New stellar sources for high-density, presolar graphite grains

WepresentC,N,O,Si,Al-Mg,K,Ca,andTiisotopicanalyses ofsevenhigh-density(ORG1f, � � 2:02 2:04 gcm � 3 ) graphite grains from Orgueil with 12 C/ 13 C ratios smaller than 20. The presence of 44Ti in three of these grains indicates an origin in Type II supernovae (SNe). The 13 C excesses in these SNe grains, however, remain enigmatic. The remaining grains have extremely large Ca and Ti isotopic anomalies, some of which are much larger than those predicted for envelopes of asymptotic giant branch (AGB) stars. These anomalies in conjunction with low 12 C/ 13 C ratios can only be explained by pure nucleosynthetic He-shell components of AGB stars. Born-again AGB stars that experience a late He flash are able to explain the low 12 C/ 13 C ratios of some of the grains along with the presence of extreme enrichments in the Ca and Ti isotopes. This study indicates that high-density graphite grains havemultiple stellar sources: SNe and born-again AGB stars, in addition to the previously established low-metallicity AGB stars. Subject headingg dust, extinction — meteors, meteoroids — nuclear reactions, nucleosynthesis, abundances — stars: abundances — stars: AGB and post-AGB — supernovae: genera

Validity of self-reported diagnoses of gynaecological and breast cancers in a prospective cohort study: the Japan Nurses' Health Study

Objectives To validate the self-reported diagnoses of gynaecological and breast cancers in a nationwide prospective cohort study of nursing professionals: the Japan Nurses’ Health Study (JNHS).Design and setting Retrospective analysis of the JNHS.Participants and measures Data were reviewed for 15 717 subjects. The mean age at baseline was 41.6±8.3 years (median: 41), and the mean follow-up period was 10.5±3.8 years (median: 12). Participants are regularly mailed a follow-up questionnaire once every 2 years. Respondents who self-reported a positive cancer diagnosis were sent an additional confirmation questionnaire and contacted the diagnosing facility to confirm the diagnosis based on medical records. A review panel of experts verified the disease status. Regular follow-up, confirmation questionnaires and expert review were validated for their positive predictive value (PPV) and negative predictive value (NPV).Results New incidences were verified in 37, 47, 26 and 300 cervical, endometrial, ovarian and breast cancer cases, respectively. The estimated incidence rates were 22.0, 25.4, 13.8 and 160.4 per 100 000 person-years. These were comparable with those of national data from regional cancer registries in Japan. For regular follow-up, the corresponding PPVs for cervical, endometrial, ovarian and breast cancer were 16.9%, 54.2%, 45.1% and 81.4%, and the NPVs were 100%, 99.9%, 99.9% and 99.9%, respectively. Adding the confirmation questionnaire improved the PPVs to 31.5%, 88.9%, 76.7% and 99.9%; the NPVs were uniformly 99.9%. Expert review yielded PPVs and NPVs that were all ~100%.Conclusions Gynaecological cancer cannot be accurately assessed by self-reporting alone. Additionally, the external validity of cancer incidence in this cohort was confirmed

Geological structure of an arsenic-contaminated aquifer at Sonargaon, Bangladesh

ArticleJOURNAL OF GEOLOGY. 116(3):288-302(2008)journal articl

The effect of maternal anthropometric characteristics and social factors on gestational age and birth weight in Sudanese newborn infants

<p>Abstract</p> <p>Background</p> <p>In Africa low birth weight (LBW) (<2500 g), is the strongest determinant of infant morbidity and mortality. The aim of this study was to quantify the effect of maternal anthropometry, education and socio-economic status on gestational age and birth weight.</p> <p>Methods</p> <p>In 1000 Sudanese mothers with singleton births, anthropometric measurements (weight, height, mid-arm circumference) and newborn birth weight were taken within 24 hours of delivery. Furthermore, maternal education and socio-economic status were recorded. The effect of these maternal variables on gestational age and birth weight was investigated by receiver operating characteristic (ROC) curves and by multivariate logistic regression analysis.</p> <p>Results</p> <p>Although maternal height was significantly correlated (p = 0.002) with gestational age, we did not find maternal characteristics of value in determining the risk for preterm birth. Birth order was the strongest determinant of birth weight compared to other maternal characteristics. The LBW rate of first born babies of 12.2% was nearly twice that of infants of multiparous mothers. Maternal age and all maternal anthropometric measurements were positively correlated (p < 0.001) with birth weight. A maternal height of <156 cm, a maternal weight of <66 kg, a maternal mid arm circumference of <27 cm and years of education of ≤ 8 years were found to increase the relative risk of LBW but this was statistically significant only in the case of maternal height. Maternal age and BMI had no statistically significant effect on determining the risk for LBW. The social class did not affect the birth weight, while the number of years of education was positively correlated with birth weight (p = 0.01). The LBW rate decreased from 9.2% for ≤ 8 years of education to 6.0% for >12 years of education.</p> <p>Conclusion</p> <p>Birth order and maternal height were found to be the most important maternal parameters which influences birth weight and the risk for LBW. The duration of maternal education and not social class was found to significantly affect the risk for LBW.</p

Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y 6 Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications †

The P2Y6 receptor is a cytoprotective G protein-coupled receptor (GPCR) activated by UDP (EC50, 0.30 μM). We compared and combined modifications to enhance P2Y6 receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as α,β-methylene and extension of the terminal phosphate group into γ-esters of UTP analogues. The conformationally constrained (S)-methanocarba UDP is a full agonist (EC50 0.042 μM). 4-Methoxyimino modification of pyrimidine enhanced P2Y6, preserved P2Y2 and P2Y4, and abolished P2Y14 receptor potency, in the appropriate nucleotide. N4-Benzyloxy-CDP (15, MRS2964) and N4-methoxy-Cp3U (23, MRS2957) were potent, selective P2Y6 receptor agonists (EC50 0.026 μM and 0.012 μM, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-γ-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y6 receptor potency, but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N4-methoxy-cytidine 5′-triphospho-γ-[1]glucose were active (EC50 of 2.47 μM and 0.18 μM, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y6 receptor agonists may be enhanced by modest structural changes

Preparation of unsymmetrical ketones from tosylhydrazones and aromatic aldehydes via formyl C–H bond insertion

Preparation of ketones by insertion of diazo compounds into the formyl C−H bond of an aldehyde is an attractive procedure, but use of structurally diverse diazo compounds is hampered by preparation and safety issues. A convenient procedure for the synthesis of unsymmetrical ketones from bench-stable tosylhydrazones and aryl aldehydes is reported. The procedure can be performed in one pot from the parent carbonyl compound and needs only a base, with no additional promoters being required

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker

Different Requirement for Wnt/β-Catenin Signaling in Limb Regeneration of Larval and Adult Xenopus

BACKGROUND:In limb regeneration of amphibians, the early steps leading to blastema formation are critical for the success of regeneration, and the initiation of regeneration in an adult limb requires the presence of nerves. Xenopus laevis tadpoles can completely regenerate an amputated limb at the early limb bud stage, and the metamorphosed young adult also regenerates a limb by a nerve-dependent process that results in a spike-like structure. Blockage of Wnt/β-catenin signaling inhibits the initiation of tadpole limb regeneration, but it remains unclear whether limb regeneration in young adults also requires Wnt/β-catenin signaling. METHODOLOGY/PRINCIPAL FINDINGS:We expressed heat-shock-inducible (hs) Dkk1, a Wnt antagonist, in transgenic Xenopus to block Wnt/β-catenin signaling during forelimb regeneration in young adults. hsDkk1 did not inhibit limb regeneration in any of the young adult frogs, though it suppressed Wnt-dependent expression of genes (fgf-8 and cyclin D1). When nerve supply to the limbs was partially removed, however, hsDkk1 expression blocked limb regeneration in young adult frogs. Conversely, activation of Wnt/β-catenin signaling by a GSK-3 inhibitor rescued failure of limb-spike regeneration in young adult frogs after total removal of nerve supply. CONCLUSIONS/SIGNIFICANCE:In contrast to its essential role in tadpole limb regeneration, our results suggest that Wnt/β-catenin signaling is not absolutely essential for limb regeneration in young adults. The different requirement for Wnt/β-catenin signaling in tadpoles and young adults appears to be due to the projection of nerve axons into the limb field. Our observations suggest that nerve-derived signals and Wnt/β-catenin signaling have redundant roles in the initiation of limb regeneration. Our results demonstrate for the first time the different mechanisms of limb regeneration initiation in limb buds (tadpoles) and developed limbs (young adults) with reference to nerve-derived signals and Wnt/β-catenin signaling