The Complexity of Model Checking (Collapsible) Higher-Order Pushdown Systems

We study (collapsible) higher-order pushdown systems --- theoretically robust and well-studied models of higher-order programs --- along with their natural subclass called (collapsible) higher-order basic process algebras. We provide a comprehensive analysis of the model checking complexity of a range of both branching-time and linear-time temporal logics. We obtain tight bounds on data, expression, and combined-complexity for both (collapsible) higher-order pushdown systems and (collapsible) higher-order basic process algebra. At order-$k$, results range from polynomial to $(k+1)$-exponential time. Finally, we study (collapsible) higher-order basic process algebras as graph generators and show that they are almost as powerful as (collapsible) higher-order pushdown systems up to MSO interpretations

The impact of a night confinement policy on patients in a high secure inpatient mental health service.

Purpose – From 2012, all high-secure forensic mental health services in England began operating a policy of confining patients to their locked bedrooms overnight to increase service efficiency and reduce costs. The purpose of this paper is to assess the views of staff and patients concerning the policy and examine the specific impact of the policy on patients. Design/methodology/approach – Measures of patients’ sleep hygiene, patients’ behaviour, ward atmosphere, engagement with therapy and adverse incidents were taken both before and after the night confinement (NC) policy was implemented. Both patients and staff also expressed their views of the impact of the NC policy. Findings – Results provide converging evidence that the impact of the NC policy on patients is negligible. There were no consistent negative effects of confining patients overnight. Rather, patients and staff were broadly positive about the impact that the practice had on patients. Practical implications – Confining patients to locked bedrooms overnight does not exert any consistent influence, positive or negative, on patients’ sleep hygiene, behaviour or engagement with therapy, and patients expressed a broadly positive view of the practice of NC. Thus, a NC policy may have a contribution to make to the provision an effective high-secure mental health service. Originality/value – The study provides convincing evidence that secure inpatient mental health services that are considering the adoption of a NC policy may do so without fear of a negative impact on patients

A Decision Procedure for Path Feasibility of String Manipulating Programs with Integer Data Type

Strings are widely used in programs, especially in web applications. Integer data type occurs naturally in string-manipulating programs, and is frequently used to refer to lengths of, or positions in, strings. Analysis and testing of string-manipulating programs can be formulated as the path feasibility problem: given a symbolic execution path, does there exist an assignment to the inputs that yields a concrete execution that realizes this path? Such a problem can naturally be reformulated as a string constraint solving problem. Although state-of-the-art string constraint solvers usually provide support for both string and integer data types, they mainly resort to heuristics without completeness guarantees. In this paper, we propose a decision procedure for a class of string-manipulating programs which includes not only a wide range of string operations such as concatenation, replaceAll, reverse, and finite transducers, but also those involving the integer data-type such as length, indexof, and substring. To the best of our knowledge, this represents one of the most expressive string constraint languages that is currently known to be decidable. Our decision procedure is based on a variant of cost register automata. We implement the decision procedure, giving rise to a new solver OSTRICH+. We evaluate the performance of OSTRICH+ on a wide range of existing and new benchmarks. The experimental results show that OSTRICH+ is the first string decision procedure capable of tackling finite transducers and integer constraints, whilst its overall performance is comparable with the state-of-the-art string constraint solvers

CSS Minification via Constraint Solving

Minification is a widely-accepted technique which aims at reducing the size of the code transmitted over the web. We study the problem of minifying Cascading Style Sheets (CSS) --- the de facto language for styling web documents. Traditionally, CSS minifiers focus on simple syntactic transformations (e.g. shortening colour names). In this paper, we propose a new minification method based on merging similar rules in a CSS file. We consider safe transformations of CSS files, which preserve the semantics of the CSS file. The semantics of CSS files are sensitive to the ordering of rules in the file. To automatically identify a rule merging opportunity that best minimises file size, we reduce the rule-merging problem to a problem on CSS-graphs, i.e., node-weighted bipartite graphs with a dependency ordering on the edges, where weights capture the number of characters (e.g. in a selector or in a property declaration). Roughly speaking, the corresponding CSS-graph problem concerns minimising the total weight of a sequence of bicliques (complete bipartite subgraphs) that covers the CSS-graph and respects the edge order. We provide the first full formalisation of CSS3 selectors and reduce dependency detection to satisfiability of quantifier-free integer linear arithmetic, for which highly-optimised SMT-solvers are available. To solve the above NP-hard graph optimisation problem, we show how Max-SAT solvers can be effectively employed. We have implemented our algorithms using Max-SAT and SMT-solvers as backends, and tested against approximately 70 real-world examples (including the top 20 most popular websites). In our benchmarks, our tool yields larger savings than six well-known minifiers (which do not perform rule-merging, but support many other optimisations). Our experiments also suggest that better savings can be achieved in combination with one of these six minifiers

Multi-Collector Inductively Coupled Plasma Mass Spectrometer – Operational Performance Report

The INL made an assessment of the commercially available inductively coupled plasma mass spectrometers (ICPMS) for actinide analysis; emphasizing low detection limits for plutonium. INL scientists subsequently determined if plutonium was present on a swipe, at a 10 million atom decision level. This report describes the evaluation of ICPMS instruments and the operational testing of a new process for the dissolution, separation and analysis via ICPMS of swipes for plutonium and uranium. The swipe dissolution, plutonium and uranium isolation, separation and purification are wet chemistry methods following established procedures. The ICPMS is a commercially available multi-collector magnetic sector mass spectrometer that utilizes five ion counting detectors operating simultaneously. The instrument includes a sample introduction system allowing for sample volumes of < 1 mL to be reproducibly injected into the instrument with minimal waste of the sample solution, while maximizing the useable signal. The performance of the instrument was measured using SRM 996 (244Pu spike) at concentrations of 12 parts per quadrillion (ppq, fg/mL) and with SRM 4350B Columbia River Sediment samples spiked onto swipes at the 10 million atom level. The measured limit of detection (LOD, defined as 3s) for 239Pu is 310,000 atoms based upon the instrument blank data. The limit of quantification (LOQ defined as 10 s) for 239Pu is 105,000 atoms. The measured limit of detection for 239Pu from the SRM 4350B spiked onto a swipe was 2.7 million atoms with the limit of quantification being 9.0 million atoms

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. RESULTS: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. CONCLUSION: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.T.C. is supported by National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland. A.C. has a Wellcome Trust Postdoctoral Training Fellowship for Clinicians (103413/Z/13/Z). K.O. is supported by funding from BBSRC, MRC, Wellcome Trust and GSK. R.D. and D.S.K are funded by National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK. C.S. and S.E. are supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803 grant to the Center of Chronic immunodeficiency and BMBF 01GM1111B grant to the PID-NET initiative). S.N.F is supported in part by the Southampton UK National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility and NIHR Respiratory Biomedical Research Unit. M.A.A.I. is funded by NHS Innovation London and King’s College Hospital Charitable Trust. A.F., S.L., A.D., F.R-L and S.K. are supported by the European Union’s 7th RTD Framework Programme (ERC advanced grant PID-IMMUNE contract 249816) and a government grant managed by the French Agence Nationale de la Recherche as part of the "Investments for the Future" program (ANR-10-IAHU-01). S.L. is supported by the Agence Nationale de la Recherche (ANR) (ANR-14-CE14-0028-01), the Foundation ARC pour la Recherche sur le Cancer (France), the Rare Diseases Foundation (France) and François Aupetit Association (France). S.L. is a senior scientist and S.K is a researcher at the Centre National de la Recherche Scientifique-CNRS (France). A.D. and S.K. are supported by the “Institut National de la Santé et de la Recherche Médicale". S.K. also supported by the Fondation pour la Recherche Médicale (grant number: ING20130526624), la Ligue Contre le Cancer (Comité de Paris) and the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH). S.O.B is supported by the Higher Education Funding Council for England. B.V. is supported by the UK Biotechnology and Biological Sciences Research Council [BB/I007806/1], Cancer Research UK [C23338/A15965) and the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. B.V. is consultant to Karus Therapeutics (Oxford, UK). S.N. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (095198/Z/10/Z). S.N. is also supported by the European Research Council Starting grant 260477, the EU FP7 collaborative grant 261441 (PEVNET project) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, UK. A.M.C. is funded by the Medical Research Council, British Lung Foundation, University of Sheffield and Cambridge NIHR-BRC. Research in A.M.C. laboratory has received non-commercial grant support from GSK, Novartis, and MedImmune.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jaci.2016.06.02