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Background: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover.Aims: We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men.Participants: A total of 3384 community-dwelling men aged 70 to 89 years.Methods: Collagen type I C-terminal cross-linked telopeptide, N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllysine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained.Results: Median age was 76.3 years (interquartile range, 74.2 to 79.1 years). Plasma CML was measured in 3011 men, methylglyoxal and glyoxal in 766 men, and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal, and esRAGE were similar in men without and with diabetes (all P > 0.05). CML was positively associated with fasting glucose (r = 0.06, P < 0.001), and esRAGE was inversely associated (r = -0.08, P = 0.045). esRAGE was positively associated with bone formation (P1NP, r = 0.17, P < 0.001; ucOC, r = 0.11, P = 0.008; TOC, r = 0.16, P < 0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared with men in the lowest quartile (hazard ratio, 0.49; 95% CI, 0.24 to 0.99; P = 0.045).Conclusions: Glycemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men, whereas CML predicts incidence of hip fracture.

Background and Objectives: Despite the demonstrated protective effects of green tea and coffee intake against several chronic diseases, finding between studies have not been consistent. One potential reason of this discrepancy is the imprecision in the measurement of tea or coffee consumption using food frequency questionnaire (FFQ) and food record (FR) in epidemiological studies. Methods and Study Design: In a sample of 57 healthy Japanese women, intake of green tea and coffee was estimated by a validated FFQ and a 3-day FR, while their plasma and urine concentrations of polyphenol biomarkers were measured by HPLC. The polyphenols assessed included (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)- epicatechin (EC), caffeic acid (CA) and chlorogenic acid (CGA). Results: Green tea consumption estimated by FFQ and FR showed moderate association, while strong association was detected for coffee consumption. Urinary green tea polyphenol concentrations were moderately-strongly associated with FR-estimated intake, while the associations were weak with FFQ. Similarly, coffee polyphenols in urine were moderately associated with FR-estimated coffee intake, whereas FFQ showed poor correlation. The associations between urinary and plasma polyphenols ranged from moderate to high. Conclusions: The results indicated that firstly, the FFQ tends to overestimate green tea intake. Secondly, the urinary polyphenols are preferred over plasma polyphenols as a potential surrogate marker of the short-term green tea and coffee intake, while their use as an indicator of long-term consumption is not reliable.

© 2018 John Wiley & Sons Ltd Objective: Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community-dwelling older men without known thyroid disease. Design: Prospective cohort study. Patients: Four thousand two hundred forty-eight men aged 70-89 years. Measurements: Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression. Results: After excluding men with pre-existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older, and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there were no associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population. Conclusions: In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in postmenopausal women.

© 2017 John Wiley & Sons Ltd. Objective: Insulin-like growth factor 1 (IGF1) has anabolic and growth-promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF1 is bound to binding proteins, which modulate bioavailability of IGF1. This study assessed the associations of IGF1 and its binding proteins 1 (IGFBP1) and 3 (IGFBP3) with cancer risk. Design: A prospective cohort study of 4042 men aged =70 years. Methods: Plasma total IGF1, IGFBP1 and IGFBP3 were measured between 2001 and 2004. Cancer-related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios (SHR). Results: There were 907 men who were diagnosed with cancer during a median of 9-year follow-up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully-adjusted model, higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR = 1.20, 95% CI 1.01-1.43; P = .041 for every 1 standard deviation increase in IGFBP3) but not other cancers. This effect was not attenuated by inclusion of total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03-1.58; P = .025). Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer-related deaths. Conclusion: Higher IGFBP3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF1. Further studies are warranted to explore potential underlying mechanisms.

© 2016 Diabetes UK Aims: To investigate behavioural, physical and biochemical characteristics associated with diabetes in the oldest age group of elderly men. Methods: We conducted a cross-sectional analysis of community-dwelling men aged 79–97 years from Perth, Western Australia. Lifestyle behaviours, self-rated health, physical function, and fasting glucose and HbA 1c levels were assessed. Results: Of 1426 men, 315 had diabetes (22%). Men with diabetes were of similar age to men without (84.9 vs 84.5 years; P = 0.14). Only 26.5% of men with diabetes self-rated their health as excellent or very good, compared with 40.6% of men without diabetes (P < 0.001). Diabetes was associated with less involvement with recreational walking (32.7 vs 41.0%; P < 0.01) and leisure activities (19.0 vs 26.5%; P < 0.01). Men with diabetes had poorer physical function on multiple measures, including longer times for the Timed Up-and-Go test (15.0 ± 6.9 s vs 13.4 ± 5.3 s; P < 0.001) and weaker knee extension (20.2 vs 21.9 kg; P < 0.001). In multivariate analyses, diabetes was associated with an increased prevalence of myocardial infarction (odds ratio 1.80, 95% CI 1.25–2.60; P < 0.001) and falls resulting in injury (odds ratio 1.55, 95% CI 1.06–2.26; P = 0.02). Average HbA 1c was 49 ± 8 mmol/mol (6.6 ± 0.8%) in men with diabetes, with 90.6% of these men on diet or oral hypoglycaemic therapy. Conclusions: In older men, diabetes is associated with poorer self-perceived health, reduced healthy lifestyle behaviours and physical function, heart disease and injurious falls. The majority of these men with diabetes had good glycaemic control. Encouraging healthy lifestyle behaviours and improving physical function should be evaluated as interventions to improve quality-of-life and health outcomes.

© 2017 The Author(s). Background: Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD). Methods: Community living 60-80 year olds with SMC or MCI who do not engage in more than 60 min per week of moderate intensity PA will be recruited from memory clinics and the community via media advertisements to participate in this randomized, single-blind controlled trial. All participants will receive an individually tailored home-based PA program of 150 min of moderate intensity walking/week for 6 months. The intervention group will undertake individual goal-setting and behavioral education workshops with mentor support via telephone (GM-PA). Those randomized to the control group will have standard education workshops and Physical Activity Liaison (PAL) contact via telephone (CO-PA). Increase in PA is the primary outcome, fitness, cognitive, personality, demographic and clinical parameters will be measured and a health economic analysis performed. A saliva sample will be collected for APOE e4 genotyping. All participants will have a goal-setting interview to determine their PA goals. Active volunteers aged 50-85 years will be recruited from the community randomized and trained to provide peer support as mentors (intervention group) or PALS (control group) for the 6-month intervention. Mentors and PALS will have PA, exercise self-efficacy and mentoring self-efficacy measured. Participants in both groups are asked to attend 3 workshops in 6 months. At the first workshop, they will meet the

© 2017, Springer Science+Business Media New York. Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06–1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08–1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.

Objectives: The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Methods: Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Results: Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). Conclusion: Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis.

Objectives: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM. Methods: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression. Results: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR=3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work. Conclusions: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure."

Background: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. Methods: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. Results: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4–77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5–19.2) vs histology 11.1 (4.8–19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. Conclusions: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing.

© 2016 John Wiley & Sons Ltd.Context: Thyroid hormones regulate cellular survival and metabolism; however, their association with cancer incidence and death has not been well explored. Objectives: Our aim was to examine the relationship between thyrotropin (TSH) and free thyroxine (FT4) with cancer incidence (all cancers, prostate, colorectal and lung cancer). Associations with cancer-related deaths were also explored. Design and setting: A prospective cohort study involving community-dwelling men aged 70-89 years. Main outcome measures: Thyroid hormones were measured in 3836 men between 2001 and 2004. Competing risks analyses were used to perform longitudinal analyses with results expressed as subhazard ratios (SHR). Outcomes were ascertained through electronic linkage until 20 June 2013. Results: Mean age was 77·0 ± 3·6 years. A total of 864 men developed cancers, and 506 experienced cancer-related deaths. A total of 340, 136 and 119 men developed prostate, colorectal and lung cancers, respectively. After adjustments, there were no associations between TSH and incidence of all cancers, prostate or lung cancer. Higher TSH was associated with increased colorectal cancer incidence (SHR = 1·19, 95% CI 1·00-1·42; P = 0·048 for every 1 SD increase in log TSH). This association was strengthened after excluding the first year of follow-up (SHR = 1·23, 95% CI 1·02-1·48, P = 0·028). FT4 was not associated with incidence of all cancers, prostate, colorectal or lung cancer. Thyroid hormones were not associated with cancer-related deaths. Conclusion: In community-dwelling older men, FT4 was not associated with cancer incidence. Higher TSH is independently associated with increased incidence of colorectal cancer. Further investigation is warranted to determine whether a causal relationship exists.

This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea c

Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38-73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended.

Background and objective: Computed tomography (CT)-based studies of asbestos-exposed individuals report a high prevalence of lung cancer, but the utility of low dose CT (LDCT) to screen asbestos-exposed populations is not established. We aimed to describe the prevalence of indeterminate pulmonary nodules and incidental findings on chest LDCT of asbestos-exposed subjects in Western Australia. Methods: A total of 906 subjects from the Western Australian Asbestos Review Programme underwent LDCT of the chest as part of regular annual review. An indeterminate (solid) nodule was defined as >50mm3 and part-solid/non-solid nodules >5mm. The presence of asbestos-related diseases was recorded with a standardized report. Results: Subjects were mostly (81%) men with a median age of 70years. Fifty-eight (6.5%) participants were current smokers, 511 (56.4%) ex-smokers and 325 (36.4%) never-smokers. One hundred and four indeterminate nodules were detected in 77 subjects (8.5%); of these, eight cases had confirmed lung cancer (0.88%). Eighty-seven subjects (9.6%) had incidental findings that required further investigation, 42 (4.6%) from lower airways inflammation. The majority of nodules were solid, 4-6mm and more common with age. Five hundred and eighty (64%) subjects had pleural plaques, and 364 (40.2%) had evidence of interstitial lung disease. Conclusion: The prevalence of LDCT-detected indeterminate lung nodules in 906 individuals with significant asbestos exposure was 8.5%, lower than many other CT studies. Clinically important incidental findings were found in 9.4%, predominantly related to lower respiratory tract inflammation. LDCT appears to effectively describe asbestos-related diseases and is likely to be an acceptable modality to monitor asbestos-exposed individuals.

Background and objective Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. Methods A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. Results Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. Conclusions No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

CONTEXT: Undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity in mice, and higher ucOC is associated with lower prevalence of diabetes in men. The influence of ucOC distinct from other markers of bone turnover on incidence of cardiovascular events is unclear. PARTICIPANTS: Community-dwelling men aged 70-89 years resident in Perth, Western Australia. MAIN OUTCOME MEASURES: Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. The ratio ucOC/TOC was calculated. Hospital admissions and deaths from myocardial infarction (MI) and stroke were ascertained. RESULTS: There were 3384 men followed for 7.0 years, during which 293 experienced an MI, 251 stroke, and 2840 neither. In multivariate analyses, higher ratio of ucOC/TOC (expressed as %) was associated with lower incidence of MI (quartiles Q2-4, =49% versus Q1,<49%, hazard ratio 0.70, 95% confidence interval = 0.54-0.91), but not of stroke (0.99, 0.73-1.34). Higher P1NP was associated with higher incidence of MI (Q2-4, =28.2 µg/L versus Q1, <28.2 µg/L, hazard ratio 1.45, 95% confidence interval = 1.06-1.97), but not of stroke (0.94, 0.70-1.26). CTX was not associated with incident MI or stroke. CONCLUSIONS: A reduced proportion of undercarboxylated osteocalcin or higher P1NP are associated with increased incidence of MI. UcOC/TOC ratio and P1NP predict risk of MI but not stroke, in a manner distinct from CTX. Further studies are needed to investigate potential mechanisms by which bone turnover markers related to metabolic risk and to collagen formation could modulate cardiovascular risk.

Context: In mice, undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity and increases testosterone (T) secretion from Leydig cells, but human data are lacking. We hypothesized that ucOC is associated with diabetes risk and modulates sex hormone concentrations in older men, distinct from other bone turnover markers. Participants: Participants were community-dwelling men aged 70 to 89 years resident in Perth, Western Australia. Main Outcome Measures: Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. Plasma total T, DHT, and estradiol (E2) were assayed by mass spectrometry.Results: Excluding men with osteoporosis or conditions affecting sex hormones or on bisphosphonates, glucocorticoids, or warfarin, 2966 men were included. In multivariate analyses, higher ucOC was associated with reduced diabetes risk (odds ratio [OR] per 1 SD increase = 0.55, P < .001). Similar results were seen for TOC (OR = 0.60, P < .001), P1NP (OR = 0.64, P < .001), and CTX (OR = 0.60, P < .001) but not ucOC/TOC. When all 4 markers were included in the fully adjusted model, higher ucOC (OR = 0.56, P < .001) and CTX (OR = 0.76, P = .008) remained associated with reduced diabetes risk. E2 was inversely associated with ucOC (coefficient −0.04, P = .031), TOC (−0.05, P = .001) and CTX (−0.04, P = .016); and positively with ucOC/TOC (0.05, P = .002). DHT was inversely associated with ucOC/TOC (−0.04, P = .040). T was not associated with bone turnover. Conclusions: Higher bone remodeling rates are associated with reduced diabetes risk in older men. Higher ucOC is both a marker of bone remodeling and an independent predictor of reduced diabetes risk. E2 is inversely associated with bone turnover markers. We found no evidence ucOC modulates circulating T in older men.

Introduction: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. Objective: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. Methods: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. Results: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; =2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml-1. Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. Conclusion: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asb

Global public health is increasingly being seen as a speciality field within the university education of public health. However, the exact meaning of global public health is still unclear, resulting in varied curricula and teaching units among universities. The contextual differences between high- and low- and middle-income countries, and the process of globalization need to be taken into account while developing any global public health course. Global public health and public health are not separable and global public health often appears as an extension of public health in the era of globalization and interdependence. Though global public health is readily understood as health of global population, it is mainly practiced as health problems and their solutions set within low- and middle-income countries. Additional specialist competencies relevant to the context of low- and middle-income countries are needed to work in this field. Although there can be a long list of competencies relevant to this broad topic, available literature suggests that knowledge and skills related with ethics and vulnerable groups/issues; globalization and its impact on health; disease burden; culture, society, and politics; and management are important.

ObjectiveObservational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007.MethodsParticipants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models.ResultsOver a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 μmol/L; 95% confidence interval [CI], 0.65–1.14) or osteoporotic fracture (HR, 0.97 μmol/L; 95% CI, 0.66–1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 μmol/L; 95% CI, 0.71–1.01).ConclusionsThis study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Methods: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models.Results: Over a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 μmol/L; 95% confidence interval [CI], 0.65–1.14) or osteoporotic fracture (HR, 0.97 μmol/L; 95% CI, 0.66–1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 μmol/L; 95% CI, 0.71–1.01). Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

Objective: To evaluate the efficacy of a home-based exercise programme added to usual medical care for the treatment of depression. Design: Prospective, two group parallel, randomised controlled study. Setting: Community-based. Patients: 200 adults aged 50 years or older deemed to be currently suffering from a clinical depressive illness and under the care of a general practitioner. Interventions: Participants were randomly allocated to either usual medical care alone (control) or usual medical care plus physical activity (intervention). The intervention consisted of a 12-week home-based programme to promote physical activity at a level that meets recently published guidelines for exercise in people aged 65 years or over. Main outcome measurements: Severity of depression was measured with the structured interview guide for the Montgomery-Asberg Depression Rating Scale (SIGMA), and depression status was assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Results: Remission of depressive illness was similar in both the usual care (59%) and exercise groups (63%; OR = 1.18, 95% CI 0.61 to 2.30) at the end of the 12-week intervention, and again at the 52-week follow-up (67% vs 68%) (OR=1.07, 95% CI 0.56 to 2.02). There was no change in objective measures of fitness over the 12-week intervention among the exercise group. Conclusions: This home-based physical activity intervention failed to enhance fitness and did not ameliorate depressive symptoms in older adults, possibly due to a lack of ongoing supervision to ensure compliance and optimal engagement.

Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma. Materials and methods: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50. mg/kg or 250. mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site). Results: Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p < 0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR = 0.85; 95% CI = 0.53-1.37, p= 0.50), (HR = 0.69; 95% CI = 0.21-2.30, p= 0.55) and (HR = 0.43; 95% CI = 0.16-1.13, p= 0.087) respectively. Conclusion: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.

Background: Population-based studies, as well as clinicians, often rely on self-report and hospital records to obtain a history of stroke. This study aimed to compare the validity of the diagnosis of stroke by self-report and by hospital coding according to their cross-sectional association with prevalent vascular risk factors, and longitudinal association with recurrent stroke and major cardiovascular outcomes in a large cohort of older Australian men. Methods: Between 1996 and 1999, 11,745 older men were surveyed for a self-reported history of stroke as part of the Health in Men Study (HIMS). Previous hospitalization for stroke was obtained with consent from linked medical records via the Western Australian Data Linkage System (WADLS). Subjects were followed by WADLS until December 31, 2010, for hospitalization for stroke, cardiovascular events, and all-cause mortality. The primary outcome was hospitalisation for stroke during follow-up. Secondary outcomes included incident vascular events and composite vascular endpoints. Results: At baseline, a history of stroke was reported by 903 men (7.7%), previous hospitalisation for stroke was recorded in 717 (6.1%), both self-report and hospitalisation in 467 (4.0%), and no history of stroke in 10,696 men (91.1%). Prevalent cardiovascular disease and peripheral arterial disease were more common among men with previous hospitalisation for stroke than a history of self-reported stroke (p < 0.001). In longitudinal analyses, incident aortic aneurysm was also more common among men with baseline history of hospitalization for stroke (adjusted hazard ratio (HR) 1.71, 95% CI 1.12-2.60) than among men with self-reported stroke (HR 0.88, 95% CI 0.56-1.36) compared to men with no history of stroke. With regard to the primary outcome, the rate of hospitalisation for stroke during follow-up was significantly higher among men with self-reported stroke (HR 2.44, 95% CI 2.03-2.94), hospital-coded stroke (adjusted HR 3.02, 2.42-3.78) a

Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos. © 2014 Robinson et al.

Context: Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial. Objective: We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men. Participants and Methods: Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70–89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage. Results: Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66–1.28; DHT: 0.83, 95% CI 0.59–1.15; E2: 0.84, 95% CI 0.62–1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39–0.81, P = .002; DHT: 0.57, 95% CI 0.40–0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54–1.08, P = .123). Conclusions: Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.

Context: Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined. Objective: We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men. Participants: Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia. Main Outcome Measures: Plasma total T, DHT, and E2 were assayed using liquid chromatographytandem mass spectrometry in early morning samples collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage. Results: There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8 ± 5.1 vs 13.2 ± 4.8 nmol/L [mean ± SD], P = .013), DHT (1.4 ± 0.7 vs 1.5 ± 0.7 nmol/L, P = .002), and E2 (71.6 ± 29.3 vs 74.0 ± 29.0 pmol/L, P = .022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR] = 0.82, P = .033; Q3:Q1, HR = 0.78, P = .010; Q4:Q1, HR = 0.86, P > .05; DHT: Q3:Q1, HR = 0.76, P = .003; Q4:Q1, HR=0.84, P > .05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR = 0.58, P = .002; Q4:Q1, HR = 0.69, P = .026). E2 was not associated with either all-cause or IHD mortality. Conclusions: Optimal androgen levels are abiomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed. (J Clin Endocrinol Metab 99: E9-E18, 2014). © Copyright 2014 by The Endocrine Society.

Aims: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow-up period of 2 years. Methods and results: This was a 24-month longitudinal study of 19 participants with systolic HF, 43 with IHD, and 45 controls. Subjects were older than 45 years and free of cognitive impairment at the start of follow-up. We acquired magnetic resonance images and used Statistical Parametric Mapping version 8 (SPM8) to investigate changes in the distribution of cerebral grey matter volume over time. We used the Cambridge Cognitive Examination of the Elderly (CAMCOG) and the Hospital Anxiety and Depression Scale (HADS) to assess 2-year changes in cognitive function and mood. Changes in total grey matter volume and cognitive function were similar across the three study groups, but participants with HF showed evidence of increasing severity of anxiety and depressive symptoms. HF was associated with subtle regional loss of grey matter in the right and left thalamus, left caudate, left and right posterior cingulate, left and right parahippocampal gyri, left superior and middle temporal gyri, and right inferior parietal lobule compared with controls and, to a lesser extent, participants with IHD. Conclusion: HF and IHD are not associated with a disproportional loss of cerebral grey matter or cognitive decline over 2 years compared with cardiologically healthy controls. Adults with HF experience increasing symptoms of anxiety and depression over 2 years compared with controls, and this increased vulnerability is associated with a relative loss of grey matter in brain regions that are import

Aims: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow-up period of 2 years. Methods and results: This was a 24-month longitudinal study of 19 participants with systolic HF, 43 with IHD, and 45 controls. Subjects were older than 45 years and free of cognitive impairment at the start of follow-up. We acquired magnetic resonance images and used Statistical Parametric Mapping version 8 (SPM8) to investigate changes in the distribution of cerebral grey matter volume over time. We used the Cambridge Cognitive Examination of the Elderly (CAMCOG) and the Hospital Anxiety and Depression Scale (HADS) to assess 2-year changes in cognitive function and mood. Changes in total grey matter volume and cognitive function were similar across the three study groups, but participants with HF showed evidence of increasing severity of anxiety and depressive symptoms. HF was associated with subtle regional loss of grey matter in the right and left thalamus, left caudate, left and right posterior cingulate, left and right parahippocampal gyri, left superior and middle temporal gyri, and right inferior parietal lobule compared with controls and, to a lesser extent, participants with IHD. Conclusion: HF and IHD are not associated with a disproportional loss of cerebral grey matter or cognitive decline over 2 years compared with cardiologically healthy controls. Adults with HF experience increasing symptoms of anxiety and depression over 2 years compared with controls, and this increased vulnerability is associated with a relative loss of grey matter in brain regions that are import

Objective: To evaluate the efficacy of a home-based exercise programme added to usual medical care for the treatment of depression. Design: Prospective, two group parallel, randomised controlled study. Setting: Community-based. Patients: 200 adults aged 50 years or older deemed to be currently suffering from a clinical depressive illness and under the care of a general practitioner. Interventions: Participants were randomly allocated to either usual medical care alone (control) or usual medical care plus physical activity (intervention). The intervention consisted of a 12-week home-based programme to promote physical activity at a level that meets recently published guidelines for exercise in people aged 65 years or over. Main outcome measurements: Severity of depression was measured with the structured interview guide for the Montgomery-Asberg Depression Rating Scale (SIGMA), and depression status was assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Results: Remission of depressive illness was similar in both the usual care (59%) and exercise groups (63%; OR = 1.18, 95% CI 0.61 to 2.30) at the end of the 12-week intervention, and again at the 52-week follow-up (67% vs 68%) (OR=1.07, 95% CI 0.56 to 2.02). There was no change in objective measures of fitness over the 12-week intervention among the exercise group. Conclusions: This home-based physical activity intervention failed to enhance fitness and did not ameliorate depressive symptoms in older adults, possibly due to a lack of ongoing supervision to ensure compliance and optimal engagement.

Aims: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic

Aims: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow-up period of 2 years. Methods and results: This was a 24-month longitudinal study of 19 participants with systolic HF, 43 with IHD, and 45 controls. Subjects were older than 45 years and free of cognitive impairment at the start of follow-up. We acquired magnetic resonance images and used Statistical Parametric Mapping version 8 (SPM8) to investigate changes in the distribution of cerebral grey matter volume over time. We used the Cambridge Cognitive Examination of the Elderly (CAMCOG) and the Hospital Anxiety and Depression Scale (HADS) to assess 2-year changes in cognitive function and mood. Changes in total grey matter volume and cognitive function were similar across the three study groups, but participants with HF showed evidence of increasing severity of anxiety and depressive symptoms. HF was associated with subtle regional loss of grey matter in the right and left thalamus, left caudate, left and right posterior cingulate, left and right parahippocampal gyri, left superior and middle temporal gyri, and right inferior parietal lobule compared with controls and, to a lesser extent, participants with IHD. Conclusion: HF and IHD are not associated with a disproportional loss of cerebral grey matter or cognitive decline over 2 years compared with cardiologically healthy controls. Adults with HF experience increasing symptoms of anxiety and depression over 2 years compared with controls, and this increased vulnerability is associated with a relative loss of grey matter in brain regions that are import

Summary: Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. Introduction: There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. Methods: The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. Results: Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE = 0.83; 95 % CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE = 0.95; 95 % CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g = 0.89; 95 % CI 0.81-0.98) and osteoporotic fracture (OR per 10 g = 0.84; 95 % CI 0.72-0.97). Conclusions: This study

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers. What's new? Familial clustering has long been observed in cases of malignant mesothelioma but it was difficult to separate increased exposure of families to asbestos at home from genetic factors. The Wittenoom cohorts in Australia are unique because they provide thorough estimates of asbestos exposure levels for families of workers

The aim of this study was to determine the factors that mediate changes in Health Related Quality of Life (HRQoL) ratings by community-dwelling people with Alzheimer disease (AD) and carers over a period of 18 months. We completed an 18-month longitudinal study of 80 community-dwelling older adults diagnosed with probable AD of mild or moderate severity (NINCDS-ADRD criteria) and their family carers. The primary outcome of interest was the 18-month change in HRQoL ratings as measured with the Quality of Life-AD (QoL-AD) (by carer and by self). Explanatory variables included demographics, lifestyle, cognition, awareness, psychopathology, burden-of-care, use of medication, and functionality in daily life. We found a significant decline (8.7%, P=0.003) in QoL-AD carer-ratings, but not in self-ratings. The final parsimonious model of predictors of changes in QoL-AD self-ratings explained 22.6% of the variance; only changes on Hospital Anxiety and Depression Scale Anxiety retained significance. The final model of predictors of changes in carer-ratings explained 55.0% of the variance: that is, changes on Informant Questionnaire on Cognitive Decline in the Elderly, changes on Hospital Anxiety and Depression Scale Depression, practicing hobbies at 18 months, and number of visit(s) or admission(s) to hospital. HRQoL self-ratings and carer-ratings of community-dwelling people with AD do not decline at same rate over 18 months and changes are associated with different factors. Interventions designed to optimize quality of life of people with AD should consider carefully whose HRQoL ratings they wish to change. Copyright © 2013 by Lippincott Williams & Wilkins.

Aims: Heart failure (HF) has been associated with cognitive dysfunction, a high prevalence of mood disorders, and a relative loss of grey matter in several brain regions. This study aimed to determine if, compared with controls with and without ischaemic heart disease (IHD), adults with HF show evidence of progressive loss of cerebral grey matter, and whether morphological changes are associated with changes in cognition, depression and anxiety symptoms over a follow-up period of 2 years. Methods and results: This was a 24-month longitudinal study of 19 participants with systolic HF, 43 with IHD, and 45 controls. Subjects were older than 45 years and free of cognitive impairment at the start of follow-up. We acquired magnetic resonance images and used Statistical Parametric Mapping version 8 (SPM8) to investigate changes in the distribution of cerebral grey matter volume over time. We used the Cambridge Cognitive Examination of the Elderly (CAMCOG) and the Hospital Anxiety and Depression Scale (HADS) to assess 2-year changes in cognitive function and mood. Changes in total grey matter volume and cognitive function were similar across the three study groups, but participants with HF showed evidence of increasing severity of anxiety and depressive symptoms. HF was associated with subtle regional loss of grey matter in the right and left thalamus, left caudate, left and right posterior cingulate, left and right parahippocampal gyri, left superior and middle temporal gyri, and right inferior parietal lobule compared with controls and, to a lesser extent, participants with IHD. Conclusion: HF and IHD are not associated with a disproportional loss of cerebral grey matter or cognitive decline over 2 years compared with cardiologically healthy controls. Adults with HF experience increasing symptoms of anxiety and depression over 2 years compared with controls, and this increased vulnerability is associated with a relative loss of grey matter in brain regions that are import

Background: There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years. Methods: Method followed was a prospective cohort study of 4,181 men aged 65-84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996-1998 and 2001-2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI. Results: Compared with men with a stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32-2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI >1 kg/m 2; this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse J-shaped association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable. Conclusions: Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men. © International Psychogeriatric Association 2012.