DRG Undersea Consulting (United States)

The lifetime risk of silicosis associated with low-level occupational exposure to respirable crystalline silica remains unclear because most previous radiographic studies included workers with varying exposure concentrations and durations. This study assessed the prevalence of silicosis after lengthy exposure to respirable crystalline silica at levels ≤ 0.10 mg/m3. Vermont granite workers employed any time during 1979-1987 were traced and chest radiographs were obtained for 356 who were alive in 2017 and residing in Vermont. Work history, smoking habits and respiratory symptoms were obtained by interview, and exposure was estimated using a previously developed job-exposure matrix. Associations between radiographic findings, exposure, and respiratory symptoms were assessed by ANOVA, chi-square tests and binary regression. Fourteen workers (3.9%) had radiographic evidence of silicosis, and all had been employed ≥30 years. They were more likely to have been stone cutters or carvers and their average exposure concentrations and cumulative exposures to respirable crystalline silica were significantly higher than workers with similar durations of employment and no classifiable parenchymal abnormalities. This provides direct evidence that workers with long-term exposure to low-level respirable crystalline silica (≤0.10 mg/m3) are at risk of developing silicosis.

We address the problem of configuring a power distribution network with reliability and resilience objectives by satisfying the demands of the consumers and saturating each production source as little as possible. We consider power distribution networks containing source nodes producing electricity, nodes representing electricity consumers and switches between them. Configuring this network consists in deciding the orientation of the links between the nodes of the network. The electric flow is a direct consequence of the chosen configuration and can be computed in polynomial time. It is valid if it satisfies the demand of each consumer and capacity constraints on the network. In such a case, we study the problem of determining a feasible solution that balances the loads of the sources, that is their production rates. We use three metrics to measure the quality of a solution: minimizing the maximum load, maximizing the minimum load and minimizing the difference of the maximum and the minimum loads. This defines optimization problems called respectively min-M, max-m and min-R. In the case where the graph of the network is a tree, it is known that the problem of building a valid configuration is polynomial. We show the three optimization variants have distinct properties regarding the theoretical complexity and the approximability. Particularly, we show that min-M is polynomial, that max-m is NP-Hard but belongs to the class FPTAS and that min-R is NP-Hard, cannot 1 be approximated to within any exponential relative ratio but, for any $\epsilon$ > 0, there exists an algorithm for which the value of the returned solution equals the value of an optimal solution shifted by at most $\epsilon$.

Abstract Background: Immunotherapy with checkpoint inhibition is active in mTNBC. Both pembrolizumab and atezolizumab are FDA approved for programmed cell death ligand 1 positive (PDL1+) mTNBC. Vaccines may further induce host immune response and enhance therapeutic activity of checkpoint inhibitors. PVX-410 (PVX) (OncoPep, Inc.) is a novel, HLA-A2 restricted, tetra-peptide vaccine, with 3 of its 4 antigens (XBP1[2 splice variants] and CD138) commonly overexpressed in TNBC. We present results from a phase 1b study evaluating the immune response, safety and tolerability, and clinical activity of PVX and pembrolizumab (PEM) in mTNBC. Methods: Eligibility for this phase 1b multi-center, single-arm study included HLA-A2+, PD-L1 unselected female patients (pts) ≥18 years with metastatic or inoperable locally advanced TNBC, measurable disease, and any number of prior therapies, including prior checkpoint inhibitor therapy. Pts received 6 doses of 800µg PVX emulsified in Montanide ISA 720 VG by subcutaneous injection co-administered with intramuscular Hiltonol weekly for 6 weeks (wks) followed by booster vaccine doses at wks 10 and 28, with concurrent intravenous 200 mg PEM every 3 wks starting with the second PVX dose. Therapy was given until progressive disease, unacceptable toxicity or a maximum of 24 months. Blood samples were scheduled for immune response assessment at baseline and at weeks 2, 5, 10, 28, and 52 post-treatment initiation. The primary objective was PVX- specific immune response at week 10. Immune response was defined as a ≥2-fold change over baseline in the proportion of CD3+CD8+ T cells that expressed IFNγ and the proportion of CD3+CD8+ T cells positive for PVX tetramers following an in vitro stimulation of PBMC with PVX peptides using a flow cytometric assay. Secondary objectives were immune response at wk 28, safety and tolerability, and clinical endpoints (RR, CBR, DCR, DoR, PFS, and OS). Results: Between 3/2018 and 8/2020, 19 pts enrolled. Median age was 62 yrs (range 46-79), with median 2 (range 0-9) lines of prior therapy for metastatic disease. Median disease-free interval among 16 pts with prior early TNBC was 3.3 years. Among 19 enrolled patients, 16 were available for analysis at the time of abstract submission. Among the 16, 10 pts were evaluable at week 10 and 7(70%) demonstrated a PVX specific immune response. There were 6 patients who progressed before week 10, of whom 3 (50%) had a positive immune response at the EOT visit. Immune response persisted in all evaluable pts assessed at week 28 (n=4). Immune response data for all evaluable patients will be updated at the presentation. Among 19 patients evaluable for safety analysis, the most common adverse events (AEs) attributable to PVX (grade ≥2) included: fatigue (21%), arthralgia (11%) injection site reaction (5 %) pain (5%) lymphocyte count decreased (5%), maculopapular rash (5%) and skin infection (5%) . There were two grade 3 AEs attributed to PEM (AST elevation, hyponatremia) and one grade 4 AE (ALT elevation). There were no grade 5 AEs. The clinical benefit rate (CR+PR+SD for ≥16 weeks) was 31.6% with no confirmed partial or complete responses. Best overall response was SD in 9 (47%) patients. Analysis of additional clinical endpoints including PFS and OS is ongoing and will be presented at the meeting. Conclusions: PVX plus PEM is safe with manageable toxicity in pts with mTNBC. No new unexpected adverse events were identified. Immune response data show PVX induces antigen-specific T cell expansion as observed by increases in PVX tetramer and IFN positive T cells. Clinical disease control was observed with a CBR of 31.6%. Based on these promising immune response results in this pretreated population, a phase 2 study with PVX+PEM in combination with standard chemotherapy in treatment naïve, PD-L1+ mTNBC is underway (NCT04634747). Citation Format: Steven J Isakoff, Nadine M. Tung, Jun Yin, Nabihah Tayob, Joanne Parker, Julie Rosenberg, Aditya Bardia, Laura Spring, Hannah Park, Maya Collins, William T. Barry, Mariano Severgnini, Doris Peterkin, Sara M. Tolaney. A phase 1b study of PVX-410 vaccine in combination with pembrolizumab in metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-17.

This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.

Grounded in signaling theory, this paper investigates the signals reflecting product quality, innovativeness, reputation and cultural background which influence film performance, that is, film survival (duration on cinema screen) and box office success, in China’s changing institutional context. This market has grown substantially and still possesses potential for further development. However, China’s unique institutional context presents challenges. By examining an expanded range of potential signals, two of which have not previously been examined in the literature, namely imported films and enhanced format film formats such as 3D and IMAX, we develop a conceptual framework and argue that signaling theory needs to be combined with institutional context. Similar to findings for film industries in other countries, we find quality and reputational signals including budget, star power, sequels, and online consumer reviews to be important in China. However, unique results are also revealed. Chinese consumers react to an innovativeness signal in that they are specifically attracted to enhanced format films. Film award nominations and prizes are insignificant reputational signals. Once other signals are taken into account, imported films on average do not perform as well as domestic films. We link these findings to China’s unique institutional setting and offer important implications for management, recognizing the challenges to film companies of competing in an increasingly globalized market. This paper is also of relevance to policymakers given their continued efforts in shaping the development of China’s film industry.

Graphing calculators – how wonderful they are! My older TI-83 Plus can do lots. Unfortunately, I don’t have the latest and greatest TI-89 yet.

A linear regression examines the correlation of an independent variable to a dependent variable. In other words, a linear regression represents the degree to which an independent variable predicts a dependent variable. (The "linear" portion refers to the one independent variable.) Two or more groups may be examined. Both independent and dependent variables should be interval. The data should have an approximate normal distribution.

A structural equation model is a multivariate model that permits variables to be related in chains or paths, whose analysis allows you to find a model that fits data very well, whose lack of fit is not significant. This seems counterintuitive. Stated another way, if the model is significant, then it does not fit the data.

As previously explained, a multiple regression analysis is a type of test that analyzes the amount of variance explained in a dependent variable by more than one predictor variable. The variables are interval, but sometimes they may have continuous predictors, meaning they are not discrete. For example, weight is a continuous variable, since someone may weigh 125.6 pounds. Sometimes, a researcher wishes to examine the interactions between predictors, when the data are centered.

The concept of expected value is a mystery to many students (and many teachers, as well). Most students understand that it is an average, of some sort. Specifically stated, for one trial, the expected value is the average of possible outcomes.