Methodological Issues in Multistage Genome-Wide Association Studies

Because of the high cost of commercial genotyping chip technologies, many investigations have used a two-stage design for genome-wide association studies, using part of the sample for an initial discovery of ``promising'' SNPs at a less stringent significance level and the remainder in a joint analysis of just these SNPs using custom genotyping. Typical cost savings of about 50% are possible with this design to obtain comparable levels of overall type I error and power by using about half the sample for stage I and carrying about 0.1% of SNPs forward to the second stage, the optimal design depending primarily upon the ratio of costs per genotype for stages I and II. However, with the rapidly declining costs of the commercial panels, the generally low observed ORs of current studies, and many studies aiming to test multiple hypotheses and multiple endpoints, many investigators are abandoning the two-stage design in favor of simply genotyping all available subjects using a standard high-density panel. Concern is sometimes raised about the absence of a ``replication'' panel in this approach, as required by some high-profile journals, but it must be appreciated that the two-stage design is not a discovery/replication design but simply a more efficient design for discovery using a joint analysis of the data from both stages. Once a subset of highly-significant associations has been discovered, a truly independent ``exact replication'' study is needed in a similar population of the same promising SNPs using similar methods.Comment: Published in at http://dx.doi.org/10.1214/09-STS288 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Antibody-Based Immunotherapy of Cancer

By targeting surface antigens expressed on tumor cells, monoclonal antibodies have demonstrated efficacy as cancer therapeutics. Recent successful antibody-based strategies have focused on enhancing antitumor immune responses by targeting immune cells, irrespective of tumor antigens. We discuss these innovative strategies and propose how they will impact the future of antibody-based cancer therapy

ACCURACY OF ANTLER METRICS IN PREDICTING AGE OF WHITE-TAILED DEER AND MULE DEER

Electronic deer check systems offer state natural resource agencies alternatives to mandatory in-person check stations, resulting in potential savings in money and personnel. However, a reliable means for hunters to classify the age of harvested antlered deer must be established so that important management indices such as antlered yearling harvest can continue to be used to set future management goals. Therefore, we evaluated the use of six different antler metrics to predict age class of white-tailed and mule deer (1.5 and \u3e/= 2.5 years). We used discriminant analysis to determine the number of deer correctly classified into each age class based on the antler metric with the greatest degree of separation for each species. Of those evaluated, main beam length and inside spread were the two most accurate measurements for both species. For white-tailed deer, 93% (114 of 123) of the 1.5-year age class and 93% (251 of 271) of the \u3e/= 2.5-year age class were correctly classified using main beam length with a cutoff of 364 mm. For mule deer, 100% (12 of 12) of the 1.5-year age class and 97% (35 of 36) of the \u3e/= 2.5-year age class were correctly classified using main beam length with a cutoff of 352 mm. Antler metrics of both deer species can be used to accurately classify age class while likely saving funds and personnel hours

Transition Probabilities for Trichoplusia ni (Lepidoptera: Noctuidae) Larvae on Cabbage as a Function of Microclimate

To identify factors affecting the spatial dynamics of Trichoplusia ni (Hübner) on cabbage, the movements of individual larvae were monitored. Larvae were marked with 32p and released individually, one per plant, on cabbage plants in research plots. Their movements were monitored by recording their position on the plant daily, locating them with a Geiger counter. In the same plots, hourly measurements of temperature and relative humidity were recorded in three different parts of the crop canopy. Transition probabilities for the larvae from and to each of five vertical plant strata were modeled as definite integrals of the Beta probability density function (pdf). The shape parameters for these Beta pdf's were modeled as a function of microclimate, and the necessary parameters to do so were estimated by the method of maximum likelihood. This model predicted the data well and was more efficient than logistic regression. The model predicts that under high temperatures and low vapor pressure deficit (vpd), larvae move down to the shaded, cooler, lower parts of the plant; whereas under low temperatures and high vpd, they moved upward toward the economically important wrapper leaves and cabbage head

The baculovirus anti-apoptotic protein Op-IAP does not inhibit Drosophila caspases or apoptosis in Drosophila S2 cells and instead sensitizes S2 cells to virus-induced apoptosis

AbstractThe Op-IAP protein from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) is highly effective at inhibiting apoptosis triggered by a variety of different stimuli in lepidopteran cells as well as in several different mammalian cell types, suggesting that it functions at a highly conserved step in the apoptotic pathway. However, the mechanism by which Op-IAP inhibits apoptosis is unclear. Since some IAP proteins can bind and inhibit caspases, we tested whether Op-IAP could inhibit the activity of caspases from Drosophila melanogaster. We found that recombinant Op-IAP protein was not able to bind or directly inhibit the activity of the Drosophila caspases DRONC, DrICE, or DCP-1 in vitro. In addition, expression of Op-IAP was unable to inhibit apoptosis triggered by either actinomycin D or UV light in D. melanogaster S2 cells. Surprisingly, Op-IAP expression in S2 cells enhanced apoptosis caused by baculovirus infection, but did not cause increased sensitivity to either actinomycin D or UV damage-induced apoptosis. The observation that Op-IAP cannot inhibit these insect caspases suggests that it functions by a mechanism that does not involve direct caspase inhibition

Shaping frontline practices: a scoping review of human factors implicated in electrical safety incidents

Injuries sustained while performing electrical work are a significant threat to the health and safety of workers and occur frequently. In some jurisdictions, non-fatal serious incidents have increased in recent years. Although significant work has been carried out on electrical safety from a human factor perspective, reviews of this literature are sparse. Thus, the purpose of this review is to collate and summarize human factors implicated in electrical safety events. Articles were collected from three databases (Scopus, Web of Science, and Google Scholar), using the search terms: safety, electri*, human factors, and arc flash. Titles and abstracts were screened, full-text reviews were conducted, and 18 articles were included in the final review. Quality checks were undertaken using the Mixed Methods Appraisal Tool and the Critical Appraisal Skills Program. Environmental, individual, team, organizational, and macro factors were identified in the literature as factors which shape frontline electrical worker behavior, highlighting the complexity of injury prevention. The key contributions of this paper include: (1) a holistic and integrated summary of human factors implicated in electrical safety events, (2) the application of an established theoretical model to explain dynamic forces implicated in electrical safety incidents, and (3) several practical implications and recommendations to improve electrical safety. It is recommended that this framework is used to develop and test future interventions at the individual, team, organizational, and regulator level to mitigate risk and create meaningful and sustainable change in the electrical safety spac