1,392 research outputs found

    The Cost of Majority-Party Bias: Amending Activity under Structured Rules

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    All major legislation in the House necessitates a special rule from the Rules Committee before it can be brought to the chamber floor. These rules often strictly limit floor amendments to bills considered by the House. Scholars of political parties have argued that the House majority party can bias policy output away from the floor median through its usage of restrictive rules. In this article, we argue that in order to secure the passage of restrictive rules, the majority often makes concessions to centrist legislators through the amending process. We examine this theory using a newly collected data set that includes all amendments considered by the Rules Committee during the construction of structured rules in the 109th, 110th, and 111th Congresses (2005–2010). Our results are mixed, but they do suggest that moderate members of the majority party often receive concessions via amendments for their support of the majority party's agenda-setting regime

    Mutual Fund Survivorship

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    This article provides a comprehensive study of survivorship issues using the mutual fund data of Carhart (1997). We demonstrate theoretically that when survival depends on multiperiod performance, the survivorship bias in average performance typically increases with the sample length. This is empirically relevant because evidence suggests a multiyear survival rule for U.S. mutual funds. In the data we find the annual bias increases from 0.07% for 1-year samples to 1% for samples longer than 15 years. We find that survivor conditioning weakens evidence of performance persistence. Finally, we explain how survivor conditioning affects the relation between performance and fund characteristics

    Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

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    Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan

    Bone seeking matrix metalloproteinase-2 inhibitors prevent bone metastatic breast cancer growth

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    Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorÎČ (TGFÎČ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed. Therefore, to overcome potential toxicities noted with previous broad-spectrum MMP inhibitors (MMPIs), we used highly selective bisphosphonic based MMP-2 inhibitors (BMMPIs) that allowed for specific bone targeting. In vitro, BMMPIs impacted the viability of breast cancer cell lines and osteoclast precursors but not osteoblasts. In vivo, we demonstrated using two bone metastatic models (PyMT-R221A and 4T1) that BMMPI treatment significantly reduced tumor growth and tumor associated bone destruction. Additionally, BMMPIs are superior in promoting tumor apoptosis compared to the standard of care bisphosphonate, zoledronate. We demonstrated MMP-2 selective inhibition in the bone microenvironment using specific and broad spectrum MMP probes. Further, compared to zoledronate, BMMPI treated mice had significantly lower levels of TGFÎČ signaling and MMP generated type I collagen carboxy-terminal (ICTP) fragments. Taken together, our data show the feasibility of selective inhibition of MMPs in the bone metastatic breast cancer microenvironment. We posit that BMMPIs could be easily translated to the clinical setting for the treatment of bone metastases given the well-tolerated nature of bisphosphonates

    Effect of room temperature transport vials on DNA quality and phylogenetic composition of faecal microbiota of elderly adults and infants

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    Background: Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal microbiota is widely used as a non-invasive and ethically simple proxy for intestinal biopsies. There is an urgent need for collection and transport media that would allow faecal sampling at distance from the processing laboratory, obviating the need for same-day DNA extraction recommended by previous studies of freezing and processing methods for stool. We compared the faecal bacterial DNA quality and apparent phylogenetic composition derived using a commercial kit for stool storage and transport (DNA Genotek OMNIgene GUT) with that of freshly extracted samples, 22 from infants and 20 from older adults. Results: Use of the storage vials increased the quality of extracted bacterial DNA by reduction of DNA shearing. When infant and elderly datasets were examined separately, no differences in microbiota composition were observed due to storage. When the two datasets were combined, there was a difference according to a Wilcoxon test in the relative proportions of Faecalibacterium, Sporobacter, Clostridium XVIII, and Clostridium XlVa after 1 week's storage compared to immediately extracted samples. After 2 weeks' storage, Bacteroides abundance was also significantly different, showing an apparent increase from week 1 to week 2. The microbiota composition of infant samples was more affected than that of elderly samples by storage, with significantly higher Spearman distances between paired freshly extracted and stored samples (

    Drivers of potentially avoidable emergency admissions in Ireland: an ecological analysis

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    Background: Many emergency admissions are deemed to be potentially avoidable in a well-performing health system. Objective: To measure the impact of population and health system factors on county-level variation in potentially avoidable emergency admissions in Ireland over the period 2014–2016. Methods: Admissions data were used to calculate 2014–2016 age-adjusted emergency admission rates for selected conditions by county of residence. Negative binomial regression was used to identify which a priori factors were significantly associated with emergency admissions for these conditions and whether these factors were also associated with total/other emergency admissions. Standardised incidence rate ratios (IRRs) associated with a 1 SD change in risk factors were reported. Results: Nationally, potentially avoidable emergency admissions for the period 2014–2016 (266 395) accounted for 22% of all emergency admissions. Of the population factors, a 1 SD change in the county-level unemployment rate was associated with a 24% higher rate of potentially avoidable emergency admissions (IRR: 1.24; 95% CI 1.04 to 1.41). Significant health system factors included emergency admissions with length of stay equal to 1 day (IRR: 1.20; 95% CI 1.11 to 1.30) and private health insurance coverage (IRR: 0.92; 95% CI 0.89 to 0.96). The full model accounted for 50% of unexplained variation in potentially avoidable emergency admissions in each county. Similar results were found across total/other emergency admissions. Conclusion: The results suggest potentially avoidable emergency admissions and total/other emergency admissions are primarily driven by socioeconomic conditions, hospital admission policy and private health insurance coverage. The distinction between potentially avoidable and all other emergency admissions may not be as useful as previously believed when attempting to identify the causes of regional variation in emergency admission rates

    Engaging with terminology in the multilingual classroom:Teachers’ practices for bridging the gap between L1 lectures and English reading

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    In some academic settings where English is not the first language it is nonetheless common for reading to be assigned in English, and the expectation is often that students will acquire subject terminology incidentally in the first language as well as in English as a result of listening and reading. It is then a prerequisite that students notice and engage with terminology in both languages. To this end, teachers’ classroom practices for making students attend to and engage with terms are crucial for furthering students’ vocabulary competence in two languages. Using transcribed video recordings of eight undergraduate lectures from two universities in such a setting, this paper provides a comprehensive picture of what teachers ‘do’ with terminology during a lecture, i.e., how terms are allowed to feature in the classroom discourse. It is established, for example, that teachers nearly always employ some sort of emphatic practice when using a term in a lecture. However, the repertoire of such practices is limited. Further, teachers rarely adapt their repertoires to cater to the special needs arguably required in these settings, or to exploit the affordances of multilingual environments

    Zooming in and out : studying practices by switching theoretical lenses and trailing connections

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    This paper contributes to re-specifying a number of the phenomena of interest to organisational studies in terms of patterns of socio-material practices and their effects. It does so by outlining a vocabulary and strategy that make up a framework for theorising work and organisational practices. The vocabulary is based on number of sensitising concepts that connote practice as an open-ended, heterogeneous accomplishment which takes place within a specific horizon of sense and a set of concerns which the practice itself brings to bear. The strategy is based on the metaphorical movement of "zooming in" and "zooming out of" practice. The zooming in and out are obtained through switching theoretical lenses and repositioning in the field, so that certain aspects of the practice are fore-grounded while others are bracketed. Building on the results of an extended study of telemedicine, the paper discusses in detail the different elements of the framework and how it enhances our capacity to re-present practice. The paper concludes with some considerations on how the proposed approach can assist us in advancing the research agenda of organizational and work studies

    All-optical synchronization of self-pulsating laser diodes

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    We examine the behavior of self‐pulsating laser diodes when injected with periodic optical signals. We experimentally and theoretically investigate the phase difference between the injected optical signal and the synchronized self‐pulsating laser diode emission. We explore the phase difference dependence on detuning between the laser free‐running self‐pulsation frequency and the applied signal frequency, and on the injected signal power. The determined sensitive dependence of the phase difference on these factors has important consequences when self‐pulsating lasers are used as optical signal processing elements in all‐optical communication networks, where such sensitivity may lead to timing problems
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