Hypothesis Testing in GWAS and Statistical Issues with Compensation in Clinical Trials

We first show theoretically and in simulation how power varies as a function of SNP correlation structure with currently-implemented gene-based testing methods. We propose alternative testing methods whose power does not vary with the correlation structure. We then propose hypothesis tests for detecting prevalence-incidence bias in case-control studies, a bias perhaps overrepresented in GWAS due to currently used study designs. Lastly, we hypothesize how different incentive structures used to keep clinical trial participants in studies may interact with a background of dependent censoring and result in variation in the bias of the Kaplan-Meier survival curve estimator

Interdisciplinary Mathematics Education

Mathematics Education; Learning; Teachin

The association between intrapartum opioid fentanyl and early breastfeeding: A prospective observational study

publishedVersionPaid Open AccessUNIT agreemen

Aspen biology, community classification, and management in the Blue Mountains

Quaking aspen (Populus tremuloides Michx.) is a valuable species that is declining in the Blue Mountains of northeastern Oregon. This publication is a compilation of over 20 years of aspen management experience by USDA Forest Service workers in the Blue Mountains. It includes a summary of aspen biology and occurrence in the Blue Mountains, and a discussion of aspen conservation and management techniques such as fencing, conifer removal, and artificial propagation. Local data on bird use of aspen stands, insects and diseases in aspen, and genetic studies of aspen are also included. An aspen community classification developed from over 200 sample plots is presented, with plant species composition and cover, environment and soils, and management considerations

PIP3-dependent macropinocytosis is incompatible with chemotaxis

In eukaryotic chemotaxis, the mechanisms connecting external signals to the motile apparatus remain unclear. The role of the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) has been particularly controversial. PIP3 has many cellular roles, notably in growth control and macropinocytosis as well as cell motility. Here we show that PIP3 is not only unnecessary for Dictyostelium discoideum to migrate toward folate, but actively inhibits chemotaxis. We find that macropinosomes, but not pseudopods, in growing cells are dependent on PIP3. PIP3 patches in these cells show no directional bias, and overall only PIP3-free pseudopods orient up-gradient. The pseudopod driver suppressor of cAR mutations (SCAR)/WASP and verprolin homologue (WAVE) is not recruited to the center of PIP3 patches, just the edges, where it causes macropinosome formation. Wild-type cells, unlike the widely used axenic mutants, show little macropinocytosis and few large PIP3 patches, but migrate more efficiently toward folate. Tellingly, folate chemotaxis in axenic cells is rescued by knocking out phosphatidylinositide 3-kinases (PI 3-kinases). Thus PIP3 promotes macropinocytosis and interferes with pseudopod orientation during chemotaxis of growing cells

Combinations of Griffithsin with Other Carbohydrate-Binding Agents Demonstrate Superior Activity Against HIV Type 1, HIV Type 2, and Selected Carbohydrate-Binding Agent-Resistant HIV Type 1 Strains

Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to ?12-fold (against HIV-1), ?8-fold (against HIV-2), and ?6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synergy with HHA and GNA was observed against 2G12 mAb- and MVN-resistant HIV-1 strains (CI, 0.64 and 0.49, respectively). Overall, combinations of GRFT and other CBAs showed synergistic activity against HIV-1, HIV-2, and even against certain CBA-resistant HIV-1 strains. The CBAs tested appear to have distinct binding patterns on the gp120 envelope and therefore do not necessarily compete with each other's glycan binding sites on gp120. As a result, there might be no steric hindrance between two different CBAs in their competition for glycan binding (except for the HHA/GNA combination). These data are encouraging for the use of paired CBA combinations in topical microbicide applications (e.g., creams, gels, or intravaginal rings) to prevent HIV transmission.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98459/1/aid%2E2012%2E0026.pd

Usability of Image Generation Platforms to Produce Oblique World Views

The interpretation of oblique aerial views in UAV operations is an important task, yet one that provides unique challenges. The human visual system is mal-adapted to visual perception from the air, especially when oblique views are involved. Hence, UAV operators have to be given training in the interpretation of oblique aerial visual stimuli. A novel way to train operators on how to accurately inspect and perceive oblique aerial images is to administer multiple trials of discrimination tasks for paired oblique images. In discrimination training, trainees view pairs of oblique aerial views and determine whether the images are taken from comparable positions, or contain similar information, etc. For such training, a number of images need to be developed. There are a number of ways that these training images can be generated: The methods differ in the amount of detail they provide and with respect to the resources they require for their development. This paper examines the feasibility and usability of different methods of image generation for aerial UAV imagery. Development of stimuli from sources such as aerial photographs, web-based models, and off-the-shelf simulations are discussed

Surgeons' Volume-Outcome Relationship for Lobectomies and Wedge Resections for Cancer Using Video-Assisted Thoracoscopic Techniques

This study examined the effect of surgeons' volume on outcomes in lung surgery: lobectomies and wedge resections. Additionally, the effect of video-assisted thoracoscopic surgery (VATS) on cost, utilization, and adverse events was analyzed. The Premier Hospital Database was the data source for this analysis. Eligible patients were those of any age undergoing lobectomy or wedge resection using VATS for cancer treatment. Volume was represented by the aggregate experience level of the surgeon in a six-month window before each surgery. A positive volume-outcome relationship was found with some notable features. The relationship is stronger for cost and utilization outcomes than for adverse events; for thoracic surgeons as opposed to other surgeons; for VATS lobectomies rather than VATS wedge resections. While there was a reduction in cost and resource utilization with greater experience in VATS, these outcomes were not associated with greater experience in open procedures

Development and Testing of the CRYOTSU Flight Experiment

This paper describes the development and ground testing of the CRYOTSU thermal management flight experiment. CRYOTSU incorporates three cryogenic temperature experiments and one ambient temperature experiment into a Hitchhiker (HH) Get Away Special (GAS) Canister that is currently scheduled to fly on STS-95 in October 1998. The cryogenic experiments consist of a nitrogen triple-point cryogenic thermal storage unit (CTSU), a nitrogen cryogenic capillary pumped loop (CCPL), and a hydrogen gas-gap cryogenic thermal switch (CTSW). The ambient experiment is a carbon-fiber core, paraffin-filled thermal storage unit. Test results of integrated flight canister testing are provided herein for the CTSU and CCPL experiments. Pre-integration laboratory test results are provided for the CTSW. Design information and test results for the ambient experiment are not included