Competing risks of cancer mortality and cardiovascular events in individuals with multimorbidity

Background: Cancer patients with cardiovascular and other comorbidities are at concurrent risk of multiple adverse outcomes. However, most treatment decisions are guided by evidence from single-outcome models, which may be misleading for multimorbid patients. Objective: We assessed the interacting effects of cancer, cardiovascular, and other morbidity burdens on the competing outcomes of cancer mortality, serious cardiovascular events, and other-cause mortality. Design: We analyzed a cohort of 6,500 adults with initial cancer diagnosis between 2001 and 2008, SEER 5-year survival ≥26%, and a range of cardiovascular risk factors. We estimated the cumulative incidence of cancer mortality, a serious cardiovascular event (myocardial infarction, coronary revascularization, or cardiovascular mortality), and other-cause mortality over 5 years, and identified factors associated with the competing risks of each outcome using cause-specific Cox proportional hazard models. Results: Following cancer diagnosis, there were 996 (15.3%) cancer deaths, 328 (5.1%) serious cardiovascular events, and 542 (8.3%) deaths from other causes. In all, 4,634 (71.3%) cohort members had none of these outcomes. Although cancer prognosis had the greatest effect, cardiovascular and other morbidity also independently increased the hazard of each outcome. The effect of cancer prognosis on outcome was greatest in year 1, and the effect of other morbidity was greater in individuals with better cancer prognoses. Conclusion: In multimorbid oncology populations, comorbidities interact to affect the competing risk of different outcomes. Quantifying these risks may provide persons with cancer plus cardiovascular and other comorbidities more accurate information for shared decision-making than risks calculated from single-outcome models. Journal of Comorbidity 2014:4(1):29–3

The SnoDog: Preliminary design of a close air support aircraft

U.S. military forces are presently searching for the next generation Close Air Support aircraft. The following report presents the SnoDog, a low-cost ($14.8 million) aircraft capable of operating from remote battlefields and unimproved airstrips. The configuration consists of a conventional, low aspect-ratio wing, twin booms, twin canted vertical stabilizers along with a high-mounted joined horizontal tail. A supercritical airfoil for the wing enhances aerodynamic performance, while the SnoDog's instability increases maneuverability over current close air support aircraft. Survivability was incorporated into the design by the use of a titanium tub to protect the cockpit from anti-aircraft artillery, as well as, the twin booms and retracted gear disposition. The booms aid survivability by supplying separated, redundant controls, and the landing gear are slightly exposed when retracted to enable a belly landing in emergencies. Designed to fly at Mach .76, the SnoDog is powered by two low-bypass turbofan engines. Engine accessibility and interchangeable parts make the SnoDog highly maintainable. The SnoDog is adaptable to many different missions, as it is capable of carrying advanced avionics pods, carrying external fuel tanks or refueling in-air, and carrying various types of munitions. This makes the SnoDog a multirole aircraft capable of air-to-air and air-to-ground combat. This combination of features make the SnoDog unique as a close air support aircraft, capable of meeting the U.S. military's future needs

Evaluation of spontaneous retinal venous pulsation in primary open-angle and primary angle-closure glaucoma patients

Introduction: Spontaneous retinal venous pulsation (SRVP) is a rhythmic variation in the calibre of one or more retinal veins. The incidence of SRVP was reduced in glaucoma patients. It was also reduced in people with raised intracranial pressure compared to a healthy population. Purpose: The main objective was to report the frequency and rate of SRVP in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) patients and to associate these with the severity of glaucoma in Malay patients. Design of study: A comparative cross-sectional study. Materials and methods: A comparative cross-sectional study involving primary glaucoma patients attending the eye clinic at Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia, was performed between December 2015 and June 2017. The main outcomes measured were the presence and rate of SRVP using a confocal scanning laser ophthalmoscope (Spectralis High-Resolution Optical Coherence Tomography Angiography, Heidelberg Engineering GmbH, Heidelberg, Germany). In the presence of SRVP, the rate of SRVP in one minute was counted manually based on the real-time fundus movie recorded using the confocal scanning laser ophthal-moscope

Cool-SPS: Pulling down the temperature, pushing up the reactivity

The use of materials, especially in the field of electronics, but also for catalysis, health (…), requires the control of their shaping (dense or porous materials, spherical or anisotropic particles…). This objective is frequently reached through the preparation of ceramics by conventional, high temperature sintering. Spark Plasma Sintering (SPS) is a particularly efficient densification method, initially dedicated to refractory materials, that is now extremely versatile and allows for the elaboration of nanostructured and/or transparent ceramics, among many other applications. Please click Additional Files below to see the full abstract

Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases

Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of (35)S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset

Waste NR latex based-precursors as carbon source for CNTs eco-fabrications

In this work, the potential of utilizing a waste latex‐based precursor (i.e., natural rubber glove (NRG)) as a carbon source for carbon nanotube (CNT) fabrication via chemical vapor deposition has been demonstrated. Gas chromatography‐mass spectroscopy (GC‐MS) analysis reveals that the separation of the lightweight hydrocarbon chain from the heavier long chain differs in hydrocarbon contents in the NRG fraction (NRG‐L). Both solid NRG (NRG‐S) and NRG‐L samples contain >63% carbon, <0.6% sulfur and <0.08% nitrogen content, respectively, as per carbon‐nitrogen‐sulfur (CNS) analysis. Growth of CNTs on the samples was confirmed by Raman spectra, SEM and TEM images, whereby it was shown that NRG‐S is better than NRG‐L in terms of synthesized CNTs yield percentage with similar quality. The optimum vaporization and reaction temperatures were 350 and 800 °C, respectively, considering the balance of good yield percentage (26.7%) and quality of CNTs (ID/IG = 0.84 ± 0.08, diameter ≈ 122 nm) produced. Thus, utilization of waste NRG as a candi-date for carbon feedstock to produce value‐added CNTs products could be a significant approach for eco‐technology

Assessing Health Research and Innovation Impact: Evolution of a Framework and Tools in Alberta, Canada

Publicly funded research and innovation (R&amp;I) organizations around the world are facing increasing demands to demonstrate the impacts of their investments. In most cases, these demands are shifting from academically based outputs to impacts that benefit society. Funders and other organizations are grappling to understand and demonstrate how their investments and activities are achieving impact. This is compounded with challenges that are inherent to impact assessment, such as having an agreed understanding of impact, the time lag from research to impact, establishing attribution and contribution, and consideration of diverse stakeholder needs and values. In response, many organizations are implementing frameworks and using web-based tools to track and assess academic and societal impact. This conceptual analysis begins with an overview of international research impact frameworks and emerging tools that are used by an increasing number of public R&amp;I funders to demonstrate the value of their investments. From concept to real-world, this paper illustrates how one organization, Alberta Innovates, used the Canadian Academy of Health Sciences (CAHS) impact framework to guide implementation of its fit-for-purpose impact framework with an agnostic international six-block protocol. The implementation of the impact framework at Alberta Innovates is also supported by adopting emerging web-based tools. Drawing on the lessons learned from this continuous organizational endeavor to assess and measure R&amp;I impact, we present preliminary plans for developing an impact strategy for Alberta Innovates that can be applied across sectors, including energy, environment and agriculture, and may possibly be adopted by other international funders

Discovery of estrogen receptor α target genes and response elements in breast tumor cells

BACKGROUND: Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. RESULTS: Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells, of which only 89 were direct target genes. Meta-analysis of heterogeneous in vitro and in vivo datasets showed that the expression profiles in T-47D and MCF-7 cells are remarkably similar and overlap with genes differentially expressed between ER-positive and ER-negative tumors. Computational analysis revealed a significant enrichment of putative estrogen response elements (EREs) in the cis-regulatory regions of direct target genes. Chromatin immunoprecipitation confirmed ligand-dependent ER binding at the computationally predicted EREs in our highest ranked ER direct target genes, NRIP1, GREB1 and ABCA3. Wider examination of the cis-regulatory regions flanking the transcriptional start sites showed species conservation in mouse-human comparisons in only 6% of predicted EREs. CONCLUSIONS: Only a small core set of human genes, validated across experimental systems and closely associated with ER status in breast tumors, appear to be sufficient to induce ER effects in breast cancer cells. That cis-regulatory regions of these core ER target genes are poorly conserved suggests that different evolutionary mechanisms are operative at transcriptional control elements than at coding regions. These results predict that certain biological effects of estrogen signaling will differ between mouse and human to a larger extent than previously thought

Renal dysfunction is associated with shorter telomere length in heart failure

Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P <0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure