85 research outputs found

    Text Mining Analysis of Acquisition Reforms and Expert Views

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    Legislation, in the form of acquisition reforms, is historically enacted to address perceived cost, schedule, and performance problems in the defense acquisition system. Text mining is utilized to examine five major reforms and a compendium of views from 32 acquisition experts to identify commonalities and disconnects

    Examining the reversibility of long-term behavioral disruptions in progeny of maternal SSRI exposure

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    Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring. It is unclear from these studies whether ASD susceptibility is purely related to maternal psychiatric diagnosis, or if treatment poses additional risk. We sought to determine whether maternal SSRI treatment alone or in combination with genetically vulnerable background was sufficient to induce offspring behavior disruptions relevant to ASD. We exposed C57BL/6J or Celf6(+/-) mouse dams to fluoxetine (FLX) during different periods of gestation and lactation and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations (USVs) and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity. Celf6 mutant mice demonstrate social communicative deficits and perseverative behaviors, without further interaction with FLX. FLX re-exposure in adulthood ameliorates the tactile hypersensitivity yet exacerbates the dominance phenotype. This suggests acute deficiencies in serotonin levels likely underlie the abnormal responses to sensory stimuli, while the social alterations are instead due to altered development of social circuits. These findings indicate maternal FLX treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy

    Commensal Bacteria Modulate Innate Immune Responses of Vaginal Epithelial Cell Multilayer Cultures

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    The human vaginal microbiome plays a critical but poorly defined role in reproductive health. Vaginal microbiome alterations are associated with increased susceptibility to sexually-transmitted infections (STI) possibly due to related changes in innate defense responses from epithelial cells. Study of the impact of commensal bacteria on the vaginal mucosal surface has been hindered by current vaginal epithelial cell (VEC) culture systems that lack an appropriate interface between the apical surface of stratified squamous epithelium and the air-filled vaginal lumen. Therefore we developed a reproducible multilayer VEC culture system with an apical (luminal) air-interface that supported colonization with selected commensal bacteria. Multilayer VEC developed tight-junctions and other hallmarks of the vaginal mucosa including predictable proinflammatory cytokine secretion following TLR stimulation. Colonization of multilayers by common vaginal commensals including Lactobacillus crispatus, L. jensenii, and L. rhamnosus led to intimate associations with the VEC exclusively on the apical surface. Vaginal commensals did not trigger cytokine secretion but Staphylococcus epidermidis, a skin commensal, was inflammatory. Lactobacilli reduced cytokine secretion in an isolate-specific fashion following TLR stimulation. This tempering of inflammation offers a potential explanation for increased susceptibility to STI in the absence of common commensals and has implications for testing of potential STI preventatives

    Mycoplasma genitalium: An Emerging Cause of Sexually Transmitted Disease in Women

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    Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women including cervicitis, pelvic inflammatory disease (PID), and infertility. This comprehensive review critically examines epidemiologic studies of M. genitalium infections in women with the goal of assessing the associations with reproductive tract disease and enhancing awareness of this emerging pathogen. Over 27,000 women from 48 published reports have been screened for M. genitalium urogenital infection in high- or low-risk populations worldwide with an overall prevalence of 7.3% and 2.0%, respectively. M. genitalium was present in the general population at rates between those of Chlamydia trachomatis and Neisseria gonorrhoeae. Considering more than 20 studies of lower tract inflammation, M. genitalium has been positively associated with urethritis, vaginal discharge, and microscopic signs of cervicitis and/or mucopurulent cervical discharge in seven of 14 studies. A consistent case definition of cervicitis is lacking and will be required for comprehensive understanding of these associations. Importantly, evidence for M. genitalium PID and infertility are quite convincing and indicate that a significant proportion of upper tract inflammation may be attributed to this elusive pathogen. Collectively, M. genitalium is highly prevalent in high- and low-risk populations, and should be considered an etiologic agent of select reproductive tract disease syndromes in women

    What are the experiences of people with dementia in employment?

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    Statistics show that an increase in the statutory retirement age in the UK will mean that many more people will develop a dementia while still in employment. A review of the literature confirmed that there are no existing studies in the UK which examine this issue in any detail. The aim of this study was to investigate the experiences of people who develop a dementia while still in employment and to understand how they make sense of these experiences; therefore a qualitative explorative inquiry based on an Interpretive Phenomenological Analysis methodology was used. Interviews with five people who had developed a dementia while still in employment were carried out, with ages ranging from 58 to 74 years. Interview transcripts were analysed and four super-ordinate themes were identified: the realization that something is wrong; managing the situation in the workplace; trying to make sense of change; and coming to terms with retirement or unemployment. The results showed that people who develop a dementia while still in employment do not always receive the 'reasonable adjustments' in the workplace to which they are entitled under the Equality Act (2010). Some of the participants felt that they were poorly treated by their workplace and described some distressing experiences. The study highlights the need for more effective specialized advice and support regarding employment issues and more research into the numbers of people in the UK that are affected by this issue

    The influence of date and place of birth on youth player selection to a National Football Association elite development programme

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    Aim: This study sought to examine whether the place and date of birth of elite youth Irish footballers influences their selection onto the Football Association of Ireland's primary development pathway; 12 regional centres of excellences called the “Emerging Talent Programme” (ETP). The proposed hypothesis was that players born earlier in the year would be over-represented compared to those born later in their age band. A secondary hypothesis was that access to the ETP would be independent of place of birth. Methods: The dates and place of birth of all elite youth footballers (n = 1936) selected onto the ETP since its inception were examined. χ2 tests were used to establish if the dates of birth differed from the expected population distribution. Odds ratios were used to identify spatial variation in relation to place of birth and talent production. Results: The results showed that admission to the ETP is not independent of quarter of birth (P .05, χ2 = 256.817, w = .388). Place of birth analysis showed an unequal geographical distribution of players gaining selection onto the ETP. Selection onto the ETP was not independent of place of birth (P < .05, χ2 = 149.457, w = .278). Footballers developed in counties that had an ETP centre were almost 50% more likely to gain selection than those without a centre (OR 1.455, 95% CI 1.314 -1.612). Conclusion: The current programme demonstrates inequitable distribution of opportunities to access elite development pathways due to biases related to date and place of birth

    Ethical implications of the perception and portrayal of dementia

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    yesThe way we perceive and portray dementia has implications for how we act towards people with dementia and how we address the issue of dementia within society. As a multi-disciplinary working group, established within the framework of the European Dementia Ethics Network of Alzheimer Europe, we aimed to describe the different ways that people with dementia are perceived and portrayed within society and to consider the moral implications of this. In the current paper, we address perceptions of dementia as reflected in explanatory models of its cause and nature, descriptions of characteristics of people with dementia, the use of language, media portrayals and the views of people living with dementia. Academics and professionals could use this exploration to reflect on their behaviour and their use of language regarding people with dementiaThe taskforce’s work arises from the 2013 Work Plan of Alzheimer Europe, which received funding from the European Union in the framework of the Health Programme

    Methionine Sulfoxide Reductase A (MsrA) Deficient Mycoplasma genitalium Shows Decreased Interactions with Host Cells

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    Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells
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