Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We ...propose using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability.
Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants.
We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022).
A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 12% received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval CI, 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.
Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).
The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and ...COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses. For diseases like COVID-19 and dengue fever caused by RNA viruses that exist as families of viral variants with the potential to escape vaccine-induced immunity, the development of more efficacious vaccines is also necessary. Here, we describe the development and characterisation of novel VLP vaccine candidates using SARS-CoV-2 and dengue virus (DENV), containing the major viral structural proteins, as protypes for a novel approach to produce VLP vaccines. The VLPs were characterised by Western immunoblot, enzyme immunoassay, electron and atomic force microscopy, and
and
immunogenicity studies. Microscopy techniques showed proteins self-assemble to form VLPs authentic to native viruses. The inclusion of the glycolipid adjuvant, α-galactosylceramide (α-GalCer) in the vaccine formulation led to high levels of natural killer T (NKT) cell stimulation
, and strong antibody and memory CD8
T cell responses
, demonstrated with SARS-CoV-2, hepatitis C virus (HCV) and DEN VLPs. This study shows our unique vaccine formulation presents a promising, and much needed, new vaccine platform in the fight against infections caused by enveloped RNA viruses.
Objective The purpose of this study was to assess knowledge of the human papillomavirus (HPV), cervical cancer, and HPV vaccination in African American women (AAW). Study Design This study was a ...quantitative cross-sectional survey of English-speaking, AAW, 18-70 years old who were recruited from a community fair in Chicago, IL. Surveys were distributed to a convenience sample to assess knowledge of HPV, cervical cancer, and the HPV vaccine. Cumulative knowledge scores were calculated for each participant, and analysis was performed to identify factors that were associated with adequate knowledge scores. Results Three hundred twenty-two surveys were distributed; 242 surveys were collected, and 215 surveys met inclusion criteria. Mean knowledge score was 12.3 ± 4.2 (mean ± SD) of a maximum score of 28 (range, 3–23); 73% of participants scored <65% on the knowledge portion of the survey. Education level ( P = .007), household income ( P = .010), and having a child who had been offered the HPV vaccine ( P = .041) were associated with adequate (≥65% accuracy) knowledge scores. Conclusion Knowledge of HPV, cervical cancer, and HPV vaccination was low in this urban African American adult female population. Targeted educational health programs are needed to increase awareness among these women who have the highest rate of cervical cancer mortality in the United States. Such patient educational programs must be developed by physicians and should address the cultural and literacy needs of this particular group of women. In addition, AAW exert influence on the health of their communities and are integral in health-related decision-making; thus, educating them through their health care providers will have far ranging impact.
Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts ...have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure.
We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA).
The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρS = 0.88, pFDR < .001) and negatively related to whole-brain FA (r = −0.20), as well as FA of the corticospinal tract (all pFWE < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = −0.16, pFWE < .05). Inattention-specific and irritability-specific factors were not linked to FA.
Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation.
In many countries health system data remain too weak to accurately enumerate Plasmodium falciparum malaria cases. In response, cartographic approaches have been developed that link maps of infection ...prevalence with mathematical relationships to predict the incidence rate of clinical malaria. Microsimulation (or 'agent-based') models represent a powerful new paradigm for defining such relationships; however, differences in model structure and calibration data mean that no consensus yet exists on the optimal form for use in disease-burden estimation. Here we develop a Bayesian statistical procedure combining functional regression-based model emulation with Markov Chain Monte Carlo sampling to calibrate three selected microsimulation models against a purpose-built data set of age-structured prevalence and incidence counts. This allows the generation of ensemble forecasts of the prevalence-incidence relationship stratified by age, transmission seasonality, treatment level and exposure history, from which we predict accelerating returns on investments in large-scale intervention campaigns as transmission and prevalence are progressively reduced.
Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms ...mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards.
To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology.
Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R2 = 0.42) and more sadness (p < .001, marginal R2 = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R2 = 0.076), reduced connectivity between the somatic–motor–salience and the control network (p = .041, marginal R2 = 0.040), and fewer provincial hubs in the somatic–motor–salience, control, and default mode networks (all pFWE < .05).
The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence.
One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.
Boosting is the induction of autonomic dysreflexia (AD) to reflexively activate otherwise dormant thoracolumbar sympathetic circuitry to "boost" the capacity of the cardiovascular system and enhance ...exercise performance. AD is a life-threatening condition unique to individuals with spinal cord injury (SCI) characterized by a sudden increase in sympathetic activity below the level of the SCI. Here we report on the temporal HR response to an episode of unintentional boosting during a validated field-based exercise performance test in an athlete with tetraplegia.An athlete with SCI (C6 motor-complete, sensory-incomplete) completed a 20 ×20 m repeated sprint field test on two consecutive days. During the 13th sprint on day 2, the athlete unintentionally boosted via bladder overdistension. Average HR when boosted (i.e., sprints 14-20) was considerably higher than before boosting (141 ± 4 vs 116 ± 7 bpm) and compared with corresponding sprints on day 1 (141 ± 4 bpm vs 120 ± 1 bpm). Average time to complete 20 m sprints when boosted was also faster than the corresponding sprints on day 1 (6.70 ± 0.05 s vs 6.87 ± 0.05 s).This case report highlights the immediate effect of boosting on HR and field-based exercise performance and supports the suggestion that exercise performance in athletes with SCI is limited by cardiovascular capacity.
Objective To comprehensively evaluate the effect of parental presence on pediatric intensive care unit rounds. Study design A prospective, observational and survey-based study comprised of (1) ...observation of rounds (2) “rounding event assessments” (brief surveys specific to 1 rounding event, completed by health care providers HCPs n = 375) (3) qualitative interviews with parents (36 who joined rounds and 16 who elected not to join), and (4) qualitative written surveys from HCPs (63 nurses, 39 doctors). Results Eighty-one percent of parents who chose to join rounds reported that participation increased their overall satisfaction with their child's care. In 57% of rounding events, at least 1 HCP learned new, pertinent information from the parents. However, in 32% of rounding events, at least 1 HCP believed parental presence limited discussion. Forty-seven percent of parents who participated in rounds and 88% of those who chose not to participate volunteered that participation has the potential to increase parental confusion and anxiety ( P = .02). Conclusions Most parents and physicians agree that parents should be invited to participate on rounds. Parents report increased satisfaction from participation, and parents provide new information when on rounds. However, parental presence may limit discussion during rounds which may adversely affect patient care.
Epidemiological rate parameters of host generalist parasites are difficult to estimate, especially in cases where variation in parasite performance can be attributed to host species. Such cases are ...likely common for generalist parasites of sympatric grazing mammals. In this study, we combined data from experimental exposures in cattle and sheep and natural infections in elk to compare the recruitment, morphology and reproduction of adult Dicrocoelium dendriticum, a generalist trematode that has emerged in sympatric grazing hosts in Cypress Hills Provincial Park, Alberta. Overall, there were no significant differences in the recruitment of metacercariae and in the pre-patency period of adults in experimentally exposed cattle and sheep. All flukes reached reproductive maturity and the degree of reproductive inequality between individual flukes within each infrapopulation was moderate and approximately equal among the three host species. Neither fluke size nor per capita fecundity was constrained by density dependence. Thus, fitness parameters associated with growth and reproduction were approximately equivalent among at least three species of definitive host, two of which are sympatric on pastures in this Park. The generalist life-history strategy of this trematode, which is known to extend to other stages of its life cycle, has likely contributed to its invasion history outside its native range in Europe.
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