Precondition Inference via Partitioning of Initial States

Precondition inference is a non-trivial task with several applications in program analysis and verification. We present a novel iterative method for automatically deriving sufficient preconditions for safety and unsafety of programs which introduces a new dimension of modularity. Each iteration maintains over-approximations of the set of \emph{safe} and \emph{unsafe} \emph{initial} states. Then we repeatedly use the current abstractions to partition the program's \emph{initial} states into those known to be safe, known to be unsafe and unknown, and construct a revised program focusing on those initial states that are not yet known to be safe or unsafe. An experimental evaluation of the method on a set of software verification benchmarks shows that it can solve problems which are not solvable using previous methods.Comment: 19 pages, 8 figure

A Simple and Practical Index to Measure Dementia-Related Quality of Life

AbstractBackgroundResearch on new treatments for dementia is gaining pace worldwide in an effort to alleviate this growing health care problem. The optimal evaluation of such interventions, however, calls for a practical and credible patient-reported outcome measure.ObjectivesTo describe the refinement of the Dementia Quality-of-life Instrument (DQI) and present its revised version.MethodsA prototype of the DQI was adapted to cover a broader range of health-related quality of life (HRQOL) and to improve consistency in the descriptions of its domains. A valuation study was then conducted to assign meaningful numbers to all DQI health states. Pairs of DQI states were presented to a sample of professionals working with people with dementia and a representative sample of the Dutch population. They had to repeatedly select the best DQI state, and their responses were statistically modeled to obtain values for each health state.ResultsIn total, 207 professionals working with people with dementia and 631 members of the general population completed the paired comparison tasks. Statistically significant differences between the two samples were found for the domains of social functioning, mood, and memory. Severe problems with physical health and severe memory problems were deemed most important by the general population. In contrast, severe mood problems were considered most important by professionals working with people with dementia.DiscussionThe DQI is a simple and feasible measurement instrument that expresses the overall HRQOL of people suffering from dementia in a single meaningful number. Current results suggest that revisiting the discussion of using values from the general population might be warranted in the dementia context

Predictive validity of a two-step tool to map frailty in primary care

Background EASY-Care Two step Older people Screening (EASY-Care TOS) is a stepped approach to identify frail older people at risk for negative health outcomes in primary care, and makes use of General Practitioners’ (GPs) readily-available information. We aimed to determine the predictive value of EASY-Care TOS for negative health outcomes within the year from assessment. Methods A total of 587 patients of four GP practices in and around Nijmegen (The Netherlands) consented to participate in a longitudinal primary care registry based cohort study. Participants’ frailty was judged by their GP following the EASY-Care TOS procedure and by a Comprehensive Geriatric Assessment (CGA) at baseline. After one year health outcomes of the participants were measured by reassessment with the EASY-Care TOS procedure. Results Follow up information was available for 520 of 587 participants. In the non-frail group 9 % showed any negative health outcomes (death, ADL decline, institutionalisation, too ill to undergo assessment), against 30 % in the frail group (95 % confidence interval of the difference (CI): 14 %–28 %). Area under the receiver operating curve (AUC) of the EASY-Care TOS frailty judgement for a composite of negative health outcomes mentioned was 0.67 (95 % CI: 0.62-0.73). Compared with discrimination on the basis of age, sex and GP practice (AUC 0.70), adding EASY-Care TOS frailty judgement increased the AUC to 0.75 (+0.05, p = 0.02). The AUC on the basis of a full CGA is almost comparable to the AUC of the model with age, sex, and frailty judgement with EASY-Care TOS: 0.76 (+0.07, p = 0.005). Conclusions GPs applying the EASY-Care TOS procedure, where they only perform additional assessment when they judge this as necessary, can predict negative health outcomes in their older populations efficiently and almost as accurately as a complete specialist CGA

Economic Issues in Funding and Supplying Public Sector Information

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD). OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-beta (Abeta) 1-42, total tau (t-tau), and phosphorylated tau (p-tau) by INNOTEST enzyme-linked-immunosorbent assays (ELISA) in a memory clinic population (n = 126). Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Abeta1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal) of 26% of the subjects based on Abeta1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Abeta1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Abeta1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Abeta1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice

The design of the Dutch EASYcare study: a randomised controlled trial on the effectiveness of a problem-based community intervention model for frail elderly people [NCT00105378]

BACKGROUND: Because of their complex clinical presentations and needs frail elderly people require another approach than people who age without many complications. Several inpatient geriatric health services have proven effectiveness in frail persons. However, the wish to live independently and policies that promote independent living as an answer to population aging call for community intervention models for frail elderly people. Maybe models such as preventive home visits, comprehensive geriatric assessment, and intermediate care qualify, but their efficacy is controversial, especially in frail elderly persons living in the community. With the Dutch EASYcare Study Geriatric Intervention Programme (DGIP) we developed a model to study effectiveness of problem based community intervention models in frail elderly people. METHODS/DESIGN: DGIP is a community intervention model for frail elderly persons where the GP refers elderly patients with a problem in cognition, mood, behaviour, mobility, and nutrition. A geriatric specialist nurse applies a guideline-based intervention with a limited number of follow up visits. The intervention starts with the application of the EASYcare instrument for geriatric screening. The EASYcare instrument assesses (instrumental) activities of daily life, cognition, mood, and includes a goal setting item. During the intervention the nurse regularly consults the referring GP and a geriatrician. Effects on functional performance (Groningen Activity Restriction Scale), health related quality of life (MOS-20), and carer burden (Zarit Burden Interview) are studied in an observer blinded randomised controlled trial. 151 participants were randomised over two treatment arms – DGIP and regular care – using pseudo cluster randomisation. We are currently performing the follow up visits. These visits are planned three and six months after inclusion. Process measures and cost measures will be recorded. Intention to treat analyses will focus on post intervention differences between treatment groups. DISCUSSION: The design of a trial evaluating the effects of a community intervention model for frail elderly people was presented. The problem-based participant selection procedure satisfied; few patients that the GP referred did not meet our eligibility criteria. The use of standard terminology makes detailed insight into the contents of our intervention possible using terminology others can understand well

Frailty as a predictor of mortality in older adults within 5 years of psychiatric admission

Objectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital. Methods Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity). Results Of the 120 patients, 63 (53%) patients were frail (FI >= 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated. Conclusions Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy

Establishing a composite endpoint for measuring the effectiveness of geriatric interventions based on older persons' and informal caregivers' preference weights:a vignette study

Background: The Older Persons and Informal Caregivers Survey Minimal Dataset's (TOPICS-MDS) questionnaire which measures relevant outcomes for elderly people was successfully incorporated into over 60 research projects of the Dutch National Care for the Elderly Programme. A composite endpoint (CEP) for this instrument would be helpful to compare effectiveness of the various intervention projects. Therefore, our aim is to establish a CEP for the TOPICS-MDS questionnaire, based on the preferences of elderly persons and informal caregivers. Methods: A vignette study was conducted with 200 persons (124 elderly and 76 informal caregivers) as raters. The vignettes described eight TOPICS-MDS outcomes of older persons (morbidity, functional limitations, emotional wellbeing, pain experience, cognitive functioning, social functioning, self-perceived health and self-perceived quality of life) and the raters assessed the general well-being (GWB) of these vignette cases on a numeric rating scale (0-10). Mixed linear regression analyses were used to derive the preference weights of the TOPICS-MDS outcomes (dependent variable: GWB scores; fixed factors: the eight outcomes; unstandardized coefficients: preference weights). Results: The mixed regression model that combined the eight outcomes showed that the weights varied from 0.01 for social functioning to 0.16 for self-perceived health. A model that included "informal caregiver" showed that the interactions between this variable and each of the eight outcomes were not significant (p > 0.05). Conclusion: A preference-weighted CEP for TOPICS-MDS questionnaire was established based on the preferences of older persons and informal caregivers. With this CEP optimal comparing the effectiveness of interventions in older persons can be realized

MadGraph/MadEvent v4: The New Web Generation

We present the latest developments of the MadGraph/MadEvent Monte Carlo event generator and several applications to hadron collider physics. In the current version events at the parton, hadron and detector level can be generated directly from a web interface, for arbitrary processes in the Standard Model and in several physics scenarios beyond it (HEFT, MSSM, 2HDM). The most important additions are: a new framework for implementing user-defined new physics models; a standalone running mode for creating and testing matrix elements; generation of events corresponding to different processes, such as signal(s) and backgrounds, in the same run; two platforms for data analysis, where events are accessible at the parton, hadron and detector level; and the generation of inclusive multi-jet samples by combining parton-level events with parton showers. To illustrate the new capabilities of the package some applications to hadron collider physics are presented: 1) Higgs search in pp \to H \to W^+W^-: signal and backgrounds. 2) Higgs CP properties: pp \to H jj$in the HEFT. 3) Spin of a new resonance from lepton angular distributions. 4) Single-top and Higgs associated production in a generic 2HDM. 5) Comparison of strong SUSY pair production at the SPS points. 6) Inclusive W+jets matched samples: comparison with the Tevatron data.Comment: 38 pages, 15 figure

Single-top t-channel hadroproduction in the four-flavour scheme with POWHEG and aMC@NLO

We present results for the QCD next-to-leading order (NLO) calculation of single-top t-channel production in the 4-flavour scheme, interfaced to Parton Shower (PS) Monte Carlo programs according to the POWHEG and MC@NLO methods. Comparisons between the two methods, as well as with the corresponding process in the 5-flavour scheme are presented. For the first time results for typical kinematic distributions of the spectator-b jet are presented in an NLO+PS approach.Comment: 16+1 pages, 8 figures, matches version accepted for publication in JHE