Application of family-based association testing to assess the genotype-phenotype association involved in complex traits using single-nucleotide polymorphisms

BACKGROUND: We used the FBAT (family-based association test) software to test for association between 300 individual single-nucleotide polymorphisms and P1 (a latent trait of Kofendred Personality Disorder) in 100 simulated replicates of the Aipotu population. Using the Genetic Analysis Workshop 14 dataset, we calculated the power of FBAT to detect linkage disequilibrium on chromosome 3 (D2). Also, we calculated the false-positive rate on chromosome 1, which contains a true locus (D1) but no linkage disequilibrium was simulated between the trait and all the surrounding single-nucleotide polymorphisms. RESULTS: We were able to detect the associations between phenotype P1 and three adjacent markers B03T3056 (average p-value = 0.0002), B03T3057 (average p-value = 0.00072), and B03T3058 (average p-value = 0.0038) with power of 98%, 87%, 71% on chromosome 3, respectively. The overall false positve rate to detect association was 0.06 on chromosome 1. CONCLUSION: The power to detect a significant association in 100 nuclear families affected with the latent trait of Kofendred Personality Disorder by using FBAT was reasonable (based on 100 replicates). In the future, we will compare the performance of FBAT with alternative approaches, such as using FBAT-generalized estimating equations methods to test for association in families affected with complex traits

Impact of ovarian preservation in women with endometrial cancer

AbstractBackgroundBilateral salpingo-oophorectomy (BSO) is standardly performed in the treatment of endometrial cancer. The purpose of this study was to evaluate the impact of ovarian preservation on the outcome of patients with endometrial cancer.MethodsA retrospective cohort study was performed using the 2000–2010 database of endometrial cancer patients who were treated at Taipei Veterans General Hospital. Information regarding patient age, pathologic reports, and follow-up results was abstracted from medical records.ResultsFive hundred and twenty-nine patients were reviewed in this study. Mean age and follow-up duration were 55.7 ± 11.4 years and 37.5 ± 30.1 months, respectively. The median disease-free survival was 31.2 months (range 0.2–126.9 months). There were no significant differences in disease-free survival between stage I patients with ovarian preservation versus those with oophorectomy (p = 0.473). In a multivariate Cox model, ovarian preservation had no effect on disease-free survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48–15.59]; however, it was not significantly related to stage and para-aortic lymph node involvement.ConclusionOvarian preservation may be considered in premenopausal women with early-stage low-risk endometrial cancer

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

<p>Abstract</p> <p>Background</p> <p>To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer.</p> <p>Methods</p> <p>Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m²intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0).</p> <p>Results</p> <p>The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully.</p> <p>Conclusion</p> <p>HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted.</p

The Association Between the Sedative Loads and Clinical Severity Indicators in the First-Onset Major Depressive Disorder

Background: High sedative use in a major depressive episode may imply specific clinical features. This study aims to examine the correlation between sedative use and clinical severity indicators in the initial treatment phase of first-onset major depressive disorder.Methods: A study cohort in the first episode of major depressive disorder was used to conduct pharmacological dissection. All participants had at least a 2-year follow-up period with a complete treatment record. The defined daily dose of antidepressants and augmentation agents were calculated as the antidepressant load and augmentation load, respectively. Sedative use, which was calculated as the equivalent dosage of lorazepam, were defined as the sedative load. These psychotropic loads were measured monthly and the averaged psychotropic loads for each day were obtained.Results: A total of 106 individuals (75.5% female) were included. The mean duration of disease course in participants was 5.5 ± 3.5 years. In the multiple regression analysis, after controlling for other classes of psychotropics and comorbid anxiety disorders, the sedative load independently correlated with higher number of antidepressants used, higher number of antidepressant used with an adequate dose and duration, more psychiatric emergency and outpatient visits within 2 years of disease onset.Conclusion: High loading of sedatives correlated with several indicators of clinical severity in major depressive disorder. The sedative load may be used as a specifier to identify subgroups in patients with major depressive disorder

Longitudinal stage profiles forecasting in rivers for flash floods

Copyright © 2010 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Hydrology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Hydrology Vol. 388 (2010), DOI: 10.1016/j.jhydrol.2010.05.028A flash flood routing model with artificial neural networks predictions was developed for stage profiles forecasting. The artificial neural network models were used to predict the 1-3 h lead time river stages at gauge stations along a river. The predictions were taken as interior boundaries in the flash flood routing model for the forecast of longitudinal stage profiles, including the un-gauged sites of a whole river. The flash flood routing model was based on the dynamic wave equations with discretization processes of the four-point finite difference method. Five typhoon events were applied to calibrate the rainfall-stage model and the other three events were simulated to verify the model's capability. The results revealed that the flash flood river routing model conjunction with artificial neural networks can provide accurate river stages for flood forecasting.National Science Council of Taiwa

High yield expression in a recombinant E. coli of a codon optimized chicken anemia virus capsid protein VP1 useful for vaccine development

<p>Abstract</p> <p>Background</p> <p>Chicken anemia virus (CAV), the causative agent chicken anemia, is the only member of the genus <it>Gyrovirus </it>of the <it>Circoviridae </it>family. CAV is an immune suppressive virus and causes anemia, lymph organ atrophy and immunodeficiency. The production and biochemical characterization of VP1 protein and its use in a subunit vaccine or as part of a diagnostic kit would be useful to CAV infection prevention.</p> <p>Results</p> <p>Significantly increased expression of the recombinant full-length VP1 capsid protein from chicken anemia virus was demonstrated using an <it>E. coli </it>expression system. The VP1 gene was cloned into various different expression vectors and then these were expressed in a number of different <it>E. coli </it>strains. The expression of CAV VP1 in <it>E. coli </it>was significantly increased when VP1 was fused with GST protein rather than a His-tag. By optimizing the various rare amino acid codons within the N-terminus of the VP1 protein, the expression level of the VP1 protein in <it>E. coli </it>BL21(DE3)-pLysS was further increased significantly. The highest protein expression level obtained was 17.5 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 2 h. After purification by GST affinity chromatography, the purified full-length VP1 protein produced in this way was demonstrated to have good antigenicity and was able to be recognized by CAV-positive chicken serum in an ELISA assay.</p> <p>Conclusions</p> <p>Purified recombinant VP1 protein with the gene's codons optimized in the N-terminal region has potential as chimeric protein that, when expressed in <it>E. coli</it>, may be useful in the future for the development of subunit vaccines and diagnostic tests.</p

Predicting the Severity and Prognosis of Trismus after Intensity-Modulated Radiation Therapy for Oral Cancer Patients by Magnetic Resonance Imaging

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal–Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p