Movement ecology of an endangered mesopredator in a mining landscape.

BACKGROUND: Efficient movement and energy expenditure are vital for animal survival. Human disturbance can alter animal movement due to changes in resource availability and threats. Some animals can exploit anthropogenic disturbances for more efficient movement, while others face restricted or inefficient movement due to fragmentation of high-resource habitats, and risks associated with disturbed habitats. Mining, a major anthropogenic disturbance, removes natural habitats, introduces new landscape features, and alters resource distribution in the landscape. This study investigates the effect of mining on the movement of an endangered mesopredator, the northern quoll (Dasyurus hallucatus). Using GPS collars and accelerometers, we investigate their habitat selection and energy expenditure in an active mining landscape, to determine the effects of this disturbance on northern quolls. METHODS: We fit northern quolls with GPS collars and accelerometers during breeding and non-breeding season at an active mine site in the Pilbara region of Western Australia. We investigated broad-scale movement by calculating the movement ranges of quolls using utilisation distributions at the 95% isopleth, and compared habitat types and environmental characteristics within observed movement ranges to the available landscape. We investigated fine-scale movement by quolls with integrated step selection functions, assessing the relative selection strength for each habitat covariate. Finally, we used piecewise structural equation modelling to analyse the influence of each habitat covariate on northern quoll energy expenditure. RESULTS: At the broad scale, northern quolls predominantly used rugged, rocky habitats, and used mining habitats in proportion to their availability. However, at the fine scale, habitat use varied between breeding and non-breeding seasons. During the breeding season, quolls notably avoided mining habitats, whereas in the non-breeding season, they frequented mining habitats equally to rocky and riparian habitats, albeit at a higher energetic cost. CONCLUSION: Mining impacts northern quolls by fragmenting favoured rocky habitats, increasing energy expenditure, and potentially impacting breeding dispersal. While mining habitats might offer limited resource opportunities in the non-breeding season, conservation efforts during active mining, including the creation of movement corridors and progressive habitat restoration would likely be useful. However, prioritising the preservation of natural rocky and riparian habitats in mining landscapes is vital for northern quoll conservation.

Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2.

BACKGROUND: Acquired ESR1 mutations in estrogen receptor-positive (ER+) metastatic breast cancer (mBC) drive treatment resistance and tumor progression; new treatment strategies are needed. Lasofoxifene, a next-generation, oral, endocrine therapy and tissue-specific ER antagonist, provided preclinical antitumor activity, alone or combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in ESR1-mutated mBC. PATIENTS AND METHODS: In the open-label, phase II, ELAINE 2 trial (NCT04432454), women with ESR1-mutated, ER+/human epidermal growth factor receptor 2-negative (HER2-) mBC who progressed on prior therapies (including CDK4/6i) received lasofoxifene 5 mg/day and abemaciclib 150 mg b.i.d until disease progression/toxicity. The primary endpoint was safety/tolerability. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and objective response rate (ORR). RESULTS: Twenty-nine women (median age 60 years) participated; all but one were previously treated with a CDK4/6i (median duration 2 years). The lasofoxifene-abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting. One patient (with no prior CDK4/6i) discontinued treatment due to grade 2 diarrhea. No deaths occurred during the study. Median PFS was 56.0 weeks [95% confidence interval (CI) 31.9 weeks-not estimable; ∼13 months]; PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. CBR at 24 weeks was 65.5% (95% CI 47.3% to 80.1%). In 18 patients with measurable lesions, ORR was 55.6% (95% CI 33.7% to 75.4%). ESR1-mutant circulating tumor DNA (ctDNA) allele fraction decreased from baseline to week 4 in 21/26 (80.8%) patients. CONCLUSIONS: Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.

Mapping healthy planning frameworks.

AIMS: The aim of this research was to map available healthy planning frameworks to discover the range, composition, design, and implementation of healthy planning frameworks. METHODS: A systematic scoping review with date, location, and usability limitations was augmented by a grey literature search. Data were extracted on key details, design, outcomes considered, and implementation features of the final 61 frameworks. RESULTS: Data extracted indicated that most frameworks tend to focus on one element of the built environment, with active mobility, active environments, and transport being the most prevalent ones (34%). Most frameworks (40) stated their intended outcomes on health in general terms, rather than targeting specific health outcomes. Very few frameworks (12%) were aimed at the public, and only 11% of frameworks included an evaluation. CONCLUSIONS: While there are a wide variety and number of frameworks available in the field of healthy urban planning, they are generally siloed, focusing on highly specific individual urban determinants, and rarely consider health outcomes in detail. There is significantly less provision available for citizen and community use. Frameworks tend to offer limited updating mechanisms and very rarely include ongoing evaluation processes, making their success difficult to assess.

Regulatory mechanisms to create healthier environments: planning appeals and hot food takeaways in England.

AIMS: To explore existing regulatory mechanisms to restrict hot food takeaway (HFT) outlets through further understanding processes at local and national levels. METHODS: The Planning Appeals Portal was utilised to identify recent HFT appeal cases across England between December 2016 and March 2020. Eight case study sites were identified using a purposive sampling technique and interviews carried out with 12 professionals involved in planning and health to explore perceptions of and including factors that may impact on the HFT appeal process. Additionally, documents applicable to each case were analysed and a survey completed by seven Local Authority (LA) health professionals. To confirm findings, interpretation meetings were conducted with participants and a wider group of planning and public health professionals, including a representative from the Planning Inspectorate. RESULTS: Eight case study sites were identified, and 12 interviews conducted. Participants perceived that LAs would be better able to work on HFT appeal cases if professionals had a good understanding of the planning process/the application of local planning policy and supplementary planning documents; adequate time and capacity to deal with appeals cases; access to accurate, robust, and up to date information; support and commitment from elected members and senior management; good lines of communication with local groups/communities interested in the appeal; information and resources that are accessible and easy to interpret across professional groups. CONCLUSIONS: Communication across professional groups appeared to be a key factor in successfully defending decisions. Understanding the impact of takeaway outlets on health and communities in the long term was also important. To create a more robust appeals case and facilitate responsiveness, professionals involved in an appeal should know where to locate current records and statistical data. The enthusiasm of staff and support from senior management/elected officials will play a significant role in driving these agendas forward.

Development, sensitivity and reliability of a French version of the Leeds food preference questionnaire (LFPQ-fr) for the evaluation of food preferences and reward.

BACKGROUND: There is a growing global interest in the evaluation of food reward, necessitating the adaptation of culturally appropriate instruments for use in empirical studies. This work presents the development and validation of a culturally adapted French version of the Leeds Food Preference Questionnaire (LFPQ-fr). METHODS: The LFPQ-fr was developed and validated in healthy-weight adults using the following systematic approach: i) selection and validation of appropriate food pictures; ii) linguistic translation of liking and wanting constructs in the target population (n = 430; 81% female; 42.2 ± 12.7 years); iii) validation of the sensitivity and reliability of the task performed in a fasted state and in response to a standardized test meal (n = 50; 50% female; 30.0 ± 8.4 years). RESULTS: During the first and second phases, the nutritional and perceptual validation of culturally appropriate food pictures and pertinent reward constructs, respectively, was demonstrated in a healthy-weight French sample. Findings from the third phase indicated that all food reward components were sensitive to the test meal and showed moderate to high agreement in both fasted (Lin's CCC =0.72-0.94) and fed (Lin's CCC = 0.53-0.80) appetitive states between visit 1 (V1) and visit (V2). Except for explicit liking fat bias, all primary outcomes were statistically consistent in fasted and fed states between V1 and V2. Changes in fat and taste biases in response to a standardized meal for all primary outcomes were also consistent between V1 and V2 except for explicit liking fat bias (Lin's CCC = 0.49- 0.72). CONCLUSION: The LFPQ-fr developed and tested in this study is a reproducible and reliable method to assess food reward in both the fasted and fed states in a healthy-weight French population.

The impact of COVID-19 on the hot food takeaway planning regulatory environment: perspectives of local authority professionals in the North East of England.

BACKGROUND & AIMS: Planning regulations have been used to prevent the over-proliferation of hot food takeaways, minimising the impact of local obesogenic environments. To help mitigate the effects of lockdown, the UK government introduced temporary changes in March 2020 to Planning Regulations for England, allowing food retailers to open for takeaway services beyond 'ancillary' level without needing to apply for planning permission through permitted development rights (PDR). Businesses are required to notify their local authority (LA) when they implement PDRs. To better understand the impact of regulations on the policy and practice of key professional groups, Public Health England commissioned Teesside University to undertake scoping research in the North East of England. METHODS: A focus group and interviews were conducted with 15 professionals from 7 of 12 North East LAs. Professions included Planners, Public Health Leads, Environmental Health Officers and Town Centre Managers. Data were analysed using a codebook thematic analysis approach. An interpretation meeting with some participants was conducted. RESULTS: LAs were not aware of most businesses notifying them of new regulation adherence despite taking up PDRs, but were considered low-priority with many lacking formal recording procedures. There were concerns about health consequences of the changes, and consensus relating to ongoing issues with capacity across all professional groups, largely due to the continuing pandemic and absence of a strategy out of temporary measures. Concerns existed around ensuring cessation of restaurants trading as takeaways, and hygiene inspections backlog. Many (personally) saw new takeaways as a lifeline, offering broader menus and preserving local economies. CONCLUSION: Lack of information around the number of restaurants/pubs using PDR to trade as takeaway services, ongoing capacity issues of LAs and, at the time, the absence of a strategy post regulation changes, meant there were high levels of uncertainty regarding the impacts of these temporary measures.

Juvenile hormone: Production, regulation, current application in vector control and its future applications.

Juvenile hormone is an exclusive hormone found in insects which involves regulating various insect physiology. A total of eight juvenile hormones have been identified in insects which include JH 0, JH I, JH II, JH III, 4-methyl JH I (Iso- JH 0), JHB III, JHSB III, and MF. Corpora allata are the glands responsible for the production and synthesis of these hormones. They are involved in moulting, reproduction, polyethism, and behavioural regulations in different orders of insects. Factors such as diet temperatures, photoperiods, and plant compounds affect the biosynthesis and regulation of juvenile hormones. Juvenile hormones analogue is usually used to disrupt normal regulation of JH and this analogue is categorized as insect-growth regulators (IGRs) and is widely used in pest control as an alternative to chemical insecticides. Other applications of biosynthesis activities of this hormone have not been explored in the area of JHs. In this review, current applications of JHs with an addition of their future application will be discussed.

Hypothalamic-Extended Amygdala Circuit Regulates Temporal Discounting.

Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards given a choice between immediate and delayed rewards. Agouti-related peptide (AgRP)-expressing neurons located in the arcuate nucleus of the hypothalamus (ARC) regulate food intake and energy homeostasis, yet whether AgRP neurons influence choice behavior and temporal discounting is unknown. Here, we demonstrate that motivational state potently modulates temporal discounting. Hungry mice (both male and female) strongly preferred immediate food rewards, yet sated mice were largely indifferent to reward delay. More importantly, selective optogenetic activation of AgRP-expressing neurons or their axon terminals within the posterior bed nucleus of stria terminalis (BNST) produced temporal discounting in sated mice. Furthermore, activation of neuropeptide Y (NPY) type 1 receptors (Y1Rs) within the BNST is sufficient to produce temporal discounting. These results demonstrate a profound influence of hypothalamic signaling on temporal discounting for food rewards and reveal a novel circuit that determine choice behavior.SIGNIFICANCE STATEMENT Temporal discounting is a universal phenomenon found in many species, yet the underlying neurocircuit mechanisms are still poorly understood. Our results revealed a novel neural pathway from agouti-related peptide (AgRP) neurons in the hypothalamus to the bed nucleus of stria terminalis (BNST) that regulates temporal discounting in decision-making.

Bariatric Surgery for Congestive Heart Failure Patients Improves Access to Transplantation and Long-term Survival.

INTRODUCTION: Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient's who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. CONCLUSIONS: When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

Exploring the fast food and planning appeals system in England and Wales: decisions made by the Planning Inspectorate (PINS).

BACKGROUND: The National Planning Policy Framework advocates the promotion of 'healthy communities'. Controlling availability and accessibility of hot food takeaways is a strategy which the planning system may use to promote healthier environments. Under certain circumstances, for example, local authorities can reject applications for new hot food takeaways. However, these decisions are often subject to appeal. The National Planning Inspectorate decide appeals - by upholding or dismissing cases. The aim of this research is to explore and examine the National Planning Inspectorate's decision-making. METHODS: The appeals database finder was searched to identify hot food takeaway appeal cases. Thematic analysis of appeals data was carried out. Narrative synthesis provided an overview of the appeals process and explored factors that were seen to impact on the National Planning Inspectorate's decision-making processes. RESULTS: The database search identified 52 appeals cases. Results suggest there is little research in this area and the appeals process is opaque. There appears to be minimal evidence to support associations between the food environment and health and a lack of policy guidance to inform local planning decisions. Furthermore, this research has identified non-evidence-based factors that influence the National Planning Inspectorate's decisions. CONCLUSION: Results from this research will provide public health officers, policy planners and development control planners with applied public health research knowledge from which they can draw upon to make sound decisions in evaluating evidence to ensure they are successfully equipped to deal with and defend hot food takeaway appeal cases.

Juvenile hormone: Production, regulation, current application in vector control and its future applications

@#Juvenile hormone is an exclusive hormone found in insects which involves regulating various insect physiology. A total of eight juvenile hormones have been identified in insects which include JH 0, JH I, JH II, JH III, 4-methyl JH I (Iso- JH 0), JHB III, JHSB III, and MF. Corpora allata are the glands responsible for the production and synthesis of these hormones. They are involved in moulting, reproduction, polyethism, and behavioural regulations in different orders of insects. Factors such as diet temperatures, photoperiods, and plant compounds affect the biosynthesis and regulation of juvenile hormones. Juvenile hormones analogue is usually used to disrupt normal regulation of JH and this analogue is categorized as insect-growth regulators (IGRs) and is widely used in pest control as an alternative to chemical insecticides. Other applications of biosynthesis activities of this hormone have not been explored in the area of JHs. In this review, current applications of JHs with an addition of their future application will be discussed.

Low volumetric bone density is a risk factor for early complications after spine fusion surgery.

This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. INTRODUCTION: Lumbar spine (LS) fusion surgery is increasingly performed worldwide. Complications after fusion result in significant morbidity and healthcare costs. Multiple factors, including osteoporosis, have been suggested to contribute to risk of complications and re-operation. However, most studies have used DXA, which is subject to artifact in patients with spine pathology, and none have investigated the relationship between BMD and timing of post-operative complications. This study aims to investigate LS volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. METHODS: We evaluated a cohort of 359 patients who had initial LS fusion surgery at our institution, had pre-operative LS CTs and post-operative imaging available for review. Demographic factors, smoking status, vBMD, and details of surgical procedure were related to likelihood and timing of post-operative complications. RESULTS: Mean age was 60 ± 14 years, vBMD 122 ± 37 g/cm3. Median follow-up was 11 months. Skeletal complications occurred in 47 patients (13%); 34 patients (10%) required re-operation. Low vBMD (directly measured and estimated using HU) and smoking were associated with increased risk of skeletal complications. Each increase in baseline vBMD of 10 g/cm3 decreased the complication hazard and increased the complication-free duration in time-to-event analysis (hazard ratio 0.91, 95% CI 0.83-0.98, p < 0.02). CONCLUSIONS: Low vBMD was a significant risk factor for early post-operative complications in patients undergoing LS fusion. Prospective studies are needed to confirm these findings and to elucidate the optimal timing for follow-up and strategies for prevention of post-operative complications in this population.

Evaluation of treatment outcome using the Patient Specific Functional Scale in knee osteoarthritis patients undergoing multidisciplinary rehabilitation.

Objective: First, to make an inventory of activity limitations commonly reported by knee osteoarthritis (OA) patients undergoing multidisciplinary rehabilitation. Second, to evaluate treatment outcome using the Patient Specific Functional Scale (PSFS) and compare it to the Western Ontario and McMasters Universities Osteoarthritis Index physical function subscale (WOMAC-pf). Design: An observational study with assessments before and immediately after multidisciplinary rehabilitation. Five hundred and thirteen patients used the PSFS, a patient-reported tool to identify activity limitations and score the patient's ability to perform the activity on an 11-point Numeric Rating Scale (NRS), to report three activities in which they were limited. Frequencies and percentages of their highest-prioritized activity were calculated and categorized according to the International Classification of Functioning, Disability, and Health (ICF). Paired-samples T-tests were used to analyze the change in ability to perform the activities. Effect sizes of PSFS and WOMAC-pf were compared. Results: Most patients indicated limitations in walking, walking up/down stairs, prolonged standing, and standing up from a chair. Following these common activities, 26 different activities were identified. The majority of these highest-prioritized activities fell under the first-level ICF category of Mobility. The ability to perform all activities significantly improved after treatment. Effect sizes ranged between 0.60 and 0.97 and were greater than the effect size of the WOMAC-pf (0.41). Conclusion: Knee OA patients who undergo multidisciplinary rehabilitation exhibit improvements in performing daily activities. The PSFS is a valuable tool to evaluate patient-specific activity limitations and seems to capture improvements in activity limitations beyond the WOMAC-pf.

Systematic review of cognitive deficits in adult mitochondrial disease.

The profile and trajectory of cognitive impairment in mitochondrial disease are poorly defined. This systematic review sought to evaluate the current literature on cognition in mitochondrial disease, and to determine future research directions. A systematic review was conducted, employing PubMed, Medline, Psycinfo, Embase and Web of Science, and 360-degree citation methods. English language papers on adult patients were included. The literature search yielded 2421 articles, of which 167 met inclusion criteria. Case reports and reviews of medical reports of patients yielded broad diagnoses of dementia, cognitive impairment and cognitive decline. In contrast, systematic investigations of cognitive functioning using detailed cognitive batteries identified focal cognitive rather than global deficits. Results were variable, but included visuospatial functioning, memory, attention, processing speed and executive functions. Conclusions from studies have been hampered by small sample sizes, variation in genotype and the breadth and depth of assessments undertaken. Comprehensive cognitive research with concurrent functional neuroimaging and physical correlates of mitochondrial disease in larger samples of well-characterized patients may discern the aetiology and progression of cognitive deficits. These data provide insights into the pattern and trajectory of cognitive impairments, which are invaluable for clinical monitoring, health planning and clinical trial readiness.

Recurrent ACTG2 gene variation in African degenerative visceral leiomyopathy.

INTRODUCTION: Visceral myopathies remain difficult and frustrating clinical entities, a distinctive form of acquired degenerative visceral myopathy, African degenerative leiomyopathy, a myogenic functional intestinal obstruction without aganglionosis which affects smooth muscle of the intestine, in young indigenous African children. The Actin G2 gene is the main gene encoding smooth muscle actin found in enteric tissues. Recent research has identified Actin G2 alpha gene variation as an important causative biomarker in visceral myopathies and megacystis microcolon. This study of the Actin G2 gene (ACTG2) in an African population explores a possible molecular basis abnormal muscle function in a visceral myopathy. PATIENTS AND METHODS: Following ethical permission and informed consent, DNA was extracted from whole blood samples in five patients with histologically proven African degenerative leiomyopathy. PCR amplification of ACTG2 alpha gene products by semi-automated bi-directional sequencing analysis. Results were analysed using FinchTV Sequence Alignment Software and predicting bioinformatic investigation by PolyPhen 2 software. RESULTS: Five new patients with the ADL phenotypes were prospectively investigated for variation in the Actin G2 gamma gene (ACTG2). ACTG2 gene variation occurred in exon 5 (c.463 A>G K119R), in three (60%). In addition, intronic variation t > c-IVS3 was identified in three with the K119 mutation plus further g > c -IVS12 and t > c + IVS16(2), suggesting a possible haplotype. Bioinformatic modelling showed that these ACTG2 gene variations are highly non-conservative altering protein expression. CONCLUSIONS: Recurrent Actin G2 smooth muscle gene variation in African degenerative visceral leiomyopathy is associated with abnormal muscle actin development.

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia.

BACKGROUND: Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. METHODS: Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. RESULTS: Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. CONCLUSION: Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.

Life Goals Over Time Among Homeless Adults in Permanent Supportive Housing.

Permanent supportive housing (PSH) is a widely-accepted solution to the challenge of chronic homelessness. While housing support and retention, physical health, and healthcare continue to be important for formerly homeless persons in PSH, "higher-order" and humanistic needs such as thriving have received less attention and as a result are less well understood in this population. One important indicator of thriving is the ability to establish and articulate life goals. This study utilizes longitudinal data from 421 formerly homeless adults prior to their move into PSH, and at 3-, 6- and 12-months after move-in (369 respondents completed all four interviews), to examine what life goals are articulated by this population and how those goals change over time. Prior to housing, most respondents articulated housing attainment as their primary life goal, whereas at follow-up interviews health goals, housing relocation, and financial goals became more prevalent. Aspirational goals (e.g., independence, self-improvement, artistic pursuits) were also common, but demonstrated a decrease over time in housing. Relationship goals remained common and consistent over time. Findings indicate that housing is a necessary, but perhaps not sufficient, step for improving thriving among formerly homeless adults. Implications for practice and future research are discussed.

Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention.

Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis. As the illness progresses, this pathological process expands to other regions of the hippocampal circuit and projection fields in other anatomic areas including the frontal cortex, and induces an atrophic process in which hippocampal neuropil is reduced and interneurons are lost. This paper will describe the studies of our group and other investigators supporting this pathophysiological hypothesis, as well as its implications for early detection and therapeutic intervention.

Epidemiology of seasonal influenza infection in pregnant women and its impact on birth outcomes.

Seasonal influenza can cause significant morbidity in pregnant women. Much of the existing epidemiological evidence on influenza during pregnancy has focused on the 2009 A/H1N1 pandemic. To measure the epidemiological characteristics of seasonal influenza infection among pregnant women and the impact on infant health, a cohort of 86 779 pregnancies during the influenza season (2012-2014) was established using probabilistic linkage of notifiable infectious disease, hospital admission, and birth information. A total of 192 laboratory-confirmed influenza infections were identified (2·2 per 1000 pregnancies), 14·6% of which were admitted to hospital. There was no difference in the proportion of infections admitted to hospital by trimester or subtype of infection. Influenza B infections were more likely to occur in second trimester compared with influenza A/H3N2 and influenza A/H1N1 infections (41·3%, 23·6%, and 33·3%, respectively), and on average, infants born to women with influenza B during pregnancy had 4·0% (95% CI 0·3-7·6%) lower birth weight relative to optimal compared with infants born to uninfected women (P = 0·03). Results from this linked population-based study suggest that there are differences in maternal infection by virus type and subtype and support the provision of seasonal influenza vaccine to pregnant women.

A 2-Year Holistic Health and Stress Intervention: Results of an RCT in Clergy.

INTRODUCTION: This study sought to determine the effect of a 2-year, multicomponent health intervention (Spirited Life) targeting metabolic syndrome and stress simultaneously. DESIGN: An RCT using a three-cohort multiple baseline design was conducted in 2010-2014. SETTING/PARTICIPANTS: Participants were United Methodist clergy in North Carolina, U.S., in 2010, invited based on occupational status. Of invited 1,745 clergy, 1,114 consented, provided baseline data, and were randomly assigned to immediate intervention (n=395), 1-year waitlist (n=283), or 2-year waitlist (n=436) cohorts for a 48-month trial duration. INTERVENTION: The 2-year intervention consisted of personal goal setting and encouragement to engage in monthly health coaching, an online weight loss intervention, a small grant, and three workshops delivering stress management and theological content supporting healthy behaviors. Participants were not blinded to intervention. MAIN OUTCOME MEASURES: Trial outcomes were metabolic syndrome (primary) and self-reported stress and depressive symptoms (secondary). Intervention effects were estimated in 2016 in an intention-to-treat framework using generalized estimating equations with adjustment for baseline level of the outcome and follow-up time points. Log-link Poisson generalized estimating equations with robust SEs was used to estimate prevalence ratios (PRs) for binary outcomes; mean differences were used for continuous/score outcomes. RESULTS: Baseline prevalence of metabolic syndrome was 50.9% and depression was 11.4%. The 12-month intervention effect showed a benefit for metabolic syndrome (PR=0.86, 95% CI=0.79, 0.94, p<0.001). This benefit was sustained at 24 months of intervention (PR=0.88; 95% CI=0.78, 1.00, p=0.04). There was no significant effect on depression or stress scores. CONCLUSIONS: The Spirited Life intervention improved metabolic syndrome prevalence in a population of U.S. Christian clergy and sustained improvements during 24 months of intervention. These findings offer support for long-duration behavior change interventions and population-level interventions that allow participants to set their own health goals. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01564719.