How Important Are Wages to the Elderly? Evidence from the New Beneficiary Data System and the Social Security Earnings Test

More than 40 percent of Social Security beneficiaries continue to work after age 65. This research investigates the extent to which these individuals substitute labor across periods in response to anticipated wage changes induced by the Social Security earnings test. While we find that a disproportionate number of individuals choose earnings within a few percentage points of the earnings limit, we find no evidence that these individuals substitute labor supply between

Emergence of a STAT3 mutated NK clone in LGL leukemia

AbstractLarge granular lymphocyte (LGL) leukemia is a chronic clonal lymphoproliferative disorder. Here, a T-LGL leukemia patient developed NK-LGL leukemia with residual leukemic T-LGL. TCRVβ usage and CDR3 sequence drifts were observed with disease progression. A STAT3 S614R mutation was identified in NK but not T-cells in the mixed leukemic stage. Multiple, non-dominant T-cell clones with distinct STAT3 mutations were present throughout. Our results suggest that T and NK-LGL leukemia may share common pathogenesis mechanisms and that STAT3 mutation alone is insufficient to bring about clonal expansion. Mutational and immunological monitoring may provide diagnostic and therapeutic significance in LGL leukemia

Automating the Verification of the Low Voltage Network Cables and Topologies

Low Voltage (LV) networks are increasingly required to cope with challenges they were not designed for, requiring for more active network management (ANM). Crucially, ANM solutions require the availability of accurate network information. In practice, available data on LV networks can be incomplete, a problem often overlooked in prior ANM research. For example, in the U.K. and many developed countries, the lifetime of distribution networks assets spans several decades, with some of the available asset data gathered and maintained over many years. This can often lead to incomplete cable data being available to network operators. To overcome this, we propose a novel machine learning technique to autonomously approximate the missing cable information in LV networks. Our proposed algorithm uses a tree-based search methodology, which approximates the missing cable's cross section area (XSA) data based on rules engineers used when designing the LV networks. We validate our approach using a large database of real LV networks, where some of the cables' XSA are treated as unknown and used as ground truth to evaluate the accuracy of the predictions. Moreover, we propose a mechanism that scores the confidence level of the prediction, information which is then presented to the human network planners

Enhanced Neutrophil Extracellular Trap Formation in Acute Pancreatitis Contributes to Disease Severity and Is Reduced by Chloroquine

Background: Neutrophil extracellular traps (NETs) are generated when activated neutrophils, driven by PAD4, release their DNA, histones, HMGB1, and other intracellular granule components. NETs play a role in acute pancreatitis, worsening pancreatic inflammation, and promoting pancreatic duct obstruction. The autophagy inhibitor chloroquine (CQ) inhibits NET formation; therefore, we investigated the impact of CQ mediated NET inhibition in murine models of pancreatitis and human correlative studies. Methods: L-arginine and choline deficient ethionine supplemented (CDE) diet models of acute pancreatitis were studied in wild type and PAD4−/− mice, incapable of forming NETs. Isolated neutrophils were stimulated to induce NET formation and visualized with fluorescence microscopy. CQ treatment (0.5 mg/ml PO) was initiated after induction of pancreatitis. Biomarkers of NET formation, including cell-free DNA, citrullinated histone H3 (CitH3), and MPO-DNA conjugates were measured in murine serum and correlative human patient serum samples. Results: We first confirmed the role of NETs in the pathophysiology of acute pancreatitis by demonstrating that PAD4−/− mice had decreased pancreatitis severity and improved survival compared to wild-type controls. Furthermore, patients with severe acute pancreatitis had elevated levels of cell-free DNA and MPO-DNA conjugates, consistent with NET formation. Neutrophils from mice with pancreatitis were more prone to NET formation and CQ decreased this propensity to form NETs. CQ significantly reduced serum cell-free DNA and citrullinated histone H3 in murine models of pancreatitis, increasing survival in both models. Conclusions: Inhibition of NETs with CQ decreases the severity of acute pancreatitis and improves survival. Translating these findings into clinical trials of acute pancreatitis is warranted

The Grizzly, November 19, 1982

Dorm Intrusion: Attack Prompts Security Changes • Council Approves Precalc • Student Apathy: Who Cares? • Elephants and Donkeys Revived on Campus • President\u27s Corner • Pledging Changes Planned • Commentary: Be a Good Boy, Johnny - Take Back Your Tray • Lewis on Wall Street • Applying for the Job • Robert Hazard: The Grizzly Interview • Final Exam Schedule • Grizzly Paws Boost Football Program • Women\u27s Basketball Set to Have Big Season • X-Country Takes a Disappointing Sixth • Soccer Team Was Tough All Year • Men\u27s Swimming Falls to Dickinson in Openerhttps://digitalcommons.ursinus.edu/grizzlynews/1089/thumbnail.jp

Identifying barriers and facilitators of hearing protection use in early-career musicians:a basis for designing interventions to promote uptake and sustained use

Objective The current study aimed to: i) determine the patterns of hearing protection device (HPD) use in early-career musicians, ii) identify barriers to and facilitators of HPD use, and iii) use the Behaviour Change Wheel (BCW) to develop an intervention to increase uptake and sustained use of HPDs. Design A mixed-methods approach using questionnaires and semi-structured interviews. Study sample Eighty early-career musicians (age range = 18–26 years; women n = 39), across all categories of musical instrument. Results 42.5% percent of participants reported using HPDs at least once a week, 35% less than once a week, and 22.5% reported never using HPDs for music-related activities. Six barriers and four facilitators of HPD use were identified. Barriers include the impact of HPDs on listening to music and performing, and a lack of concern about noise exposure. Barriers/facilitators were mapped onto the Theoretical Domains Framework. Following the systematic process of the BCW, our proposed intervention strategies are based on ‘Environmental Restructuring’, such as providing prompts to increase awareness of noisy settings, and ‘Persuasion/Modelling’, such as providing credible role models. Conclusions For the first time, the present study demonstrates the use of the BCW for designing interventions in the context of hearing conservation

miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia

T-LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of constitutive activation of the STAT3 and ERK pathway. Notably, in 40% of patients, constitutive STAT3 activation is due to STAT3 activating mutations, whereas in 60% this is unknown. As miRNAs are amongst the most potent regulators in health and disease, we hypothesized that aberrant miRNA expression could contribute to dysregulation of these pathways. miRNA sequencing in T-LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miR-181a. Furthermore, geneset enrichment analysis (GSEA) of downregulated targets of miR-181a implicated involvement in regulating STAT3 and ERK1/2 pathways. Flow cytometric analyses showed increased SOCS3+ and DUSP6+ T-LGL cells upon miR-181a inhibition. In addition, miR-181a-transfected human CD8+ T cells showed increased basal STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line, we could show that miR-181a is an actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition and ERK1/2 phosphorylation by DUSP6 inhibition and verified this mechanism in an independent cell line. In addition, miR-181a inhibition resulted in a higher sensitivity to FAS-mediated apoptosis. Collectively, our data show that miR-181a could be the missing link to explain why STAT3-unmutated patients show hyperactive STAT3

Default Risk and Equity Returns: A Comparison of the Bank-Based German and the U.S. Financial System

In this paper, we address the question whether the impact of default risk on equity returns depends on the financial system firms operate in. Using an implementation of Merton's option-pricing model for the value of equity to estimate firms' default risk, we construct a factor that measures the excess return of firms with low default risk over firms with high default risk. We then compare results from asset pricing tests for the German and the U.S. stock markets. Since Germany is the prime example of a bank-based financial system, where debt is supposedly a major instrument of corporate governance, we expect that a systematic default risk effect on equity returns should be more pronounced for German rather than U.S. firms. Our evidence suggests that a higher firm default risk systematically leads to lower returns in both capital markets. This contradicts some previous results for the U.S. by Vassalou/Xing (2004), but we show that their default risk factor looses its explanatory power if one includes a default risk factor measured as a factor mimicking portfolio. It further turns out that the composition of corporate debt affects equity returns in Germany. Firms' default risk sensitivities are attenuated the more a firm depends on bank debt financing

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).