639 research outputs found

    Trading on Preconceptions: Why World War I Was Not a Failure of Economic Interdependence

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    World War I is generally viewed by both advocates and critics of commercial liberal theory as the quintessential example of a failure of economic integration to maintain peace. Yet this consensus relies on both methodologically flawed inference and an incomplete accounting of the antecedents to the war. Crucially, World War I began in a weakly integrated portion of Europe with which highly integrated powers were entangled through the alliance system. Crises among the highly interdependent European powers in the decades leading up to the war were generally resolved without bloodshed. Among the less interdependent powers in Eastern Europe, however, crises regularly escalated to militarized violence. Moreover, the crises leading to the war created increased incentives for the integrated powers to strengthen commitments to their less interdependent partners. In attempting to make these alliances more credible, Western powers shifted foreign policy discretion to the very states that lacked strong economic disincentives to fight. Had globalization pervaded Eastern Europe, or if the rest of Europe had been less locked into events in the east, Europe might have avoided a “Great War.” </jats:p

    The ecological and biogeochemical state of the North Pacifi c Subtropical Gyre is linked to sea surface height

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    Sea surface height (SSH) is routinely measured from satellites and used to infer ocean currents, including eddies, that affect the distribution of organisms and substances in the ocean. SSH not only reflects the dynamics of the surface layer, but also is sensitive to the fluctuations of the main pycnocline; thus it is linked to events of nutrient upwelling. Beyond episodic upwelling events, it is not clear if and how SSH is linked to broader changes in the biogeochemical state of marine ecosystems. Our analysis of 23 years of satellite observations and biogeochemical measurements from the North Pacific Subtropical Gyre shows that SSH is associated with numerous biogeochemical changes in distinct layers of the water column. From the sea surface to the depth of the chlorophyll maximum, dissolved phosphorus and nitrogen enigmatically increase with SSH, enhancing the abundance of heterotrophic picoplankton. At the deep chlorophyll maximum, increases in SSH are associated with decreases in vertical gradients of inorganic nutrients, decreases in the abundance of eukaryotic phytoplankton, and increases in the abundance of prokaryotic phytoplankton. In waters below ∼100 m depth, increases in SSH are associated with increases in organic matter and decreases in inorganic nutrients, consistent with predicted consequences of the vertical displacement of isopycnal layers. Our analysis highlights how satellite measurements of SSH can be used to infer the ecological and biogeochemical state of open-ocean ecosystems

    In-situ Discovery of a Cluster of Refractory Grains in an Allende Ferromagnesian Chondrule

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    During our nano-mineralogy investigation of the Allende meteorite, we discovered a unique corundum-rich cluster of irregular micrometer-sized refractory grains in a type IA chondrule. The presence of relatively oxidized (rutile) and highly reduced (a new mineral Ti_2O_3, khamrabaevite) phases in the same cluster reflects distinctly different environments prior to incorporation of the cluster into the chondrule. To our knowledge, this is the first occurrence of such a cluster. Investigation of phases that are clearly exotic to the host chondrule and may predate its formation can provide not only important constraints on the materials present when chondrules formed and the enviroments within or outside the Protoplanetary disk, but also on the chondrule formation event. Herein we report our prelimary results on the mineralogy of these grains and the overall petrology of their host chondrule

    Feasibility of Iodine and Bromine Analysis in Genesis Solar Wind Collectors

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    Comparison of elemental abundances in sun, meteorites and earth provides understanding of the formation and evolution of the solar system. Yet, the majority of the solar system abundances are based on meteoritic values [1–6]. Here we report an attempt to estimate a feasibility of direct measurements of iodine and bromine in the GENESIS solar wind Aluminum on Sapphire collector (AloS) using neutron induced conversions: ^(127)I(n,γβ)^(128)Xe, ^(79)Br(n,γβ)^(80)Kr and ^(81)Br(n,γβ)^(82)Kr

    Biomarker Testing for People With Advanced Lung Cancer in England

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    Introduction: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England. // Methods: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information. // Results: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy. // Conclusions: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved

    XANES and Mg isotopic analyses of spinels in Ca-Al-rich inclusions: Evidence for formation under oxidizing conditions

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    Ti valence measurements in MgAl_2O_4 spinel from calcium-aluminum-rich inclusions (CAIs) by X-ray absorption near-edge structure (XANES) spectroscopy show that many spinels have predominantly tetravalent Ti, regardless of host phases. The average spinel in Allende type B1 inclusion TS34 has 87% Ti^(+4). Most spinels in fluffy type A (FTA) inclusions also have high Ti valence. In contrast, the rims of some spinels in TS34 and spinel grain cores in two Vigarano type B inclusions have larger amounts of trivalent titanium. Spinels from TS34 have approximately equal amounts of divalent and trivalent vanadium. Based on experiments conducted on CAI-like compositions over a range of redox conditions, both clinopyroxene and spinel should be Ti^(+3)-rich if they equilibrated with CAI liquids under near-solar oxygen fugacities. In igneous inclusions, the seeming paradox of high-valence spinels coexisting with low-valence clinopyroxene can be explained either by transient oxidizing conditions accompanying low-pressure evaporation or by equilibration of spinel with relict Ti^(+4)-rich phases (e.g., perovskite) prior to or during melting. Ion probe analyses of large spinel grains in TS34 show that they are enriched in heavy Mg, with an average Δ^(25)Mg of 4.25 ± 0.028‰, consistent with formation of the spinel from an evaporating liquid. Δ^(25)Mg shows small, but significant, variation, both within individual spinels and between spinel and adjacent melilite hosts. The Δ^(25)Mg data are most simply explained by the low-pressure evaporation model, but this model has difficulty explaining the high Ti^(+4) concentrations in spinel

    Hepatic P450 Enzyme Activity, Tissue Morphology and Histology of Mink (Mustela vison) Exposed to Polychlorinated Dibenzofurans

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    Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQTCDF/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQPeCDF/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQTCDF/kg bw/day and 2.8 ng TEQPeCDF/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes

    Mammography screening: views from women and primary care physicians in Crete

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    Background: Breast cancer is the most commonly diagnosed cancer among women and a leading cause of death from cancer in women in Europe. Although breast cancer incidence is on the rise worldwide, breast cancer mortality over the past 25 years has been stable or decreasing in some countries and a fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies, in contrast, in Greece have not reported these favourable trends. In Greece, the age-standardised incidence and mortality rate for breast cancer per 100.000 in 2006 was 81,8 and 21,7 and although it is lower than most other countries in Europe, the fall in breast cancer mortality that observed has not been as great as in other European countries. There is no national strategy for screening in this country. This study reports on the use of mammography among middleaged women in rural Crete and investigates barriers to mammography screening encountered by women and their primary care physicians. Methods: Design: Semi-structured individual interviews. Setting and participants: Thirty women between 45–65 years of age, with a mean age of 54,6 years, and standard deviation 6,8 from rural areas of Crete and 28 qualified primary care physicians, with a mean age of 44,7 years and standard deviation 7,0 serving this rural population. Main outcome measure: Qualitative thematic analysis. Results: Most women identified several reasons for not using mammography. These included poor knowledge of the benefits and indications for mammography screening, fear of pain during the procedure, fear of a serious diagnosis, embarrassment, stress while anticipating the results, cost and lack of physician recommendation. Physicians identified difficulties in scheduling an appointment as one reason women did not use mammography and both women and physicians identified distance from the screening site, transportation problems and the absence of symptoms as reasons for non-use. Conclusion: Women are inhibited from participating in mammography screening in rural Crete. The provision of more accessible screening services may improve this. However physician recommendation is important in overcoming women's inhibitions. Primary care physicians serving rural areas need to be aware of barriers preventing women from attending mammography screening and provide women with information and advice in a sensitive way so women can make informed decisions regarding breast caner screening

    Effects of intensive blood pressure treatment on orthostatic hypotension a systematic review and individual participant-based meta-analysis

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    Background: Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). Purpose: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. Data Sources: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20mmHg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing. Data Extraction: 2 investigators independently abstracted articles and rated risk of bias. Data Synthesis: 5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged. Limitations: Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available. Conclusion: Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension

    Diversity in Functional Organization of Class I and Class II Biotin Protein Ligase

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    The cell envelope of Mycobacterium tuberculosis (M.tuberculosis) is composed of a variety of lipids including mycolic acids, sulpholipids, lipoarabinomannans, etc., which impart rigidity crucial for its survival and pathogenesis. Acyl CoA carboxylase (ACC) provides malonyl-CoA and methylmalonyl-CoA, committed precursors for fatty acid and essential for mycolic acid synthesis respectively. Biotin Protein Ligase (BPL/BirA) activates apo-biotin carboxyl carrier protein (BCCP) by biotinylating it to an active holo-BCCP. A minimal peptide (Schatz), an efficient substrate for Escherichia coli BirA, failed to serve as substrate for M. tuberculosis Biotin Protein Ligase (MtBPL). MtBPL specifically biotinylates homologous BCCP domain, MtBCCP87, but not EcBCCP87. This is a unique feature of MtBPL as EcBirA lacks such a stringent substrate specificity. This feature is also reflected in the lack of self/promiscuous biotinylation by MtBPL. The N-terminus/HTH domain of EcBirA has the self-biotinable lysine residue that is inhibited in the presence of Schatz peptide, a peptide designed to act as a universal acceptor for EcBirA. This suggests that when biotin is limiting, EcBirA preferentially catalyzes, biotinylation of BCCP over self-biotinylation. R118G mutant of EcBirA showed enhanced self and promiscuous biotinylation but its homologue, R69A MtBPL did not exhibit these properties. The catalytic domain of MtBPL was characterized further by limited proteolysis. Holo-MtBPL is protected from proteolysis by biotinyl-5′ AMP, an intermediate of MtBPL catalyzed reaction. In contrast, apo-MtBPL is completely digested by trypsin within 20 min of co-incubation. Substrate selectivity and inability to promote self biotinylation are exquisite features of MtBPL and are a consequence of the unique molecular mechanism of an enzyme adapted for the high turnover of fatty acid biosynthesis
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