On the combination of omics data for prediction of binary outcomes

Enrichment of predictive models with new biomolecular markers is an important task in high-dimensional omic applications. Increasingly, clinical studies include several sets of such omics markers available for each patient, measuring different levels of biological variation. As a result, one of the main challenges in predictive research is the integration of different sources of omic biomarkers for the prediction of health traits. We review several approaches for the combination of omic markers in the context of binary outcome prediction, all based on double cross-validation and regularized regression models. We evaluate their performance in terms of calibration and discrimination and we compare their performance with respect to single-omic source predictions. We illustrate the methods through the analysis of two real datasets. On the one hand, we consider the combination of two fractions of proteomic mass spectrometry for the calibration of a diagnostic rule for the detection of early-stage breast cancer. On the other hand, we consider transcriptomics and metabolomics as predictors of obesity using data from the Dietary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study, a population-based cohort, from Finland

The Incidence of Molluscum contagiosum among American Indians and Alaska Natives

The epidemiology of Molluscum contagiosum (MC) in the United States is largely unknown, despite the fact that the virus is directly communicable and large outbreaks occur. This study provides population-based estimates to describe the epidemiology of MC in the United States among American Indian and Alaska Native (AI/AN) persons. This population was selected because of the comprehensiveness and quality of available data describing utilization of out-patient services.Outpatient visits listing MC as a diagnosis in the Indian Health Service National Patient Information Reporting System during 2001-2005 were analyzed to assess patient characteristics, visit frequency and concurrent skin conditions. Outpatient visit rates and incidence rates were calculated based on known population denominators (retrospective cohort). Overall outpatient visit rates were also calculated for the general US population using national data. The average annual rate of MC-associated outpatient visits was 20.15/10,000 AI/AN persons for 2001-2005 (13,711 total visits), which was similar to the rate for the general US population (22.0/10,000 [95% CI: 16.9-27.1]). The incidence of MC-associated visits was 15.34/10,000. AI/AN children 1-4 years old had the highest incidence (77.12), more than twice that for children 5-14 years old (30.79); the incidence for infants (<1 year) was higher than that for adults. AI/AN persons living in the West region had the highest incidence, followed by those in the East and Alaska regions (26.96, 22.88 and 21.38, respectively). There were age-specific associations between MC and concurrent skin conditions (e.g., atopic dermatitis, eczema).This study highlights the need for periodic population-based measurements to assess trends in incidence and healthcare utilization for MC in the United States. High rates of MC were found among AI/AN persons, especially among children <15 years old. The AI/AN population would benefit from greater availability of effective strategies for prevention and treatment of MCV infection

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

BACKGROUND: \u3b1/\u3b2-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5' regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies

‘My child did not like using sun protection’: practices and perceptions of child sun protection among rural black African mothers

Abstract Background Photodamage is partially mitigated by darker skin pigmentation, but immune suppression, photoaging and cataracts occur among individuals with all skin types. Methods To assess practices and acceptability to Black African mothers of sun protection equipment for their children living in a rural area, participants were recruited at the time of their child’s 18-month vaccinations. Mothers completed a baseline questionnaire on usual sun behaviours and sun protection practices. They were then provided with sun protection equipment and advice. A follow-up questionnaire was administered two weeks later. Results Mothers reported that during the week prior to the baseline questionnaire, children spent on average less than 1 hour of time outdoors (most often spent in the shade). Most mothers (97%) liked the sun protection equipment. However, many (78 of 86) reported that their child did not like any of the sun protection equipment and two-thirds stated that the sun protection equipment was not easy to use. Conclusions Among Black Africans in rural northern South Africa, we found a mismatch between parental preferences and child acceptance for using sun protection when outdoors. A better understanding of the health risks of incidental excess sun exposure and potential benefits of sun protection is required among Black Africans

Vitiligo in children

Background: Vitiligo is an acquired depigmentary disorder affecting around 1% of the world&apos;s population. In 25% of cases it has its onset prior to the age of 14 years. Data sources: Articles on vitiligo in children published after 1995 were retrieved from PubMed. The prevalence, etiology, clinical presentation, differential diagnosis, treatment and management of vitiligo in children were summarized. Results: Vitiligo is characterized by acquired, sharply demarcated depigmented macules or patches on the skin, the mucous membranes and/or white hair and it is mainly differentiated from congenital achromic skin lesions. It is frequently associated with various autoimmune diseases. Hashimoto&apos;s thyroiditis is the most common association in children. Information on the nature, possible causes and course of the disease leads to acceptance of the disorder and higher compliance with the treatment. The choice of medical treatment depends on the type, location and duration of lesions as well as the eagerness of the child and his/her parents to pursue therapy. Conclusion: The management of childhood vitiligo includes information and reassurance of young patients and their parents on the disease, thyroid investigation, avoidance of trigger factors, topical treatment and proper follow-up. © 2009 Children&apos;s Hospital, Zhejiang University School of Medicine and Springer Berlin Heidelberg