Purpose This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. Methods EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task ...force was established to find ways of improving the instrument's sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Results Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording 'slight-moderate-severe' problems, with anchors of 'no problems' and 'unable to do' in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. Conclusions A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a 'knockout' rat model of fragile-X, we examined whether deletion of the
gene that causes ...this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X 'knockout' rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.
Abstract Objective: To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D questionnaire. Design: Stratified random sample representative ...of the general population aged 18 and over and living in the community. Setting: United Kingdom. Subjects: 3395 people resident in the United Kingdom. Main outcome measures: Average values for mobility, self care, usual activities, pain or discomfort, and anxiety or depression. Results: One in three respondents reported problems with pain or discomfort. There were differences in the perception of health according to the respondent's age, social class, education, housing tenure, economic position, and smoking behaviour. Conclusions: The EQ-5D questionnaire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population. Key messages Measurement of health outcome requires the observation of states of health Patients' involvement in recording and assessing their own state of health is a major element in the process of evaluating the impact of health care The EuroQoL EQ-5D questionnaire highlights variations in states of health which are consistent with previously published results High degrees of pain are reported in the general population. A category for pain is absent and thus undetected in the survey of disability by the Office of Population Censuses and Surveys
Abstract
During the ATLAS phase II upgrade, the tracking system of the ATLAS experiment will be
replaced by an all-silicon detector called the inner tracker (ITK) with a pixel detector as the
most ...inner part. The monitoring data of the new system will be aggregated from an on-detector ASIC
called Monitoring Of Pixel System (MOPS) and sent to the Detector Control System (DCS) using a new
interface called MOPS-HUB. The hardware components of the MOPS-HUB, firmware specifications for
the FPGA of the MOPS-HUB and its integration plan will be presented. In
addition, an irradiation plan for the new system will be introduced.
Abstract
The MOPSv2 chip is an Application Specific Integrated Circuit (ASIC) to provide the
temperature and the voltage monitoring data of individual front-end detector modules to the DCS of
the ...ATLAS ITk Pixel detector. The chip implements CANopen in a hardwired logic, provides the
possibility of remote reset without a power cycle and automated on-chip frequency trimming using
CAN messages. The chip has proven to be radiation hard during testing up to an ionizing dose of
500 Mrad, immune to Single Event Upsets (SEUs) and works reliably under irradiation at
high operating temperatures of up to 40 °C. In this paper, the functionality and
performance of the second version of the chip will be discussed, and also results from the
irradiation campaigns will be presented.
Alternative promoter usage and alternative splicing enable diversification of the transcriptome. Here we demonstrate that the function of Synaptic GTPase-Activating Protein (SynGAP), a key synaptic ...protein, is determined by the combination of its amino-terminal sequence with its carboxy-terminal sequence. 5' rapid amplification of cDNA ends and primer extension show that different N-terminal protein sequences arise through alternative promoter usage that are regulated by synaptic activity and postnatal age. Heterogeneity in C-terminal protein sequence arises through alternative splicing. Overexpression of SynGAP α1 versus α2 C-termini-containing proteins in hippocampal neurons has opposing effects on synaptic strength, decreasing and increasing miniature excitatory synaptic currents amplitude/frequency, respectively. The magnitude of this C-terminal-dependent effect is modulated by the N-terminal peptide sequence. This is the first demonstration that activity-dependent alternative promoter usage can change the function of a synaptic protein at excitatory synapses. Furthermore, the direction and degree of synaptic modulation exerted by different protein isoforms from a single gene locus is dependent on the combination of differential promoter usage and alternative splicing.
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