Do Patient-Reported Outcomes Have a Role in the Management of Patients with Cystic Fibrosis?

Background: Health-related quality of life (HRQoL) is a rapidly growing area of expertise and the most commonly used patient-reported outcome (PRO). The impact of cystic fibrosis (CF) on HRQoL is liable to be great, making CF patients ideal candidates for the application of HRQoL instruments. The aims of this study were to assess the affect of CF on HRQoL, to ascertain the reliability and validity of the United Kingdom Sickness Impact Profile (UKSIP) and the Cystic Fibrosis Quality of Life Questionnaire (CFQoL) in the adult CF population, and to examine their role in the management of patients. Methods: Seventy participants were recruited from the All Wales Adult Cystic Fibrosis Centre at Llandough Hospital, UK. There were two stages to the study: self-report of the UKSIP and CFQoL; and completion of the same two questionnaires 7–10 days later. Results: The areas of HRQoL most impaired by CF were employment and concerns regarding the future. The UKSIP and CFQoL showed high internal consistency (rα = 0.89–0.93) and test–retest reliability (rs = 0.57–0.94, p < 0.005) in the CF population. Validity was variable with the UKSIP showing discrimination across socio-demographic factors, whilst the CFQoL showed increased sensitivity to clinical variables. Many parameters influenced patient-reported HRQoL, with the greatest correlations seen with the Borg score (p < 0.005). The use of a HRQoL instrument in CF annual reviews is recommended to provide holistic patient care. The results of this study underpin the value of HRQoL as a patient-reported outcome measure in the management of adult CF

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results:Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.</br

Earthquake vulnerability assessment for urban areas using an ann and hybrid swot-qspm model

Tabriz city in NW Iran is a seismic-prone province with recurring devastating earthquakes that have resulted in heavy casualties and damages. This research developed a new computational framework to investigate four main dimensions of vulnerability (environmental, social, economic and physical). An Artificial Neural Network (ANN) Model and a SWOT-Quantitative Strategic Planning Matrix (QSPM) were applied. Firstly, a literature review was performed to explore indicators with significant impact on aforementioned dimensions of vulnerability to earthquakes. Next, the twenty identified indicators were analyzed in ArcGIS, a geographic information system (GIS) software, to map earthquake vulnerability. After classification and reclassification of the layers, standardized maps were presented as input to a Multilayer Perceptron (MLP) and Self-Organizing Map (SOM) neural network. The resulting Earthquake Vulnerability Maps (EVMs) showed five categories of vulnerability ranging from very high, to high, moderate, low and very low. Accordingly, out of the nine municipality zones in Tabriz city, Zone one was rated as the most vulnerable to earthquakes while Zone seven was rated as the least vulnerable. Vulnerability to earthquakes of residential buildings was also identified. To validate the results data were compared between a Multilayer Perceptron (MLP) and a Self-Organizing Map (SOM). The scatter plots showed strong correlations between the vulnerability ratings of the different zones achieved by the SOM and MLP. Finally, the hybrid SWOT-QSPM paradigm was proposed to identify and evaluate strategies for hazard mitigation of the most vulnerable zone. For hazard mitigation in this zone we recommend to diligently account for environmental phenomena in designing and locating of sites. The findings are useful for decision makers and government authorities to reconsider current natural disaster management strategies

Identifying the most appropriate classifier for underpinning assistive technology adoption for people with dementia: an integration of Fuzzy AHP and VIKOR methods

Recently, the number of People with Dementia (PwD) has been rising exponentially across the world. The main symptoms that PwD experience include AQ1 impairments of reasoning, memory, and thought. Owing to the burden faced by this chronic condition, Assistive Technology-based solutions (ATS) have been prescribed as a form of treatment. Nevertheless, it is widely acknowledged that low adoption rates of ATS have hampered their benefits within a health and social care context. It is then necessary to effectively discriminate between adopters and non-adopters of such solutions to avoid cost implications, improve the life quality of adopters, and find intervention alternatives for non-adopters. Several classifiers have been proposed as advancement towards the personalisation of self-management interventions for dementia in a scalable way. As multiple algorithms have been developed, an important step in technology adoption is to select the most appropriate classification alternative based on different criteria. This paper presents the integration of Fuzzy AHP (FAHP) and VIKOR to address this challenge. First, FAHP was used to calculate the criteria and sub-criteria weights under uncertainty and then VIKOR was implemented to rank the classifiers. A case study considering a mobile-based self-management and reminding solution for PwD is described to validate the proposed approach. The results revealed that Easiness of interpretation (GW = 0.192) and Handling of missing data (GW = 0.145) were the two most important criteria. Furthermore, SVM (Qj = 1.0) and AB (Qj = 0.891) were concluded to be the most suitable classifiers for supporting ATS adoption in PwD

Surgical rates for Crohn’s Disease are decreasing: a population-based time trend analysis and validation study

Objectives: Temporal changes for intestinal resections for Crohn’s disease (CD) are controversial. We validated administrative database codes for CD diagnosis and surgery in hospitalized patients and then evaluated temporal trends in CD surgical resection rates. Methods: First, we validated International Classification of Disease (ICD)-10-CM coding for CD diagnosis in hospitalized patients and Canadian Classification of Health Intervention coding for surgical resections. Second, we used these validated codes to conduct population-based surveillance between fiscal years 2002 and 2010 to identify adult CD patients undergoing intestinal resection (n=981). Annual surgical rate was calculated by dividing incident surgeries by estimated CD prevalence. Time trend analysis was performed and annual percent change (APC) with 95% confidence intervals (CI) in surgical resection rates were calculated using a generalized linear model assuming a Poisson distribution. Results: In the validation cohort, 101/104 (97.1%) patients undergoing surgery and 191/200 (95.5%) patients admitted without surgery were confirmed to have CD on chart review. Among the 116 administrative database codes for surgical resection, 97.4% were confirmed intestinal resections on chart review. From 2002 to 2010, the overall CD surgical resection rate was 3.8 resections per 100 person-years. During the study period, rate of surgery decreased by 3.5% per year (95% CI: -1.1%, -5.8%), driven by decreasing emergent operations (-10.1% per year [95% CI: -13.4%, -6.7%]) whereas elective surgeries increased by 3.7% per year (95% CI: 0.1%, 7.3%). Conclusions: Overall surgical resection rates in CD are decreasing, but a paradigm shift has occurred whereby elective operations are now more commonly performed than emergent surgeries

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson