Health-related quality of life improves with treatment-related GERD symptom resolution after adjusting for baseline severity

Severity and frequency of gastroesophageal reflux disease (GERD) related symptoms are associated with impaired health-related quality of life (HRQL). This study evaluated the association between baseline heartburn severity and endpoint HRQL of patients treated for heartburn and the relationship between complete resolution of heartburn symptoms and HRQL outcomes after controlling for baseline severity. We completed a secondary analysis of clinical symptom and HRQL data from three clinical trials in adult patients receiving either omeprazole or ranitidine treatment for GERD. HRQL was assessed using the Psychological General Well-Being Index (PGWB) in each of the three clinical trials, and two of the trials also included the Medical Outcomes Study Sleep disturbance scale. Gastrointestinal symptoms were evaluated using either the Gastrointestinal Symptom Rating Scale or a modified version of the scale. Baseline heartburn severity (none/minor, mild, moderate or severe) was defined based on patient-reported symptoms. Analysis of covariance (ANCOVA) models were used to compare mean HRQL scores by baseline level of heartburn symptom severity and whether or not patients experienced complete heartburn resolution. At baseline, PGWB scores were significantly worse (p < 0.05) for patients with more severe heartburn symptoms. There were no statistically significant baseline severity by symptom resolution interactions in any of the ANCOVA models. For all three trials and across all follow-up assessments, mean PGWB scores were statistically significantly higher for patients with completely resolved heartburn symptoms versus those whose symptoms were unresolved (all p-values < 0.05). Few significant effects were observed for sleep disturbance scores. While the severity of heartburn symptoms at the start of medical treatment for GERD is not associated with improvements in HRQL in subsequent weeks of treatment, complete resolution of symptoms is associated with improvements in psychological well-being

Immune-active microenvironment in small cell carcinoma of the ovary, hypercalcemic type : rationale for immune checkpoint blockade

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive monogenic cancer driven by SMARCA4 mutations. Here, we report responses to anti-PD1 immunotherapy in four patients and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors (eight of 11 cases) demonstrated PD-L1 expression with strong associated T-cell infiltration (R2 = 0.60–0.95). PD-L1 expression was detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1-positive cells in some tumors (three of 11 cases). Transcriptional profiling revealed increased expression of genes related to Th1 and cytotoxic cell function in PD-L1-high tumors, suggesting that PD-L1 acts as a pathway of adaptive immune resistance in SCCOHT. These findings suggest that although SCCOHT are low–mutational burden tumors, their immunogenic microenvironment resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade

Evolution on a smooth landscape

We study in detail a recently proposed simple discrete model for evolution on smooth landscapes. An asymptotic solution of this model for long times is constructed. We find that the dynamics of the population are governed by correlation functions that although being formally down by powers of $N$ (the population size) nonetheless control the evolution process after a very short transient. The long-time behavior can be found analytically since only one of these higher-order correlators (the two-point function) is relevant. We compare and contrast the exact findings derived herein with a previously proposed phenomenological treatment employing mean field theory supplemented with a cutoff at small population density. Finally, we relate our results to the recently studied case of mutation on a totally flat landscape.Comment: Revtex, 15 pages, + 4 embedded PS figure

Spitzer Space Telescope observatory planning and scheduling team

Launched as the space infrared telescope facility (SIRTF) in August, 2003 and renamed in early 2004, the Spitzer space telescope is performing an extended series of science observations at wavelengths ranging from 3 to 180 microns. The California Institute of Technology is the home of the Spitzer Science Center (SSC) and operates the science operations system (SOS), which supports science operations of the observatory. A key function supported by the SOS is the long-range planning and short-term scheduling of the observatory. This paper describes the role and function of the SSC observatory planning and scheduling team (OPST), its operational interfaces, processes, and tools

SRTR Program-Specific Reports on Outcomes: A Guide for the New Reader

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72405/1/j.1600-6143.2008.02178.x.pd

Abstract 2988: DOK2 suppression by methylation induces platinum resistance via suppression of apoptosis in ovarian cancer cells.

Ovarian cancers are highly heterogeneous and while chemotherapy is the preferred treatment, many patients are intrinsically resistant or quickly develop resistance. Furthermore, all tumors that recur will become resistant. Recent evidence suggests that epigenetic deregulation may be a key factor in the onset and maintenance of chemoresistance. To examine the ovarian epigenome, we first analyzed a set of 43 primary ovarian tumors and 9 normal ovarian samples. Since therapy response is a significant issue for ovarian cancer patients we analyzed the epigenetic differences that segregate with platinum response. We then associated expression data to identify genes with expression changes potentially altered by promoter methylation to generate a list of candidate platinum resistance genes. Next, we developed a tissue culture carboplatin resistance screen to determine which candidates functionally affect resistance. The screen utilized pools of shRNAs of the candidate genes to identify genes that when repressed allowed survival from carboplatin treatment, in order to validate that our epigenetics screen identified genes involved in resistance. Of the genes identified in the screen we further characterized one gene, docking protein 2 (DOK2), an adapter protein downstream of tyrosine kinase, to determine if we could elucidate what mechanism was used to increase resistance. Our analysis determined that loss of DOK2 decreased the level of apoptosis in response to carboplatin. In addition, we determined that in cells with reduced DOK2, the level of anoikis was decreased, a mechanism of possible importance in ovarian cancer where there is a large number of cells floating in ascites. Functional analysis of the DOK2 genes ability to affect resistance validates this approach to finding genes involved in carboplatin resistance

White Light Demonstration of One Hundred Parts per Billion Irradiance Suppression in Air by New Starshade Occulters

A new mission concept for the direct imaging of exo-solar planets called the New Worlds Observer (NWO) has been proposed. The concept involves flying a meter-class space telescope in formation with a newly-conceived, specially-shaped, deployable star-occulting shade several meters across at a separation of some tens of thousands of kilometers. The telescope would make its observations from behind the starshade in a volume of high suppression of incident irradiance from the star around which planets orbit. The required level of irradiance suppression created by the starshade for an efficacious mission is of order 0.1 to 10 parts per billion in broadband light. This paper discusses the experimental setup developed to accurately measure the suppression ratio of irradiance produced at the null position behind candidate starshade forms to these levels. It also presents results of broadband measurements which demonstrated suppression levels of just under 100 parts per billion in air using the Sun as a light source. Analytical modeling of spatial irradiance distributions surrounding the null are presented and compared with photographs of irradiance captured in situ behind candidate starshades

Wall-Crossing from Boltzmann Black Hole Halos

A key question in the study of N=2 supersymmetric string or field theories is to understand the decay of BPS bound states across walls of marginal stability in the space of parameters or vacua. By representing the potentially unstable bound states as multi-centered black hole solutions in N=2 supergravity, we provide two fully general and explicit formulae for the change in the (refined) index across the wall. The first, "Higgs branch" formula relies on Reineke's results for invariants of quivers without oriented loops, specialized to the Abelian case. The second, "Coulomb branch" formula results from evaluating the symplectic volume of the classical phase space of multi-centered solutions by localization. We provide extensive evidence that these new formulae agree with each other and with the mathematical results of Kontsevich and Soibelman (KS) and Joyce and Song (JS). The main physical insight behind our results is that the Bose-Fermi statistics of individual black holes participating in the bound state can be traded for Maxwell-Boltzmann statistics, provided the (integer) index \Omega(\gamma) of the internal degrees of freedom carried by each black hole is replaced by an effective (rational) index \bar\Omega(\gamma)= \sum_{m|\gamma} \Omega(\gamma/m)/m^2. A similar map also exists for the refined index. This observation provides a physical rationale for the appearance of the rational Donaldson-Thomas invariant \bar\Omega(\gamma) in the works of KS and JS. The simplicity of the wall crossing formula for rational invariants allows us to generalize the "semi-primitive wall-crossing formula" to arbitrary decays of the type \gamma\to M\gamma_1+N\gamma_2 with M=2,3.Comment: 71 pages, 1 figure; v3: changed normalisation of symplectic form 3.22, corrected 3.35, other cosmetic change