Completed cohomology of Shimura curves and a p-adic Jacquet-Langlands correspondence

We study indefinite quaternion algebras over totally real fields F, and give an example of a cohomological construction of p-adic Jacquet-Langlands functoriality using completed cohomology. We also study the (tame) levels of p-adic automorphic forms on these quaternion algebras and give an analogue of Mazur's `level lowering' principle.Comment: Updated version. Contains some minor corrections compared to the published versio

Percutaneous endoscopic gastrostomy: Indications, technique and complications at Groote Schuur Hospital

Percutaneous endoscopic gastrostomy (PEG) is a relatively new technique in South Africa. It is useful in the management of patients with neurological and oropharyngeal disorders in whom long-term feeding is necessary. The PEGs inserted in patients at Groote Schuur Hospital between June 1986 and March 1990 as part of an on-going study to evaluate this procedure are reported

Relative Equilibria in the Four-Vortex Problem with Two Pairs of Equal Vorticities

We examine in detail the relative equilibria in the four-vortex problem where two pairs of vortices have equal strength, that is, \Gamma_1 = \Gamma_2 = 1 and \Gamma_3 = \Gamma_4 = m where m is a nonzero real parameter. One main result is that for m > 0, the convex configurations all contain a line of symmetry, forming a rhombus or an isosceles trapezoid. The rhombus solutions exist for all m but the isosceles trapezoid case exists only when m is positive. In fact, there exist asymmetric convex configurations when m < 0. In contrast to the Newtonian four-body problem with two equal pairs of masses, where the symmetry of all convex central configurations is unproven, the equations in the vortex case are easier to handle, allowing for a complete classification of all solutions. Precise counts on the number and type of solutions (equivalence classes) for different values of m, as well as a description of some of the bifurcations that occur, are provided. Our techniques involve a combination of analysis and modern and computational algebraic geometry

Midlife systemic inflammation is associated with frailty in later life: The ARIC study

Background: Evidence suggests that systemic inflammation may have a mechanistic role in age-related frailty, yet prospective data is limited. We examined whether systemic inflammation during midlife was associated with late-life frailty within the community-based Atherosclerosis Risk in Communities Study. Methods: Plasma levels of four inflammatory markers (fibrinogen, von Willebrand factor, and Factor VIII, and white blood cell count) were measured during Visit 1 (1987-1989; mean age: 52 [5]), standardized into z-scores, and combined to create an inflammation composite score. High-sensitivity C-reactive protein (CRP) was measured 3 (Visit 2, 1990-1992) and 9 (Visit 4, 1996-1999) years later. Frailty was evaluated in 5,760 participants during late life (Visit 5, 2011-2013; mean age: 75 [5]). Analyses were adjusted for demographic and physiological variables, and midlife medical comorbidity using logistic regression. Results: A 1 SD increase in midlife inflammation composite score was associated with higher odds of frailty 24 years later (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.18-1.65). Similarly, each standard deviation increase in Visit 2 CRP (OR = 1.24, 95% CI: 1.09-1.40) and Visit 4 CRP (OR = 1.35, 95% CI: 1.19-1.53) was associated with a higher odds of frailty 21 and 15 years later. Participants who maintained elevated CRP (≥3 mg/L) at Visits 2 and 4 or transitioned to a state of elevated CRP during this period were more likely to subsequently meet frailty criteria compared to those who maintained low CRP. These associations were stronger among white, compared to African American, participants (p-interactions <.038). Conclusions: Systemic inflammation during midlife may independently promote pathophysiological changes underlying frailty in a subset of the population

Dementia in late-onset epilepsy: The Atherosclerosis Risk in Communities study

OBJECTIVE: To determine the risk of dementia after the development of late-onset epilepsy. METHODS: We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987 to 1989 with 15,792 mostly Black and White men and women from 4 US communities. We identified late-onset epilepsy (LOE; seizures starting at age 67 or later) from linked Medicare claims data. We used a Cox proportional hazards regression model to evaluate associations between LOE and dementia through 2017 as ascertained from neuropsychological testing, interviews, and hospital discharge surveillance, and we used multinomial logistic regression to assess the risk of dementia and mild cognitive impairment in the subset with full neuropsychological assessments available. We adjusted for demographics and vascular and Alzheimer disease risk factors. RESULTS: Of 9,033 ARIC participants with sufficient Medicare coverage data (4,980 [55.1%] female, 1993 [22.1%] Black), 671 met the definition of LOE. Two hundred seventy-nine (41.6%) participants with and 1,408 (16.8%) without LOE developed dementia (p < 0.001). After a diagnosis of LOE, the adjusted hazard ratio for developing subsequent dementia was 3.05 (95% confidence interval 2.65-3.51). The median time to dementia ascertainment after the onset of LOE was 3.66 years (quartile 1-3, 1.28-8.28 years). INTERPRETATION: The risk of incident dementia is substantially elevated in individuals with LOE. Further work is needed to explore causes for the increased risk of dementia in this growing population

Results of the First Coincident Observations by Two Laser-Interferometric Gravitational Wave Detectors

We report an upper bound on the strain amplitude of gravitational wave bursts in a waveband from around 800Hz to 1.25kHz. In an effective coincident observing period of 62 hours, the prototype laser interferometric gravitational wave detectors of the University of Glasgow and Max Planck Institute for Quantum Optics, have set a limit of 4.9E-16, averaging over wave polarizations and incident directions. This is roughly a factor of 2 worse than the theoretical best limit that the detectors could have set, the excess being due to unmodelled non-Gaussian noise. The experiment has demonstrated the viability of the kind of observations planned for the large-scale interferometers that should be on-line in a few years time.Comment: 11 pages, 2 postscript figure

Predictors of Medication Adherence in the Elderly: The Role of Mental Health

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky–Green–Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence

Late-onset epilepsy and 25-year cognitive change: The Atherosclerosis Risk in Communities (ARIC) study

Objective: To define the association between late-onset epilepsy (LOE) and 25-year change in cognitive performance. Methods: The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure-related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in-person visits at intervals of 3-15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z-score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors. Results: From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by −0.43 z-score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] −0.59 to −0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z-scores in those who would later develop LOE than it was in non-LOE participants. Results were similar after excluding data from participants with dementia. Significance: Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE

Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Objectives: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults. Design: Prospective cohort study. Setting: Atherosclerosis Risk in Communities (ARIC) Study. Participants: A community sample of adults who were 44 to 66 years of age at study baseline. Measurements: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=–0.27 to –0.06; 0.16-SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm3, 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm3, 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm3, 95% CI= 0.81–6.77). Conclusions: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study

Rationale, aims, and objectives: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval–prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. Method: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. Results: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. Conclusion: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors