The Type II Error Probability of a Group Sequential Test of Efficacy and Futility,and Considerations for Power and Sample Size

For a clinical trial incorporating a group sequential test that allows early stopping for efficacy or futility (GSTEF), the primary hypothesis concerns efficacy. However, the type II error probability of the tests of efficacy is neither specified nor known. The type II error probability of a GSTEF is partitioned into the sum of its component type II error probabilities of futility and efficacy. This partitioning provides transparency, allowing researchers flexibility to set these component error probabilities directly and to know the impact on the total type II error probability and vice versa. This transparency and flexibility should improve the application of GSTEF to clinical trials.     

Biplane Correlation Imaging: A Feasibility Study Based on Phantom and Human Data

The objective of this study was to implement and evaluate the performance of a biplane correlation imaging (BCI) technique aimed to reduce the effect of anatomic noise and improve the detection of lung nodules in chest radiographs. Seventy-one low-dose posterior–anterior images were acquired from an anthropomorphic chest phantom with 0.28° angular separations over a range of ±10° along the vertical axis within an 11 s interval. Similar data were acquired from 19 human subjects with institutional review board approval and informed consent. The data were incorporated into a computer-aided detection (CAD) algorithm in which suspect lesions were identified by examining the geometrical correlation of the detected signals that remained relatively constant against variable anatomic backgrounds. The data were analyzed to determine the effect of angular separation, and the overall sensitivity and false-positives for lung nodule detection. The best performance was achieved for angular separations of the projection pairs greater than 5°. Within that range, the technique provided an order of magnitude decrease in the number of false-positive reports when compared with CAD analysis of single-view images. Overall, the technique yielded ~1.1 false-positive per patient with an average sensitivity of 75%. The results indicated that the incorporation of angular information can offer a reduction in the number of false-positives without a notable reduction in sensitivity. The findings suggest that the BCI technique has the potential for clinical implementation as a cost-effective technique to improve the detection of subtle lung nodules with lowered rate of false-positives.     

Comparing retrospective reports to real-time/real-place mobile assessments in individuals with schizophrenia and a nonclinical comparison group

Retrospective reports are often used as the primary source of information for important diagnostic decisions, treatment, and clinical research. Whether such reports accurately represent individuals' past experiences in the context of a serious mental illness such as schizophrenia is unclear. In the current study, 24 individuals with schizophrenia and 26 nonclinical participants used a mobile device to complete multiple real-time/real-place assessments daily, over 7 consecutive days. At the end of the week, participants were also asked to provide a retrospective report summarizing the same period. Comparison of the data captured by the 2 methods showed that participants from both groups retrospectively overestimated the intensity of negative and positive daily experiences. In the clinical group, overestimations for affect were greater than for psychotic symptoms, which were relatively comparable to their retrospective reports. In both samples, retrospective reports were more closely associated with the week's average than the most intense or most recent ratings captured with a mobile device. Multilevel modeling revealed that much of the variability in weekly assessments was not explained by between-person differences and could not be captured by a single retrospective estimate. Based on the findings of this study, clinicians and researchers should be aware that while retrospective summary reports of the severity of certain symptoms compare relatively well with average momentary ratings, they are limited in their ability to capture variability in one's affective or psychotic experiences over time.     

Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes

Although family history is a major risk factor for colorectal cancer (CRC) a genetic diagnosis cannot be obtained in over 50 % of familial cases when screened for known CRC cancer susceptibility genes. The genetics of undefined-familial CRC is complex and recent studies have implied additional clinically actionable mutations for CRC in susceptibility genes for other cancers. To clarify the contribution of non-CRC susceptibility genes to undefined-familial CRC we conducted a mutational screen of 114 cancer susceptibility genes in 847 patients with early-onset undefined-familial CRC and 1609 controls by analysing high-coverage exome sequencing data. We implemented American College of Medical Genetics and Genomics standards and guidelines for assigning pathogenicity to variants. Globally across all 114 cancer susceptibility genes no statistically significant enrichment of likely pathogenic variants was shown (6.7 % cases 57/847, 5.3 % controls 85/1609; P = 0.15). Moreover there was no significant enrichment of mutations in genes such as TP53 or BRCA2 which have been proposed for clinical testing in CRC. In conclusion, while we identified genes that may be considered interesting candidates as determinants of CRC risk warranting further research, there is currently scant evidence to support a role for genes other than those responsible for established CRC syndromes in the clinical management of familial CRC.     

同种异体黑素细胞移植治疗白癜风

0　引言　白癜风患者免疫紊乱 ,黑素细胞 (melanocyte,MC)异体移植有可能不被排斥 ,治疗如成功将有很大临床前景 [1 ] .探索同种异体黑素细胞移植后的效果很有意义 .1　病例报告　女 ,2 7岁 ,确诊白癜风 (稳定期 ) ,患者皮肤自幼出现色素脱失斑 ,逐渐增多扩大 . 1996年外用“敏白灵”,前2 mo有效 . 1999- 0 7外用补骨酯酊 ,日服 5 g· L- 1 硫酸铜 10m L和中药 1剂 ,转移因子 4m L ,sc,1· 2 d- 1 .皮损缩小 ,4mo后稳定 .用健康男青年环切的包皮培养 MC,第 4代大约80 %融合时 ,用 2 .5 g· L- 1 胰酶消化 5 min,加入含 2 0 0 g·L- 1小…     

Allergy and glioma risk: Test of association by genotype

Although epidemiological studies have suggested an association between atopy and glioma risk, these observations have been based on self‐reporting of allergic conditions raising the possibility that associations may be noncausal and arise as a consequence of bias, reverse causation or other artifacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analyzed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13 and 17q21 that are associated with asthma or eczema risk at p < 5.0 × 10^?7. The SNP rs7216389, which tags the 3′ flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01–1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses.     

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma‐tocotrienols (γ‐T3) is one of the vitamin‐E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ‐T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel‐induced apoptosis, suggesting that γ‐T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ‐T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen‐independent prostate cancer cell lines (PC‐3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ‐T3 treatment. In addition, pretreatment of PC‐3 cells with γ‐T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133‐enriched PC‐3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ‐T3 treatment as the CD133‐depleted population. Our data suggest that γ‐T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.     

A knowledge management tool for public health: health-evidence.ca

Background

The ultimate goal of knowledge translation and exchange (KTE) activities is to facilitate incorporation of research knowledge into program and policy development decision making. Evidence-informed decision making involves translation of the best available evidence from a systematically collected, appraised, and analyzed body of knowledge. Knowledge management (KM) is emerging as a key factor contributing to the realization of evidence-informed public health decision making. The goal of health-evidence.ca is to promote evidence-informed public health decision making through facilitation of decision maker access to, retrieval, and use of the best available synthesized research evidence evaluating the effectiveness of public health interventions.

Methods

The systematic reviews that populate health evidence.ca are identified through an extensive search (1985-present) of 7 electronic databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Sociological Abstracts, BIOSIS, and SportDiscus; handsearching of over 20 journals; and reference list searches of all relevant reviews. Reviews are assessed for relevance and quality by two independent reviewers. Commonly-used public health terms are used to assign key words to each review, and project staff members compose short summaries highlighting results and implications for policy and practice.

Results

As of June 2010, there are 1913 reviews in the health-evidence.ca registry in 21 public health and health promotion topic areas. Of these, 78% have been assessed as being of strong or moderate methodological quality. Health-evidence.ca receives approximately 35,000 visits per year, 20,596 of which are unique visitors, representing approximately 100 visits per day. Just under half of all visitors return to the site, with the average user spending six minutes and visiting seven pages per visit. Public health nurses, program managers, health promotion workers, researchers, and program coordinators are among the largest groups of registered users, followed by librarians, dieticians, medical officers of health, and nutritionists. The majority of users (67%) access the website from direct traffic (e.g., have the health-evidence.ca webpage bookmarked, or type it directly into their browser).

Conclusions

Consistent use of health-evidence.ca and particularly the searching for reviews that correspond with current public health priorities illustrates that health-evidence.ca may be playing an important role in achieving evidence-informed public health decision making.