Metrics and spectral triples for Dirichlet and resistance forms

The article deals with intrinsic metrics, Dirac operators and spectral triples induced by regular Dirichlet and resistance forms. We show, in particular, that if a local resistance form is given and the space is compact in resistance metric, then the intrinsic metric yields a geodesic space. Given a regular Dirichlet form, we consider Dirac operators within the framework of differential 1-forms proposed by Cipriani and Sauvageot, and comment on its spectral properties. If the Dirichlet form admits a carr\'e operator and the generator has discrete spectrum, then we can construct a related spectral triple, and in the compact and strongly local case the associated Connes distance coincides with the intrinsic metric. We finally give a description of the intrinsic metric in terms of vector fields

Variation in suicide rates between Health Board areas

This paper examines variations in suicide in the eight Health Boards of the Republic of Ireland for the years 1976 to 1995. It is found that while all have experienced a rise in male suicide, it has been much less pronounced in the Eastern Health Board which is somewhat surprising when one considers Dublin’s much-publicised problems with homelessness and hard drug misuse. Since the mid-eighties, female rates have been somewhat higher in the southern half of the country, comprising the Southern, Mid-Western and South-Eastern Health Boards. This variation may reflect a difficulty with contacting services for psychological distress in rural areas, either because of stigma or simple practical problems associated with transport. The development of appropriate services, especially in rural areas, should be at the top of the agenda of any Resource Officer to be appointed subsequent to the Final Report of the Task Force

The European CCS Demonstration Project Network — A forum for first movers

AbstractThe European CCS Demonstration Project Network was initiated by the European Commission in 2009. The main objective of the network is to accelerate development of CCS technologies by creating a forum for exchange and dissemination of new knowledge generated by the first large scale CCS plants in Europe. This paper provides an overview and understanding of the activities of the network and the political and theoretical context of their development. The paper focuses on how the Network has been structured to add value to demonstration projects and create vital new channels of information for enabling CCS demonstration and deployment to be advanced worldwide

The Software Required for the Computer Generation of Virtual Environments

Presence, Vol. 2, No. 2, pp. 130-140..Accepted/Published Paper (Refereed

Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study

INTRODUCTION: Asymmetrical dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which functions by metabolising ADMA to citrulline. The aim of this study was to examine the association between ADMA levels and the severity of organ failure and shock in severe sepsis and also to assess the influence of a promoter polymorphism in DDAH II on ADMA levels. METHODS: A prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position -449 in the DDAH II gene was assessed in each patient. Clinical and demographic details were also collected. RESULTS: On day 1 more ADMA was detectable in the ICU group than in the control group (p = 0.005). Levels subsequently increased during the first week in ICU (p = 0.001). ADMA levels were associated with vasopressor requirements on day one (p = 0.001). ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMA concentrations at both time points (p < 0.05). CONCLUSION: Severity of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMA levels. ADMA concentrations may be influenced by a polymorphism in the DDAH II gene

Parasuicide and general practice: a pilot study

General Practitioners from Cork City and its environs were sent a questionnaire regarding their experience of parasuicide in the previous twelve months. Replies were received from 133 of the 185 GPs. 189 individuals, accounting for 212 episodes of parasuicide, were seen by 78 doctors, indicating a lower level of repetition than that found in hospital-referred cases. Almost a third of doctors saw no cases, just over one fifth saw one episode and the same proportion dealt with two. A small number of general practitioners saw many cases. Regarding management, 128 (60%) were referred to Casualty, 31 of whom were also referred for psychiatric care. Thirty percent were referred directly for psychiatric care. While only fourteen were retained within general practice without referral, 40% of the GPs felt that, ideally, acts of parasuicide should be retained with more specialised advice being obtained. Furthermore, 88.1% believed that management of parasuicide should form part of an integral part of post-graduate or continued general practitioner medical training. Clearly, GPs are willing to play a more active role in the management of parasuicide

Genetic selection for hoof health traits and cow mobility scores can accelerate the rate of genetic gain in producer-scored lameness in dairy cows

peer-reviewedCattle breeding programs that strive to reduce the animal-level incidence of lameness are often hindered by the availability of informative phenotypes. As a result, indicator traits of lameness (i.e., hoof health and morphological conformation scores) can be used to improve the accuracy of selection and subsequent genetic gain. Therefore, the objectives of the present study were to estimate the variance components for hoof health traits using various phenotypes collected from a representative sample of Irish dairy cows. Also of interest to the present study was the genetic relationship between both hoof health traits and conformation traits with producer-scored lameness. Producer-recorded lameness events and linear conformation scores from 307,657 and 117,859 Irish dairy cows, respectively, were used. Data on hoof health (i.e., overgrown sole, white line disease, and sole hemorrhage), mobility scores, and body condition scores were also available from a research study on up to 11,282 Irish commercial dairy cows. Linear mixed models were used to quantify variance components for each trait and to estimate genetic correlations among traits. The estimated genetic parameters for hoof health traits in the present study were greater (i.e., heritability range: 0.005 to 0.27) than previously reported in dairy cows. With the exception of analyses that considered hoof health traits in repeatability models, little difference in estimated variance components existed among the various hoof-health phenotypes. Results also suggest that producer-recorded lameness is correlated with both hoof health (i.e., genetic correlation up to 0.48) and cow mobility (i.e., genetic correlation = 0.64). Moreover, cows that genetically tend to have rear feet that appear more parallel when viewed from the rear are also genetically more predisposed to lameness (genetic correlation = 0.39); genetic correlations between lameness and other feet and leg type traits, as well as between lameness and frame type traits, were not different from zero. Results suggest that if the population breeding goal was to reduce lameness incidence, improve hoof health, or improve cow mobility, genetic selection for either of these traits should indirectly benefit the other traits. Results were used to quantify the genetic gains achievable for lameness when alternative phenotypes are available

Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals

Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies

GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation