Search results for "Goal"
showing 10 items of 848 documents
Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model
2020
Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes we…
Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults
2019
© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the associa…
Is it time to combine untargeted antifungal strategies to reach the goal of 'early' effective treatment?
2016
A recently published retrospective study by Posteraro et al. [1] investigated the use of (1–3)-β-D-glucan (BDG) as a strategy for antifungal drug administration in patients at high risk of candidemia. The strategy consisted of the administration of antifungals (anidulafungin in most cases) to septic patients with a Candida score ≥ 3a nd a positive BDG result (≥80 pg/ml). This untargeted strategy led to better selection of patients, avoiding exposure to antifungals in approximately 73 % of patients with negative BDG results and leading to shortened treatment duration in another 20 % of patients. Untargeted antifungal treatments (including prophylaxis, pre-emptive and empiric approaches) are …
Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease
2018
Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and …
Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society …
2021
International audience; Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.MethodsEvidence-based review.ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-h…
Ubiquitous Structural Signaling in Bacterial Phytochromes
2015
The phytochrome family of light-switchable proteins has long been studied by biochemical, spectroscopic and crystallographic means, while a direct probe for global conformational signal propagation has been lacking. Using solution X-ray scattering, we find that the photosensory cores of several bacterial phytochromes undergo similar large-scale structural changes upon red-light excitation. The data establish that phytochromes with ordinary and inverted photocycles share a structural signaling mechanism and that a particular conserved histidine, previously proposed to be involved in signal propagation, in fact tunes photoresponse.
Me, Myself and I - Supporting People with Intellectual Disabilities Towards Self-determination
2020
The transition into work is challenging for people with intellectual disabilities (ID) and there are few digital services that support this process. The transition involves several organizations and professionals that need to collaborate and coordinate their documentation and their initiatives. This prototype paper describes a self-reflective career tool designed to support young adults with ID towards self-determination and transitions into work. The users are supported through features such as mapping of interests, skills and abilities, goal setting and progress overview. The prototype of the self-reflective career tool has been evaluated formatively and is continuously redesigned and fur…
Association between playing tactics and creating scoring opportunities in counterattacks from United States Major League Soccer games
2016
The aim of this study was to examine the effects of playing tactics on creating scoring opportunities in counterattacks from the United States Major League Soccer (MLS) 2014 season. The sample included 452 counterattack possessions, corresponding to 30 randomly selected matches. Multidimensional data from 14 categorical variables were analysed by means of a descriptive analysis and binary logistic regression. Counterattacks that started in the pre-offensive zone and had initial penetration were more effective in creating scoring opportunities than those that started in the defensive zone (OR=3.825; 95% IC: 1.765 to 8.289; p<0.01), and those without initial penetration (OR=8.689; 95% IC: 1.1…
Speaking out against everyday sexism : Gender and epistemics in accusations of “mansplaining”
2021
In everyday interaction, subtle manifestations of sexism often pass unacknowledged and become internalised and thus perceived as “natural” conduct. The introduction of new vocabularies for referring to previously unnamed sexist conduct would presumably enable individuals to start problematising hitherto unchallengeable sexism. In this paper, we investigate whether and how these vocabularies empower people to speak out against sexism. We focus on the use of the term “mansplaining” which, although coined over 10 years ago, remains controversial and contested. Using Conversation Analysis and Membership Categorisation Analysis, this paper excavates the interactional methods individuals use to f…
Assessing the costs and cost-effectiveness of ICare internet-based interventions (protocol)
2019
Background: Mental health problems are common and place a burden on the individual as well as on societal resources. Despite the existence of evidence-based treatments, access to treatment is often prevented or delayed due to insufficient health care resources. Effective internet-based self-help interventions have the potential to reduce the risk for mental health problems, to successfully bridge waiting time for face-to-face treatment and to address inequities in access. However, little is known about the cost-effectiveness of such interventions. This paper describes the study protocol for the economic evaluation of the studies that form the ICare programme of internet-based interventions …