Incorporating Policymaker Costs and Political Competition into Rent-Seeking Games

We incorporate policymaker costs of supplying rents and variable intensities of competition among rent seekers into the standard rent-seeking game. By incorporating these aspects, the game has greater verisimilitude to the lobbying process. The first aspect captures the fact that in rent-seeking contests there is a positive probability that neither firm will obtain the rent. The second aspect captures the fact that firms seeking different rents still must compete for policymakers\u27 resources. We find that lobbying expenditures, rent-seeking profits, and rent dissipation depend on the intensity of competition and the value of the rent relative to policymaker costs. For example, if the value of the rent is sufficiently high relative to policymakers\u27 costs, an increase in the intensity of political competition will increase lobbying expenditures; otherwise, expenditures fall as competitive intensity increases. In addition, the model establishes pure-strategy equilibria with underdissipation where only mixed-strategy equilibria exist in the standard model

CAIRNS: The Cluster And Infall Region Nearby Survey III. Environmental Dependence of H-alpha Properties of Galaxies

We investigate the environmental dependence of star formation in cluster virial regions and infall regions as part of CAIRNS (Cluster And Infall Region Nearby Survey), a large spectroscopic survey of the infall regions surrounding nine nearby rich clusters of galaxies. Our long-slit spectroscopy yields estimates of star formation rates in environments from cluster cores to the general large-scale structure. The fraction of galaxies with current star formation in their inner disks as traced by H-alpha emission increases with distance from the cluster and converges to the ``field'' value only at 2-3 virial radii, in agreement with other investigations. However, among galaxies with significant current star formation (EW[Ha]geq2\AA), there is no difference in the distribution of EW[Ha] inside and outside the virial radius. This surprising result, first seen by Carter et al., suggests that (1) star formation is truncated on either very short timescales or only at moderate and high redshifts or (2) that projection effects contaminate the measurement. The number density profiles of star-forming and non-star-forming galaxies indicate that, among galaxies projected inside the virial radius, at least half of the former and 20% of the latter are ``infall interlopers,'' galaxies in the infall region but outside the virial region. The kinematics of star-forming galaxies in the infall region closely match those of absorption-dominated galaxies. This result shows that the star forming galaxies in the infall regions are not interlopers from the field and excludes one model of the backsplash scenario of galaxy transformation. Finally, we quantify systematic uncertainties in estimating the global star formation in galaxies from their inner disks.Comment: 25 pages, 21 figures, accepted for publication in A

Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro

<p>Abstract</p> <p>Background</p> <p>Imatinib mesylate has significantly improved survival and quality of life of patients with gastrointestinal stromal tumors (GISTs). However, the molecular mechanism through which imatinib exerts its anti-tumor effects is not clear. Previously, we found up-regulation of insulin-like growth factor binding protein-3 (IGFBP3) expression in imatinib-responsive GIST cells and tumor samples. Because IGFBP3 regulates cell proliferation and survival and mediates the anti-tumor effects of a number of anti-cancer agents through both IGF-dependent and IGF-independent mechanisms, we hypothesized that IGFBP3 mediates GIST cell response to imatinib. To test this hypothesis, we manipulated IGFBP3 levels in two imatinib-responsive GIST cell lines and observed cell viability after drug treatment.</p> <p>Results</p> <p>In the GIST882 cell line, imatinib treatment induced endogenous IGFBP3 expression, and IGFBP3 down-modulation by neutralization or RNA interference resulted in partial resistance to imatinib. In contrast, IGFBP3 overexpression in GIST-T1, which had no detectable endogenous IGFBP3 expression after imatinib, had no effect on imatinib-induced loss of viability. Furthermore, both the loss of IGFBP3 in GIST882 cells and the overexpression of IGFBP3 in GIST-T1 cells was cytotoxic, demonstrating that IGFBP3 has opposing effects on GIST cell viability.</p> <p>Conclusion</p> <p>This data demonstrates that IGFBP3 has dual, opposing roles in modulating GIST cell viability and response to imatinib <it>in vitro</it>. These preliminary findings suggest that there may be some clinical benefits to IGFBP3 therapy in GIST patients, but further studies are needed to better characterize the functions of IGFBP3 in GIST.</p

Tasas mínimas de captura-recaptura y años de funcionamiento de la estación de anillamiento para obtener estimaciones confiables de la supervivencia anual de los adultos

We examined variability in adult annual survival rate estimates for 33 breeding bird species, using 2011&ndash;2019 data from a 38-station Monitoring Avian Productivity and Survivorship (MAPS) program in Alberta, Canada. Using coefficient of variation (CV) as a metric, we provide recommendations for number of years a station should be operated and numbers of captures and between-year recaptures required to achieve acceptable levels of precision for adult survival estimation. Our primary aim was to provide minimum sample-size guidelines for MAPS banding station operators. The proportion of individual species &times; spatial scale scenarios for which we could obtain adult survival estimates, as well as the precision of those estimates, increased substantially once six years of data were collected, and we recommend six years as a target minimum level of continuity for banding station operation. Across 33 species analyzed, averages of 23.4 captures (3.9/yr) and 2.1 recaptures (0.4/yr) were needed to yield marginally precise survival estimates (CV of 20% to 30%, inclusive), while averages of 89.2 captures (14.9/yr) and 6.3 recaptures (1.1/yr) were needed to achieve more precise estimates (CV &lt; 20%). We suggest these as guidelines for minimum capture and recapture rates at the scale of individual banding stations and for clusters of stations, e.g., multiple stations operated in a selected habitat type or sampling region, respectively. It should be noted, however, that sample-size requirements will vary markedly among species. For example, reliable estimates of survival for species with low between-year site fidelity, e.g., Tennessee Warbler (Leiothlypis peregrina), will not be obtainable at any sample size; while species with high inter-annual site fidelity and recapture probabilities, e.g., some flycatchers, thrushes, sparrows, and wood warblers, will require smaller sample sizes than those proposed here as guidelines.</p

AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: a SWOG report.

Background: The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. Methods: In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, Results: Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age \u3c 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for Conclusions: While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification

Severity and justness do not moderate the relation between corporal punishment and negative child outcomes: A multicultural and longitudinal study

There is strong evidence of a positive association between corporal punishment and negative child outcomes, but previous studies have suggested that the manner in which parents implement corporal punishment moderates the effects of its use. This study investigated whether severity and justness in the use of corporal punishment moderate the associations between frequency of corporal punishment and child externalizing and internalizing behaviors. This question was examined using a multicultural sample from eight countries and two waves of data collected one year apart. Interviews were conducted with 998 children aged 7–10 years, and their mothers and fathers, from China, Colombia, Italy, Jordan, Kenya, Philippines, Thailand, and the United States. Mothers and fathers responded to questions on the frequency, severity, and justness of their use of corporal punishment; they also reported on the externalizing and internalizing behavior of their child. Children reported on their aggression. Multigroup path models revealed that across cultural groups, and as reported by mothers and fathers, there is a positive relation between the frequency of corporal punishment and externalizing child behaviors. Mother-reported severity and father-reported justness were associated with child-reported aggression. Neither severity nor justness moderated the relation between frequency of corporal punishment and child problem behavior. The null result suggests that more use of corporal punishment is harmful to children regardless of how it is implemented, but requires further substantiation as the study is unable to definitively conclude that there is no true interaction effect

International evaluation of an AI system for breast cancer screening.

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful1. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives2. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.Professor Fiona Gilbert receives funding from the National Institute for Health Research (Senior Investigator award)

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations