189 research outputs found

    Differences in mtDNA haplogroup distribution among 3 Jewish populations alter susceptibility to T2DM complications

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    BACKGROUND: Recent genome-wide association studies searching for candidate susceptibility loci for common complex diseases such as type 2 diabetes mellitus (T2DM) and its common complications have uncovered novel disease-associated genes. Nevertheless these large-scale population screens often overlook the tremendous variation in the mitochondrial genome (mtDNA) and its involvement in complex disorders. RESULTS: We have analyzed the mitochondrial DNA (mtDNA) genetic variability in Ashkenazi (Ash), Sephardic (Seph) and North African (NAF) Jewish populations (total n = 1179). Our analysis showed significant differences (p < 0.001) in the distribution of mtDNA genetic backgrounds (haplogroups) among the studied populations. To test whether these differences alter the pattern of disease susceptibility, we have screened our three Jewish populations for an association of mtDNA genetic haplogroups with T2DM complications. Our results identified population-specific susceptibility factors of which the best example is the Ashkenazi Jewish specific haplogroup N1b1, having an apparent protective effect against T2DM complications in Ash (p = 0.006), being absent in the NAF population and under-represented in the Seph population. We have generated and analyzed whole mtDNA sequences from the disease associated haplogroups revealing mutations in highly conserved positions that are good candidates to explain the phenotypic effect of these genetic backgrounds. CONCLUSION: Our findings support the possibility that recent bottleneck events leading to over-representation of minor mtDNA alleles in specific genetic isolates, could result in population-specific susceptibility loci to complex disorders

    Shot noise limited characterization of femtosecond light pulses

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    Probing the evolution of physical systems at the femto- or attosecond timescale with light requires accurate characterization of ultrashort optical pulses. The time profiles of such pulses are usually retrieved by methods utilizing optical nonlinearities, which require significant signal powers and operate in a limited spectral range\cite{Trebino_Review_of_Scientific_Instruments97,Walmsley_Review_09}. We present a linear self-referencing characterization technique based on time domain localization of the pulse spectral components, operated in the single-photon regime. Accurate timing of the spectral slices is achieved with standard single photon detectors, rendering the technique applicable in any spectral range from near infrared to deep UV. Using detection electronics with about 7070 ps response, we retrieve the temporal profile of a picowatt pulse train with 10\sim10 fs resolution, setting a new scale of sensitivity in ultrashort pulse characterization.Comment: Supplementary information contained in raw dat

    The Impact of the COVID-19 Pandemic on Care Delivery and Quality of Life in Lung Cancer Surgery

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    Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) pandemic and associated restrictions have altered the delivery of surgical care. The purpose of this study was to explore the impact of COVID-19 on care delivery and quality of life (QOL) from the perspectives of lung cancer surgery patients, family caregivers (FCGs), and thoracic surgery teams. Methods Patients/FCGs enrolled in a randomized trial of a self-management intervention for lung cancer surgery preparation/recovery were invited to participate in this qualitative study. Patients/FCGs data were collected separately 1-month postdischarge. Interviews were also conducted with thoracic surgery team members. Content analysis approaches were used to develop themes. Results Forty-one respondents including 19 patients, 18 FCGs, three thoracic surgeons, and one nurse practitioner participated in the study. Patient themes included isolation, psychological distress, delayed/impacted care, and financial impact. FCGs themes included caregiving challenges, worry about COVID-19, financial hardship, isolation, and physical activity limitations. Surgical team themes included witnessing patient/FCG\u27s distress, challenges with telehealth, communication/educational challenges, and delays in treatment. Conclusions COVID-19 had a varied impact on care delivery and QOL for lung cancer surgery dyads. Some dyads reported minimal impact, while others experienced added psychological distress, isolation, and caregiving challenges. Surgical teams also experienced challenges in the approach used to provide care

    Legal coercion, respect & reason-responsive agency

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    Legal coercion seems morally problematic because it is susceptible to the Hegelian objection that it fails to respect individuals in a way that is ‘due to them as men’. But in what sense does legal coercion fail to do so? And what are the grounds for this requirement to respect? This paper is an attempt to answer these questions. It argues that (a) legal coercion fails to respect individuals as reason-responsive agents; and (b) individuals ought to be respected as such in virtue of the fact that they are human beings. Thus it is in this sense that legal coercion fails to treat individuals with the kind of respect ‘due to them as men’.The Leverhulme Trust (ECF-2012-032); AHRC (AH/H015655/1

    Epidemiology of Non-small Cell Lung Cancer in Asian Americans: Incidence Patterns Among Six Subgroups by Nativity

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    BackgroundDifferences in the epidemiology of lung cancer between Asians and non-Hispanic whites have brought to light the relative influences of genetic and environmental factors on lung cancer risk. We set out to describe the epidemiology of non-small cell lung cancer (NSCLC) among Asians living in California, and to explore the effects of acculturation on lung cancer risk by comparing lung cancer rates between U.S.-born and foreign-born Asians.MethodsAge-adjusted incidence rates of NSCLC were calculated for Chinese, Filipino, Japanese, Korean, Vietnamese, and South Asians in California between 1988 and 2003 using data from the California Cancer Registry. Incidence rates were calculated and stratified by sex and nativity. We analyzed population-based tobacco smoking prevalence data to determine whether differences in rates were associated with prevalence of tobacco smoking.ResultsAsians have overall lower incidence rates of NSCLC compared with whites (29.8 and 57.7 per 100,000, respectively). South Asians have markedly low rates of NSCLC (12.0 per 100,000). Foreign-born Asian men and women have an approximately 35% higher rate of NSCLC than U.S.-born Asian men and women. The incidence pattern by nativity is consistent with the population prevalence of smoking among Asian men; however, among women, the prevalence of smoking is higher among U.S.-born, which is counter to their incidence patterns.ConclusionsForeign-born Asians have a higher rate of NSCLC than U.S.-born Asians, which may be due to environmental tobacco smoke or nontobacco exposures among women. South Asians have a remarkably low rate of NSCLC that approaches white levels among the U.S.-born. More studies with individual-level survey data are needed to identify the specific environmental factors associated with differential lung cancer risk occurring with acculturation among Asians

    Entangled Stories: The Red Jews in Premodern Yiddish and German Apocalyptic Lore

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    “Far, far away from our areas, somewhere beyond the Mountains of Darkness, on the other side of the Sambatyon River…there lives a nation known as the Red Jews.” The Red Jews are best known from classic Yiddish writing, most notably from Mendele's Kitser masoes Binyomin hashlishi (The Brief Travels of Benjamin the Third). This novel, first published in 1878, represents the initial appearance of the Red Jews in modern Yiddish literature. This comical travelogue describes the adventures of Benjamin, who sets off in search of the legendary Red Jews. But who are these Red Jews or, in Yiddish, di royte yidelekh? The term denotes the Ten Lost Tribes of Israel, the ten tribes that in biblical times had composed the Northern Kingdom of Israel until they were exiled by the Assyrians in the eighth century BCE. Over time, the myth of their return emerged, and they were said to live in an uncharted location beyond the mysterious Sambatyon River, where they would remain until the Messiah's arrival at the end of time, when they would rejoin the rest of the Jewish people. This article is part of a broader study of the Red Jews in Jewish popular culture from the Middle Ages through modernity. It is partially based on a chapter from my book, Umstrittene Erlöser: Politik, Ideologie und jüdisch-christlicher Messianismus in Deutschland, 1500–1600 (Göttingen: Vandenhoeck & Ruprecht, 2011). Several postdoctoral fellowships have generously supported my research on the Red Jews: a Dr. Meyer-Struckmann-Fellowship of the German Academic Foundation, a Harry Starr Fellowship in Judaica/Alan M. Stroock Fellowship for Advanced Research in Judaica at Harvard University, a research fellowship from the Heinrich Hertz-Foundation, and a YIVO Dina Abramowicz Emerging Scholar Fellowship. I thank the organizers of and participants in the colloquia and conferences where I have presented this material in various forms as well as the editors and anonymous reviewers of AJS Review for their valuable comments and suggestions. I am especially grateful to Jeremy Dauber and Elisheva Carlebach of the Institute for Israel and Jewish Studies at Columbia University, where I was a Visiting Scholar in the fall of 2009, for their generous encouragement to write this article. Sue Oren considerably improved my English. The style employed for Romanization of Yiddish follows YIVO's transliteration standards. Unless otherwise noted, translations from the Yiddish, Hebrew, German, and Latin are my own. Quotations from the Bible follow the JPS translation, and those from the Babylonian Talmud are according to the Hebrew-English edition of the Soncino Talmud by Isidore Epstein

    Precision Medicine and Actionable Alterations in Lung Cancer: A Single Institution Experience

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    OBJECTIVES: Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients. MATERIALS AND METHODS: In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic and clinical data in a recently created thoracic patient registry. RESULTS: Of the 415 patients with lung adenocarcinoma, 59% (n = 245) were female; the median age was 64 (range, 22-92) years with a median OS of 33.29 months (95% CI, 29.77-39.48). The most common actionable alterations were identified in EGFR (n = 177/415 [42.7%]), ALK (n = 28/377 [7.4%]), and BRAF V600E (n = 7/288 [2.4%]). There was also a discernible difference in survival for 222 patients, who had an actionable alteration, with a median OS of 39.8 months as compared to 193 wild-type patients with a median OS of 26.0 months (P CONCLUSION: The use of patient registries, focused genomic panels and the appropriate use of clinical guidelines in community and academic settings may influence cohort selection for clinical trials and improve survival outcomes

    To whom does the law speak? Canvassing a neglected picture of law’s interpretive field

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    Among the most common strategies underlying the so-called indeterminacy thesis is the following two-step argument: (1) that law is an interpretive practice, and that evidently legal actors more generally hold different (and competing) theories of meaning, which lead to disagreements as to what the law says (that is, as to what the law is); (2) and that, as there is no way to establish the prevalence of one particular theory of meaning over the other, indeterminacy is pervasive in law. In this paper I offer some reflections to resist this trend. In particular I claim that a proper understanding of law as an authoritative communicative enterprise sheds new light on the relation between the functioning of the law and our theories of interpretation, leading to what can be considered a neglected conclusion: the centrality of the linguistic criterion of meaning in our juridical interpretive practices. In the first part of the chapter I discuss speech-act theory in the study of law, assessing its relevance between alternative options. Then I tackle the ‘to whom does the law speak?’ question, highlighting the centrality of lay-people for our juridical practices. Lastly, I examine the consequences of this neglected fact for our interpretive theories
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