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Background We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥65-years.Research design and methods We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model.Results XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65–79-year-olds and in ≥80-year-olds, respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time.Conclusion Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥65.

Adversarial robustness and generalization are both crucial properties of reliable machine learning models. In this paper, we study these properties in the context of quantum machine learning based on Lipschitz bounds. We derive parameter-dependent Lipschitz bounds for quantum models with trainable encoding, showing that the norm of the data encoding has a crucial impact on the robustness against data perturbations. Further, we derive a bound on the generalization error which explicitly involves the parameters of the data encoding. Based on these theoretical results, we propose a practical strategy for training robust and generalizable quantum models by regularizing the Lipschitz bound in the cost. Moreover, we show that, for fixed and nontrainable encodings, as those frequently employed in quantum machine learning, the Lipschitz bound cannot be influenced by tuning the parameters. Thus trainable encodings are crucial for systematically adapting robustness and generalization during training. The practical implications of our theoretical findings are illustrated with numerical results.

ABSTRACT We investigated whether the introduction of polymerase chain reaction (PCR) to replace culture as the primary diagnostic method for Campylobacter species in the Danish Departments of Clinical Microbiology (DCMs) was associated with a systematic change in the number of reported episodes of human campylobacteriosis from 2015 to 2022. We described a hypothetical scenario where PCR was solely used from 2018 to 2021. We analyzed the effect of primary diagnostic methods (culture or PCR) on the number of weekly episodes of human campylobacteriosis in a negative binomial regression adjusting for time, seasonality, COVID-19 restrictions, and DCMs. Furthermore, we applied the estimated PCR effect to the number of episodes that was identified using culture. Overall, PCR was associated with a 43% estimated increase of weekly campylobacteriosis episodes [rate ratio (RR) 1.43, 95% confidence interval (95% CI) 1.34–1.53]. Up to 17%–25% additional episodes would have been reported yearly from 2018 to 2021, had PCR been solely used. Through the lens of laboratory diagnostic methods, we described a systematic change in the number of reported episodes of human campylobacteriosis in Denmark. This is operationally relevant as considerably more episodes would have been identified had PCR been solely used. Changes in diagnostic methods should be considered in the epidemiological analysis of historical data. IMPORTANCE This study is important because it shows the potential epidemiological silence associated with the use of culture as the primary diagnostic method for the laboratory identification of human campylobacteriosis. Also, we show how polymerase chain reaction methods are associated with a systematic increase in the number of human campylobacteriosis episodes as reported by routine disease surveillance. These findings are operationally relevant and have public health implications because they tell how crucial it is to consider changes in diagnostic methods, e.g., in the epidemiological analysis of historical data and in the interpretation of future data in light of the past. We also believe that this study highlights how the synergy between microbiology and epidemiology is essential for disease surveillance.

Abstract Particle-Based (PB) simulations, including Molecular Dynamics (MD), provide access to system observables that are not easily available experimentally. However, in most cases, PB data needs to be processed after a simulation to extract these observables. One of the main challenges in post-processing PB simulations is managing the large amounts of data typically generated without incurring memory or computational capacity limitations. In this work, we introduce the post-processing tool: MDSuite. This software, developed in Python, combines state-of-the-art computing technologies such as TensorFlow, with modern data management tools such as HDF5 and SQL for a fast, scalable, and accurate PB data processing engine. This package, built around the principles of FAIR data, provides a memory safe, parallelized, and GPU accelerated environment for the analysis of particle simulations. The software currently offers 17 calculators for the computation of properties including diffusion coefficients, thermal conductivity, viscosity, radial distribution functions, coordination numbers, and more. Further, the object-oriented framework allows for the rapid implementation of new calculators or file-readers for different simulation software. The Python front-end provides a familiar interface for many users in the scientific community and a mild learning curve for the inexperienced. Future developments will include the introduction of more analysis associated with ab-initio methods, colloidal/macroscopic particle methods, and extension to experimental data.

In this paper, we present exemplarity as an alternative to the dominant evidence framework, and as the proper foundation for pedagogical reflection and action. This paper focuses attention on how exemplarity can serve to elicit and develop educational judgement. In other words, rather than evidence, teachers need good and bad examples of ways of acting and being to shape and sharpen their educational judgement. By turning to the exemplary approach, the space of reflection is widened, and educational judgement is challenged and provoked. The paper highlights how teacher judgement is formed through the challenge of examples.

Summary: Background: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. Methods: HIV-negative males 13–24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. Findings: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65–1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. Interpretation: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. Funding: EDCTP2, Gilead Sciences, Vetenskapsrådet.

Reinforcement learning (RL) is a flexible and efficient method for programming micro-robots in complex environments. Here we investigate whether RL can provide insights into biological systems when trained to perform chemotaxis. Namely, whether we can learn about how intelligent agents process given information in order to swim towards a target. We run simulations covering a range of agent shapes, sizes, and swim speeds to determine if the physical constraints on biological swimmers, namely Brownian motion, lead to regions where reinforcement learners’ training fails. We find that the RL agents can perform chemotaxis as soon as it is physically possible and, in some cases, even before the active swimming overpowers the stochastic environment. We study the efficiency of the emergent policy and identify convergence in agent size and swim speeds. Finally, we study the strategy adopted by the RL algorithm to explain how the agents perform their tasks. To this end, we identify three emerging dominant strategies and several rare approaches taken. These strategies, whilst producing almost identical trajectories in simulation, are distinct and give insight into the possible mechanisms behind which biological agents explore their environment and respond to changing conditions.

Background Individuals with a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, Coronavirus Disease 2019 (COVID-19)-related hospitalization, and COVID-19-related death, in individuals with prior SARS-CoV-2 infection, and to assess the effect of time since vaccination during periods with different dominant SARS-CoV-2 variants. Methods and findings This study used a nationwide cohort design including all individuals with a confirmed SARS-CoV-2 infection, who were alive, and residing in Denmark between 1 January 2020 and 31 January 2022. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, COVID-19 vaccination, age, sex, comorbidity, staying at hospital, and country of origin. The study population included were individuals with prior SARS-CoV-2 infection. Estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using a Poisson regression model and adjusted for age, sex, country of origin, comorbidity, staying at hospital, calendar time, and test incidence using a Cox regression model. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference. In total, 148,527 person-years and 44,192 SARS-CoV-2 infections were included for the analysis regarding reinfections. The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period, and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%), and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 71% (95% CI: -Inf to 100%) at 104 days or more after vaccination during the Alpha period, 94% (95% CI: 92% to 96%) 14 to 43 days after vaccination during the Delta period, and 60% (95% CI: 58% to 62%) 14 to 43 days after vaccination during the Omicron period. Waning immunity following vaccination was observed and was most pronounced during the Omicron period. Due to too few events, it was not possible to estimate VE for hospitalization and death. Study limitations include potentially undetected reinfections, differences in health-seeking behavior, or risk behavior between the compared groups. Conclusions This study shows that in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods. Katrine Finderup Nielsen and colleagues investigate vaccine effectiveness against SARS-CoV-2 reinfection, COVID-19 related hospitalization and COVID-19 related death, in previously infected individuals in Denmark. Author summary Why was this study done? Vaccination is one of the best tools we have to curb the spread of Coronavirus Disease 2019 (COVID-19). This study was conducted to gain knowledge on whether previously infected individuals would still benefit from vaccination against COVID-19. What did the researchers do and find? Using nationwide, Danish register data for three separate periods of different Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant dominance (Alpha, Delta, Omicron), more than 200,000 previously infected individuals were included in each period. For each period, the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, COVID-19-related admission, and COVID-19-related death was investigated. This study showed that among previously infected individuals who have completed a primary vaccination series, vaccines are still effective against SARS-CoV-2 reinfection during periods with SARS-CoV-2 variants Alpha, Delta, and Omicron, ranging from 60% (95% confidence interval (CI): 58% to 62%) to 94% (95% CI: 92% to 96%) and lasting up to 9 months. What do these findings mean? These findings show that previously infected individuals still benefit from COVID-19 vaccination during all three variant periods. Insight into VE in individuals with natural immunity is important to help decision makers plan vaccination strategies. Unmeasured biases such as changes in risk behavior might influence the result, but the completeness of the national, Danish registries counteract this. Future studies with longer follow-up time are necessary to ascertain VE against severe outcomes in those with previous infection.

The risk of severe adult respiratory coronavirus-2 (SARS-CoV-2) infection and the course of the infection among individuals with common variable immunodeficiency (CVID) relative to the general population have been a matter of debate. We conducted a Danish nationwide study comparing the timing of SARS-CoV-2 vaccination, the risk of first confirmed SARS-CoV-2 infection, re-infection, and the outcome of infection among individuals with CVID relative to an age- and gender matched control group. Cox regression was used to calculate incidence rate ratios. The CVID patients received SARS-CoV-2 vaccinations earlier than those included in the population control group. Even so, the risks of both first infection and re-infection were increased among the individuals with CVID. The CVID group also had increased risk for hospital contacts due to SARS-CoV-2 infection relative to the general population. However, reassuringly, the risk of mechanical ventilation and death did not differ between the groups, but the numbers were low in both groups, making the estimates uncertain. Though this is the largest study to investigate the risk of SARS-CoV-2 infections and outcomes hereof among individuals with CVID relative to the general population, we cannot rule out minor differences in severity, which might only be detectable with an even larger sample size.

Summary: Background: The level of protection after a SARS-CoV-2 infection against reinfection and COVID-19 disease remains important with much of the world still unvaccinated. Methods: Analysing nationwide, individually referable, Danish register data including RT-PCR-test results, we conducted a cohort study using Cox regression to compare SARS-CoV-2 infection rates before and after a primary infection among still unvaccinated individuals, adjusting for sex, age, comorbidity and residency region. Estimates of protection against infection were calculated as 1 minus the hazard ratio. Estimates of protection against symptomatic infections and infections leading to hospitalisation were also calculated. The prevalence of infections classified as symptomatic or asymptomatic was compared for primary infections and reinfections. The study also assessed protection against each of the main viral variants after a primary infection with an earlier variant by restricting follow-up time to distinct, mutually exclusive periods during which each variant dominated. Findings: Until 1 July 2021 the estimated protection against reinfection was 83.4% (95%CI: 82.2–84.6%); but lower for the 65+ year-olds (72.2%; 95%CI: 53.2–81.0%). Moderately higher estimates were found for protection against symptomatic disease, 88.3% overall (95%CI: 85.9–90.3%). First-time cases who reported no symptoms were more likely to experience a reinfection (odds ratio: 1.48; 95%CI: 1.35–1.62). By autumn 2021, when infections were almost exclusively caused by the Delta variant, the estimated protection following a recent first infection was 91.3% (95%CI: 89.7–92.7%) compared to 71.4% (95%CI: 66.9–75.3%) after a first infection over a year earlier. With Omicron, a first infection with an earlier variant in the past 3-6 months gave an estimated 51.0% (95%CI: 50.1–52.0%) protection, whereas a first infection longer than 12 months earlier provided only 19.0% (95%CI: 17.2–20.5%) protection. Protection by an earlier variant-infection against hospitalisation due to a new infection was estimated at: 86.6% (95%CI: 46.3–96.7%) for Alpha, 97.2% (95%CI: 89.0–99.3%) for Delta, and 69.8% (95%CI: 51.5–81.2%) for the Omicron variant. Interpretation: SARS-CoV-2 infection offered a high level of sustained protection against reinfection, comparable with that offered by vaccines, but decreased with the introduction of new main virus variants; dramatically so when Omicron appeared. Protection was lower among the elderly but appeared more pronounced following symptomatic compared to asymptomatic infections. The level of estimated protection against serious disease was somewhat higher than that against infection and possibly longer lasting. Decreases in protection against reinfection, seemed primarily to be driven by viral evolution. Funding: None.

BackgroundThe continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period.Methods and findingsA Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals.ConclusionsTwo vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Narrowing pores filled with an electrolyte usually slows down their charge-discharge dynamics. Here the authors demonstrate through molecular dynamics simulations and experiments with novolac-derived carbon electrodes how non-linear voltage sweeps can accelerate charging and discharging of subnanometer pores.

Abstract The Rivet library is an important toolkit in particle physics, and serves as a repository for analysis data and code. It allows for comparisons between data and theoretical calculations of the final state of collision events. This paper outlines several recent additions and improvements to the framework to include support for analysis of heavy ion collision simulated data. The paper also presents examples of these recent developments and their applicability in implementing concrete physics analyses.

Abstract Background Immediate uptake of antiretroviral therapy (ART) after an HIV-positive diagnosis (Test and Treat) is now being implemented in Uganda. Data are limited on lost to follow-up (LTFU) in high-risk cohorts that have initiated ‘Test and Treat’. We describe LTFU in a cohort of women of high-risk sexual behaviour who initiated ART under “Test and Treat”. Methods We performed a retrospective cohort study of participant records at the Good Health for Women Project (GHWP) clinic, a clinic in Kampala for women at high-risk of HIV-infection. We included HIV positive women ≥18 years who initiated ART at GHWP between August 2014 and March 2018. We defined LTFU as not taking an ART refill for ≥3 months from the last clinic appointment among those not registered as dead or transferred to another clinic. We used the Kaplan-Meier technique to estimate time to LTFU after ART initiation. Predictors of LTFU were assessed using a multivariable Cox proportional hazards model. Results The mean (±SD) age of the 293 study participants was 30.3 (± 6.5) years, with 274 (94%) reporting paid sex while 38 (13%) had never tested for HIV before enrolment into GHWP. LTFU within the first year of ART initiation was 16% and the incidence of LTFU was estimated at 12.7 per 100 person-years (95%CI 9.90–16.3). In multivariable analysis, participants who reported sex work as their main job at ART initiation (Adjusted Hazards Ratio [aHR] =1.95, 95%CI 1.10–3.45), having baseline WHO clinical stage III or IV (aHR = 2.75, 95% CI 1.30–5.79) were more likely to be LTFU. Conclusion LTFU in this cohort is high. Follow up strategies are required to support women on Test and Treat to remain on treatment, especially those who engage in sex work and those who initiate ART at a later stage of disease.

Objective To determine the association between baseline kidney function and subsequent all-cause mortality.Design and setting A general population-based cohort study from rural Uganda.Participants People aged 18 years and above with measured baseline estimated glomerular filtration rate (eGFR), recruited from survey rounds in 2011–2012 or 2014–2015 and followed up to March 2019.Outcome measure The primary outcome was all-cause mortality, identified through reports from community health workers and verified by verbal autopsy. The association between baseline eGFR category and mortality was determined using multivariable Cox regression.Results Of 5812 participants in both rounds, we included 5678 (97.7%) participants with kidney function and mortality data; the median age was 36 years (IQR 24–50), 60.7% were female, 10.3% were hypertensive, 9.8% were HIV-positive and 1.5% were diabetic. During a median follow-up of 5.0 years (IQR 3.7–6.0) there were 140 deaths. In age-adjusted and sex-adjusted analyses, eGFR 90 mL/min/1.73 m2. After inclusion of additional confounders (HIV, body mass index, diabetes, hypertension, alcohol and smoking status) into the model, eGFR

Measures to restrict physical inter-personal contact in the community have been widely implemented during the COVID-19 pandemic. We studied determinants for infection with SARS-CoV-2 with the aim of informing future public health measures. We conducted a national matched case-control study among unvaccinated not previously infected adults aged 18-49 years. Cases were selected among those testing positive for SARS-CoV-2 by RT-PCR over a five-day period in June 2021. Controls were selected from the national population register and were individually matched on age, sex and municipality of residence. Cases and controls were interviewed via telephone about contact with other persons and exposures in the community. We determined matched odds ratios (mORs) and 95% confidence intervals (95%CIs) by conditional logistical regression with adjustment for household size and immigration status. For reference, we provide a timeline of non-pharmaceutical interventions in place in Denmark from February 2020 to March 2022. We included 500 cases and 529 controls. We found that having had contact with another individual with a known infection was the main determinant for SARS-CoV-2 infection: reporting close contact with an infected person who either had or did not have symptoms resulted in mORs of 20 (95%CI:9.8-39) and 8.5 (95%CI 4.5-16) respectively. Community exposures were generally not associated with disease; several exposures were negatively associated. Consumption of alcohol in restaurants or cafés, aOR = 2.3 (95%CI:1.3-4.2) and possibly attending fitness centers, mOR = 1.4 (95%CI:1.0-2.0) were weakly associated with SARS-CoV-2 infection. Apart from these two factors, no community activities were more common amongst cases under the community restrictions in place during the study. The strongest risk factor for transmission was contact to an infected person. Results were in agreement with findings of our similar study conducted six month earlier.

A theory of neural networks (NNs) built upon collective variables would provide scientists with the tools to better understand the learning process at every stage. In this work, we introduce two such variables, the entropy and the trace of the empirical neural tangent kernel (NTK) built on the training data passed to the model. We empirically analyze the NN performance in the context of these variables and find that there exists correlation between the starting entropy, the trace of the NTK, and the generalization of the model computed after training is complete. This framework is then applied to the problem of optimal data selection for the training of NNs. To this end, random network distillation (RND) is used as a means of selecting training data which is then compared with random selection of data. It is shown that not only does RND select data-sets capable of outperforming random selection, but that the collective variables associated with the RND data-sets are larger than those of the randomly selected sets. The results of this investigation provide a stable ground from which the selection of data for NN training can be driven by this phenomenological framework.

Active goal-directed motion requires real-time adjustment of control signals depending on the system’s status, also known as control. The amount of information that needs to be processed depends on the desired motion and control, and on the system’s morphology. The morphology of the system may directly effectuate or support the desired motion. This morphology-based reduction to the neuronal ‘control effort’ can be quantified by a novel information-entropy-based approach. Here, we apply this novel measure of ‘control effort’ to active microswimmers of different morphology. Their motion is a combination of directed deterministic and stochastic motion. In spherical microswimmers, the active propulsion leads to linear velocities. Active propulsion of asymmetric L-shaped particles leads to circular or—on tilted substrates—directed motion. Thus, the difference in shape, i.e. the morphology of the particles, directly influence the motion. Here, we quantify how this morphology can be exploited by control schemes for the purpose of steering the particles towards targets. Using computer simulations, we found in both cases a significantly lower control effort for L-shaped particles. However, certain movements can only be achieved by spherical particles. This demonstrates that a suitably designed microswimmer’s morphology might be exploited to perform specific tasks.

Introduction Violence against women is a global public health concern; around a quarter of women will experience intimate partner physical or sexual violence during their lifetime. We assessed the impact of a gender transformative intervention for women designed to prevent intimate partner violence (IPV).Methods We conducted a cluster randomised controlled trial in Mwanza city, Tanzania, among women in newly formed neighbourhood groups to evaluate a 10-session participatory intervention that aims to empower women, prevent IPV and promote healthy relationships. Following a baseline interview, groups were randomly assigned (1:1 ratio) to the intervention or control arm. An intention-to-treat analysis was conducted to assess the impact of the intervention on the main outcomes, assessed 24 months postintervention. These included past-year physical IPV and sexual IPV (primary); past-year emotional abuse; and acceptability and tolerance of IPV.Results Between September 2015 and February 2017, 1265 women were recruited in 66 neighbourhoods and randomly allocated to intervention (n=627 women in 33 neighbourhoods) or control (n=638 women in 33 neighbourhoods). Assessment of outcomes was completed for 551 (88%) intervention and 575 (90%) control women. Among intervention women, 113 (21%) reported physical IPV compared with 117 (20%) control women (adjusted OR (aOR) 0.98, 95% CI 0.72 to 1.33, p=0.892), and 109 (20%) intervention women reported sexual IPV compared with 121 (21%) control women (aOR 0.98, 95% CI 0.72 to 1.32, p=0.881). Intervention women reported less emotional abuse (aOR 0.74, 95% CI 0.56 to 0.98, p=0.035), and were less likely to express attitudes accepting of IPV (aOR 0.49, 95% CI 0.36 to 0.66, p

Background: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? Methods: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21–42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment.Primary outcome, change in average MBL from screening to ‘treatment’, was analysed by allocated treatment, for all with data. Trial Registration: ClinicalTrials.gov NCT01769820; EudractCT 2012–003,405–98 Findings: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. Interpretation: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. Funding: UK MRC DCS/DPFS grant MR/J003611/1.

The aetiology of bacterial vaginosis (BV) is not well-understood, and prevalence appears to be higher among women living in sub-Saharan Africa. A recent conceptual model implicates three main bacteria (Gardnerella vaginalis; Atopobium vaginae; and Prevotella bivia), sexual activity, sialidase activity, and biofilm formation in the pathogenesis of BV. We describe the vaginal microbiota, presence of the putative sialidase A gene of G. vaginalis, and biofilm among 386 adolescent girls aged 17 and 18 years in a cross-sectional study in Mwanza, Tanzania around the time of expected sexual debut. Vaginal swabs were collected and tested by quantitative polymerase chain reaction (qPCR) for five Lactobacillus species, G. vaginalis, A. vaginae, P. bivia, the sialidase A gene of G. vaginalis, and by fluorescence in situ hybridisation (FISH) for evidence of G. vaginalis and A. vaginae biofilm. We conducted a risk factor analysis of G. vaginalis, A. vaginae and P. bivia, and explored the associations between biofilm, the presence of the sialidase A gene, and non-optimal vaginal microbiota (Nugent 4–7). L. crispatus and L. iners were detected in 69 and 82% of girls, respectively. The prevalence of L. crispatus was higher than previously reported in earlier studies among East and Southern African women. G. vaginalis, A. vaginae, P. bivia were independently associated with reported penile-vaginal sex. Samples with all three BV-associated bacteria made up the highest proportion of samples with Nugent-BV compared to samples with each bacterium alone or together in pairs. Of the 238 girls with G. vaginalis, 63% had the sialidase A gene detected, though there was no difference by reported sexual activity (p = 0.197). Of the 191 girls with results for sialidase A gene and FISH, there was strong evidence for an increased presence of sialidase A gene among those with evidence of a biofilm (p < 0.001). There was a strong association between biofilm and non-optimal microbiota (aOR67.00; 95% CI 26.72–190.53). These results support several of the steps outlined in the conceptual model, although the role of sexual activity is less clear. We recommend longitudinal studies to better understand changes in vaginal microbiota and biofilm formation around the time of sexual debut.

Abstract Background Information on the size of populations is crucial for planning of service and resource allocation to communities in need of health interventions. In resource limited settings, reliable census data are often not available. Using publicly available Google Earth Pro and available local household survey data from fishing communities (FC) on Lake Victoria in Uganda, we compared two simple methods (using average population density) and one simple linear regression model to estimate populations of small rural FC in Uganda. We split the dataset into two sections; one to obtain parameters and one to test the validity of the models. Results Out of 66 FC, we were able to estimate populations for 47. There were 16 FC in the test set. The estimates for total population from all three methods were similar, with errors less than 2.2%. Estimates of individual FC populations were more widely discrepant. Conclusions In our rural Ugandan setting, it was possible to use a simple area based model to get reasonable estimates of total population. However, there were often large errors in estimates for individual villages.

Introduction Globally, around 30% of ever-partnered women have experienced physical and/or sexual intimate partner violence (IPV) during their lifetime. To date, most research into causes and prevention of IPV involves surveys of women, with little research into risk-factors for male perpetration. This paper describes a survey of male partners of women participating in the MAISHA cluster randomised trial (CRT) of an IPV prevention intervention, in Mwanza City, Tanzania. Using linked couples’ data, we explore man-, woman-, and relationship-/household-level factors associated with physical and sexual IPV. Methods Women were interviewed at baseline and 29-months follow-up. At follow-up, women were asked for consent to invite their partner to participate in the male survey. We describe response rates for the women’s follow-up and male partners’ surveys, and identify factors associated with women’s consent to approach partners. Multivariate logistic regression was used to explore factors associated with women’s past-year experiences of physical and sexual IPV. Results 512 (65%) partnered women consented for the partner to be approached, higher among intervention than control women. 425 (83%) male partners were interviewed. Women consenting were disproportionately likely to be in longer-term relationships. Past-year IPV was associated with lower consent among control women, but greater consent in the intervention arm. Factors associated with increased odds of physical IPV were women’s childhood experiences of abuse, young age, women’s lower income and women’s attitudes justifying IPV. Sexual IPV was associated with women’s childhood experiences of abuse, young age, educational disparity within couple, men’s alcohol use and women’s poor mental health. Conclusions We successfully conducted a survey of male partners with the full consent of women trial participants. The breadth of factors associated with IPV demonstrates the need for IPV prevention interventions to work with women and men, and specifically couples. Interventions should address risk-factors for both physical and sexual IPV.

Summary: Background: Globally, about 30% of women have experienced physical or sexual violence, or both, from an intimate partner during their lifetime. Associations between poverty and women's increased risk of intimate partner violence have been observed. We therefore aimed to assess the effect of a violence prevention intervention delivered to women participating in a group-based microfinance scheme in Tanzania. Methods: We did a cluster randomised controlled trial among women taking part in a microfinance loan scheme in Mwanza city, Tanzania. A microfinance loan group was only enrolled if at least 70% of members consented. We randomly assigned the microfinance groups in blocks of six to receive either the intervention (ie, the intervention arm) or be wait-listed for the intervention after the trial (ie, the control arm). Women in both arms of the trial met weekly for loan repayments. Only those in the intervention arm participated in the ten-session MAISHA intervention that aims to empower women and prevent intimate partner violence. Given the nature of the intervention, it was not possible to mask participants or the research team. The primary outcome was a composite of reported past-year physical or sexual intimate partner violence, or both. Secondary outcome measures were past-year physical, sexual, and emotional intimate partner violence; acceptability and tolerance of intimate partner violence; and attitudes and beliefs related to intimate partner violence. These outcomes were assessed 24 months after the intervention. An intention-to-treat analysis was done, adjusting for age, education, and baseline measure of the respective outcome. The study is registered with ClinicalTrials.gov, number NCT02592252. Findings: Between September, 2014, and June, 2015, 66 (65%) of 101 microfinance groups approached in the study area met the trial eligibility criteria and were enrolled, of which 33 (n=544 women) were allocated to the intervention arm and 33 (n=505 women) to the control arm. Overall, 485 (89%) of 544 women in the intervention arm and 434 (86%) of 505 in the control arm completed the outcomes assessment. Among the intervention arm, 112 (23%) of 485 women reported past-year physical or sexual intimate partner violence, or both, compared with 119 (27%) of 434 in the control arm (adjusted odds ratio [aOR] 0·69, 95% CI 0·47–1·01; p=0·056). Women in the intervention arm were less likely to report physical intimate partner violence (aOR 0·64, 95% CI 0·41–0·99; p=0·043) and were less likely to express attitudes accepting of intimate partner violence (0·45, 0·34–0·61; p

We analyze the internal structure and hydration properties of poly(diallyl dimethyl ammonium chloride)/poly(styrene sulfonate sodium salt) oligoelectrolyte multilayers at early stages of their layer-by-layer growth process. Our study is based on large-scale molecular dynamics simulations with atomistic resolution that we presented recently [Sánchez et al., Soft Matter 2019, 15, 9437], in which we produced the first four deposition cycles of a multilayer obtained by alternate exposure of a flat silica substrate to aqueous electrolyte solutions of such polymers at 0.1M of NaCl. In contrast to any previous work, here we perform a local structural analysis that allows us to determine the dependence of the multilayer properties on the distance to the substrate. We prove that the large accumulation of water and ions next to the substrate observed in previous overall measurements actually decreases the degree of intrinsic charge compensation, but this remains as the main mechanism within the interface region. We show that the range of influence of the substrate reaches approximately 3 nm, whereas the structure of the outer region is rather independent from the position. This detailed characterization is essential for the development of accurate mesoscale models able to reach length and time scales of technological interest.

The vaginal murine HSV-2 infection model is very useful in studying mucosal immunity against HSV-2 (Overall et al., 1975; Renis et al., 1976; Parr and Parr, 2003). Histologically, the vagina of Depo-Provera-treated mice is lined by a single layer of mucus secreting columnar epithelial cells overlying two to three layers of proliferative cells. Even though this is morphologically different from the human vagina, it closely resembles the endocervical epithelium, which is thought to be the primary site of HSV-2 infection in women (Parr et al., 1994; Kaushic et al., 2011). In the protocol presented here, mice are pre-treated with Depo-Provera before intra-vaginal inoculation with HSV-2. The virus replicates in the mucosal epithelium from where it spreads to and replicates in the CNS including the spinal cord, brain stem, cerebrum and cerebellum. Cytokine responses can be detected in vaginal washings using ELISA or in vaginal tissues using qPCR. Further, the recruitment of leukocytes to the vagina can be determined by flow cytometry. The model is suitable for research of both innate and adaptive immunity to HSV-2 infection.

Coarse-grained models of soft matter are usually combined with implicit solvent models that take the electrostatic polarizability into account via a dielectric background. In biophysical or nanoscale simulations that include water, this constant can vary greatly within the system. Performing molecular dynamics or other simulations that need to compute exact electrostatic interactions between charges in those systems is computationally demanding. We review here several algorithms developed by us that perform exactly this task. For planar dielectric surfaces in partial periodic boundary conditions, the arising image charges can be either treated with the MMM2D algorithm in a very efficient and accurate way or with the electrostatic layer correction term, which enables the user to use his favorite 3D periodic Coulomb solver. Arbitrarily-shaped interfaces can be dealt with using induced surface charges with the induced charge calculation (ICC*) algorithm. Finally, the local electrostatics algorithm, MEMD(Maxwell Equations Molecular Dynamics), even allows one to employ a smoothly varying dielectric constant in the systems. We introduce the concepts of these three algorithms and an extension for the inclusion of boundaries that are to be held fixed at a constant potential (metal conditions). For each method, we present a showcase application to highlight the importance of dielectric interfaces.

We investigate the chemical equilibria of weak polyelectrolyte nanogels with reaction ensemble Monte Carlo simulations. With this method, the chemical identity of the nanogel monomers can change between neutral or charged following the acid-base equilibrium reaction HA ⇌ A− + H+. We investigate the effect of changing the chemical equilibria by modifying the dissociation constant K a . These simulations allow for the extraction of static properties like swelling equilibria and the way in which charge—both monomer and ionic—is distributed inside the nanogel. Our findings reveal that, depending on the value of K a , added salt can either increase or decrease the gel size. Using the calculated mean-charge configurations of the nanogel from the reaction ensemble simulation as a quenched input to coupled lattice-Boltzmann molecular dynamics simulations, we investigate dynamical nanogel properties such as the electrophoretic mobility μ and the diffusion coefficient D.