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BACKGROUND Research funders use a wide variety of application assessment processes yet there is little evidence on their relative advantages and disadvantages. A broad distinction can be made between processes with a single stage assessment of full proposals and those that first invite an outline, with full proposals invited at a second stage only for those which are shortlisted. This paper examines the effects of changing from a one-stage to a two-stage process within the UK's National Institute for Health Research's (NIHR) Research for Patient Benefit (RfPB) Programme which made this change in 2015. METHODS A retrospective comparative design was used to compare eight one-stage funding competitions (912 applications) with eight two-stage funding competitions (1090 applications). Comparisons were made between the number of applications submitted, number of peer and lay reviews required, the duration of the funding round, average external peer review scores, and the total costs involved. RESULTS There was a meat a two-stage application process increases the number of applications submitted to a funding round, is less burdensome and more efficient for all those involved with the process, is cost effective and has a small increase in peer reviewer scores. For the addition of fewer than 11 weeks to the process substantial efficiencies are gained which benefit funders, applicants and science. Funding agencies should consider adopting a two-stage application assessment process.BACKGROUND Several anti-D immunoglobulin strategies exist for preventing Rh hemolytic disease of the fetus and newborn. This study systematically assessed the clinical value of those therapeutic strategies. METHODS The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for eligible studies that evaluated the value of different anti-D immunoglobulin strategies in preventing maternal anti-D antibody sensitization. Combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. The network meta-analysis was conducted using Stata 14.2 and WinBUGS 1.4.3 software. RESULTS Twenty-four original studies involving 64860 patients were included. Among all therapeutic measures, injecting 300 μg anti-D immunoglobulin at 28 and 34 gestational weeks (antenatal 5/E) appeared to be the most effective measure for preventing maternal antibody sensitization (surface under the cumulative ranking curve [SUCRA] = 96.8%), while a single injection at 28 gestational weeks (SUCRA = 89.2%) was the second most effective. Administering no injection or a placebo (SUCRA = 0.0%) was the least effective intervention measure. CONCLUSION Among the therapeutic measures, antenatal 5/E appeared to be the best method for reducing the positive incidence of anti-D antibodies in the maternal serum; thus, it may be the most effective treatment for preventing fetal hemolytic disease.OBJECTIVE To elucidate the relationship between lipid layer thickness (LLT), incomplete blinking rate and tear film stability in patients with different myopia degrees after small-incision lenticule extraction (SMILE) and to determine whether there is a difference in the prevalence of dry eye disease (DED) after SMILE among patients with different myopia degrees. check details METHODS Fifty patients (100 eyes) were enrolled in this study; they were divided into 3 groups according to the degree of spherical refraction a low-myopia group (LMG; spherical refraction ≤-3.00 D, 20 eyes), a moderate-myopia group (MMG; -3.00 D 0.05), except preoperative age (p = 0.006). There were significant differences in the FBUT among the three groups at postoperative 1 w and 1 mo (p less then 0.05). There were significant differences in the incomplete blinking rate and FBUT between the LMG and the HMG at postoperative 1 mo (p less then 0.05). The number of first tear film breakup points located beyond the 6 mm diameter of the cornea was higher in the HMG than in the other groups. The prevalence of DED in the LMG, the MMG, the HMG was 15%, 8% and 23%, respectively, at 1 w postoperative and 30%, 45% and 53%, respectively, at postoperative 1 mo. The change in LLT was significantly correlated with the changes in FBUT (r = 0.408, p less then 0.001) and incomplete blinking rate (r = -0.266, p = 0.007). The change in OSDI was negatively correlated with the change in SI (r = -0.502, p = 0.000). CONCLUSIONS The changes in LLT and incomplete blinking rate decreased the stability of the tear film. The changes in LLT, FBUT and incomplete blinking rate differed postoperatively with different myopia degrees. The prevalence of DED was higher in the HMG than in the other two groups.The Caulobacter genus, including the widely-studied model organism Caulobacter crescentus, has been thought to be non-pathogenic and thus proposed as a bioengineering vector for various environmental remediation and medical purposes. However, Caulobacter species have been implicated as the causative agents of several hospital-acquired infections, raising the question of whether these clinical isolates represent an emerging pathogenic species or whether Caulobacters on whole possess previously-unappreciated virulence capability. Given the proposed environmental and medical applications for C. crescentus, understanding the potential pathogenicity of this bacterium is crucial. Consequently, we sequenced a clinical Caulobacter isolate to determine if it has acquired novel virulence determinants. We found that the clinical isolate represents a new species, Caulobacter mirare that, unlike C. crescentus, grows well in standard clinical culture conditions. C. mirare phylogenetically resembles both C. crescentus and the related C. segnis, which was also thought to be non-pathogenic. The similarity to other Caulobacters and lack of obvious pathogenesis markers suggested that C. mirare is not unique amongst Caulobacters and that consequently other Caulobacters may also have the potential to be virulent. We tested this hypothesis by characterizing the ability of Caulobacters to infect the model animal host Galleria mellonella. In this context, two different lab strains of C. crescentus proved to be as pathogenic as C. mirare, while lab strains of E. coli were non-pathogenic. Further characterization showed that Caulobacter pathogenesis in the Galleria model is mediated by lipopolysaccharide (LPS), and that differences in LPS chemical composition across species could explain their differential toxicity. Taken together, our findings suggest that many Caulobacter species can be virulent in specific contexts and highlight the importance of broadening our methods for identifying and characterizing potential pathogens.

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