Measurement of the Muon Decay Parameter delta

The muon decay parameter delta has been measured by the TWIST collaboration. We find delta = 0.74964 +- 0.00066(stat.) +- 0.00112(syst.), consistent with the Standard Model value of 3/4. This result implies that the product Pmuxi of the muon polarization in pion decay, Pmu, and the muon decay parameter xi falls within the 90% confidence interval 0.9960 < Pmuxi < xi < 1.0040. It also has implications for left-right-symmetric and other extensions of the Standard Model.Comment: Extended to 5 pages. Referee's comments answere

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures

Informative noncompliance in endpoint trials

Noncompliance with study medications is an important issue in the design of endpoint clinical trials. Including noncompliant patient data in an intention-to-treat analysis could seriously decrease study power. Standard methods for calculating sample size account for noncompliance, but all assume that noncompliance is noninformative, i.e., that the risk of discontinuation is independent of the risk of experiencing a study endpoint. Using data from several published clinical trials (OPTIMAAL, LIFE, RENAAL, SOLVD-Prevention and SOLVD-Treatment), we demonstrate that this assumption is often untrue, and we discuss the effect of informative noncompliance on power and sample size

Sample size requirements to detect the effect of a group of genetic variants in case-control studies

<p>Abstract</p> <p>Background</p> <p>Because common diseases are caused by complex interactions among many genetic variants along with environmental risk factors, very large sample sizes are usually needed to detect such effects in case-control studies. Nevertheless, many genetic variants act in well defined biologic systems or metabolic pathways. Therefore, a reasonable first step may be to detect the effect of a group of genetic variants before assessing specific variants.</p> <p>Methods</p> <p>We present a simple method for determining approximate sample sizes required to detect the average joint effect of a group of genetic variants in a case-control study for multiplicative models.</p> <p>Results</p> <p>For a range of reasonable numbers of genetic variants, the sample size requirements for the test statistic proposed here are generally not larger than those needed for assessing marginal effects of individual variants and actually decline with increasing number of genetic variants in many situations considered in the group.</p> <p>Conclusion</p> <p>When a significant effect of the group of genetic variants is detected, subsequent multiple tests could be conducted to detect which individual genetic variants and their combinations are associated with disease risk. When testing for an effect size in a group of genetic variants, one can use our global test described in this paper, because the sample size required to detect an effect size in the group is comparatively small. Our method could be viewed as a screening tool for assessing groups of genetic variants involved in pathogenesis and etiology of common complex human diseases.</p

Would loss to follow-up bias the outcome evaluation of patients operated for degenerative disorders of the lumbar spine?: A study of responding and non-responding cohort participants from a clinical spine surgery registry

Loss to follow-up may bias the outcome assessments of clinical registries. In this study, we wanted to determine whether outcomes were different in responding and non-responding patients who were included in a clinical spine surgery registry, at two years of follow-up. In addition, we wanted to identify risk factors for failure to respond. 633 patients who were operated for degenerative disorders of the lumbar spine were followed for 2 years using a local clinical spine registry. Those who did not attend the clinic and those who did not answer a postal questionnaire—for whom 2 years of outcome data were missing—and who would be lost to follow-up according to the standard procedures of the registry protocols, were defined as non-respondents. They were traced and interviewed by telephone. Outcome measures were: improvement in health-related quality of life (EQ-5D), leg pain, and back pain; and also general state of health, employment status, and perceived benefits of the operation. We found no statistically significant differences in outcome between respondents (78% of the patients) and nonrespondents (22%). Receipt of postal questionnaires (not being summoned for a follow-up visit) was the strongest risk factor for failure to respond. Forgetfulness appeared to be an important cause. Older patients and those who had complications were more likely to respond. Interpretation A loss to follow-up of 22% would not bias conclusions about overall treatment effects and, importantly, there were no indications of worse outcomes in non-respondents

Design, rationale, and baseline characteristics of a cluster randomized controlled trial of pay for performance for hypertension treatment: study protocol

<p>Abstract</p> <p>Background</p> <p>Despite compelling evidence of the benefits of treatment and well-accepted guidelines for treatment, hypertension is controlled in less than one-half of United States citizens.</p> <p>Methods/design</p> <p>This randomized controlled trial tests whether explicit financial incentives promote the translation of guideline-recommended care for hypertension into clinical practice and improve blood pressure (BP) control in the primary care setting. Using constrained randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to four study arms: physician-level incentive; group-level incentive; combination of physician and group incentives; and no incentives (control). All participants at the hospital (cluster) were assigned to the same study arm. We enrolled 83 full-time primary care physicians and 42 non-physician personnel. The intervention consisted of an educational session about guideline-recommended care for hypertension, five audit and feedback reports, and five disbursements of incentive payments. Incentive payments rewarded participants for chart-documented use of guideline-recommended antihypertensive medications, BP control, and appropriate responses to uncontrolled BP during a prior four-month performance period over the 20-month intervention. To identify potential unintended consequences of the incentives, the study team interviewed study participants, as well as non-participant primary care personnel and leadership at study sites. Chart reviews included data collection on quality measures not related to hypertension. To evaluate the persistence of the effect of the incentives, the study design includes a washout period.</p> <p>Discussion</p> <p>We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether performance-based payment arrangements such as financial incentives result in meaningful quality improvements.</p> <p>Trial Registration</p> <p><url>http://www.clinicaltrials.gov</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT00302718">NCT00302718</a></p

Are migraineur women really more vulnerable to stress and less able to cope?

Abstract Background In this study, we aimed to investigate the differences between a sample of migraineurs and non-migraineurs with regard to their stress symptoms, tendency to stress, coping styles and life satisfaction. Methods This study was carried out on a migraineur group (n = 62, mean age: 37.5 ± 11.3, range: 18 to 61 years) and a non-migraineur group (n = 58, mean age: 32.0 ± 11.2, range: 18 to 61 years). Stress Audit (Symptoms), Stress Audit (Vulnerability), Turkish version of Ways of Coping Inventory Scales and Life Satisfaction were applied to the migraineur and non-migraineur groups. Results No significant differences were found between the groups in the scores of the stress symptoms except in the sub scores of the sympathetic system. There was no significant difference between the groups in the tendency to stress and life satisfaction (p > .05). For scores of the coping styles, the mean scores of the seeking social support subscale was higher in the control group than that of the migraineur group. However, migraineur women had higher mean scores in the submissive and the optimistic subscales. Conclusion We consider that, these outcomes may emphasize the necessity to be careful when using negative expressions about stress relating to migraineurs. Further comprehensive studies are required considering the multiple triggers of the disease in various cultural contexts.</p

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS)

textabstractBackground. A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. Methods/design. The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm. The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. Discussion. This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. Trial registration. ISRCTN80832026

Measurement of the Michel Parameter ρ\rho in Muon Decay

The TWIST Collaboration has measured the Michel parameter $\rho$ in normal muon decay, $\mu^+ \to e^+ \nu_e \bar{\nu}_{\mu}$. In the Standard Model, $\rho$ = 3/4. Deviations from this value require mixing of left- and right-handed muon and electron couplings in the muon-decay Lagrangian. We find $\rho$ = 0.75080 $\pm$ 0.00044(stat.) $\pm$ 0.00093(syst.) $\pm$ 0.00023, where the last uncertainty represents the dependence of $\rho$ on the Michel parameter $\eta$. This result sets new limits on the $W_L-W_R$ mixing angle in left-right symmetric models.Comment: 4 pages, 3 figures, submitted to PR