Intracranial haemorrhage in a dobermann puppy with von Willebrand's disease

Neurological examination of a lethargic, ataxic 12-week-old dobermann revealed decreased conscious proprioception in all its limbs. Haematological examination revealed a low platelet count. Cytological examination of a sample of cerebrospinal fluid revealed evidence of haemorrhage and chronic inflammation. The levels of von Willebrand's factor antigen were extremely low. Skull radiographs were consistent with mild hydrocephalus. Treatment resulted in little clinical improvement and the animal was euthanased. Post mortem examination of the brain revealed an internal hydrocephalus with haemorrhage into the ventricles. It was considered that the animal had suffered severe intracranial haemorrhage as a result of its low level of von Willebrand's factor antigen and that the bleeding may have been potentiated by the low platelet count

Proceedings of the Oak Ridge Electron Linear Accelerator (ORELA) Workshop

The Oak Ridge National Laboratory (ORNL) organized a workshop at ORNL July 14-15, 2005, to highlight the unique measurement capabilities of the Oak Ridge Electron Linear Accelerator (ORELA) facility and to emphasize the important role of ORELA for performing differential cross-section measurements in the low-energy resonance region that is important for nuclear applications such as nuclear criticality safety, nuclear reactor and fuel cycle analysis, stockpile stewardship, weapons research, medical diagnosis, and nuclear astrophysics. The ORELA workshop (hereafter referred to as the Workshop) provided the opportunity to exchange ideas and information pertaining to nuclear cross-section measurements and their importance for nuclear applications from a variety of perspectives throughout the U.S. Department of Energy (DOE). Approximately 50 people, representing DOE, universities, and seven U.S. national laboratories, attended the Workshop. The objective of the Workshop was to emphasize the technical community endorsement for ORELA in meeting nuclear data challenges in the years to come. The Workshop further emphasized the need for a better understanding of the gaps in basic differential nuclear measurements and identified the efforts needed to return ORELA to a reliable functional measurement facility. To accomplish the Workshop objective, nuclear data experts from national laboratories and universities were invited to provide talks emphasizing the unique and vital role of the ORELA facility for addressing nuclear data needs. ORELA is operated on a full cost-recovery basis with no single sponsor providing complete base funding for the facility. Consequently, different programmatic sponsors benefit by receiving accurate cross-section data measurements at a reduced cost to their respective programs; however, leveraging support for a complex facility such as ORELA has a distinct disadvantage in that the programmatic funds are only used to support program-specific measurements. As a result, ORELA has not received base funding to support major upgrades and significant maintenance operations that are essential to keep the facility in a state of readiness over the long term. As a result, ORELA has operated on a ''sub-bare-minimum'' budget for the past 10 to 15 years, and the facility has not been maintained at a level for continued reliable operation for the long term. During the Workshop, Jerry McKamy (NNSA/NA-117) used a hospital patient metaphor that accurately depicts the facility status. ORELA is currently in the intensive care unit (ICU) on life support, and refurbishment efforts are needed to get the ''patient'' off life support and out to an ordinary hospital room. McKamy further noted that the DOE NCSP is planning to fund immediate refurbishment tasks ($1.5 M over three years) to help reestablish reliable ORELA operation (i.e., move ORELA from ICU to an ordinary hospital room). Furthermore, the NCSP will work to identify and carry out the actions needed to discharge ORELA from the ''hospital'' over the next five to seven years. In accordance with the Workshop objectives, the technical community publicly endorsed the need for a reliable ORELA facility that can meet current and future nuclear data needs. These Workshop proceedings provide the formal documentation of the technical community endorsement for ORELA. Furthermore, the proceedings highlight the past and current contributions that ORELA has made to the nuclear industry. The Workshop further emphasized the operational and funding problems that currently plague the facility, thereby limiting ORELA's operational reliability. Despite the recent operational problems, ORELA is a uniquely capable measurement facility that must be part of the overall U.S. nuclear data measurement portfolio in order to support current and emerging nuclear applications. The Workshop proceedings further emphasize that ORNL, the technical community, and programmatic sponsors are eager to see ORELA reestablish reliable measurement operation and be readily available to address nuclear data challenges in the United States

A Simulation Model Articulation of the REA Ontology

This paper demonstrates how the REA enterprise ontology can be used to construct simulation models for business processes, value chains and collaboration spaces in supply chains. These models support various high-level and operational management simulation applications, e.g. the analysis of enterprise sustainability and day-to-day planning. First, the basic constructs of the REA ontology and the ExSpect modelling language for simulation are introduced. Second, collaboration space, value chain and business process models and their conceptual dependencies are shown, using the ExSpect language. Third, an exhibit demonstrates the use of value chain models in predicting the financial performance of an enterprise

Thermodynamics of non-local materials: extra fluxes and internal powers

The most usual formulation of the Laws of Thermodynamics turns out to be suitable for local or simple materials, while for non-local systems there are two different ways: either modify this usual formulation by introducing suitable extra fluxes or express the Laws of Thermodynamics in terms of internal powers directly, as we propose in this paper. The first choice is subject to the criticism that the vector fluxes must be introduced a posteriori in order to obtain the compatibility with the Laws of Thermodynamics. On the contrary, the formulation in terms of internal powers is more general, because it is a priori defined on the basis of the constitutive equations. Besides it allows to highlight, without ambiguity, the contribution of the internal powers in the variation of the thermodynamic potentials. Finally, in this paper, we consider some examples of non-local materials and derive the proper expressions of their internal powers from the power balance laws.Comment: 16 pages, in press on Continuum Mechanics and Thermodynamic

Annual Research Review: interparental conflict and youth psychopathology: an evidence review and practice focused update

The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically-oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity – ranging from silence to violence. Further, new evidence highlights that children’s emotional, behavioral, social, academic outcomes and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology

PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families

Purpose: Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. Methods: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results: Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. Conclusion: We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.Anne Guimier ... Liza K. Phillips ... et al

Linear Collider Physics Resource Book for Snowmass 2001, 3: Studies of Exotic and Standard Model Physics

This Resource Book reviews the physics opportunities of a next-generation e+e- linear collider and discusses options for the experimental program. Part 3 reviews the possible experiments on that can be done at a linear collider on strongly coupled electroweak symmetry breaking, exotic particles, and extra dimensions, and on the top quark, QCD, and two-photon physics. It also discusses the improved precision electroweak measurements that this collider will make available.This Resource Book reviews the physics opportunities of a next-generation e+e- linear collider and discusses options for the experimental program. Part 3 reviews the possible experiments on that can be done at a linear collider on strongly coupled electroweak symmetry breaking, exotic particles, and extra dimensions, and on the top quark, QCD, and two-photon physics. It also discusses the improved precision electroweak measurements that this collider will make available

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved