Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: Context: Although Alzheimer's disease (AD) is associated with early death, its life expectancy differs greatly between patients. A better understanding of this heterogeneity may reveal important disease mechanisms underlying the malignancy of AD. The aim of this study was to examine the relation between AD pathologies and early death in AD caused by dementia.", 'At a memory clinic, 247 referred consecutive patients with AD were monitored during 12.61.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (A) pathology (APOE genotype, cerebrospinal fluid (CSF) A42) tau pathology (CSF phosphorylated tau and total tau), cerebrovascular pathology (white-matter lesions and CSF/serum albumin ratio), neuroinflammatory pathology (CSF soluble vascular cell adhesion molecule-1, sVCAM-1), frontal, temporal, and central brain atrophies, global cognition, sex, and age. Comorbidities and medications also were analyzed. All continuous variables were transformed to z scores to compare hazard ratios (HRs) and 95% confidence intervals (CIs).', 'At follow-up, 89% of the patients had died. The mean survival time was 6.43.0 years. The AD pathology that independently predicted an early death caused by dementia was cerebral inflammation (sVCAM-1; HR, 1.32; 95% CI, 1.07-1.64). Other independent predictors were lower global cognition (HR, 0.51; 95% CI, 0.43-0.61), frontal atrophy (HR, 1.38; 95% CI, 1.12-1.70), and medial temporal atrophy (HR, 1.23; 95% CI, 1.02-1.49). When examining death caused by dementia and related causes (vascular diseases and infections), age (HR, 1.23; 95% CI, 1.04-1.46) and cerebrovascular pathology (white-matter lesions: HR, 1.17; 95% CI, 1.01-1.36; and CSF/serum albumin ratio: HR, 1.16; 95% CI, 1.001-1.34) were also significant risk factors in addition to the previous variables. No comorbidity or medication was significant in the specific-cause models.
Answer: This is the first study to link neuroinflammation independently to early death in AD and, hence, a rapidly progressing disease. Frontal and medial temporal atrophies and low cognition were also significant predictors. These are probably downstream biomarkers that reflect neuronal degeneration and late-stage disease. Our results suggest that inflammation, and not amyloid or tau pathology, is an independent underlying mechanism in the malignancy of AD.

Answer: Is cerebral inflammation an underlying mechanism of early death in Alzheimer 's disease : a 13-year cause-specific multivariate mortality study?

Question: Context: Pulmonary vein (PV) isolation is a curative treatment for patients with atrial fibrillation. The aim of this study was to evaluate prospectively the effects of adenosine administration on the PV activity and atrio-venous conduction after PV isolation.', 'Twenty-nine patients (21 m; age: 55+/-8 years) were submitted to ostial PV isolation guided by basket catheter recordings. After successful isolation, the effects of a 12 mg intravenous bolus of adenosine were tested in 62 PVs. In 22/62 PVs (35%), left atrium (LA)-to-PV conduction was transiently (16.6+/-7.1 s, range: 3.8-27.9 s) or permanently (3 PVs) restored in response to adenosine administration. The prevalence of this phenomenon was 39% in left superior PVs, 43% in right superior PVs, and 22% in left inferior PVs (p=0.365). It occurred more frequently in the presence of dissociated PV activity (11/15 PVs, 73% vs. 11/47 PVs, 23%; p=0.002), whereas it was not influenced by the median duration of the radiofrequency current (RFC) delivery for each PV [19 (IQR: 12-26) min vs. 16 (IQR: 11-24) min: p=0.636]. A lengthening or shortening of the LA-PV conduction time was observed at LA-PV conduction appearance and disappearance in 36% and 55% of the cases, respectively. Further RFC applications (median: 5.5 min, IQR: 4-11 min) at the residual conduction breakthrough(s) indicated by the basket catheter recordings definitively eliminated adenosine-induced recovery of LA-PV conduction in all cases. Finally, when present, intrinsic PV discharge was invariably depressed by adenosine administration.
Answer: Adenosine may transiently or permanently re-establish LA-PV conduction after apparently successful PV isolation. This phenomenon is abolished by additional RFC delivery. However, its possible influence on the clinical results of PV ablation must be evaluated by properly designed, randomized studies.

Answer: Does adenosine restore atrio-venous conduction after apparently successful ostial isolation of the pulmonary veins?

Question: Context: Decreases in mate and/or pollinator availability would be expected to affect the selective pressure on plant mating systems. An increase in self-fertilization may evolve to compensate for the negative effects of pollination failure. However, the benefit of selfing in variable pollination environments depends on the relative fitnesses of selfed and outcrossed progeny. We investigated the potential for selfing to provide reproductive assurance over the lifetime of a long-lived perennial species and its variation between plant patches of various sizes. Patch size is likely to affect mate and pollinator availabilities, thereby affecting pollination success and the rate of selfing. We estimated fruit and seed set, reproductive assurance, self-compatibility, the multilocus patch selfing rate and lifetime inbreeding depression in natural patches of Rhododendron ferrugineum (Ericaceae), a mass-flowering species characterized by considerable patch size variation (as estimated by the total number of inflorescences).', 'Open seed set declined linearly with increasing patch size, whereas pollinator-mediated seed set (emasculated flowers) was not significantly affected. Progeny array analysis indicated that the selfing rate declined with increasing patch size, consistent with greater reproductive assurance in small sparse patches than in large, dense patches. However, fruit set and adult fitness decreased with decreasing patch size, with an estimated mean lifetime inbreeding depression of 0.9 (obtained by comparing F values in adults and progenies).
Answer: Lifetime inbreeding depression strongly counteracts the advantage of reproductive assurance due to selfing in this long-lived species. The poor fitness of selfed offspring should counteract any evolution towards selfing, despite its potential to alleviate the negative consequences of pollen limitation. This study highlights the need to estimate lifetime inbreeding depression, together with mating system and pollination parameters, if we are to understand the actual benefit of selfing and avoid the overestimation of reproductive assurance.

Answer:
Does high lifetime inbreeding depression counteract the reproductive assurance benefit of selfing in a mass-flowering shrub?