Melatonin decreases human adipose tissue insulin sensitivity.

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

Territorial gaps on quality of causes of death statistics over the last forty years in Spain.

BACKGROUND: The quality of the statistics on causes of death (CoD) does not present consolidated indicators in literature further than the coding group of ill-defined conditions of the International Classification of Diseases. Our objective was to assess the territorial quality of CoD by reliability of the official mortality statistics in Spain over the years 1980-2019. METHODS: A descriptive epidemiological design of four decades (1980-, 1990-, 2000-, and 2010-2019) by region (18) and sex was implemented. The CoD cases, age-adjusted rates and ratios (to all-cause) were assigned by reliability to unspecific and ill-defined quality categories. The regional mortality rates were contrasted to the Spanish median by decade and sex by the Comparative Mortality Ratio (CMR) in a Bayesian perspective. Statistical significance was considered when the CMR did not contain the value 1 in the 95% credible intervals. RESULTS: Unspecific, ill-defined, and all-cause rates by region and sex decreased over 1980-2019, although they scored higher in men than in women. The ratio of ill-defined CoD decreased in both sexes over these decades, but was still prominent in 4 regions. CMR of ill-defined CoD in both sexes exceeded the Spanish median in 3 regions in all decades. In the last decade, women's CMR significantly exceeded in 5 regions for ill-defined and in 6 regions for unspecific CoD, while men's CMR exceeded in 4 and 2 of the 18 regions, respectively on quality categories. CONCLUSIONS: The quality of mortality statistics of causes of death has increased over the 40 years in Spain in both sexes. Quality gaps still remain mostly in Southern regions. Authorities involved might consider to take action and upgrading regional and national death statistics, and developing a systematic medical post-grade training on death certification.

COVID-19, social determinants of transmission in the home. A population-based study.

BACKGROUND: Studying transmission within the home is essential to understand the transmission dynamics of numerous infectious diseases. For Coronavirus Disease-2019 (COVID-19), transmission within the home constitutes the majority exposure context. The risk of infection in this setting can be quantified by the household/intra-family secondary attack rate (SAR). In the literature, there are discrepancies in these values and little information about its social determinants. The aim of this study was to investigate transmission in the home by analyzing the influence of occupational social class, country of origin and gender/sex. METHODS: This was a retrospective cohort study of a population registry of cohabiting contacts with COVID-19 cases diagnosed from 15 June to 23 December 2020, in the Murcia Region. The household SAR was analyzed considering the characteristics of the primary case (sex, age, symptoms, occupational social class, country of origin and number of people in the household) and contact (age and sex) using a multilevel binary logistic regression model. RESULTS: Among the 37 727 contacts included, the intra-family SAR was 39.1%. The contacts of confirmed primary cases in the migrant population (Africa and Latin America) had higher attack rates, even after adjusting for the other variables. Older age and female sex were independent risk factors for contracting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the home. CONCLUSION: There was greater intra-domiciliary transmission among immigrants, likely related to the conditions of the home and situation of social vulnerability. Women were more likely to be infected by transmission from a cohabiting infected individual.

Estimating Country-Specific Incidence Rates of Rare Cancers: Comparative Performance Analysis of Modeling Approaches Using European Cancer Registry Data.

Estimating incidence of rare cancers is challenging for exceptionally rare entities and in small populations. In a previous study, investigators in the Information Network on Rare Cancers (RARECARENet) provided Bayesian estimates of expected numbers of rare cancers and 95% credible intervals for 27 European countries, using data collected by population-based cancer registries. In that study, slightly different results were found by implementing a Poisson model in integrated nested Laplace approximation/WinBUGS platforms. In this study, we assessed the performance of a Poisson modeling approach for estimating rare cancer incidence rates, oscillating around an overall European average and using small-count data in different scenarios/computational platforms. First, we compared the performance of frequentist, empirical Bayes, and Bayesian approaches for providing 95% confidence/credible intervals for the expected rates in each country. Second, we carried out an empirical study using 190 rare cancers to assess different lower/upper bounds of a uniform prior distribution for the standard deviation of the random effects. For obtaining a reliable measure of variability for country-specific incidence rates, our results suggest the suitability of using 1 as the lower bound for that prior distribution and selecting the random-effects model through an averaged indicator derived from 2 Bayesian model selection criteria: the deviance information criterion and the Watanabe-Akaike information criterion.

Birth-sex cohort alcohol use transitions in the general population: the cross-sectional PEGASUS-Murcia project. / Las transiciones en el uso de alcohol en una cohorte de nacimiento-sexo en la población general: el proyecto transversal PEGASUS-Murcia.

To examine the potential impact of prevalence of alcohol use in a birth-sex cohort on subsequent initiation and progression of alcohol use in the PEGASUS-Murcia project, a cross-sectional survey of a representative sample of non-institutionalized adults in Murcia (Spain). Data on lifetime history of alcohol use, DSM-IV use disorders, and remission were collected from 1,459 adults using face-to-face interviewers based on the Composite International Diagnostic Interview (CIDI 3.0). Life-table estimates based on survival functions for alcohol use age-of-onset and remission were used as time-varying predictors of subsequent individual-level alcohol use in discrete-time survival models. Nearly nine out of ten adults had a lifetime alcohol use history at time of interview. Of these lifetime users, 84.3% became regular users (>12 drinks a year) and 5.5-1.6% went on to meet criteria for DSM-IV alcohol abuse or dependence, respectively. By the age of 18, 70.9% of respondents had used alcohol, and one half (50.2%) had used regularly. Regular use sharply increased during early adulthood to reach 90.8% by age 22. Birth-sex cohort alcohol use was significantly and positively associated with increased odds of all subsequent transitions examined except for the transition from use to abuse. The findings highlight sensitive periods with rapid transitions to higher levels of alcohol use and emphasize the importance of cohort experiences in the full spectrum of stages of alcohol use. These results may contribute to predicting population-levels trends in alcohol-related problems in Spain.

Examinar el impacto potencial de la prevalencia de uso de alcohol en una cohorte de nacimiento-sexo en el inicio y progresión del uso de alcohol en el proyecto PEGASUS-Murcia, encuesta transversal en una muestra representativa de adultos no institucionalizados de Murcia (España). Se entrevistaron personalmente a 1.459 adultos sobre consumo de alcohol a lo largo de la vida, trastornos por uso de alcohol (criterios DSM-IV) y remisión utilizando la Entrevista Diagnóstica Internacional Compuesta (CIDI 3.0). Se calcularon estimaciones de tablas de vida basadas en las funciones de supervivencia para la edad de inicio en el uso de alcohol y su remisión en modelos de supervivencia de tiempo discreto. Casi nueve de cada diez adultos tuvieron una historia de uso de alcohol a lo largo de la vida. Entre ellos, 84,3% desarrolló un uso regular (>12 bebidas por año) y 5,5% y 1,6% cumplieron criterios DSM-IV de Abuso y Dependencia de alcohol, respectivamente. A los 18 años, 70,9% había usado alcohol, 50,2% de forma regular, con un aumento brusco en adultos jóvenes (90,8% a los 22 años). El uso de alcohol de la cohorte de nacimiento-sexo se asoció significativamente con mayores probabilidades para todas las transiciones examinadas, excepto en la transición uso-abuso. Se detectan períodos sensibles con transiciones rápidas a niveles más altos de uso de alcohol. Las experiencias de cohortes en todas las etapas del consumo de alcohol son importantes. Estos resultados podrían contribuir a la predicción de las tendencias poblacionales de los problemas con el alcohol en España.

Increasing therapy-related myeloid neoplasms in multiple myeloma.

BACKGROUND: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28-year follow-up period (1991-2018) in a tertiary single institution. MATERIAL AND METHODS: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs. RESULTS: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy-related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months). CONCLUSIONS: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach.

Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2).

OBJECTIVE: Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. METHODS: The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). RESULTS: Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). CONCLUSIONS: There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology.

Work, household, and leisure-time physical activity and risk of mortality in the EPIC-Spain cohort.

OBJECTIVE: Large-scale longitudinal data on the association of domain-specific physical activity (PA) and mortality is limited. Our objective was to evaluate the association of work, household (HPA), and leisure time PA (LTPA) with overall and cause-specific mortality in the EPIC-Spain study. METHODS: 38,379 participants (62.4% women), 30-65years old, and free of chronic disease at baseline were followed-up from recruitment (1992 - 1996) to December 31st, 2008 to ascertain vital status and cause of death. PA was evaluated at baseline and at a 3-year follow-up with a validated questionnaire (EPIC-PAQ) and combined variables were used to classify the participants by sub-domains of PA. Associations with overall, cancer, and cardiovascular mortality risks were assessed using competing risk Cox regression models adjusted by potential confounders. RESULTS: After 13.6years of mean follow-up, 1371 deaths were available for analyses. HPA was strongly associated to reduced overall (hazard ratio (HR) for Q4 vs. Q1=0.47 (0.34, 0.64)) and cause-specific mortalities in women and to lower cancer mortality in men (P for trend=0.004), irrespective of age, education, and lifestyle and morbidity variables. LTPA was associated with lower mortality in women (HR for Q4 vs. Q1=0.71 (0.52, 0.98)), but not men. No relationships were found between sedentariness at work and overall mortality. CONCLUSIONS: HPA was associated to lower mortality risk in men and women from the EPIC-Spain cohort, whereas LTPA also contributed to reduce risk of death in women. Considering the large proportion of total daily PA that HPA represents in some population groups, these results are of public health importance.

A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. DESIGN: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. SETTING: The European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: Women (n 334 850) from the EPIC study. RESULTS: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in ß-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). CONCLUSIONS: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.

Trends in socioeconomic inequalities in mortality in small areas of 33 Spanish cities.

BACKGROUND: In Spain, several ecological studies have analyzed trends in socioeconomic inequalities in mortality from all causes in urban areas over time. However, the results of these studies are quite heterogeneous finding, in general, that inequalities decreased, or remained stable. Therefore, the objectives of this study are: (1) to identify trends in geographical inequalities in all-cause mortality in the census tracts of 33 Spanish cities between the two periods 1996-1998 and 2005-2007; (2) to analyse trends in the relationship between these geographical inequalities and socioeconomic deprivation; and (3) to obtain an overall measure which summarises the relationship found in each one of the cities and to analyse its variation over time. METHODS: Ecological study of trends with 2 cross-sectional cuts, corresponding to two periods of analysis: 1996-1998 and 2005-2007. Units of analysis were census tracts of the 33 Spanish cities. A deprivation index calculated for each census tracts in all cities was included as a covariate. A Bayesian hierarchical model was used to estimate smoothed Standardized Mortality Ratios (sSMR) by each census tract and period. The geographical distribution of these sSMR was represented using maps of septiles. In addition, two different Bayesian hierarchical models were used to measure the association between all-cause mortality and the deprivation index in each city and period, and by sex: (1) including the association as a fixed effect for each city; (2) including the association as random effects. In both models the data spatial structure can be controlled within each city. The association in each city was measured using relative risks (RR) and their 95 % credible intervals (95 % CI). RESULTS: For most cities and in both sexes, mortality rates decline over time. For women, the mortality and deprivation patterns are similar in the first period, while in the second they are different for most cities. For men, RRs remain stable over time in 29 cities, in 3 diminish and in 1 increase. For women, in 30 cities, a non-significant change over time in RR is observed. However, in 4 cities RR diminishes. In overall terms, inequalities decrease (with a probability of 0.9) in both men (RR = 1.13, 95 % CI = 1.12-1.15 in the 1st period; RR = 1.11, 95 % CI = 1.09-1.13 in the 2nd period) and women (RR = 1.07, 95 % CI = 1.05-1.08 in the 1st period; RR = 1.04, 95 % CI = 1.02-1.06 in the 2nd period). CONCLUSIONS: In the future, it is important to conduct further trend studies, allowing to monitoring trends in socioeconomic inequalities in mortality and to identify (among other things) temporal factors that may influence these inequalities.

Reducing Monte Carlo error in the Bayesian estimation of risk ratios using log-binomial regression models.

In cohort studies, binary outcomes are very often analyzed by logistic regression. However, it is well known that when the goal is to estimate a risk ratio, the logistic regression is inappropriate if the outcome is common. In these cases, a log-binomial regression model is preferable. On the other hand, the estimation of the regression coefficients of the log-binomial model is difficult owing to the constraints that must be imposed on these coefficients. Bayesian methods allow a straightforward approach for log-binomial regression models and produce smaller mean squared errors in the estimation of risk ratios than the frequentist methods, and the posterior inferences can be obtained using the software WinBUGS. However, Markov chain Monte Carlo methods implemented in WinBUGS can lead to large Monte Carlo errors in the approximations to the posterior inferences because they produce correlated simulations, and the accuracy of the approximations are inversely related to this correlation. To reduce correlation and to improve accuracy, we propose a reparameterization based on a Poisson model and a sampling algorithm coded in R.

[Results of two surveys of immigrants and natives in Southeast Spain: health, use of services, and need for medical assistance]. / Resultados de dos encuestas dirigidas a inmigrantes y nativos del sureste español: salud, uso de servicios y necesidad de asistencia médica.

OBJECTIVE: To compare the self-perceived health, use of health services and unmet need for health care (UNHC) among immigrants and native populations of Southeast Spain. MATERIALS AND METHODS: Cross-sectional study of two representative samples of 1150 immigrants, and 1303 native participants from the National Health Survey. A single database was created with specific weights for each sample, and prevalence ratios (PR) were estimated by multivariate regression. RESULTS: Moroccans, Ecuadorians and Eastern Europeans (EE) reported poorer health than the native population (PRs [CI95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] and 1.44 [1.08-1.93], respectively). Immigrants made greater use of emergencies that natives (except for EE) and had lower use of medication. Moroccan showed the greatest difference in the frequency of UNHC (PR [CI95%]:12.20 [5.25 - 28.37]), mainly because of working limitations (46%). CONCLUSIONS: The health status and use of health services among immigrants differ significantly from those of natives. Results highlight the higher frequency of UNHC among immigrants, especially high in Moroccans.

Children with obesity have poorer circadian health as assessed by a global circadian health score.

BACKGROUND: Circadian health refers to individuals' well-being and balance in terms of their circadian rhythm. It is influenced by external cues. In adults, a close relationship between circadian-related alterations and obesity has been described. However, studies in children are scarce, and circadian health and its association with obesity have not been evaluated globally. We aimed to assess whether circadian health differed between children with and without obesity as determined by a global circadian score (GCS) in a school-age population. METHODS: Four hundred and thirty-two children (7-12 years) were recruited in Spain. Non-invasive tools were used to calculate the GCS: (1) 7-day rhythm of wrist temperature (T), activity (A), position (P), an integrative variable that combines T, A, and P (TAP); (2) cortisol; and (3) 7-day food and sleep records. Body mass index, body fat percentage, waist circumference (WC), melatonin concentration, and cardiometabolic marker levels were determined. RESULTS: Circadian health, as assessed by the GCS, differed among children with obesity, overweight, and normal weight, with poorer circadian health among children with obesity. Children with obesity and abdominal obesity had 3.54 and 2.39 greater odds of having poor circadian health, respectively, than did those with normal weight or low WC. The percentage of rhythmicity, a marker of the robustness of the TAP rhythm, and the amplitude, both components of the GCS, decreased with increasing obesity. Different lifestyle behaviors were involved in the association between circadian health and obesity, particularly protein intake (P = 0.024), physical activity level (P = 0.076) and chronotype (P = 0.029). CONCLUSIONS: The GCS can capture the relationship between circadian health and obesity in school-age children. Protein intake, physical activity level, and chronotype were involved in this association. Early intervention based on improving circadian health may help to prevent childhood obesity.

Risk of type 2 diabetes according to traditional and emerging anthropometric indices in Spain, a Mediterranean country with high prevalence of obesity: results from a large-scale prospective cohort study.

BACKGROUND: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM). A proper anthropometric characterisation of T2DM risk is essential for disease prevention and clinical risk assessement. METHODS: Longitudinal study in 37 733 participants (63% women) of the Spanish EPIC (European Prospective Investigation into Cancer and Nutrition) cohort without prevalent diabetes. Detailed questionnaire information was collected at baseline and anthropometric data gathered following standard procedures. A total of 2513 verified incident T2DM cases occurred after 12.1 years of mean follow-up. Multivariable Cox regression was used to calculate hazard ratios of T2DM by levels of anthropometric variables. RESULTS: Overall and central obesity were independently associated with T2DM risk. BMI showed the strongest association with T2DM in men whereas waist-related indices were stronger independent predictors in women. Waist-to-height ratio revealed the largest area under the ROC curve in men and women, with optimal cut-offs at 0.60 and 0.58, respectively. The most discriminative waist circumference (WC) cut-off values were 99.4 cm in men and 90.4 cm in women. Absolute risk of T2DM was higher in men than women for any combination of age, BMI and WC categories, and remained low in normal-waist women. The population risk of T2DM attributable to obesity was 17% in men and 31% in women. CONCLUSIONS: Diabetes risk was associated with higher overall and central obesity indices even at normal BMI and WC values. The measurement of waist circumference in the clinical setting is strongly recommended for the evaluation of future T2DM risk in women.

Time trends and geographical variations in mortality due to suicide and causes of undetermined intent in Spain, 1991-2008.

BACKGROUND: This study analyses the trends, geographical variations, seasonal patterns and methods of mortality due to the combination of suicide and causes of undetermined intent in Spain between 1991 and 2008. METHODS: Age-adjusted suicide rates were calculated. Poisson models were used to estimate rate ratios and annual percentage changes. RESULTS: Suicide rates decreased in all age groups with the exception of the 35-44 and 45-54 age groups. There were important geographic variations in suicide rates. Spring and summer were the seasons with the highest suicide rates. Suicide rates for hanging decreased, although the rates increased in the 35-44 age group of males. A significant upward trend in suicide by jumping was observed for males aged 15-54 and for females aged 25-64. There were almost no differences when the deaths of undetermined intent were excluded. CONCLUSIONS: Suicide rates decreased in both males and females, although the downward trend was not observed in males and females aged 35-44 or in females in the 45-54 age group. A significant upward trend in suicide rates for jumping was observed in some age groups. Substantial geographical variations in suicide rates were observed. The highest rates were observed in the warmest months.

Lifestyle mediators of associations among siestas, obesity, and metabolic health.

OBJECTIVE: The aim of this study was to determine the association between siestas/no siestas and obesity, considering siesta duration (long: >30 minutes, short: ≤30 minutes), and test whether siesta traits and/or lifestyle factors mediate the association of siestas with obesity and metabolic syndrome (MetS). METHODS: This was a cross-sectional study of 3275 adults from a Mediterranean population (the Obesity, Nutrigenetics, TIming, and MEditerranean [ONTIME] study) who had the opportunity of taking siestas because it is culturally embedded. RESULTS: Thirty-five percent of participants usually took siestas (16% long siestas). Compared with the no-siesta group, long siestas were associated with higher values of BMI, waist circumference, fasting glucose, systolic blood pressure, and diastolic blood pressure, as well as with a higher prevalence of MetS (41%; p = 0.015). In contrast, the probability of having elevated SBP was lower in the short-siesta group (21%; p = 0.044) than in the no-siesta group. Smoking a higher number of cigarettes per day mediated the association of long siestas with higher BMI (by 12%, percentage of association mediated by smoking; p < 0.05). Similarly, delays in nighttime sleep and eating schedules and higher energy intake at lunch (the meal preceding siestas) mediated the association between higher BMI and long siestas by 8%, 4%, and 5% (all p < 0.05). Napping in bed (vs. sofa/armchair) showed a trend to mediate the association between long siestas and higher SBP (by 6%; p = 0.055). CONCLUSIONS: Siesta duration is relevant in obesity/MetS. Timing of nighttime sleep and eating, energy intake at lunch, cigarette smoking, and siesta location mediated this association.

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

BACKGROUND: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? METHODS: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. RESULTS: ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CONCLUSIONS: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Bayesian beta nonlinear models with constrained parameters to describe ruminal degradation kinetics.

The models used to describe the kinetics of ruminal degradation are usually nonlinear models where the dependent variable is the proportion of degraded food. The method of least squares is the standard approach used to estimate the unknown parameters but this method can lead to unacceptable predictions. To solve this issue, a beta nonlinear model and the Bayesian perspective is proposed in this article. The application of standard methodologies to obtain prior distributions, such as the Jeffreys prior or the reference priors, involves serious difficulties here because this model is a nonlinear non-normal regression model, and the constrained parameters appear in the log-likelihood function through the Gamma function. This paper proposes an objective method to obtain the prior distribution, which can be applied to other models with similar complexity, can be easily implemented in OpenBUGS, and solves the problem of unacceptable predictions. The model is generalized to a larger class of models. The methodology was applied to real data with three models that were compared using the Deviance Information Criterion and the root mean square prediction error. A simulation study was performed to evaluate the coverage of the credible intervals.