Evaluation of perampanel as monotherapy for focal seizures: Experience from open-label extension studies

Perampanel, a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is approved for adjunctive treatment of focal seizures, with or without secondarily generalized seizures, and for primary generalized tonic–clonic seizures in patients with epilepsy aged ≥ 12 years. Perampanel was recently approved for monotherapy use for focal seizures in the U.S.A. Anti-seizure drug monotherapy may be preferable to polytherapy, which is generally associated with increased toxicity, non-compliance, and cost. Here, we report cases where patients had converted to perampanel monotherapy during open-label extension (OLEx) portions of 9 Phase II and III studies. Of 2245 patients who enrolled in the OLEx studies, we identified 7 patients with drug-resistant focal seizures who discontinued all non-perampanel anti-seizure drugs and were maintained on perampanel monotherapy for ≥ 91 days until the end of data cut-off. Patients received perampanel monotherapy for up to 1099 days (157 weeks), most at a modal dose of 12 mg. Seizure data were available for 6 patients, of whom 5 had a ≥ 90% reduction in overall seizure frequency between baseline and their last 13-week period of monotherapy (3 were seizure-free). Perampanel monotherapy was generally well tolerated and the safety profile during perampanel monotherapy was consistent with clinical and post-marketing experience in the adjunctive setting. This analysis included a small proportion of patients with highly drug-resistant focal seizures who converted to monotherapy during OLEx studies. While these limited data are encouraging in suggesting that perampanel might be useful as a monotherapy, further studies are required to explore outcomes in a less drug-resistant population, where a larger proportion of patients might benefit from monotherapy. © 2017 The Author

Towards a Java Subtyping Operad

The subtyping relation in Java exhibits self-similarity. The self-similarity in Java subtyping is interesting and intricate due to the existence of wildcard types and, accordingly, the existence of three subtyping rules for generic types: covariant subtyping, contravariant subtyping and invariant subtyping. Supporting bounded type variables also adds to the complexity of the subtyping relation in Java and in other generic nominally-typed OO languages such as C# and Scala. In this paper we explore defining an operad to model the construction of the subtyping relation in Java and in similar generic nominally-typed OO programming languages. Operads, from category theory, are frequently used to model self-similar phenomena. The Java subtyping operad, we hope, will shed more light on understanding the type systems of generic nominally-typed OO languages.Comment: 13 page

An all-optical approach for probing microscopic flows in living embryos

Living systems rely on fluid dynamics from embryonic development to adulthood. To visualize biological fluid flow, devising the proper labeling method compatible with both normal biology and in vivo imaging remains a major experimental challenge. Here, we describe a simple strategy for probing microscopic fluid flows in vivo that meets this challenge. An all-optical procedure combining femtosecond laser ablation, fast confocal microscopy and 3D-particle tracking was devised to label, image and quantify the flow. This approach is illustrated by studying the flow generated within a micrometer scale ciliated vesicle located deep inside the zebrafish embryo and involved in breaking left-right embryonic symmetry. By mapping the velocity field within the vesicle and surrounding a single beating cilium, we show this method can address the dynamics of cilia-driven flows at multiple length scales, and can validate the flow features as predicted from previous simulations. This approach provides new experimental access to questions of microscopic fluid dynamics in vivo

Implementation of the updated NICE haematological cancers (NG47) improving outcomes guidelines across Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) in England : a UK NEQAS LI survey

AIMS: Haematological malignancies represent a diverse group of diseases with complex diagnostic requirements. National Institute for Health and Care Excellence (NICE) Haematological Cancer: Improving Outcomes Guidance was published in 2003 and updated in 2016 (NG47), providing recommendations for service delivery including Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDSs). This survey assessed the implementation of NG47 guidelines, with a specific focus on implementation in relation to laboratory SIHMDS delivery. METHODS: A survey was issued to the 17 SIHMDSs identified in England. The questionnaire covered laboratory configuration, information systems, integrated reporting and multidisciplinary team (MDT) working recommendations. RESULTS: In the 10 responding SIHMDS, full implementation of recommendations was not achieved. Higher levels of implementation were reported in 'colocated' services compared with 'networked' SIHMDS. Increased guideline implementation was reported with longer duration since initial establishment of a SIHMDS and for laboratory based as opposed to clinical (MDT) reporting recommendations. CONCLUSIONS: Our survey highlights variable implementation of NICE guidance across SIHMDS, with likely inequity of access, standardisation and quality in haemato-oncology diagnostics. Provision of a more structured framework for guideline implementation could assist in increasing compliance to meet the goals of quality and equity of access to harmonised haemato-oncology diagnostics across the NHS in England. This would provide a basis for evaluating the clinical benefits and health economic impact of the SIHMDS model on patient care and outcomes

'Colour and communion': Exploring the influences of visual art-making as a leisure activity on older women's subjective well-being

This is the post-print version of the final paper published in Journal of Aging Studies. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2009 Elsevier B.V.Research into the subjective experience of art-making for older people is limited, and has focused mostly on professional artists rather than amateurs. This study examined older women's motives for visual art-making. Thirty-two participants aged 60-86 years old were interviewed. Twelve lived with chronic illness; twenty reported good health. Nearly all had taken up art after retirement; two had since become professional artists. Participants described their art-making as enriching their mental life, promoting enjoyment of the sensuality of colour and texture, presenting new challenges, playful experimentation, and fresh ambitions. Art also afforded participants valued connections with the world outside the home and immediate family. It encouraged attention to the aesthetics of the physical environment, preserved equal status relationships, and created opportunities for validation. Art-making protected the women's identities, helping them to resist the stereotypes and exclusions which are commonly encountered in later life.AHR

Matching typed and untyped realizability

AbstractRealizability interpretations of logics are given by saying what it means for computational objects of some kind to realize logical formulae. The computational objects in question might be drawn from an untyped universe of computation, such as a partial combinatory algebra, or they might be typed objects such as terms of a PCF-style programming language. In some instances, one can show that a particular untyped realizability interpretation matches a particular typed one, in the sense that they give the same set of realizable formulae. In this case, we have a very good fit indeed between the typed language and the untyped realizability model — we refer to this condition as (constructive) logical full abstraction.We give some examples of this situation for a variety of extensions of PCF. Of particular interest are some models that are logically fully abstract for typed languages including non-functional features. Our results establish connections between what is computable in various programming languages and what is true inside various realizability toposes. We consider some examples of logical formulae to illustrate these ideas, in particular their application to exact real-number computability