Identification of new putative driver mutations and predictors of disease evolution in chronic lymphocytic leukemia

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A Three-Gene Expression Signature Identifies a Cluster of Patients with Short Survival in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by its heterogeneous clinical evolution. Despite the discovery of the most frequent cytogenomic drivers of disease during the last decade, new efforts are needed in order to improve prognostication. In this study, we used gene expression data of CLL samples in order to discover novel transcriptomic patterns associated with patient survival. We observed that a 3-gene expression signature composed of SCGB2A1, KLF4, and PPP1R14B differentiate a group of circa 5% of cases with short survival. This effect was independent of the main cytogenetic markers of adverse prognosis. Finally, this finding was reproduced in an independent retrospective cohort. We believe that this small gene expression pattern will be useful for CLL prognostication and its association with CLL response to novel drugs should be explored in the future

New Recurrent Structural Aberrations in the Genome of Chronic Lymphocytic Leukemia Based on Exome-Sequencing Data

Chronic lymphocytic leukemia (CLL) is the most frequent lymphoproliferative syndrome in Western countries, and it is characterized by recurrent large genomic rearrangements. During the last decades, array techniques have expanded our knowledge about CLL’s karyotypic aberrations. The advent of large sequencing databases expanded our knowledge cancer genomics to an unprecedented resolution and enabled the detection of small-scale structural aberrations in the cancer genome. In this study, we have performed exome-sequencing-based copy number aberration (CNA) and loss of heterozygosity (LOH) analysis in order to detect new recurrent structural aberrations. We describe 54 recurrent focal CNAs enriched in cancer-related pathways, and their association with gene expression and clinical evolution. Furthermore, we discovered recurrent large copy number neutral LOH events affecting key driver genes, and we recapitulate most of the large CNAs that characterize the CLL genome. These results provide “proof-of-concept” evidence supporting the existence of new genes involved in the pathogenesis of CLL.S

Predictors of administrative innovation: functions and organizational methods - Mexican and Colombian hospitals

Objectiv e To determine to what extent functions and organizational methods influence on administrative innovation. Design/methodology/approach This research is quantitative approach, with a not experimental and transversal design. The hypothesis was supported by using a transactional study with a sample of Mexican and Colombian hospitals through the perception of their high and medium level managers. The hospital sampling was by convenience. Findings Organizational functions and methods are associated and are predictors of administrative innovation. Practical implications As long as the hospital encourages the development of training and knowledge methods, autonomy methods for employees are developed, and when performance appraisal takes place in hospital, new methods will be able to develop and organize the routines and the management procedures, allocation of responsibilities and power among employees could be developed, as well as to develop new structure concepts for workplace, organizational practices and external relationships

Gait pattern and cognitive performance during treadmill walking in Parkinson disease

[Abstract] Objective: The aim of this study was to explore whether attentional demands are involved in gait improvements in Parkinson disease (PD) patients when they walk on a treadmill. Design: Nineteen individuals with idiopathic PD and 19 age-matched healthy controls participated in this study. Participants walked on a treadmill and on overground under single task (walk only) and dual task (walk performing a simultaneous cognitive task) conditions. The dual-task paradigm was used to reveal the attention allocation behavior. Gait pattern and cognitive performance was measured. Results: The PD group showed reduced gait variability when walking on a treadmill in comparison with overground. However, this reduction did not deteriorate during the dual task. Moreover, there were no differences in the cognitive performance between treadmill and overground walking. Conclusions: This study does not support the proposition attentional resource allocation as a possible mechanism for the treadmill-associated gait improvements observed in PD.Ministerio de Ciencia e Innovación; DEP2011-2246

LiDARgrammetry: A New Method for Generating Synthetic Stereoscopic Products from Digital Elevation Models

There are currently several new technologies being used to generate digital elevation models that do not use photogrammetric techniques. For example, LiDAR (Laser Imaging Detection and Ranging) and RADAR (RAdio Detection And Ranging) can generate 3D points and reflectivity information of the surface without using a photogrammetric approach. In the case of LiDAR, the intensity level indicates the amount of energy that the object reflects after a laser pulse is transmitted. This energy mainly depends on the material and the wavelength used by LiDAR. This intensity level can be used to generate a synthetic image colored by this attribute (intensity level), which can be viewed as a RGB (red, green and blue) picture. This work presents the outline of an innovative method, designed by the authors, to generate synthetic pictures from point clouds to use in classical photogrammetric software (digital restitution or stereoscopic vision). This is conducted using available additional information (for example, the intensity level of LiDAR). This allows mapping operators to view the LiDAR as if it were stereo-imagery, so they can manually digitize points, 3D lines, break lines, polygons and so on

The Effects of Startle and Non-Startle Auditory Stimuli on Wrist Flexion Movement in Parkinson's Disease

[Abstract] Startle stimuli lead to shorter reaction times in control subjects and Parkinson's disease (PD) patients. However, non-startle stimuli also enhance movement initiation in PD. We wanted to examine whether a startle-triggered movement would retain similar kinematic and EMG-related characteristics compared to one induced by a non-startle external cue in PD patients. In this study we investigated the electromyography pattern and the reaction time during a wrist flexion movement in response to three different stimuli: a visual imperative stimulus; visual stimulus simultaneous with a non-startle auditory stimulus and with a startle auditory stimulus. Ten PD patients and ten aged matched controls participated in this study. The reaction times were faster for startle and non-startle stimuli in comparison with the visual imperative stimulus, in both patients and control subjects. The startle cue induced a faster reaction than the non-startle cue. The electromyography pattern remained unchanged across the conditions. The results suggest that the startle reaction effect for upper limb movements are unimpaired in PD patients and has different characteristics than the effect of non-startle stimuli.Ministerio de Ciencia e Innovación; DEP2011-2246

Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency

Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studiesFinancial support from the Xunta de Galicia (10PXIB2200122PR and GRC2010/12) and the Spanish Ministry of Science and Innovation (SAF2010-15076) is gratefully acknowledged. BB, AS and AP thank the Spanish Ministry of Science and Innovation for FPU fellowshipsS

Postural Stability and Cognitive Performance of Subjects With Parkinson's Disease During a Dual-Task in an Upright Stance

[Abstract] Background: The reviewed studies on center of pressure (COP) displacement in Parkinson’s disease (PD) subjects show important methodological differences and contradictory results with regard to healthy subjects. The dual-task paradigm method has been used to examine cognitive prioritization strategies to control concurrent postural and cognitive tasks. The motor requirements, such as pronouncing words, involved in the cognitive tasks used in double-task conditions could be related to the heterogeneity of the results. Research Objective: To compare postural sway and cognitive performance in subjects with PD and controls using a dual-task paradigm with a cognitive task free of motor demands. We tried to examine the prioritization strategy of PD patients regarding healthy adults to control for concurrent postural and cognitive tasks. Materials and Methods: 25 subjects with PD and 20 healthy controls carried out a postural task under both single-task and dual-task conditions. The postural task was to stand as still as possible, with eyes first open and then closed. The dual-task condition added a concurrent cognitive task based on phoneme monitoring. COP displacement variables and cognitive performance were compared between the groups and within-subject factors were also examined. Results: PD participants showed higher COP displacement results than the controls. All participants shortened the mean sway radius in dual-task conditions compared with single-task conditions; only healthy subjects presented less transversal COP sway in dual-task conditions than in single-task conditions. The cognitive performance of PD patients on a phoneme monitoring task worsened when they carried it out while maintaining balance in a standing position compared to sitting. The opposite effect occurred in control subjects. Conclusion: This study confirms the negative influence of Parkinson’s disease on the control of standing stability, increasing the COP sway amplitude. The attentional demands of a postural task, such as standing balance, may be greater in PD patients than in healthy subjects. This would affect the performance of patients during dual-task conditions to be able to control a postural task while performing other cognitive tasks. In these conditions, cognitive performance would be negatively affected. These results suggest that subjects with PD, at least during initial disease stages, prioritize postural control over other concurrent tasks, as is also seen in healthy subjects.The authors gratefully acknowledge the financial support for the research received from the Spanish Ministry of Economy, Industry, and Competitiveness (ref. DEP2017-87384-R

An exact stochastic analysis of priority-driven periodic real-time systems and its approximations.

Abstract This paper describes a stochastic analysis framework which computes the response time distribution and the deadline miss probability of individual tasks, even for systems with a maximum utilization greater than one. The framework is uniformly applied to fixed-priority and dynamic-priority systems and can handle tasks with arbitrary relative deadlines and execution time distributions