42 research outputs found

    A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa

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    In cross-sectional studies increased vaginal bacterial diversity has been associated with vaginal inflammation which can be detrimental for health. We describe longitudinal changes at 5 visits over 8 weeks in vaginal microbiota and immune mediators in African women. Women (N = 40) with a normal Nugent score at all visits had a stable lactobacilli dominated microbiota with prevailing Lactobacillus iners. Presence of prostate-specific antigen (proxy for recent sex) and being amenorrhoeic (due to progestin-injectable use), but not recent vaginal cleansing, were significantly associated with microbiota diversity and inflammation (controlled for menstrual cycle and other confounders). Women (N = 40) with incident bacterial vaginosis (Nugent 7-10) had significantly lower concentrations of lactobacilli and higher concentrations of Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia, at the incident visit and when concentrations of proinflammatory cytokines (IL-1β, IL-12p70) were increased and IP-10 and elafin were decreased. A higher 'composite-qPCR vaginal-health-score' was directly associated with decreased concentrations of proinflammatory cytokines (IL-1α, IL-8, IL-12(p70)) and increased IP-10. This longitudinal study confirms the inflammatory nature of vaginal dysbiosis and its association with recent vaginal sex and progestin-injectable use. A potential role for proinflammatory mediators and IP-10 in combination with the vaginal-health-score as predictive biomarkers for vaginal dysbiosis merits further investigation

    Reintegration of child soldiers in Burundi: A tracer study

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    Background Substantial attention and resources are aimed at the reintegration of child soldiers, yet rigorous evaluations are rare. Methods This tracer study was conducted among former child soldiers (N=452) and never-recruited peers (N=191) who participated in an economic support program in Burundi. Socio-economic outcome indicators were measured retrospectively for the period before receiving support (T1; 2005–06); immediately afterwards (T2; 2006–07); and at present (T3; 2010). Participants also rated present functional impairment and mental health indicators. Results Participants reported improvement on all indicators, especially economic opportunity and social integration. At present no difference existed between both groups on any of the outcome indicators. Socio-economic functioning was negatively related with depression- and, health complaints and positively with intervention satisfaction. Conclusion The present study demonstrates promising reintegration trajectories of former child soldiers after participating in a support program

    Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease

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    RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson’s coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I–V β = −1.06, P < 0.001; lobules VI–VII β = −0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion

    CEO remuneration, board composition and firm performance: Empirical evidence from Australian listed companies

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    Classical economic theories establishing a relationship between CEO remuneration and firm performance has paid particular attention to solve conflict of interest between managerial team and firm shareholders, by designing an optimum CEO remuneration that motivate executives to work in the best interest of shareholders. Many international and less Australian empirical researches suggest that there is overwhelming evidence that firm performance is strongly linked with CEO remuneration. In this paper, we reassess the association of firm performance and CEO remuneration variables using dynamic econometric models and comprehensive data from Australian Stock Exchange (ASX). We find a positive and strong association between CEO pay of top 200 Australian public listed companies and company performance. Obtained findings are similar to USA, UK and Canada studies results. We further test the effect of board and ownership features on CEO remuneration-performance sensitivity in the top 200 Australian public companies listed on ASX. Specifically, for the period of 2003-2007, our results highlight the importance of ownership structure in influencing remuneration-performance relationship. Monitoring block holders boost the responsiveness of long term incentives (LTI) remuneration to performance, thus straightening shareholder and manager welfares. However, based on a short term investment horizon strategy, insider block holders increase (decrease) the sensitivity of short-term incentives remuneration (long term incentives pay). Surprisingly, for the period 2008-2013, our findings suggest that ownership and board features did not influence significantly CEO pay-performance sensitivities. Finally, we find that larger boards increase (decrease) the responsiveness of CEO&#039;s known remuneration (long term incentives) to performance

    Do regulatory standards help align CEO compensation and banks performance association?

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    This study aims to assess the impact of APS 510 standard on CEO remuneration-performance association in Australian Authorized deposits taking institutions (ADIs). Using panel data GLS and dynamic GMM estimation models, a key objective of this research is to investigate the role of regulatory standards on the empirical association between executive compensation and firm performance. The research uses data from 45 listed Australian financial institutions for the period 2004-2015. We observe no statistically significant evidence to show that CEO cash bonus is excessive in banking sector as claimed by various financial press and business media. Further analyses reveal the differing but substantial functions of APS 510 in shaping the association between a firm&#039;s CEO short -term incentives and corporate performance depending on the nature and characteristics of the firm (ADIs vs non-ADIs). As the regulatory standard is legally binding for all ADIs and not necessarily for non-ADI companies, CEO&#039;s ann ual variable remuneration for the ADI category is somehow lower. This implies that the standard plays a critical role in reducing the level of CEO short-term incentives in the ADI group of firms. Empirical results show no significant statistical influence of the standard in shaping the relationship between CEO long-term incentive and market based performance of the Australian banking system. Our findings here are consistent with prior studies in developed countries such as the US. Policy-wise, we conclude that regulators should encourage corporate board of firms to increase long-term incentives in CEO remuneration in order to align managements&#039; actions and shareholders interest of enhancing firm value

    Detecting nocturnal hypertension in Parkinson's disease and multiple system atrophy: proposal of a decision-support algorithm

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    A pathological nocturnal blood pressure (BP) profile, either non-dipping or reverse dipping, occurs in more than 50 % of subjects diagnosed with multiple system atrophy (MSA) or Parkinson's disease (PD). This may play a negative prognostic role in α-synucleinopathies, but, being mostly asymptomatic, remains largely underdiagnosed. In this proof-of-concept study, we aimed at developing a decision-support algorithm to predict pathological nocturnal BP profiles during a standard tilt-table examination in PD and MSA. Sixteen MSA and 16 PD patients underwent standard tilt-table examination and 24-h ambulatory BP monitoring (24-h ABPM). Clinical and tilt test differences between patients with a normal and a pathological nocturnal BP profile at 24-h ABPM were assessed, and a decision-support algorithm was developed accordingly. 75 % of MSA and 31 % of PD patients showed a pathological nocturnal BP profile. This was associated with more pronounced orthostatic BP drop (p = 0.03), joint occurrence of orthostatic hypotension and supine hypertension (p = 0.046), and lack of BP overshoot in the late phase II (II_L, p = 0.002) and in the phase IV (p = 0.007) of the Valsalva manoeuvre. Combined ∆BP ≤0.5 mmHg in the II_L and ≤-7 mmHg in the IV phase of Valsalva manoeuvre correctly predicted a pathological nocturnal BP profile with 87.5 % sensitivity and 85.7 % specificity. Pathological nocturnal BP profiles are associated with evidence of cardiovascular noradrenergic failure in PD and MSA. The Valsalva manoeuvre is routinely performed during standard tilt-table examinations. We propose the naked-eye evaluation of Valsalva phase II_L and phase IV BP behaviour as time-sparing screening tool for pathological nocturnal BP profiles in PD and MSA

    Evaluation of latent class analysis and decision thresholds to guide the diagnosis of pediatric tuberculosis in a Rwandan reference hospital [electronic only]

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    SETTING: A pediatric ward of a university hospital in Kigali, Rwanda, a region with a high HIV seroprevalence. OBJECTIVE: To estimate the diagnostic accuracy of symptoms, signs, and paraclinical investigations for tuberculosis in children, and to propose a clinical rule based on the results. DESIGN: During a 2-year period all children with cough for more than 2 weeks and/or fever for more than 2 weeks and/or reported weight loss were prospectively included. A set of clinical and paraclinical data were analyzed with latent class analysis. Comparison of post-test probability based on this analysis with a therapeutic threshold for TB was used to develop a guideline. RESULTS: In the 309 children HIV prevalence was 56%, bacteriology was positive in 9%, and the tuberculin skin test (TST) was >10 mm in 20%. TB prevalence was 32%. Bacteriology and TST had a specificity of 97% and cough had a sensitivity of 91%. Decision analysis suggests treating children presenting one of the inclusion criteria, combined with positive bacteriology or TST >10 mm or contact with a TB patient. CONCLUSIONS: Latent class analysis confirmed earlier identified predictors for TB and allowed development of an easy to use clinical rule, applicable in reference hospitals of countries with high HIV endemicity
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