The turn of the gradient? Educational differences in breast cancer mortality in 18 European populations during the 2000s.

This study aims to investigate the association between educational level and breast cancer mortality in Europe in the 2000s. Unlike most other causes of death, breast cancer mortality tends to be positively related to education, with higher educated women showing higher mortality rates. Research has however shown that the association is changing from being positive over non-existent to negative in some countries. To investigate these patterns, data from national mortality registers and censuses were collected and harmonized for 18 European populations. The study population included all women aged 30-74. Age-standardized mortality rates, mortality rate ratios, and slope and relative indexes of inequality were computed by education. The population was stratified according to age (women aged 30-49 and women aged 50-74). The relation between educational level and breast cancer mortality was predominantly negative in women aged 30-49, mortality rates being lower among highly educated women and higher among low educated women, although few outcomes were statistically significant. Among women aged 50-74, the association was mostly positive and statistically significant in some populations. A comparison with earlier research in the 1990s revealed a changing pattern of breast cancer mortality. Positive educational differences that used to be significant in the 1990s were no longer significant in the 2000s, indicating that inequalities have decreased or disappeared. This evolution is in line with the "fundamental causes" theory which stipulates that whenever medical insights and treatment become available to combat a disease, a negative association with socio-economic position will arise, independently of the underlying risk factors.

The change in the sex ratio in multiple sclerosis is driven by birth cohort effects.

BACKGROUND AND PURPOSE: Birth cohort effects have greatly shaped long-term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. METHODS: Age-period-cohort analyses were applied to Swiss mortality data, 1901-2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. RESULTS: Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. CONCLUSION: The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors.

Contribution of smoking to socioeconomic inequalities in mortality: a study of 14 European countries, 1990-2004.

BACKGROUND: Smoking contributes to socioeconomic inequalities in mortality, but the extent to which this contribution has changed over time and driven widening or narrowing inequalities in total mortality remains unknown. We studied socioeconomic inequalities in smoking-attributable mortality and their contribution to inequalities in total mortality in 1990-1994 and 2000-2004 in 14 European countries. METHODS: We collected, harmonised and standardised population-wide data on all-cause and lung-cancer mortality by age, gender, educational and occupational level in 14 European populations in 1990-1994 and 2000-2004. Smoking-attributable mortality was indirectly estimated using the Preston-Glei-Wilmoth method. RESULTS: In 2000-2004, smoking-attributable mortality was higher in lower socioeconomic groups in all countries among men, and in all countries except Spain, Italy and Slovenia, among women, and the contribution of smoking to socioeconomic inequalities in mortality varied between 19% and 55% among men, and between -1% and 56% among women. Since 1990-1994, absolute inequalities in smoking-attributable mortality and the contribution of smoking to inequalities in total mortality have decreased in most countries among men, but increased among women. CONCLUSIONS: In many European countries, smoking has become less important as a determinant of socioeconomic inequalities in mortality among men, but not among women. Inequalities in smoking remain one of the most important entry points for reducing inequalities in mortality.

Lower Body vs. Upper Body Resistance Training and Arterial Stiffness in Young Men.

Resistance training has been shown to increase arterial stiffness. The purpose of the present study was to examine and compare the systemic arterial stiffness responses to acute lower body (LRT) and upper body (URT) resistance training. 20 healthy young men [median age: 26 years (interquartile range 23, 32)] underwent LRT, URT and whole body resistance training (WRT). Before and immediately after, as well as 20, 40 and 60 min after each training session, we measured the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) using VaSera VS-1500 N. We used mixed models for repeated measurements to estimate the post-exercise differences in CAVI and baPWV between the 3 resistance training modes. Immediately after exercise cessation, both CAVI and baPWV were lower for LRT compared with URT [CAVI: - 0.93 (95% confidence interval [CI] - 1.15, - 0.70); baPWV: - 2.08 m/s (95% CI - 2.48, - 1.67)]. Differences between LRT and URT gradually decreased during follow-up. Compared with WRT, LRT induced a decrease and URT an increase in arterial stiffness across all time points. In conclusion, LRT presents more favorable post-exercise arterial stiffness than URT. Our results suggest that LRT or WRT may be preferred over URT in individuals with impaired arterial stiffness.

Missed epidemics and missing links: international birth cohort trends in multiple sclerosis.

BACKGROUND AND PURPOSE: Many hypotheses on the etiopathogenesis of multiple sclerosis (MS) focus on risk factors occurring early in life. This study examined the variability of birth cohort trends in international MS data by means of age-period-cohort (APC) analysis. METHODS: The data from 25 countries were taken from the WHO mortality database. Data were encoded according to the International Classification of Diseases and covered slightly varying periods between 1951 and 2009. The APC analyses were based on logit models applied to cohort tables with 5-year age- and period intervals. RESULTS: In most countries, the birth cohort estimates peaked in those born in the first half of the 20th century. In countries from Central and Western Europe, the peak concerned those born before and around 1920. A second group of countries (Denmark, Sweden, Italy, Ireland, Scotland) shared a later peak amongst cohorts born in the 1920s and 1930s. Group 3 included Commonwealth countries, the USA and Norway, with a double or extended peak starting in the 1910s or 1920s, and ending by the 1950s. The fourth group, consisting of Mediterranean countries and Finland, was characterized by a steady increase in the birth cohort estimates until the 1950s. The fifth group with countries from Eastern Europe and Japan showed no particular pattern. CONCLUSIONS: Birth cohort trends have influenced the change in MS risk across the 20th century in many Western countries. This silent epidemic points to a most important but unknown latent risk factor in MS.

Inverse association between circulating vitamin D and mortality--dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Effects of dietary protein on the composition of weight loss in post-menopausal women.

OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent the loss of lean mass that is commonly associated with weight loss. DESIGN: An intervention study comparing a hypocaloric diet moderately high in protein to one lower in protein. SETTING: Study measurements were taken at the Wake Forest University General Clinical Research Center (GCRC) and Geriatric Research Center (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/- 6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d; LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body composition, including total body mass, total lean mass, total fat mass, and appendicular lean mass, assessed by dual energy x-ray absorptiometry, was measured before and after the diet interventions. RESULTS: The HI PROT group lost 8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p = 0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8% and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate protein intake may reduce lean mass losses associated with voluntary weight loss in older women.

BUN as an Independent Predictor of Post-Hospital-Discharge Mortality among Older Veterans.

BACKGROUND/OBJECTIVES: An elevated blood urea nitrogen (BUN) in known to be an important prognostic indicator in patients with end-stage heart or kidney disease or certain other life-threatening illnesses. However, it is less certain as to whether an elevated BUN is an independent predictor of long-term mortality risk in less seriously ill patients. To address this issue, we examined the relationship between BUN and long-term mortality after adjusting for potential confounders and other indicators of health status/disease severity, in a select population of older medically stable Veterans. DESIGN: Long-term prospective cohort study. SETTING: Outpatient follow-up of patients discharged from a recuperative care and rehabilitation unit (RCRU) of a Department of Veterans Affairs Community Living Center. PARTICIPANTS: 383 older Veterans (mean age = 78.6±7.6 years, 98% male, and 87% white) discharged alive and in stable medical condition. MEASUREMENTS: At discharge, each subject completed a comprehensive assessment and was then monitored as an outpatient for up to 9.3 years. Associations between blood urea nitrogen at RCRU discharge and mortality were identified utilizing Cox proportional hazards (PH) regression analyses adjusting for conditions known to confound this relationship. RESULTS: Within the follow-up period, 255 subjects (67%) died. In the unadjusted Cox PH model, a BUN ≥ 30 mg/dL was associated with a nearly 2-fold increased risk of mortality (hazard ratio 1.90, 95%CI 1.41 - 2.56). The association between BUN and long-term mortality remained highly significant after adjusting for potential confounders (hazard ratio 1.78, 95%CI 1.29 - 2.44). CONCLUSION: Our findings support BUN levels as an independent predictor of long-term mortality in older, medically stable Veterans. An elevated BUN may be reflective of global health status rather than solely an indicator of the severity of acute illness or unstable chronic disease.

Single-Arm Resistance Training Study to Determine the Relationship between Training Outcomes and Muscle Growth Factor mRNAs in Older Adults Consuming Numerous Medications and Supplements.

OBJECTIVES: Determine if the muscle mRNA levels of three growth factors (insulin-like growth factor-1 [IGF1], ciliary neurotropic factor [CNTF], and vascular endothelial growth factor-D [VEGFD]) are correlated with muscle size and strength gains from resistance exercise while piloting a training program in older adults taking medications and supplements for age-associated problems. DESIGN: Single-arm prospective study. SETTING: US Veterans Affairs hospital. PARTICIPANTS: Older (70±6 yrs) male Veterans (N=14) of US military service. INTERVENTION: Thirty-five sessions of high-intensity (80% one-rep max) resistance training including leg press, knee curl, and knee extension to target the thigh muscles. MEASUREMENTS: Vastus lateralis biopsies were collected and body composition (DEXA) was determined pre- and post-training. Simple Pearson correlations were used to compare training outcomes to growth factor mRNA levels and other independent variables such as medication and supplement use. RESULTS: Average strength increase for the group was ≥ 25% for each exercise. Subjects averaged taking numerous medications (N=5±3) and supplements (N=2±2). Of the growth factors, a significant correlation (R>0.7, P≤0.003) was only found between pre-training VEGFD and gains in lean thigh mass and extension strength. Mass and strength gains were also correlated with use of α-1 antagonists (R=0.55, P=0.04) and pre-training lean mass (R=0.56, P=0.04), respectively. CONCLUSIONS: Muscle VEGFD, muscle mass, and use of α-1 antagonists may be predisposing factors that influence the response to training in this population of older adults but additional investigation is required to determine if these relationships are due to muscle angiogenesis and blood supply.

Inequalities in tuberculosis mortality: long-term trends in 11 European countries.

SETTING: Previous studies in many countries have shown that mortality due to tuberculosis (TB) is higher among people of lower socio-economic status. OBJECTIVE: To assess the magnitude and direction of trends in educational inequalities in TB mortality in 11 European countries. DESIGN: Data on TB mortality between 1980 and 2011 were collected among persons aged 35-79 years. Age-standardised mortality rates by educational level were calculated. Inequalities were estimated using the relative and slope indices of inequality. RESULTS: In the first decade of the twenty-first century, educational inequalities in TB mortality occurred in all countries in this study. The largest absolute inequalities were observed in Lithuania, and the smallest in Denmark. In most countries, relative inequalities have remained stable since the 1980s or 1990s, while absolute inequalities remained stable or went down. In Lithuania and Estonia, however, absolute inequalities increased substantially. CONCLUSION: The reduction in absolute inequalities in TB mortality, as seen in many European countries, is a major achievement; however, inequalities persist and are still a major cause for concern in the twenty-first century. Interventions aimed at preventing TB disease and reducing TB case fatality in lower socio-economic groups should be intensified, especially in the Baltic countries.

Understanding weekly cycles in suicide: an analysis of Austrian and Swiss data over 40 years.

BACKGROUND: Seasonal as well as weekly cycles in suicide have been described, replicated and poorly understood for a long time. In Western countries, suicides are typically least frequent on weekends and most frequent on Mondays and Tuesdays. To improve understanding of this phenomenon a strategy is required which focuses on anomalous findings beyond the regular patterns. Here, we focused on instances where the weekly suicide patterns disappear or are interrupted. METHODS: We used data from Swiss and Austrian mortality statistics for the periods 1969-2010 and 1970-2010, respectively. First, the data were cross-tabulated by days of the week and the available socio-demographic information (sex, age, religious affiliation and region). Second, time series of cumulated daily frequencies of suicide were analysed by seasonal Autoregressive Integrated Moving Average (ARIMA) models which included intervention effects accounting for Easter and Pentecost (Whit) holidays. RESULTS: First, the cross tabulations showed that weekly cycles may be smoothed above all in young persons and smoothed in drowning, jumping and car gas exhaustion suicides. Second, the ARIMA analyses displayed occasional preventive effects for holidays Saturdays and Sundays, and more systematic effects for holiday Mondays. There were no after effects on Tuesdays following holiday Mondays. CONCLUSIONS: In general, the weekend dip and the Monday backlog effect in suicide show striking similarities to the Advent season effect and are interpretable within the same template. The turning points between low and high frequencies possibly provide promising frames for the timing of prevention activities.

Protein-energy undernutrition and the risk of mortality within one year of hospital discharge: a follow-up study.

OBJECTIVE: The primary objective of this study was to confirm the results of a previous study that demonstrated a strong independent correlation between the severity of protein-energy undernutrition and the risk of 1-year postdischarge mortality in a population of older rehabilitation patients. DESIGN: Prospective survey (cohort study). SETTING: The Geriatric Rehabilitation Unit (GRU) of a Veterans Administration hospital. PARTICIPANTS: Of 350 randomly selected admissions to the GRU, 322 were discharged alive from the hospital. These 322 patients represented the study population, of whom 99% were male, and 75% were white. The average age of the study patients was 76 years. MEASUREMENTS: At admission and again at discharge, each patient completed a comprehensive medical, functional, neuropsychological, socioeconomic, and nutritional assessment. After discharge, each subject was tracked for 1 year. MAIN RESULTS: Within the 1-year posthospital discharge follow-up period, 64 study subjects (20%) died. This included 17% of the patients discharged home and 34% of the patients discharged to a nursing home (P < .01). Based on the Cox Proportional Hazards survival model, the variable most strongly associated with mortality was the discharge serum albumin, followed by discharge weight expressed as a percentage of ideal, self-dressing ability, and a discharge diagnosis of cardiac arrhythmia (usually atrial fibrillation). When all four of these variables were included in the analysis, the model was able to differentiate the survivors from those who died by years end with a sensitivity of 69%, a specificity of 69%, and an overall predictive accuracy of 69%. When tested using the data from the previous study, the model differentiated the patients who died from those who had not at a sensitivity of 62%, a specificity of 68%, and an overall predictive accuracy of 64%. CONCLUSIONS: Protein-energy undernutrition appears to be a strong independent risk factor for 1-year postdischarge mortality.

A neuroheptapeptide influence on cognitive functioning in the elderly.

The heptapeptide core common to melanocyte-stimulating hormone (MSH) and adrenocorticotropin (ACTH) was administered as a single subcutaneous dose of 30 mg to 13 elderly human subjects (9 men, 4 women) in a double-blind, cross-over design. Significant improvement was found in the Benton Visual Retention Test after MSH/ACTH 4--10 as compared with administration of saline. This appeared to be greater in men than women. No side effects or laboratory abnormalities were observed. The behavioral results are consistent with our earlier findings in men and rats of improved visual attention after administration of MSH and extend them to the elderly population.

Two-photon fluorescence excitation of macroscopic areas on planar waveguides.

In this paper, we report the first successful demonstration, to our knowledge, of two-photon fluorescence excitation (TPFE) using planar thin-film waveguide structures of macroscopic excitation dimensions (square millimeters to square centimeters in size). The high intensity of excitation light required for TPFE is available not only at a single focus point but along the whole trace of the beam guided in the waveguide structure. Line profiles of the fluorescence excited by TPFE show excellent correlation with the geometry of the launched laser beams. A clear second-order dependence of the fluorescence intensity on the excitation intensity confirms the two-photon character of fluorescence generation. Spectra of the emission generated by one-photon excitation and by two-photon excitation show only minor differences.

Socioeconomic inequalities in mortality among elderly people in 11 European populations.

STUDY OBJECTIVE: To describe mortality inequalities related to education and housing tenure in 11 European populations and to describe the age pattern of relative and absolute socioeconomic inequalities in mortality in the elderly European population. DESIGN AND METHODS: Data from mortality registries linked with population census data of 11 countries and regions of Europe were acquired for the beginning of the 1990s. Indicators of socioeconomic status were educational level and housing tenure. The study determined mortality rate ratios, relative indices of inequality (RII), and mortality rate differences. The age range was 30 to 90+ years. Analyses were performed on the pooled European data, including all populations, and on the data of populations separately. Data were included from Finland, Norway, Denmark, England and Wales, Belgium, France, Austria, Switzerland, Barcelona, Madrid, and Turin. MAIN RESULTS: In Europe (populations pooled) relative inequalities in mortality decreased with increasing age, but persisted. Absolute educational mortality differences increased until the ages 90+. In some of the populations, relative inequalities among older women were as large as those among middle aged women. The decline of relative educational inequalities was largest in Norway (men and women) and Austria (men). Relative educational inequalities did not decrease, or hardly decreased with age in England and Wales (men), Belgium, Switzerland, Austria, and Turin (women). CONCLUSIONS: Socioeconomic inequalities in mortality among older men and women were found to persist in each country, sometimes of similar magnitude as those among the middle aged. Mortality inequalities among older populations are an important public health problem in Europe.

Exploration of interactions between prognostic factors of stage I malignant melanoma.

While many studies have sought prognostic factors of malignant melanoma using multivariate survival models, the interaction between predictors has been much less studied. We have studied data from 1,560 patients with stage I melanoma collected at the Cancer Registry of the Canton of Zurich over the period 1980-1990 and explored interactions between predictors by identifying two separate multivariate Cox models for men and women and investigating two-way interactions between predictors in each model. Considerable differences between models for man and women were observed. In particular, in women a pronounced interaction between 'histology' and 'Clark level' was identified. Without this interaction 'histology' and 'Clark level' are not significant but when the interaction term was included both predictors become significant. Thus, omission of an interaction term may preclude the recognition of main effects ('masking'). For female patients with nodular tumours prognosis is essentially independent of Clark level. In contrast, for female patients with non-nodular tumours, prognosis was found to be strongly dependent on Clark level. In the case of Clark level 2 prognosis was extremely good: no patient was observed to die from melanoma. We conclude that it may be worth considering interaction terms. With large enough sample sizes it may be preferable to stratify patients into subgroups and to identify separate models for each stratum instead of having to cope with interactions of higher order.

Ethylene synthesis in moss protonema.

In sterile cultivated protonema of the moss Funaria hygrometrica we found a promotion of ethylene formation by ACC but not by other possible precursors such as 2-ketoglutarate or glutamate. The ACC contents and ethylene formation during development of protonema were correlated. Both ACC contents and ethylene formation were promoted by exogenous IAA. These findings indicate that ethylene production in Funaria protonema follows the normal pathway as in higher plants. The rate of ethylene production lay in the same order of magnitude as in higher plants and depended on the developmental stage of the protonema.

[Cartography as an instrument in epidemiology: methodologic considerations for the new Swiss cancer atlas]. / Kartographie als Instrument in der Epidemiologie: Methodologische Uberlegungen für den neuen Schweizer Krebsatlas.

Maps not following the syntactical rules of the graphical language entail the risk of being misunderstood. Maps aim at demonstrating spatial patterns and visualizing dividing lines. Representation of tabular values is not a principal goal. Maps should be "seen" as a whole, not be "read" element by element. Some technical aspects of cartography are discussed (distortion of information, grouping of data, adequacy and use of colour). The guidelines for the new Swiss cancer atlas are based on these general principles. A continuous-shading technique avoiding class intervals is being used. It allows the combination of maps and diagrams of different aggregations of the same data using a common shading scale. Indications of significance are integrated into all figures. Geographical maps are enriched by diagrams showing data for 9 cities, 5 language regions, for a grouping by size of community and for a socioeconomical classification of regions. The universal shading scale enables to compare the figures separately and crossways. Relationships not apparent in a traditional map might be revealed.

[Occupation-specific indicators for strategic prevention in risk groups]. / Berufsspezifischer Indikator für die risikogruppenstrategische Prävention.

Using graphical representations to compare undistorted information it was attempted to bridge the gap between medicine and concerned risk-groups. Age-standardized mortality rates in 1979-1983 for 55 occupational groups (in 11 categories) of males aged 35 to 74 years were computed and compared to the Swiss national average; simultaneously the quantitative importance and the total mortality without accidents is shown for each occupational group: as an example the figure for lung cancer is reproduced. The elevated total mortality in the upper tertile of occupational groups is significantly explained by an increased risk of dying from circulatory or respiratory diseases, liver cirrhosis or malignancies of the lung, oropharynx, oesophagus or stomach. Foreseeable decrease of high-risk occupational groups will result in a further decline in mortality due to stomach cancer and cerebrovascular diseases in Switzerland.

Alcohol consumption and gender in the 20th century: the case of Switzerland.

Given the changes of gender roles in this century it is hardly justified to assume constant proportions of alcohol consumption for males and females. The purpose of the study was to reconstruct the consumption trends of males and females in Switzerland since the beginning of the 20th century. Cirrhosis mortality and survey data were used to disaggregate by sex the per capita alcohol consumption derived from sales data. The disaggregation of the per capita alcohol consumption based on liver cirrhosis mortality suggests that the evolution of alcohol consumption in Switzerland followed a parallel course for both sexes only until the 1930s. The low consumption during World War II and the evident increase until the beginning of the '60s seem to have resulted above all from the variations in consumption of beer by men. The decrease in total alcohol consumption observed since the '70s is also most probably due only to men; there is no indication of a decreasing consumption by women. The tendency of male and female consumption patterns to become more similar should be taken into account in the prevention of alcohol misuse.