Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death

Background: Risk of Encapsulating Peritoneal Sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate risk of EPS. There is a need to determine this risk to better inform clinical decision-making, but previous studies have not allowed for the competing risk of death. Methods: This study included new adult PD patients in either Australia and New Zealand (ANZ 1990-2010) or Scotland (2000-2008) followed until 2012. Age, time on PD, primary renal disease, gender, dataset and diabetic status were evaluated as predictors at start of PD, then at three and five years after starting PD using flexible parametric competing risks models. Results: In 17,396 patients (16,162 ANZ, 1,234 Scotland), EPS was observed in 99 (0.57%) patients less frequently in ANZ patients (n=65, 0.4%) than in Scottish patients (n=34, 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1-KM=0.0126, CIF=0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74 to 0.79) and this improved at 3 and 5 years after starting PD (C-statistic = 0.81 to 0.92). Conclusions: EPS risk estimates are lower when calculated using competing risk of death analyses. A patient’s estimated risk of EPS is country-specific, and can be predicted using age, primary renal disease and duration of PD

System-level determinants of immunization coverage disparities among health districts in Burkina Faso: a multiple case study

<p>Abstract</p> <p>Background</p> <p>Despite rapid and tangible progress in vaccine coverage and in premature mortality rates registered in sub-Saharan Africa, inequities to access remain firmly entrenched, large pockets of low vaccination coverage persist, and coverage often varies considerably across regions, districts, and health facilities' areas of responsibility. This paper focuses on system-related factors that can explain disparities in immunization coverage among districts in Burkina Faso.</p> <p>Methods</p> <p>A multiple-case study was conducted of six districts representative of different immunization trends and overall performance. A participative process that involved local experts and key actors led to a focus on key factors that could possibly determine the efficiency and efficacy of district vaccination services: occurrence of disease outbreaks and immunization days, overall district management performance, resources available for vaccination services, and institutional elements. The methodology, geared toward reconstructing the evolution of vaccine services performance from 2000 to 2006, is based on data from documents and from individual and group interviews in each of the six health districts. The process of interpreting results brought together the field personnel and the research team.</p> <p>Results</p> <p>The districts that perform best are those that assemble a set of favourable conditions. However, the leadership of the district medical officer (DMO) appears to be the main conduit and the rallying point for these conditions. Typically, strong leadership that is recognized by the field teams ensures smooth operation of the vaccination services, promotes the emergence of new initiatives and offers some protection against risks related to outbreaks of epidemics or supplementary activities that can hinder routine functioning. The same is true for the ability of nurse managers and their teams to cope with new situations (epidemics, shortages of certain stocks).</p> <p>Conclusion</p> <p>The discourse on factors that determine the performance or breakdown of local health care systems in lower and middle income countries remains largely concentrated on technocratic and financial considerations, targeting institutional reforms, availability of resources, or accessibility of health services. The leadership role of those responsible for the district, and more broadly, of those we label "the human factor", in the performance of local health care systems is mentioned only marginally. This study shows that strong and committed leadership promotes an effective mobilization of teams and creates the conditions for good performance in districts, even when they have only limited access to supports provided by external partners.</p> <p>Abstract in French</p> <p>See the full article online for a translation of this abstract in French.</p

Living on a flammable planet: interdisciplinary, cross-scalar and varied cultural lessons, prospects and challenges: Table 1.

Living with fire is a challenge for human communities because they are influenced by socio-economic, political, ecological and climatic processes at various spatial and temporal scales. Over the course of 2 days, the authors discussed how communities could live with fire challenges at local, national and transnational scales. Exploiting our diverse, international and interdisciplinary expertise, we outline generalizable properties of fire-adaptive communities in varied settings where cultural knowledge of fire is rich and diverse. At the national scale, we discussed policy and management challenges for countries that have diminishing fire knowledge, but for whom global climate change will bring new fire problems. Finally, we assessed major fire challenges that transcend national political boundaries, including the health burden of smoke plumes and the climate consequences of wildfires. It is clear that to best address the broad range of fire problems, a holistic wildfire scholarship must develop common agreement in working terms and build across disciplines. We must also communicate our understanding of fire and its importance to the media, politicians and the general public. This article is part of the themed issue ‘The interaction of fire and mankind’

Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

<p>Abstract</p> <p>Background</p> <p>Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH₃/B₆/F₁₀, originally subcloned from GH₃cells based on its ability to express high levels of the membrane estrogen receptor-α.</p> <p>Methods</p> <p>We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities.</p> <p>Results</p> <p>Four phytoestrogens (coumestrol, daidzein, genistein, and <it>trans</it>-resveratrol) were studied over wide concentration ranges. Except <it>trans</it>-resveratrol, all phytoestrogens increased GH₃/B₆/F₁₀cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for <it>trans</it>-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens.</p> <p>Conclusion</p> <p>Phytoestrogens can block physiological estrogen-induced tumor cell growth <it>in vitro </it>and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary.</p

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

<p>Abstract</p> <p>Background</p> <p>Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens.</p> <p>Methods</p> <p>We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH₃/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively).</p> <p>Results</p> <p>All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses.</p> <p>Conclusions</p> <p>Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes.</p

Structure and dynamics of the shark assemblage off recife, northeastern Brazil

Understanding the ecological factors that regulate elasmobranch abundance in nearshore waters is essential to effectively manage coastal ecosystems and promote conservation. However, little is known about elasmobranch populations in the western South Atlantic Ocean. An 8-year, standardized longline and drumline survey conducted in nearshore waters off Recife, northeastern Brazil, allowed us to describe the shark assemblage and to monitor abundance dynamics using zero-inflated generalized additive models. This region is mostly used by several carcharhinids and one ginglymostomid, but sphyrnids are also present. Blacknose sharks, Carcharhinus acronotus, were mostly mature individuals and declined in abundance throughout the survey, contrasting with nurse sharks, Ginglymostoma cirratum, which proliferated possibly due to this species being prohibited from all harvest since 2004 in this region. Tiger sharks, Galeocerdo cuvier, were mostly juveniles smaller than 200 cm and seem to use nearshore waters off Recife between January and September. No long-term trend in tiger shark abundance was discernible. Spatial distribution was similar in true coastal species (i.e. blacknose and nurse sharks) whereas tiger sharks were most abundant at the middle continental shelf. The sea surface temperature, tidal amplitude, wind direction, water turbidity, and pluviosity were all selected to predict shark abundance off Recife. Interspecific variability in abundance dynamics across spatiotemporal and environmental gradients suggest that the ecological processes regulating shark abundance are generally independent between species, which could add complexity to multi-species fisheries management frameworks. Yet, further research is warranted to ascertain trends at population levels in the South Atlantic Ocean.State Government of Pernambuco, Brazil; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/37065/2007]info:eu-repo/semantics/publishedVersio