A study of the relation of industrial arts to school failures

Thesis (M.S.

Impact of DNA damage repair alterations on prostate cancer progression and metastasis

Prostate cancer is among the most common diseases worldwide. Despite recent progress with treatments, patients with advanced prostate cancer have poor outcomes and there is a high unmet need in this population. Understanding molecular determinants underlying prostate cancer and the aggressive phenotype of disease can help with design of better clinical trials and improve treatments for these patients. One of the pathways often altered in advanced prostate cancer is DNA damage response (DDR), including alterations in BRCA1/2 and other homologous recombination repair (HRR) genes. Alterations in the DDR pathway are particularly prevalent in metastatic prostate cancer. In this review, we summarise the prevalence of DDR alterations in primary and advanced prostate cancer and discuss the impact of alterations in the DDR pathway on aggressive disease phenotype, prognosis and the association of germline pathogenic1 alterations in DDR genes with risk of developing prostate cancer

Continuity and individuality in Medieval Hereford, England: A stable isotope approach to bulk bone and incremental dentine

In this study, bulk bone collagen carbon (δ13C) and nitrogen (δ15N) isotope data from 49 individuals, recovered from two Medieval burial grounds in Hereford, England, are coupled with incremental dentine data from five individuals with high δ15N bone values who survived into old age, to see whether the high δ15N values were consistent throughout their childhood and adolescence. There are statistically insignificant differences between mean bone δ13C and δ15N values from the two Hereford populations, exhumed at Cathedral Close and St. Guthlac's Priory, despite temporal and demographic differences (St Guthlac's mean: δ13C −19.4 ± 0.5‰ and δ15N 10.9 ± 1.2‰; Hereford Cathedral mean: δ13C −19.6 ± 0.4‰ and δ15N 10.4 ± 0.9‰, 1σ). In comparison to other contemporary urban populations, the Hereford individuals present significantly lower but more variable δ15N values, suggesting a diet low in protein from high trophic level foods such as meat and milk, possibly the result of differing social status or geographic factors. The approximately 23-year long incremental dentine profiles all show considerable fluctuation in stable isotope values during childhood and adolescence for all individuals until around age 20, suggesting possible influence by physiological processes related to growth and development

Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation : OPINION primary analysis

Objective: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. Methods: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. Results: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6–10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. Conclusion: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals