Associations between combinations of job demands and job control among 6,16,818 people aged 55-64 in paid work with their labour market status 11 years later: a prospective cohort study.

BACKGROUND: Given current discussions about extending working lives, more knowledge is needed on working conditions associated with labour market status in older age. OBJECTIVE: To explore associations between combinations of job demands and job control among workers aged 55-64 years and their labour market status 11 years later. METHODS: A population-based prospective cohort study using nationwide register data. The 616,818 individuals in Sweden aged 55-64 who in 2001 were in paid work were categorised using a job exposure matrix based on tertiles (reference = medium control/medium demands). Participants were followed up in 2012 regarding their main labour market status (paid work, old-age pension, no income/social assistance, sickness absence/disability pension, emigrated, dead; reference = old-age pension) using multinomial logistic regression for odds ratios (OR) and 95% confidence intervals (CI). The fully adjusted analyses included adjustment for sociodemographic factors and unemployment or sickness absence/disability pension for more than half the year in 2001. RESULTS: Those in occupations with low job control at baseline were less likely to be in paid work at follow-up (OR low demands/low control 0.74, CI 0.71-0.78; high demands/low control 0.81, CI 0.75-0.87). Those in occupations with baseline high demands were less likely to have no income/social assistance at follow-up (OR high demands/low control 0.71, CI 0.52-0.96; high demands/high control 0.59, CI 0.47-0.75). CONCLUSION: Job demands and control when aged 55-64 were associated with labour market status 11 years later: high control was associated with greater chance of being in paid work, and high demands were associated with lower risk of no income/social assistance.

Sick leave among people in paid work after age 65: A Swedish population-based study covering 1995, 2000, 2005 and 2010.

AIMS: Extending working life into older age groups is discussed in many countries. However, there is no knowledge about how this affects rates of sick leave. The aim of this work was to investigate rates of sick leave among people in paid work after retirement age and if such rates have changed over time. METHODS: Swedish nationwide register data on people aged >65 years and living in Sweden in 1995, 2000, 2005 and 2010 were analysed. All people with a sufficiently high work income to be eligible for public sick leave benefits were included. The proportions in paid work and compensated rates of sick leave for people aged 66-70 and ≥71 were analysed by sex, educational level, country of birth, living area, and employment type and sector. RESULTS: The percentage of people in paid work at ages 66-70 years increased from <10% in 1995 to 24% in 2010 and among those aged ≥71 years from 2.7% in 1995 to 3.5% in 2010. The rates of sick leave among working people aged 66-70 years were 3.3% in 1995 and 2.4% in 2010 and for people aged ≥71 years the rates of sick leave were 2.2% in 1995 and 0.2% in 2010. Women had higher rates of sick leave than men in 2005 and 2010, but lower in 1995 and 2000. In 2010, the rates of sick leave were similar between employees and the self-employed, and higher among employees in the public sector than among employees in the private sector. CONCLUSIONS: Rates of sick leave among workers aged >65 years were lower in 2010 than in 1995, despite much higher rates of labour market participation in 2010.

Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75: a multicohort study.

BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m-2) to obesity class II (⩾35 kg m-2). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category. RESULTS: The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts. CONCLUSIONS: Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.

Impact of childhood and adulthood psychological health on labour force participation and exit in later life.

BACKGROUND: Adulthood psychological health predicts labour force activity but few studies have examined childhood psychological health. We hypothesized that childhood psychological ill-health would be associated with labour force exit at 55 years. METHOD: Data were from the 55-year follow-up of the National Child Development Study (n = 9137). Labour force participation and exit (unemployment, retirement, permanent sickness, homemaking/other) were self-reported at 55 years. Internalizing and externalizing problems in childhood (7, 11 and 16 years) and malaise in adulthood (23, 33, 42, 50 years) were assessed. Education, social class, periods of unemployment, partnership separations, number of children, and homemaking activity were measured throughout adulthood. RESULTS: Childhood internalizing and externalizing problems were associated with unemployment, permanent sickness and homemaking/other at 55 years, after adjustment for adulthood psychological health and education: one or two reports of internalizing was associated with increased risk for unemployment [relative risk (RR) 1.59, 95% confidence interval (CI) 1.12-2.25; RR 2.37, 95% CI 1.48-3.79] and permanent sickness (RR 1.32, 95% CI 1.00-1.74; RR, 1.48, 95% CI 1.00-2.17); three reports of externalizing was associated with increased risk for unemployment (RR 2.26, 95% CI 1.01-5.04), permanent sickness (RR 2.63, 95% CI 1.46-4.73) and homemaking/other (RR 1.95, 95% CI 1.00-3.78). CONCLUSIONS: Psychological ill-health across the lifecourse, including during childhood, reduces the likelihood of working in older age. Support for those with mental health problems at different life stages and for those with limited connections to the labour market, including homemakers, is an essential dimension of attempts to extend working lives.

Psychosocial factors associated with work disability in men and women with diabetes: a pooled analysis of three occupational cohort studies.

AIMS: To examine the extent to which adverse psychosocial factors, such as living alone, psychological distress, job strain and low support from supervisor, increase the risk of work disability (sickness absence and disability pension) among employees with diabetes. METHODS: In this pooled analysis of individual-participant data from three occupational cohort studies (the Finnish Public Sector Study, the British Whitehall II study, and the French GAZEL study), 1088 women and 949 men with diabetes were followed up to determine the duration (number of days) and frequency (number of spells) of work disability. The mean follow-up periods were 3.2 years in the GAZEL study, 4.6 years in the Whitehall II study and 4.7 years in the Finnish Public Sector Study. Psychosocial factors and potential confounding factors were assessed at baseline using standard questionnaires. Study-specific estimates were pooled using fixed-effects meta-analysis. RESULTS: In analysis adjusted for sociodemographic factors, health behaviours and comorbidities, participants with psychological distress had longer (rate ratio 1.66; 95% CI 1.31-2.09) and more frequent absences (rate ratio 1.33; 95% CI 1.19-1.49) compared with those with no psychological distress. Job strain was associated with slightly increased absence frequency (rate ratio 1.19 95% CI 1.05-1.35), but not with absence duration. Living alone and low supervisor support were not associated with absence duration or frequency. We observed no sex differences in these associations. CONCLUSIONS: Psychological distress was associated with increased duration and frequency of work disability among employees with diabetes. Job strain was associated with increased absence frequency but not with absence duration.

Big cat, small cat: reconstructing body size evolution in living and extinct Felidae.

The evolution of body mass is a fundamental topic in evolutionary biology, because it is closely linked to manifold life history and ecological traits and is readily estimable for many extinct taxa. In this study, we examine patterns of body mass evolution in Felidae (Placentalia, Carnivora) to assess the effects of phylogeny, mode of evolution, and the relationship between body mass and prey choice in this charismatic mammalian clade. Our data set includes 39 extant and 26 extinct taxa, with published body mass data supplemented by estimates based on condylobasal length. These data were run through 'SURFACE' and 'bayou' to test for patterns of body mass evolution and convergence between taxa. Body masses of felids are significantly different among prey choice groupings (small, mixed and large). We find that body mass evolution in cats is strongly influenced by phylogeny, but different patterns emerged depending on inclusion of extinct taxa and assumptions about branch lengths. A single Ornstein-Uhlenbeck optimum best explains the distribution of body masses when first-occurrence data were used for the fossil taxa. However, when mean occurrence dates or last known occurrence dates were used, two selective optima for felid body mass were recovered in most analyses: a small optimum around 5 kg and a large one around 100 kg. Across living and extinct cats, we infer repeated evolutionary convergences towards both of these optima, but, likely due to biased extinction of large taxa, our results shift to supporting a Brownian motion model when only extant taxa are included in analyses.

Lifestyle-related risk factors and trajectories of work disability over 5 years in employees with diabetes: findings from two prospective cohort studies.

AIMS: To examine work disability trajectories among employees with and without diabetes and identify lifestyle-related factors associated with these trajectories. METHODS: We assessed work disability using records of sickness absence and disability pension among participants with diabetes and age- sex-, socio-economic status- and marital status-matched controls in the Finnish Public Sector Study (1102 cases; 2204 controls) and the French GAZEL study (500 cases; 1000 controls), followed up for 5 years. Obesity, physical activity, smoking and alcohol consumption were assessed at baseline and the data analysed using group-based trajectory modelling. RESULTS: Five trajectories described work disability: 'no/very low disability' (41.1% among cases and 48.0% among controls); 'low-steady' (35.4 and 34.7%, respectively); 'high-steady' (13.6 and 12.1%, respectively); and two 'high-increasing' trajectories (10.0 and 5.2%, respectively). Diabetes was associated with a 'high-increasing' trajectory only (odds ratio 1.90, 95% CI 1.47-2.46). Obesity and low physical activity were similarly associated with high work disability in people with and without diabetes. Smoking was associated with 'high-increasing' trajectory in employees with diabetes (odds ratio 1.88, 95% CI 1.21-2.93) but not in those without diabetes (odds ratio 1.32, 95% CI 0.87-2.00). Diabetes was associated with having multiple ( ≥ 2) risk factors (21.1 vs. 11.4%) but the association between multiple risk factors and the 'high-increasing' trajectory was similar in both groups. CONCLUSIONS: The majority of employees with diabetes have low disability rates, although 10% are on a high and increasing disability trajectory. Lifestyle-related risk factors have similar associations with disability among employees with and without diabetes, except smoking which was only associated with poorer prognosis in diabetes.

Serum total hCGß level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

BACKGROUND: Serum total human chorionic gonadotrophin ß subunit (hCGß) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. METHODS: We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGß level was dichotomised at < vs ≥2 IU l(-1). RESULTS: A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGß level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. CONCLUSIONS: Serum total hCGß level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

Socioeconomic position predicts long-term depression trajectory: a 13-year follow-up of the GAZEL cohort study.

Individuals with low socioeconomic position have high rates of depression; however, it is not clear whether this reflects higher incidence or longer persistence of disorder. Past research focused on high-risk samples, and risk factors of long-term depression in the population are less well known. Our aim was to test the hypothesis that socioeconomic position predicts depression trajectory over 13 years of follow-up in a community sample. We studied 12 650 individuals participating in the French GAZEL study. Depression was assessed by the Center for Epidemiological Studies-Depression scale in 1996, 1999, 2002, 2005 and 2008. These five assessments served to estimate longitudinal depression trajectories (no depression, decreasing depression, intermediate/increasing depression, persistent depression). Socioeconomic position was measured by occupational grade. Covariates included year of birth, marital status, tobacco smoking, alcohol consumption, body mass index, negative life events and preexisting psychological and non-psychological health problems. Data were analyzed using multinomial regression, separately in men and women. Overall, participants in intermediate and low occupational grades were significantly more likely than those in high grades to have an unfavorable depression trajectory and to experience persistent depression (age-adjusted ORs: respectively 1.40, 95% confidence interval (CI) 1.16-1.70 and 2.65, 95% CI 2.04-3.45 in men, 2.48, 95% CI 1.36-4.54 and 4.53, 95% CI 2.38-8.63 in women). In multivariate models, the socioeconomic gradient in long-term depression decreased by 21-59% in men and women. Long-term depression trajectories appear to follow a socioeconomic gradient; therefore, efforts aiming to reduce the burden of depression should address the needs of the whole population rather than exclusively focus on high-risk groups.

Maternal separation in childhood and diurnal cortisol patterns in mid-life: findings from the Whitehall II study.

BACKGROUND: Animal studies suggest that maternal separation is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis through effects that occur in a critical period following birth. Evidence for an association of the diurnal cortisol rhythm with maternal separation in humans is equivocal. METHOD: We examined whether maternal separation in childhood is associated with diurnal cortisol pattern in 3712 middle-aged men and women. Two aspects of cortisol release were examined: the cortisol awakening response (CAR) and the diurnal slope in cortisol throughout the day. RESULTS: Maternal separation in childhood was reported by 12% of participants. Those participants who reported maternal separation had a larger CAR and flatter slopes in cortisol levels compared to those who did not report maternal separation [adjusted mean CAR in those reporting no separation versus separation: 7.1, 95% confidence interval (CI) 6.7-7.5 v. 8.4, 95% CI 7.3-9.5, p = 0.02, corresponding to adjusted mean diurnal slope: -0.129 (95% CI -0.130 to -0.128) v. -0.126 (95% CI -0.128 to -0.124), p = 0.01]. In participants who reported maternal separation, the age of separation was not associated with either cortisol measure (p = 0.11). The association between maternal separation and slope in cortisol secretion was largely explained by smoking behaviour and marital status at the time of sample collection whereas that of the CAR was explained by childhood psychosocial, material factors and adult health behaviours. CONCLUSIONS: Our findings suggest that maternal separation in childhood is associated with alterations in the diurnal cortisol pattern in middle age. These associations are predominantly accounted for by adult circumstances and behaviours.

Use of self-administered instruments to assess psychiatric disorders in older people: validity of the General Health Questionnaire, the Center for Epidemiologic Studies Depression Scale and the self-completion version of the revised Clinical Interview Schedule.

BACKGROUND: Diagnosis of depressive disorder using interviewer-administered instruments is expensive and frequently impractical in large epidemiological surveys. The aim of this study was to assess the validity of three self-completion measures of depressive disorder and other psychiatric disorders in older people against an interviewer-administered instrument. METHOD: A random sample stratified by sex, age and social position was selected from the Whitehall II study participants. This sample was supplemented by inclusion of depressed Whitehall II participants. Depressive disorder and other mental disorders were assessed by the interviewer-administered structured revised Clinical Interview Schedule (CIS-R) in 277 participants aged 58-80 years. Participants also completed a computerized self-completion version of the CIS-R in addition to the General Health Questionnaire (GHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: The mean total score was similar for the interviewer-administered (4.43) and self-completion (4.35) versions of the CIS-R [95% confidence interval (CI) for difference -0.31 to 0.16]. Differences were not related to sex, age, social position or presence of chronic physical illness. Sensitivity/specificity of self-completion CIS-R was 74%/98% for any mental disorder and 75%/98% for depressive episode. The corresponding figures were 86%/87% and 78%/83% for GHQ and 77%/89% and 89%/86% for CES-D. CONCLUSIONS: The self-completion computerized version of the CIS-R is feasible and has good validity as a measure of any mental disorder and depression in people aged ≥ 60 years. GHQ and CES-D also have good criterion validity as measures of any mental disorder and depressive disorder respectively.

Gullies on Mars could have formed by melting of water ice during periods of high obliquity.

Gullies on Mars resemble water-carved channels on Earth, but they are mostly at elevations where liquid water is not expected under current climate conditions. It has been suggested that sublimation of carbon dioxide ice alone could have formed Martian gullies. We used a general circulation model to show that the highest-elevation Martian gullies coincide with the boundary of terrain that experienced pressures above the triple point of water when Mars' rotational axis tilt reached 35°. Those conditions have occurred repeatedly over the past several million years, most recently ~630,000 years ago. Surface water ice, if present at these locations, could have melted when temperatures rose >273 kelvin. We propose a dual gully formation scenario that is driven by melting of water ice followed by carbon dioxide ice sublimation.

Mitochondria organelle transplantation: introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity.

Mitochondrial dysfunction of cancer cells includes increased aerobic glycolysis, elevated levels of ROS, decreased apoptosis, and resistance to chemotherapeutic agents. We hypothesized that the introduction of normal mitochondria into cancer cells might restore mitochondrial function and inhibit cancer cell growth, and reverse chemoresistance. First, in the present study, we tested if mitochondria of immortalized, untransformed mammary epithelial MCF-12A cells could enter into human cancer cell lines. Second, if introducing normal mitochondria into cancer cells would inhibit proliferation. And third, would the addition of normal mitochondria increase the sensitivity of human breast cancer MCF-7 cells to chemotherapy. We found that JC-1-stained mitochondria of immortalized, untransformed mammary epithelial MCF-12A cells can enter into the cancer cell lines MCF-7, MDA-MB-231, and NCI/ADR-Res, but cannot enter immortalized, untransformed MCF-12A cells. The normal mitochondria from immortalized, untransformed MCF-12A cells suppressed the proliferation of MCF-7 and NCI/ADR-Res cells in a dose-dependent pattern, but did not affect the proliferation of immortalized, untransformed MCF-12A cells. The normal mitochondria from immortalized, untransformed MCF-12A cells increased the sensitivity of human breast cancer MCF-7 cells to doxorubicin, Abraxane, and carboplatin. In conclusion, the introduction of normal mammary mitochondria into human breast cancer cells inhibits cancer cell proliferation and increases the sensitivity of the MCF-7 human breast cancer cell line to doxorubicin, Abraxane, and carboplatin. These results support the role of mitochondrial dysfunction in cancer and suggest the possible use of targeted mitochondria for cancer therapeutics.

Exposure to Contaminated River Water is Associated with Early Hatching and Dysregulation of Gene Expression in Early Life Stages of the Endangered Copper Redhorse (Moxostoma hubbsi).

The copper redhorse (Moxostoma hubbsi) is an endangered fish that spawns exclusively in the Richelieu River (Quebec, Canada). Tributaries of the Richelieu are contaminated with high levels of current-use pesticides, which may impact early-life stage (ELS) copper redhorse and other native fishes. We assessed the effects of exposure to contaminated river water on ELS copper redhorse and river redhorse (Moxostoma carinatum), a related fish that shares the copper redhorse's spawning grounds and nursery habitat. A riverside flow-through system was used to expose copper and river redhorse embryos (1000 each) to Richelieu River water or laboratory water as a control. Fish were maintained until 14 days posthatch, and water samples were taken daily for chemical analysis. Following a heavy rain event, concentrations of two neonicotinoid pesticides, clothianidin and thiamethoxam, exceeded water quality guidelines for aquatic life (20 ng/L). Using nontargeted screening, we tentatively identified an additional 24 pharmaceutical and personal care products and 23 pesticides in river water. Effects of river water on ELS fish were observed in both species, but the copper redhorse appeared to be more sensitive. Fish exposed to river water hatched 10.7 (copper redhorse) and 2.4 (river redhorse) cumulative degree days earlier than controls. Copper redhorse survival was significantly lower in river water (73 ± 16%) compared to laboratory water (93 ± 3%), whereas river redhorse survival was similar between treatments (84 ± 6% and 89 ± 4%, respectively). Sequencing of copper redhorse larvae RNA revealed 18 differentially expressed genes (DEGs) following 14 days of exposure to river water. Eight up-regulated DEGs were linked to immune function and injury response, and seven down-regulated DEGs were involved with digestion and nutrient absorption. The present study provided valuable data on the effects of ELS exposure to a real-world mixture of contaminants in two fish species of concern. Environ Toxicol Chem 2022;41:1950-1966. © 2022 SETAC.

Tropical to mid-latitude snow and ice accumulation, flow and glaciation on Mars.

Images from the Mars Express HRSC (High-Resolution Stereo Camera) of debris aprons at the base of massifs in eastern Hellas reveal numerous concentrically ridged lobate and pitted features and related evidence of extremely ice-rich glacier-like viscous flow and sublimation. Together with new evidence for recent ice-rich rock glaciers at the base of the Olympus Mons scarp superposed on larger Late Amazonian debris-covered piedmont glaciers, we interpret these deposits as evidence for geologically recent and recurring glacial activity in tropical and mid-latitude regions of Mars during periods of increased spin-axis obliquity when polar ice was mobilized and redeposited in microenvironments at lower latitudes. The data indicate that abundant residual ice probably remains in these deposits and that these records of geologically recent climate changes are accessible to future automated and human surface exploration.

Occupation and mental health in a national UK survey.

OBJECTIVES: To measure the prevalence of common mental disorder (CMD) by occupation in a representative sample of Great Britain and to identify occupations with increased and decreased risk of CMD. METHODS: A cross-sectional interview-based survey was carried out including 5,497 working male and female respondents, 16-64 years from a stratified random survey of private households in Britain. Occupations were classified by the Standard Occupational Classification (SOC) into four groups: major, sub-major, minor and constituent unit groups. Common Mental Disorder was measured by the Revised Clinical Interview Schedule. RESULTS: Major SOC groups with higher prevalence of common mental disorder included clerical and secretarial, sales, and personal and protective services whereas craft and related, 'other' professional occupations and plant and machine operatives had lower prevalence compared to 13% overall prevalence in all adults. In sub-major SOC groups managers and administrators, teaching professionals, clerical and secretarial, 'other' sales and personal service occupations had higher prevalence whereas many professional and skilled occupations had lower prevalence. Specific SOC unit groups with higher prevalence included primary and secondary teachers, welfare community, youth workers, security staff, waiters, bar staff, nurse auxiliaries and care assistants. General managers in government and large organizations (OR=2.79, 95% CI 1.41-5.54), managers in transport and storing (OR=2.44, 95% CI 1.18-5.03), buyers and mobile sales persons (OR=2.48, 95% CI 1.09-5.60), sales occupations (NES) (OR=2.78, 95% CI 1.25-6.19) and clerks (NES) (OR=2.71, 95% CI 1.59-4.61) had increased risk of common mental disorder relative to specialist managers adjusting for social and financial factors and physical ill-health. CONCLUSIONS: Occupations with higher risk of common mental disorder may be typified by high levels of job demands, especially emotional demands and lack of job security. The reasons why occupations have low rates of common mental disorder are varied and may include high levels of job discretion, good job training and clearly defined job tasks.

Addressing unpredictability may be the key to improving performance with current clinically prescribed myoelectric prostheses.

The efferent control chain for an upper-limb myoelectric prosthesis can be separated into 3 key areas: signal generation, signal acquisition, and device response. Data were collected from twenty trans-radial myoelectric prosthesis users using their own clinically prescribed devices, to establish the relative impact of these potential control factors on user performance (user functionality and everyday prosthesis usage). By identifying the key factor(s), we can guide future developments to ensure clinical impact. Skill in generating muscle signals was assessed via reaction times and signal tracking. To assess the predictability of signal acquisition, we inspected reaction time spread and undesired hand activations. As a measure of device response, we recorded the electromechanical delay between electrode stimulation and the onset of hand movement. Results suggest abstract measures of skill in controlling muscle signals are poorly correlated with performance. Undesired activations of the hand or incorrect responses were correlated with almost all kinematics and gaze measures suggesting unpredictability is a key factor. Significant correlations were also found between several measures of performance and the electromechanical delay; however, unexpectedly, longer electromechanical delays correlated with better performance. Future research should focus on exploring causes of unpredictability, their relative impacts on performance and interventions to address this.

The role of loneliness in the development of depressive symptoms among partnered dementia caregivers: Evidence from the English Longitudinal Study of Aging.

BACKGROUND: Depressive symptoms are highly prevalent among partnered dementia caregivers, but the mechanisms are unclear. This study examined the mediating role of loneliness in the association between dementia and other types of care on subsequent depressive symptoms. METHODS: Prospective data from partnered caregivers were drawn from the English Longitudinal Study of Aging. The sample consisted of 4,672 partnered adults aged 50-70 living in England and Wales, followed up between 2006-2007 and 2014-2015. Caregiving was assessed across waves 3 (2006-2007), 4 (2008-2009), and 5 (2010-2011), loneliness at wave 6 (2012-2013), and subsequent depressive symptoms at wave 7 (2014-15). Multivariable logistic regression models were used to assess the association between caregiving for dementia and depressive symptoms compared to caregiving for other illnesses (e.g., diabetes, coronary heart disease (CHD), cancer, and stroke). Binary mediation analysis was used to estimate the indirect effects of caregiving on depressive symptoms via loneliness. RESULTS: Care for a partner with dementia was associated with higher odds of depressive symptoms at follow-up compared to those not caring for a partner at all (odds ratio [OR] = 2.6, 95% confidence intervals [CI]: 1.4, 5.1). This association was partially mediated by loneliness (34%). Care for a partner with other conditions was also associated with higher odds of depressive symptoms compared to non-caregiving partners (OR = 1.7, 95% CI: 1.2, 2.5), but there was no evidence of an indirect pathway via loneliness. CONCLUSION: Loneliness represents an important contributor to the relationship between dementia caregiving and subsequent depressive symptoms; therefore, interventions to reduce loneliness among partnered dementia caregivers should be considered.

Increasing antiviral activity of surfactant protein d trimers by introducing residues from bovine serum collectins: dissociation of mannan-binding and antiviral activity.

Collectins contribute to host defence through interactions with glycoconjugates on pathogen surfaces. We have prepared recombinant trimeric neck and carbohydrate recognition domains (NCRD) of collectins, and we now show that the NCRD of bovine conglutinin and CL-46 (like that of CL-43) have greater intrinsic antiviral activity for influenza A virus (IAV) than the human SP-D NCRD (hSP-D-NCRD). The three serum collectins differ from SP-D by having insertions adjacent to amino acid 325 and substitution of hydrophobic residues for arginine 343. We previously showed that a three amino acid (RAK) insertion, as found in CL-43, increases antiviral activity and mannan-binding activity of the hSP-D-NCRD, while the substitution of valine at 343, as in conglutinin, more strongly increased these activities. Mannan-binding activity of collectins has been considered to predict for ability to bind to high mannose glycans on viruses or other pathogens. We now show, however, that combined mutants containing the RAK insertion and R343V or R343I substitutions have greatly increased mannan-binding ability, but lower IAV binding or inhibiting activity than mutants containing R343V or R343I substitutions only. These findings indicate differences in the recognition of glycan structures of mannan and IAV by the NCRD and emphasize the importance of the flanking sequences in determining the differing interactions of human SP-D and bovine serum collectins with mannose-rich glycoconjugates on IAV and other pathogens. Of interest, we show conservation of some monoclonal antibody-binding epitopes between bovine collectin NCRD and hSP-D, suggesting shared structural motifs.