The global atmospheric electrical circuit and climate

Evidence is emerging for physical links among clouds, global temperatures, the global atmospheric electrical circuit and cosmic ray ionisation. The global circuit extends throughout the atmosphere from the planetary surface to the lower layers of the ionosphere. Cosmic rays are the principal source of atmospheric ions away from the continental boundary layer: the ions formed permit a vertical conduction current to flow in the fair weather part of the global circuit. Through the (inverse) solar modulation of cosmic rays, the resulting columnar ionisation changes may allow the global circuit to convey a solar influence to meteorological phenomena of the lower atmosphere. Electrical effects on non-thunderstorm clouds have been proposed to occur via the ion-assisted formation of ultra-fine aerosol, which can grow to sizes able to act as cloud condensation nuclei, or through the increased ice nucleation capability of charged aerosols. Even small atmospheric electrical modulations on the aerosol size distribution can affect cloud properties and modify the radiative balance of the atmosphere, through changes communicated globally by the atmospheric electrical circuit. Despite a long history of work in related areas of geophysics, the direct and inverse relationships between the global circuit and global climate remain largely quantitatively unexplored. From reviewing atmospheric electrical measurements made over two centuries and possible paleoclimate proxies, global atmospheric electrical circuit variability should be expected on many timescale

Risk of prevalent and incident dementia associated with insulin-like growth factor and insulin-like growth factor-binding protein 3

Insulin-like growth factor 1 (IGF-1) influences cell proliferation and survival. In the extracellular environment, IGF-1 circulates bound to proteins (IGF-binding proteins; IGFBP), some of which have physiological effects that seem independent of IGF-1, including the brain (for example, IGFBP-3). We completed a systematic review of the association between dementia and IGF-1 and IGFBP-3, and a cross-sectional and longitudinal study designed to investigate if lower plasma concentration of these proteins increased the risk of prevalent and incident dementia. A total of 3967 men aged 71–89 years joined the study, of whom 535 (13.5%) showed evidence of prevalent cognitive impairment. The plasma concentrations of IGF-1 and IGFBP-3 were similar for men with and without cognitive impairment. The 3432 men free of cognitive impairment were then followed for up to 13 years. During this time 571 (16.6%) developed dementia. The plasma concentration of IGF-1 had no association with incident dementia. The doubling of the plasma concentration of IGFBP-3 decreased the hazard ratio of dementia by 23% (95% confidence interval=5–37%). The results were not affected by age, body mass index and history of smoking, diabetes, hypertension, coronary heart disease or stroke. If these findings are confirmed by others, the plasma concentration of IGFBP-3 could be used to improve the accuracy of predictive models of dementia and as a potential new factor to assist in the development of prevention and treatment strategies

Associations of total testosterone, sex hormone-binding globulin, calculated free testosterone, and luteinizing hormone with prevalence of abdominal aortic aneurysm in older men

Context: Abdominal aortic aneurysm (AAA) is associated with mortality in older adults, and increasing aortic diameter predicts incident cardiovascular events. Although AAA occurs predominantly in men, its association with male sex hormones is unclear.\ud \ud Objective: The objective of the study was to examine whether male sex hormones are independently associated with AAA or increased abdominal aortic diameter.\ud \ud Design: This was a cross-sectional analysis.\ud \ud Setting and Participants: Participants included 3620 community-dwelling men aged 70–88 yr.\ud \ud Main Outcome Measures: Abdominal aortic diameter was measured with ultrasound. Early morning sera were assayed for total testosterone, SHBG, and LH. Free testosterone was calculated using mass action equations.\ud \ud Results: AAA (aortic diameter ≥30 mm) was present in 262 men (7.2%). Men with AAA had lower serum total and free testosterone (mean ± SD 14.5 ± 6.0 vs. 15.5 ± 5.6 nmol/liter, P = 0.005 and 256 ± 87 vs. 280 ± 97 pmol/liter, P < 0.001, respectively) compared with men without. LH was higher in men with AAA (median, interquartile range: 4.9, 3.1–7.9 vs. 4.3, 3.0–6.4 IU/liter, P = 0.013). In multivariate analysis adjusting for potential confounders, free testosterone was negatively associated with AAA (odds ratio per 1 SD increase: 0.84, 95% confidence interval 0.72–0.98, P = 0.026). LH was positively associated (odds ratio 1.14, 95% confidence interval 1.03–1.25, P = 0.008). Comparable results were seen with aortic diameter analyzed as a continuous variable.\ud \ud Conclusions: Lower free testosterone and higher LH levels are independently associated with AAA in older men. Impaired gonadal function may be involved in arterial dilatation as well as occlusive vascular disease in older men. Additional studies are needed to clarify direction of causality and determine possible scope for preventive intervention

Reference ranges for thyroid-stimulating hormone and free thyroxine in older men: results from the Health In Men Study

Background: In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men. Methods: We conducted the study on community-dwelling men aged 70–89 years. Baseline TSH and FT4 levels were assayed (Elecsys 2010, Roche Diagnostics). Conventional reference intervals for TSH and FT4 were 0.4–4.0 mIU/L and 10–23 pmol/L, respectively. Incident deaths were ascertained using data linkage. Results: Of the 3,885 men included in the analysis, the 2.5th and 97.5th centiles for TSH and FT4 were 0.64–5.9 mIU/L and 12.1–20.6 pmol/L (0.94–1.60ng/dL), respectively. Of the 411 very healthy men defined by excellent or very good self-rated health and absence of major medical comorbidities, 2.5th to 97.5th centiles for TSH and FT4 were 0.67–4.98 mIU/L and 12.1–20.5 pmol/L (0.94–1.59ng/dL), respectively. TSH was not associated with mortality, whereas higher FT4 was associated with increased mortality. Applying intervals based on very healthy older men to the cohort as a whole led to the reclassification of 310 men (8.0%). More men were classified as being hyperthyroid or hypothyroid, or having subclinical hyperthyroidism, and fewer as having subclinical hypothyroidism. Conclusions: In older men, the reference interval for TSH in older men is shifted upward, whereas the reference interval for FT4 is compressed compared with the conventional reference ranges. Applying reference intervals based on healthy older men identifies a substantial number of older men as having overt thyroid disease or subclinical hyperthyroidism and reduces the number classified as having subclinical hypothyroidism

Insulin resistance and depressive symptoms in older men: the health in men study

Objective: A positive association between depression and diabetes has been reported, but the direction and nature of this association is unclear. Insulin resistance is a state of reduced responsiveness of target tissues to normal circulating levels of insulin and predisposes to diabetes in the presence of beta cell dysfunction.\ud \ud Methods: We conducted this cross-sectional and prospective study in a community representative sample of 3,140 older men free of diabetes to determine if insulin resistance was associated with prevalent and incident depressive symptoms.\ud \ud Results: Men with insulin resistance had increased odds of depression cross-sectionally (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.08–2.40), although this was not significant after adjustment for possible confounding (OR: 1.32; 95% CI: 0.85–2.03). In the longitudinal analysis, men with insulin resistance were more likely to develop clinically significant depressive symptoms (adjusted risk ratio [RR]: 2.33; 95% CI: 1.17–4.62), and this risk was greatest for men in the highest quartile of insulin resistance compared with those in the lowest quartile (adjusted RR: 2.54; 95% CI: 1.04–6.18).\ud \ud Conclusion: Older men with clinically significant depressive symptoms were more likely to have higher markers of insulin resistance. Additionally, the odds of depression increased with increasing levels of insulin resistance, and insulin resistance increased the risk of developing depression over 5 years later. Because depression is now a leading cause of disability worldwide, addressing the rising challenge of insulin resistance may prove important in improving the future health of our communities

Sex hormones and incident dementia in older men: the health in men study

Background: Low circulating testosterone has been associated with dementia in older men but existing evidence from prospective studies is inconsistent. Methods: We conducted a prospective longitudinal study of 4069 community-dwelling older men free of dementia aged 71-88 years at baseline. The main objective of the study was to determine if men with low circulating sex hormones were more likely to develop dementia over time. The main biochemical exposures of interest were collected at baseline between 2001 and 2004 and men were assessed for incident dementia via an electronic health records database to the 31 st of December 2013. Results: Dementia developed in 499 men over a median of 10.5 years (range 9.4-12.2 years). The risk of developing dementia increased with decreasing total (hazard ratio [Hit] 1.14, 95% confidence interval [95%CI] 1.03-1.26 per standard deviation decrease) and calculated free testosterone (HR 1.18, 95%CI 1.06-1.31 per standard deviation decrease) after adjustment for age, baseline cognitive function, depression, body mass, hypertension, cardiovascular disease and total plasma homocysteine. Men in the lowest quartiles of total (adjusted HR L39, 95%CI 1.04-1.85) and calculated free testosterone (adjusted HR 1.43, 95%CI 1.08-1.90) had increased risk of developing dementia compared to those in the highest quartiles. Conclusions: Lower plasma total and calculated free testosterone were associated with increased risk of developing dementia independent of relevant measured clinical and biochemical factors and was not explained due to differential mortality in those with lower testosterone levels. The association between low testosterone and dementia is biologically plausible but data on the role of testosterone treatment in preventing dementia is lacking and adequately powered trials in men at risk would be welcome

Bone turnover markers: defining a therapeutic target

[Extract] Bone turnover markers (BTM) in widespread clinical use include urine NTX, plasma βCTX and plasma total procollagen type 1 amino terminal propeptide (P1NP). An important application of BTMs is in monitoring anti-osteoporosis therapy, and specifically, in indicating whether current therapy is likely to achieve optimal reduction of fracture risk. Of the 3 BTMs mentioned above, only urine NTX (as NTX/creatinine ratio) has an evidence-based threshold indicating optimum fracture risk reductio. However measurement of βCTX and P1NP is preferred owing to their smaller biological variation and greater response to treatment. We recently published provisional therapeutic thresholds for plasma βCTX assays that were equivalent to the urine NTX/creatinine ratio indicative of maximal fracture risk reduction for patients treated with risedronate

Clinical usefulness of bone turnover marker concentrations in osteoporosis

Current evidence continues to support the potential for bone turnover markers (BTM) to provide clinically useful information particularly for monitoring the efficacy of osteoporosis treatment. Many of the limitations identified earlier remain, principally in regard to the relationship between BTM and incident fractures. Important data are now available on reference interval values for CTX and PINP across a range of geographic regions and for individual clinical assays. An apparent lack of comparability between current clinical assays for CTX has become evident indicating the possible limitations of combining such data for meta-analyses. Harmonization of units for reporting serum/plasma CTX (ng/L) and PINP (?g/L) is recommended. The development of international collaborations continues with an important initiative to combine BTM results from clinical trials in osteoporosis in a meta-analysis and an assay harmonization program are likely to be beneficial. It is possible that knowledge derived from clinical studies can further enhance fracture risk estimation tools with inclusion of BTM together with other independent risk factors. Further data of the relationships between the clinical assays for CTX and PINP as well as physiological and pre-analytical factors contributing to variability in BTM concentrations are required

Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the Health In Men Study

Context: Reference intervals for bone turnover markers (BTMs) and relationships between BTM and fracture risk in older men are not well characterized.\ud \ud Objective: The purpose of this article was to determine the reference intervals for serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (PINP), and collagen type I C-terminal cross-linked telopeptide (CTX-I) in healthy older men and to explore factors associated with BTMs, including hip fracture risk.\ud \ud Participants and Setting: We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum samples available for analysis.\ud \ud Interventions: Morning blood samples were collected at the study visit. Comorbid conditions were assessed by questionnaire. The reference sample comprised fasting men (n = 298, median age 75.3 years [interquartile range 73.9–78.1 years) reporting excellent or very good health, without a history of diabetes, cardiovascular disease, cancer, depression, or dementia.\ud \ud Main Outcome Measures: Serum tOC, PINP, and CTX-I were estimated by automated electrochemiluminescence immunoassays, ucOC was estimated using hydroxyapatite binding, and incident hip fractures were captured from hospital admission data.\ud \ud Results: Reference intervals for tOC, ucOC, PINP, and CTX-I were 10.2 to 41.0, 5.2 to 21.9, 18 to 129 μg/L, and 117 to 740 ng/L, respectively. tOC, ucOC and CTX-I were associated with hip fracture incidence, but after adjustment for other risk factors only tOC remained significantly associated.\ud \ud Conclusions: Reference intervals for BTMs in older men have been defined. tOC may be more informative for hip fracture risk in older men than CTX-I and PINP. Further studies are needed to clarify the utility of BTM reference intervals in the management of aging men at risk of osteoporosis