Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

The combined positive impact of Lean methodology and Ventana Symphony autostainer on histology lab workflow

<p>Abstract</p> <p>Background</p> <p>Histologic samples all funnel through the H&E microtomy staining area. Here manual processes intersect with semi-automated processes creating a bottleneck. We compare alternate work processes in anatomic pathology primarily in the H&E staining work cell.</p> <p>Methods</p> <p>We established a baseline measure of H&E process impact on personnel, information management and sample flow from historical workload and production data and direct observation. We compared this to performance after implementing initial Lean process modifications, including workstation reorganization, equipment relocation and workflow levelling, and the Ventana Symphony stainer to assess the impact on productivity in the H&E staining work cell.</p> <p>Results</p> <p>Average time from gross station to assembled case decreased by 2.9 hours (12%). Total process turnaround time (TAT) exclusive of processor schedule changes decreased 48 minutes/case (4%). Mean quarterly productivity increased 8.5% with the new methods. Process redesign reduced the number of manual steps from 219 to 182, a 17% reduction. Specimen travel distance was reduced from 773 ft/case to 395 ft/case (49%) overall, and from 92 to 53 ft/case in the H&E cell (42% improvement).</p> <p>Conclusions</p> <p>Implementation of Lean methods in the H&E work cell of histology can result in improved productivity, improved through-put and case availability parameters including TAT.</p

Robotic ubiquitous cognitive ecology for smart homes

Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent- based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feed- back received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work

Embodied cognition and circular causality: on the role of constitutive autonomy in the reciprocal coupling of perception and action.

addendum: [OA] owner: this timestamp: 2015.07.2

Association of global coagulation profiles with cardiovascular risk factors and atherosclerosis: A sex disaggregated analysis from the BioHEART-CT study

Background: Although the association between dysregulated coagulation and atherosclerosis is well recognized, individual assays have been of minimal value in understanding disease susceptibility. Here we investigated the association of global coagulation profiles with coronary artery disease with consideration of sex differences. Methods and Results: The study included patients from the BioHEART-CT (The BioHEART Study: Assessing Patients With Suspected Cardiovascular Disease for New Disease Markers and Risk Factors) biobank who had computed tomography coronary angiograms scored for coronary artery calcium score (CACS) and Gensini score. The cohort included 206 adult patients who were referred for clinically indicated computed tomography coronary angiography and had a median of 2 major cardiac risk factors; 50% were women and the average age was 62.6 years (±9.9 years). The overall hemostatic potential (OHP) and calibrated automated thrombography generation assays were performed on platelet-poor plasma. CACS and Gensini score in men were significantly correlated in bivariate analysis with measures from the OHP assay, and regression models predicting disease severity by CACS or Gensini score were improved by adding the OHP assay variables in men but not in women. The calibrated automated thrombography generation assay demonstrated a more hypercoagulable profile in women than in men. The OHP assay showed hypercoagulable profiles in women with hyperlipidemia and men with obesity. Conclusions: The OHP assay identified hypercoagulable profiles associated with different risk factors for each sex and was associated with CACS and Gensini score severity in men, emphasizing the associations between increased fibrin generation and reduced fibrinolysis with cardiac risk factors and early atherosclerosis. Registration Information: www.anzctr.org.au. Identifier: ACTRN12618001322224.Katharine A. Kott, Marie-Christine Morel-Kopp, Stephen T. Vernon, Yuki Takagi, Belinda A. Di Bartolo, Karlheinz Peter, Jean Y. Yang, Stuart M. Grieve, Christopher Ward, Gemma A. Figtre

Individual Differences in Processing Speed and Working Memory Speed as Assessed with the Sternberg Memory Scanning Task

The Sternberg Memory Scanning (SMS) task provides a measure of processing speed (PS) and working memory retrieval speed (WMS). In this task, participants are presented with sets of stimuli that vary in size. After a delay, one item is presented, and participants indicate whether or not the item was part of the set. Performance is assessed by speed and accuracy for both the positive (item is part of the set) and the negative trials (items is not part of the set). To examine the causes of variation in PS and WMS, 623 adult twins and their siblings completed the SMS task. A non-linear growth curve (nLGC) model best described the increase in reaction time with increasing set size. Genetic analyses showed that WMS (modeled as the Slope in the nLGC model) has a relatively small variance which is not due to genetic variation while PS (modeled as the Intercept in the nLGC model) showed large individual differences, part of which could be attributed to additive genetic factors. Heritability was 38% for positive and 32% for negative trials. Additional multivariate analyses showed that the genetic effects on PS for positive and negative trials were completely shared. We conclude that genetic influences on working memory performance are more likely to act upon basic processing speed and (pre)motoric processes than on the speed with which an item is retrieved from short term memory

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

Contains fulltext : 88910.pdf (publisher's version ) (Open Access)BACKGROUND: Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. METHODS/DESIGN: This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands.The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks.Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). DISCUSSION: This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00713843