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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. Author summary: Reinforcement-based and error-based processes play a pivotal role in regulating our movements. Converging neuroanatomical evidence show interconnected reinforcement-based and error-based neural circuits. Yet is unclear how reinforcement-based and error-based processes interact to influence sensorimotor behavior. In our past work we showed that reinforcement-based and error-based processes are dissociable. Building on this work, here we show that these process can also interact to influence trial-by-trial sensorimotor behaviour. [ABSTRACT FROM AUTHOR]

Several structured noncoding RNAs in bacteria are essential contributors to fundamental cellular processes. Thus, discoveries of additional ncRNA classes provide opportunities to uncover and explore biochemical mechanisms relevant to other major and potentially ancient processes. A candidate structured ncRNA named the “raiA motif” has been found via bioinformatic analyses in over 2,500 bacterial species. The gene coding for the RNA typically resides between the raiA and comFC genes of many species of Bacillota and Actinomycetota. Structural probing of the raiA motif RNA from the Gram-positive anaerobe Clostridium acetobutylicum confirms key features of its sophisticated secondary structure model. Expression analysis of raiA motif RNA reveals that the RNA is constitutively produced but reaches peak abundance during the transition from exponential growth to stationary phase. The raiA motif RNA becomes the fourth most abundant RNA in C. acetobutylicum, excluding ribosomal RNAs and transfer RNAs. Genetic disruption of the raiA motif RNA causes cells to exhibit substantially decreased spore formation and diminished ability to aggregate. Restoration of normal cellular function in this knock-out strain is achieved by expression of a raiA motif gene from a plasmid. These results demonstrate that raiA motif RNAs normally participate in major cell differentiation processes by operating as a trans-acting factor. [ABSTRACT FROM AUTHOR]

From a baby's babbling to a songbird practising a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species' neural firing, gait patterns and reaching behaviour. The past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here, we test a fundamentally different idea—that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments, we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development or when recovering from a neurological disorder to discover and learn new motor actions. [ABSTRACT FROM AUTHOR]

From a baby's babbling to a songbird practising a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species' neural firing, gait patterns and reaching behaviour. The past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here, we test a fundamentally different idea—that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments, we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development or when recovering from a neurological disorder to discover and learn new motor actions. [ABSTRACT FROM AUTHOR]

Riboswitches rely on structured aptamer domains to selectively sense their target ligands and regulate gene expression. However, some riboswitch aptamers in bacteria carry mutations in their otherwise strictly conserved binding pockets that change ligand specificities. The aptamer domain of a riboswitch class originally found to selectively sense guanine forms a three-stem junction that has since been observed to exploit numerous alterations in its ligand-binding pocket. These rare variants have modified their ligand specificities to sense other purines or purine derivatives, including adenine, 2'-deoxyguanosine (three classes), and xanthine. Herein, we report the characteristics of a rare variant that is narrowly distributed in the Paenibacillaceae family of bacteria. Known representatives are always associated with genes encoding 8-oxoguanine deaminase. As predicted from this gene association, these variant riboswitches tightly bind 8-oxoguanine (8-oxoG), strongly discriminate against other purine derivatives, and function as genetic "ON" switches. Following exposure of cells to certain oxidative stresses, a representative 8-oxoG riboswitch activates gene expression, likely caused by the accumulation of 8-oxoG due to oxidative damage to G nucleobases in DNA, RNA, and the nucleotide pool. Furthermore, an engineered version of the variant aptamer was prepared that exhibits specificity for 8-oxoadenine, further demonstrating that RNA aptamers can acquire mutations that expand their ability to detect and respond to oxidative damage. [ABSTRACT FROM AUTHOR]

Background: In Sweden, vaccine uptake is exceptionally high due to an efficient child immunization program. More than 97% of Swedish children were vaccinated at child health care centers (CHCs) according to the schedule at 2 years of age in 2021. From the age of 6 years, vaccinations are given within the school health care. Maintaining high vaccination coverage over time is one of the central motives to explore and understand drivers for vaccine acceptance. The current study aimed to assess parental vaccine acceptance concerning the national immunization program and explore factors contributing to the high vaccine acceptance in Sweden. Methods: Parents of children aged 1–2 years and 8–12 years were recruited through purposive sampling and asked to participate in focus groups held in three cities in Sweden, in February and March 2019. In total, 47 parents participated in two focus groups per city, one session for parents of younger (1–2 years) and older (8–12 years) children respectively. The focus group discussions were analyzed using qualitative content analysis. Results: Parents of children aged 1–2 years expressed the themes; strong compliance to and protection of the value of vaccinations; parents feel safe with an attentive relationship with their nurse; the spectrum of communication needs is essential to meet. For parents to children aged 8–12 years, the themes expressed were; vaccinate to do good for the individual and society; a foundation of trust is built at CHCs for decisions later on; decisions for vaccination become more complex as children get older; communication changes as children get older and need to be explicit and tailored to the situation. Conclusion: Both individual and societal perspectives were shown to influence the vaccination decision for childhood immunizations, as manifested in parental reflections and experiences. As nurses have a key role, it is important to provide them with continued support and tools to facilitate their support for parents in making informed decisions. Continuous work for supporting driving factors for vaccination over time is needed to maintain high vaccine acceptance in Sweden. [ABSTRACT FROM AUTHOR]

We routinely have physical interactions with others, whether it be handing someone a glass of water or jointly moving a heavy object together. These sensorimotor interactions between humans typically rely on visual feedback and haptic feedback. Recent single-participant studies have highlighted that the unique noise and time delays of each sense must be considered to estimate the state, such as the position and velocity, of one's own movement. However, we know little about how visual feedback and haptic feedback are used to estimate the state of another person. Here, we tested how humans utilize visual feedback and haptic feedback to estimate the state of their partner during a collaborative sensorimotor task. Across two experiments, we show that visual feedback dominated haptic feedback during collaboration. Specifically, we found that visual feedback led to comparatively lower task-relevant movement variability, smoother collaborative movements, and faster trial completion times. We also developed an optimal feedback controller that considered the noise and time delays of both visual feedback and haptic feedback to estimate the state of a partner. This model was able to capture both lower task-relevant movement variability and smoother collaborative movements. Taken together, our empirical and modeling results support the idea that visual accuracy is more important than haptic speed to perform state estimation of a partner during collaboration. [ABSTRACT FROM AUTHOR]

The naturally occurring variability in our movements often poses a significant challenge when attempting to produce precise and accurate actions, which is readily evident when playing a game of darts. Two differing, yet potentially complementary, control strategies that the sensorimotor system may use to regulate movement variability are impedance control and feedback control. Greater muscular co-contraction leads to greater impedance that acts to stabilize the hand, while visuomotor feedback responses can be used to rapidly correct for unexpected deviations when reaching toward a target. Here, we examined the independent roles and potential interplay of impedance control and visuomotor feedback control when regulating movement variability. Participants were instructed to perform a precise reaching task by moving a cursor through a narrow visual channel. We manipulated cursor feedback by visually amplifying movement variability and/or delaying the visual feedback of the cursor. We found that participants decreased movement variability by increasing muscular co-contraction, aligned with an impedance control strategy. Participants displayed visuomotor feedback responses during the task but, unexpectedly, there was no modulation between conditions. However, we did find a relationship between muscular co-contraction and visuomotor feedback responses, suggesting that participants modulated impedance control relative to feedback control. Taken together, our results highlight that the sensorimotor system modulates muscular co-contraction, relative to visuomotor feedback responses, to regulate movement variability and produce accurate actions. NEW & NOTEWORTHY The sensorimotor system has the constant challenge of dealing with the naturally occurring variability in our movements. Here, we investigated the potential roles of muscular co-contraction and visuomotor feedback responses to regulate movement variability. When we visually amplified movements, we found that the sensorimotor system primarily uses muscular co-contraction to regulate movement variability. Interestingly, we found that muscular co-contraction was modulated relative to inherent visuomotor feedback responses, suggesting an interplay between impedance and feedback control. [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma. A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models. A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (β = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (β = 16.1, 95% CI: 1.5 to 30.8). Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children. [ABSTRACT FROM AUTHOR]

Background and Objectives Social connectedness has been linked prospectively to cognitive aging, but there is little agreement about the social mechanisms driving this relationship. This study evaluated 9 measures of social connectedness, focusing on 2 forms of social enrichment—access to an expansive and diverse set of loosely connected individuals (i.e. social bridging) and integration in a supportive network of close ties (i.e. social bonding). Research Design and Methods This study used egocentric network and cognitive data from 311 older adults in the Social Networks in Alzheimer Disease study. Linear regressions were used to estimate the association between social connectedness and global cognitive function, episodic memory, and executive function. Results Measures indicative of social bridging (larger network size, lower density, presence of weak ties, and proportion of non-kin) were consistently associated with better cognitive outcomes, while measures of social bonding (close ties, multiplex support, higher frequency of contact, better relationship quality, and being married) largely produced null effects. Discussion and Implications These findings suggest that the protective benefits of social connectedness for cognitive function and memory may operate primarily through a cognitive reserve mechanism that is driven by irregular contact with a larger and more diverse group of peripheral others. [ABSTRACT FROM AUTHOR]

Objectives The cognitive reserve hypothesis has been proposed as a key mechanism explaining the link between social networks and cognitive function but has rarely been empirically tested using neuroimaging data. This study examines whether social network attributes moderate the association between amygdalar volume and cognitive function. Methods Data were from the Social Networks in Alzheimer Disease study (N = 154) and Indiana Alzheimer's Disease Research Center. Social networks were measured using the PhenX Social Network Battery. Regional data from magnetic resonance imaging (amygdalar volume [AV]) were analyzed using FreeSurfer software. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and consensus diagnosis. Linear regression analyses were conducted to test the moderating role of social networks on the association between AV and cognitive function. Results Participants with greater ability to span multiple social roles and subgroups within their networks scored higher on the MoCA after adjusting for sociodemographic variables, depression, frequency of contact, and AV. Social networks moderated the association between AV and cognitive function. Discussion Among participants who engaged in diverse and loosely connected social networks, the expected adverse cognitive effects of brain volume in regions implicated in socioemotional processing were attenuated. These findings suggest that cognitive stimulation achieved through social interaction with a diverse array of social relationships across multiple contexts may help promote cognitive reserve. [ABSTRACT FROM AUTHOR]

Purpose: To determine the correlation of the T1-weighted signal intensity ratio (T1 SIR, or T1 Score) and arterial-to-delayed venous enhancement ratio (ADV ratio) of the pancreas with pancreatic fibrosis on histopathology. Methods: Sixty consecutive adult CP patients who had an MRI/MRCP study prior to pancreatic surgery were analyzed. Three blinded observers measured T1 SIR of pancreas to spleen (T1 SIR p/s), pancreas-to-paraspinal muscle (T1 SIR p/m), ADV ratio, and Cambridge grade. Histopathologic grades were given by a gastrointestinal pathologist using Ammann's fibrosis score. Statistical analysis included Spearman's correlation coefficient of the T1 SIR, ADV ratio, Cambridge grade with the fibrosis score, and weighted kappa for interobserver agreement. Results: The study population included 31 female and 29 male patients, with an average age of 52.1 (26–78 years). Correlations between fibrosis score and T1 SIR p/s, T1 SIR p/m, and ADV ratio were ρ = − 0.54 (p = 0.0001), ρ = − 0.19 (p = 0.19), and ρ = − 0.39 (p = 0.003), respectively. The correlation of Cambridge grade with fibrosis score was ρ = 0.26 (p = 0.07). There was substantial interobserver agreement (weighted kappa) for T1 SIR p/s (0.78), T1 SIR p/m (0.71), and ADV ratio (0.64). T1 SIR p/s of ≤ 1.20 provided a sensitivity of 74% and specificity of 50% (AUC: 0.74), while ADV ratio of ≤ 1.10 provided a sensitivity of 75% and specificity of 55% (AUC: 0.68) to detect a fibrosis score of ≥ 6. Conclusion: There is a moderate negative correlation between the T1 Score (SIR p/s) and ADV ratio with pancreatic fibrosis and a substantial interobserver agreement. These parenchymal metrics show a higher correlation than the Cambridge grade. [ABSTRACT FROM AUTHOR]

Objectives The potential impact of social distancing policies during the coronavirus disease 2019 (COVID-19) pandemic on social isolation and loneliness is of increasing global concern. Although many studies focus primarily on loneliness, patterns of social isolation—particularly physical and digital isolation—are understudied. We examined changes in social isolation, physical isolation, digital isolation, and loneliness in U.S. adults older than 50 before and during the lockdown. Methods Two waves of the Health and Retirement Study, a national panel sample of U.S. adults older than 50 years, were used. Fixed-effects regression models were fitted to identify within-person change from 2016 to 2020 to examine the impact of social distancing policies during the pandemic. Results There was an increase in physical isolation and social isolation among respondents during the COVID-19 social distancing policies. However, respondents experienced no change in digital isolation or loneliness. The increase in physical isolation was only present for people with high COVID-19 concern, whereas people with low concern experienced no change in physical isolation. Discussion Despite an increase in physical isolation due to the social distancing policies, U.S. adults aged older than 50 stayed connected through digital contact and were resilient in protecting themselves from loneliness. [ABSTRACT FROM AUTHOR]

The aptamer portions of previously reported riboswitch classes that sense guanine, adenine, or 2'-deoxyguanosine are formed by a highly similar three-stem junction with distinct nucleotide sequences in the regions joining the stems. The nucleotides in these joining regions form the major features of the selective ligand-binding pocket for each aptamer. Previously, we reported the existence of additional, rare variants of the predominant guanine-sensing riboswitch class that carry nucleotide differences in the ligand-binding pocket, suggesting that these RNAs have further diversified their structures and functions. Herein, we report the discovery and analysis of three naturally occurring variants of guanine riboswitches that are narrowly distributed across Firmicutes. These RNAs were identified using comparative sequence analysis methods, which also revealed that some of the gene associations for these variants are atypical for guanine riboswitches or their previously known natural variants. Binding assays demonstrate that the newfound variant riboswitch representatives recognize xanthine, guanine, or 20 -deoxyguanosine, with the guanine class exhibiting greater discrimination against related purines than the more common guanine riboswitch class reported previously. These three additional variant classes, together with the four previously discovered riboswitch classes that employ the same three-stem junction architecture, reveal how a simple structural framework can be diversified to expand the range of purine-based ligands sensed by RNA. [ABSTRACT FROM AUTHOR]

We often acquire sensory information from another person's actions to make decisions on how to move, such as when walking through a crowded hallway. Past interactive decision-making research has focused on cognitive tasks that did not allow for sensory information exchange between humans prior to a decision. Here, we test the idea that humans accumulate sensory evidence of another person's intended action to decide their own movement. In a competitive sensorimotor task, we show that humans exploit time to accumulate sensory evidence of another's intended action and utilize this information to decide how to move. We captured this continuous interactive decision-making behaviour with a drift-diffusion model. Surprisingly, aligned with a 'paralysis-by-analysis' phenomenon, we found that humans often waited too long to accumulate sensory evidence and failed to make a decision. Understanding how humans engage in interactive and online decision-making has broad implications that spans sociology, athletics, interactive technology, and economics. [ABSTRACT FROM AUTHOR]

Objectives Personal networks play a fundamental role in the daily lives of older adults. Although many studies examine how life course factors and personal preferences shape network formation, fewer consider how the places in which older adults live present opportunities and obstacles to cultivate social relationships. In the present study, we explore how geographic context is associated with the ability to bridge social ties within one's personal network. Methods We use data from the Person-to-Person Health Interview Survey (N = 709), a representative sample of Indiana residents. Personal network data were collected using 4 name-generating prompts. Logistic regression models and linear regression models were used to assess 2 measures of network bridging. Results A minority of respondents reported the ability to bridge ties within their networks. Respondents residing in rural and mixed counties were less likely than urban respondents to have at least one member of their network who was completely disconnected from all other members. Discussion These findings suggest that the communities in which older adults live condition opportunities for accessing unique network resources. Additional research adopting a network perspective is needed to provide insight into geographic disparities occurring among the older population. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the association between non-spousal support and mortality risk differs by marital status. Methods: Using data from the National Social Life, Health, and Aging Project (N = 2460), we estimate a series of logistic regression models to assess how non-spousal support moderates the relationship between marital status and mortality across a 5-year period. Results: Never married respondents who had minimal perceived access to non-spousal support had a greater probability of death compared to married respondents with similar levels of non-spousal support. The disparity in mortality risk between these two groups disappeared when non-spousal support was high. Discussion: Although family and friends play an important role in mortality risk in later life, these findings suggest that never married older adults exhibit a heightened dependence on support from non-spousal sources. Future research and policies should explore ways in which never married older adults can be integrated into a supportive social environment. [ABSTRACT FROM AUTHOR]

A large literature highlights the link between cognitive function and social networks in later life. Yet there remains uncertainty about the factors driving this relationship. In the present study, we use measures of subjective cognitive decline and clinical cognitive assessments on a sample of older adults to investigate whether the relationship between cognitive function and social networks is driven by psychosocial factors. We found a consistent link between clinical cognitive assessments and social network type, but no association between subjective concerns of cognitive decline and networks. Participants who exhibited signs of clinical cognitive impairment were more likely to have restricted networks (i.e., smaller networks consisting of fewer contacts, more interconnectivity, and less social diversity) compared to their cognitively normal counterparts, regardless of subjective measures of cognitive decline – both from the participant's perspective and study partner's perspective. These findings suggest that neither cognitively impaired older adults nor their network members appear to consciously dissolve social ties on the basis of perceived cognitive decline. However, it remains unclear whether the association between clinical cognitive impairment and social network type indicates the protective nature of social networks against cognitive decline or a subconscious process leading to social contraction. [ABSTRACT FROM AUTHOR]

Background Social network characteristics are associated with health outcomes in later life, including mortality. Moreover, there are well-established mortality disparities across race and ethnicity. Although previous studies have documented these associations separately, limited research considers the two in tandem. The present study addressed how the associations between social network characteristics and mortality differ across race and ethnicity in later life. Methods Data were from the National Social Life, Health, and Aging Project. At baseline, 3005 respondents were interviewed with regards to their health and social networks. Five years later, 430 respondents had died. Logistic regression models were used to estimate the odds of all-cause mortality over the study period. Results Network size and kin composition were negatively associated with mortality, whereas density was positively associated with mortality. There was a stronger negative association between the kin composition and mortality for Hispanic respondents compared with white and Black respondents. Conclusion The present study contributes to the large literature documenting the link between social networks and health by highlighting the importance of analyzing networks through a sociocultural lens. [ABSTRACT FROM AUTHOR]

Access to cognitive stimulation through social interactions is a key mechanism used to explain the association between personal networks, cognitive health, and brain structure in older adults. However, little research has assessed how best to operationalize access to novel or diverse social stimuli using social network measures, many of which were designed to study information diffusion within large whole networks (e.g., structural holes and bridging social capital). Using data from 277 adults in the Social Networks and Alzheimer Disease (SNAD) study, we aimed to evaluate such measures for use in research on cognitive aging using personal social networks. We found a positive association between individual measures of structural holes and cognitive health, but not with brain structure. Further, we extracted a latent measure of bridging social capital using multiple individual measures (i.e., structural holes, network diversity, weak ties, and network size) and found it was significantly associated with cognitive health and brain structure, supporting the utility of this concept and related measures in the study of cognitive aging. Finally, individual measures may underestimate the effects of multidimensional bridging social capital on cognitive health and brain structure compared to a latent measure that combines them. [ABSTRACT FROM AUTHOR]

Soybean [Glycine max (L.) Merr.] seeding rate is one of the most important management decisions. Although seeding rate effect on yield is one of the most examined management practices, its interactive effect with seeding method is often ignored. Two field trials were conducted in Arlington, WI, between 2019 and 2020. In the first trial, the interactive effect of seeding rate with seeding method (precision vs. random) and two cultivars was examined. Precision method used a vacuum seed meter and soybean seed plate, whereas the random method used a cone seed distribution system. The second trial was hand planted to mimic precision planting (exact seeding rates and within row spacings), and the effect of seeding rate on total and partitioned (branch and stem) soybean yield was assessed. The effect of seeding rate on yield varied due to seeding method and cultivar. Precision seeding increased yield for the lowest seeding rate (99,000 seeds ha–1) and was associated with increased canopy closure and more uniform within‐row plant‐to‐plant spacing compared with the random seeding method. When soybean was hand planted (precision planting), total yield was greater only in the highest seeding rate. In the lowest rates, branch‐ and stem‐derived yields were similar. Overall results show that precision planting can mitigate yield loss at suboptimal seeding rates. Results from these studies reveal the complexity of seeding rate optimization for maximizing soybean yield and resulting profit and highlight the need for farm‐specific economic analysis for different management‐related costs and soybean price scenarios. Core Ideas: The interactive effect of seeding rate and seeding method is often ignored.Precision method used a vacuum seed meter, whereas the random method was cone‐seeded.Precision seeding resulted in more uniform spacing than random at the lowest seeding rate.Precision seeding increased yield compared with random seeding at the lowest seeding rate.Precision planting can mitigate yield loss at suboptimal seeding rates. [ABSTRACT FROM AUTHOR]

Objectives: Comprehensive cost-effectiveness analyses of introducing varicella and/or herpes zoster vaccination in the Swedish national vaccination programme. Design: Cost-effectiveness analyses based on epidemiological results from a specifically developed transmission model. Setting: National vaccination programme in Sweden, over an 85- or 20-year time horizon depending on the vaccination strategy. Participants: Hypothetical cohorts of people aged 12 months and 65-years at baseline. Interventions: Four alternative vaccination strategies; 1, not to vaccinate; 2, varicella vaccination with one dose of the live attenuated vaccine at age 12 months and a second dose at age 18 months; 3, herpes zoster vaccination with one dose of the live attenuated vaccine at 65 years of age; and 4, both vaccine against varicella and herpes zoster with the before-mentioned strategies. Main outcome measures: Accumulated cost and quality-adjusted life years (QALY) for each strategy, and incremental cost-effectiveness ratios (ICER). Results: It would be cost-effective to vaccinate against varicella (dominant), but not to vaccinate against herpes zoster (ICER of EUR 200,000), assuming a cost-effectiveness threshold of EUR 50,000 per QALY. The incremental analysis between varicella vaccination only and the combined programme results in a cost per gained QALY of almost EUR 1.6 million. Conclusions: The results from this study are central components for policy-relevant decision-making, and suggest that it was cost-effective to introduce varicella vaccination in Sweden, whereas herpes zoster vaccination with the live attenuated vaccine for the elderly was not cost-effective–the health effects of the latter vaccination cannot be considered reasonable in relation to its costs. Future observational and surveillance studies are needed to make reasonable predictions on how boosting affects the herpes zoster incidence in the population, and thus the cost-effectiveness of a vaccination programme against varicella. Also, the link between herpes zoster and sequelae need to be studied in more detail to include it suitably in health economic evaluations. [ABSTRACT FROM AUTHOR]

This article is a result of the way in which the design of a fi rst-year anthropology course attempted to undo stern structural hierarchies between students and teachers. Instead, the participants regarded one another as fellow anthropologists undertaking ethnographic research on the university context. This article examines the intimate relations that came available to participants when the course moved from in-person to Zoom format. Participants moved into homes to document the unfurling COVID-19 crisis, (back) into intimate familial relations. But this was not the only intimacy with which participants had to grapple anthropologically. The lecture materials, too, connected themselves to things and experiences in immediacy as they arrived into homes through laptop screens. The screens themselves off ered up new insights into the lives of others -- something newly minted anthropologists had to account for as they completed the course. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum L.) is the third‐most cultivated field crop in the United States and a very important source of nutrition globally. The economic value of wheat motivates farmers to optimize yield and grain quality, which can be obtained with additional inputs that are often expensive. This study investigated three management intensity levels on grain yield, straw yield, grain test weight, and disease on winter wheat in Wisconsin across 4 yr and 20 varieties. All management practices included a pre‐emergence herbicide and N application, with a mid‐level management strategy adding another N application and a single fungicide application to the current strategy, and a high‐level management intensity strategy adding a growth regulator, two micronutrient applications, and another fungicide application to the mid‐level strategy. Our study revealed that increasing management intensity from current strategies to mid‐ or high levels significantly increased grain yields by 0.81–1.22 kg ha−1, straw yields by 1.2–1.2 t ha−1, and grain test weights by 2.6–3.2 kg hl−1, respectively (P <.05). In addition, the high‐level management intensity led to significant reductions in stripe rust incidence and severity, whereas both mid‐ and high‐level management intensity reduced Fusarium head blight incidence and severity, and mycotoxin contamination (P <.001). The economic considerations of intensified management were also examined, and the mid‐ and high‐level management practices resulted in US$306 and US$242 ha−1 greater profit than current management, respectively, as a result of the improved disease protection and yields. [ABSTRACT FROM AUTHOR]

A large literature emphasizes the importance of social relationships during the caregiving process. Yet these issues are seldom presented in a social network framework that examines the structure of caregivers' personal networks. In this study, I examine how older caregivers experience changes in personal network structure. Using two waves from the National Social Life, Health, and Aging Project, I investigate whether caregivers are more or less likely to exhibit bridging or bonding capital potential compared to noncaregivers. I find that older adults transitioning into caregiving are more likely to develop the ability to bridge social ties within their personal networks than noncaregivers despite potential constraints in their personal freedom. Caregivers in the latter stages, meanwhile, do not differ from noncaregivers in terms of network change. These findings have implications for older adults' potential to pool resources across social domains as well as negotiate stress and well-being during the caregiving process. [ABSTRACT FROM AUTHOR]

Late life is a period frequently marked by decline in personal health and heightened need for social support. Consequently, the social networks in which individuals are embedded assume an increasingly central role in the health and wellbeing of older adults. In the present article, I review the state of the literature on social networks and health in later life. By drawing on insights from the sociology of ageing and the life course, I address new developments and current challenges within the field. Chief among these developments and challenges is the recognition that the ageing process does not occur in a vacuum. Rather, individuals are consistently exposed to numerous changes to their social lives which have strong implications for current and future health outcomes. Upon highlighting the latest innovations within the field of networks and health, I conclude with useful directions for future research. [ABSTRACT FROM AUTHOR]

Objectives Personal network turnover, a combination of lost and added network contacts, is suggested to affect health as well as moderate access to social support and resources. This article tests whether the caregiving process is associated with network turnover in later life and whether the process is different for men and women. Methods Network turnover was assessed using two waves of personal network data from the National Social Life, Health, and Aging Project. Network contacts were uniquely identified in each wave making it possible to document contact loss and addition. Rates of change were modeled using Poisson regression. Results Respondents transitioning into caregiving lost and added network contacts at higher rates than non-caregivers. Conversely, respondents providing care during both waves and respondents transitioning out of the role saw no significant levels of network turnover. The analysis provided minimal evidence of gender differences. Discussion Findings suggest that the initial shift into the caregiving role is associated with notable personal network change. This is an important consideration given that long-term network instability may lead to poor health and limited access to social resources whereas adaptive network change tends to elicit more positive outcomes. [ABSTRACT FROM AUTHOR]

It is widely recognized that planting soybean [Glycine max (L.) Merr.] early is critical to maximizing yield, but the influence of changing management factors when soybean planting is delayed is not well understood. The objectives of this research were to (a) identify management decisions that increase seed yield in either early‐ or late‐planted soybean scenarios, and (b) estimate the maximum break‐even price of each management factor identified to influence soybean seed yield in early‐ or late‐planted soybean. Producer data on seed yield and management decisions were collected from 5682 fields planted with soybean during 2014−2016 and grouped into 10 technology extrapolation domains (TEDs) based on growing environment. A subsample of 1512 fields was classified into early‐ and late‐planted categories using terciles. Conditional inference trees were created for each TED to evaluate the effect of management decisions within the two planting date timeframes on seed yield. Management strategies that maximized yield and associated maximum break‐even prices varied across TEDs and planting date. For early‐planted fields, higher yields were associated with artificial drainage, insecticide seed treatment, and lower seeding rates. For late‐planted fields, herbicide application timing and tillage intensity were related to higher yields. There was no individual management decision that consistently increased seed yield across all TEDs. [ABSTRACT FROM AUTHOR]

Objectives To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children. Design Prospective cohort study. Setting Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases. Participants Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up. Methods Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017. Main outcome measure HR for neonatal BCG compared with no neonatal BCG by TB-exposure status. Results Among the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG. Conclusion Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted. [ABSTRACT FROM AUTHOR]

Natural polyamines such as spermidine and spermine cations have characteristics that make them highly likely to be sensed by riboswitches, such as their general affinity to polyanionic RNA and their broad contributions to cell physiology. Despite previous claims that polyamine riboswitches exist, evidence of their biological functions has remained unconvincing. Here, we report that rare variants of bacterial S -adenosylmethionine-I (SAM-I) riboswitches reject SAM and have adapted to selectively sense spermidine. These spermidine-sensing riboswitch variants are associated with genes whose protein products are directly involved in the production of spermidine and other polyamines. Biochemical and genetic assays demonstrate that representatives of this riboswitch class robustly function as genetic "off" switches, wherein spermidine binding causes premature transcription termination to suppress the expression of polyamine biosynthetic genes. These findings confirm the existence of natural spermidine-sensing riboswitches in bacteria and expand the list of variant riboswitch classes that have adapted to bind different ligands. [Display omitted] • Natural spermidine-sensing riboswitches exist in bacteria • Rare SAM-I riboswitch variants have adapted to sense spermidine • Spermidine riboswitches repress polyamine biosynthesis genes Salvail et al. demonstrate that rare variants of bacterial S -adenosylmethionine-I (SAM-I) riboswitches reject SAM and selectively sense spermidine to repress the expression of polyamine biosynthesis genes. This unusual class of RNA genetic switches expands the list of variant riboswitches that have evolved altered ligand-binding specificity. [ABSTRACT FROM AUTHOR]

One of the goals of relation extraction is to identify protein-protein interactions (PPIs) in biomedical literature. Current systems are capturing binary relations and also the direction and type of an interaction. Besides assisting in the curation PPIs into databases, there has been little real-world application of these algorithms. We describe UPSITE, a text mining tool for extracting evidence in support of a hypothesized interaction. Given a predicted PPI, UPSITE uses a binary relation detector to check whether a PPI is found in abstracts in PubMed. If it is not found, UPSITE retrieves documents relevant to each of the two proteins separately, and extracts contextual information about biological events surrounding each protein, and calculates semantic similarity of the two proteins to provide evidential support for the predicted PPI. In evaluations, relation extraction achieved an Fscore of 0.88 on the HPRD50 corpus, and semantic similarity measured with angular distance was found to be statistically significant. With the development of PPI prediction algorithms, the burden of interpreting the validity and relevance of novel PPIs is on biologists. We suggest that presenting annotations of the two proteins in a PPI side-by-side and a score that quantifies their similarity lessens this burden to some extent. [ABSTRACT FROM AUTHOR]

Objectives: To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration.Study Design: Institutional review board-approved prospective cohort study.Methods: Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified.Results: Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm2 vs. 66 ± 8 μm2 ; P < 0.05) and 4 mm diameter (70 ± 8 μm2 vs. 50 ± 3 μm2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips.Conclusion: Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing.Level Of Evidence: NA. Laryngoscope, 128:E41-E46, 2018. [ABSTRACT FROM AUTHOR]

Background. The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. Methods. We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46 239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. Results. Bacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36-1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43-1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46-0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10-0.75) as follows: women, aOR = 0.18 (95% CI, 0.05-0.64); men, aOR = 0.52 (95% CI, 0.12-2.33); sex-differential effect, P = .29. Conclusions. The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine. [ABSTRACT FROM AUTHOR]

Background: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population.Methods: In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes.Results: A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42).Conclusions: Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Alcohol use is a leading risk factor for disease and injury in Pacific Island countries and territories (PICT). This paper examines drinking patterns across 20 PICTs.Design and Methods: We synthesised published data from the STEPwise approach to surveillance or similar surveys for adults 25-64 years, and from the Global School-Based Student Health surveys and Youth Risk Behavior Surveillance System (YRBSS) for youth. We examined current and heavy drinking, and for adults also frequency of consumption. Using YRBSS, we studied trends in youth alcohol use in US-affiliated PICTs between 2001 and 2013.Results: Alcohol consumption in adults and youth varied considerably across PICTs. In eight PICT populations, over 60% of male adults were current drinkers. Male adults consumed alcohol more frequently and engaged in heavy drinking more than female adults. Similar gender differences occurred in current and heavy drinking among youth. Across 10 PICTs, current drinking prevalence in males 13-15 years ranged from 10% to over 40%. Declines in alcohol use among grade 9-12 students were observed in YRBSS, although the magnitude differed by island and sex.Discussion and Conclusions: Alcohol consumption varies widely between PICTs. There are marked gender differences in use and abstention. There is scope in PICTs for implementation of best practice strategies to reduce alcohol-related harm. These need to be gender responsive and cognisant of concerning patterns of youth drinking. Strengthening surveillance of alcohol use and its consequences is vital to inform and monitor the impact of national and regional policies. [Kessaram T, McKenzie J, Girin N, Roth A, Vivili P, Williams G, Hoy D. Alcohol use in the Pacific region: Results from the STEPwise approach to surveillance, Global School-Based Student Health Survey and Youth Risk Behavior Surveillance System. Drug Alcohol Rev 2016;35:412-423]. [ABSTRACT FROM AUTHOR]

Aim: To provide in New Caledonian school children (i) the prevalence of rheumatic heart disease (RHD) detected by annual screening program using new World Heart Federation diagnostic criteria; (ii) the point prevalence of acute rheumatic fever (ARF); and (iii) to investigate socio-demographic risk factors associated with RHD.Methods: This study linked data from national ARF/RHD programs by combining ARF incidence data from the register with RHD prevalence data from echocardiographic screening data for a single age year of the population for overall point prevalence ARF/RHD rates. For the analysis, cases of echocardiographic detection of RHD are presumed to be synonymous with undiagnosed ARF. All results were weighted to minimise the bias introduced from absent pupils of each annual screening program. Incidence and prevalence were age-standardised to the WHO World Standard Population. Each 2013 cumulative prevalence of definite and borderline RHD was studied using a multivariate logistic regression adjusted for socio-demographic factors.Results: The overall age-standardised incidence of clinical and undiagnosed ARF (i.e. echocardiographic-detected RHD) was combined as point prevalence and estimated to be 99/10 000 cases in 2012 and 114/10 000 cases in 2013. This included 40/10 000 prevalent cases of asymptomatic RHD detected by screening each year. Being Melanesian, OR 23.2 (95% CI: 3.4-157.3), or Polynesian, OR 21.5 (95% CI: 2.9-157.7), was associated with a higher prevalence of having definite RHD compared with being Caucasian. Being a girl was associated with a higher risk of having borderline RHD, OR 1.9 (95% CI: 1.03-3.3).Conclusion: Without echocardiographic screening, ARF/RHD burden is substantially underestimated. [ABSTRACT FROM AUTHOR]

Purpose – Health care organizations are increasingly demanded to balance the institutional logic of “medical professionalism” and “business-like health care,” that is, to both recognize physicians’ professional expertise while locating it in a wider social, economic, and political organizational setting. The purpose of this paper is to examine the implications from this shift in terms of leadership work in health care organizations. Design/methodology/approach – Case study methodology including interviews with 15 residents in Swedish health care organizations. Findings – A study of the willingness of residents to take on leadership positions show that leadership roles are treated as what is potentially hindering the acquisition of the know-how, skills, and expertise demanded to excel in the clinical work. Consequently, taking on leadership positions in the future was relatively unattractive for the residents. In order to overcome such perceived conflict between professional skill development and leadership roles, top management of health care organizations must help residents overcome such beliefs, or other professional groups may increasingly populate leadership positions, a scenario not fully endorsed by the community of physicians. Originality/value – The paper demonstrates how complementary or completing institutional logics are influencing debates and identities on the “shop floors” of organizations. [ABSTRACT FROM AUTHOR]

Background: Overweight, obesity and their consequences are challenges to sustainable social and economic development in Pacific island countries and territories (PICTs). Complementing previous analyses for adults, the purpose of this paper is to synthesise available data on overweight, obesity and their risk factors in adolescents in the region. The resulting Pacific perspective for the younger generation will inform both the national and regional public health response to the crisis of noncommunicable diseases. Methods: We examined the prevalence of overweight, obesity, physical activity and carbonated sugar-sweetened beverage (SSB) consumption, by using published results of two cross-sectional surveys: the Global School-Based Student Health Survey (GSHS) and the Youth Risk Behavior Surveillance System (YRBSS). GSHS was conducted in ten PICTs between 2010 and 2013 and provided results for 13-15 year olds. YRBSS surveys, conducted repeatedly in five PICTs between 1999 and 2013, provided results for grade 9-12 students (approximately 14-18 years) and enabled examination of trends. Results: Obesity prevalence ranged from 0% in female students in Vanuatu to 40% in males in Niue (GSHS). Among grade 9-12 students (YRBSS), obesity was highest in American Samoa (40% of males; 37% of females). Approximately 60% of students in the Cook Islands, Niue and Tonga (GSHS) and American Samoa (YRBSS), were overweight. In both surveys, less than half of students reported engaging in sixty minutes of physical activity on at least 5 days of the past week. Daily consumption of carbonated SSBs in the past month was reported by over 42% of students in six PICTs (GSHS), and in the past week by more than 18% of students in three PICTs (YRBSS). In PICTs conducting YRBSS, obesity prevalence remained high or increased within the period 1999-2013. Conclusion: There is a need for urgent action on overweight, obesity and their risk factors in Pacific youth. The multiple social, economic and physical determinants of this public health crisis must be addressed. This requires all sectors within government and society in PICTs to implement and evaluate policies that will protect and promote the health of their populations across the life course. [ABSTRACT FROM AUTHOR]

Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment. Forty healthy male subjects were randomized to receive placebo or efavirenz 600 mg nightly for 7 days after completion of a 3-day placebo run-in period. Treatment with efavirenz was associated with reduced time to sleep onset in the Maintenance of Wakefulness Test, an increase in non-rapid eye movement sleep, a large exposure-related decrease in sigma band spectral density and sleep spindle density during non-rapid eye movement sleep, and reduced performance on an attention switching task. Because efavirenz has been shown to have serotonin 2A receptor partial-agonist properties, we reasoned that antagonism of serotonin 2A receptor signalling in the thalamic reticular nucleus, which generates sleep spindles and promotes attention, may be responsible. Consistent with predictions, treatment of healthy volunteers with a single dose of a serotonin 2A receptor antagonist was found to significantly suppress sigma band spectral density in an exposure-related manner and modulated the overall spectral profile in a manner highly similar to that observed with efavirenz, consistent with the notion that efavirenz exhibits serotonin 2A receptor partial-agonist pharmacology in humans. [ABSTRACT FROM AUTHOR]

The climate is changing and this poses significant threats to human health. Climate change is one of the greatest challenges facing Pacific Island countries and territories due to their unique geophysical features, and their social, economic and cultural characteristics. The Pacific region also faces challenges with widely dispersed populations, limited resources and fragmented health systems. Over the past few years, there has been a substantial increase in international aid for health activities aimed at adapting to the threats of climate change. This funding needs to be used strategically to ensure an effective approach to reducing the health risk from climate change. Respecting the principles of development effectiveness will result in more effective and sustainable adaptation, in particular, 1) processes should be owned and driven by local communities, 2) investments should be aligned with existing national priorities and policies, and 3) existing systems must not be ignored, but rather expanded upon and reinforced. [ABSTRACT FROM AUTHOR]

Background: Innate defence mechanisms of the airways are impaired in chronic obstructive pulmonary disease (COPD), predisposing patients to lower respiratory tract infections, but less is known about the association with other infections. In this population-based cohort study, we investigated the associations between COPD and invasive bacterial disease by comparing incidence rates of bacteraemia in COPD patients and randomly selected reference individuals from the general population. Methods: In this population based cohort study all patients with COPD, ≥40 years of age, who were discharged from hospitals in southern Sweden between 1990 and 2003 were identified in the Swedish Inpatient Register (n = 15,403). Age and gender matched reference individuals were randomly selected from the general population. Records were cross-referenced to the microbiological databases covering the region, 1990–2010. The hazard ratios (HR) of bloodstream infections and hospitalisations for infections were estimated by Cox proportional hazards regression. Results: We found that individuals with COPD had a 2.5-fold increased incidence of bacteraemia compared to the reference individuals from the general population adjusted for other co-morbidity and socio-economic status (hazard ratio: 2.5, 95% confidence interval: 2.2-2.7). The increased incidence of bacteraemia was paralleled by an increased incidence of hospitalisation for non-respiratory infections, i.e., skin infections, pyelonephritis, or septic arthritis. Despite higher absolute rates of bloodstream infections among COPD patients than among the general population, the distribution of different pathogens was similar. Conclusions: In summary this population-based study shows COPD is associated with an increased incidence of invasive bacterial infections compared to the general population, indicating a general frailty of acquiring severe infections in addition to the specific susceptibility to infections of respiratory origin. The underlying contributory factors (e.g. smoking, corticosteroid use, co-morbid diseases or a frailty inherent to COPD itself) need to be disentangled in further studies. [ABSTRACT FROM AUTHOR]