Regression-Based Association Analysis with Clustered Haplotypes through Use of Genotypes

Haplotype-based association analysis has been recognized as a tool with high resolution and potentially great power for identifying modest etiological effects of genes. However, in practice, its efficacy has not been as successfully reproduced as expected in theory. One primary cause is that such analysis tends to require a large number of parameters to capture the abundant haplotype varieties, and many of those are expended on rare haplotypes for which studies would have insufficient power to detect association even if it existed. To concentrate statistical power on more-relevant inferences, in this study, we developed a regression-based approach using clustered haplotypes to assess haplotype-phenotype association. Specifically, we generalized the probabilistic clustering methods of Tzeng to the generalized linear model (GLM) framework established by Schaid et al. The proposed method uses unphased genotypes and incorporates both phase uncertainty and clustering uncertainty. Its GLM framework allows adjustment of covariates and can model qualitative and quantitative traits. It can also evaluate the overall haplotype association or the individual haplotype effects. We applied the proposed approach to study the association between hypertriglyceridemia and the apolipoprotein A5 gene. Through simulation studies, we assessed the performance of the proposed approach and demonstrate its validity and power in testing for haplotype-trait association

Stretchable Conjugated Rod–Coil Poly(3-hexylthiophene)-<i>block</i>-poly(butyl acrylate) Thin Films for Field Effect Transistor Applications

We report the synthesis, morphology, and properties of poly­(3-hexylthiophene)-<i>block</i>-poly­(butyl acrylate) (P3HT-<i>b</i>-PBA) for stretchable electronics applications, which are consisted of semiconducting P3HT and low glass transistion temperature (<i>T</i>_g) PBA blocks. The P3HT-<i>b</i>-PBA thin films self-assembled into fibrillar-like nanostructures and maintained the edge-on oreientation even at a low P3HT composition, based on the results from atomic force microscopy (AFM) and grazing incidence X-ray diffraction (GIXD). By varying the P3HT/PBA ratio, the tensile modulus decreased as the block length of PBA increased, from 0.93 GPa for P3HT to 0.19 GPa for P3HT-<i>b</i>-PBA_12k. The field effect transistor (FET) using P3HT-<i>b</i>-PBA as the active layer exhibited a high p-type mobility over 10^–2 cm² V^–1 s^–1, indicating its good charge transporting ability. Furthermore, the P3HT-<i>b</i>-PBA_6k based FET under 100% strain had a high mobility of 2.5 × 10^–2 cm² V^–1 s^–1 with an on/off ratio of 7.2 × 10⁶, and it maintained over 10^–2 cm² V^–1 s^–1 for 1000 cycles, suggesting the promising stability and reproducbility. The result demonstrated that the newly designed conjugated rod–coil block copolymers could have potential applications in stretchable electronic devices

Isoindigo-Based Semiconducting Polymers Using Carbosilane Side Chains for High Performance Stretchable Field-Effect Transistors

Isoindigo-based conjugated polymers, PII2T-C6 and PII2T-C8, with carbosilane side chains have been designed and synthesized for stretchable electronic applications. The carbosilane side chains offerred a simple synthetic pathway to evaluate long and branched side chains in high yields and were prepared with a six or eight linear spacer plus two hexyl or octyl chains after branching. The studied polymers showed a high charge carrier mobility of 8.06 cm² V^–1 s^–1 with an on/off current ratio of 10⁶ as probed using a top-contact transistor device with organized solid state molecular packing structures, as investigated through grazing-incidance X-ray diffreaction (GIXD) and atomic force microscopy (AFM) technique systematically. The studied polymers, more attractive, exhibited superior thin film ductility with a low tensile modulus in a range of 0.27–0.43 GPa owing to the branched carbosilane side chain, and their mobility was remained higher than 1 cm² V^–1 s^–1 even under a 60% strain along parallel or perpendicular direction to the tensile strain. Such polymer films, in addition, can be simultaneously operated over 400 stretching/releasing cycles and maintained stable electrical properties, suggesting the newly designed materials possessed great potential for next-generation skin-inspired wearable electronic application with high charge carrier mobility, low tensile modulus, and stable device characteristics during stretching

Assess the Performance and Cost-Effectiveness of LACE and HOSPITAL Re-Admission Prediction Models as a Risk Management Tool for Home Care Patients: An Evaluation Study of a Medical Center Affiliated Home Care Unit in Taiwan

The LACE index and HOSPITAL score models are the two most commonly used prediction models identifying patients at high risk of readmission with limited information for home care patients. This study compares the effectiveness of these two models in predicting 30-day readmission following acute hospitalization of such patients in Taiwan. A cohort of 57 home care patients were enrolled and followed-up for one year. We compared calibration, discrimination (area under the receiver operating curve, AUC), and net reclassification improvement (NRI) to identify patients at risk of 30-day readmission for both models. Moreover, the cost-effectiveness of the models was evaluated using microsimulation analysis. A total of 22 readmissions occurred after 87 acute hospitalizations during the study period (readmission rate = 25.2%). While the LACE score had poor discrimination (AUC = 0.598, 95% confidence interval (CI) = 0.488&ndash;0.702), the HOSPITAL score achieved helpful discrimination (AUC = 0.691, 95% CI = 0.582&ndash;0.785). Moreover, the HOSPITAL score had improved the risk prediction in 38.3% of the patients, compared with the LACE index (NRI = 0.383, 95% CI = 0.068&ndash;0.697, p = 0.017). Both prediction models effectively reduced readmission rates compared to an attending physician&rsquo;s model (readmission rate reduction: LACE, 39.2%; HOSPITAL, 43.4%; physician, 10.1%; p &lt; 0.001). The HOSPITAL score provides a better prediction of readmission and has potential as a risk management tool for home care patients

Inflammation’s Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder

<div><p></p><p>Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (<i>P</i> = 1.7E-7) and triglyceride (<i>P</i> = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (<i>P</i> = 8.2E-6), cholesterol (<i>P</i> = 0.004), and triglyceride (<i>P</i> = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (<i>P</i> = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (<i>P</i> = 0.006) and TNF-α (<i>P</i> = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01188148" target="_blank">NCT01188148</a>.</p></div

Correlation of changes in metabolic profiles and cytokines before and after 12 weeks of pharmacological treatment.

<p>CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p>**<p><b><i>P</i></b><0.001.</p

Mean HDRS score, YMRS score, and cytokine and metabolic profiles before and after pharmacological treatment.

<p>VPA: valproate; HDRS: Hamilton Depression Rating Scale; YMRS: Young Mania Rating Scale; CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p

Consort flow chart of recruitment.

<p>Consort flow chart of recruitment.</p