Barriers and Solutions to Advance Care Planning among Homeless-Experienced Older Adults.

Background/Objectives: Older homeless-experienced adults have low rates of advance care planning (ACP) engagement despite high rates of morbidity and mortality. To inform intervention development, we examined potential barriers and solutions to ACP engagement. Design: Cross-sectional qualitative study. Setting: We recruited adults who were homeless in the prior three years and ≥50 years of age in the San Francisco Bay Area, and recruited clinical stakeholders from a national meeting of homeless providers. We analyzed qualitative data using thematic analysis. Measurements: We conducted semistructured interviews with homeless-experienced older adults (n = 20) and focus groups with clinical stakeholders (n = 24) about perceived barriers and solutions to ACP engagement. Results: Participants considered ACP important, reflecting on deaths of people in their networks who had died. Participant-identified barriers to ACP included poor ACP knowledge, lack of familial ties and social isolation, competing priorities, avoidance and lack of readiness, fatalism and mistrust, and lack of ACP training for clinical and nonclinical staff. They identified solutions that included framing ACP as a way to provide meaning and assert choice, providing easy-to-read written documents focused on the populations' unique needs, tailoring content and delivery, initiating ACP in nonclinical settings, such as permanent supportive housing, and providing incentives. Conclusions: Both older homeless-experienced adults and clinical stakeholders believe that ACP is important, but acknowledge multiple barriers that impede engagement. By focusing on potential solutions, including capitalizing on opportunities outside of health care settings, focusing on the period after housing, and tailoring content, there are opportunities to improve ACP uptake

Non-affine geometrization can lead to nonphysical instabilities

Geometrization of dynamics consists of representing trajectories by geodesics on a configuration space with a suitably defined metric. Previously, efforts were made to show that the analysis of dynamical stability can also be carried out within geometrical frameworks, by measuring the broadening rate of a bundle of geodesics. Two known formalisms are via Jacobi and Eisenhart metrics. We find that this geometrical analysis measures the actual stability when the length of any geodesic is proportional to the corresponding time interval. We prove that the Jacobi metric is not always an appropriate parametrization by showing that it predicts chaotic behavior for a system of harmonic oscillators. Furthermore, we show, by explicit calculation, that the correspondence between dynamical- and geometrical-spread is ill-defined for the Jacobi metric. We find that the Eisenhart dynamics corresponds to the actual tangent dynamics and is therefore an appropriate geometrization scheme.Comment: Featured on the Cover of the Journal. 9 pages, 6 figures: http://iopscience.iop.org/1751-8121/48/7/07510

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

Determinación del eje de la carretera y la distancia de visibilidad utilizando datos GPS y herramientas SIG

Hoy en día, tanto en el proceso de diseño de las carreteras como en el análisis del funcionamiento de las ya construidas, se está dando cada vez más importancia a la seguridad vial. Entre los distintos aspectos que se consideran se encuentra la distancia de visibilidad. Por otra parte, uno de los problemas que aparecen en la práctica al tratar de analizar carreteras en servicio es la falta de datos de la geometría del eje que estén actualizados y tengan la precisión requerida. En esta comunicación se presenta un procedimiento para determinar el eje de la carretera mediante información GPS y calcular la distancia de visibilidad aplicando herramientas SIG. El procedimiento se ha aplicado a un tramo de carretera convencional de doble sentido de circulación. El método propuesto puede ser especialmente útil en aquellas carreteras en servicio y de las que, por no contar con la información sobre su trazado (original o posteriores modificaciones), no es posible utilizar los programas de diseño de carreteras para el cálculo de la distancia de visibilidad.Nowadays road safety aspects are very important, both for the designing process and for the analysis of already built roads. Sight distance is one of the most important road safety aspects to consider. On the other hand, the geometric definition of already built roads is one of the most difficult issues that arise in practice. This road geometry must be accurate and up to date. In this paper, a procedure to determine the alignment of a road using a GPS and to calculate sight distances using GIS tools is presented. Also, the use of this procedure in a two-lane rural road is described. The proposed method can be especially useful for those roads whose design data are not available because, on them, road design software could not be used for sight distance calculation

Development of the Incontinence Utility Index: estimating population-based utilities associated with urinary problems from the Incontinence Quality of Life Questionnaire and Neurogenic Module

BACKGROUND: Generic utility instruments may not fully capture the impact and consequences of urinary problems. Condition-specific preference-based measures, developed from previously validated disease-specific patient-reported outcomes instruments, may add relevant information for economic evaluations. The aim of this study was to develop a condition-specific preference-based measure, the Incontinence Utility Index (IUI), for valuing health states associated with urinary problems. METHODS: A two-step process was implemented. First, an abbreviated health state classification system was developed from the Incontinence Quality of Life Questionnaire (I-QOL) and Neurogenic Module by applying Rasch modelling, classical psychometrical testing and expert criteria to data from two pivotal trials comprised of neurogenic detrusor overactivity (NDO) patients. Criterion, convergent validity and concordance with the original instrument was assessed in the abbreviated version. Then, a multi-attribute utility function (MAUF) was estimated from a representative sample of the UK non-institutionalized adult general population. Visual analogue and time-trade off (TTO) evaluations were applied in the elicitation process. Predictive validity of the MAUF was tested comparing estimated and direct utility scores. RESULTS: The abbreviated health state classification system generated from the NDO sample contained 5 attributes with 3 levels of response and had adequate psychometrical properties: significant differences in scores according to the reduction in the frequency of urinary incontinence episodes [UIE] (p < 0.001); Spearman correlation coefficient with number of daily UIE = −0.43; p < 0.01 and Intraclass Correlation Coefficient (ICC, 95% CI) with the original version = 0.90 (0.89-0.91; p < 0.001). Next, 442 participants were interviewed (398 cases were valid, generating 2,388 TTO evaluations) to estimate the social preferences for derived health states. Mean age was 44.75 years (interquartile range 33.5-55.5) and 60.1% were female. An overall algorithm for the IUI was estimated and transformed onto a dead = 0.00 and full health = 1.00 scale. Model fits were acceptable (R-squared = 0.923 and 0.978). Predictive validity was adequate: ICC (95% CI) = 0.928 (0.648-0.985) and Mean of Absolute Differences = 0.038. CONCLUSIONS: The newly developed IUI is a preference-based measure for urinary problems related to NDO that provides general population-based utility scores with adequate predictive validity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00461292, NCT00311376. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12955-014-0147-7) contains supplementary material, which is available to authorized users

Caregiving For and By Hispanic Elders: Perceptions of Four Generations of Women

So as to learn about the experiences of acculturation among older Hispanic women, four generations were interviewed about their ethnic identity, perceptions of gender equity in the home, life satisfaction, and beliefs regarding family caregiving responsibilities. Findings reveal general differences between hopes for, and experiences with, gender equity and in their self-identification as a member of a minority group and their perceptions of others toward them. Differences were also found among the four age groups of Hispanic women

The influence of the complex topography and dynamic history of the montane Neotropics on the evolutionary differentiation of a cloud forest bird (Premnoplex brunnescens, Furnariidae)

Aim: To examine the effect of geographical barriers and habitat dynamics related to climatic oscillations on the phylogeography of a widespread passerine of Neotropical cloud forests, the spotted barbtail (Premnoplex brunnescens). Location: Neotropical humid forests of montane areas in lower Central America and South America. Methods: We sequenced two mitochondrial genes and one nuclear intron from specimens collected across the distribution of P. brunnescens. Phylogenetic relationships were inferred using Bayesian and maximum-likelihood methods. Groups with maximum differentiation were estimated with spatial analysis of molecular variance (SAMOVA). We estimated timing of differentiation and relationships among groups with a species-tree approach and historical demography with extended Bayesian skyline plots. Results: Six highly differentiated clades of P. brunnescens are distributed in lower Central America, Sierra Nevada de Santa Marta, northern Venezuelan mountains, the Northern Andes, central Peru, and southern Peru and Bolivia. Within the Northern Andes clade, six phylogroups were identified associated with different slopes and isolated cordilleras. Most clades occupy opposite sides of low-lying valleys and ridgelines, but little differentiation was observed across several putative barriers. Population divergence occurred in the late Miocene and Pliocene, perhaps in association with Andean uplift. Historical fluctuations in population sizes suggest that populations tracked the spatial dynamics of montane forests associated with glacial cycles. Main conclusions: Extensive genetic differentiation in mitochondrial and nuclear DNA exists among populations of P. brunnescens. Such marked divergence was probably promoted by the rugged topography and dynamic ecological history of the Neotropical mountains. Our study sheds light on mechanisms promoting population differentiation in the montane Neotropics. © 2014 John Wiley & Sons Ltd

Validation of a specific measure to assess health-related quality of life in patients with schizophrenia and bipolar disorder: the 'Tolerability and quality of life' (TOOL) questionnaire

<p>Abstract</p> <p>Background</p> <p>Perception of quality of life may differ depending on the perspective. The aim of the study was to assess the psychometric properties of the Spanish version of the 'TOlerability and quality Of Life' (TOOL) questionnaire, a specific self-rated instrument to evaluate the impact of side effects of antipsychotic drugs on health-related quality of life (HRQoL). The questionnaire consists of eight items answered on a four-point Likert scale.</p> <p>Methods</p> <p>A psychometric study was conducted with clinically stable outpatients with schizophrenia and bipolar disorder under antipsychotic treatment. The translation and cultural adaptation of the questionnaire was performed according to international standards. Internal consistency using the Cronbach α coefficient and test-retest reliability using the intraclass correlation coefficient (ICC) was used to assess the reliability of the instrument. Patients completed generic and specific measures of quality of life and clinical severity.</p> <p>Results</p> <p>A total of 238 patients were analysed, with a mean age of 42 years (SD 10.9). The mean completion time was 4.9 min (SD 4.4). Internal consistency and intraclass correlation coefficient were adequate (Cronbach α = 0.757 and ICC = 0.90). Factorial analysis showed a unidimensional structure (a single eigenvalue >1, accounting for 39.1% of variance). Significant Spearman's rank correlations between the TOOL and both generic and specific measures were found. The questionnaire was able to discriminate among the Clinical Global Impression - Severity scores (Mann-Whitney U test, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>The TOOL questionnaire shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome. TOOL constitutes a valuable addition to measure the impact of adverse events of antipsychotic drugs from the patient perspective.</p

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species