Linkage analysis of longitudinal data and design consideration

BACKGROUND: Statistical methods have been proposed recently to analyze longitudinal data in genetic studies. So far, little attention has been paid to examine the relationship among key factors in genetic longitudinal studies including power, the number of families or sibships, and the number of repeated measures per individual subjects. RESULTS: We proposed a variance component model that extends classic variance component models for a single quantitative trait to mapping longitudinal traits. Our model includes covariate effects and allows genetic effects to vary over time. Using our proposed model, we examined the power, pedigree structures, and sample size through simulation experiments. CONCLUSION: Our simulation results provide useful insights into the study design for genetic, longitudinal studies. For example, collecting a small number of large sibships is much more powerful than collecting a large number of small sibships or increasing the number of repeated measures, when the total number of measurements is comparable

Holocene evolution of a barrier island system, Ria Formosa, South Portugal

Holocene evolution of the Ria Formosa barrier island system was studied through the examination of a large subsurface dataset acquired from 191 boreholes and five seismic refraction profiles. Two boreholes with total depths of 26 and 16.5 m were selected for a multi-proxy detailed laboratory analysis, including mean grain size distribution, organic matter (OM) content, color variation, shell identification, and benthic foraminifera assemblages. Selected cores are thought to be representative of the identified depositional sub-basins. Subsurface age data from 16 AMS C-14 dated samples were plotted against depth and resulted in a coherent age model of sedimentary infill. The system evolution was largely controlled by sediment availability, accommodation space, and Holocene sea level rise, first at a rapid rate of 7 mm/yr from 10 kcal yr BP to 7.25 kcal yr BP, followed by a slowdown to 1.1 mm/yr until present. A conceptual model for the origin and Holocene evolution of the Ria Formosa barrier island system implies three main steps, leading to the present system geomorphology: (1) marine flooding of incised palaeovalleys by the rapid transgression of palaeovalleys in the early Holocene(2) development of a proto-barrier island chain perched on Pleistocene detritic headlands and steeper interfluve areas during the early to middle Holoceneand (3) full development of the barrier islands chain and enclosing of the coastal lagoon, followed by the maturation of the system with subsequent siltation and salt marsh expansion from the middle Holocene until present. The onset of barrier system formation dates back to ca. 8 kcal yr BP, predating previously proposed age.SIHER project [PTDC/CTE-GIX112236/2009]EU Erasmus Mundus Joint Doctorate in Marine and Coastal Management (MACOMA) fellowship grant, under University of AlgarveEU Erasmus Mundus Joint Doctorate in Marine and Coastal Management (MACOMA) fellowship grant, under University of Cadi

Giant serous cystadenoma arising from an accessory ovary in a morbidly obese 11-year-old girl: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ectopic ovarian tissue is an unusual entity, especially if it is an isolated finding thought to be of embryological origin.</p> <p>Case presentation</p> <p>An 11-year-old, morbidly obese female presented with left flank pain, nausea, and irregular menses. Various diagnostic procedures suggested a large ovarian cyst, and surgical resection was performed.</p> <p>Conclusion</p> <p>Histologically, the resected mass was not of tubal origin as suspected, but a serous cystadenoma arising from ovarian tissue. The patient's two normal, eutopic ovaries were completely uninvolved and unaffected. A tumor arising from ectopic ovarian tissue of embryological origin seems the most likely explanation. We suggest refining the descriptive nomenclature so as to more precisely characterize the various presentations of ovarian ectopia.</p

Depression among women living in the outskirts of São Paulo, Southeastern Brasil

OBJECTIVE: To assess the meaning of depression in women diagnosed with the disorder, and the context of care given by the psychiatrists who follow them up. METHODS: Qualitative study performed in Embu, outskirt of São Paulo, between August 2002 and January 2003. Etnographic observation and in-depth interview were carried out with 16 women diagnosed with depression in primary care, and four psychiatrists. After exhaustive reading, data were grouped into categories and assessed. The assessment of outcomes was based on the concept of culture. RESULTS: Women interviewed are well aware of the disorder, and accept treatment based on medication. For psychiatrists, depression is a term understood by the common sense. All women interviewed identified the onset of the disease from a past event such as: death of a son, violent episodes connected with drug traffic, unemployment, and partners' aggressiveness. Violence was common in the every day life of the interviewed women both inside and outside their homes. CONCLUSIONS: For these women, depression is a way to express their feelings, such as unhappiness in a context of poverty and violence. Psychiatrists go beyond their clinical functions and play an important role on reorganizing the daily life of these women.OBJETIVO: Analisar o significado da depressão para mulheres diagnosticadas com o transtorno e o contexto do atendimento realizado pelos psiquiatras que as acompanham. MÉTODOS: Estudo qualitativo realizado no município de Embu, na Grande São Paulo, entre agosto de 2002 e janeiro de 2003. Foram realizadas observação etnográfica e entrevistas em profundidade com 16 mulheres diagnosticadas com depressão, pacientes de uma Unidade Básica de Saúde, e quatro psiquiatras. Após a leitura exaustiva, os dados foram agrupados em categorias e analisados. A interpretação dos resultados baseou-se no conceito de cultura. RESULTADOS: As entrevistadas tinham ampla noção do transtorno, aceitando o tratamento com medicação. Para os psiquiatras, a depressão é um termo assimilado pelo senso-comum. Todas as entrevistadas identificaram a origem da doença em eventos passados, como: morte de filho, episódios violentos ligados ao tráfico de drogas, desemprego e agressividade do companheiro. A violência era comum no cotidiano das entrevistadas, tanto fora como dentro de casa. CONCLUSÕES: Para essas mulheres, a depressão era uma forma de expressar sentimentos, como a infelicidade num contexto de pobreza e violência. Os psiquiatras extrapolam as suas funções clínicas e têm um papel na reorganização do cotidiano dessas mulheres.Universidade Católica de Santos Programa de Mestrado em Saúde ColetivaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsiquiatriaUNIFESP, Depto. de PsiquiatriaSciEL

Factors Associated with Colposcopy-Histopathology Confirmed Cervical Intraepithelial Neoplasia among HIV-Infected Women from Rio De Janeiro, Brazil

Introduction: Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods:Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+diagnosis. Results:The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+was 6.0%. Factors associated with CIN2+diagnosis in the multivariate model were age,years compared to$35 years (aPR = 3.22 95CD4 T-cell count,350 cells/mm3 when compared to$350 cells/mm3 (aPR = 6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR = 2.68 95%CI 0.99–7.24). Discussion:Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of wome

Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin

A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%). We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington's disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments