TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers.', 'Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy.', 'Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers.\Question: Is better life expectancy in women with BRCA2 compared with BRCA1 mutations attributable to lower frequency and later onset of ovarian cancer?

SOLUTION: Interventions to reduce ovarian cancer incidence are likely to have a greater effect on life expectancy in BRCA1 compared with BRCA2 carriers.

PROBLEM: Context: To evaluate the relevance of systematic screening for neonatal metabolic acidosis at birth as part of perinatal audit.', 'For every baby, born in Ziekenhuis Oost Limburg, Genk Belgium between 1/1/2010 and 31/12/2010, cord blood was analysed to diagnose metabolic acidosis, defined as arterial or venous pH ≤ 7.05 or 7.17 respectively, in association with base excess of ≤ -10\u2008mmol/L. Three observers identified indicators for suboptimal peripartal care with likely contribution to metabolic acidosis. In a multidisciplinary consensus meeting, these indicators were classified into 5 categories : (a) fetal monitoring error (b) labour management error, (c) instrumental vaginal delivery for fetal distress within 2\u2008h of second stage, (d) non-obstetric medical complications, (e) preterm births or accidental cases at term.', 'In a total of 2117 neonates, there were 11 intra-uterine, 1 intrapartum and 3 early neonatal deaths, bringing early perinatal mortality rate at 7.1‰. Metabolic acidosis was identified in 23 (1.1%) babies, of which 21 (91.3%) left hospital in good clinical condition. Two babies (0.9‰), born in category c, had chronic neurologic symptoms.\Question: Do identification of neonatal near miss by systematic screening for metabolic acidosis at birth?

SOLUTION: Systematic screening for neonatal metabolic acidosis caused a 2.5-fold increase of case identifications eligible for perinatal audit and opened perspectives towards rationalised improvement of perinatal care, in addition to the information obtained from cases of perinatal mortality. Next to indicators of perinatal mortality, perinatal audit programs should include neonatal metabolic acidosis as an extra parameter for quality assessment of perinatal care.

PROBLEM: Context: The relationship between end-stage renal disease (ESRD), hemodialysis, and oxidative stress is controversial. To determine whether ESRD causes oxidative stress, we measured basal levels of plasma F2-isoprostanes as a marker of lipid peroxidation in vivo, and peroxynitrite-stimulated formation of F2-isoprostanes, as a marker of the oxidizibility of plasma lipids in vitro, before and after routine hemodialysis.', 'Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls. Plasma vitamin E concentrations were measured by high-performance liquid chromatography (HPLC).', 'There was no difference in basal plasma concentrations of F2-isoprostanes in the ESRD group prior to hemodialysis, 246 +/- 20 pg/mL, compared to controls, 252 +/- 28 pg/mL, or immediately on completion of hemodialysis, 236 +/- 14 pg/mL. Incubation of control plasma with SIN-1 caused the formation of F2-isoprostanes with plasma concentrations increasing to 987 +/- 54 pg/mL at 6 hours. The formation of F2-isoprostanes stimulated by SIN-1 was markedly enhanced in the plasma obtained from patients undergoing hemodialysis at 1861 +/- 174 pg/mL, P < 0.001, and SIN-1-induced formation of F2-isoprostanes was further increased in plasma obtained immediately after hemodialysis at 2437 +/- 168 pg/mL, P < 0.001. Incubation of plasma with SIN-1 resulted in the net consumption of vitamin E.\Question: Is peroxynitrite-induced oxidation of plasma lipids enhanced in stable hemodialysis patients?

SOLUTION:
Although basal plasma F2-isoprostanes were similar in patients with ESRD compared with controls, the presence of oxidative stress in patients with ESRD was unmasked when the plasma was stressed by peroxynitrite generated from SIN-1, and this was enhanced further by hemodialysis.