Testing a non-destructive assay to track Plasmodium sporozoites in mosquitoes over time

Abstract Background The extrinsic incubation period (EIP), defined as the time it takes for malaria parasites in a mosquito to become infectious to a vertebrate host, is one of the most influential parameters for malaria transmission but remains poorly understood. The EIP is usually estimated by quantifying salivary gland sporozoites in subsets of mosquitoes, which requires terminal sampling. However, assays that allow repeated sampling of individual mosquitoes over time could provide better resolution of the EIP. Methods We tested a non-destructive assay to quantify sporozoites of two rodent malaria species, Plasmodium chabaudi and Plasmodium berghei, expelled throughout 24-h windows, from sugar-soaked feeding substrates using quantitative-PCR. Results The assay is able to quantify sporozoites from sugar-soaked feeding substrates, but the prevalence of parasite-positive substrates was low. Various methods were attempted to increase the detection of expelled parasites (e.g. running additional technical replicates; using groups rather than individual mosquitoes), but these did not increase the detection rate, suggesting that expulsion of sporozoites is variable and infrequent. Conclusions We reveal successful detection of expelled sporozoites from sugar-soaked feeding substrates. However, investigations of the biological causes underlying the low detection rate of sporozoites (e.g. mosquito feeding behaviour, frequency of sporozoite expulsion or sporozoite clumping) are needed to maximise the utility of using non-destructive assays to quantify sporozoite dynamics. Increasing detection rates will facilitate the detailed investigation on infection dynamics within mosquitoes, which is necessary to explain the highly variable EIP of Plasmodium and to improve understanding of malaria transmission dynamics. Graphical Abstrac

Differential attraction in mosquito-human interactions and implications for disease control.

Mosquito-borne diseases are a major burden on human health worldwide and their eradication through vector control methods remains challenging. In particular, the success of vector control interventions for targeting diseases such as malaria is under threat, in part due to the evolution of insecticide resistance, while for other diseases effective control solutions are still lacking. The rate at which mosquitoes encounter and bite humans is a key determinant of their capacity for disease transmission. Future progress is strongly reliant on improving our understanding of the mechanisms leading to a mosquito bite. Here, we review the biological factors known to influence the attractiveness of mosquitoes to humans, such as body odour, the skin microbiome, genetics and infection by parasites. We identify the knowledge gaps around the relative contribution of each factor, and the potential links between them, as well as the role of natural selection in shaping vector-host-parasite interactions. Finally, we argue that addressing these questions will contribute to improving current tools and the development of novel interventions for the future. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'

From Targets to Solutions: Implementing a Trauma Quality Improvement Bundle in Cameroon

BackgroundGlobal surgery research efforts have been criticized for failure to transition from problem identification to intervention implementation. We developed a context-appropriate trauma quality improvement (TQI) bundle to ameliorate care gaps at a regional referral hospital in Cameroon. We determined associations between bundle implementation and improvement in trauma resuscitation practices.MethodsWe implemented a TQI bundle consisting of a hospital-specific trauma protocol, staff training, a trauma checklist, provision of essential emergency trauma supplies in the resuscitation area, and monthly quality improvement meetings. We compared trends in target process measures (e.g., frequency and timing of vital sign collection and primary survey interventions) in the six-month period pre- and post-bundle implementation using Wilcoxon rank-sum and Fisher's exact tests.ResultsWe compared 246 pre-bundle patients with 203 post-bundle patients. Post-bundle patients experienced a greater proportion of all vital signs collected compared to the pre-intervention cohort (0 % pre-bundle vs. 69 % post-bundle, p < 0.001); specifically, the proportion of respiratory rate (0.8 % pre-bundle vs. 76 % post-bundle, p < 0.001) and temperature (7 % pre-bundle vs. 91 % post-bundle, p < 0.001) vital sign collection significantly increased. The post-bundle cohort had vital signs measured sooner (74 % vital signs measured within 15 min of arrival pre-bundle vs. 90 % post-bundle, p < 0.001) and more frequently per patient (7 % repeated vitals pre-bundle vs 52 % post-bundle, p < 0.001). Key primary survey interventions such as respiratory interventions (1 % pre-bundle vs. 8 % post-bundle, p < 0.001) and cervical collar placement (0 % pre-bundle vs. 7 % post-bundle, p < 0.001) also increased in the post-bundle cohort.ConclusionsThe implementation of a context-appropriate TQI bundle was associated with significant improvements in previously identified trauma care deficits at a single regional hospital. Data-derived interventions targeting frontline capacity at the local level can bridge the gap between identifying care limitations and improvement in resource-limited settings

On the variability of quasars: a link between Eddington ratio and optical variability?

Repeat scans by the Sloan Digital Sky Survey (SDSS) of a 278 square degree stripe along the Celestial equator have yielded an average of over 10 observations each for nearly 8,000 spectroscopically confirmed quasars. Over 2500 of these quasars are in the redshift range such that the CIV emission line is visible in the SDSS spectrum. Utilising the width of these CIV lines and the luminosity of the nearby continuum, we estimate black hole masses for these objects. In an effort to isolate the effects of black hole mass and luminosity on the photometric variability of our dataset, we create several subsamples by binning in these two physical parameters. By comparing the ensemble structure functions of the quasars in these bins, we are able to reproduce the well-known anticorrelation between luminosity and variability, now showing that this anticorrelation is independent of the black hole mass. In addition, we find a correlation between variability and the mass of the central black hole. By combining these two relations, we identify the Eddington ratio as a possible driver of quasar variability, most likely due to differences in accretion efficiency.Comment: 13 pages, 5 figures, Accepted for publication in MNRA

Who seeks care after intimate partner violence in Cameroon? sociodemographic differences between a hospital and population sample of women

IntroductionLittle is known regarding health care seeking behaviors of women in sub-Saharan Africa, specifically Cameroon, who experience violence. The proportion of women who experienced violence enrolled in the Cameroon Trauma Registry (CTR) is lower than expected.MethodsWe concatenated the databases from the October 2017-December 2020 CTR and 2018 Cameroon Demographic and Health Survey (DHS) into a singular database for cross-sectional study. Continuous and categorical variables were compared with Wilcoxon rank-sum and Fisher's exact test. Multivariable logistic regression examined associations between demographic factors and women belonging to the DHS or CTR cohort. We performed additional classification tree and random forest variable importance analyses.Results276 women (13%) in the CTR and 197 (13.1%) of women in the DHS endorsed violence from any perpetrator. A larger percentage of women in the DHS reported violence from an intimate partner (71.6% vs. 42.7%, p<0.001). CTR women who experienced IPV demonstrated greater university-level education (13.6% vs. 5.0%, p<0.001) and use of liquid petroleum gas (LPG) cooking fuel (64.4% vs. 41.1%, p<0.001). DHS women who experienced IPV reported greater ownership of agricultural land (29.8% vs. 9.3%, p<0.001). On regression, women who experienced IPV using LPG cooking fuel (aOR 2.55, p = 0.002) had greater odds of belonging to the CTR cohort while women who owned agricultural land (aOR 0.34, p = 0.007) had lower odds of presenting to hospital care. Classification tree variable observation demonstrated that LPG cooking fuel predicted a CTR woman who experienced IPV while ownership of agricultural land predicted a DHS woman who experienced IPV.ConclusionWomen who experienced violence presenting for hospital care have characteristics associated with higher SES and are less likely to demonstrate factors associated with residence in a rural setting compared to the general population of women experiencing violence

Student Learning Outcomes Poster Session for CSB/SJU Joint Board of Trustees Meeting, December 5th, 2014

A faculty and student poster session was held focusing on student learning outcomes at the December 5th, 2014 joint Board of Trustee meeting. The posters focused on using assessment of student learning to improve teaching and learning and covered student learning outcomes at the course, departmental, and institutional levels

Automated Diabetic Retinopathy Image Assessment Software: Diagnostic Accuracy and Cost-Effectiveness Compared with Human Graders.

OBJECTIVE: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders. DESIGN: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS. PARTICIPANTS: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013. METHODS: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration. MAIN OUTCOME MEASURES: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome. RESULTS: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective. CONCLUSIONS: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Spermiogenesis in the African sideneck turtle (Pelusios castaneus): Acrosomal vesicle formation and nuclear morphogenesis

Testicular samples were collected from African sideneck turtles (Pelusios castaneus) at the peak of spermiogenesis in order to describe spermatid acrosomal vesicle formation and nuclear morphogenesis. Acrosomal vesicle formation commences with a Golgi transport vesicle attaching to a round spermatid, followed by the emergence of an acrosome granule. This is followed by the development of the sub-acrosomal space, which becomes enlarged as nuclear elongation and condensation continue. The round spermatid elongates and the emerging elongating spermatid successively becomes surrounded by circular, longitudinal and slanting microtubules of the manchette. The acrosomal vesicle becomes visible with an acrosome granule resting on the base of the electron dense material. Acrosomal vesicle morphogenesis in the African sideneck turtle results in a highly compartmentalized acrosome divisible into the acrosomal cortex and medulla. The future position of the flagellum starts to develop, being encircled by mitochondria while the distal centriole becomes obvious and the emerging flagellum grossly divisible into the connecting piece, midpiece, principal piece and endpiece. Although acrosomal vesicle formation and nuclear morphogenesis during spermiogenesis in the turtle are consistent with other reptilian species, a few differences were observed. The major difference observed was the formation of a single acrosome granule, which manifests prior to the attachment of the acrosomal vesicle to spermatid nucleus. The other differences observed were the emergence of two endonuclear canals in the elongating spermatid and the presence of slanting microtubules of the manchette. The observed developmental variations are expected to be valuable in future phylogenetic studies and potentially serve to test certain hypotheses concerning the reproductive status of turtle species. Findings from this study add to the growing database of spermatid morphology in turtles, thereby providing insights into variations in mature sperm morphology in the species. Keywords: Acrosomal vesicle, Spermatid, Spermiogenesis, Turtle, Ultrastructur