138 research outputs found

    Japan Prepares for Total War

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    Quantifying the stratigraphic completeness of delta shoreline trajectories

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    Understanding the incomplete nature of the stratigraphic record is fundamental for interpreting stratigraphic sequences. Methods for quantifying stratigraphic completeness for one-dimensional stratigraphic columns, defined as the proportion of time intervals of some length that contain stratigraphy, are commonplace; however, quantitative assessments of completeness in higher dimensions are lacking. Here we present a metric for defining stratigraphic completeness of two-dimensional shoreline trajectories using topset-foreset rollover positions in dip-parallel sections and describe the preservation potential of a shoreline trajectory derived from the geometry of the delta surface profile and the kinematics of the geomorphic shoreline trajectory. Two end-member forward models are required to fully constrain the preservation potential of the shoreline dependent on whether or not a topset is eroded during base level fall. A laboratory fan-delta was constructed under nonsteady boundary conditions, and one-dimensional stratigraphic column and two-dimensional shoreline completeness curves were calculated. Results are consistent with the hypothesis derived from conservation of sediment mass that completeness over all timescales should increase given increasing dimensions of analysis. Stratigraphic trajectories and completeness curves determined from forward models using experimental geomorphic trajectories compare well to values from transects when subsampled to the equivalent stratigraphic resolution as observed in the actual preserved sequence. The concept of stratigraphic completeness applied to two-dimensional trajectory analysis and the end-member forward models presented here provide novel tools for a conceptual understanding of the nature of stratigraphic preservation at basin scales

    Amoxicillin-Clavulanate-Induced Liver Injury

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    Background and Aims Amoxicillin–clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Methods Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. Results One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. Conclusion AC-DILI causes a moderately severe, mixed hepatocellular–cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation

    Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug‐Induced Liver Injury Network (DILIN)

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    Background & AimsBecause of the lack of objective tests to diagnose drug‐induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test–retest reliability is unknown. To determine the test–retest reliability of the expert opinion process used by the Drug‐Induced Liver Injury Network (DILIN).MethodsThree DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow‐up information. One hundred randomly selected DILIN cases were re‐assessed using the same processes for initial assessment but by three different reviewers in 92% of cases.ResultsThe median time between assessments was 938 days (range 140–2352). Thirty‐one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50–0.71) and 0.60 (0.52–0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury.ConclusionsThe DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as ≥50% likely to be DILI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111130/1/liv12540.pd

    Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries

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    <p>Abstract</p> <p>Background</p> <p>There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children.</p> <p>Methods</p> <p>In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire</p> <p>Results</p> <p>In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008.</p> <p>Conclusions</p> <p>While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.</p

    Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome

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    BACKGROUND Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes. Full Text of Background... METHODS In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period. Full Text of Methods... RESULTS Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P Full Text of Results... CONCLUSIONS As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.

    Prevalence of Diabetes Among Hispanics/Latinos From Diverse Backgrounds: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

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    OBJECTIVEWe examine differences in prevalence of diabetes and rates of awareness and control among adults from diverse Hispanic/Latino backgrounds in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).RESEARCH DESIGN AND METHODSThe HCHS/SOL, a prospective, multicenter, population-based study, enrolled from four U.S. metropolitan areas from 2008 to 2011 16,415 18–74-year-old people of Hispanic/Latino descent. Diabetes was defined by either fasting plasma glucose, impaired glucose tolerance 2 h after a glucose load, glycosylated hemoglobin (A1C), or documented use of hypoglycemic agents (scanned medications).RESULTSDiabetes prevalence varied from 10.2% in South Americans and 13.4% in Cubans to 17.7% in Central Americans, 18.0% in Dominicans and Puerto Ricans, and 18.3% in Mexicans (P < 0.0001). Prevalence related positively to age (P < 0.0001), BMI (P < 0.0001), and years living in the U.S. (P = 0.0010) but was negatively related to education (P = 0.0005) and household income (P = 0.0043). Rate of diabetes awareness was 58.7%, adequate glycemic control (A1C <7%, 53 mmol/mol) was 48.0%, and having health insurance among those with diabetes was 52.4%.CONCLUSIONSPresent findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background. The low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies

    Sample Design and Cohort Selection in the Hispanic Community Health Study/Study of Latinos

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    The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a multi-center, community based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this paper

    Phenotype Fingerprinting Suggests the Involvement of Single-Genotype Consortia in Degradation of Aromatic Compounds by Rhodopseudomonas palustris

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    Anaerobic degradation of complex organic compounds by microorganisms is crucial for development of innovative biotechnologies for bioethanol production and for efficient degradation of environmental pollutants. In natural environments, the degradation is usually accomplished by syntrophic consortia comprised of different bacterial species. This strategy allows consortium organisms to reduce efforts required for maintenance of the redox homeostasis at each syntrophic level. Cellular mechanisms that maintain the redox homeostasis during the degradation of aromatic compounds by one organism are not fully understood. Here we present a hypothesis that the metabolically versatile phototrophic bacterium Rhodopseudomonas palustris forms its own syntrophic consortia, when it grows anaerobically on p-coumarate or benzoate as a sole carbon source. We have revealed the consortia from large-scale measurements of mRNA and protein expressions under p-coumarate, benzoate and succinate degrading conditions using a novel computational approach referred as phenotype fingerprinting. In this approach, marker genes for known R. palustris phenotypes are employed to determine the relative expression levels of genes and proteins in aromatics versus non-aromatics degrading condition. Subpopulations of the consortia are inferred from the expression of phenotypes and known metabolic modes of the R. palustris growth. We find that p-coumarate degrading conditions may lead to at least three R. palustris subpopulations utilizing p-coumarate, benzoate, and CO2 and H2. Benzoate degrading conditions may also produce at least three subpopulations utilizing benzoate, CO2 and H2, and N2 and formate. Communication among syntrophs and inter-syntrophic dynamics in each consortium are indicated by up-regulation of transporters and genes involved in the curli formation and chemotaxis. The N2-fixing subpopulation in the benzoate degrading consortium has preferential activation of the vanadium nitrogenase over the molybdenum nitrogenase. This subpopulation in the consortium was confirmed in an independent experiment by consumption of dissolved nitrogen gas under the benzoate degrading conditions
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