An approach to computing downward closures

The downward closure of a word language is the set of all (not necessarily contiguous) subwords of its members. It is well-known that the downward closure of any language is regular. While the downward closure appears to be a powerful abstraction, algorithms for computing a finite automaton for the downward closure of a given language have been established only for few language classes. This work presents a simple general method for computing downward closures. For language classes that are closed under rational transductions, it is shown that the computation of downward closures can be reduced to checking a certain unboundedness property. This result is used to prove that downward closures are computable for (i) every language class with effectively semilinear Parikh images that are closed under rational transductions, (ii) matrix languages, and (iii) indexed languages (equivalently, languages accepted by higher-order pushdown automata of order 2).Comment: Full version of contribution to ICALP 2015. Comments welcom

Development of evidence-based clinical practice guidelines (CPGs): comparing approaches

<p>Abstract</p> <p>Background</p> <p>While the potential of clinical practice guidelines (CPGs) to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it.</p> <p>Methods</p> <p>CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'.</p> <p>Results</p> <p>Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO).</p> <p>There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting recommendations, consultation with others beyond the guideline development group, and ongoing review and updating of the CPG.</p> <p>Conclusion</p> <p>The key elements of an evidence-based CPG development process are addressed with strong concordance by existing CPG development handbooks. Further research is required to determine why these key elements are often not addressed by CPG developers.</p

Transauricular embolization of the rabbit coronary artery for experimental myocardial infarction: comparison of a minimally invasive closed-chest model with open-chest surgery

<p>Abstract</p> <p>Introduction</p> <p>To date, most animal studies of myocardial ischemia have used open-chest models with direct surgical coronary artery ligation. We aimed to develop a novel, percutaneous, minimally-invasive, closed-chest model of experimental myocardial infarction (EMI) in the New Zealand White rabbit and compare it with the standard open-chest surgical model in order to minimize local and systemic side-effects of major surgery.</p> <p>Methods</p> <p>New Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD) coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG), cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP) measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining.</p> <p>Results</p> <p>In total, 38 subjects underwent EMI with a surgical (n = 17) or endovascular (n = 21) approach. ST-segment elevation (1.90 ± 0.71 mm) occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68) within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05). Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68).</p> <p>Conclusion</p> <p>The proposed model of transauricular coronary coil embolization avoids thoracotomy and major surgery and may be an equally reliable and reproducible platform for the experimental study of myocardial ischemia.</p

Post Eclosion Age Predicts the Prevalence of Midgut Trypanosome Infections in Glossina

The teneral phenomenon, as observed in Glossina sp., refers to the increased susceptibility of the fly to trypanosome infection when the first bloodmeal taken is trypanosome-infected. In recent years, the term teneral has gradually become synonymous with unfed, and thus fails to consider the age of the newly emerged fly at the time the first bloodmeal is taken. Furthermore, conflicting evidence exists of the effect of the age of the teneral fly post eclosion when it is given the infected first bloodmeal in determining the infection prevalence. This study demonstrates that it is not the feeding history of the fly but rather the age (hours after eclosion of the fly from the puparium) of the fly when it takes the first (infective) bloodmeal that determines the level of fly susceptibility to trypanosome infection. We examine this phenomenon in male and female flies from two distinct tsetse clades (Glossina morsitans morsitans and Glossina palpalis palpalis) infected with two salivarian trypanosome species, Trypanosoma (Trypanozoon) brucei brucei and Trypanosoma (Nannomonas) congolense using Fisher's exact test to examine differences in infection rates. Teneral tsetse aged less than 24 hours post-eclosion (h.p.e.) are twice as susceptible to trypanosome infection as flies aged 48 h.p.e. This trend is conserved across sex, vector clade and parasite species. The life cycle stage of the parasite fed to the fly (mammalian versus insect form trypanosomes) does not alter this age-related bias in infection. Reducing the numbers of parasites fed to 48 h.p.e., but not to 24 h.p.e. flies, increases teneral refractoriness. The importance of this phenomenon in disease biology in the field as well as the necessity of employing flies of consistent age in laboratory-based infection studies is discussed

Rationale and study design for a randomised controlled trial to reduce sedentary time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time ANd diabetes)

<p>Abstract</p> <p>Background</p> <p>The rising prevalence of Type 2 Diabetes Mellitus (T2DM) is a major public health problem. There is an urgent need for effective lifestyle interventions to prevent the development of T2DM. Sedentary behaviour (sitting time) has recently been identified as a risk factor for diabetes, often independent of the time spent in moderate-to-vigorous physical activity. Project STAND (<it>Sedentary Time ANd Diabetes</it>) is a study which aims to reduce sedentary behaviour in younger adults at high risk of T2DM.</p> <p>Methods/Design</p> <p>A reduction in sedentary time is targeted using theory driven group structured education. The STAND programme is subject to piloting and process evaluation in line with the MRC framework for complex interventions. Participants are encouraged to self-monitor and self-regulate their behaviour. The intervention is being assessed in a randomised controlled trial with 12 month follow up. Inclusion criteria are a) aged 18-40 years with a BMI in the obese range; b) 18-40 years with a BMI in the overweight range plus an additional risk factor for T2DM. Participants are randomised to the intervention (n = 89) or control (n = 89) arm. The primary outcome is a reduction in sedentary behaviour at 12 months as measured by an accelerometer (count < 100/min). Secondary outcomes include physical activity, sitting/lying time using the ActivPAL posture monitor, fasting and 2 h oral glucose tolerance test, lipids, inflammatory biomarkers, body weight, waist circumference, blood pressure, illness perceptions, and efficacy beliefs for behaviour change.</p> <p>Conclusions</p> <p>This is the first UK trial to address sedentary behaviour change in a population of younger adults at risk of T2DM. The results will provide a platform for the development of a range of future multidisciplinary interventions in this rapidly expanding high-risk population.</p> <p>Trial registration</p> <p>Current controlled trials <a href="http://www.controlled-trials.com/ISRCTN08434554">ISRCTN08434554</a>, MRC project 91409.</p

Investigation of autism and GABA receptor subunit genes in multiple ethnic groups

Autism is a neurodevelopmental disorder of complex genetics, characterized by impairment in social interaction and communication, as well as repetitive behavior. Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism. Previous studies in our lab indicated association of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients. Studies of genetic variation in African-American autism families are rare. Analysis of 557 Caucasian and an independent population of 54 African-American families with 35 SNPs within GABRB1 and GABRA4 strengthened the evidence for involvement of GABRA4 in autism risk in Caucasians (rs17599165, p=0.0015; rs1912960, p=0.0073; and rs17599416, p=0.0040) and gave evidence of significant association in African-Americans (rs2280073, p=0.0287 and rs16859788, p=0.0253). The GABRA4 and GABRB1 interaction was also confirmed in the Caucasian dataset (most significant pair, rs1912960 and rs2351299; p=0.004). Analysis of the subset of families with a positive history of seizure activity in at least one autism patient revealed no association to GABRA4; however, three SNPs within GABRB1 showed significant allelic association; rs2351299 (p=0.0163), rs4482737 (p=0.0339), and rs3832300 (p=0.0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype

Evidence-based practice in neonatal health: knowledge among primary health care staff in northern Viet Nam

<p>Abstract</p> <p>Background</p> <p>An estimated four million deaths occur each year among children in the neonatal period. Current evidence-based interventions could prevent a large proportion of these deaths. However, health care workers involved in neonatal care need to have knowledge regarding such practices before being able to put them into action.</p> <p>The aim of this survey was to assess the knowledge of primary health care practitioners regarding basic, evidence-based procedures in neonatal care in a Vietnamese province. A further aim was to investigate whether differences in level of knowledge were linked to certain characteristics of community health centres, such as access to national guidelines in reproductive health care, number of assisted deliveries and geographical location.</p> <p>Methods</p> <p>This cross-sectional survey was completed within a baseline study preparing for an intervention study on knowledge translation (Implementing knowledge into practice for improved neonatal survival: a community-based trial in Quang Ninh province, Viet Nam, the NeoKIP project, ISRCTN44599712). Sixteen multiple-choice questions from five basic areas of evidence-based practice in neonatal care were distributed to 155 community health centres in 12 districts in a Vietnamese province, reaching 412 primary health care workers.</p> <p>Results</p> <p>All health care workers approached for the survey responded. Overall, they achieved 60% of the maximum score of the questionnaire. Staff level of knowledge on evidence-based practice was linked to the geographical location of the CHC, but not to access to the national guidelines or the number of deliveries at the community level. Two separated geographical areas were identified with differences in staff level of knowledge and concurrent differences in neonatal survival, antenatal care and postnatal home visits.</p> <p>Conclusion</p> <p>We have identified a complex pattern of associations between knowledge, geography, demographic factors and neonatal outcomes. Primary health care staff knowledge regarding neonatal health is scarce. This is a factor that is possible to influence and should be considered in future efforts for improving the neonatal health situation in Viet Nam.</p