Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Objective: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.

Design: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.

Setting: General population.

Participants: 26 018 men and women aged 50-79 years

Main outcome measures: All-cause, cardiovascular, and cancer mortality.

Results: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.

Conclusions: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

Prognostic role of lemur tyrosine kinase-3 germline polymorphisms in adjuvant gastric cancer in Japan and the United States

Lemur tyrosine kinase-3 (LMTK3) was recently identified as an estrogen receptor (ER)-α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Because different predominant ER distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was carried out to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and 137 U.S. patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival [HR, 4.37; 95% confidence interval (CI), 2.08-9.18; P < 0.0001] and overall survival (OS; HR, 3.69; 95% CI, 1.65-8.24; P = 0.0014) in the Japanese males and time to recurrence (HR, 7.29; 95% CI, 1.07-49.80; P = 0.043) in the U.S. females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR, 3.04; 95% CI, 1.08-8.56; P = 0.035) and the U.S. males (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patients with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

The resilience of democratic institutions in Britain, Australia and the United States under conditions of total war

To what extent are democratic institutions resilient when nation states mobilise for war? Normative and empirical political theorists have long argued that wars strengthen the executive and threaten constitutional politics. In modern democracies, national assemblies are supposed to hold the executive to account by demanding explanations for events and policies; and by scrutinising, reviewing and, if necessary, revising legislative proposals intended to be binding on the host society or policies that have been implemented already. This article examines the extent to which the British and Australian parliaments and the United States Congress held their wartime executives to account during World War II. The research finds that under conditions approaching those of total war, these democratic institutions not only continued to exist, but also proved to be resilient in representing public concerns and holding their executives to account, however imperfectly and notwithstanding delegating huge powers. In consequence, executives—more so British and Australian ministers than President Roosevelt—were required to be placatory as institutional and political tensions within national assemblies and between assemblies and executives continued, and assemblies often asserted themselves. In short, even under the most onerous wartime conditions, democratic politics mattered and democratic institutions were resilient.

Naval Occurrences of the Late War Between Great Britain and the United States of America- 1817

Full title is "A Full and Correct Account of the Chief Naval Occurrences of the Late War Between Great Britain and the United States of America; preceded by a Cursory Examination of the American Accounts of their Naval Actions Fought Previous to that Period: to Which is Added an Appendix; with Plates" This is an expanded version of author William James' pamphlet "An Inquiry into the Merits of the Principal Naval Actions between Great Britain and the United States." (Halifax, Nova Scotia, 1816) In this work he discussed how American ships, during the War of 1812, were larger and more heavily armed and manned than those of the British. He therefore, stated that American victories were due only to their greater numerical force and not their superior seamanship. Naval Occurrences is a thorough documentation of the naval operations from the British perspective that addresses contradictions and inconsistencies within the American official documents as well as political and media accounts. This is perhaps his motivation for the words "Corrected Account" within the title. James' sentiments towards the US most likely sprouted from being held prisoner while visiting in 1812. (He was falsely accused of being a renegade seeking revenge on the US.) In 1813, he escaped to Halifax where he began writing on various naval topics. James became one of the leading authorities on British Naval History.

Indenture between Alfred Sanderson Woodruff and the United States Trust Company of New York

Indenture between Alfred Sanderson Woodruff and the United States Trust Company of New York. The proceeds would be paid to his estate for his successors. January 12, 1894.

Indenture between Hamilton Killaly Woodruff and the United States Trust Company of New York

Indenture between Hamilton Killaly Woodruff and the United States Trust Company of New York. The proceeds would be paid to his successors. (This is a handwritten copy)

Indenture between Hamilton Killaly Woodruff and the United States Trust Company of New York (3rd Trust Deed)

Indenture between Hamilton Killaly Woodruff and the United States Trust Company of New York. This is listed as the 3rd trust deed. The proceeds would be paid to successors (2 copies). Most of the first page of copy no. 2 is torn away which does affect the text. These 2 documents are in an envelope marked "vouchers", June 20, 1899.

History of the Late War between Great Britain and the United States of America

History of the Late War between Great Britain and the United States of America by David Thompson, late of the Royal Scots, Niagara U.C. , 1832. There is an inscription in the front of the book which says “[illegible] Nelles, Grimsby and it is signed by Joseph Williams [?]” The book is stained from dampness, but this does not affect the text, 1832.

Federalism and Fiscal Equalization in Canada and the United States, 1990-1999.

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