A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data

Project Learn: The Development and Assessment of a Cross-Platform Tutor Finder

creation of an online tutor finder application, called "Project Learn", aimed to address the difficulty in finding a tutor for any subject in today's fast-paced world. To achieve this, the study utilized a developmental research design to create an application that connects students with qualified tutors. Students can view a tutor's background and the subjects they teach before choosing the best fit for their needs. To evaluate the system's technical quality, a survey was conducted with 20 end-users and 10 IT-experts. The survey was based on ISO 25010 software quality standards and included components such as functional suitability, reliability, usability, performance efficiency, security, compatibility, portability, and maintainability. The survey results indicated that both the end-users and IT-experts rated the system above 3.26, which equates to a "very acceptable" grade. This suggests that the system's overall internal and external performance exhibited consistency and met the compliance requirements. However, there is still room for improvement to better serve the needs of its users. The success of the development and assessment of the online tutor finder application demonstrates the potential impact it can have in connecting students with qualified tutors. The study's use of a developmental research design and adherence to ISO 25010 software quality standards ensured the technical quality of the system. With further improvements, the application can continue to make a significant impact in helping students find the right tutor to achieve academic success

Supplementary Materials for U-Th dating of carbonate crusts reveals Neanderthal origin of Iberian cave art

Materiales suplementarios al artículo de Science 2018 sobre las dataciones de arte rupestre en la Península Ibérica mediante U-TH

The karst site of Las Palomas (Guadalteba County, Málaga, Spain): A preliminary study of its MiddleeLate Pleistocene archaeopaleontological record

Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Consortium, have provided a number of lithic tools and knapping products that may be ascribed to the Mode III technotypological tradition as well as remains of a number of large mammal species typical of MiddleeLate Pleistocene times. Topographic measurements help to place this ancient cave within a karst landform. This discovery opens up new perspectives in the research on the Neanderthal groups that inhabited the valleys of Guadalteba and Turón rivers in the middle basin of the Guadalhorce River, and thus in the southern region of the Iberian Peninsula

A plasma fatty acid profile associated to type 2 diabetes development: from the CORDIOPREV study

Purpose: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. Methods: We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. Results: FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04–3.37) in the Training set, and an HR of 2.14 (95% CI 1.50–2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). Conclusión: Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias

<p>Abstract</p> <p>Background</p> <p>Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias.</p> <p>Methods</p> <p>A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables.</p> <p>Results</p> <p>Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93).</p> <p>Conclusion</p> <p>Pre-hospital oral antibiotherapy appears to reduce IMD mortality.</p

An epidemiological model for prediction of endometrial cancer risk in Europe

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation

Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model