Predicting Alzheimer's risk: why and how?

Because the pathologic processes that underlie Alzheimer's disease (AD) appear to start 10 to 20 years before symptoms develop, there is currently intense interest in developing techniques to accurately predict which individuals are most likely to become symptomatic. Several AD risk prediction strategies - including identification of biomarkers and neuroimaging techniques and development of risk indices that combine traditional and non-traditional risk factors - are being explored. Most AD risk prediction strategies developed to date have had moderate prognostic accuracy but are limited by two key issues. First, they do not explicitly model mortality along with AD risk and, therefore, do not differentiate individuals who are likely to develop symptomatic AD prior to death from those who are likely to die of other causes. This is critically important so that any preventive treatments can be targeted to maximize the potential benefit and minimize the potential harm. Second, AD risk prediction strategies developed to date have not explored the full range of predictive variables (biomarkers, imaging, and traditional and non-traditional risk factors) over the full preclinical period (10 to 20 years). Sophisticated modeling techniques such as hidden Markov models may enable the development of a more comprehensive AD risk prediction algorithm by combining data from multiple cohorts. As the field moves forward, it will be critically important to develop techniques that simultaneously model the risk of mortality as well as the risk of AD over the full preclinical spectrum and to consider the potential harm as well as the benefit of identifying and treating high-risk older patients

Long time dynamics following a quench in an integrable quantum spin chain: local versus non-local operators and effective thermal behavior

We study the dynamics of the quantum Ising chain following a zero-temperature quench of the transverse field strength. Focusing on the behavior of two-point spin correlation functions, we show that the correlators of the order parameter display an effective asymptotic thermal behavior, i.e., they decay exponentially to zero, with a phase coherence rate and a correlation length dictated by the equilibrium law with an effective temperature set by the energy of the initial state. On the contrary, the two-point correlation functions of the transverse magnetization or the density-of-kinks operator decay as a power-law and do not exhibit thermal behavior. We argue that the different behavior is linked to the locality of the corresponding operator with respect to the quasi-particles of the model: non-local operators, such as the order parameter, behave thermally, while local ones do not. We study which features of the two-point correlators are a consequence of the integrability of the model by analizing their robustness with respect to a sufficiently strong integrability-breaking term.Comment: 18 pages, 11 figures, published version. Extensive changes, one author adde

Development and Validation of eRADAR: A Tool Using EHR Data to Detect Unrecognized Dementia.

ObjectivesEarly recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR]).DesignRetrospective cohort study.SettingKaiser Permanente Washington (KPWA), an integrated healthcare delivery system.ParticipantsA total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples.MeasurementsEHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills).ResultsOverall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia.ConclusionThe eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019

Emergency department visits and hospitalizations by tube-fed nursing home residents with varying degrees of cognitive impairment: a national study

BACKGROUND: Numerous studies indicate that the use of feeding tubes (FT) in persons with advanced cognitive impairment (CI) does not improve clinical outcomes or survival, and results in higher rates of hospitalization and emergency department (ED) visits. It is not clear, however, whether such risk varies by resident level of CI and whether these ED visits and hospitalizations are potentially preventable. The objective of this study was to determine the rates of ED visits, hospitalizations and potentially preventable ambulatory care sensitive (ACS) ED visits and ACS hospitalizations for long-stay NH residents with FTs at differing levels of CI. METHODS: We linked Centers for Medicare and Medicaid Services inpatient & outpatient administrative claims and beneficiary eligibility data with Minimum Data Set (MDS) resident assessment data for nursing home residents with feeding tubes in a 5% random sample of Medicare beneficiaries residing in US nursing facilities in 2006 (n = 3479). Severity of CI was measured using the Cognitive Performance Scale (CPS) and categorized into 4 groups: None/Mild (CPS = 0-1, MMSE = 22-25), Moderate (CPS = 2-3, MMSE = 15-19), Severe (CPS = 4-5, MMSE = 5-7) and Very Severe (CPS = 6, MMSE = 0-4). ED visits, hospitalizations, ACS ED visits and ACS hospitalizations were ascertained from inpatient and outpatient administrative claims. We estimated the risk ratio of each outcome by CI level using over-dispersed Poisson models accounting for potential confounding factors. RESULTS: Twenty-nine percent of our cohort was considered “comatose” and “without any discernible consciousness”, suggesting that over 20,000 NH residents in the US with feeding tubes are non-interactive. Approximately 25% of NH residents with FTs required an ED visit or hospitalization, with 44% of hospitalizations and 24% of ED visits being potentially preventable or for an ACS condition. Severity of CI had a significant effect on rates of ACS ED visits, but little effect on ACS hospitalizations. CONCLUSIONS: ED visits and hospitalizations are common in cognitively impaired tube-fed nursing home residents and a substantial proportion of ED visits and hospitalizations are potentially preventable due to ACS conditions

Dynamical structure factors of S=1/2S=1/2 two-leg spin ladder systems

We investigate dynamical properties of $S=1/2$ two-leg spin ladder systems. In a strong coupling region, an isolated mode appears in the lowest excited states, while in a weak coupling region, an isolated mode is reduced and the lowest excited states become a lower bound of the excitation continuum. We find in the system with equal intrachain and interchain couplings that due to a cyclic four-spin interaction, the distribution of the weights for the dynamical structure factor and characteristics of the lowest excited states are strongly influenced. The dynamical properties of two systems proposed for ${\rm SrCu_2O_3}$ are also discussed.Comment: 5 pages, 6 figure

Optical absorption spectra in SrCu_2O_3 two-leg spin ladder

We calculate the phonon-assisted optical-absorption spectra in SrCu_2O_3 two-leg spin-ladder systems. The results for two models proposed for SrCu_2O_3 are compared. In the model including the effects of a cyclic four-spin interaction, the shoulder structure appears at 978 cm^{-1} and the peak appears at 1975 cm^{-1} in the spectrum for polarization of the electric field parallel to the legs. In the other model which describes a pure two-leg ladder, the peak appears around the lower edge of the spectrum at 1344 cm^{-1}. The feature can be effective in determining the proper model for SrCu_2O_3.Comment: 5 pages, 5 figures, to appear in PRB vol. 67 (2003

No association between islet cell antibodies and coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7–19 years

Viral antibodies were tested in a cohort of 44 isletcell antibody-positive individuals age 7–19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalo virus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections

Gravitating σ\sigma Model Solitons

We study axially symmetric static solitons of O(3) nonlinear $\sigma$ model coupled to (2+1)-dimensional anti-de Sitter gravity. The obtained solutions are not self-dual under static metric. The usual regular topological lump solution cannot form a black hole even though the scale of symmetry breaking is increased. There exist nontopological solitons of half integral winding in a given model, and the corresponding spacetimes involve charged Ba$\tilde n$ados-Teitelboim-Zanelli black holes without non-Abelian scalar hair.Comment: 35 pages, RevTe

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio