Revealing nuclear receptor hub modules from Basal-like breast cancer expression networks

Nuclear receptors are a class of transcriptional factors. Together with their co-regulators, they regulate development, homeostasis, and metabolism in a ligand-dependent manner. Their ability to respond to environmental stimuli rapidly makes them versatile cellular components. Their coordinated activities regulate essential pathways in normal physiology and in disease. Due to their complexity, the challenge remains in understanding their direct associations in cancer development. Basal-like breast cancer is an aggressive form of breast cancer that often lacks ER, PR and Her2. The absence of these receptors limits the treatment for patients to the non-selective cytotoxic and cytostatic drugs. To identify potential drug targets it is essential to identify the most important nuclear receptor association network motifs in Basal-like subtype progression. This research aimed to reveal the transcriptional network patterns, in the hope to capture the underlying molecular state driving Basal-like oncogenesis. In this work, we illustrate a multidisciplinary approach of integrating an unsupervised machine learning clustering method with network modelling to reveal unique transcriptional patterns (network motifs) underlying Basal-like breast cancer. The unsupervised clustering method provides a natural stratification of breast cancer patients, revealing the underlying heterogeneity in Basal-like. Identification of gene correlation networks (GCNs) from Basal-like patients in both the TCGA and METABRIC databases revealed three critical transcriptional regulatory constellations that are enriched in Basal-like. These represent critical NR components implicated in Basal-like breast cancer transcription. This approach is easily adaptable and applicable to reveal critical signalling relationships in other diseases

Comportamento e bem-estar de peixe beta (Betta splendens) em aquário.

O trabalho será realizado no Instituto Federal de Educação, Ciência e Tecnologia do Espírito Santo/Campus Alegre, no laboratório de Nutrição e Produção de Espécies Ornamentais, localizado no município de Alegre, região Sul do estado do Espírito Santo, Brasil. Serão utilizados 70 exemplares machos de peixe Beta (Betta splendens) com idade entre 90 e 120 dias. Dos quais 15 exemplares de peixe Beta, machos adultos, com aproximadamente 90 dias serão manejados em aquário tipo cruzeta com quatro pontas de mesmo comprimento e distância do centro. Quatro testes serão realizados para analisar a preferência dos peixes quanto a tipo de (T1) substrato, de (T2) vegetações, de (T3) abrigos e de (T4) cores. Em cada teste será oferecido quatro tipos de preferências (P1, P2, P3 e P4) distribuídos aleatoriamente por sorteio. Serão analisados os comportamentos de frequência em cada preferência, duração em cada preferência e tempo de latência. No segundo trabalho serão utilizados 35 exemplares machos de peixe Beta com aproximadamente 90 dias distribuídos aleatoriamente em cinco tipos de alojamento (tratamentos); (T1) copos de 0,3 litros, (T2) beteiras 3 litros sem enriquecimento, (T3) beteiras 3 litros enriquecidas, (T4) aquários 38 litros sem enriquecimento e (T5) aquários 38 litros enriquecidos. Os comportamentos dos animais serão gravados durante todo o período experimental. Será realizado um total de dezesseis horas de observações para cada tratamento. Durante o mesmo período também será realizado observação focal durante cinco minutos intermitentes alternando entre os tratamentos no total de 150 minutos por período. Os comportamentos registrados serão organizados formando um etograma e comparados entre os diferentes tratamentos. No último trabalho serão utilizados os 35 exemplares machos de peixe Beta, advindos do experimento de enriquecimento, com aproximadamente 120 dias em aquário tipo labirinto. Localizado dentro do labirinto haverá quatro pontos; dois objetos estressores, espelho (E1) e predador (E2), e dois objetos recompensa ambiente enriquecido (R1) e alimento (R2). Comportamentos como lateralidade, latência, preferência, frequência e duração serão analisados durante 15 minutos na parta da manhã e 15 minutos na parte da tarde durante dois dias consecutivos. Então os animais terão cinco dias de descanso e retornarão ao labirinto para mais 15 minutos de observações comportamentais na parta da manhã e 15 minutos na parte da tarde durante dois dias consecutivos

The impact of atrial fibrillation on prognosis in aortic stenosis

Background Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor. Objective To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function. Methods Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality. Results In total, 2849 patients with significant AS (mean age 72 +/- 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P < 0.001). On univariable (HR: 1.42; 95% CI: 1.25-1.62; P < 0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02-1.38; P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality. Conclusion Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS.Cardiolog

The impact of atrial fibrillation on prognosis in aortic stenosis

Background: Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor. Objective: To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function. Methods: Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality. Results: In total, 2849 patients with significant AS (mean age 72 +/- 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P P P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality. Conclusion: Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS.</p

Role of computed tomography imaging for transcatheter valvular repair/insertion

During the last decade, the development of transcatheter based therapies has provided feasible therapeutic options for patients with symptomatic severe valvular heart disease who are deemed inoperable. The promising results of many nonrandomized series and recent landmark trials have increased the number of percutaneous transcatheter valve procedures in high operative risk patients. Pre-procedural imaging of the anatomy of the aortic or mitral valve and their spatial relationships is crucial to select the most appropriate device or prosthesis and to plan the percutaneous procedure. Multidetector row computed tomography provides 3-dimensional volumetric data sets allowing unlimited plane reconstructions and plays an important role in pre-procedural screening and procedural planning. This review will describe the evolving role of multidetector row computed tomography in patient selection and strategy planning of transcatheter aortic and mitral valve procedures

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on four research projects and a list of publications.National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD13U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD30U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1DARPA/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-5876

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3 and reports on four research projects.California Institute of Technology/Jet Propulsion Laboratory Agreement 959548National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616U.S. Navy - Office of Naval Research Grant N00014-92-J-4098Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Agreement N00014-90-J-1002U.S. Navy - Office of Naval Research Agreement N00014-89-J-1019DEMACOU.S. Army Cold Regions Research and Engineering Laboratory Contract DACA89-93-K-0009U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1Advanced Research Projects Agency/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-58764National Science Foundatio

Cardiovascular imaging 2011 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700