57 research outputs found

    Strontium to calcium ratios in the marine gastropod Conus ermineus: Growth rate effects and temperature calibration

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    Here we investigate the potential of Sr/Ca ratios in the marine gastropod Conus ermineus for reconstructing seawater temperatures. We present annually resolved records of Sr/Ca and ÎŽ 18O for four shells collected alive from the Flower Garden Banks National Marine Sanctuary in the Gulf of Mexico. Our results show that variations in Sr/Ca and ÎŽ 18O covary with the in situ seasonal temperature cycle. Sr/Ca and temperature are positively correlated, in contrast with the inverse relationship found in inorganically precipitated aragonite. The seasonal Sr/Ca variability is superimposed on a long-term trend of increasing Sr/Ca with age. Both the seasonal and long-term ontogenetic changes in Sr/Ca are associated with variations in growth rate, defined here as the shell linear extension rate (LER); the seasonal variability in LER is superimposed on a long-term decrease with ontogeny. Thus the covariance of Sr/Ca ratios with temperature and LER suggests that Sr incorporation is likely driven by temperature influence on growth rate, rather than by thermodynamic effects. Unlike the seasonal variability, the ontogenetic effect is characterized by inverse covariation between Sr/Ca and LER, suggesting that Sr/Ca variability is not controlled by growth rate alone, but probably by two different biomineralization mechanisms, one related to temperature and the other related to age. We use the seasonal Sr/Ca signal of four shells to construct a temperature calibration. To minimize the ontogenetic effects, we separate the records into juvenile and adult growth stages and calculate the Sr/Ca-temperature (T) relationships: Juvenile: Sr/Ca (mmol mol−1) = 0.042 (±0.008) * T (°C) + 0.24 (±0.21) (R2 = 0.66) Adult: Sr/Ca(mmol mol−1) = 0.072 (±0.014) * T (°C) − 0.05 (±0.34) (R2 = 0.68) Applying the calibration to a single specimen provides mean annual temperature estimates within ±1°C of the in situ temperature record but resolves the seasonal variability only within ±3.5°C. The large error in the seasonal estimates reflects the high variability among specimens. To reduce the uncertainty on seasonal temperatures, we propose combining records from multiple shells to generate an average temperature record. The potential of this approach needs, however, to be validated in other locations

    Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

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    Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≄1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≀6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

    Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

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    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    The Somatic Genomic Landscape of Glioblastoma

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    We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

    Stable isotope and Sr/Ca profiles from the marine gastropod Conus ermineus: testing a multiproxy approach for inferring paleotemperature and paleosalinity

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    This study tests the fidelity of shallow-water gastropod skeletons as multiproxy archives of paleoenvironmental change by comparing isotopic and trace-metal analyses of specimens of Conus ermineus. Four adult specimens were collected live from Stetson Bank in the northwestern Gulf of Mexico during the summer of 2003. Shells were sampled along axes of growth to produce time-series profiles spanning up to 8 years. ή18O and Sr/Ca profiles show seasonal cyclicity modified by fast summer and slow winter shell growth. The profiles were combined to estimate paleosalinity. This yields variable results that overestimate salinity range; nevertheless, annual salinity minima and maxima are still evident. The overestimates are attributed to interspecimen Sr/Ca variability and error in the ή18Osw-salinity regression. Profiles of ή13C show seasonal variation superimposed on a decreasing ontogenetic trend, the latter ascribed to decreasing metabolic efficiency also reflected by an ontogenetic increase in Sr/Ca. Seasonal ή13C variation reflects changes in the ή13C of dissolved inorganic carbon (ή13CDIC). Salinity and ή13CDIC at Stetson Bank strongly correlate (R2 = 0.80, p < 0.0001), and shell ή13C minima coincide with local salinity minima following times of peak river discharge. These ή13C minima terminate during annual shelf current reversals. Low-salinity waters directly account for less than half the variability in shell ή13C but enhance summer stratification and trap respired CO2 from sediment pore waters. Specimens from this study show mean ή13C values 1‰ lower than C. ermineus collected from Stetson Bank in 1971, reflecting the decrease in ή13CDIC from anthropogenic CO2

    Special Session on Experiential Teaching

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    The concepts of delivered cost and differentiation initially advanced by Hall (1980) and Porter (1980, 1985) have become central concepts in the field of business strategy and policy (Dess and Miller, 1993). Cost (Managerial) accounting addresses cost chain issues under the topic ‘value chain’ which is gaining emphasis in managerial accounting (Horngren and Foster, 1991)
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