is both descriptive and multivariable.</p> <p>Results</p> <p>Surveys were distributed to 146 medical schools in 40 of 48 Sub-Saharan African countries. One hundred and five responses were received (72% response rate). An additional 23 schools were identified after the close of the survey period. Fifty-eight respondents have been founded since 1990, including 22 private schools. Enrolments for medical schools range from 2 to 1800 and graduates range from 4 to 384. Seventy-three percent of respondents (n = 64) increased first year enrolments in the past five years. On average, 26% of respondents' graduates were reported to migrate out of the country within five years of graduation (n = 68). The most significant reported barriers to increasing the number of graduates, and improving quality, related to infrastructure and faculty limitations, respectively. Significant correlations were seen between schools implementing increased faculty salaries and bonuses, and lower percentage loss of faculty over the previous five years (<it>P </it>= 0.018); strengthened institutional research tools (<it>P </it>= 0.00015) and funded faculty research time (<it>P </it>= 0.045) and greater faculty involvement in research; and country compulsory service requirements (<it>P </it>= 0.039), a moderate number (1-5) of post-graduate medical education programs (<it>P </it>= 0.016) and francophone schools (<it>P </it>= 0.016) and greater rural general practice after graduation.</p> <p>Conclusions</p> <p>The results of the SAMSS survey increases the level of data and understanding of medical schools in Sub-Saharan Africa. This data serves as a baseline for future research, policies and investment in the health care workforce in the region which will be necessary for improving health.</p

    The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

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    Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)

    The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters. XV. The Dynamical Clock: Reading Cluster Dynamical Evolution from the Segregation Level of Blue Straggler Stars

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    The parameter A +, defined as the area enclosed between the cumulative radial distribution of blue straggler stars (BSSs) and that of a reference population, is a powerful indicator of the level of BSS central segregation. As part of the Hubble Space Telescope UV Legacy Survey of Galactic globular clusters (GCs), here we present the BSS population and the determination of A + in 27 GCs observed out to about one half-mass radius. In combination with 21 additional clusters discussed in a previous paper, this provides us with a global sample of 48 systems (corresponding to ~32% of the Milky Way GC population), for which we find a strong correlation between A + and the ratio of cluster age to the current central relaxation time. Tight relations have also been found with the core radius and the central luminosity density, which are expected to change with the long-term cluster dynamical evolution. An interesting relation is emerging between A + and the ratio of the BSS velocity dispersion relative to that of main sequence turn-off stars, which measures the degree of energy equipartition experienced by BSSs in the cluster. These results provide further confirmation that BSSs are invaluable probes of GC internal dynamics and that A + is a powerful dynamical clock

    A prospective study of peri-diagnostic and surgical wait times for patients with presumptive colorectal, lung, or prostate cancer

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    The objective of this study was to prospectively measure peri-diagnostic and surgical time intervals for patients with suspected colorectal, lung, or prostate cancer. Prospective eligible patients were referred to a regional hospital in Ottawa, Canada between February 2004 and February 2005 for diagnostic assessment of presumptive colorectal, lung, or prostate cancer. Chart abstractions were used to measure nine time intervals; the primary interval was the date of referral for diagnostic assessment to the date the patient was informed of the diagnosis. Health-related quality-of-life (HRQL) was assessed 5 days following the patient being informed of their diagnosis. The median (IQR) time for the primary interval was 71 (30–110), 37 (29–49), and 81 (56–100) days for colorectal, lung, and prostate patients, respectively (Kruskal–Wallis P=0.0001). This interval was significantly less for colorectal patients diagnosed with cancer than for those without cancer (median difference=59.0 days; Wilcoxon P=0.003). No differences in HRQL existed for patients with cancer and those without. Colorectal and prostate patients wait longer between referral for suspected cancer and being informed of their diagnosis than current recommendations. The shorter diagnostic intervals for colorectal patients with cancer suggest clinicians have an effective process for triaging patients referred for diagnostic assessment

    Membrane-mediated interactions

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    Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

    Vision in high-level football officials

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    YesOfficiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R) and assistant referees (AR) participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9%) and ten of the 49 ARs (20.4%) were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS) and the Quality-of-Vision (QoV) questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis) were gathered in a subset (n = 44, 62%) of the participants. Data were analysed according to the type (R/AR) and level (international/national) of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of p<0.01, PVVS scores did not differ between R and AR (p = 0.88), or between national- and international-level officials (p = 0.66). Similarly, QoV scores did not differ between R and AR in frequency (p = 0.50), severity (p = 0.71) or bothersomeness (p = 0.81) of symptoms, or between international-level vs national-level officials for frequency (p = 0.03) or bothersomeness (p = 0.07) of symptoms. However, international-level officials reported less severe symptoms than their national-level counterparts (p<0.01). Overall, 18.3% of officials had either never had an eye examination or if they had, it was more than 3 years previously. Regarding refractive correction, 4.2% had undergone refractive surgery and 23.9% wear contact lenses when officiating. Clinical vision measures in the football officials were similar to published normative values for young, adult populations and similar between R and AR. Clinically-measured vision did not differ according to officiating level. Visual acuity measured with and without a pinhole disc indicated that around one quarter of participants may be capable of better vision when officiating, as evidenced by better acuity (≥1 line of letters) using the pinhole. Amongst the clinical visual tests we used, we did not find evidence for above-average performance in elite-level football officials. Although the impact of uncorrected mild to moderate refractive error upon officiating performance is unknown, with a greater uptake of eye examinations, visual acuity may be improved in around a quarter of officials.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013

    Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

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    Contains fulltext : 110505.pdf (publisher's version ) (Open Access)BACKGROUND: Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. METHODS: Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. RESULTS: Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). CONCLUSIONS: In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00761813

    Gene Expression Studies in Major Depression

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    The dramatic technical advances in methods to measure gene expression on a genome-wide level thus far have not been paralleled by breakthrough discoveries in psychiatric disorders—including major depression (MD)—using these hypothesis-free approaches. In this review, we first describe the methodologic advances made in gene expression analysis, from quantitative polymerase chain reaction to next-generation sequencing. We then discuss issues in gene expression experiments specific to MD, ranging from the choice of target tissues to the characterization of the case group. We provide a synopsis of the gene expression studies published thus far for MD, with a focus on studies using mRNA microarray methods. Finally, we discuss possible new strategies for the gene expression studies in MD that circumvent some of the addressed issues
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