Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children

Aim: The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Materials & Methods: Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches. Results: 95% reference intervals for each biomarker in each cohort are presented and stratified by sex or ethnicity where necessary, and age-related variability is explored using quantile regression. We identified consistently higher NGAL concentrations in females than males (p < 0.0001), and lower KIM-1 concentrations in African–Americans than Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher concentrations in the morning (p < 0.001). Conclusion: This is the first report of reference intervals for KIM-1 and NGAL using two analytical methods in a healthy pediatric population in both UK and US-based populations

Factors affecting post-fire crown regeneration in cork oak (Quercus suber L.) trees

Cork oak (Quercus suber) forests are acknowledged for their biodiversity and economic (mainly cork production) values. WildWres are one of the main threats contributing to cork oak decline in the Mediterranean Basin, and one major question that managers face after Wre in cork oak stands is whether the burned trees should be coppiced or not. This decision can be based on the degree of expected crown regeneration assessed immediately after Wre. In this study we carried out a post-Wre assessment of the degree of crown recovery in 858 trees being exploited for cork production in southern Portugal, 1.5 years after a wildWre. Using logistic regression, we modelled good or poor crown recovery probability as a function of tree and stand variables. The main variables inXuencing the likelihood of good or poor crown regeneration were bark thickness, charring height, aspect and tree diameter. We also developed management models, including simpler but easier to measure variables, which had a lower predictive power but can be used to help managers to identify, immediately after Wre, trees that will likely show good crown regeneration, and trees that will likely die or show poor regeneration (and thus, potential candidates for trunk coppicin

Implementing evidence-based recommended practices for the management of patients with mild traumatic brain injuries in Australian emergency care departments: study protocol for a cluster randomised controlled trial

Background: Mild head injuries commonly present to emergency departments. The challenges facing clinicians in emergency departments include identifying which patients have traumatic brain injury, and which patients can safely be sent home. Traumatic brain injuries may exist with subtle symptoms or signs, but can still lead to adverse outcomes. Despite the existence of several high quality clinical practice guidelines, internationally and in Australia, research shows inconsistent implementation of these recommendations. The aim of this trial is to test the effectiveness of a targeted, theory- and evidence-informed implementation intervention to increase the uptake of three key clinical recommendations regarding the emergency department management of adult patients (18 years of age or older) who present following mild head injuries (concussion), compared with passive dissemination of these recommendations. The primary objective is to establish whether the intervention is effective in increasing the percentage of patients for which appropriate post-traumatic amnesia screening is performed. / Methods/design: The design of this study is a cluster randomised trial. We aim to include 34 Australian 24-hour emergency departments, which will be randomised to an intervention or control group. Control group departments will receive a copy of the most recent Australian evidence-based clinical practice guideline on the acute management of patients with mild head injuries. The intervention group will receive an implementation intervention based on an analysis of influencing factors, which include local stakeholder meetings, identification of nursing and medical opinion leaders in each site, a train-the-trainer day and standardised education and interactive workshops delivered by the opinion leaders during a 3 month period of time. Clinical practice outcomes will be collected retrospectively from medical records by independent chart auditors over the 2 month period following intervention delivery (patient level outcomes). In consenting hospitals, eligible patients will be recruited for a follow-up telephone interview conducted by trained researchers. A cost-effectiveness analysis and process evaluation using mixed-methods will be conducted. Sample size calculations are based on including 30 patients on average per department. Outcome assessors will be blinded to group allocation. / Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612001286831 (date registered 12 December 2012)

Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration

Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80+ macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines, including the homeostatic chemokines CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease

Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease

Optimal-Foraging Predator Favors Commensalistic Batesian Mimicry

BACKGROUND:Mimicry, in which one prey species (the Mimic) imitates the aposematic signals of another prey (the Model) to deceive their predators, has attracted the general interest of evolutionary biologists. Predator psychology, especially how the predator learns and forgets, has recently been recognized as an important factor in a predator-prey system. This idea is supported by both theoretical and experimental evidence, but is also the source of a good deal of controversy because of its novel prediction that in a Model/Mimic relationship even a moderately unpalatable Mimic increases the risk of the Model (quasi-Batesian mimicry). METHODOLOGY/PRINCIPAL FINDINGS:We developed a psychology-based Monte Carlo model simulation of mimicry that incorporates a "Pavlovian" predator that practices an optimal foraging strategy, and examined how various ecological and psychological factors affect the relationships between a Model prey species and its Mimic. The behavior of the predator in our model is consistent with that reported by experimental studies, but our simulation's predictions differed markedly from those of previous models of mimicry because a more abundant Mimic did not increase the predation risk of the Model when alternative prey were abundant. Moreover, a quasi-Batesian relationship emerges only when no or very few alternative prey items were available. Therefore, the availability of alternative prey rather than the precise method of predator learning critically determines the relationship between Model and Mimic. Moreover, the predation risk to the Model and Mimic is determined by the absolute density of the Model rather than by its density relative to that of the Mimic. CONCLUSIONS/SIGNIFICANCE:Although these predictions are counterintuitive, they can explain various kinds of data that have been offered in support of competitive theories. Our model results suggest that to understand mimicry in nature it is important to consider the likely presence of alternative prey and the possibility that predation pressure is not constant

Childhood lead exposure in France: benefit estimation and partial cost-benefit analysis of lead hazard control

<p>Abstract</p> <p>Background</p> <p>Lead exposure remains a public health concern due to its serious adverse effects, such as cognitive and behavioral impairment: children younger than six years of age being the most vulnerable population. In Europe, the lead-related economic impacts have not been examined in detail. We estimate the annual costs in France due to childhood exposure and, through a cost benefit analysis (CBA), aim to assess the expected social and economic benefits of exposure abatement.</p> <p>Methods</p> <p>Monetary benefits were assessed in terms of avoided national costs. We used results from a 2008 survey on blood-lead (B-Pb) concentrations in French children aged one to six years old. Given the absence of a threshold concentration being established, we performed a sensitivity analysis assuming different hypothetical threshold values for toxicity above 15 μg/L, 24 μg/L and 100 μg/L. Adverse health outcomes of lead exposure were translated into social burden and economic costs based on literature data from literature. Direct health benefits, social benefits and intangible avoided costs were included. Costs of pollutant exposure control were partially estimated in regard to homes lead-based paint decontamination, investments aiming at reducing industrial lead emissions and removal of all lead drinking water pipes.</p> <p>Results</p> <p>The following overall annual benefits for the three hypothetical thresholds values in 2008 are: €22.72 billion, €10.72 billion and €0.44 billion, respectively. Costs from abatement ranged from €0.9 billion to 2.95 billion/year. Finally, from a partial CBA of lead control in soils and dust the estimates of total net benefits were € 3.78 billion, € 1.88 billion and €0.25 billion respectively for the three hypothesized B-Pb effect values.</p> <p>Conclusions</p> <p>Prevention of childhood lead exposure has a high social benefit, due to reduction of B-Pb concentrations to levels below 15 μg/L or 24 μg/L, respectively. Reducing only exposures above 100 μg/L B-Pb has little economic impact due to the small number of children who now exhibit such high exposure levels. Prudent public policies would help avoiding future medical interventions, limit the need for special education and increase future productivity, and hence lifetime income for children exposed to lead.</p

Cork oak vulnerability to fire: the role of bark harvesting, tree characteristics and abiotic factors

Forest ecosystems where periodical tree bark harvesting is a major economic activity may be particularly vulnerable to disturbances such as fire, since debarking usually reduces tree vigour and protection against external agents. In this paper we asked how cork oak Quercus suber trees respond after wildfires and, in particular, how bark harvesting affects post-fire tree survival and resprouting. We gathered data from 22 wildfires (4585 trees) that occurred in three southern European countries (Portugal, Spain and France), covering a wide range of conditions characteristic of Q. suber ecosystems. Post-fire tree responses (tree mortality, stem mortality and crown resprouting) were examined in relation to management and ecological factors using generalized linear mixed-effects models. Results showed that bark thickness and bark harvesting are major factors affecting resistance of Q. suber to fire. Fire vulnerability was higher for trees with thin bark (young or recently debarked individuals) and decreased with increasing bark thickness until cork was 3–4 cm thick. This bark thickness corresponds to the moment when exploited trees are debarked again, meaning that exploited trees are vulnerable to fire during a longer period. Exploited trees were also more likely to be top-killed than unexploited trees, even for the same bark thickness. Additionally, vulnerability to fire increased with burn severity and with tree diameter, and was higher in trees burned in early summer or located in drier south-facing aspects. We provided tree response models useful to help estimating the impact of fire and to support management decisions. The results suggested that an appropriate management of surface fuels and changes in the bark harvesting regime (e.g. debarking coexisting trees in different years or increasing the harvesting cycle) would decrease vulnerability to fire and contribute to the conservation of cork oak ecosystemsinfo:eu-repo/semantics/publishedVersio

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study

Background: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. Methods: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993–95), ISAAC Phase III (2001–03), or both. We included individuals from two age groups (children aged 6–7 years and adolescents aged 13–14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. Findings: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993–2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (–0·37, 95% CI –0·69 to –0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (–1·37, –2·47 to –0·27], in children and –1·67, –2·70 to –0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. Interpretation: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. Funding: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III