Table II: Baseline Values of Primary and Secondary Outcomes for Placebo and Botox Groups

Table of supplemental data to accompany an article submitted for publication by the author

Cost-Utility of Routine Endometrial Evaluation Prior to Le Fort Colpocleisis

Objective: Endometrial evaluation is routinely performed in elderly women undergoing Le Fort colpocleisis. There is little evidence to support this practice. We sought to investigate the cost-utility of routine evaluation of the uterine cavity prior to performing a Le Fort colpocleisis. Study Design: A decision analysis model was created to compare uterine evaluation, by either endometrial biopsy or transvaginal ultrasound, to no evaluation for a cohort of women \u3e 80 years old undergoing Le Fort colpocleisis. Baseline assumptions for our model were made to reflect women who did not carry significant risk for the development of endometrial cancer, such as history of postmenopausal bleeding, abnormal uterine pathology, obesity, diabetes, and tamoxifen use. Decision paths included no screening, ultrasound evaluation, and biopsy. The horizon was five years until the endpoint of survival, death, or the development of cancer. Those pathways in which cancer was diagnosed were carried out to the endpoint of either five-year survival or death. Treatment arms for endometrial cancer were based on management methods used at our institution. Probabilities and utilities for health outcomes were estimated through literature review or, when unavailable, by expert opinion. Costs were obtained from US Medicare charges for the appropriate CPT and DRG codes and are reported in 2012 US Dollars. Cost-utility analysis was performed using US recommendations from a societal perspective. Sensitivity analysis using Monte Carlo simulation was performed to test the validity of our model. Results: Analysis of our decision tree demonstrates that a strategy of no evaluation is superior to that of either biopsy or ultrasound. Univariate sensitivity analysis demonstrates that at a 0.55 probability of cancer, biopsy surpasses both no evaluation and ultrasound as the dominant strategy. Using Monte Carlo simulation, at willingness-to-pay thresholds of $50,000 and$100,000, no evaluation was superior to both biopsy and ultrasound from the patient, health-plan, and societal perspectives. Biopsy appears to be a more effective strategy than ultrasound when uterine evaluation is needed. Conclusions: Our model shows that a practice of not evaluating the endometrial cavity prior to performing Le Fort colpocleisis is superior to either biopsy or ultrasound. These results are likely being driven by the low incidence of endometrial cancer in this population. It may not be necessary to perform uterine evaluation prior to Le Fort colpocleisis in a low-risk population. If uterine evaluation is needed, biopsy appears to be the preferred strategy over ultrasound. More studies are needed to determine utility values for health states experienced by women with pelvic organ prolapse and with endometrial cancer. This will enhance our ability to develop more accurate cost-utility models for treating these women

Exploiting Fine-Grain Concurrency Analytical Insights in Superscalar Processor Design

This dissertation develops analytical models to provide insight into various design issues associated with superscalar-type processors, i.e., the processors capable of executing multiple instructions per cycle. A survey of the existing machines and literature has been completed with a proposed classification of various approaches for exploiting fine-grain concurrency. Optimization of a single pipeline is discussed based on an analytical model. The model-predicted performance curves are found to be in close proximity to published results using simulation techniques. A model is also developed for comparing different branch strategies for single-pipeline processors in terms of their effectiveness in reducing branch delay. The additional instruction fetch traffic generated by certain branch strategies is also studied and is shown to be a useful criterion for choosing between equally well performing strategies. Next, processors with multiple pipelines are modelled to study the tradeoffs associated with deeper pipelines versus multiple pipelines. The model developed can reveal the cause of performance bottleneck: insufficient resources to exploit discovered parallelism, insufficient instruction stream parallelism, or insufficient scope of concurrency detection. The cost associated with speculative (i.e., beyond basic block) execution is examined via probability distributions that characterize the inherent parallelism in the instruction stream. The throughput prediction of the analytic model is shown, using a variety of benchmarks, to be close to the measured static throughput of the compiler output, under resource and scope constraints. Further experiments provide misprediction delay estimates for these benchmarks under scope constraints, assuming beyond-basic-block, out-of-order execution and run-time scheduling. These results were derived using traces generated by the Multiflow TRACE SCHEDULING™(*) compacting C and FORTRAN 77 compilers. A simplified extension to the model to include multiprocessors is also proposed. The extended model is used to analyze combined systems, such as superpipelined multiprocessors and superscalar multiprocessors, both with shared memory. It is shown that the number of pipelines (or processors) at which the maximum throughput is obtained is increasingly sensitive to the ratio of memory access time to network access delay, as memory access time increases. Further, as a function of inter-iteration dependency distance, optimum throughput is shown to vary nonlinearly, whereas the corresponding Optimum number of processors varies linearly. The predictions from the analytical model agree with published results based on simulations. (*)TRACE SCHEDULING is a trademark of Multiflow Computer, Inc

Patient-focused Websites Related to Stress Urinary Incontinence and Pelvic Organ Prolapse: a DISCERN Quality Analysis

Objective: To evaluate the quality of information presented on English-language websites regarding treatment options for POP and SUI using a validated instrument. Methods: Utilizing the International Urogynecology Association list of continence societies worldwide, faculty nomination and a complementary Google search using the terms “professional organizations stress urinary incontinence / pelvic organ prolapse” English-language, patient-focused websites related to POP and SUI were identified. The websites were evaluated by faculty at an academic medical center, including 4 faculty members of the urogynecology division, 2 urogynecology fellows, 3 urologists, and 1 obstetrician gynecologist. The websites were independently evaluated using the validated DISCERN instrument assessing the reliability and quality of consumer health information.Results: From the IUGA continence societies worldwide list, 47 websites were identified. Five provided patient information in English. Eight additional websites were identified from the Google search or provider nomination. One website provided information only for POP (rectocele), 5 for SUI, and 7 for both. The lowest mean total score for any website was 38.7 and the highest mean total score was 61.5 across all the websites. There were no statistically significant differences in the website mean total scores (p value \u3c0.40 for POP and 0.14 for SUI). For websites covering both topics, POP scores were generally higher than SUI scores, but not statistically significantly different (p value\u3c3.75). The overall quality item scores were also not significantly different (SUI: p\u3c0.923; POP: p \u3c0.813). Missing information most commonly included lack of clear objectives, sources, and information related to the expected outcome of no intervention.Conclusions: Available English-language professional websites written to inform patients about management choices for SUI and POP miss key components of quality patient information

Anatomy of Cirrus Clouds: Results from the Emerald Airborne Campaigns

2000 FLORIDA AVE NW, WASHINGTON, USA, DC, 2000

In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease

Reciprocal Interactions of Pit1 and GATA2 Mediate Signaling Gradient–Induced Determination of Pituitary Cell Types

AbstractThe mechanisms by which transient gradients of signaling molecules lead to emergence of specific cell types remain a central question in mammalian organogenesis. Here, we demonstrate that the appearance of four ventral pituitary cell types is mediated via the reciprocal interactions of two transcription factors, Pit1 and GATA2, which are epistatic to the remainder of the cell type–specific transcription programs and serve as the molecular memory of the transient signaling events. Unexpectedly, this program includes a DNA binding–independent function of Pit1, suppressing the ventral GATA2-dependent gonadotrope program by inhibiting GATA2 binding to gonadotrope- but not thyrotrope-specific genes, indicating that both DNA binding–dependent and –independent actions of abundant determining factors contribute to generate distinct cell phenotypes

The extended tails of Palomar 5: A ten degree arc of globular cluster tidal debris

Using wide-field photometric data from the Sloan Digital Sky Survey (SDSS) we recently showed that the Galactic globular cluster Palomar 5 is in the process of being tidally disrupted. Its tidal tails were initially detected in a 2.5 degree wide band along the celestial equator. A new analysis of SDSS data for a larger field now reveals that the tails of Pal 5 have a much larger spatial extent and can be traced over an arc of 10 deg across the sky, corresponding to a projected length of 4 kpc at the distance of the cluster. The number of former cluster stars found in the tails adds up to about 1.2 times the number of stars in the cluster. The radial profile of stellar surface density in the tails follows approximately a power law r^gamma with -1.5 < gamma < -1.2. The stream of debris from Pal 5 is significantly curved, which demonstrates its acceleration by the Galactic potential. The cluster is presently near the apocenter but has repeatedly undergone disk crossings in the inner part of the Galaxy leading to strong tidal shocks. Our results suggest that the observed debris originates mostly from mass loss within the last 2 Gyrs. The cluster is likely to be destroyed after the next disk crossing, which will happen in about 100 Myr. (abridged)Comment: 44 pages, including 14 figures (Figs.1,3 & 14 with decreased resolution), accepted for publication in the Astronomical Journa

Leptonic Decays of Heavy Quarks on the Lattice

The status of lattice calculations of heavy-light decay constants and of the $B$ parameter $B_B$ is reviewed. After describing the lattice approach to heavy quark systems, the main results are discussed, with special emphasis on the systematic errors in present lattice calculations. A detailed analysis of the continuum limit for decay constants is performed. The implications of lattice results on studies of CP violation in the Standard Model are discussed.Comment: Invited review to be published in Int. J. Mod. Phys. A, 63 pages, LaTeX, ijmpa1.sty (included), 8 postscript figure