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The funding policy for defined benefit pension plans covering government employees represents an important decision for governments sponsoring those plans. Many state and local government plans have become severely underfunded (e.g., New Jersey, Illinois, and Detroit), raising concerns about whether governments are contributing enough to their pensions. Governmental Accounting Standards Board Statements 67/68 (GASB 67/68) fundamentally alter the financial reporting of pension liabilities, by (i) requiring pension liabilities to be estimated using a potentially lower discount rate (increasing estimated liabilities and any funding deficits), and (ii) mandating balance sheet recognition of funding deficits/surpluses. Although GASB 67/68 only change financial reporting and acknowledge specifically that funding is outside their scope, we find, for 100 large state-administered plans, that governments increase pension contributions significantly upon applying GASB 67/68. This funding response is stronger from governments likely to face greater political consequences once pension deficits are made prominent by GASB 67/68. Benefit cuts are also more likely post GASB 67/68, but plans that increase funding are less likely to cut benefits—suggesting that these responses substitute for each other and that pension funding is more of a fiscal priority in some states than others. Overall, our findings suggest that purely accounting changes can have "real" effects on governmental pension policy. [ABSTRACT FROM AUTHOR]

Biogenic amines such as norepinephrine, dopamine, and serotonin play a well-described role in the treatment of mood disorders and some types of pain. As a2A-adrenoceptors regulate the release of these neurotransmitters, we examined the therapeutic potential of BRL 44408, a potent (Ki=8.5 nM) and selective (>50-fold) a2A-adrenoceptor antagonist (KB=7.9 nM). In rats, BRL 44408 penetrated the central nervous system resulting in peak brain and plasma concentrations of 586 ng/g and 1124 ng/ml, respectively. In a pharmacodynamic assay, pretreatment with BRL 44408 to rats responding under a fixed-ratio 30 operant response paradigm resulted in a rightward shift of the clonidine dose-response curve, an effect indicative of a2-adrenoceptor antagonism in vivo. Consistent with presynaptic autoreceptor antagonism and tonic regulation of neurotransmitter release, acute administration of BRL 44408 elevated extracellular concentrations of norepinephrine and dopamine, but not serotonin, in the medial prefrontal cortex. Additionally, BRL 44408, probably by inhibiting a2A heteroceptors, produced a significant increase in cortical levels of acetylcholine. In the forced swim test and schedule-induced polydipsia assay, BRL 44408 produced an antidepressant-like response by dose-dependently decreasing immobility time and adjunctive water intake, respectively, while in a model of visceral pain, BRL 44408 exhibited analgesic activity by decreasing para-phenylquinone (PPQ)-induced abdominal stretching. Finally, BRL 44408 did not produce deficits in overall motor coordination nor alter general locomotor activity. This preclinical characterization of the neurochemical and behavioural profile of BRL 44408 suggests that selective antagonism of a2Aadrenoceptors may represent an effective treatment strategy for mood disorders and visceral pain. [ABSTRACT FROM AUTHOR]

Objective: To investigate symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes (NHs). Methods: Secondary cross-sectional analyses of two prospective cohort studies involving 12 Australian NHs and four Japanese NHs. Frailty was measured using the FRAIL-NH scale (non-frail 0–2; frail 3–6; most-frail 7–14). Regular medications were classified as symptomatic or preventive based on published lists and expert consensus. Descriptive statistics were used to compare the prevalence and ratio of symptomatic to preventive medications. Results: Overall, 550 Australian residents (87.7 ± 7.3 years; 73.3% females) and 333 Japanese residents (86.5 ± 7.0 years; 73.3% females) were included. Australian residents used a higher mean number of medications than Japanese residents (9.8 ± 4.0 vs 7.7 ± 3.7, p < 0.0001). Australian residents used more preventive than symptomatic medications (5.5 ± 2.5 vs 4.3 ± 2.6, p < 0.0001), while Japanese residents used more symptomatic than preventive medications (4.7 ± 2.6 vs 3.0 ± 2.2, p < 0.0001). In Australia, symptomatic medications were more prevalent with increasing frailty (non-frail 3.4 ± 2.6; frail 4.0 ± 2.6; most-frail 4.8 ± 2.6, p < 0.0001) but less prevalent with age (< 80 years 5.0 ± 2.9; 80–89 years 4.4 ± 2.6; ≥ 90 years 3.9 ± 2.5, p = 0.0042); while preventive medications remained similar across age and frailty groups. In Japan, there was no significant difference in the mean number of symptomatic and preventive medications irrespective of age and frailty. Conclusions: The ratio of symptomatic to preventive medications was higher with increasing frailty but lower with age in Australia; whereas in Japan, the ratio remained consistent across age and frailty groups. Preventive medications remained prevalent in most-frail residents in both cohorts, albeit at lower levels in Japan. [ABSTRACT FROM AUTHOR]

Objectives: To explore the experiences of Australian and New Zealand clinicians with respect to care pathways, their awareness and use of non‐invasive ventilation guidelines, and their perspectives on delivering quality non‐invasive ventilation services to people with neuromuscular disorders. Design, setting, participants: Qualitative study; semi‐structured focus groups and individual interviews with Australian and New Zealand clinicians who provide non‐invasive ventilation services to people with neuromuscular disorders, recruited from participants at a 2017 sleep medicine conference. Interviews were conducted during 1 October 2017 – 31 May 2018. Main outcome measures: Major themes identified by an iterative, semantic, and inductive analysis. Results: A total of 28 participants attended the four focus group sessions and five individual interviews; fourteen each from New Zealand and Australia, seventeen women and eleven men, eighteen physicians and ten other clinicians. Two major themes were identified: decision making for current practice, and resource constraints. Participants noted variable use of clinical guidelines and limited training to meet the needs of people with neuromuscular disorders who require non‐invasive ventilation. They described a lack of dedicated funding, unstructured care pathways, equipment supply levels that do not meet need, low staff‐to‐patient ratios and staff shortages, and the inability to deliver quality multidisciplinary care. The need for clinical guidelines and service specifications was highlighted as requisite for reducing variation in clinical care. Conclusions: Systemic factors influence the needs‐based provision of non‐invasive ventilation for people with neuromuscular disorders. Development of clinical guidelines for Australia and New Zealand, dedicated funding for respiratory services for people with neuromuscular disorders, and specialist clinician training are important for equitable and high quality non‐invasive ventilation care. [ABSTRACT FROM AUTHOR]

I The story which we think is over is only a chapter in a story which will not be over. i - Robert Penn Warren On March 11, 2020, the World Health Organization declared COVID-19 a global pandemic. Taken together, these three articles provide insights into how consumers utilized social capital to persevere through the pandemic and how the pandemic transformed how consumers connect, communicate, and present themselves. The second set of articles in this special issue focuses on examining how consumers accumulate human capital in coping with the pandemic as well as pandemic-induced aloneness and loneliness. [Extracted from the article]

The current article presents a descriptive analysis of marketplace data from an online freelance platform in the early months of COVID-19. We investigate changes in the behavioral patterns of buyers and sellers on the platform to study consumer coping responses during the pandemic. We draw from the literature on coping with loss and personal adversity to present a consumer pandemic coping model derived from a synthesis of existing stage theories of coping and adaptation. The model presented can explain the aggregate changes in marketplace activity (e.g., traffic, sentiment, adoption, transaction patterns) we observe during the first several months of the pandemic. Our findings suggest that temporal coping processes can drive market behavior. This article provides insights about consumer coping to researchers and policy makers, as well as to firms who aim to be more prepared in the face of future crises. [ABSTRACT FROM AUTHOR]

Background: Self-perceived risk of fracture (SPR) is associated with fracture independent of FRAX calculated risk. To understand this better we considered whether lifestyle factors not included in the FRAX algorithm and psychosocial factors (social isolation, self-efficacy, or mental health status) explain the relationship between SPR and fracture. Methods: We studied 146 UK community-dwelling older adults from the Hertfordshire Cohort Study. SPR ranked as 'lower', 'similar' and 'higher' relative to others of the same age, was assessed by questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale; self-efficacy was assessed using a shortened General Self-Efficacy Scale (GSE); mental health status was assessed using the anxiety/depression item from the EuroQoL questionnaire. SPR in relation to previous self-reported fracture was examined using logistic regression. Results: Among participants of median age 83.4 (IQR 81.5–85.5) years, SPR was lower for 54.1% of participants, similar for 30.8%, and higher for 15.1%; 74.7% reported no previous fractures. Greater SPR was associated with increased odds of previous fractures when adjusting for sex and age only (OR 1.72, 95% CI 1.03–2.87, per higher band of SPR). While further individual adjustment for social isolation (1.73, 1.04–2.89), self-efficacy (1.71, 1.02–2.85), or mental health (1.77, 1.06–2.97) did not attenuate the relationship, individual adjustment for diet quality and number of comorbidities did. Conclusions: Adjustment for social isolation, self-efficacy or mental health status did not attenuate the relationship between SPR and fracture. By contrast, lifestyle factors not included in FRAX, such as diet quality, did attenuate relationships, suggesting a possible future area of investigation. [ABSTRACT FROM AUTHOR]

Background: Older adults have been especially vulnerable to adverse effects from the COVID-19 pandemic including higher mortality and more severe disease complications. At the same time, social isolation, malnutrition and physical inactivity are serious concerns among older adults. The pandemic and associated restrictions may serve to exacerbate these issues, presenting increased risks to physical and mental health. The aims of this qualitative study were: i) to explore how community-living older people in the UK experienced the first wave of the COVID-19 pandemic, specifically how it impacted their well-being and associated health behaviours; ii) to explore how older people's experiences and behaviours changed over time throughout the first wave. Methods: Qualitative data were collected by conducting serial telephone interviews, with an interval of approximately three months. Participants were from the Hertfordshire Cohort Study, all aged over 80 years. Discussions were audio-recorded, information related to the COVID-19 pandemic was transcribed verbatim and transcripts analysed thematically. Interviews were conducted from March to October 2020. Results: Data for twelve participants (7 men and 5 women) from a total of 35 interviews were used, comprising two or three timepoints per participant. Analysis identified five overarching themes: 1) shopping strategies and food accessibility, 2) limitations on activities and going out, 3) disruption to healthcare, 4) social and psychological repercussions, and 5) coping strategies. Findings highlight challenges associated with accessing shops, healthcare, and usual activities due to pandemic-related restrictions. Longitudinal findings showed that for some, the ongoing pandemic and related restrictions appeared to aggravate mental health issues (low mood, anxiety) over time, as well as greater feelings of isolation or loneliness, reduced activity and functional limitations; this was despite some relaxation of restrictions later on. Coping strategies used by participants included finding ways to keep busy and to do physical activity safely, maintaining social contact remotely, and having an optimistic or positive outlook, a 'do what you can' attitude. Conclusions: Interventions are likely to be needed in the wake of the COVID-19 pandemic to support health behaviours, such as increasing physical activity, social engagement and improving mental health among community-living older adults. [ABSTRACT FROM AUTHOR]

We considered how weight-bearing physical activity (WBPA) through the lifecourse related to bone health in late adulthood in the Hertfordshire Cohort Study (HCS), a cohort of community dwelling adults born 1931–9, to identify sex-specific differences and periods critical for optimal bone health. Available questionnaire data from 258 participants (128 men and 130 women) included current reported lifestyle factors (including physical activity) and WBPA, coded as participation in WBPA aged < 18 years; aged 18–29 years; aged 30–49 years and aged ≥ 50 years. Responses were recorded as none/once a month/once a week/> once a week. Hip bone mineral density (BMD) was measured using a Lunar Prodigy DXA scanner. The mean age was 75.4 (SD 2.5) years in men and 75.7 (SD 2.6) years in women. Men reported significantly higher levels of past WBPA aged < 18 years (p = 0.006) and aged 18–29 years than women (p < 0.001). We observed greater BMD at total hip in women who reported regular WBPA at ages 18–29 years (p = 0.02) and 30–49 years (p = 0.02) compared with those who reported no WBPA (p = 0.019), after adjustment for confounders including current activity levels. In this cohort of older adults, recalled regular WBPA around the time of peak bone mass acquisition was less common in women than men, but associated with higher hip BMD in women in late adulthood. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is a serious concern in older populations. Simple screening approaches are needed to identify signs of early nutritional risk in older people, to allow intervention before overt malnutrition develops, along with the poorer health outcomes associated with it, such as sarcopaenia and frailty. The main aim of this study was to compare nutrition risk scores, calculated from the DETERMINE Checklist ('Determine Your Nutritional Health', also known as the Nutrition Screening Initiative Checklist), with physical function variables in a group of community-dwelling older adults. Another aim was to assess the prevalence of nutrition risk using the DETERMINE and the MUST (Malnutrition Universal Screening Tool). Methods: Participants of the Hertfordshire Cohort Study (HCS) were recruited and visited at home by a trained researcher. Self-reported physical function was assessed using the SF-36 PF (Short Form-36 Physical Function) scale. The Short Physical Performance Battery (SPPB) was performed, which included the assessment of gait speed, chair rise time and standing balance. Handgrip strength was measured using a Jamar dynamometer. Frailty was assessed according to the presence of at least three of the following Fried frailty criteria: unintentional weight loss, weakness, self-reported exhaustion, slow gait speed and low physical activity. Nutrition risk scores were calculated from the DETERMINE checklist (range 0–21). Nutritional risk was also assessed using the MUST. Analyses were adjusted for sex, age, age left education and number of comorbidities. Results: In the study, 176 participants (94 men and 82 women), median age 83.3 (IQR 81.5–85.7) years, were assessed. Almost half (47%) scored either 'moderate' (score 3–5) or 'high' (score ≥ 6) nutritional risk (9% were at high risk), using the DETERMINE checklist, whereas 8% were at risk using the MUST. Higher nutrition risk scores, calculated from DETERMINE, were associated with poorer self-reported physical function (difference in SF-36 PF score: − 0.36, 95% CI (− 0.60, − 0.12) SD per unit increase in nutrition risk score, P = 0.004) and higher odds of being frail (odds ratio Fried frailty: 2.23, 95% CI (1.15, 4.33), P = 0.017). There were no significant associations between DETERMINE nutrition risk scores and the other variables examined. Conclusion: Cross-sectional associations between higher nutrition risk scores, assessed from the DETERMINE checklist, and poorer self-reported physical function and greater likelihood of frailty suggest that this screening tool may have utility for screening older populations. Prospective studies are required to explore the ability of the tool to predict poor physical function and frailty, though these data suggest it has potential for early, simple detection of nutritional problems in community-living older adults. [ABSTRACT FROM AUTHOR]

Background: Physical activity, nutrition and other lifestyle factors play important roles in maintaining musculoskeletal health. The coronavirus disease (COVID-19) originated in late 2019, spread globally to be declared a pandemic by the World Health Organisation in March 2020, and led to widespread behaviour change. The aim of this study was to use two existing cohorts, the Hertfordshire Cohort Study (HCS) and Health and Employment After Fifty Study (HEAF), to understand how wave one of the COVID-19 pandemic impacted lifestyle factors associated with musculoskeletal health in the UK. Methods: 125 eligible participants, 65 males and 60 females (drawn from the HCS study, median (IQR) age 84.3 (82.4-86.6) years, all Caucasian, and community dwelling) were contacted by telephone and asked to complete a questionnaire administered by a trained researcher. Data collection occurred over the period July 2020 to February 2021. 2469 participants, 1086 men and 1383 women (drawn from the HEAF study, median age 65.7 (62.0-69.3) years, mostly Caucasian and community dwelling) completed an online questionnaire in March 2021. Results: In HCS, 47% respondents reported being less physically active than before the pandemic (and only 5% more so), 27% said they consumed less alcohol compared to pre-pandemic times (and only 3% more so), and 18% reported eating less than before, although quality of diet was generally unchanged over this timeframe surveyed. In HEAF, 44% participants said they were less active than before the pandemic, while 17% reported being more active. The majority of participants reported no changes in alcohol consumption and diet; however, 19% said they drank more than before (32% of which was above recommended levels), 16% said their diet was less healthy, and 19% reported eating more than before. Conclusion: We have reported the experience of the first wave of the COVID-19 pandemic among participants of two Caucasian community dwelling UK cohorts, highlighting the impact of the pandemic on lifestyle factors associated with musculoskeletal health. Changed physical activity levels were reported in a high proportion of respondents in both studies; an investigation of reversibility of these changes is required. [ABSTRACT FROM AUTHOR]

Aim: Sarcopenia is a common disorder of loss of muscle mass and function among older adults; however, few studies have examined screening instruments for sarcopenia risk in residential aged care services (RACS). The aims of this study were to measure sarcopenia risk in RACS residents using the SARC‐F, describe factors associated with sarcopenia risk and examine the predictive validity of the SARC‐F for 12‐month mortality. Methods: This was a prospective cohort study carried out in South Australian RACS across 12 sites. In total, 541 residents (mean age 87.7 [7.3] years, 72.6% women) were included in the study. Sarcopenia risk was measured using a modified SARC‐F (≥4 point cut point). Results: We identified 89.5% (n = 484) of residents at risk of sarcopenia. Significant (P > 0.05) predictors of sarcopenia risk in multivariable analysis included the presence of diabetes (relative risk [RR] = 1.08), classification as most‐frail (RR = 1.06) and smaller Nursing Home Life Space Diameter (NHLSD) score (RR = 0.99). Mortality was observed in 20.9% (n = 113) of residents over a 12‐month follow‐up. Classification as at‐risk of sarcopenia was a significant predictor of 12‐month mortality; however, it had a poor area under the receiver operator curve (0.56), and a low positive predictive value (23.1%). The best performing cut‐point of ≥7 also had poor discriminative ability (under the receiver operator curve = 0.66, positive predictive value = 30.8%). Conclusions: Sarcopenia risk is extremely common among RACS residents and its presence is a significant contributor to 12‐month mortality. Low discriminative ability for the SARC‐F was noted across multiple cut‐off scores for predicting mortality at 12 months. Diabetes management and promoting physical activity and nutrition among RACS residents are likely to influence sarcopenia risk positively. Geriatr Gerontol Int 2022; 22: 206–212. [ABSTRACT FROM AUTHOR]

Background: The health benefits of physical activity (PA) participation in later life are widely recognised. Understanding factors that can influence the participation of community-dwelling older adults in PA is crucial in an ageing society. This will be paramount in aiding the design of future interventions to effectively promote PA in this population. The main aim of this qualitative study was to explore influences on PA among community-dwelling older people, and the secondary aim was to explore gender differences. Methods: Qualitative data were collected in 2014 by conducting focus group discussions using a semi-structured discussion guide with older people resident in Hertfordshire, UK. Discussions were audio-recorded, transcribed verbatim and transcripts analysed thematically. Results: Ninety-two participants were recruited to the study (47% women; 74–83 years) and a total of 11 focus groups were conducted. Findings indicated six themes that appeared to affect older adults' participation in PA: past life experiences; significant life events; getting older; PA environment; psychological/personal factors; and social capital. Overall, the findings emphasised the role of modifiable factors, namely psychological factors (such as self-efficacy, motivation, outcome expectancy) and social factors (such as social support and social engagement). These factors exerted their own influence on physical activity participation, but also appeared to mediate the effect of other largely non-modifiable background and ageing-related factors on participants' engagement with PA in later life. Conclusion: In view of these findings, intervention designers could usefully work with behavioural scientists for insight as to how to enhance psychological and social factors in older adults. Our data suggest that interventions that aim to build self-efficacy, motivation and social networks have the potential to indirectly promote PA participation in older adults. This would be best achieved by developing physical activity interventions through working with participants in an empowering and engaging way. [ABSTRACT FROM AUTHOR]

While there are many known health benefits to maintained physical activity levels in late adulthood, there have been very few studies that have considered relationships between morbidity profile and physical activity in the eighth decade of life. We studied 1097 participants, 555 men and 542 women from the Hertfordshire Cohort Study, a UK community based sample. Validated questionnaire based data were used to relate self-reported physical activity (PA) levels to medical history, and medication use. Regression analyses were adjusted for age, BMI, smoker status, alcohol consumption. The mean (SD) age of participants in the study was 80.2 (2.7) years for men and 80.2 (2.6) for women. A higher proportion of men (33.7 %) than women (24 %) were in the high activity score group. 20.8 % of female participants and 22.6 % male participants reported having no comorbid disease; 10.5 % men and 8.4 % women were taking no medication. Higher number of chronic conditions was associated with lower levels of PA [men (OR 0.73, 95 % CI 0.63-0.84, p<0.001); women (OR 0.74, 95 % CI 0.64-0.86, p<0.001)] as was being prescribed a higher number of medications [men (OR 0.88, 95 % CI 0.84-0.93, p<0.001); women (OR 0.86, 95 % CI 0.82-0.91, p<0.001)]. All these associations remained robust following adjustments. Strong relationships were seen in both sexes between PA and taking medication for disorders of the central nervous system and gastrointestinal system, with relationships generally stronger in men. We have observed relationships between comorbid medical history and medication use with physical activity in a cohort of community dwelling older adults. These highlight the need to consider medical history when considering how best to optimize PA in older adults. [ABSTRACT FROM AUTHOR]

Background: Social relationships play a fundamental role in individuals' lives and health, and social isolation is prevalent among older people. Chronic non-communicable diseases (NCDs) and frailty are also common in older adults. Aims: To examine the association between number of NCDs and social isolation in a cohort of community-dwelling older adults in the UK, and to consider whether any potential association is mediated by frailty. Methods: NCDs were self-reported by 176 older community-dwelling UK adults via questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale. Frailty was assessed by the Fried phenotype of physical frailty. Results: The median (IQR) age of participants in this study was 83.1 (81.5–85.5) years for men and 83.8 (81.5–85.9) years for women. The proportion of socially isolated individuals was 19% in men and 20% in women. More women (18%) than men (13%) were identified as frail. The number of NCDs was associated with higher odds of being isolated in women (unadjusted odds ratio per additional NCD: 1.65, 95% CI 1.08, 2.52, p = 0.021), but not in men, and the association remained robust to adjustment, even when accounting for frailty (OR 1.85, 95% CI 1.06, 3.22, p = 0.031). Discussion: Number of self-reported NCDs was associated with higher odds of social isolation in women but not in men, and the association remained after considering frailty status. Conclusions: Our observations may be considered by healthcare professionals caring for community-dwelling older adults with multiple NCDs, where enquiring about social isolation as part of a comprehensive assessment may be important. [ABSTRACT FROM AUTHOR]

Understanding of protein-ligand interactions and its influences on protein stability is necessary in the research on all biological processes and correlative applications, for instance, the appropriate affinity ligand design for the purification of bio-drugs. In this study, computational methods were applied to identify binding site interaction details between trastuzumab and its natural receptor. Trastuzumab is an approved antibody used in the treatment of human breast cancer for patients whose tumors overexpress the HER2 (human epidermal growth factor receptor 2) protein. However, rational design of affinity ligands to keep the stability of protein during the binding process is still a challenge. Herein, molecular simulations and quantum mechanics were used on protein-ligand interaction analysis and protein ligand design. We analyzed the structure of the HER2-trastuzumab complex by molecular dynamics (MD) simulations. The interaction energies of the mutated peptides indicate that trastuzumab binds to ligand through electrostatic and hydrophobic interactions. Quantitative investigation of interactions shows that electrostatic interactions play the most important role in the binding of the peptide ligand. Prime/MM-GBSA calculations were carried out to predict the binding affinity of the designed peptide ligands. A high binding affinity and specificity peptide ligand is designed rationally with equivalent interaction energy to the wild-type octadecapeptide. The results offer new insights into affinity ligand design. [ABSTRACT FROM AUTHOR]

Purpose: Social isolation has been associated with both physical and psychological adverse outcomes and is prevalent in older adults. We investigated the impact of social isolation on bone mineral density (BMD) and physical capability in community-dwelling older adults. Methods: Data were collected in 2011 and 2017 from the Hertfordshire Cohort Study. In 2011, we assessed social isolation using the six-item Lubben Social Network Scale (LSNS-6) and the Maastricht Social Participation Profile (MSSP) and depressive and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Physical capability was assessed by performing tests of gait speed, chair stands, timed up and go and balance at both time points. BMD was assessed using dual X-ray absorptiometry (DXA) at both time points. Results: Data were available from 369 participants in 2011 and 184 in 2017. Forty percent of men and 42.4% of women were socially isolated. Isolated participants had higher odds of depressive disorder (OR 3.01, 95% CI 1.27–7.11, p < 0.02). Social isolation at baseline was associated with poor physical capability scores at follow-up (OR 5.53, 95% CI 1.09–27.99, p < 0.04). No associations were found between social isolation and BMD at either time point. Conclusions: Social isolation was associated with higher odds of having depressive symptoms and predicted the development of poor physical capability 6 years later. Further longitudinal studies that include loneliness as a covariate are warranted. [ABSTRACT FROM AUTHOR]

Background: The Frailty In Residential Sector over Time (FIRST) Study is a 3-year prospective cohort study investigating the health of residents living in residential aged care services (RACS) in South Australia. The study aims to examine the change in frailty status and associated health outcomes.Methods: This interim report presents data from March 2019-October 2020. The study setting is 12 RACS from one organisation across metropolitan and rural South Australia involving 1243 residents. All permanent (i.e. respite or transition care program excluded) residents living in the RACS for at least 8 weeks were invited to participate. Residents who were deemed to be medically unstable (e.g. experiencing delirium), have less than 3 months to live, or not fluent in English were excluded. Data collected included frailty status, medical diagnoses, medicines, pain, nutrition, sarcopenia, falls, dementia, anxiety and depression, sleep quality, quality of life, satisfaction with care, activities of daily living, and life space use at baseline and 12-months. Data Linkage will occur over the 3 years from baseline.Results: A total of 561 permanent residents (mean age 87.69 ± 7.25) were included. The majority of residents were female (n = 411, 73.3%) with 95.3% (n = 527) being classified as either frail (n = 377, 68.2%) or most-frail (n = 150, 27.1%) according to the Frailty Index (FI). Most residents were severely impaired in their basic activities of daily living (n = 554, 98.8%), and were at-risk of malnutrition (n = 305, 55.0%) and at-risk of sarcopenia (n = 492, 89.5%). Most residents did not experience pain (n = 475, 85.4%), had normal daytime sleepiness (n = 385, 69.7%), and low anxiety and depression scores (n = 327, 58.9%).Conclusion: This study provides valuable information on the health and frailty levels of residents living in RACS in South Australia. The results will assist in developing interventions that can help to improve the health and wellbeing of residents in aged care services.Trial Registration: Prospectively registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12619000500156 ). [ABSTRACT FROM AUTHOR]

Although often used as a nuisance in resting-state functional magnetic resonance imaging (rsfMRI), the global brain signal in humans and anesthetized animals has important neural basis. However, our knowledge of the global signal in awake rodents is sparse. To bridge this gap, we systematically analyzed rsfMRI data acquired with a conventional single-echo (SE) echo planar imaging (EPI) sequence in awake rats. The spatial pattern of rsfMRI frames during peaks of the global signal exhibited prominent co-activations in the thalamo-cortical and hippocampo-cortical networks, as well as in the basal forebrain, hinting that these neural networks might contribute to the global brain signal in awake rodents. To validate this concept, we acquired rsfMRI data using a multi-echo (ME) EPI sequence and removed non-neural components in the rsfMRI signal. Consistent co-activation patterns were obtained in extensively de-noised ME-rsfMRI data, corroborating the finding from SE-rsfMRI data. Furthermore, during rsfMRI experiments, we simultaneously recorded neural spiking activities in the hippocampus using GCaMP-based fiber photometry. The hippocampal calcium activity exhibited significant correspondence with the global rsfMRI signal. These data collectively suggest that the global rsfMRI signal contains significant neural components that involve coordinated activities in the thalamo-cortical and hippocampo-cortical networks. These results provide important insight into the neural substrate of the global brain signal in awake rodents. [ABSTRACT FROM AUTHOR]

This study investigates how higher ability CEOs behave differently from lower ability CEOs in making investment decisions and, particularly, whether CEO managerial ability contributes to improved investment efficiency. I show evidence that more able CEOs make more efficient investment decisions. Specifically, talented CEOs increase (decrease) capital expenditures, acquisition expenditures, and total investments when their firms operate in settings more prone to under-investment (over-investment). These results suggest that high managerial ability helps with overcoming the two sources of investment inefficiency: over- and under-investment. I also find that the positive impact of CEO managerial ability on investment efficiency generally persists across different levels of board monitoring, whereas it gets weaker as the CEOs are overly exposed to equity risk. Robustness tests of using alternative measures of CEO managerial ability and controlling for potential endogeneity issues generate consistent results. Overall, the findings suggest that higher managerial ability leads to more efficient investment decision-making. [ABSTRACT FROM AUTHOR]

Summary: Clustering of factors linked with poor bone health is common in older adults and is associated with lower bone density and increased fracture risk in women. Purpose: Many factors are associated with bone mineral density, which in turn is strongly linked with risk of fragility fracture. We assessed how commonly clustering of risk factors occurs and related such clustering to bone mineral density in a population of older community-dwelling men and women. Method: This is a cross-sectional study with 498 men and 498 women aged 59 to 72 years, who were participants in the Hertfordshire Cohort Study, in whom incident fracture was recorded. Physical activity, diet quality, history of prior fracture, family history of fracture, cigarette and alcohol consumption and comorbidities were obtained through baseline questionnaire. Measurements of grip strength and bone mineral density of the lumbar spine and total femur were also taken. Results: Clustering of risk factors was common, with over 30 % having two or more. In women, a graded association between the number of risk factors and low bone density was seen, and strong relationships were also seen between the number of risk factors and incident fracture; women with three or more risk factors had an adjusted hazard ratio (HR) of incident fracture of 5.98 (1.67, 21.43; p = 0.006) compared to women with no risk factors; women with two risk factors had an adjusted HR of 2.97 (1.14, 7.74; p = 0.03) and those with one, 2.28 (0.90, 5.75; p = 0.08). Conclusion: Clustering of risk factors for poor bone health is common in community-dwelling older adults and is associated with increased risk of fracture and adverse bone health in women. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies on epidemiology of rheumatology which include the correlation of comorbidity and functional disability in early rheumatoid arthritis (RA), the risk of pneumonia in patients with RA and the impact of small spinal curves in adolescents.

The article presents abstracts of studies on primary care management of rheumatology which include the integration of care for joint pain and anxiety, the cost of rheumatoid factor testing in Spanish primary care and the prevalence of depression in patients with polymyalgia rheumatica.

Purpose: Dexamethasone intravitreal implant (DEX implant, Ozurdex®; Allergan, Inc.) is used to treat noninfectious posterior uveitis and macular edema associated with retinal vein occlusion and diabetic retinopathy. Two recently published reports of DEX implant fragmentation shortly after injection have raised concerns about the potential for faster implant dissolution and elevated ocular dexamethasone concentrations. This study compared the in vivo release profile and pharmacokinetic behavior of intact and fragmented DEX implants. Methods: DEX implant was surgically implanted as a single unit or fragmented into 3 pieces in the posterior segment of opposing eyes of 36 New Zealand white rabbits. The release of dexamethasone over time from 1-piece and 3-piece fragmented implants dissolved in solution in vitro was compared with that from the 1-piece and 3-piece fragmented implants placed in the rabbit eyes. In addition, dexamethasone concentrations in the vitreous and aqueous humors of each eye were measured at 3 h and days 1, 7, 14, 21, and 28. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used for assays. Results: Dexamethasone release from the 1-piece and 3-piece DEX implants in vivo was not different and was consistent with the in vitro release pattern. Moreover, the concentration profile of dexamethasone in the vitreous and aqueous humors was similar for the 1-piece and 3-piece DEX implants at each time point measured. Conclusions: DEX implant fragmentation neither accelerated its dissolution nor increased the dexamethasone concentration delivered at a given time. Accordingly, DEX implant fragmentation is unlikely to have clinically significant effects in patients. [ABSTRACT FROM AUTHOR]

Daniel Bergstresser provides a detailed description of the 14 papers and discussions about them that were presented at the Brandeis International Business School's First Municipal Finance Conference, held on August 3, 2012. [ABSTRACT FROM AUTHOR]

Firstly, increased Ki67 and MUM-1 staining has been associated with worse prognosis in marginal zone B cell lymphomas (MZL). However, ours is the first study to assess the impact of proliferative indices on chemotherapy response. Secondly, loss of p53 and p16 tumor suppressor genes (TSG) has traditionally been associated with cancer progression. The significance of these markers in MZL was investigated. Thirdly, we explored the role of proliferative indices and tumor suppressor genes in identifying MZLs with significant plasmacytic differentiation (PD). Consecutive MZL cases (2006-2008) were identified. Slides were reviewed to confirm the diagnosis; immunohistochemical stains for Ki67, MUM-1, WT-1, p53, and p16 were subsequently performed and graded for percentage staining. Wilcoxon two-sample test and Pearson correlation coefficient were performed. Twenty-nine cases were analyzed. None of the assayed markers were correlated with treatment response. Ki67 and MUM1 expression, however, were correlated with PD ( p = 0.0136 and p = 0.0042). A correlation between MUM1 and p16 staining was also seen ( p = 0.0006). IHC assay for TSGs, p53 and p16, and proliferative indices (Ki67, MUM1, WT1) is unlikely to predict treatment response in low-grade MZL. Ki67 and MUM1 staining, however, may serve as a useful adjunct in ascribing PD. [ABSTRACT FROM AUTHOR]

''Use it and improve it, or lose it'' is one of the axioms of motor therapy after stroke. There is, however, little understanding of the interactions between arm function and use in humans post-stroke. Here, we explored putative non-linear interactions between upper extremity function and use by developing a first-order dynamical model of stroke recovery with longitudinal data from participants receiving constraint induced movement therapy (CIMT) in the EXCITE clinical trial. Using a Bayesian regression framework, we systematically compared this model with competitive models that included, or not, interactions between function and use. Model comparisons showed that the model with the predicted interactions between arm function and use was the best fitting model. Furthermore, by comparing the model parameters before and after CIMT intervention in participants receiving the intervention one year after randomization, we found that therapy increased the parameter that controls the effect of arm function on arm use. Increase in this parameter, which can be thought of as the confidence to use the arm for a given level of function, lead to increase in spontaneous use after therapy compared to before therapy. INSET: Author Summary. [ABSTRACT FROM AUTHOR]

The article discusses a study on the factors that influence product yield in microbial fermentation. Interest in green biotechnology focused on the metabolic engineering of selected microbes to produce pharmaceuticals and biofuels. Several techniques have been developed to achieve maximum product yield. Results of the study using a statistical model to analyze 10 years worth of research data from engineering Escherichia coli showed that cultivation modes, nutrient supplementation, and oxygen conditions influence product yields in fermentation processes.

Background: Sigma-2 receptors are over-expressed in proliferating cancer cells, making an attractive target for the targeted treatment of pancreatic cancer. In this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to induce apoptosis and augment standard chemotherapy. Results: The binding affinity for sigma-2 ligands is high in pancreas cancer, and they induce apoptosis with a rank order of SV119 < SW43 < SRM in vitro. Combining these compounds with gemcitabine further increased apoptosis and decreased viability. Our in vivo model showed that sigma-2 ligand treatment decreased tumor volume to the same extent as gemcitabine. However, SW43 combination treatment with gemcitabine was superior to the other compounds and resulted in stabilization of tumor volume during treatment, with minimal toxicities. Conclusions: This study shows that the sigma-2 ligand SW43 has the greatest capacity to augment gemcitabine in a pre-clinical model of pancreas cancer and has provided us with the rationale to move this compound forward with clinical investigations for patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

We compare characteristics of municipal debt issues in states that mandate GAAP for municipalities with issues in states that impose no annual financial disclosure requirements. Cross-sectional comparisons indicate that the use of public (versus private) debt is greater, and municipal debt costs are 14 to 25 basis points lower, in states where GAAP is mandated. Moreover, municipalities in states that impose the GAAP requirement realize lower debt costs following the effective date of the regulation. These results suggest that GAAP requirements reduce municipal borrowing costs. More generally, the evidence indicates that financial reporting regulation reduces contracting costs between borrowers and lenders. [ABSTRACT FROM AUTHOR]

Objective: To describe the investigation and management of patients admitted to hospitals in China with suspected acute coronary syndromes (ACS) and to identify potential areas for improvement in practice. Design: A multicentre prospective survey of socio-demographic characteristics, medical history, clinical features, in-hospital investigations, treatment practices and major events among patients with suspected ACS. Setting: Large urban public hospitals. Patients: Consecutive patients admitted to in-patient facilities with a diagnosis of suspected acute myocardial infarction (Ml) or unstable angina pectoris. Main outcome measures: Myocardial infarction/re- infarction, heart failure, death. Results: Between September 2004 and May 2005, data were collected prospectively from 2973 patients admitted to 51 hospitals in 18 provinces of China. An initial diagnosis of ST elevation Ml, non-ST elevation Ml and unstable angina was made in 43%, 11% and 46% of patients, respectively. Diagnosis was inconsistent with objective measures in up to 20% of cases. At both tertiary and non-tertiary centres, there was little evidence that clinical risk stratification was used to determine the intensity of investigation and management. The mortality rate during hospitalisation was 5% overall and similar in tertiary and non-tertiary centres, but reported in-hospital re-infarction rates (8%) and heart failure rates (16%) were substantially higher at non-tertiary centres. Conclusion: This study has identified a number of areas in the management of ACS patients, including diagnosis and risk stratification, which deviate from current guide- lines. These findings will help inform the introduction of widely used quality improvement initiatives such as clinical pathways. [ABSTRACT FROM AUTHOR]

We present evidence that the 5-hydroxytryptamine1A (5-HT1A) receptor antagonist, N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl}- N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635), can induce receptor internalization in a human (h)5-HT1A receptor Chinese hamster ovary (CHO-K1) cell system. Exposure of h5-HT1A CHO cells to WAY-100635 decreased the cell-surface h5-HT1A receptor density in a way that was both time (24–72 h) and concentration (1–100 nm) dependent.[3H]WAY-100635 and [3H]8-hydroxy-dipropylaminotetralin ([3H]8-OH-DPAT) saturation analyses demonstrated a significant reduction (50–60%) in total h5-HT1A receptor number in the WAY-100635-treated (100 nm; 72 h) compared with control cells. In WAY-100635-treated cells, the 8-OH-DPAT-mediated inhibition of forskolin (FSK)-stimulated cAMP accumulation was right-shifted and the maximal inhibitory response of 8-OH-DPAT was impaired compared with control cells. Similar results were obtained for 8-OH-DPAT-mediated Ca2+ mobilization after WAY-100635 treatment. h5-HT1A receptors labeled with [3H]WAY-100635, as well as [3H]4-(2′-Methoxy)-phenyl-1-[2′-( N-2′′-pyridinyl)-p-fluorobenzamido]ethyl-piperazine (MPPF), exhibited a time-dependent rate of cellular internalization that was blocked by endocytotic suppressors and was pertussis-toxin insensitive. In contrast, quantitative autoradiographic studies demonstrated that chronic treatment of rats with WAY-100635 for two weeks produced a region-specific increase in the 5-HT1A receptor density. In conclusion, prolonged exposure of an h5-HT1A cell-based system to the 5-HT1A antagonist, WAY-100635, induced a paradoxical internalization of cell surface receptor resulting in depressed functional activity. This suggests that an antagonist can influence 5-HT1A receptor recycling in vitro differently to in vivo regulatory conditions. [ABSTRACT FROM AUTHOR]

Presents abstracts related to neuropsychopharmacology. "Diffusion Tensor Imaging in Cocaine Dependence: Evidence for Reduced Myelin in the Anterior Corpus Callosum," by F. Gerard Moeller, Khader M. Hassan and Joel L. Steinberg; "Effects of Self-Administered and Passive Cocaine Infusions on Dopamine, Norepinephrine and Corticosterone Concentrations in the Medial Prefrontal Cortex," by Nicholas E. Goeders, Gennady N. Smagin and Marie F. Lanfranco; "Decreased Corticolimbic Responset To Monetary Reward in Cocaine Addiction: Association with Motivation and Self-Control," by Rita Z. Goldstein, Dardo Tomasi and Nelly Alia-Klein; "Interactions Between Nalbuphine,Mood and Hypothalamic- Pituitary-Axis (HPA) Hormones," by Nathalie V. Goletiani, Jack H. Mendelson and Michelle B. Sholar.

Gene expression of osteopontin (OPN) has been investigated in mice by application of laser capture microdissection (LCM) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. LCM permits individual cells to be isolated ("captured") from tissue sections for molecular analyses. In this study, chondrocytes were captured from growth plate zones in frozen sections of tibiae from 1-11-day-old postnatal mice. RNA was extracted from cells, DNAse-treated, and reverse-transcribed. cDNA was amplified by PCR and OPN mRNA was revealed on agarose gels. Whole cartilage and brain (a positive control) from the same animals also were examined. Reactions containing no RT were negative controls, and 18S rRNA standardized expressed message from captured cells. RT-PCR analysis of laser-captured whole cartilage showed a general qualitative loss of OPN mRNA as animal age increased. Youngest mice gave equivalent OPN expression over all laser-microdissected cartilage zones. For 7-11 day-old mice, OPN expression was qualitatively greatest in resting and lowest in hypertrophic regions of cartilage. Expression of OPN correlated with mineral in the tissue suggests that OPN functionally may inhibit normal vertebrate growth plate mineralization, and its loss with increasing tissue maturation appears permissive to mineral development. [ABSTRACT FROM AUTHOR]

Summary It is generally accepted that the interaction between CD40 and its ligand (CD154) plays a decisive role in contact-dependent help for T and B cells. In CD154-deficient MRL/Mp-Fas lpr (MRL/lpr ) mice, however, high titres of IgG2a-type autoantibodies against small nuclear ribonucleoproteins (snRNPs) are observed. We successfully isolated two CD154-deficient MRL/lpr Th1 lines, which could provide B cell help for anti-snRNP antibody production. The proliferative responses of the Th1 cell lines were MHC class II (I-Ek )-restricted. Although syngeneic B cell proliferation was induced by Th1 lines in both a contact-dependent and -independent manner, the soluble form of TNF-α (sTNF-α ) was not involved in contact-independent B cell proliferation. On the other hand, both anti-TNF-α and TNF-receptor 2 (TNF-R2, p75) monoclonal antibody (MoAb) blocked contact-dependent B cell proliferation, suggesting that the transmembrane form of TNF-α (mTNF-α )–TNF-R2 co-stimulation participates in B cell activation. Similarly, anti-TNF-α and TNF-R2 MoAb inhibited anti-snRNP antibody production in vitro , but anti-CD154 or TNF-R1 MoAb did not. These results indicate that the interaction of mTNF-α on activated Th1 cells with TNF-R2 on B cells may be involved in the autoimmunity seen in MRL mice, and that the blockade of CD40-CD154 co-stimulation may not always be able to suppress some Th1-related manifestations of lupus. [ABSTRACT FROM AUTHOR]