Access to Hospice Care: Expanding Boundaries, Overcoming Barriers

This report looks at issues of social justice, access, and public policy in hospice and palliative care. As it examines the issues from the perspectives of social justice and fairness, it also recommends ways in which the definition of hospice can be expanded to include more Americans for a longer period of time than simply the days or months shortly before death

Uptake Coefficients of Some Volatile Organic Compounds by Soot and Their Application in Understanding Particulate Matter Evolution in Aircraft Engine Exhaust Plumes

To assist microphysical modeling on particulate matter (PM) evolution emitted from aircraft engines, uptake coefficients of some volatile organic compounds on soot were experimentally determined in this study. The determined values vary from (1.0±0.1)×10⁻⁶ for water-miscible propylene glycol to (2.5±0.1)×10⁻⁵ for 2,6-dimethylnaphthalene, a polycyclic aromatic hydrocarbon. An inverse power-law correlation between uptake coefficient on soot and solubility in water was observed. Using the correlation, microphysical simulations were performed for the exhaust plume evolution from an idling aircraft, and we found that the model-predicted volatile PM composition on soot is comparable with those results from past field measurements.United States. Department of Defense (Contract W912HQ-08-C-0052

Accuracy and Usability of a Novel Algorithm for Detection of Irregular Pulse Using a Smartwatch Among Older Adults: Observational Study

BACKGROUND: Atrial fibrillation (AF) is often paroxysmal and minimally symptomatic, hindering its diagnosis. Smartwatches may enhance AF care by facilitating long-term, noninvasive monitoring. OBJECTIVE: This study aimed to examine the accuracy and usability of arrhythmia discrimination using a smartwatch. METHODS: A total of 40 adults presenting to a cardiology clinic wore a smartwatch and Holter monitor and performed scripted movements to simulate activities of daily living (ADLs). Participants\u27 clinical and sociodemographic characteristics were abstracted from medical records. Participants completed a questionnaire assessing different domains of the device\u27s usability. Pulse recordings were analyzed blindly using a real-time realizable algorithm and compared with gold-standard Holter monitoring. RESULTS: The average age of participants was 71 (SD 8) years; most participants had AF risk factors and 23% (9/39) were in AF. About half of the participants owned smartphones, but none owned smartwatches. Participants wore the smartwatch for 42 (SD 14) min while generating motion noise to simulate ADLs. The algorithm determined 53 of the 314 30-second noise-free pulse segments as consistent with AF. Compared with the gold standard, the algorithm demonstrated excellent sensitivity (98.2%), specificity (98.1%), and accuracy (98.1%) for identifying irregular pulse. Two-thirds of participants considered the smartwatch highly usable. Younger age and prior cardioversion were associated with greater overall comfort and comfort with data privacy with using a smartwatch for rhythm monitoring, respectively. CONCLUSIONS: A real-time realizable algorithm analyzing smartwatch pulse recordings demonstrated high accuracy for identifying pulse irregularities among older participants. Despite advanced age, lack of smartwatch familiarity, and high burden of comorbidities, participants found the smartwatch to be highly acceptable

Distinct tau prion strains propagate in cells and mice and define different tauopathies

Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (“strains”) in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers

Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1

Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold

The Movember Global Action Plan 1 (GAP1) : Unique Prostate Cancer Tissue Microarray Resource

BACKGROUND: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. METHODS: Three separate TMA sets were built that differ by purpose and disease state. RESULTS: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases. CONCLUSIONS: The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation. IMPACT: This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.publishedVersionPeer reviewe

Investigation of the use of charge-injection-device detectors for multielement atomic absorption spectrometry

Graphite furnace atomic absorption spectrometry has excellent detection limits and accepts a wide variety of samples with little or no sample preparation. The method does, however, suffer from matrix interferences and a lack of highly capable multielement instrumentation. Continuum sources have been employed to GFAAS for multielement determinations, but the one dimensional array detectors used in these instruments can only observe a limited spectral range, limiting the multielement capabilities of these instruments. A continuum source, multielement graphite furnace atomic absorption spectrometer was developed here which employed a prototype echelle polychromator with charge injection device(CID) detection. The detection system employed a new device, the CID∼38, and camera control unit, the SCM5000E, with previously unavailable abilities. The camera system was developed and evaluated to determine its spectroscopic characteristics, and reprogrammed to provide rapid, continuous monitoring of many absorption signals simultaneously. A data acquisition and analysis scheme was developed for the prototype system, and the instrument demonstrated detection limits comparable to single-element line source GFAAS. The low ultraviolet throughput of the prototype echelle limited the spectral range that could be observed. Light scattering inside the spectrometer caused the sensitivity to decrease as the number of elements observed increased. A second echelle spectrometer system with higher wavelength resolution and increased throughput in the far ultraviolet was incorporated in to the instrument. The new system increased the spectral range which could be monitored, allowing more elements farther in the ultraviolet to be determined. The detection limits for the new system are comparable to single-element GFAAS, but degrade farther in the ultraviolet due largely to decreasing source output