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.

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 12.6\u2009±\u20091.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (Aβ) pathology (APOE genotype, cerebrospinal fluid (CSF) Aβ42) 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 6.4\u2009±\u20093.0 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.
Is cerebral inflammation an underlying mechanism of early death in Alzheimer 's disease : a 13-year cause-specific multivariate mortality study?

Context: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome.', 'All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved.', 'The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test.
Answer: In this population, ThinPrep was superior to the conventional Pap test.
Does comparative study of the ThinPrep Pap test and conventional cytology result in a Canadian cohort?

Context: Recent studies indicate that a1-adrenergic receptors (a1-ARs) are cardioprotective by preventing cardiac myocyte death and augmenting contractility in heart failure. Although G-protein-coupled receptors are assumed to localize to and signal at the plasma membrane, we previously demonstrated that endogenous a1-ARs localize to the nuclei in adult cardiac myocytes. However, the functional consequence of this nuclear localization remains unclear. Here, we attempted to reconcile nuclear localization of a1-ARs with their physiologic function by examining a1-AR-induced contractility in adult cardiac myocytes.', 'By measuring shortening in unloaded, cultured adult cardiac myocytes, we found that the a1A-subtype regulated contractility through phosphorylation of cardiac troponin I (cTnI) at the protein kinase C (PKC) site, threonine 144. Reconstitution of an a1A-subtype nuclear localization mutant in cardiac myocytes lacking a1-ARs failed to rescue nuclear a1A-mediated phosphorylation of cTnI and myocyte contractility. Leptomycin B, the nuclear export inhibitor, also blocked a1A-mediated phosphorylation of cTnI. These data indicate that a1-AR signaling originates in the nucleus. Consistent with these observations, we localized the a1A-subtype to the inner nuclear membrane, identified PKCa, d, and e in the nucleus, and found that a1-ARs activate PKCd in nuclei isolated from adult cardiac myocytes. Finally, we found that a PKCd nuclear localization mutant blunted a1-induced phosphorylation of cTnI.
Answer: Together, our data identify a novel, “inside-out” nuclear a1A-subtype/PKCd/cTnI-signaling pathway that regulates contractile function in adult cardiac myocytes. Importantly, these data help resolve the discrepancy between nuclear localization of a1-ARs and a1-AR-mediated physiologic function.

Is nuclear localization of a1A-adrenergic receptors required for signaling in cardiac myocytes : an “ inside-out ” a1-AR signaling pathway?