CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials

Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients’ lifestyle behaviors that may affect cancer’s progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation’s 2007 report “Cyberinfrastructure Vision for 21st Century Discovery” has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in advancing health-related CI

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development

A randomized trial of mailed questionnaires versus telephone interviews: Response patterns in a survey

<p>Abstract</p> <p>Background</p> <p>Data for health surveys are often collected using either mailed questionnaires, telephone interviews or a combination. Mode of data collection can affect the propensity to refuse to respond and result in different patterns of responses. The objective of this paper is to examine and quantify effects of mode of data collection in health surveys.</p> <p>Methods</p> <p>A stratified sample of 4,000 adults residing in Denmark was randomised to mailed questionnaires or computer-assisted telephone interviews. 45 health-related items were analyzed; four concerning behaviour and 41 concerning self assessment. Odds ratios for more positive answers and more frequent use of extreme response categories (both positive and negative) among telephone respondents compared to questionnaire respondents were estimated. Tests were Bonferroni corrected.</p> <p>Results</p> <p>For the four health behaviour items there were no significant differences in the response patterns. For 32 of the 41 health self assessment items the response pattern was statistically significantly different and extreme response categories were used more frequently among telephone respondents (Median estimated odds ratio: 1.67). For a majority of these mode sensitive items (26/32), a more positive reporting was observed among telephone respondents (Median estimated odds ratio: 1.73). The overall response rate was similar among persons randomly assigned to questionnaires (58.1%) and to telephone interviews (56.2%). A differential nonresponse bias for age and gender was observed. The rate of missing responses was higher for questionnaires (0.73 – 6.00%) than for telephone interviews (0 – 0.51%). The "don't know" option was used more often by mail respondents (10 – 24%) than by telephone respondents (2 – 4%).</p> <p>Conclusion</p> <p>The mode of data collection affects the reporting of self assessed health items substantially. In epidemiological studies, the method effect may be as large as the effects under investigation. Caution is needed when comparing prevalences across surveys or when studying time trends.</p

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

The DCDC2 deletion is not a risk factor for dyslexia

Dyslexia is a specific impairment in learning to read and has strong heritability. An intronic deletion within the DCDC2 gene, with ~8% frequency in European populations, is increasingly used as a marker for dyslexia in neuroimaging and behavioral studies. At a mechanistic level, this deletion has been proposed to influence sensory processing capacity, and in particular sensitivity to visual coherent motion. Our re-assessment of the literature, however, did not reveal strong support for a role of this specific deletion in dyslexia. We also analyzed data from five distinct cohorts, enriched for individuals with dyslexia, and did not identify any signal indicative of associations for the DCDC2 deletion with reading-related measures, including in a combined sample analysis (N=526). We believe we conducted the first replication analysis for a proposed deletion effect on visual motion perception and found no association (N=445 siblings). We also report that the DCDC2 deletion has a frequency of 37.6% in a cohort representative of the general population recruited in Hong Kong (N=220). This figure, together with a lack of association between the deletion and reading abilities in this cohort, indicates the low likelihood of a direct deletion effect on reading skills. Therefore, on the basis of multiple strands of evidence, we conclude that the DCDC2 deletion is not a strong risk factor for dyslexia. Our analyses and literature re-evaluation are important for interpreting current developments within multidisciplinary studies of dyslexia and, more generally, contribute to current discussions about the importance of reproducibility in science

Standard Outpatient Re-Evaluation for Patients Not Admitted to the Hospital After Emergency Department Evaluation for Acute Abdominal Pain

The aim of the present study was to investigate the efficacy and safety of standard outpatient re-evaluation for patients who are not admitted to the hospital after emergency department surgical consultation for acute abdominal pain. All patients seen at the emergency department between June 2005 and July 2006 for acute abdominal pain were included in a prospective study using a structured diagnosis and management flowchart. Patients not admitted to the hospital were given appointments for re-evaluation at the outpatient clinic within 24 h. All clinical parameters, radiological results, diagnostic considerations, and management proposals were scored prospectively. Five-hundred patients were included in this analysis. For 148 patients (30%), the final diagnosis was different from the diagnosis after initial evaluation. Eighty-five patients (17%) had a change in management after re-evaluation, and 20 of them (4%) were admitted to the hospital for an operation. Only 6 patients (1.2%) had a delay in diagnosis and treatment, which did not cause extra morbidity. Standard outpatient re-evaluation is a safe and effective means of improving diagnostic accuracy and helps to adapt management for patients that are not admitted to the hospital after surgical consultation for acute abdominal pain at the emergency department.Vascular Surger

Is Privacy Controllable?

One of the major views of privacy associates privacy with the control over information. This gives rise to the question how controllable privacy actually is. In this paper, we adapt certain formal methods of control theory and investigate the implications of a control theoretic analysis of privacy. We look at how control and feedback mechanisms have been studied in the privacy literature. Relying on the control theoretic framework, we develop a simplistic conceptual control model of privacy, formulate privacy controllability issues and suggest directions for possible research.Comment: The final publication will be available at Springer via http://dx.doi.org/ [in press

The action of a multidisciplinary team in the nutritional care of critically ill patients

Hospitalized patients may have special nutrient requirements imposed by a combination of malnutrition and enhanced utilization of nutrients resulting from the disease process. Nutritional support, mainly during critical stages of disease, should be provided safely and effectively. Several studies have evaluated the paper of a multidisciplinary team in the administration of a nutritional therapy. Individually, the majority of these studies are underpowered to evaluate an effect on the quality of nutritional care. With the objective to identify problems inherent to the supply of nutritional support to hospitalized patients and verify the impact of the actions of a multidisciplinary team on the quality of these procedures, we analysed articles that have been published between 1980 and 2004 about the role of the action of multidisciplinary teams in the care and nutritional outcome of hospitalized patients, especially those undergoing intensive care. The terms used for the search were: multidisciplinary team, nutritional support, parenteral nutrition, enteral feeding, critically ill, intensive care unit, critically ill child. Of 130 studies, intially identified, just 24 were selected, of which 14 compared the standard of nutritional therapy with and without the presence of a multidisciplinary team. The inadequate supply of nutrients, infection and metabolic complications and the excessive use of parenteral nutrition were the main problems detected in the supply of nutritional support to hospitalized patients. In the comparative studies, the presence of the multidisciplinary team improved the pattern of nutritional support, and reduced the incidence of complications and the costs.Pacientes hospitalizados podem ter necessidades nutricionais especiais em função da desnutrição e dos desequilíbrios metabólicos impostos pelas doenças. A terapia nutricional, principalmente nos estágios críticos das enfermidades, deve ser administrada de modo seguro e eficaz. Vários estudos têm avaliado o papel da equipe multidisciplinar na administração da terapia nutricional. Com o objetivo de identificar os problemas inerentes à administração da terapia nutricional em pacientes hospitalizados e verificar o impacto da atuação de uma equipe multidisciplinar na qualidade dos procedimentos, foi realizada uma revisão que analisou artigos publicados entre 1980 e 2004 sobre o papel da atuação de equipes multidisciplinares no cuidado e na evolução nutricional de pacientes hospitalizados, principalmente os que se encontravam sob cuidados intensivos. Os termos utilizados na pesquisa foram: multidisciplinary team, nutritional support, parente-ral nutrition, enteral feeding, critically ill, intensive care unit,critically ill child. Dos 130 estudos inicialmente identificados, foram selecionados 24, dos quais 14 compararam o padrão de terapia nutricional com e sem a presença da equipe multidisciplinar. Os principais problemas detectados na administração de terapia nutricional em pacientes hospitalizados foram a oferta inadequada de nutrientes, as complicações infecciosas e metabólicas e o uso excessivo de nutrição parenteral. Nos estudos comparativos, a presença da equipe multidisciplinar melhorou o padrão de oferta nutricional, reduziu a incidência de complicações e os custos.Universidade Federal de São Paulo (UNIFESP) Departamento de PediatriaHospital São Paulo Unidade de Cuidados Intensivos PediátricosHospital São Paulo Equipe Multidisciplinar de Terapia NutricionalUNIFESP, Depto. de PediatriaHospital São Paulo Unidade de Cuidados Intensivos PediátricosHospital São Paulo Equipe Multidisciplinar de Terapia NutricionalSciEL