Paleogene time scale miscalibration: Evidence from the dating of the North Atlantic igneous province

Jolley et al. (2002) have proposed that the date of the Paleocene - Eocene thermal maximum is ca. 60 Ma, at least 5 m.y. older than currently estimated and, as a result, argue that the Paleogene time scale of Berggren et al. (1995) is grossly miscalibrated. The implications of this proposal are implausible, and we attribute the discrepancy in age noted by Jolley et al. (2002) to miscorrelation of the Staffa-type palynofloras and ambiguous isotopic dates from the North Atlantic igneous province

Pleistocene magnetochronology of early hominin sites at Ceprano and Fontana Ranuccio, Italy

Paleomagnetic analyses were conducted on two cores drilled at Ceprano in central Italy where an incomplete hominin cranium was discovered in 1994, as well as on two additional cores from the nearby site of Fontana Ranuccio that yielded hominin remains associated with an Acheulean industry. No evidence for the 0.78 Ma Brunhes–Matuyama boundary was found at Ceprano down to 45 m below the level that yielded the hominin cranium. The Ceprano lithostratigraphy and the paleomagnetic age constraints are broadly consistent with the stratigraphy of the Liri lacustrine sequence of the Latina Valley, constrained by published K–Ar ages between ~ 0.6 and ~ 0.35 Ma, and according to an age model with magnetic susceptibility supported by pollen facies data, suggest that the level that yielded the hominin cranium has an age of ~ 0.45 (+ 0.05, − 0.10) Ma. Evidence for the Brunhes–Matuyama boundary was found at Fontana Ranuccio about 40 m below the hominin level, consistent with a K–Ar age of ~ 0.46 Ma reported for this level. Hence the Ceprano and Fontana Ranuccio hominin occurrences may be of very similar mid-Brunhes age

Pleistocene magnetochronology of early hominin sites at Ceprano and Fontana Ranuccio, Italy

Paleomagnetic analyses were conducted on two cores drilled at Ceprano in central Italy where an incomplete hominin cranium was discovered in 1994, as well as on two additional cores from the nearby site of Fontana Ranuccio that yielded hominin remains associated with an Acheulean industry. No evidence for the 0.78 Ma Brunhes–Matuyama boundary was found at Ceprano down to 45 m below the level that yielded the hominin cranium. The Ceprano lithostratigraphy and the paleomagnetic age constraints are broadly consistent with the stratigraphy of the Liri lacustrine sequence of the Latina Valley, constrained by published K–Ar ages between ~ 0.6 and ~ 0.35 Ma, and according to an age model with magnetic susceptibility supported by pollen facies data, suggest that the level that yielded the hominin cranium has an age of ~ 0.45 (+ 0.05, − 0.10) Ma. Evidence for the Brunhes–Matuyama boundary was found at Fontana Ranuccio about 40 m below the hominin level, consistent with a K–Ar age of ~ 0.46 Ma reported for this level. Hence the Ceprano and Fontana Ranuccio hominin occurrences may be of very similar mid-Brunhes age

Organizational Support for Sexual Minority Adolescents: Effects of Level of Youth Involvement and Diversity Training

A two-phase, cross-section and case study design examined the level of youth involvement in the decision-making processes of youth-serving organizations and the effects of diversity training on organizational support for LGBT (lesbian, gay, bisexual and transgendered) adolescents. Results indicate the organizations studied differed with respect to levels of youth involvement, but did not significantly differ with respect to the outcome variable. In-depth analysis to open-response questions indicated organizational support is extremely varied and organizations do support diversity, but not necessarily in regard to LGBT adolescents. The LGBT content within diversity training programs is also discussed. Finally, some religious ideas or beliefs seem to negatively affect the environment in youth-serving organizations in regard to support for LGBT adolescents. Implications for further research, youth practitioners and organizations are discussed

Organizational Support for Sexual Minority Adolescents: Effects of Level of Youth Involvement and Diversity Training

A two-phase, cross-section and case study design examined the level of youth involvement in the decision-making processes of youth-serving organizations and the effects of diversity training on organizational support for LGBT (lesbian, gay, bisexual and transgendered) adolescents. Results indicate the organizations studied differed with respect to levels of youth involvement, but did not significantly differ with respect to the outcome variable. In-depth analysis to open-response questions indicated organizational support is extremely varied and organizations do support diversity, but not necessarily in regard to LGBT adolescents. The LGBT content within diversity training programs is also discussed. Finally, some religious ideas or beliefs seem to negatively affect the environment in youth-serving organizations in regard to support for LGBT adolescents. Implications for further research, youth practitioners and organizations are discussed

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)

Càncer d'ovaris; Biomarcadors tumoralsCáncer de ovarios; Biomarcadores tumoralesOvarian cancer; Tumour biomarkersARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity

Toward a Revised Paleogene Geochronology

New information has become available that requires a revision of Paleogene chronology incorporated in most current Cenozoic time scales. Age estimates for the limits of the Paleogene (the Oligocene/Miocene and Cretaceous/Paleogene boundaries) have not changed appreciably and remain at about 24 Ma and about 66 Ma, respectively. However, new radioisotope data indicate that boundaries of subdivisions within the Paleogene are generally younger than previously estimated, for example, the Paleocene/Eocene and Eocene/Oligocene, by about 2 to 3 m.y. We review the current status of magnetobiostratigraphic correlations and new radioisotope data, with particular reference to late Eocene~early Oligocene geochronology and provide a reassessment of the age of the Eocene/Oligocene boundary as 34 Ma. We anticipate that with concurrent work on a fundamental revision of the geomagnetic polarity sequence, a comprehensive and detailed new time scale for the Cenozoic will soon be developed

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Acute pancreatitis following medical abortion: Case report

BACKGROUND: Acute pancreatitis rarely complicates pregnancy. Although most pregnant women with acute pancreatitis have associated gallstones, less common causes such as drugs have been reported. CASE PRESENTATION: We report the case of a 34-year-old woman who underwent medical abortion with mifepristone and gemeprost and received codeine as pain-relief during the induction of abortion. She developed a severe acute necrotizing pancreatitis which required 14 days of intensive care. Other possible etiological factors, i.e. gallstone, alcohol intake and hyperlipidemia, were excluded. CONCLUSIONS: The reported case of acute pancreatitis was most likely drug-induced