Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

<p>Abstract</p> <p>Background</p> <p>Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.</p> <p>Results</p> <p>Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.</p> <p>Conclusion</p> <p>This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.</p

Construction and psychometric testing of the EMPATHIC questionnaire measuring parent satisfaction in the pediatric intensive care unit

Abstract PURPOSE: To construct and test the reliability and validity of the EMpowerment of PArents in THe Intensive Care (EMPATHIC) questionnaire measuring parent satisfaction in the pediatric intensive care unit (PICU). METHODS: Structured development and psychometric testing of a parent satisfaction-with-care instrument with the results of two cohorts of parents (n = 2,046) from eight PICUs in the Netherlands. RESULTS: In the first cohort, 667/1,055 (63%) parents participated followed by 551/991 (56%) parents in the second cohort. The empirical structure of the instrument was established by confirmatory factor analysis with the first sample of parents confirming 65 statements within five theoretically conceptualized domains: information, care and cure, organization, parental participation, and professional attitude. The standardized factor loadings were greater than 0.40 in 63 statements. Cronbach's α, a measure of reliability, per domain ranged from 0.73 to 0.93 in both cohorts with no significant difference documenting the reliability over time. Beside rigorous content and face validity, the congruent validity of the instrument showed adequate correlation with four gold standard questions measuring overall satisfaction. The non-differential validity was confirmed with no significant differences between the population characteristics and the domains, except that parents with a child for a surgical admission were more satisfied on information issues. CONCLUSIONS: The final EMPATHIC questionnaire incorporates 65 statements. The empirical structure of the satisfaction statements and domains was satisfactory. The reliability and validity proved to be adequate. The EMPATHIC questionnaire is a valid quality performance indicator to measure quality of care as perceived by parents

Modelling and prevention of acute kidney injury through ischemia and reperfusion in a combined human renal proximal Tubule/Blood Vessel-on-a-Chip

Analytical BioScience

Negative incentive steering in a policy network

In this article the process of developing a policy for the recent comprehensive retrenchment operation in the Dutch university system is analysed from a theoretical point of view on decisionmaking. The article especially addresses the question whether some empirical evidence can be found for the rationalist view of collective decision-making, which states that a process of social communication should eventually lead to a unanimous and rational consensus concerning the selection of the optimal policy.\ud \ud The actual analysis concerns the way a retrenchment policy has been developed in a process of social communication between the most important actors: the Minister of Education and Science and the thirteen Dutch universities. It is assumed that the various communicative linkages between these actors can be interpreted as a policy network in which both governmental and non-governmental actors operate.\ud \ud The article concludes that in the Dutch university policy-network a complicated balance of interdependencies exists and that several sub-networks can be distinguished. It is also concluded that the Minister, while recognizing the interdependencies in the network, was able to use a special kind of (negative) incentive, inducing the universities to act as he wished.\ud \ud This negative incentive steering, however, also persuaded the universities to go to the utmost in their consultation efforts, thus trying to reach the rationalist ideal of collective decision-making. The final conclusion therefore is that the rationalist view of collective decision-making does not appear to be unrealistic. The article ends with a warning against a common mistake made regarding the normative appearance of the rationalist perspective

Construction and psychometric testing of the EMPATHIC questionnaire measuring parent satisfaction in the pediatric intensive care unit

General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Purpose: To construct and test the reliability and validity of the EMpowerment of PArents in THe Intensive Care (EMPATHIC) questionnaire measuring parent satisfaction in the pediatric intensive care unit (PICU). Methods: Structured development and psychometric testing of a parent satisfaction-withcare instrument with the results of two cohorts of parents (n = 2,046) from eight PICUs in the Netherlands. Results: In the first cohort, 667/ 1,055 (63%) parents participated followed by 551/991 (56%) parents in the second cohort. The empirical structure of the instrument was established by confirmatory factor analysis with the first sample of parents confirming 65 statements within five theoretically conceptualized domains: information, care and cure, organization, parental participation, and professional attitude. The standardized factor loadings were greater than 0.40 in 63 statements. Cronbach&apos;s a, a measure of reliability, per domain ranged from 0.73 to 0.93 in both cohorts with no significant difference documenting the reliability over time. Beside rigorous content and face validity, the congruent validity of the instrument showed adequate correlation with four gold standard questions measuring overall satisfaction. The nondifferential validity was confirmed with no significant differences between the population characteristics and the domains, except that parents with a child for a surgical admission were more satisfied on information issues. Intensive Care Med (2011) 37:310-318 DOI 10.1007/s00134-010-2042 PEDIATRIC ORIGINAL Conclusions: The final EMPATHIC questionnaire incorporates 65 statements. The empirical structure of the satisfaction statements and domains was satisfactory. The reliability and validity proved to be adequate. The EMPATHIC questionnaire is a valid quality performance indicator to measure quality of care as perceived by parents

The Epidemic of Hip Fractures: Are We on the Right Track?

Background: Hip fractures are a public health problem, leading to hospitalization, long-term rehabilitation, reduced quality of life, large healthcare expenses, and a high 1-year mortality. Especially older adults are at greater risk of fractures than the general population, due to the combination of an increased fall risk and osteoporosis. The aim of this study was to determine time trends in numbers and incidence rates of hip fracture-related hospitalizations and admission duration in the older Dutch population. Methods and Findings: Secular trend analysis of all hospitalizations in the older Dutch population (≥65 years) from 1981 throughout 2008, using the National Hospital Discharge Registry. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of hospital admissions and hospital days due to a hip fracture were used as outcome measures in each year of the study. Between 1981 and 2008, the absolute number of hip fractures doubled in the older Dutch population. Incidence rates of hip fracture-related hospital admissions increased with age, and were higher in women than in men. The age-adjusted incidence rate increased from 52.0 to 67.6 per 10,000 older persons. However, since 1994 the incidence rate decreased (percentage annual change -0.5%, 95% CI: -0.7; -0.3), compared with the period 1981-1993 (percentage annual change 2.3%, 95% CI: 2.0; 2.7). The total number of hospital days was reduced by a fifth, due to a reduced admission duration in all age groups. A possible limitation was that data were obtained from a linked administrative database, which did not include information on medication use or co-morbidities. Conclusions: A trend break in the incidence rates of hip fracture-related hospitalizations was observed in the Netherlands around 1994, possibly as a first result of efforts to prevent falls and fractures. However, the true cause of the observation is unknown

Evolving missions and university entrepreneurship:Academic spin-offs and graduate start-ups in the entrepreneurial society

A recent call has urged to broaden the conceptualization of university entrepreneurship in order to appreciate the heterogeneity of contexts and actors involved in the process of entrepreneurial creation. A gap still persists in the understanding of the variety of ventures generated by different academic stakeholders, and the relationships between these entrepreneurial developments and university missions, namely, teaching and research. This paper addresses this particular gap by looking at how university teaching and research activities influence universities’ entrepreneurial ventures such as academic spin-offs and graduate start-ups. Empirically, we analyse the English higher education sector, drawing on institutional data at the university level. First, we explore the ways in which teaching and research activities are configured, and secondly, we examine how such configurations relate to academic spin-offs and graduate start-ups across different universities over time. Our findings suggest, first, that the evolution of USOs and graduate start-ups exhibit two different pathways over time; and second, that teaching and research both affect entrepreneurial ventures but their effect is different.JRC.B.4-Human Capital and Employmen