A Genome-Wide Association Study of Pulmonary Function Measures in the Framingham Heart Study

The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09). One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04). The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation

A semidefinite programming approach for solving multiobjective linear programming

Several algorithms are available in the literature for finding the entire set of Pareto-optimal solutions in MultiObjective Linear Programming (MOLP). However, it has not been proposed so far an interior point algorithm that finds all Pareto-optimal solutions of MOLP. We present an explicit construction, based on a transformation of any MOLP into a finite sequence of SemiDefinite Programs (SDP), the solutions of which give the entire set of Pareto-optimal extreme points solutions of MOLP. These SDP problems are solved by interior point methods; thus our approach provides a pseudopolynomial interior point methodology to find the set of Pareto-optimal solutions of MOLP.Junta de AndalucíaFondo Europeo de Desarrollo RegionalMinisterio de Ciencia e Innovació

Neuroendocrine carcinoma of the seminal vesicles presenting with Lambert Eaton syndrome: a case report

Lambert Eaton syndrome may be the initial symptom of a seminal vesicle mass. Diagnosis needs to be obtained by transrectal biopsy and chemotherapy may delay progression of the tumor

Evaluation of mobile learning: Students' experiences in a new rural-based medical school

<p>Abstract</p> <p>Background</p> <p>Mobile learning (ML) is an emerging educational method with success dependent on many factors including the ML device, physical infrastructure and user characteristics. At Gippsland Medical School (GMS), students are given a laptop at the commencement of their four-year degree. We evaluated the educational impact of the ML program from students' perspectives.</p> <p>Methods</p> <p>Questionnaires and individual interviews explored students' experiences of ML. All students were invited to complete questionnaires. Convenience sampling was used for interviews. Quantitative data was entered to SPSS 17.0 and descriptive statistics computed. Free text comments from questionnaires and transcriptions of interviews were thematically analysed.</p> <p>Results</p> <p>Fifty students completed the questionnaire (response rate 88%). Six students participated in interviews. More than half the students owned a laptop prior to commencing studies, would recommend the laptop and took the laptop to GMS daily. Modal daily use of laptops was four hours. Most frequent use was for access to the internet and email while the most frequently used applications were Microsoft Word and PowerPoint. Students appreciated the laptops for several reasons. The reduced financial burden was valued. Students were largely satisfied with the laptop specifications. Design elements of teaching spaces limited functionality. Although students valued aspects of the virtual learning environment (VLE), they also made many suggestions for improvement.</p> <p>Conclusions</p> <p>Students reported many educational benefits from school provision of laptops. In particular, the quick and easy access to electronic educational resources as and when they were needed. Improved design of physical facilities would enhance laptop use together with a more logical layout of the VLE, new computer-based resources and activities promoting interaction.</p

Therapeutic issues in HIV/HCV-coinfected patients

The importance of treating hepatitis C virus (HCV)-associated morbidities in a growing population of patients coinfected with human immunodeficiency virus (HIV) has increased since the introduction of highly active antiretroviral therapy. As a result, investigative attention is turning to HCV-related liver disease and treatment-associated issues in coinfection. HIV/HCV-coinfected patients have higher HCV RNA loads and show more rapid progression of fibrosis than do monoinfected patients. Combination therapy with pegylated interferon plus ribavirin (RBV) is the standard of care for HCV in coinfected patients. Therapy slows fibrosis progression, but toxicity prevents identification of the most effective RBV dose. Coinfected patients have about a threefold greater risk of antiretroviral therapy-associated hepatotoxicity than patients with HIV only. Other challenges include anaemia, mitochondrial toxicity, drug–drug interactions and leucopenia. Thus, chronic hepatitis C should be treated in HIV/HCV-coinfected patients, but steps must be taken to prevent and treat potential toxicities. The first European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients was held March 2005 in Paris to address these issues. This article reviews the peer-reviewed literature and expert opinion published from 1990 to 2005, and compares results with presentations and recommendations from the Consensus Conference to best present current issues in coinfection

Abstinence-Only Education and Teen Pregnancy Rates: Why We Need Comprehensive Sex Education in the U.S

The United States ranks first among developed nations in rates of both teenage pregnancy and sexually transmitted diseases. In an effort to reduce these rates, the U.S. government has funded abstinence-only sex education programs for more than a decade. However, a public controversy remains over whether this investment has been successful and whether these programs should be continued. Using the most recent national data (2005) from all U.S. states with information on sex education laws or policies (N = 48), we show that increasing emphasis on abstinence education is positively correlated with teenage pregnancy and birth rates. This trend remains significant after accounting for socioeconomic status, teen educational attainment, ethnic composition of the teen population, and availability of Medicaid waivers for family planning services in each state. These data show clearly that abstinence-only education as a state policy is ineffective in preventing teenage pregnancy and may actually be contributing to the high teenage pregnancy rates in the U.S. In alignment with the new evidence-based Teen Pregnancy Prevention Initiative and the Precaution Adoption Process Model advocated by the National Institutes of Health, we propose the integration of comprehensive sex and STD education into the biology curriculum in middle and high school science classes and a parallel social studies curriculum that addresses risk-aversion behaviors and planning for the future

Rule-based knowledge aggregation for large-scale protein sequence analysis of influenza A viruses

Background: The explosive growth of biological data provides opportunities for new statistical and comparative analyses of large information sets, such as alignments comprising tens of thousands of sequences. In such studies, sequence annotations frequently play an essential role, and reliable results depend on metadata quality. However, the semantic heterogeneity and annotation inconsistencies in biological databases greatly increase the complexity of aggregating and cleaning metadata. Manual curation of datasets, traditionally favoured by life scientists, is impractical for studies involving thousands of records. In this study, we investigate quality issues that affect major public databases, and quantify the effectiveness of an automated metadata extraction approach that combines structural and semantic rules. We applied this approach to more than 90,000 influenza A records, to annotate sequences with protein name, virus subtype, isolate, host, geographic origin, and year of isolation. Results: Over 40,000 annotated Influenza A protein sequences were collected by combining information from more than 90,000 documents from NCBI public databases. Metadata values were automatically extracted, aggregated and reconciled from several document fields by applying user-defined structural rules. For each property, values were recovered from ≥88.8% of records, with accuracy exceeding 96% in most cases. Because of semantic heterogeneity, each property required up to six different structural rules to be combined. Significant quality differences between databases were found: GenBank documents yield values more reliably than documents extracted from GenPept. Using a simple set of semantic rules and a reasoner, we reconstructed relationships between sequences from the same isolate, thus identifying 7640 isolates. Validation of isolate metadata against a simple ontology highlighted more than 400 inconsistencies, leading to over 3,000 property value corrections. Conclusion: To overcome the quality issues inherent in public databases, automated knowledge aggregation with embedded intelligence is needed for large-scale analyses. Our results show that user-controlled intuitive approaches, based on combination of simple rules, can reliably automate various curation tasks, reducing the need for manual corrections to approximately 5% of the records. Emerging semantic technologies possess desirable features to support today's knowledge aggregation tasks, with a potential to bring immediate benefits to this field

Anatomical, Clinical and Electrical Observations in Piriformis Syndrome

<p>Abstract</p> <p>Background</p> <p>We provided clinical and electrical descriptions of the piriformis syndrome, contributing to better understanding of the pathogenesis and further diagnostic criteria.</p> <p>Methods</p> <p>Between 3550 patients complaining of sciatica, we concluded 26 cases of piriformis syndrome, 15 females, 11 males, mean age 35.37 year-old. We operated 9 patients, 2 to 19 years after the onset of symptoms, 5 had piriformis steroids injection. A dorsolumbar MRI were performed in all cases and a pelvic MRI in 7 patients. The electro-diagnostic test was performed in 13 cases, between them the H reflex of the peroneal nerve was tested 7 times.</p> <p>Results</p> <p>After a followup 1 to 11 years, for the 17 non operated patients, 3 patients responded to conservative treatment. 6 of the operated had an excellent result, 2 residual minor pain and one failed. 3 new anatomical observations were described with atypical compression of the sciatic nerve by the piriformis muscle.</p> <p>Conclusion</p> <p>While the H reflex test of the tibial nerve did not give common satisfaction in the literature for diagnosis, the H reflex of the peroneal nerve should be given more importance, because it demonstrated in our study more specific sign, with six clinical criteria it contributed to improve the method of diagnosis. The cause of this particular syndrome does not only depend on the relation sciatic nerve-piriformis muscle, but the environmental conditions should be considered with the series of the anatomical anomalies to explain the real cause of this pain.</p

Calculation of molecular thermochemical data and their availability in databases

Thermodynamic properties of molecules can be obtained by experiment, by statistical mechanics in conjunction with electronic structure theory and by empirical rules like group additivity. The latter two methods are briefly re-viewed in this chapter. The overview of electronic structure methods is intended for readers less experienced in electronic structure theory and focuses on concepts without going into mathematical details. This is followed by a brief description of group additivity schemes; finally, an overview of databases listing reliable thermochemical data is given