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Rising ocean temperature is a major driver of kelp forest decline worldwide and one that threatens to intensify over the coming decades. What is not particularly well understood are the mechanisms that drive loss and how they operate at differing life stages. This study aimed to establish an understanding of the effects of increasing temperature on the early developmental stages of the giant kelp, Macrocystis pyrifera. Sporulation was carried out across 10 temperature treatments from 9.5 to 26.2°C ± 0.2°C at approximately 2°C intervals. Spores were then incubated at these temperatures under a 20.3±1.7 μmol photons m-2 s-1, 16L:8D photoperiod for 5 days. Results indicate that spore release was positively correlated with increasing temperature, whereas an inverse trend was observed between temperature and the growth of germ-tube. The thermal threshold for spore and germling development was determined to be between 21.7°C and 23.8°C. Spore settlement was the most drastically effected developmental phase by increasing temperature. This study highlights the vulnerability of early life stages of M. pyrifera development to rising ocean temperature and has implications for modelling future distribution of this valuable ecosystem engineer in a changing ocean. [ABSTRACT FROM AUTHOR]

Background: Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam. Methods and Findings: In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73-1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30-0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07-4.8]). Conclusions: A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period. Trial registration: Current Controlled Trials ISRCTN44599712 Please see later in the article for the Editors' Summary., Introduction Perinatal and late neonatal mortality remains a challenge in low- and middle-income countries in contrast to the progress in reducing post-neonatal and child mortality [1]. A number of single [...]

Objectives: The dosing interval of a primary vaccination series can significantly impact on vaccine immunogenicity and efficacy. The current study compared 3 dosing intervals for the primary vaccination series of the BNT162b2 mRNA COVID-19 vaccine, on humoral immune response and durability against SARS-CoV-2 ancestral and Beta variants up to 9 months post immunization., Methods: Three groups of age- and sex-matched healthcare workers (HCW) who received 2 primary doses of BNT162b2 separated by 35-days, 35-42 days or >42-days were enrolled. Vaccine induced antibody titers at 3 weeks, 3 and 6-9 months post-second dose were assessed., Results: There were 309 age- and sex-matched HCW (mean age 43 [sd 13], 58% females) enrolled. Anti-SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibody titers showed significant waning in levels beyond 35 days post first dose. The second dose induced a significant rise in antibody titers, which peaked at 3 weeks and then declined at variable rates across groups. The magnitude, consistency and durability of response was greater for anti-Spike than anti-RBD antibodies; and for IgG than IgA or IgM. Compared to the shorter schedules, a longer interval of >42 days offered the highest binding and neutralizing antibody titers against SARS-CoV-2 ancestral and Beta (B1.351) variants beyond 3 months post-vaccination., Conclusions: This is the first comprehensive study to compare 3 dosing intervals for the primary vaccination of BNT162b2 mRNA COVID-19 vaccine implemented in the real world. These findings suggest that delaying the second dose beyond 42 days can potentiate and prolong the humoral response against ancestral and Beta variants of SARS-CoV-2 up to 9 months post-vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Leong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Low lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV1), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population., Methods and Findings: From the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV1 with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV1 (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > -1 SD), 19% (n = 4,353) moderate (z-score -1 to > -2 SD), and 6% (n = 1,329) severely low FEV1 (z-score = < -2 SD). There was a graded association between lower FEV1 with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV1 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV1 with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred., Conclusions: We observed graded associations between lower FEV1 with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics., Methods: From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method., Results: Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation., Conclusions: In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies., Competing Interests: All authors have declared that they have no competing interests., (Copyright: © 2022 Duong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A vast range of research applications in biodiversity sciences requires integrating primary species, genetic, or ecosystem data with other environmental data. This integration requires a consideration of the spatial and temporal scale appropriate for the data and processes in question. But a versatile and scale flexible environmental annotation of biodiversity data remains constrained by technical hurdles. Existing tools have streamlined the intersection of occurrence records with gridded environmental data but have remained limited in their ability to address a range of spatial and temporal grains, especially for large datasets. We present the Spatiotemporal Observation Annotation Tool (STOAT), a cloud-based toolbox for flexible biodiversity-environment annotations. STOAT is optimized for large biodiversity datasets and allows user-specified spatial and temporal resolution and buffering in support of environmental characterizations that account for the uncertainty and scale of data and of relevant processes. The tool offers these services for a growing set of near global, remotely sensed, or modeled environmental data, including Landsat, MODIS, EarthEnv, and CHELSA. STOAT includes a user-friendly, web-based dashboard that provides tools for annotation task management and result visualization, linked to Map of Life, and a dedicated R package (rstoat) for programmatic access. We demonstrate STOAT functionality with several examples that illustrate phenological variation and spatial and temporal scale dependence of environmental characteristics of birds at a continental scale. We expect STOAT to facilitate broader exploration and assessment of the scale dependence of observations and processes in ecology., Competing Interests: The authors have declared that no competing interests exist.

Background: The current UK vaccination programme for herpes zoster (HZ) excludes people aged ≥80 years. This study aimed to quantify the number of individuals ≥80 years who missed HZ vaccination and the consequent epidemiological and economic burden of HZ and post-herpetic neuralgia (PHN)., Methods: Immunocompetent individuals aged ≥80 years between 1st September 2013 and 31st December 2017 in the Clinical Practice Research Datalink were selected and linked to Hospital Episodes Statistics, where available. Rates of HZ and PHN and healthcare resource utilisation were investigated for the overall study population and by age group (80-84, 85-89, ≥90 years old) and the burden of HZ and PHN was projected to the UK population., Results: 4,858 HZ episodes and 464 PHN cases were identified in 255,165 individuals over 576,421 person-years (PY). Rates of HZ and PHN were 8.43 (95% confidence interval [CI] 8.19-8.66) and 0.80 (0.73-0.87) per 1,000 PY respectively and lowest in those aged ≥90 (HZ rate 7.37/1,000 PY; PHN rate 0.56/1,000 PY). Within HZ episodes, 10.27% of GP visits, 5.82% of prescribed medications and 21.65% of hospitalisations were related to HZ/PHN. Median length of hospitalisation increased from 7.0 days for all-cause to 10.5 days for HZ/PHN related hospitalisations. Individuals ≥90 stayed in hospital a median of 3-4 days longer than younger groups. Approximately 2.23 million individuals in the UK missed HZ vaccination since 2013 (1.86 million had never been eligible and 365,000 lost eligibility for HZ vaccination), resulting in an estimated 43,149 HZ episodes., Conclusion: This study highlights the impact of the 80-year upper age limit policy on the health system. Our study estimates that 2.23 million individuals in the UK may have lost the opportunity to be vaccinated and that their burden of HZ and PHN remains high, especially among the very elderly., Competing Interests: IM, BG and YP were all employees of Merck Sharp & Dohme Ltd and own shares in Merck & Co., Inc., Kenilworth, NJ, USA. MD, VP and NQ were employed by OXON Epidemiology Ltd at the time of the study, which received funding from Merck Sharp & Dohme Ltd to design and conduct the study and develop the manuscript. BN is an Honorary Clinical Senior Lecturer, Department of Primary Care and Public Health, Imperial College London. He has received consultancy fees from Merck Sharp & Dohme Ltd to assist with this study and has received consultancy fees from Sanofi Pasteur MSD for attending advisory panels and other consultancy projects. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This pilot quasi-experimental trial tested a gender-responsive cognitive behavioral group intervention with 87 court-involved female adolescents (5 juvenile courts) who were at indicated risk for substance use disorder. Participants in the intervention (n = 57) received twice weekly group sessions for 10 weeks (20 sessions) focused on building emotional, thought and behavior regulation skills and generalizing these skills to relationally-based scenarios (GOAL: Girls Only Active Learning). Youth in the control condition (n = 30) received services as usual, which included non-gender-specific aggression management training, individual counseling and no services. The GOAL program was found to be acceptable to youth and parents and feasible to implement within a juvenile court setting using skilled facilitators. Compared to services as usual, the program significantly and meaningfully reduced self-reported delinquent behavior (β = 0.84, p < 0.05) over 6 months, and exhibited trend level effects for reduced substance use (β = 0.40, p = 0.07). The program had mixed or no effects on family conflict and emotion regulation skills. These findings are discussed in light of treatment mechanisms and gender-responsive services., Competing Interests: S.C.W., L.B. and C.H. are listed as inventors of the GOAL program under a University of Washington license and the invention was reported to the Department of Health and Human Services on 03/30/2018. No patent is pending. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Obesity is an independent risk factor for cardiovascular disease. Reverse cholesterol transport (RCT) is an important cardioprotective mechanism. This study aimed to investigate RCT changes in a murine model of obesity., Methods: Ob/ob and control mice were injected with [3H]-cholesterol-labelled macrophages and cholesterol accumulation quantified after 48 h. Ex vivo, cholesterol efflux and uptake were determined in hepatic and adipose tissues., Results: Ob/ob mice had more labelled cholesterol in their plasma (86%, p<0.001), suggesting impaired RCT. SR-BI-mediated cholesterol efflux was elevated from ob/ob mice (serum, 33%; apoB-depleted plasma, 14%, p<0.01) and HDL-c were also higher (60%, p<0.01). Ex vivo it was found that cholesterol uptake was significantly lower into the livers and adipose tissue of ob/ob mice, compared to non-obese wildtype controls. Furthermore, ex vivo cholesterol efflux was reduced in ob/ob liver and adipose tissue towards apoA-I and HDL. Consistent with this, protein levels of SR-BI and ABCG1 were significantly lower in ob/ob hepatic and adipose tissue than in wildtype mice. Finally, labelled cholesterol concentrations were lower in ob/ob bile (67%, p<0.01) and faeces (76%, p<0.0001)., Conclusion: Obesity causes impairment in RCT due to reduced plasma cholesterol uptake and efflux by hepatocytes and adipocytes. A reduction in the capacity for plasma cholesterol clearance may partly account for increased CVD risk with obesity., Competing Interests: The authors have declared that no competing interests exists.

Objective: To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context., Methods: In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach., Findings: Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain., Conclusions: This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders considered were essential medicines, challenges whether the EML concept is out-dated or underutilised in high income countries.