Identification of Driver Epistatic Gene Pairs Combining Germline and Somatic Mutations in Cancer.

Cancer arises from the complex interplay of various factors. Traditionally, the identification of driver genes focuses primarily on the analysis of somatic mutations. We describe a new method for the detection of driver gene pairs based on an epistasis analysis that considers both germline and somatic variations. Specifically, the identification of significantly mutated gene pairs entails the calculation of a contingency table, wherein one of the co-mutated genes can exhibit a germline variant. By adopting this approach, it is possible to select gene pairs in which the individual genes do not exhibit significant associations with cancer. Finally, a survival analysis is used to select clinically relevant gene pairs. To test the efficacy of the new algorithm, we analyzed the colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD) samples available at The Cancer Genome Atlas (TCGA). In the analysis of the COAD and LUAD samples, we identify epistatic gene pairs significantly mutated in tumor tissue with respect to normal tissue. We believe that further analysis of the gene pairs detected by our method will unveil new biological insights, enhancing a better description of the cancer mechanism.

The acetabulum as an adult age marker and the new IDADE2 (the IDADE2 web page).

OBJECTIVE: In 2006, an age estimation method was proposed utilizing Bayesian inference to interpret age-progressive changes in the acetabulum. This was accompanied by the IDADE2 software to facilitate calculations. However, the MS-DOS operating system on which the software was based became obsolete. The main goal of this article is to present the new IDADE2, which incorporates web-based facilities. MATERIALS AND METHODS: The original IDADE2 has been re-written in R and presented as a web page. As in the original, this web page uses Bayesian inference to estimate age of unidentified individuals. The materials used to create the reference datasets of this web page include acetabular scores from documented skeletal samples from Spain (n = 24♀ and 52♂), Portugal (n = 317♀ and 294♂), and the US (n = 370♀ and 456♂). RESULTS: The IDADE2 website has eight sections. Six of these are informative to guide the user. The other two (Option 1 and Option 2) are dedicated to estimating age at death. Option 1 allows users to estimate the age of individual(s) in their test sample based on our reference data of acetabular scores. Option 2 allows users to estimate age from the acetabulum with their own reference and test collections or-if the users prefer-another age marker and method of choice. DISCUSSION: The IDADE2 website is applicable both to forensic anthropological casework on single individuals and to bioarchaeological analyses of large skeletal samples. This website is easy to use and freely accessible, responding to previous critiques and incorporating method advancements.

Hospital admissions among immigrants from low-income and foreign citizens from high-income countries in Spain in 2000-2012.

Over the last decade, the number of foreign nationals in Spain has increased. Our aim was to report the trends in hospital admissions, differentiating between foreign nationals from high-income countries (HICs) and from low- and middle-income countries (LMICs) in a public hospital. A retrospective analysis of hospital admissions in patients aged ⩾15years between 2000 and 2012 was performed by means of hospital information systems at a public hospital in the city of Alicante, Spain. During the period of the study, 387,862 patients were admitted: 32,020 (8.3%) were foreign, 22,446 (5.8%) were from LMICs, and 9574 (2.5%) were from HICs. The number of foreign nationals, foreign nationals from LMICs, and foreign nationals from HICs admitted increased from 1019, 530, and 489 in 2000 to 2925, 2097, and 828, respectively in 2012. A total of 27.5% of patients were admitted for pregnancy, childbirth, and puerperium, especially foreign nationals from LMICs (34.3%), and 14.1% of foreign nationals were admitted for cardiovascular diseases (14.1%), which were more common in those from HICs (26.3%). The number of admissions among foreign nationals from LMICs increased significantly in all the diagnoses, but in pregnancy, childbirth, and puerperium, the increase was higher. In conclusion, nearly one out of 10 adult patients admitted to our hospital was foreign, mainly from LMICs, and the main reason for admission was diagnoses related to pregnancy, childbirth, and puerperium.

Hospital admissions in Alicante (Spain): a comparative analysis of foreign citizens from high-income countries, immigrants from low-income countries, and Spanish citizens.

BACKGROUND: Over the last decade, the number of foreign citizens (FCs) in Spain has increased. There is no doubt that their health has become a relevant subject from the point of view of public healthcare. Our study aimed to describe hospital admission rates, diagnoses at hospital discharge, and mortality during hospital admissions in FCs from high-income countries (FCHICs), FCs from low-income countries (FCLICs), and autochthonous citizens (ACs). METHODS: A cross-sectional study was performed at two public hospitals in the city of Alicante (Spain) and its surrounding area. Utilization rates were estimated. Multivariate analysis adjusting for age and sex was performed on hospital admission rates, diagnoses at hospital discharge, service of admission, and mortality during hospital admission in FCHICs and FCLICs compared with ACs (adjusted odds ratio [AOR] with 95% confidence intervals [CI]). RESULTS: 42,839 patients ≥15 years were discharged from the hospitals. The utilization rate was lower in FCs than ACs, whose crude rate ratio was 0.676 (95% CI: 0.656-0.696). FCHICs had more risk of being diagnosed at discharge in the categories of the circulatory system (AOR: 1.55; 95% CI: 1.35-1.77), neoplasms (AOR: 1.21; 95% CI: 1.03-1.42), and injury and poisoning (AOR: 1.33; 95% CI: 1.11-1.58). FCLICs had more risk of being diagnosed in the categories of pregnancy, childbirth & puerperium (AOR: 1.33; 95% CI: 1.29-1.59), and injury and poisoning (AOR: 1.19; 95% CI: 1.03-1.36), and less risk in the mental disorder category (AOR: 0.32; 95% CI: 0.22-0.45). The length of hospitalization (in days) was lower in FCLICs (median: 3; IQR: 2-6) than both ACs (median: 4; IQR: 2-8) and FCHICs (median: 4; IQR: 2-8) (p < 0.001). The mortality rates on admission of ACs, FCHICs, and FCLICs were 4.2%, 3.3%, and 1.3%, respectively, but after adjusting for age and sex, the mortality rate risks were similar in FCHICs and FCLICs. CONCLUSION: First, FCs utilized hospitalization less when compared with ACs. Second, the hospitalization profile for FCHICs was similar to ACs, with more problems in the circulatory system, and the hospitalization profile for FCLICs was different compared with ACs, with more admissions for pregnancy, childbirth & puerperium.

Characteristics and outcome in nonagenarians admitted in general internal medicine and other specialties.

UNLABELLED: To describe the characteristics of nonagenarians admitted to the surgical and medical divisions at a tertiary hospital and compare them with nonagenarians admitted to other hospital care services. METHODS: A retrospective study of all hospital discharge episodes via the registry of the Basic Minimum Data Set at the Hospital General Universitario de Alicante from January 2007 until December 2011. RESULTS: Of the 165,870 hospitalizations, 2461 (1.5%) were nonagenarians. The highest number of admitted nonagenarians was in the Division of General Internal Medicine (DGIM) (n=751), followed by the short stay unit (SSU) (n=633). The rate of nonagenarians per 100 admissions to the DGIM was 10.2, significantly higher than that of those admitted to the SSU (6.2) (p<0.001), the service of orthopedic and trauma surgery (2.2) (p<0.001), and other specialties. Females comprised 64.8% of the nonagenarians. Mortality was 17% for the nonagenarians admitted, while for those admitted to the DGIM it was 27.7%. Those hospitalized in the SSU had a lower risk of death during hospitalization (8.1%) (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.16-0.32) and a greater risk of being admitted for diseases and disorders of the circulatory system (OR: 1.58, 95% CI: 1.22-2.05), particularly for heart failure and shock (OR: 1.82, 95% CI: 1.30-2.53), and being discharged with home hospitalization (OR: 8.05, 95% CI: 5.5-11.8). CONCLUSIONS: Nonagenarian patients represent a tenth of those admitted to the DGIM. The profile of nonagenarians admitted to the DGIM is different from other hospital services. Hospital mortality for nonagenarians admitted to the DGIM is high and superior to other hospital services.