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In the realm of survey data analysis, encountering substantial variance relative to bias is a common occurrence. In this study, we present an innovative strategy to tackle this issue by introducing slightly biased variance estimators. These estimators incorporate a constant c within the range of 0 to 1, which is determined through the minimization of Mean Squared Error (MSE) for [Formula: see text]. This research builds upon the foundation laid by Kourouklis (2012, A new estimator of the variance based on minimizing mean squared error. The American Statistician, 66(4), 234–236) and extends their work into the domain of survey sampling. Extensive simulation studies are conducted to illustrate the superior performance of the adjusted variance estimators when compared to standard variance estimators, particularly in terms of MSE. These findings underscore the efficacy of our proposed approach in enhancing the precision of variance estimation within the context of survey data analysis.

Objectives: The association between thrombocytopenia and parasite density or disease severity is described in numerous studies. In recent years, several studies described the protective role of platelets in directly killing Plasmodium parasites, mediated by platelet factor 4 (PF4) binding to Duffy antigen. This study aimed to evaluate the protective role of platelets in young children who are Duffy antigen-negative, such as those in sub-Saharan Africa. Methods: A zero-inflated negative binomial model was used to relate platelet count and parasite density data collected in a longitudinal birth cohort. Platelet factors were measured by enzyme-linked immunosorbent assay in samples collected from malaria-infected children who participated in a cross-sectional study. Results: We described that an increase of 10,000 platelets/μl was associated with a 2.76% reduction in parasite count. Increasing levels of PF4 and CXCL7 levels were also significantly associated with a reduction in parasite count. Conclusions: Platelets play a protective role in reducing parasite burden in Duffy-negative children, possibly mediated through activation of the innate immune system.

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.

In Sub-Saharan Africa, malaria continues to be associated with adverse pregnancy outcomes including stillbirth, early neonatal death, preterm delivery, and low birth weight. Current preventive measures are insufficient and new interventions are urgently needed. However, before such interventions can be tested in pregnant women, background information on pregnancy outcomes in this target population must be collected. We conducted an observational study in Ouélessébougou, Mali, a malaria-endemic area where first antenatal visit commonly occurs during the second trimester of pregnancy, hindering calculation of miscarriage rate in the population. To accurately determine the rate of miscarriage, 799 non-pregnant women of child-bearing age were enrolled and surveyed via monthly follow up visits that included pregnancy tests. Out of 505 women that completed the study, 364 became pregnant and 358 pregnancies were analyzed: 43 (12%) resulted in miscarriage, 28 (65.1%) occurred during the first trimester of pregnancy. We also determined rates of stillbirth, neonatal death, preterm delivery, and small for gestational age. The results showed high rate of miscarriage during the first trimester and established a basis to evaluate new interventions to prevent pregnancy malaria. This survey design enabled identification of first trimester miscarriages that are often missed by studies conducted in antenatal clinics.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT0297 4608].

Coronavirus disease 2019 (COVID-19) is an infectious disease typically manifested as a respiratory infection with a range of symptoms from a mild viral illness to a severe acute respiratory syndrome with multiorgan failure and death. We report a case of a young man presenting with compartment syndrome secondary to COVID-19 viral myositis, with a protracted hospital course further complicated by extensive venous and arterial thrombosis. As the coronavirus pandemic evolves, our understanding of the virus continues to improve; however, a host of unanswered questions remain about atypical presentation and management and treatment options.

Abstract Background Plasmodium falciparum-infected erythrocytes (IE) sequester in deep vascular beds where their adhesion is mediated by an array of endothelial surface receptors. Because parasite adhesion has been associated with disease, antibodies that block this activity may confer protective immunity. Here, levels of plasma anti-adhesion activity and surface reactivity against freshly collected IEs from malaria-infected children were measured in a Malian birth cohort and related to child age and malaria infection history. Methods Plasma samples from children enrolled at birth in a longitudinal cohort study of mother–infant pairs in Ouelessebougou, Mali were collected at multiple time points during follow-up visits. Anti-adhesion antibodies (i.e., inhibit IE binding to any of several endothelial receptors) and reactivity with surface IE proteins were measured using a binding inhibition assay and by flow cytometry, respectively. Results Levels of antibodies that inhibit the binding of children’s IE to the receptors ICAM-1, integrin α3β1 and laminin increased with age. The breadth of antibodies that inhibit ICAM-1 and laminin adhesion (defined as the proportion of IE isolates whose binding was reduced by ≥ 50%) also significantly increased with age. The number of malaria infections prior to plasma collection was associated with levels of plasma reactivity to IE surface proteins, but not levels of anti-adhesion activity. Conclusions Age is associated with increased levels of antibodies that reduce adhesion of children’s IE to three of the ten endothelial receptors evaluated here. These results suggest that anti-adhesion antibodies to some but not all endothelial receptors are acquired during the first few years of life.

PlasmodiumPlasmodium falciparum

Abstract Background Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated. Methods Pregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30–32, and delivery. Antibody levels to VAR2CSA domains were measured using a multiplex bead-based assay. Results Antibody levels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibody levels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodies levels sharply declined after an infection. A relationship between any VAR2CSA antibody specificity and protection from adverse pregnancy outcomes was not detected. Conclusions During malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibody reactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.

Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼ 480 individuals from the Cermaq Canada broodstock program and search for SNPs associated with growth and age at sexual maturation. Using a mixed model approach we identified markers showing a significant association with growth, grilsing (early sexual maturation) and late sexual maturation. The most significant associations were found for grilsing, with markers located in Ssa10, Ssa02, Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28, Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13. Candidate genes, which were linked to these genetic markers, were identified and some of them show a direct relationship with developmental processes, especially for those in association with sexual maturation. However, the relatively low power to detect genetic markers associated with growth (days to 5 kg) in this GWAS indicates the need to use a higher density SNP array in order to overcome the low levels of linkage disequilibrium observed in Atlantic salmon before the information can be incorporated into a selective breeding program.

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