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The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history. During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).

Understanding what aspects of daily life protect against loneliness is increasingly important for promoting well-being among older adults. This study investigates how different types of everyday social interactions are associated with chronic loneliness. We analyze data that were collected via in-home surveys and an ecological momentary assessment module from a probability-based sample of 272 adults aged 55 and older residing in Indiana. Participants were prompted four times per day over the course of seven days to report on their current activities and social experiences. Contrary to common assumptions, the quantitative measures of daily social interactions, such as the proportion of moments spent alone, the proportion of moments spent socializing, and the mean number of interaction partners during the study period were not significantly related to loneliness. However, the qualitative measures of social interactions—specifically, the presence of bonding social capital (e.g., emotional closeness) and the absence of stressful interactions—were associated with lower levels of loneliness. These findings underscore the importance of emotionally meaningful engagement and social strain over the sheer frequency or quantity of interactions, suggesting that the quality of daily social experiences is a key factor in supporting mental well-being in later life.

This visualization provides a snapshot of social isolation in America over a 20-year period. The author leverages data from the American Time Use Survey to estimate the percentage of Americans who report a complete lack of social contact during a single day. Contrary to prior claims, there was no clear evidence of increasing isolation during the 2000s and 2010s. There was, however, a marked increase in the percentage of Americans who were socially isolated during the coronavirus pandemic. Adopting a micro view of social isolation contributes to contemporary debates by highlighting social interactions rather than broad assessments of social integration such as social relationships or group participation. Although these latter concepts are important in their own ways, focusing on social interactions speaks to issues that are often considered synonymous with social integration such as the exchange of support, resources, and feelings of belongingness.

Most riboswitches are metabolite-binding RNA structures located in bacterial messenger RNAs where they control gene expression. We have discovered a riboswitch class in many bacterial and archaeal species whose members are selectively triggered by fluoride but reject other small anions, including chloride. These fluoride riboswitches activate expression of genes that encode putative fluoride transporters, enzymes that are known to be inhibited by fluoride, and additional proteins of unknown function. Our findings indicate that most organisms are naturally exposed to toxic levels of fluoride and that many species use fluoride-sensing RNAs to control the expression of proteins that alleviate the deleterious effects of this anion.

Numerous studies highlight the value of spouses spending quality time together. Although it is undoubtedly important to make sufficient time for each other, minimal research considers the degree to which married individuals socialize with others outside the presence of their spouses. These latter interactions provide an opportunity to practice social autonomy (i.e., time during which one’s actions are not directly influenced by their spouse). Drawing on data from the American Time Use Survey, the author finds that (1) the number of minutes married women engage in nonspousal interactions peaks in midlife and declines in later life, (2) married men spend more time engaging in nonspousal interactions at work than married women, and (3) the number of minutes married men engage in nonspousal interactions in nonwork settings steadily decreases as they age. These findings suggest that age and gender play central roles in the social lives of married couples.

Negation in Tuparí (Tupían; Brazil) is an exclusively nominal category: verbs must enter into a nominalized form to accept the negator -’om and must undergo a subsequent process of reverbalization so as to combine with tense and evidential morphology. These category-changing processes leave -’om in a low position in the clause, and scopal evidence confirms that negation is also interpreted low. In keeping with the low structural position of -’om, the same negative strategy known from finite matrix clauses appears in nonfinite embedded contexts as well. Tuparí shows that negative phrases exhibit more crosslinguistic variation than standardly assumed: they may appear in either the nominal or verbal extended projection. This finding is not compatible with cartographic efforts to strictly circumscribe the distribution of NegP within the clause. Like nominal tense in Tupi-Guaraní and other languages, in Tuparí a grammatical category normally associated with the verbal domain instead surfaces within the nominal one. For the purpose of typological comparison, the Tuparí facts highlight the need for classifications of negation that take into account both constructional asymmetries between affirmative and negative clauses and individual negator morphemes’ selectional and categorical properties.

Background. Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. Methods, In the period 2004—2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children. Results. Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63—1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21—1.15) after 3 days and .55 (.34—.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing < 1.5 kg (MRR = .43 [.21—.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations. Conclusions. Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.

From a game of darts to neurorehabilitation, the ability to explore and fine tune our movements is critical for success. Past work has shown that exploratory motor behaviour in response to reinforcement (reward) feedback is closely linked with the basal ganglia, while movement corrections in response to error feedback is commonly attributed to the cerebellum. While our past work has shown these processes are dissociable during adaptation, it is unknown how they uniquely impact exploratory behaviour. Moreover, converging neuroanatomical evidence shows direct and indirect connections between the basal ganglia and cerebellum, suggesting that there is an interaction between reinforcement-based and error-based neural processes. Here we examine the unique roles and interaction between reinforcement-based and error-based processes on sensorimotor exploration in a neurotypical population. We also recruited individuals with Parkinson’s disease to gain mechanistic insight into the role of the basal ganglia and associated reinforcement pathways in sensorimotor exploration. Across three reaching experiments, participants were given either reinforcement feedback, error feedback, or simultaneously both reinforcement & error feedback during a sensorimotor task that encouraged exploration. Our reaching results, a re-analysis of a previous gait experiment, and our model suggests that in isolation, reinforcement-based and error-based processes respectively boost and suppress exploration. When acting in concert, we found that reinforcement-based and error-based processes interact by mutually opposing one another. Finally, we found that those with Parkinson’s disease had decreased exploration when receiving reinforcement feedback, supporting the notion that compromised reinforcement-based processes reduces the ability to explore new motor actions. Understanding the unique and interacting roles of reinforcement-based and error-based processes may help to inform neurorehabilitation paradigms where it is important to discover new and successful motor actions.

Television sitcoms frequently invoke social network concepts to highlight specific jokes or scenes. In this visualization, the author draws on data from NBC’s The Office to explore how show creator Greg Daniels and his writing staff leveraged a well-known social network concept in the overall development of their show. By identifying the presence of structural holes (i.e., the absence of ties between two or more network members), The Office produced multiple novel storylines in which different sets of characters who did not routinely interact were jointly forced into comedic situations. As evidenced through a network visualization—and interviews with the show’s writers—Greg Daniels was clearly thinking like a social network theorist in his careful development of one of the most successful sitcoms in television history.

Frequent and unregulated use of antimicrobials (AM) in livestock requires public health attention as a likely selection pressure for resistant bacteria. Studies among small-holders, who own a large percentage of the world's livestock, are vital for understanding how practices involving AM use might influence resistance. We present a cultural-ecological mixed-methods analysis to explore sectors of veterinary care, loosely regulated AM use, and human exposure to AMs through meat and milk consumption across three rural to peri-urban Tanzanian ethnic groups (N = 415 households). Reported use of self-administered AMs varied by ethnic group (Maasai: 74%, Arusha: 21%, Chagga: 1%) as did consultation with professional veterinarians (Maasai: 36%, Arusha: 45%, Chagga: 96%) and observation of withdrawal of meat and milk from consumption during and following AM treatment (Maasai: 7%, Arusha: 72%, Chagga: 96%). The antibiotic oxytetracycline was by far the most common AM in this sample. Within ethnic groups, herd composition differences, particularly size of small-stock and cattle herds, were most strongly associated with differences in lay AM use. Among the Arusha, proxies for urbanization, including owning transportation and reliance on \"zero-grazing\" herds had the strongest positive associations with veterinarian consultation, while distance to urban centers was negatively associated. For Maasai, consultation was negatively associated with use of traditional healers or veterinary drug-shops. Observation of withdrawal was most strongly associated with owning technology among Maasai while Arusha observance displayed seasonal differences. This \"One-Health\" analysis suggests that livelihood and cultural niche factors, through their association with practices in smallholder populations, provide insight into the selection pressures that may contribute to the evolution and dissemination of antimicrobial resistance.