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Co-based superalloys have attracted attention to replace Ni-based superalloys in high temperature structural applications because of their higher melting temperature and corrosion resistance. Strengthening is provided by Co3(Al, X) (X = W, Cr, Mo, Ni) phases and optimization of their properties requires detailed information about the free energies of the different phases and of the phase diagram of the Co–Al system. This is achieved in this paper through first principles calculations in combination with statistical mechanics. Configurational entropic contributions to the free energy were included through Monte Carlo simulations using the cluster expansion formalism. The vibrational entropy of each phase was determined through the length-stiffness relationship while the magnetic entropy was also included through the Heisenberg Hamiltonian. The computed phase diagram is compared with the currently accepted experimental phase diagram and the different contributions to the stability of each phase are analyzed independently. The potential of this strategy to predict phase diagrams of magnetic systems is clearly established.

A large number of anomalous extension twins, with low or even negative twinning Schmid factors, were found to nucleate and grow in a strongly textured Mg-1Al alloy during tensile deformation along the extruded direction. The deformation mechanisms responsible for this behaviour were investigated through in-situ electron back-scattered diffraction, grain reference orientation deviation, and slip trace-modified lattice rotation. It was found that anomalous extension twins nucleated mainly at the onset of plastic deformation at or near grain boundary triple junctions. They were associated with the severe strain incompatibility between neighbour grains as a result from the different basal slip-induced lattice rotations. Moreover, the anomalous twins were able to grow with the applied strain due to the continuous activation of basal slip in different neighbour grains, which enhanced the strain incompatibility. These results reveal the complexity of the deformation mechanisms in Mg alloys at the local level when deformed along hard orientations.

Abstract Twin nucleation in textured Mg alloys was studied by means of electron back-scattered diffraction in samples deformed in tension along different orientations in more than 3000 grains. In addition, 28 relevant parameters, categorized in four different groups (loading condition, grain shape, apparent Schmid factors, and grain boundary features) were also recorded for each grain. This information was used to train supervised machine learning classification models to analyze the influence of the microstructural features on the nucleation of extension twins in Mg alloys. It was found twin nucleation is favored in larger grains and in grains with high twinning Schmid factors, but also that twins may form in the grains with very low or even negative Schmid factors for twinning if they have at least one smaller neighboring grain and another one (or the same) that is more rigid. Moreover, twinning of small grains with high twinning Schmid factors is favored if they have low basal slip Schmid factors and have at least one neighboring grain with a high basal slip Schmid factor that will deform easily. These results reveal the role of many-body relationships, such as differences in stiffness and size between a given grain and its neighbors, to assess extension twin nucleation in grains unfavorably oriented for twinning.

Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

Abstract Purpose To build models combining circulating microRNAs (miRNAs) able to identify women with breast cancer as well as different types of breast cancer, when comparing with controls without breast cancer. Method miRNAs analysis was performed in two phases: screening phase, with a total n = 40 (10 controls and 30 BC cases) analyzed by Next Generation Sequencing, and validation phase, which included 131 controls and 269 cases. For this second phase, the miRNAs were selected combining the screening phase results and a revision of the literature. They were quantified using RT-PCR. Models were built using logistic regression with LASSO penalization. Results The model for all cases included seven miRNAs (miR-423-3p, miR-139-5p, miR-324-5p, miR-1299, miR-101-3p, miR-186-5p and miR-29a-3p); which had an area under the ROC curve of 0.73. The model for cases diagnosed via screening only took in one miRNA (miR-101-3p); the area under the ROC curve was 0.63. The model for disease-free cases in the follow-up had five miRNAs (miR-101-3p, miR-186-5p, miR-423-3p, miR-142-3p and miR-1299) and the area under the ROC curve was 0.73. Finally, the model for cases with active disease in the follow-up contained six miRNAs (miR-101-3p, miR-423-3p, miR-139-5p, miR-1307-3p, miR-331-3p and miR-21-3p) and its area under the ROC curve was 0.82. Conclusion We present four models involving eleven miRNAs to differentiate healthy controls from different types of BC cases. Our models scarcely overlap with those previously reported.

Abstract The mechanical behavior, corrosion mechanisms, and cytocompatibility at the interface of magnesium wires reinforced poly-lactic acid polymer composites were studied by in vitro degradation study of 180 days. Surface modification of Mg wires by plasma-electrolytic oxidation improved the interface shear strength from 10.9 MPa to 26.3 MPa which decreased to 8 MPa and 13.6 MPa in Mg/PLA and PEO-Mg/PLA composites, respectively, after 42 days of in vitro degradation. Cross-sections of the composite showed good cytocompatibility, although the cells tended to migrate towards the PLA regions and avoided the surface of the Mg wires. Corrosion of Mg wires (without surface modification) was very fast in composite while corrosion of surface-modified Mg wires was significantly reduced, hydrogen gas was suppressed and only 3% mass loss of Mg wires was found after 180 days. Finally, the corrosion mechanisms at interface were discussed for both composites.

Abstract Background COVID-19 pandemic has changed the way pregnancies have been controlled as well as working conditions. In countries with paid leave of work, leaving earlier has been a relevant measure for controlling the pandemic. No study has been published on factors associated with earlier leaving work in pregnancy and the consequences it could have on pregnancy outcomes. Objective We aimed to identify woman and pregnancy characteristics associated with leaving work earlier and its consequences on pregnancy results. Method: A cohort study was carried out in Cantabria, Northern Spain, including 760 women who were pregnant in 2020 and were working at the beginning of their pregnancy. Data on pregnancy characteristics and results were obtained from medical records and gestational age at leaving work was self-reported. In a logistic regression analysis, leaving work before 26th week of pregnancy was the main effect variable. Results Several factors were associated with lower probability of leaving work before 26th week, including university studies (OR = 0.49, 95% CI: 0.36, 0.68), having presential work (OR = 0.57, 95% CI: 0.40, 0.81), women born in non-European countries (OR = 0.55, 95% CI: 0.30, 1.01) and non-smokers (OR for smokers = 1.79, 95% CI: 1.12, 2.87). Neither type of delivery, gestational age at delivery nor other pregnancy results were associated with the gestational age of leaving work. Conclusion Several pregnancy and women characteristics were associated with leaving work earlier in the COVID-19 pandemic, although it was not associated with any pregnancy outcome.

IntroductionSeveral indicators were employed to manage the COVID-19 pandemic. In this study, our objective was to compare the instantaneous reproductive number and the epidemic growth rate in the Spanish population.MethodsData on daily numbers of cases, admissions into hospitals, admissions into ICUs, and deaths due to COVID-19 in Spain from March 2020 to March 2022 were obtained. The four “pandemic state indicators”, which are daily numbers of cases, admissions into hospitals, admissions into ICUs, and deaths due to COVID-19 in Spain from March 2020 to March 2022 were obtained from the Instituto de Salud Carlos III. The epidemic growth rate was estimated as the derivative of the natural logarithm of daily cases with respect to time. Both the reproductive number and the growth rate, as “pandemic trend indicators,” were evaluated according to their capacity to anticipate waves as “pandemic state indicators.”ResultsUsing both the reproductive number and the epidemic growth rate, we were able to anticipate most COVID-19 waves. In most waves, the more severe the presentation of COVID-19, the more effective the pandemic trend indicators would be.ConclusionBesides daily number of cases or other measures of disease frequency, the epidemic growth rate and the reproductive number have different roles in measuring the trend of an epidemic. Naïve interpretations and the use of any indicator as a unique value to make decisions should be discouraged.

Abstract Background Our main objective was to determine the evolution of IgG and IgA antibodies directed against SARS-CoV-2 protein S in the blood of lactating women and in breast milk. Methods A cohort of 110 uninfected and vaccinated breastfeeding women was followed-up for 6 months at the Marqués de Valdecilla University Hospital, Spain, in 2020. An additional group of 23 breastfeeding mothers who had no previously documented infection and had not been vaccinated against SARS-CoV-2 were included as a control group. The antibodies in blood and breast milk and their evolution at 6 months post-vaccination were analysed. Results One hundred ten breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) received two doses of mRNA-1273, and 20 women (18.2%) received a single dose of ChAdOx1-S. No evidence of differences between concentrations of antibodies was found according to the type of vaccine, with the exception of serum IgA antibodies, which was higher in women vaccinated with mRNA-1273: mean [95%CI]: 0.05 AU/mL [0.03,0.06] with mRNA-1273, 0.02 AU/mL [0.01,0.03] with BNT162b2 and 0.01 AU/mL [0.00,0.03] with ChAdOx1-S, ANOVA p value = 0.03. The lack of difference between vaccines was also found when anti-S1 specific IgG in serum and breast milk were measured. Conclusions In lactating women vaccinated against COVID-19, anti-SARS-CoV-2 antibodies can be detected in both serum and breastmilk 6 months after receiving the second dose, although their concentrations decreased when compared with concentrations reached immediately after vaccination.

Abstract Background Breastfeeding is associated with lower incidence and severity of lower respiratory tract disease. However, little is known about the relationship between feeding type and breastfeeding duration with bronchiolitis in a child’s first year. Methods A prospective cohort study of 969 newborn babies were followed-up for 12 months to determine breastfeeding duration, feeding type, feeding trajectory, and bronchiolitis episodes at Marqués de Valdecilla University Hospital, Spain in 2018. Type of feeding was recorded by interviewing mothers at the time of hospital discharge and at 2, 4, 6, 9 and 12 months of life, in three categories: breastfeeding, mixed feeding and infant formula. Type of feeding at hospital discharge refers to feeding from birth to discharge. In any other times studied, it refers to feeding in the last 24 h. The association between the feeding type and bronchiolitis was analysed using logistic regression. Poisson regression was used to evaluate the association between feeding type and the number of bronchiolitis episodes with Kaplan-Meier estimators presenting the cumulative probability of suffering bronchiolitis. The results were adjusted for mother and child characteristics. Results Our data shows exclusive breastfeeding and mixed breastfeeding reduce the number of episodes of bronchiolitis. Regarding feeding at 4 months, exclusive breastfeeding reduced by 41% the number of episodes of bronchiolitis (adjusted incidence Ratio (aIR) 0.59, 95% CI 0.46, 0.76) and mixed feeding by 37% (aIR 0.63, 95% CI 0.47, 0.86). Moreover, changing from exclusive breastfeeding to mixed feeding increased the incidence of bronchiolitis compared with continuing exclusive breastfeeding. An early swap to mixed breastfeeding before months 2 or 4, was associated with a reduced the number of episodes of bronchiolitis, (aIR 0.53, 95% CI 0.39, 0.73 if introduction of mixed breastfeeding before month 2, and aIR 0.61, 95% CI 0.45, 0.83 if introduction of mixed breastfeeding before month 4), when compared with infant formula alone. Conclusions Any breastfeeding was associated with lower incidence of bronchiolitis and number of episodes of bronchiolitis in the first year of life. Consequently, promoting programmes facilitating exclusive or mixed breastfeeding would be a relevant measure in the prevention of bronchiolitis.

Abstract Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

Abstract BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

Abstract Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR≥9 hours: 1.59; 95%CI 1.30–1.94) and gastric cancer (OR≥9 hours: 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer (OR≤5 hours: 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal (OR6–7 naps/week, ≥30 min: 1.32; 1.14–1.54) and gastric cancer (OR6–7 naps/week, ≥30 min: 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer.

IntroductionPatients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients.MethodsA large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA.ResultsLow irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01).ConclusionsOur results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.

Abstract Background Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA. Methods This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1. Results Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p

Abstract Background Burnout syndrome is a frequent syndrome related to people that feel a deterioration in their daily activities due to highly demandant psychological requirements in their workplaces. Within last decades, this syndrome has been studied across medical professionals, concluding that stress levels that physicians suffer is high enough to make them develop burnout syndrome. In the case of medical students, there are some recent studies, although with small samples. For this reason, given that this phenomenon may produce a huge impact in medical students’ development, the aim of this study is to analyze the influential factors that may contribute to its occurrence. Methods The necessary information was gathered through a web-based questionnaire, divided in two parts. The first part of the survey included questions related to personal aspects of the students. Burnout related questions (second part) were divided in three subscales to evaluate exhaustion, cynicism, and academic efficacy levels. Results Family support for studying medicine is associated with lower burnout levels in all three scales of the Maslach Burnout Inventory. The number of years spent in the degree show the opposite trend: the more years in the degree, the higher score in all burnout scales. Conclusions Burnout syndrome is a problem among medical students in Spain that increases with the number of years studying medicine. It should be also noticed that family support and vocational studies are independent factors related to lower levels of burnout.

Abstract The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage

Abstract Background Low birth weight rates are increasing in both developed and developing countries. Although several maternal factors have been identified as associated with low birth weight, little is known of economic or organization factors influencing this increase. This study aims to ascertain the twenty-first century relationships between the contextual country factors and low birth weight rates. Methods We analyse trends of low birth weight rates in Organisation for Economic Co-operation and Development (OECD) countries. Data from 2000 to 2015 were obtained from the OECD data base. Their relationships with demographic and economic variables, health habits, woman-related preventive measures, health care system organization and funding, health care work force and obstetric care were analysed using random-effects linear regression. Results Low birth weight rates are higher in Southern Europe (7.61%) and lower in Northern Europe (4.68%). Low birth weight rates escalated about 20% in Southern Europe and to less extent in Easter Europe (7%) and Asian/Oceanian countries, while remained stable in America, Central Europe and Northern Europe. Investment in health care, private health system coverage, ratios of paediatricians and obstetricians, average length of admission due to pregnancy or birth and Caesarean section rate were associated with higher low birth weight rates. Factors associated with lower low birth weight rates were health care coverage, public health system coverage, hospitals per million inhabitants, and ratios of health care workers, physicians, midwives and nurses. Conclusions In OECD countries, LBW rates are related to contextual country characteristics such as GDP per capita, which is inversely related to LBW rate. Health care system factors, including health care coverage or investment in public health system, are directly associated with lower LBW rates.

Abstract Background Factors associated with duration of breastfeeding have been usually studied at specific times after birth. Little is known about how much time is added to breastfeeding by each associated factor. Methods A cohort of 969 mother-child dyads was followed-up for twelve months at the Marqués de Valdecilla University Hospital, Spain, in 2018. Data on mother characteristics, pregnancy, delivery and children characteristics were obtained from medical records. Length of breastfeeding was reported by the mothers and recorded in paediatric medical record at hospital discharge and 2, 4, 6, 9 and 12 months of life. Factors associated with duration of breastfeeding were analysed via multivariate Weibull regression parameterized as accelerated time of failure. Results are presented as time ratios. Results About four out of five children were breastfed at hospital discharge, although this proportion dropped to 65% in children born from smoker women, 70% in preterm children and 68% in neonates weighting less than 2500 g. Mother’s age was associated with longer breastfeeding, adding 2% more breastfeeding time per year (adjusted time ratio 1.02; 95% confidence interval 1.00, 1.04). Children born from mothers with university studies were breastfed 53% more time than those born from mothers with primary studies (adjusted time ratio 1.53; 95% confidence interval 1.21, 1.95); smoking in pregnancy decreased length of breastfeeding by 41% (adjusted time ratio 0.59; 95% confidence interval 0.46, 0.76). Other factors associated with longer breastfeeding were single pregnancy and newborn weight over 2500 g. Conclusions Analysing factors associated with duration of breastfeeding as time parameters allows us to quantify the amount of time gained or lost by each factor, which could make it easier to evaluate the relevance of programmes directed to promote facilitating breastfeeding factors.

Abstract Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA.

Abstract Background It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n = 3), lipid lowering agents (n = 8), antihypertensive drugs (n = 1), low dose aspirin (n = 1) and lifestyle modification (n = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA.

Abstract Background The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. Methods A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex. Results The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022). Conclusions In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk.

Abstract Background The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. Methods We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. Results Higher parent’s economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. Conclusions Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy.

Background: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. Methods: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. Results: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score–C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1–0.5), p = 0.001] and ⩾2 [beta coefficient 0.5 (95% CI 0.3–0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99–4.02), p = 0.053] and ⩾2 [OR 3.39 (95%CI 1.82–6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ⩾2 over 1 CV risk factor. Conclusion: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.

Objectives: To explore the association of colorectal cancer with environmental solar radiation and sun exposure behavior, considering phenotypic variables (eye color, hair color and skin phenotype), dietary intake of vitamin D and calcium, and socio-demographic factors. Study design: Multicenter population-based frequency matched case-control study in Spain (MCC-Spain), with 2140 CRC cases and 3950 controls. Methods: Data were obtained through personal interviews using a structured epidemiological questionnaire that included socio-demographic data, residential history, environmental exposures, behavior, phenotypic and dietary information. An environmental-lifetime sun exposure score was constructed combining residential history and average daily solar radiation, direct and diffuse. Logistic regression was used to explore the association between different variables. A structural equation model was used to verify the associations of the conceptual model. Results: We found a lower risk of CRC in subjects frequently exposed to sunlight during the previous summer and skin burning due to sun exposure. No association was observed in relation to the residential solar radiation scores. Subjects with light eye or light hair colors had a lower risk of CRC that those with darker colors. Dietary calcium and vitamin D were also protective factors, but not in the multivariate model. The structural equation model analysis suggested that higher sun exposure was associated with a decreased risk of CRC, as well as dietary intake of calcium and vitamin D, and these factors are correlated among themselves and with environmental solar radiation and skin phenotypes. Conclusion: The results agree with previous observations that sun exposure, dietary vitamin D and calcium intake, and serum 25(OH)D concentration reduce the risk of CRC and indicate that these factors may be relevant for cancer prevention. Keywords: Colorectal cancer, Sunlight, Calcium, Vitamin D, Skin phenotype

Purpose The Mother and Child COVID-19 study is a cohort recruiting pregnant women and their children in Cantabria, North of Spain, during COVID-19 pandemic in order to ascertain consequences of SARS-CoV-2 infection on pregnant women and their descendants. This article reports the cohort profile and preliminary results as recruitment is still open.Participants Three subcohorts can be identified at recruitment. Subcohort 1 includes women giving birth between 23 March and 25 May 2020; they have been retrospectively recruited and could have been exposed to COVID-19 only in their third trimester of pregnancy. Subcohort 2 includes women giving birth from 26 May 2020 on; they are being prospectively recruited and could have been exposed to COVID-19 in both their second and third trimesters of pregnancy. Subcohort 3 includes women in their 12 week of pregnancy prospectively recruited from 26 May 2020 on; they could have been exposed to COVID-19 anytime in their pregnancy. All women are being tested for SARS-CoV-2 infection using both RT-PCR for RNA detection and ELISA for anti-SARS-CoV-2 antibodies. All neonates are being tested for antibodies using immunochemoluminiscency tests; if the mother is tested positive for SARS-CoV-2 RNA, a nasopharyngeal swab is also obtained from the child for RT-PCR analysis.Findings to date As of 22 October, 1167 women have been recruited (266, 354 and 547 for subcohorts 1, 2 and 3, respectively). Fourteen women tested positive to SARS-CoV-2 RNA by the day of delivery. All 14 children born from these women tested negative for SARS-CoV-2 RNA.Future plans Children from women included in subcohort 3 are expected to be recruited by the end of 2020. Children will be followed-up for 1 year in order to ascertain the effect that COVID-19 on their development.

The liquid-solid diffusion couple technique, supported by phenomenological analysis and nano-indentation tests, is proposed on account of the relatively low melting points of Mg to explore the diffusion mobility and creep deformation. The potential of this strategy is demonstrated in MgGa hcp alloys where Ga solute (i.e. impurity) and Mg solvent diffusions in hcp MgGa alloys were both unveiled. It was followed by mapping the compressive creep behavior via nanoindentation along the composition arrays within the same MgGa couple sample. The compressive creep resistance of MgGa hcp alloys increased with the Ga content, and this enhancement was similar to the one found in MgZn alloys and superior to the one reported in MgAl alloys though Al is a slower impurity diffuser in hcp-Mg than Zn and Ga. Thereby, the solvent diffusion and its variation with the composition, rather than the solute diffusion, was suggested to govern the creep properties at high temperatures and low stresses.

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. Methods Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. Results Women consumed more non-aspirin NSAIDs (38.8% [36.7–41.0]) than men (22.3 [20.5–24.2]), but men consumed more aspirin (11.7% [10.3–13.2]) than women (5.2% [4.3–6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4–49.1) in younger than 45 to 21.1% (18.3–24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Abstract Background Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. Methods One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. Results Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1–2 and > 2 deliveries were 0.48 (0.28–0.81) and 0.34 (0.19–0.59), and in C carriers they were 0.92 (0.42–1.98) and 0.71 (0.31–1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. Conclusions The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect.

Abstract Background The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. Methods We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008–2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. Results High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51–0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. Conclusion The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer.

Abstract Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

Abstract The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46–0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.

The tensile testing of a needle-punched nonwoven fabric is presented. A high-sensitivity Split-Hopkinson Tensile Bar device was specifically designed for this purpose. The strain gauge measurements were combined with high-speed photography and Digital Image Correlation to analyse the deformation micromechanisms at high strain rates. The experimental set-up allowed to determine the wave propagation velocity of the as-received nonwove fabric, the evolution of the strain field with deformation and the wave interaction inside the fabric. The deformation was accommodated by the same micromechanisms observed during quasi-static tensile testing and ballistic impact, which comprised fibre straightening, rotation and sliding. Heterogeneous strain fields were developed in the nonwoven fabric as a result of the non-linear pseudoplastic response of the fabric and the internal dissipation due to the frictional deformation micromechanisms, preventing the propagation of high magnitude strain waves into the specimen. Additionally, the output forces were analysed to determine the influence of high-strain rates in the mechanical response of the nonwoven fabric, finding an increment of the stiffness for low applied strains under dynamic loading. These findings provide the basis to develop strain-rate dependent constitutive models to predict wave propagation in needle-punched nonwoven fabrics when subjected to impact loads.

INTRODUCTION:Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. METHODS:We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype-cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. RESULTS:The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS:Phototype is not associated with breast or prostate cancer.

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an MCC-Spain case-control study, considering tumor aggressiveness and extension, as well as genetic susceptibility to PC. 733 incident cases and 1228 population-based controls were included for this study. Dietary zinc was assessed using a food frequency questionnaire, and genetic susceptibility was assessed with a single nucleotide polymorphisms (SNP)-based polygenic risk score (PRS). The association between zinc intake and PC was evaluated with mixed logistic and multinomial regression models. They showed an increased risk of PC in those with higher intake of zinc (Odds Ratio (OR) tertile 3vs1: 1.39; 95% Confidence interval (CI):1.00⁻1.95). This association was mainly observed in low grade PC (Gleason = 6 RRR tertile 3vs1: 1.76; 95% CI:1.18⁻2.63) as well as in localized tumors (cT1-cT2a RRR tertile 3vs1: 1.40; 95% CI:1.00⁻1.95) and among those with higher PRS (OR tertile 3vs1: 1.50; 95% CI:0.89⁻2.53). In conclusion, a higher dietary zinc intake could increase the risk of low grade and localized tumors. Men with higher genetic susceptibility might also have a higher risk of PC associated with this nutrient intake.

Objective:To obtain a case definition and to describe variables associated with a cluster of unspecific symptoms in healthcare workers (HCW) in a hospital building. Materials and Methods: A cross-sectional study was performed. All people working at the Residencia Cantabria building (a 200-bed building belonging to University Hospital Marqués de Valdecilla) in June 2009 were invited to complete a self-administered questionnaire, including questions on demographic data, working place and shift, working conditions and current symptoms. A cluster analysis was developed to obtain the case definition. The strength of the association between the studied variables and accomplishing the case definition was measured using odds ratios (OR) with the 95% confidence interval (CI). Multiple logistic regression was used to obtain a predictive model; its general validity was estimated with Receiver Operating Curves (ROC) and their Area Under the Curve (AUC). Results: 357 completed questionnaires were obtained. The case was defined as having at least 5 symptoms out of the eleven included. Not being ascribed to a specific shift was the strongest protective variable related with "being a case" (OR = 0.30; 95% CI: 0.17-0.54), whereas the personal antecedent of distal pain or inflammation in arms or legs was the main risk factor (OR = 4.33, 95% CI: 2.75-6.82). A six-variable predictive model has AUC equaling to 0.7378. Conclusions: A disease associated with the indoor environment quality in a hospital was characterized. A multivariate score was drafted for identifying HCW with higher risk of developing the disease in order to apply administrative prevention measures.

elacionan con la adquisición y/o consolidación de estilos y hábitos de vida que pueden determinar el estado de salud futuro. Una inadecua- da nutrición, un alto nivel de sedentarismo, conductas sexuales de ries- go, el abuso de las nuevas tecnologías o el inicio en el consumo de dro- gas tanto legales como ilegales, son algunas de las conductas más destacables de esta etapa. Con el objeto de conocer cómo se establecen y consolidan los hábitos y estilos de vida en la etapa universitaria y sus efectos sobre la salud futura nace el proyecto uniHcos. Se trata del estu- dio de una cohorte dinámica de estudiantes universitarios que se incor- poran al proyecto durante el primer curso académico y serán seguidos durante su permanencia en la universidad y vida laboral. El seguimien- to se realizará bienalmente y para la captación y recogida de informa- ción se utilizarán las nuevas tecnologías on-line. El objetivo del presen- te trabajo es dar a conocer el proyecto uniHcos a la comunidad científica así como presentar los resultados preliminares encontrados hasta el momento en las dos cohortes establecidas desde el 2011.

The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers.In this case-control study, we report the antihypertensive drugs-breast cancer relationship in 1,736 breast cancer cases and 1,895 healthy controls; results are reported stratifying by the women's characteristics (i.e., menopausal status or body mass index category) tumor characteristics and length of use of antihypertensive drugs.The relationship among breast cancer and use of calcium channel blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to 3.17). Stratifying by BMI, the OR increased significantly in the group with BMI ≥ 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to 3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+ cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were the only group in which angiotensin II receptor blockers may be associated with breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be identified with any type or stage. Use of angiotensin-converting-enzyme inhibitors, beta blockers and diuretics were not associated with risk.In this large population-based study we found that long term use of calcium channel blockers is associated with some subtypes of breast cancer (and with breast cancer in overweight women).

Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors.In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models.Our results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26-0.69), colon (OR = 0.64; 95%CI = 0.48-0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43-0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed.These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear.

Objetivo: Comprobar si las variables meteorológicas justifican el gradiente norte-sur en la mortalidad por esclerosis múltiple (EM) en España. Métodos: La tasa de mortalidad por EM ajustada por edad en cada provincia de 1975 a 1998 se correlacionó con la media anual de diferentes variables meteorológicas. Resultados: Las temperaturas mínima, media y máxima, el número medio de horas de sol y el número de días soleados se correlacionaron negativamente con la mortalidad por EM, mientras que la cantidad de lluvia se correlacionó positivamente con la EM. La mayor parte de las correlaciones desaparecen al ajustar por latitud. En cambio, la mortalidad por EM está asociada con la latitud incluso después de ajustar por los factores meteorológicos. Conclusión: El gradiente norte-sur en la mortalidad por EM en España no puede explicarse completamente por factores meteorológicos. Son necesarias otras hipótesis para justicar esta asociación.Objectives: To determine whether weather conditions explain the North-South gradient in multiple sclerosis (MS) mortality described in Spain. Methods: The age-adjusted MS mortality rate by Spanish provinces from 1975 to 1998 was correlated with several climatic variables. Results: MS mortality was negatively correlated with minimum, average and maximum temperatures, the mean number of hours of sunshine, and the mean number of sunny days. A positive correlation was found with the average amount of rain. Most correlations disappeared after adjusting by latitude. However, MS mortality was associated with latitude after adjusting by climatic factors. Conclusions: The North-South gradient in MS mortality in Spain cannot be fully explained by weather differences. Therefore, other hypotheses are required to explain this association.

To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.

Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity.Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007-2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI).Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04-5.00), and crude OR for LBW was 1.77 (95% CI: 0.74-4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14-1.32); LBW = 0.48 (95% CI: 0.15-1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92-74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28-30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58-18.62).Prenatal care and social risk factors were major confounding variables in the relationship between immigrant status and neonatal morbidity.

Objetivo: Estudiar el impacto de los riesgos competitivos sobre el equilibrio de Hardy-Weinberg y sus consecuencias en los estudios de casos y controles sobre la relación gen-enfermedades de comienzo tardío. Métodos: A partir de una población que, respecto de un determinado gen, se encuentre en equilibrio de Hardy-Weinberg al nacer, se deduce la composición genética cuando el gen está asociado con una enfermedad letal de aparición precoz, y sus consecuencias sobre una enfermedad de comienzo tardío. Cuando se realiza un estudio de casos y controles con muestreo por densidad se obtiene una estimación no sesgada de la odds ratio, a pesar de que los controles no estén en equilibrio de Hardy-Weinberg. Resultados: Se presenta un ejemplo en el que el gen mutante se asocia con una mayor mortalidad precoz al romper el equilibrio de Hardy-Weinberg y da lugar a que en un estudio realizado en edades más avanzadas los controles se encuentren en desequilibrio, con una odds ratio de 1,61. Conclusión: Aunque las principales causas de desequilibrio de Hardy-Weinberg en los controles son un sesgo de selección o un error de genotipificación, un riesgo competitivo de muerte asociado con el gen mutante puede ocasionar que la muestra de controles esté en desequilibrio de Hardy-Weinberg.Objective: To study the impact of competing risks on Hardy-Weinberg equilibrium and their consequences in case-control studies of gene-late onset disease association. Methods: Based on a population born in Hardy-Weinberg equilibrium for a particular gene, the genetic composition when the gene is associated with a lethal early-onset disease and its consequences on a late-onset disease can be deduced. Odds ratios estimates are unbiased in case-control studies when controls are sampled by density, even if the controls are in Hardy-Weinberg disequilibrium. Results: An example in which a mutant gene is associated with early mortality is presented, producing a departure from Hardy-Weinberg equilibrium; as a result, controls in later ages are in disequilibrium, producing an odds ratio equal to 1.61. Conclusion: Although the main causes of Hardy-Weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in Hardy-Weinberg disequilibrium among controls.

Objetivos: Identificar la influencia de las dimensiones del apartado personas y características sociodemográficas del modelo EFQM en la alta satisfacción de los trabajadores de un hospital comarcal. Métodos: Estudio transversal realizado en noviembre de 2003. Se ha utilizado la encuesta de satisfacción de las personas del País Vasco. Variable resultado: alto grado de satisfacción (percentil 75 o mayor). Variables independientes: características sociodemográficas de las personas y las organizacionales. Para cuantificar el grado de asociación se ha utilizado la odds ratio (OR) y su intervalo de confianza del 95% (IC del 95%). Los factores de confusión se ajustaron mediante regresión logística no condicional. Resultados: En una escala del 0 al 10, la satisfacción general obtuvo una puntuación media (desviación estándar) de 5,95 (2). El 25% de los trabajadores valoró su satisfacción general con el clima organizacional como ≥ 8. Los aspectos mejor considerados fueron: el plan medioambiental, la relación jerárquica, la promoción y el desarrollo profesional. Los apartados peor valorados han sido la retribución, el conocimiento y la identificación con los objetivos, y la formación. Las variables más relacionadas con el efecto fueron la percepción favorable de la formación (OR ajustada = 5,04; IC del 95%, 2,16-11,77), y el reconocimiento del trabajo realizado (OR ajustado = 4,68; IC del 95%, 2,20-10,08). Los factores sociodemográficos presentaron menor influencia sobre la satisfacción. Conclusiones: En nuestro hospital casi la mitad de las personas se consideran satisfechas/muy satisfechas con el clima organizacional. La satisfacción está fuertemente asociada a la valoración positiva de características propias de la organización.Objectives: To identify the influence of the dimensions of people items and sociodemographic characteristics included in the EFQM model on high satisfaction of healthcare workers in a district hospital. Methods: We performed a cross-sectional study in November 2003. The questionnaire used was the personal satisfaction survey of the Basque Country (Spain). The outcome measure was a high degree of satisfaction (75th percentile or higher). Independent variables were sociodemographic and organizational characteristics. The association among variables was assessed using odds ratios (OR) and their 95% confidence interval (CI). Adjustment for confounders was performed by unconditional logistic regression. Results: On a scale from 0 to 10, the mean general satisfaction score was 5.95 (standard deviation, 2). Twenty-five percent of workers gave their general satisfaction with the organizational climate a score of 8 or more points. The most positively considered features were the environmental policy, hierarchical relations, promotion, and professional development. The most negatively viewed items were salary, knowledge and identification of objectives, and training. The variables most closely related to outcome were a favorable perception of training (adjusted OR = 5.04; 95% CI, 2.16-11.77) and recognition of the work performed (adjusted OR = 4.68; 95% CI, 2.20-10.08). Sociodemographic factors had less influence on satisfaction. Conclusions: Almost half of the staff surveyed in our hospital were satisfied or highly satisfied with the organizational climate. Satisfaction was strongly associated with positive evaluation of organizational characteristics.