Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. (c) 2008 Movement Disorder Society

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

The concept of mindfulness in information systems research: A multi-dimensional analysis

The concept of mindfulness has garnered increasing attention during the last decade. Initially proposed within the scope of Information Systems (IS) research as a means of creating a deeper knowledge foundation for decision making regarding information technology (IT) innovations, it soon became broadly applied throughout IS research. To gain a better understanding of the evolved diversity of this concept, this paper reviews and analyzes extant IS research by means of (a) the investigated IS themes, (b) the purpose of using the concept, (c) the level of application of the concept, and (d) the tendency to focus either on mindfulness, mindlessness, or both. By synthesizing research findings, we derive a high-level IS mindfulness theory. We then propose future research opportunities, such as the explanation of the relationships between different levels of mindfulness, applying mindfulness to bridge the different phases of the software development process, and identification of guidelines for designing information systems that facilitate mindfulness. As the first review on the application of mindfulness in IS research, we contribute to the overall understanding of mindfulness and address the four abovementioned dimensions from which mindfulness emerges in order to demonstrate that mindfulness provides a meaningful platform for generating knowledge

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated

Lived Experience of Caregivers of Family-Centered Care in the Neonatal Intensive Care Unit: “Evocation of Being at Home

Background: In recent decades, family-centered care (FCC) has come to be known, accepted, and reported as the best care strategy for admitted children and their families. However, in spite of the increasing application of this approach, the experiences of the caregivers have not yet been studied. Objectives: The present study aimed at the description and interpretation of the FCC experience in two neonatal intensive care units (NICU) at Shiraz University of Medical Sciences. Methods: This study was conducted through the hermeneutic phenomenological approach. Semi-structured interviews were conducted with 17 professional and familial caregivers, and their interactions were observed in three work shifts. The interviews were audiotaped and transcribed verbatim. After observations, field notes were also written. Finally, the data were analyzed through van Manen’s methodology. Results: One of the essential themes that emerged in this study was the “evocation of being at home” among familial and even professional caregivers. This theme had three subthemes: i.e., “meta-family interaction,” “comprehensive support,” and “reconstruction of a normal family.” Accordingly, FCC eliminated borders between professional and non-professional caregivers and built close relationships among them in the NICU. It also provided for the needs of neonates, their families, and even professional caregivers through perceived and received support. Conclusions: Parents of the neonates admitted to the NICU experience hard moments. They not only play the role of primary caregivers, but they also receive the care. Focusing on the different meanings of this care from the caregivers’ points of view and having managers provide certain requirements can guarantee the establishment of comprehensive care for clients and proper support for the staff in this uni

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Strangeness Content in the Nucleon

I review recent studies of strangeness content in the nucleon pertaining to the flavor-singlet $g_A^0$, the $\bar{s}s$ matrix element and the strangeness electric and magnetic form factors $G_E^s(q^2)$ and $G_M^s(q^2)$, based on lattice QCD calculations. I shall also discuss the relevance of incorporating the strangeness content in nuclei in regard to strange baryon-antibaryon productions from proton-nucleus and nucleus-nucleus collisions at SPS and RHIC energies.Comment: 11 pages, 4 figures, Invited talk at V Int. Conf. on Strangeness in Quark Matter, Berkeley, CA, July 20--25, 200

Detecting the orientation of magnetic fields in galaxy clusters

Clusters of galaxies, filled with hot magnetized plasma, are the largest bound objects in existence and an important touchstone in understanding the formation of structures in our Universe. In such clusters, thermal conduction follows field lines, so magnetic fields strongly shape the cluster's thermal history; that some have not since cooled and collapsed is a mystery. In a seemingly unrelated puzzle, recent observations of Virgo cluster spiral galaxies imply ridges of strong, coherent magnetic fields offset from their centre. Here we demonstrate, using three-dimensional magnetohydrodynamical simulations, that such ridges are easily explained by galaxies sweeping up field lines as they orbit inside the cluster. This magnetic drape is then lit up with cosmic rays from the galaxies' stars, generating coherent polarized emission at the galaxies' leading edges. This immediately presents a technique for probing local orientations and characteristic length scales of cluster magnetic fields. The first application of this technique, mapping the field of the Virgo cluster, gives a startling result: outside a central region, the magnetic field is preferentially oriented radially as predicted by the magnetothermal instability. Our results strongly suggest a mechanism for maintaining some clusters in a 'non-cooling-core' state.Comment: 48 pages, 21 figures, revised version to match published article in Nature Physics, high-resolution version available at http://www.cita.utoronto.ca/~pfrommer/Publications/pfrommer-dursi.pd

Legal framework for small autonomous agricultural robots

Legal structures may form barriers to, or enablers of, adoption of precision agriculture management with small autonomous agricultural robots. This article develops a conceptual regulatory framework for small autonomous agricultural robots, from a practical, self-contained engineering guide perspective, sufficient to get working research and commercial agricultural roboticists quickly and easily up and running within the law. The article examines the liability framework, or rather lack of it, for agricultural robotics in EU, and their transpositions to UK law, as a case study illustrating general international legal concepts and issues. It examines how the law may provide mitigating effects on the liability regime, and how contracts can be developed between agents within it to enable smooth operation. It covers other legal aspects of operation such as the use of shared communications resources and privacy in the reuse of robot-collected data. Where there are some grey areas in current law, it argues that new proposals could be developed to reform these to promote further innovation and investment in agricultural robots