Social Work with Children Affected by Domestic Violence: An Analysis of Policy and Practice Implications

The past decade has seen an increasing awareness of the emotional harm to children that can ensue from exposure to domestic violence. This article develops a framework for understanding social work responses, using an analysis of recent developments in British policy as an example. It is argued that to understand what these developments mean in practice we need to develop our analysis of the value perspectives underpinning them. Issues facing those charged with implementing these sometimes ambiguous policy and practice changes are discussed in three levels of intervention: the macro, the intermediate, and the 'street-level.' The article concludes by calling for closer collaboration between policy makers, practitioners and service users in the co-production of policy

Relational knowledge leadership and local economic development

This paper concerns the role of spatial leadership in the development of the knowledge-based economy. It is argued within academic and practitioner circles that leadership of knowledge networks requires a particular non-hierarchical style that is required to establish an ambience conducive to networking and knowledge sharing across boundaries. In this paper, we explore this hypothesis at both theoretical and empirical levels. Theoretically, we propose a conceptualization of relational knowledge leadership, which is ‘nomadic’ in its capacity to travel across multiple scales and cross sectoral, thematic and geographical boundaries. We have operationalized this type of relational knowledge leadership along four key features, derived from literatures on regional learning, organizational leadership and place leadership. Two empirical case studies are then presented, one from Birmingham in the UK and one from Eindhoven in the Netherlands, exploring how these features are expressed on the sub-national level. Also conclusions are drawn regarding the status of relational knowledge leadership. It is argued that the concept of relational knowledge leadership as viewed through our analytical lens does accord with the experience of leadership in the two cases presented. The cases also show that this style of leadership is confronted with three types of tensions that play through knowledge networking. Furthermore, it is argued that the cases exhibit this style of leadership to different degrees, reflecting their different cultural and political context

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Quantified Lax Logic

Lax Logic is an intuitionistic modal logic which has so far been investigated at the propositional level. It has shown itself to have applications in the formal verification of hardware---a logical modality is used to capture and express the correctness of specifications `up to' behavioural constraints. A translation from Quantified Lax Logic to a quantified classical modal logic is presented which enables both model and syntactic embedding theorems to be proved. By investigating the links between these logics, the nature of the single Lax Logic modality is revealed and results of soundness and completeness are derived for two distinct classes of model-structures of QLL. 1 Introduction The logic under consideration in this paper is an intuitionistic logic which possesses a single modality. Other intuitionistic modal logics exist (see for example [BdP96], [Fit48], [PS86], [Sim94], [FS80], [Ewa86]) though it is not always clear what their semantics ought to be, or what they are useful f..

First-order Lax Logic as a Framework for Constraint Logic Programming

In this report we introduce a new proof-theoretic approach to the semantics of Constraint Logic Programming, based on an intuitionistic first-order modal logic, called QLL. The distinguishing feature of this new approach is that the logic calculus of QLL is used not only to capture the usual extensional aspects of Logic Programming, i.e. "which queries are successful, " but also some of the intensional aspects, i.e. "what is the answer constraint and how is it constructed." It provides for a direct link between the model-theoretic and the operational semantics following a formulas-as-programs and proofs-as-constraints principle. This approach makes use of logic in a different way than other approaches based on logic calculi. On the one side it is to be distinguished from the well-known provability semantics which is concerned merely with what is derivable as opposed to how it is derivable, paying attention to the fact that it is the how that determines the answer constraint. On the ot..

Abstraction and Constraints: Two Sides of the Same Coin

ion and Constraints: Two Sides of the Same Coin M.Walton November 1997 University of Sheffield Department of Computer Science Technical Report CS-97-18 Abstraction and Constraints: Two Sides of the Same Coin M. Walton PhD Supervisor: M.V.H. Fairtlough Abstract This report presents a high-level survey of some approaches to abstraction and the wide range of fields in which their applications may be found. Whilst there is much to be found in the literature about either abstraction or constraints, very little is to be found about them both, or the relationship between them. We examine the role of a novel intuitionistic modal logic (called Lax Logic) in capturing the dual notions of abstraction and constraints, and a particular notion of refinement. As a specific application of Lax Logic, we look at its use as an abstraction framework for the paradigm of Constraint Logic Programming. This provides a novel declarative and operational semantics for CLP which offers a clean separation..

A novel (paternally inherited) duplication 13q31.3q32.3 in a 12-year-old patient with facial dysmorphism and developmental delay

We report a 12-year-old boy referred to the Clinical Genetics service in view of facial dysmorphism, learning difficulties and autistic spectrum disorder. 60K arrayCGH revealed an 8.2-Mb duplication on chromosome 13q31.3q32.3, which was paternally inherited. This specific duplication on chromosome 13 has not been previously reported in the medical literature, and there are no familial or de novo patients with the same duplication breakpoints. This region contains 24 OMIM genes, including the glypicans GPC5 and GPC6, and the ZIC2 gene. We discuss the relevance of this chromosome imbalance and discuss the impact of this duplication on our patient's phenotype. Given that the duplication on 13q was paternally inherited, and although initially thought to be of uncertain significance, on exploring the family history further, it became apparent that the father had learning difficulties as a child and previous surgery for congenital diaphragmatic hernia. Here we explore the phenotype in association with this novel duplication on chromosome 13q and add to the existing literature on array findings within this region

LaxLF: Side Conditions and External Evidence as Monads

International audienceWe extend the constructive dependent type theory of the Logical Framework LF with a family of monads indexed by predicates over typed terms. These monads express the effect of factoring-out, postponing , or delegating to an external oracle the verification of a constraint or a side-condition. This new framework, called Lax Logical Framework, LaxF, is a conservative extension of LF, and hence it is the appropriate metalanguage for dealing formally with side-conditions or external evidence in logical systems. LaxF is the natural strengthening of LFP (the extension of LF introduced by the authors together with Marina Lenisa and Petar Maksimovic), which arises once the monadic nature of the lock constructors of LFP is fully exploited. The nature of these monads allows to utilize the unlock destructor instead of Moggi's monadic let_T , thus simplifying the equational theory. The rules for the unlock allow us, furthermore, to remove the monadic constructor once the constraint is satisfied. By way of example we discuss the encodings in LaxF of call-by-value-calculus, Hoare's Logic, and Elementary Affine Logic