A characterisation of the least-fixed-point operator by dinaturality

The paper addresses the question of when the least-fixed-point operator, in a cartesian closed category of domains, is characterised as the unique dinatural transformation from the exponentiation bifunctor to the identity functor. We give a sufficient condition on a cartesian closed full subcategory of the category of algebraic cpos for the characterisation to hold. The condition is quite mild, and the least-fixed-point operator is so characterised in many of the most commonly used categories of domains. By using retractions, the characterisation extends to the associated cartesian closed categories of continuous cpos. However, dinaturality does not always characterise the least-fixed-point operator. We show that in cartesian closed full subcategories of the category of continuous lattices the characterisation fails. 1 Introduction Mulry [7] showed that, under general conditions on a category of domains, the least-fixed-point operator, lfp D : D D ! D, is a dinatural transformation ..

SAFETEL randomised controlled feasibility trial of a safety planning intervention with follow-up telephone contact to reduce suicidal behaviour: study protocol

Introduction: There are no evidence-based interventions that can be administered in hospital settings following a general hospital admission after a suicide attempt. Aim: To determine whether a safety planning intervention (SPI) with follow-up telephone support (SAFETEL) is feasible and acceptable to patients admitted to UK hospitals following a suicide attempt. Methods and Analysis: Three-phase development and feasibility study with embedded process evaluation. Phase I comprises tailoring an SPI with telephone follow-up originally designed for veterans in the USA, for use in the UK. Phase II involves piloting the intervention with patients (n=30) who have been hospitalised following a suicide attempt. Phase III is a feasibility randomised controlled trial of 120 patients who have been hospitalised following a suicide attempt with a 6-month follow-up. Phase III participants will be recruited from across four National Health Service hospitals in Scotland and randomised to receive either the SPI with telephone follow-up and treatment as usual (n=80) or treatment as usual only (n=40). The primary outcomes are feasibility outcomes and include the acceptability of the intervention to participants and intervention staff, the feasibility of delivery in this setting, recruitment, retention and intervention adherence as well as the feasibility of collecting the self-harm readmission to hospital outcome data. Statistical analyses will include description of recruitment rates, intervention adherence/use, response rates and estimates of the primary outcome event rates, and intervention effect size (Phase III). Thematic analyses will be conducted on interview and focus group data. Ethics and Dissemination: The East of Scotland Research Ethics Service (EoSRES) approved this study in March 2017 (GN17MH101 Ref: 17/ES/0036). The study results will be disseminated via peer-reviewed publication and conference presentations. A participant summary paper will also be disseminated to patients, service providers and policy makers alongside the main publication. Trial Registration Number: ISRCTN62181241

Effects for Efficiency: Asymptotic Speedup with First-Class Control

We study the fundamental efficiency of delimited control. Specifically, we show that effect handlers enable an asymptotic improvement in runtime complexity for a certain class of functions. We consider the generic count problem using a pure PCF-like base language $\lambda_b$ and its extension with effect handlers $\lambda_h$. We show that $\lambda_h$ admits an asymptotically more efficient implementation of generic count than any $\lambda_b$ implementation. We also show that this efficiency gap remains when $\lambda_b$ is extended with mutable state. To our knowledge this result is the first of its kind for control operators

Axioms and (counter)examples in synthetic domain theory

AbstractAn axiomatic treatment of synthetic domain theory is presented, in the framework of the internal logic of an arbitrary topos. We present new proofs of known facts, new equivalences between our axioms and known principles, and proofs of new facts, such as the theorem that the regular complete objects are closed under lifting (and hence well-complete). In Sections 2–4 we investigate models, and obtain independence results. In Section 2 we look at a model in de Modified realizability Topos, where the Scott Principle fails, and the complete objects are not closed under lifting. Section 3 treats the standard model in the Effective Topos. Theorem 3.2 gives a new characterization of the initial lift-algebra relative to the dominance. We prove that in the standard case it is not the internal colimit of the chain 0→L(0)→L2(0)→⋯ . The models in Sections 2 and 3 compare via an adjunction. Section 4 discusses a model in a Grothendieck topos. A feature here is that N is not well-complete (where N is the natural numbers object), whereas 2 is

A novel asynchronous access method with binary interfaces

© 2008 Silva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The effectiveness of a multidisciplinary intervention strategy for the treatment of symptomatic joint hypermobility in childhood:A randomised, single Centre parallel group trial (The Bendy Study)

Introduction: Joint hypermobility is common in childhood and can be associated with musculoskeletal pain and dysfunction. Current management is delivered by a multidisciplinary team, but evidence of effectiveness is limited. This clinical trial aimed to determine whether a structured multidisciplinary, multisite intervention resulted in improved clinical outcomes compared with standard care. Method: A prospective randomised, single centre parallel group trial comparing an 8-week individualised multidisciplinary intervention programme (bespoke physiotherapy and occupational therapy in the clinical, home and school environment) with current standard management (advice, information and therapy referral if deemed necessary). The primary endpoint of the study was between group difference in child reported pain from baseline to 12 months as assessed using the Wong Baker faces pain scale. Secondary endpoints were parent reported pain (100 mm visual analogue scale), parent reported function (child health assessment questionnaire), child reported quality of life (child health utility 9-dimensional assessment), coordination (movement assessment battery for children version 2) and grip strength (handheld dynamometer). Results: 119 children aged 5 to 16 years, with symptomatic hypermobility were randomised to receive an individualised multidisciplinary intervention (I) (n = 59) or standard management (S) (n = 60). Of these, 105 completed follow up at 12 months. No additional significant benefit could be shown from the intervention compared to standard management. However, there was a statistically significant improvement in child and parent reported pain, coordination and grip strength in both groups. The response was independent of the degree of hypermobility. Conclusion: This is the first randomised controlled trial to compare a structured multidisciplinary, multisite intervention with standard care in symptomatic childhood hypermobility. For the majority, the provision of education and positive interventions aimed at promoting healthy exercise and self-management was associated with significant benefit without the need for more complex interventions. Trial registration: The trial was registered prospectively with the national database at the Clinical Research Network (UKCRN Portfolio 9366). The trial was registered retrospectively with ISRCTN (ISRCTN86573140)

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

The use of Open Reading frame ESTs (ORESTES) for analysis of the honey bee transcriptome

BACKGROUND: The ongoing efforts to sequence the honey bee genome require additional initiatives to define its transcriptome. Towards this end, we employed the Open Reading frame ESTs (ORESTES) strategy to generate profiles for the life cycle of Apis mellifera workers. RESULTS: Of the 5,021 ORESTES, 35.2% matched with previously deposited Apis ESTs. The analysis of the remaining sequences defined a set of putative orthologs whose majority had their best-match hits with Anopheles and Drosophila genes. CAP3 assembly of the Apis ORESTES with the already existing 15,500 Apis ESTs generated 3,408 contigs. BLASTX comparison of these contigs with protein sets of organisms representing distinct phylogenetic clades revealed a total of 1,629 contigs that Apis mellifera shares with different taxa. Most (41%) represent genes that are in common to all taxa, another 21% are shared between metazoans (Bilateria), and 16% are shared only within the Insecta clade. A set of 23 putative genes presented a best match with human genes, many of which encode factors related to cell signaling/signal transduction. 1,779 contigs (52%) did not match any known sequence. Applying a correction factor deduced from a parallel analysis performed with Drosophila melanogaster ORESTES, we estimate that approximately half of these no-match ESTs contigs (22%) should represent Apis-specific genes. CONCLUSIONS: The versatile and cost-efficient ORESTES approach produced minilibraries for honey bee life cycle stages. Such information on central gene regions contributes to genome annotation and also lends itself to cross-transcriptome comparisons to reveal evolutionary trends in insect genomes