Construction of endophenotypes for complex diseases in the presence of heterogeneity

Endophenotypes such as behavior disorders have been increasingly adopted in genetic studies for complex traits. For efficient gene mapping, it is essential that an endophenotype is associated with the disease of interest and is inheritable or co-segregating within families. In this study, we proposed a strategy to construct endophenotypes to analyze the Genetic Analysis Workshop 14 simulated dataset. Initially, generalized estimating equation models were employed to identify phenotypes that were correlated to the disease (affected status) in combination with the family structures in data. Endophenotypes were then constructed with consideration of heterogeneity as functions of the identified phenotypes. Genome scans on the constructed endophenotypes were carried out using family-based association analysis. For comparison, genome scans were also performed with the original affected status. The family-based association analysis using the endophenotypes correctly identified the same susceptible gene in about 80 of the 100 replicates

Momentum relaxation from the fluid/gravity correspondence

We provide a hydrodynamical description of a holographic theory with broken translation invariance. We use the fluid/gravity correspondence to systematically obtain both the constitutive relations for the currents and the Ward identity for momentum relaxation in a derivative expansion. Beyond leading order in the strength of momentum relaxation, our results differ from a model previously proposed by Hartnoll et al. As an application of these techniques we consider charge and heat transport in the boundary theory. We derive the low frequency thermoelectric transport coefficients of the holographic theory from the linearised hydrodynamics.Comment: 19 pages + appendix, v2: references added, typos corrected, v3: version published in JHE

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Numerical comparison of the closing dynamics of a new trileaflet and a bileaflet mechanical aortic heart valve

[[abstract]]The closing velocity of the leaflets of mechanical heart valves is excessively rapid and can cause the cavitation phenomenon. Cavitation bubbles collapse and produce high pressure which then damages red blood cells and platelets. The closure mechanism of the trileaflet valve uses the vortices in the aortic sinus to help close the leaflets, which differs from that of the monoleaflet or bileaflet mechanical heart valves which mainly depends on the reverse flow. We used the commercial software program Fluent to run numerical simulations of the St. Jude Medical bileaflet valve and a new trileaflet mechanical heart valve. The results of these numerical simulations were validated with flow field experiments. The closing velocity of the trileaflet valve was clearly slower than that of the St. Jude Medical bileaflet valve, which would effectively reduce the occurrence of cavitation. The findings of this study are expected to advance the development of the trileaflet valve.[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙

Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005

<p>Abstract</p> <p>Background</p> <p>The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population.</p> <p>Methods</p> <p>A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases.</p> <p>Results</p> <p>During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation,$504 for the elbow, $1,232 for the wrist,$1,103 for the hip, $1,888 for the knee, and$1,248 for the ankle.</p> <p>Conclusions</p> <p>In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture-dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure.</p

Nationwide Surveillance of Influenza during the Pandemic (2009–10) and Post-Pandemic (2010–11) Periods in Taiwan

INTRODUCTION: Although WHO declared the world moving into the post-pandemic period on August 10, 2010, influenza A(H1N1) 2009 virus continued to circulate globally. Its impact was expected to continue during the 2010-11 influenza season. This study describes the nationwide surveillance findings of the pandemic and post-pandemic influenza periods in Taiwan and assesses the impact of influenza A(H1N1) 2009 during the post-pandemic period. METHODS: The Influenza Laboratory Surveillance Network consisted of 12 contract laboratories for collecting and testing samples with acute respiratory tract infections. Surveillance of emergency room visits and outpatient department visits for influenza-like illness (ILI) were conducted using the Real-Time Outbreak and Disease Surveillance system and the National Health Insurance program data, respectively. Hospitalized cases with severe complications and deaths were reported to the National Notifiable Disease Surveillance System. RESULTS: During the 2009-10 influenza season, pandemic A(H1N1) 2009 was the predominant circulating strain and caused 44 deaths. However, the 2010-11 influenza season began with A(H3N2) being the predominant circulating strain, changing to A(H1N1) 2009 in December 2010. Emergency room and outpatient department ILI surveillance displayed similar trends. By March 31, 2011, there were 1,751 cases of influenza with severe complications; 50.1% reported underlying diseases. Of the reported cases, 128 deaths were associated with influenza. Among these, 93 (72.6%) were influenza A(H1N1) 2009 and 30 (23.4%) A(H3N2). Compared to the pandemic period, during the immediate post-pandemic period, increased number of hospitalizations and deaths were observed, and the patients were consistently older. CONCLUSIONS: Reemergence of influenza A(H1N1) 2009 during the 2010-11 influenza season had an intense activity with age distribution shift. To further mitigate the impact of future influenza epidemics, Taiwan must continue its multifaceted influenza surveillance systems, remain flexible with antiviral use policies, and revise the vaccine policies to include the population most at risk

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

<p>Abstract</p> <p>Background</p> <p>We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).</p> <p>Methods</p> <p>To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.</p> <p>Results</p> <p>As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.</p> <p>Conclusions</p> <p>We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.</p

A tryptophan-rich peptide acts as a transcription activation domain

<p>Abstract</p> <p>Background</p> <p>Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures.</p> <p>Results</p> <p>We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide <it>per se </it>retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W₅) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W₇), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W₇mediates transcription activation through interacting with the general transcription factor, TFIIB.</p> <p>Conclusions</p> <p>Since W₇shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.</p

The effect of turbulent viscous shear stress on red blood cell hemolysis

[[abstract]]Non-physiologic turbulent flow occurs in medical cardiovascular devices resulting in hemodynamic stresses that may damage red blood cells (RBC) and cause hemolysis. Hemolysis was previously thought to result from Reynolds shear stress (RSS) in turbulent flows. A more recent hypothesis suggests that turbulent viscous shear stresses (TVSS) at spatial scales similar in size to RBCs are related to their damage. We applied two-dimensional digital particle image velocimetry to measure the flow field of a free-submerged axisymmetric jet that was utilized to hemolyze porcine RBCs in selected locations. Assuming a dynamic equilibrium for the sub-grid scale (SGS) energy flux between the resolved and the sub-grid scales, the SGS energy flux was calculated from the strain rate tensor computed from the resolved velocity fields. The SGS stress was determined by the Smagorinsky model, from which the turbulence dissipation rate and then TVSS were estimated. Our results showed the hemolytic threshold of the Reynolds stresses was up to 517 Pa, and the TVSSs were at least an order of magnitude less than the RSS. The results provide further insight into the relationship between turbulence and RBC damage.[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]JP