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Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60–0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63–0·93, p=0·008). Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

Early identification of inpatient discharges to skilled nursing facilities (SNFs) facilitates care transition planning. Predictive information in admission history and physical notes (H&Ps) is dispersed across long documents. Language models adeptly predict clinical outcomes from text but have limitations: token length constraints, noisy inputs, and opaque outputs. Therefore, we developed extraction-based language model classification (ELC): generative language models distill H&Ps into task-relevant categories (“Structured Extracted Data”) before summarizing them into a concise narrative (“AI Risk Snapshot”). We hypothesized that language models utilizing AI Risk Snapshots to predict SNF discharges would perform the best. In this retrospective observational study, nine language models predicted SNF discharges from unstructured predictors (raw H&P text, truncated assessment and plan) and ELC-derived predictors (Structured Extracted Data, AI Risk Snapshots). ELC substantially reduced input length (AI Risk Snapshot median 141 tokens vs raw H&P median 2,120 tokens) and improved average AUROC and AUPRC across models. The best performance was achieved by Bio+Clinical BERT fine-tuned on AI Risk Snapshots (AUROC = .851). AI Risk Snapshots enhanced interpretability by aligning with nurse case managers’ risk assessments and facilitating prompt design. Structuring and summarizing H&Ps via ELC thus mitigates the practical limitations of language models and improves SNF discharge prediction.

Background Hospital acquired anemia is common during admission and can result in increased transfusion and length of stay. Recumbent posture is known to lead to lower hemoglobin measurements. We tested to see if an initiative promoting evening lab draws would lead to higher hemoglobin measurements due to more time in upright posture during the day and evening. Methods We included patients hospitalized on 2 medical units, beginning March 26, 2020 and discharged prior to January 25, 2021. On one of the units, we implemented an initiative to have routine laboratory draws in the evening rather than the morning starting on August 26, 2020. There were 1217 patients on the control unit and 1265 on the intervention unit during the entire study period. First we used a linear mixed-effects model to see if timing of blood draw was associated with hemoglobin level in the pre-intervention period. We then compared levels of hemoglobin before and after the intervention using a difference-in-difference analysis. Results In the pre-intervention period, evening blood draws were associated with higher hemoglobin compared to morning (0.28; 95% CI, 0.22–0.35). Evening blood draws increased with the intervention (10.3% vs 47.9%, P > 0.001). However, the intervention floor was not associated with hemoglobin levels in difference-in-difference analysis (coefficient of −0.15; 95% CI, −0.51–0.21). Conclusions While evening blood draws were associated with higher hemoglobin levels, an intervention that successfully changed timing of routine labs to the evening did not lead to an increase in hemoglobin levels.

Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners. Female partners of HIV-infected men (aged 15–49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878. 474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86–1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77–1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83–1·12; p=0·61). Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important. Bill & Melinda Gates Foundation and National Institutes of Health.

Background. The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated. Methods. A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a + dendritic cells, CD4 + T cells, and CD8 + T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial. Results. HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11—9.55] and 3.18 [95% CI, 1.14—8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a + dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm 2 [interquartile range {IQR}, 29.4—138.3 cells/mm 2 ]), compared with males who were persistently negative for HPV (32.1 cells/mm 2 [IQR, 3.1—96.2 cells/mm 2 ]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05). Conclusions. HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion.

Objectives Human papillomavirus (HPV) infection causes genital warts, penile cancer and cervical cancer. Africa has one of the highest rates of penile and cervical cancers, but there are little data on high-risk human papillomavirus (HR-HPV) prevalence in heterosexual men. Knowledge of HR-HPV prevalence, risk factors and genotype distribution among heterosexual men is important to establish risk-reduction prevention strategies. Methods 1578 uncircumcised men aged 15–49 years who enrolled in male circumcision trials in Rakai, Uganda, were evaluated for HR-HPV from swabs of the coronal sulcus/glans using Roche HPV Linear Array. Adjusted prevalence risk ratios (adjPRRs) were estimated using modified Poisson multivariable regression. Results HPV prevalence (either high risk or low risk) was 90.7% (382/421) among HIV-positive men and 60.9% (596/978) among HIV-negative men (PRR 1.49, 95% CI 1.40 to 1.58). HIV-positive men had a significantly higher risk of infection with three or more HR-HPV genotypes (PRR=5.76, 95% CI 4.27 to 7.79). Among HIV-positive men, high-risk sexual behaviours were not associated with increased HR-HPV prevalence. Among HIV-negative men, HR-HPV prevalence was associated with self-reported genital warts (adjPRR 1.57, 95% CI 1.07 to 2.31). Among all men (both HIV negative and HIV positive), HR-HPV prevalence was associated with more than 10 lifetime sexual partners (adjPRR 1.30, 95% CI 1.01 to 1.66), consistent condom use (adjPRR 1.31, 95% CI 1.08 to 1.60) and HIV infection (adjPRR 1.80, 95% CI 1.60 to 2.02). HR-HPV prevalence was lower among men who reported no sexual partners during the past year (adjPRR 0.47, 95% CI 0.23 to 0.94). Conclusion The burden of HR-HPV infection is high among heterosexual men in sub-Saharan Africa and most pronounced among the HIV-infected individuals.

A highly effective HIV vaccine has been the goal of vaccinologists for nearly 35 years. A successful vaccine would need to induce broadly neutralizing antibodies (bnAbs) that are capable of neutralizing multiple HIV strains (see the Perspective by Agazio and Torres). Steichen et al. report a strategy in which the first vaccine shot can lead to immune responses that generate desired bnAbs. By combining knowledge of human antibody repertoires and structure to guide design, they validated candidate immunogens through functional preclinical testing. Saunders et al. designed immunogens with differences in binding strength for bnAb precursors, which enabled selection of rare mutations after immunization. The immunogens promoted bnAb precursor maturation in humanized mice and macaques. Science , this issue p. eaax4380 , p. eaay7199 ; see also p. 1197 Engineering antibodies against rare HIV mutations is required for HIV neutralizing antibody development.

Action to reduce anthropogenic impact on the environment and species within it will be most effective when targeted towards activities that have the greatest impact on biodiversity. To do this effectively we need to better understand the relative importance of different activities and how they drive changes in species' populations. Here, we present a novel, flexible framework that reviews evidence for the relative importance of these drivers of change and uses it to explain recent alterations in species' populations. We review drivers of change across four hundred species sampled from a broad range of taxonomic groups in the UK. We found that species' population change (~1970-2012) has been most strongly impacted by intensive management of agricultural land and by climatic change. The impact of the former was primarily deleterious, whereas the impact of climatic change to date has been more mixed. Findings were similar across the three major taxonomic groups assessed (insects, vascular plants and vertebrates). In general, the way a habitat was managed had a greater impact than changes in its extent, which accords with the relatively small changes in the areas occupied by different habitats during our study period, compared to substantial changes in habitat management. Of the drivers classified as conservation measures, low-intensity management of agricultural land and habitat creation had the greatest impact. Our framework could be used to assess the relative importance of drivers at a range of scales to better inform our policy and management decisions. Furthermore, by scoring the quality of evidence, this framework helps us identify research gaps and needs.