Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874.

Evaluation of the relationship between nutrition and functional independence measures among stroke patients undergoing inpatient rehabilitation

Cerebrovascular accidents (CVA) or strokes are now the third leading cause of death in the United States. Many who suffer strokes are admitted to rehabilitation centers in order to receive therapy to help rebuild and recovery function. Nutrition plays a significant role in rehabilitation patient outcomes, and is an essential part of comprehensive care. The purpose of this study is to determine if nutrition and diet consistency are directly and independently associated with changes in the Functional Independence Measure (FIM) scores in stroke patients in an acute rehabilitation unit. This study was a retrospective secondary analysis review of medical chart records, and included a total of 84 patients. Patients were divided into groups based on their admission diet: Regular, Dysphagia Advanced, Dysphagia Mechanically Altered, Dysphagia Pureed, and Nutrition Support. Measurements included admission and discharge Total, Motor, and Cognitive FIM scores; BMI, albumin and prealbumin; age, sex, and race. Patients did show a significant improvement in their FIM scores during their stay, with patients on Regular diets having the highest FIM scores. Patients who were more debilitated and had lower FIM scores were usually in one of the altered texture diet groups, or on nutrition support. Prealbumin and BMI were also the highest in patients who had high FIM scores. Patients who were admitted on an altered diet also tended to advance in their diets, which show improvement in overall function. It is crucial to continue to improve nutrition administration to this population to help prevent morbidity and mortality. Proper nutrition in the acute phase of stroke can lay the essential groundwork for recovery.^

The role of Ski/Sno oncoproteins as negative regulators of the TGF-beta/SMAD signaling pathway in B -cell non -Hodgkin's lymphoma (NHL-B)

Non-Hodgkin's lymphomas are common tumors of the human immune system, primarily of B cell lineage (NHL-B). Negative growth regulation in the B cell lineage is mediated primarily through the TGF-β/SMAD signaling pathway that regulates a variety of tumor suppressor genes. Ski was originally identified as a transforming oncoprotein, whereas SnoN is an isoform of the Sno protein that shares a large region of homology with Ski. In this study, we show that Ski/SnoN are endogenously over-expressed both in patients' lymphoma cells and NHL-B cell lines. Exogenous TGF-β1 treatment induces down-regulation of Ski and SnoN oncoprotein expression in an NHL-B cell line, implying that Ski and SnoN modulate the TGF-β signaling pathway and are involved in cell growth regulation. Furthermore, we have developed an NHL-B cell line (DB) that has a null mutation in TGF-β receptor type II. In this mutant cell line, Ski/SnoN proteins are not down-regulated in response to TGF-β1 treatment, suggesting that downregulation of Ski and SnoN proteins in NHL-B require an intact functional TGF-β signaling pathway Resting normal B cells do not express Ski until activated by antigens and exogenous cytokines, whereas a low level of SnoN is also present in peripheral blood Go B cells. In contrast, autonomously growing NHL-B cells over-express Ski and SnoN, implying that Ski and SnoN are important cell cycle regulators. To further investigate a possible link between reduction of the Ski protein level and growth inhibition, Ski antisense oligodeoxynucleotides were transfected into NHL-B cells. The Ski protein level was found to decrease to less than 40%, resulting in restoring the effect of TGF-β and leading to cell growth inhibition and G1 cell cycle arrest. Co-immunoprecipitation experiments demonstrated that Ski associates with Smad4 in the nucleus, strongly suggesting that over-expression of the nuclear protein Ski and/or SnoN negatively regulates the TGF-β pathway, possibly by modulating Smad-mediated tumor suppressor gene expression. Together, in NHL-B, the TGF-β/SMAD growth inhibitory pathway is usually intact, but over-expression of the Ski and/or SnoN, which binds to Smad4, abrogates the negative regulatory effects of TGF-β/SMAD in lymphoma cell growth and potentiates the growth potential of neoplastic B cells. ^

Modelling of the TICS Catalyse : Realization of a project

An action of modelling of the Territorial Intelligence Community Systems or TICS began in 2009 at the end of the CaEnti project. It has several objectives: - Establish a set of documents understandable by computer specialists who are in charge of software developments, and by territorial intelligence specialists. - Lay the foundation of a vocabulary describing the main notions of TICS domain. - Ensure the evolution and sustainability of tools and systems, in a highly scalable research context. The definition of models representing the data manipulated by the tools of the suitcase Catalyse is not sufficient to describe in a complete way the TICS domain. We established a correspondence between this computer vocabulary and vocabulary related to the theme to allow communication between computer scientists and territorial intelligence specialists. Furthermore it is necessary to describe the roles of TICS. For that it is interesting to use other kinds of computing models. In this communication we present the modelling of TICS project with business process

Modelling of the TICS Catalyse : Realization of a project

An action of modelling of the Territorial Intelligence Community Systems or TICS began in 2009 at the end of the CaEnti project. It has several objectives: - Establish a set of documents understandable by computer specialists who are in charge of software developments, and by territorial intelligence specialists. - Lay the foundation of a vocabulary describing the main notions of TICS domain. - Ensure the evolution and sustainability of tools and systems, in a highly scalable research context. The definition of models representing the data manipulated by the tools of the suitcase Catalyse is not sufficient to describe in a complete way the TICS domain. We established a correspondence between this computer vocabulary and vocabulary related to the theme to allow communication between computer scientists and territorial intelligence specialists. Furthermore it is necessary to describe the roles of TICS. For that it is interesting to use other kinds of computing models. In this communication we present the modelling of TICS project with business process

Modelling of the TICS Catalyse : Realization of a project

An action of modelling of the Territorial Intelligence Community Systems or TICS began in 2009 at the end of the CaEnti project. It has several objectives: - Establish a set of documents understandable by computer specialists who are in charge of software developments, and by territorial intelligence specialists. - Lay the foundation of a vocabulary describing the main notions of TICS domain. - Ensure the evolution and sustainability of tools and systems, in a highly scalable research context. The definition of models representing the data manipulated by the tools of the suitcase Catalyse is not sufficient to describe in a complete way the TICS domain. We established a correspondence between this computer vocabulary and vocabulary related to the theme to allow communication between computer scientists and territorial intelligence specialists. Furthermore it is necessary to describe the roles of TICS. For that it is interesting to use other kinds of computing models. In this communication we present the modelling of TICS project with business process

Petrography and geochemical composition of the Atlantis II Fracture Zone

SeaBeam echo sounding, seismic reflection, magnetics, and gravity profiles were run along closely spaced tracks (5 km) parallel to the Atlantis II Fracture Zone on the Southwest Indian Ridge, giving 80% bathymetric coverage of a 30- * 170-nmi strip centered over the fracture zone. The southern and northern rift valleys of the ridge were clearly defined and offset north-south by 199 km. The rift valleys are typical of those found elsewhere on the Southwest Indian Ridge, with relief of more than 2200 m and widths from 22 to 38 km. The ridge-transform intersections are marked by deep nodal basins lying on the transform side of the neovolcanic zone that defines the present-day spreading axis. The walls of the transform generally are steep (25°-40°), although locally, they can be more subdued. The deepest point in the transform is 6480 m in the southern nodal basin, and the shallowest is an uplifted wave-cut terrace that exposes plutonic rocks from the deepest layer of the ocean crust at 700 m. The transform valley is bisected by a 1.5-km-high median tectonic ridge that extends from the northern ridge-transform intersection to the midpoint of the active transform. The seismic survey showed that the floor of the transform contains up to 0.5 km of sediment. Piston-coring at two locations on the transform floor recovered more than 1 m of sand and gravel, which appears to be turbidites shed from the walls of the fracture zone. Extensive dredging showed that more than two-thirds of the crust exposed in the transform valley and its walls were plutonic rocks, principally gabbros and residual mantle peridotites. In contrast, based on dredging and seafloor morphology, only relatively undisrupted pillow basalt flows have been exposed on crust of the same age spreading away from the transform. Magnetic anomalies are well defined out to 11 m.y. over the flanking transverse ridges and transform valley, even where layer 2 appears to be absent. The total opening rate is 1.6 cm/yr, but the arrangement of the anomalies indicates that the spreading for each ridge is asymmetric, with the ridge flanks facing the transform spreading at a rate of 1.0 cm/yr. Such an asymmetric spreading pattern requires that both the northern and southern ridges migrate away from each other at 0.2 cm/yr, thus lengthening the transform at 0.4 cm/yr for the last 11 m.y. To the north, the fracture zone valley is oriented differently from the present-day transform, indicating a paleospreading direction change at 17 m.y. from N10°E to due north-south. This change placed the transform into extension for the 11-m.y. period required for simple orthogonal ridge-transform geometry to be reestablished and produced a large transtensional basin within the transform valley. This basin was split by continued transform slip after 11 m.y., with the larger half moving to the north with the African Plate.

Effects of Ocean Acidification and Warming on Sperm Activity and Early Life Stages of the Mediterranean Mussel (Mytilus galloprovincialis)

Larval stages are among those most vulnerable to ocean acidification (OA). Projected atmospheric CO2 levels for the end of this century may lead to negative impacts on communities dominated by calcifying taxa with planktonic life stages. We exposed Mediterranean mussel (Mytilus galloprovincialis) sperm and early life stages to pHT levels of 8.0 (current pH) and 7.6 (2100 level) by manipulating pCO2 level (380 and 1000 ppm). Sperm activity was examined at ambient temperatures (16-17 °C) using individual males as replicates. We also assessed the effects of temperature (ambient and = 20 °C) and pH on larval size, survival, respiration and calcification of late trochophore/early D-veliger stages using a cross-factorial design. Increased pCO2 had a negative effect on the percentage of motile sperm (mean response ratio R= 71%) and sperm swimming speed (R= 74%), possibly indicating reduced fertilization capacity of sperm in low concentrations. Increased temperature had a more prominent effect on larval stages than pCO2, reducing performance (RSize = 90% and RSurvival = 70%) and increasing energy demand (RRespiration = 429%). We observed no significant interactions between pCO2 and temperature. Our results suggest that increasing temperature might have a larger impact on very early larval stages of M. galloprovincialis than OA at levels predicted for the end of the century.