Commonalities and Differences in Carotid Body Dysfunction in Hypertension and Heart Failure

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential differences, although not all mechanisms have been fully explored across all disease models. One potential commonality is that of hypoperfusion of the carotid body across hypertension and HF, where the excessive sympathetic drive may reduce blood flow in both models and, in addition, lowered cardiac output in HF may potentiate the hypoperfusion state of the carotid body. Other mechanisms are explored that focus on neurotransmitter and signalling pathways intrinsic to the carotid body (e.g. ATP, carbon monoxide) as well as extrinsic molecules carried in the blood (e.g. leptin); there are also transcription factors found in the carotid body endothelium that modulate its activity (Krüppel-like factor 2). The evidence to date fully supports that a better understanding of the mechanisms of carotid body pathophysiology is a fruitful strategy for informing potential new treatment strategies for many cardiovascular, respiratory and metabolic diseases, and this is highly relevant clinically

Cross-cultural adaptation of the disability assessment for dementia (DAD)

The original version of the Disability Assessment for Dementia (DAD) was translated into Portuguese and back translated to English. The divergences of translation were identified and discussed, resulting in a version that was used in a preliminary investigation for cross-cultural adaptation. The final version was administered to 29 patients with mild to moderate probable Alzheimer's disease. The correlation coefficients of DAD were 0.929 and 0.932 for the inter-examiner and test-retest evaluations respectively. The reliability indexes were also high (Kappa 0.72 p<0.001 inter-examiners and 0.85 p<0.001 test-retest). The Brazilian version of DAD was easy to administer and had good reliability to assess the functional status of demented patients. It will contribute to the follow-up of these patients in our population. Moreover, it can be used in transcultural studies on functional abilities in dementia.A versão original da Escala de Avaliação de Incapacidade em Demência (Disability Assessment for Dementia, DAD) foi traduzida para a língua portuguesa e retrotraduzida para o inglês. Divergências de tradução foram identificadas e discutidas, chegando-se a uma versão que foi submetida a pré-teste para adaptação sócio-cultural. A versão final foi administrada a amostra de 29 pacientes com doença de Alzheimer provável de leve a moderada. Os coeficientes de correlação da DAD foram 0,929 e 0,932 nas avaliações inter e intra-examinadores respectivamente. Os índices de confiabilidade também foram elevados (Kappa=0,72; p<0,001 inter-examinadores e Kappa=0,85; p<0,001 intra-examinadores). A versão brasileira da escala DAD mostrou-se um instrumento de fácil aplicação e boa confiabilidade para avaliação funcional de pacientes com demência e poderá contribuir para o acompanhamento desses pacientes em nosso meio. Esta versão também poderá ser utilizada em estudos transculturais sobre habilidades funcionais de pacientes com demência.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola de Paulista de Medicina Departamento de Neurologia e NeurocirurgiaUNIFESP, Escola de Paulista de Medicina Depto. de Neurologia e NeurocirurgiaSciEL

Brazilian version of the Cornell depression scale in dementia

OBJECTIVE: Translating and adapting the Cornell scale for depression in dementia to the Portuguese language and verifying the interrater and test-retest reliability of the translated and adapted version. METHOD: The Cornell scale was translated into Portuguese and back translated into English. Divergences of translation were identified and discussed, resulting in a version which was submitted to a pre-test for cross-cultural adaptation. The final version was administered to a sample of 29 patients with probable AD and to their caregivers. RESULTS: The Cornell Scale presented good interrater (Kappa=0,77; p<0,001) and test-retest reliability (Kappa=0,76; p<0,001). The final version was easy to administer and well understood by the caregivers. CONCLUSION: The Brazilian version of the Cornell Scale is an instrument with good reliability to evaluate depression in patients with dementia. This tool will contribute to the evaluation and follow-up of depressed patients with dementia in our population and may also be used in multicentric studies with Brazilian population.OBJETIVO: Tradução e adaptação da escala Cornell de depressão em demência e verificação da confiabilidade entre e intra-examinadores da versão na língua portuguesa. MÉTODO: A versão original da Escala Cornell foi traduzida para o português por firma especializada em tradução de textos médicos e retrotraduzida para o inglês por outros dois tradutores independentes. As divergências de tradução foram identificadas e discutidas, chegando-se à versão que foi submetida à pré-teste para adaptação sócio-cultural. Após esta adaptação, obteve-se a versão final que foi administrada a amostra de 29 pacientes com doença de Alzheimer provável e aos seus cuidadores. RESULTADOS: A versão final da escala mostrou-se de fácil aplicação e obteve boa confiabilidade intra-examinador (Kappa=0,77; p<0,001) e entre-examinadores (Kappa=0,76; p<0,001). CONCLUSÃO: A versão brasileira da Escala Cornell é um instrumento que pode ser utilizado para avaliação e acompanhamento de depressão em pacientes com demência.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola de Paulista de Medicina Departamento de Neurologia e NeurocirurgiaUNIFESP, Escola de Paulista de Medicina Depto. de Neurologia e NeurocirurgiaSciEL

MISSION ENGINEERING FOR HYBRID FORCE 2025

This report focuses on the mission engineering process for a hybrid force in 2025. Updated tasking from OPNAV N9I emphasized the necessity of focusing on the benefits of using cost-conservative unmanned systems. Specifically, the focus was placed on the near-peer competitor China and the problems that could be expected in an anti-access/area denial (A2/AD) situation in the South China Sea. The Naval Surface Warfare Center mission engineering approach was used to identify specific vignettes for proposed alternative fleet architectures and then analyzed using combat simulation and optimization models. Research on performance characteristics and cost were compiled on current unmanned systems, specifically those in development at a high technology readiness level. Proposed unmanned systems architectures were developed as solutions to the A2/AD problem and proposed vignettes. The unmanned systems architectures were then run through an optimization model to maximize system performance while minimizing cost. The results of the architecture optimization were then input into modeling and simulation. The overall effectiveness of each architecture in each vignette were then compared to find the most effective solution. An analysis of the results was performed to show the expected mission effectiveness and proposed cost of utilizing the proposed solution unmanned architectures. The most effective architectures included search, counter swarm, delivery, and attack systems.Lieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyMajor, Republic of Singapore NavyMajor, Singapore ArmyLieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyCommander, United States NavyApproved for public release. Distribution is unlimited

A New Clevosaurid from the Triassic (Carnian) of Brazil and the Rise of Sphenodontians in Gondwana

The early evolution of lepidosaurs is marked by an extremely scarce fossil record during the Triassic. Importantly, most Triassic lepidosaur specimens are represented by disarticulated individuals from high energy accretion deposits in Laurasia, thus greatly hampering our understanding of the initial stages of lepidosaur evolution. Here, we describe the fragmentary remains of an associated skull and mandible of Clevosaurus hadroprodon sp. nov., a new taxon of sphenodontian lepidosaur from the Late Triassic (Carnian; 237–228 Mya) of Brazil. Referral to Sphenodontia is supported by the combined presence of a marginal dentition ankylosed to the apex of the dentary, maxilla, and premaxilla; the presence of ‘secondary bone’ at the bases of the marginal dentition; and a ventrally directed mental process at the symphysis of the dentary. Our phylogenetic analyses recover Clevosaurus hadroprodon as a clevosaurid, either in a polytomy with the Late Triassic to Early Jurassic Clevosaurus and Brachyrhinodon (under Bayesian inference), or nested among different species of Clevosaurus (under maximum parsimony). Clevosaurus hadroprodon represents the oldest known sphenodontian from Gondwana, and its clevosaurid relationships indicates that these sphenodontians achieved a widespread biogeographic distribution much earlier than previously thought.Fil: Hsiou, Annie S.. Universidade de Sao Paulo; BrasilFil: Nydam, Randall L.. Midwestern University; Estados UnidosFil: Simões, Tiago R.. University of Alberta; Canadá. Harvard University; Estados UnidosFil: Pretto, Flávio A.. Universidade Federal de Santa Maria; BrasilFil: Onary, Silvio. Universidade de Sao Paulo; BrasilFil: Martinelli, Agustín Guillermo. Universidade Federal do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Liparini, Alexandre. Universidade Federal de Sergipe; BrasilFil: Romo de Vivar Martínez, Paulo Rodrigo. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Marina. Universidade Federal do Rio Grande do Sul; BrasilFil: Schultz, Cesar. Universidade Federal do Rio Grande do Sul; BrasilFil: Caldwell, Michael Wayne. University of Alberta; Canad

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

ANO1 amplification and expression in HNSCC with a high propensity for future distant metastasis and its functions in HNSCC cell lines

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is associated with poor survival. To identify prognostic and diagnostic markers and therapeutic targets, we studied ANO1, a recently identified calcium-activated chloride channel (CaCC). METHODS: High-resolution genomic and transcriptomic microarray analysis and functional studies using HNSCC cell line and CaCC inhibitors. RESULTS: Amplification and overexpression of genes within the 11q13 amplicon are associated with the propensity for future distance metastasis of HPV-negative HNSCC. ANO1 was selected for functional studies based on high correlations, cell surface expression and CaCC activity. ANO1 overexpression in cells that express low endogenous levels stimulates cell movement, whereas downregulation in cells with high endogenous levels has the opposite effect. ANO1 overexpression also stimulates attachment, spreading, detachment and invasion, which could account for its effects on migration. CaCC inhibitors decrease movement, suggesting that channel activity is required for the effects of ANO1. In contrast, ANO1 overexpression does not affect cell proliferation. INTERPRETATION: ANO1 amplification and expression could be markers for distant metastasis in HNSCC. ANO1 overexpression affects cell properties linked to metastasis. Inhibitors of CaCCs could be used to inhibit the tumourigenic properties of ANO1, whereas activators developed to increase CaCC activity could have adverse effects