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Aim To understand the origin of the most isolated endemic fish fauna of the Indo‐Pacific, Easter Island (Rapa Nui), and to infer divergence times and colonization routes of the endemic coral reef fish fauna from their closest relatives. Location Easter Island, Pacific Ocean. Methods Samples of ten species were used: six small‐range species endemic to Rapa Nui and Motu Motiro Hiva (Salas y Gómez) (i.e. small‐range endemic species) and four large‐range species endemic to the southern subtropical Pacific (i.e. large‐range endemic species). We present phylogenetic reconstruction results based on mitochondrial (1 to 5) and nuclear (1 to 6) loci to place these endemic species in their respective family phylogenies (8). Using these newly calibrated phylogenetic trees, information of species distributions and geological data, we inferred the divergence times from the closest relatives of these ten endemic fishes, compared biogeographical history estimation models to reconstruct their ancestral geographic ranges, colonization routes and underlying mechanisms of speciation. Results The divergence times (i.e. divergence times from the closest relatives) of all of the small‐range endemics studied were more recent than the age of Rapa Nui and Motu Motiro Hiva; thus, these species can be considered as neoendemics. Biogeographical history estimation models indicated that speciation following a founder‐event is the most likely scenario. In contrast, the divergence estimates of the large‐range endemic species were highly variable. This being said, the divergence times of all species were more recent than the age of the oldest islands within their distributions. Main conclusions Taken together, these results demonstrate that Rapa Nui acts as a cradle of coral reef biodiversity, being responsible for the emergence of small‐range endemic fish species, but also a route of dispersion for several large‐range endemics and as a stepping stone in the diversification of the Myripristis and Pseudolabrus genera. While no common divergence time was recovered for all of the ten endemic species studied here, the common mechanism of speciation following a founder event was recovered for most of the small‐range endemic species.

Background The Barbirostris Complex comprises six formally described species that cannot be differentiated based on morphology alone. Out of these six species, two have been reported as putative malaria vectors, An. campestris and An. wejchoochotei . Five species are present in Thailand, An. barbirostris , An. campestris , An. dissidens , An. saeungae and An. wejchoochotei , while An . vanderwulpi occurs in Indonesia. As these species cannot be accurately differentiated by morphological characters, there is a crucial lack of information on their bionomics and role in the transmission of malaria and filariasis agents. Results For differentiating the six species, an allele-specific amplification (AS-PCR) based on the second internal transcribed spacer (ITS2) sequence was developed. From 862 mosquitoes in the Barbirostris Complex collected in 23 provinces throughout Thailand, the AS-PCR was able to identify five species and its validation was undertaken on 185 specimens. Conclusions This multiplex-PCR assay is potentially able to definitely identify all six species of the Barbirostris Complex and was validated on five species present in Thailand.

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

Human antibody (Ab) response to Anopheles whole saliva, used as biomarker of Anopheles exposure, was investigated over a period of two years (2008-2009), in children between 2 to 9 years old, before and after the introduction of three different malaria vector control methods; deltamethrin treated long lasting impregnated nets (LLIN) and insecticide treated plastic sheeting (ITPS)--Zero Fly®) (ITPS-ZF), deltamethrin impregnated Durable (Wall) Lining (ITPS-DL--Zerovector®) alone, and indoor residual spraying (IRS) with lambdacyhalothrin alone. These different vector control methods resulted in considerable decreases in all three entomological (82.4%), parasitological (54.8%) and immunological criteria analyzed. The highest reductions in the number of Anopheles collected and number of positive blood smears, respectively 82.1% and 58.3%, were found in Capango and Canjala where LLIN and ITPS-ZF were implemented. The immunological data based on the level of anti-saliva IgG Ab in children of all villages dropped significantly from 2008 to 2009, except in Chissequele. These results indicated that these three vector control methods significantly reduced malaria infections amongst the children studied and IRS significantly reduced the human-Anopheles contact. The number of Anopheles, positive blood smears, and the levels of anti-saliva IgG Ab were most reduced when LLIN and ITPS-ZF were used in combination, compared to the use of one vector control method alone, either ITPS-DL or IRS. Therefore, as a combination of two vector control methods is significantly more effective than one control method only, this control strategy should be further developed at a more global scale.

Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing five ATP2B4 SNPs in LD with rs10900585. We found significant associations between SM and rs10900585 and our candidate SNPs (rs11240734, rs1541252, rs1541253, rs1541254, and rs1541255) in a Senegalese population. Then, we demonstrated that both individual SNPs and the combination of SNPs had regulatory effects. Moreover, CRISPR/Cas9-mediated deletion of this region decreased ATP2B4 transcript and protein levels and increased Ca2+ intracellular concentration in the K562 cell line. Our data demonstrate that severe malaria-associated genetic variants alter the expression of ATP2B4 encoding a plasma membrane calcium-transporting ATPase 4 (PMCA4) expressed on red blood cells. Altering the activity of this regulatory element affects the risk of SM, likely through calcium concentration effect on parasitaemia.

OBJECTIVE:There is growing interest in the NIOSH Total Worker Health program, specifically in the process of designing and implementing safer, health-promoting work and workplaces. A Total Worker Health (TWH) Research Methodology Workshop was convened to discuss research methods and future needs. METHODS:Twenty-six experts in occupational safety and health and related fields reviewed and discussed current methodological and measurement issues and those showing promise. RESULTS:TWH intervention studies face the same challenges as other workplace intervention studies and some unique ones. Examples are provided of different approaches and their applications to TWH intervention studies, and desired developments in the TWH literature. CONCLUSIONS:This report discusses and outlines principles important to building the TWH intervention research base. Rigorous, valid methodologic, and measurement approaches are needed for TWH intervention as well as for basic/etiologic, translational, and surveillance research.

Sensory abnormalities are characteristic of autism and schizophrenia. In autism, greater trial-to-trial variability (TTV) in sensory neural responses suggest that the system is more unstable. However, these findings have only been identified in the amplitude and not in the timing of neural responses, and have not been fully explored in schizophrenia. TTV in event-related potential amplitudes and inter-trial coherence (ITC) were assessed in the auditory mismatch negativity (MMN) in autism, schizophrenia, and controls. MMN was largest in autism and smallest in schizophrenia, and TTV was greater in autism and schizophrenia compared to controls. There were no differences in ITC. Greater TTV appears to be characteristic of both autism and schizophrenia, implicating several neural mechanisms that could underlie sensory instability.

Background As citizens, patients and family members are participating in numerous and expanding roles in health system organizations, attention has turned to evaluating these efforts. The context‐specific nature of engagement requires evaluation tools to be carefully designed for optimal use. We sought to address this need by assessing the appropriateness and feasibility of a generic tool across a range of health system organizations, engagement activities and patient groups. Methods We used a mixed‐methods implementation research design to study the implementation of an engagement evaluation tool in seven health system organizations in Ontario, Canada focusing on two key implementation outcome variables: appropriateness and feasibility. Data were collected through respondent feedback questions (binary and open‐ended) at the end of the tool's three questionnaires as well as interviews and debriefing discussions with engagement professionals and patient partners from collaborating organizations. Results The three questionnaires comprising the evaluation tool were collectively administered 29 times to 405 respondents yielding a 52% response rate (90% and 53% of respondents respectively assessed the survey's appropriateness and feasibility [quantitatively or qualitatively]). The questionnaires' basic properties were rated highly by all respondents. Concrete suggestions were provided for improving the appropriateness and feasibility of the questionnaires (or components within) for different engagement activity and organization types, and for enhancing the timing of implementation. Discussion and Conclusions Our study findings offer guidance for health system organizations and evaluators to support the optimal use of engagement evaluation tools across a variety of health system settings, engagement activities and respondent groups.

IntroductionKnee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.Methods and analysis Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.Ethics and disseminationResearch ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.PROSPERO registration numberCRD42017054049.

Background: Oral care is important to prevent buccal and systemic infections after an acquired brain injury (ABI). Despite recent advancements in the development of ABI clinical practice guidelines, recommendations for specific clinical processes and actions to attain adequate oral care often lack information. Objective: This systematic review will (1) identify relevant ABI clinical practice guidelines and (2) appraise the oral care recommendations existing in the selected guidelines. Methods: A search strategy was developed based on a recent systematic review of clinical practice guidelines for ABI. The protocol includes a search of MEDLINE, EMBASE, and DynaMed Plus databases, as well as organizational and best-practice websites and reference lists of accepted guidelines. Search terms will include medical subject headings and user-defined terms. Guideline appraisal will involve the Appraisal of Guidelines for Research and Evaluation II ratings, followed by a descriptive synopsis for oral care recommendations according to the National Health and Medical Research Council evidence levels. Results: This project started in April 2019, when we developed the search strategy. The preliminary search of databases and websites yielded 863 and 787 citations, respectively, for a total of 1650 citations. Data collection will start in August 2020 and we expect to begin disseminating the results in May 2021. Conclusions: Nursing staff may not have detailed recommendations on how to provide oral care for neurologically impaired patients. The findings of this review will explore the evidence for oral care in existing guidelines and improve outcomes for patients with ABI. We expect to provide adequate orientations to clinicians, inform policy and guidelines for best practices, and contribute to future directions for research in the ABI realm. International Registered Report Identifier (IRRID): PRR1-10.2196/17249