Patient-Reported Comorbidity and Survival in Older Adults with Cancer

Background: Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient-reported comorbidity and all-cause mortality using various comorbidity scoring algorithms. Materials and Methods: The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient-reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all-cause mortality. Results: The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0–10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01–1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02–1.23). Conclusion: Comorbid conditions in older adults with cancer are highly prevalent and associated with all-cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one-page patient-reported questionnaire. Implications for Practice: In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient-reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all-cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one-page patient-reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer

Geriatric assessment predicts hospitalization frequency and long-term care use in older adult cancer survivors

PURPOSE The association between geriatric assessment (GA)–identified impairments and long-term health care use in older cancer survivors remains unknown. Our objective was to evaluate whether a GA performed at cancer diagnosis was predictive of hospitalizations and long-term care (LTC) use in older adult cancer survivors. METHODS Older adults with GA performed between 3 months before through 6 months after diagnosis were included (N = 125). Patients with Medicare Parts A and B coverage and no managed care were identified. Hospitalizations and LTC use (skilled nursing or assisted living) were assessed up to 5 years postdiagnosis. GA risk measures were evaluated in separate Poisson models estimating the relative risk (RR) for hospital and LTC visits, adjusting for age and Charlson comorbidity score. RESULTS The mean age of patients was 74 years, and the majority were female (80%) and white (90%). Breast cancer (64%) and early-stage disease (stages 0 to III, 77%) were common. Prefrail/frail status (RR, 2.5; P, .001), instrumental activities of daily living impairment (RR, 5.47; P, .001), and limitations in climbing stairs (RR, 2.94; P, .001) were associated with increased hospitalizations. Prefrail/frail status (RR, 1.86; P, .007), instrumental activities of daily living impairment (RR, 4.58; P, .001), presence of falls (RR, 6.73; P, .001), prolonged Timed Up and Go (RR, 5.45; P, .001), and limitations in climbing stairs (RR, 1.89; P, .005) were associated with LTC use. CONCLUSION GA-identified impairments were associated with increased hospitalizations and LTC use among older adults with cancer. GA-focused interventions should be targeted toward high-risk patients to reduce long-term adverse health care use in this vulnerable population

Grand Unification Signal from Ultra High Energy Cosmic Rays?

The spectrum of ultrahigh energy (above \approx 10^{9} GeV) cosmic rays is consistent with the decay of GUT scale particles. The predicted mass is m_X=10^b GeV, where b=14.6_{-1.7}^{+1.6}.Comment: 4 pages, 3 figures one figure removed, one table added, conclusions essentially remained the same within errorbar

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

The Fluorescence Detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics Research Section

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure

Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs) and their relevance to proliferation and apoptosis in pulmonary arterial hypertension.</p> <p>Methods</p> <p>Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin), lipophobic (pravastatin) and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release.</p> <p>Results</p> <p>Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550) was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase.</p> <p>Conclusions</p> <p>Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.</p

A Lithium-ion Battery Using Partially Lithiated Graphite Anode and Amphi-redox LiMn2O4 Cathode

Delithiation followed by lithiation of Li+-occupied (n-type) tetrahedral sites of cubic LiMn2O4 spine! (LMO) at similar to 4V(Li/Li+). (delivering-100 mAhg(LMO)-1) has been used for energy storage by lithium ion batteries (LIBs). In this work, we utilized unoccupied (p-type) octahedral sites of LMO available for lithiation at -3V(Li/Li). (delivering additional -100 mAh gLmo(-1)) that have never been used for LI Bs in full cell configuration. The whole capacity of amphi-redox LMO, including both oxidizable n-type and reducible p-type redox sites, at -200 mAh g(LMO)-1 was realized by using the reactions both at 4 VLi/Li+ and 3 VLi/Li+. Durable reversibility of the 3 V reaction was achieved by graphene-wrapping LMO nanoparticles (LMO@Gn). Prelithiated graphite (LinC6,, n &lt; 1) was used as anodes to lithiate the unoccupied octahedral sites of LMO for the 3V reactio