963 resultados para R.D. FitzGerald


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This paper analyzes the effect of firms’ innovation activities on their growth performance. In particular, we observe how important innovation is for high-growth firms (HGFs) for an extensive sample of Spanish manufacturing and services firms. The panel data used comprises diverse waves of Spanish CIS over the the period 2004-2008. First, a probit analysis determines whether innovation affects the probability of being a high-growth firm. And second, a quantile regression technique is applied to explore the determinants and characteristics of specific groups of firms (manufacturing versus service firms and high-tech versus low-tech firms). It is revealed that R&D plays a significant role in the probability of becoming a HGF. Investment in internal and external R&D per employee has a positive impact on firm growth (although internal R&D presents a significant impact in the last quantiles, external R&D is significant up to the median). Furthermore, we show evidence that there is a positive impact of employment (sales) growth on the sales (employment) growth. Keywords: high-growth firms, firm growth, innovation activity JEL Classifications: L11, L25, O30

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A woman's risk of breast cancer is strongly affected by her reproductive history. The hormonal milieu is also a key determinant of the course of the disease. Combining mouse genetics with tissue recombination techniques, we have established that the female reproductive hormones, estrogens, progesterone, and prolactin, act sequentially on the mammary epithelium to trigger distinct developmental steps. The hormones impinge directly on a subset of luminal mammary epithelial cells that express the respective hormone receptors and act as sensor cells translating and amplifying systemic signals into local stimuli. Local signaling is stage and age specific. During puberty, estrogens promote proliferation using the EGF family member, amphiregulin, as essential paracrine mediator. In adulthood, progesterone, rather than estrogen, is the major inducer of stem cell activation and cell proliferation of the mammary epithelium. Hormonal signaling modulates crucial developmental pathways that impinge on mammary stem cell populations, while Notch signaling, by inhibiting p63, is central to mammary cell fate determination. Cell proliferation occurs in two waves. The first results from direct stimulation of the small fraction of hormone receptor positive cells. It is followed by a second wave of progesterone-induced proliferation involving mostly hormone receptor negative cells, in which RANKL is a key mediator. A model in which repeated activation of paracrine signaling by progesterone with resulting stem cell activation promotes breast carcinogenesis is proposed.

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During the last several years, the mechanism of IFN gamma-dependent signal transduction has been the focus of intense investigation. This research has recently culminated in the elucidation of a comprehensive molecular understanding of the events that underlie IFN gamma-induced cellular responses. The structure and function of the IFN gamma receptor have been defined. The mechanism of IFN gamma signal transduction has been largely elucidated, and the physiologic relevance of this process validated. Most recently, the molecular events that link receptor ligation to signal transduction have been established. Together these insights have produced a model of IFN gamma signaling that is nearly complete and that serves as a paradigm for signaling by other members of the cytokine receptor superfamily.

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The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) was created in 1998 as an institution to foster excellence in bioinformatics. It is renowned worldwide for its databases and software tools, such as UniProtKB/Swiss-Prot, PROSITE, SWISS-MODEL, STRING, etc, that are all accessible on ExPASy.org, SIB's Bioinformatics Resource Portal. This article provides an overview of the scientific and training resources SIB has consistently been offering to the life science community for more than 15 years.

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A coercive estimate for a solution of a degenerate second order di fferential equation is installed, and its applications to spectral problems for the corresponding dif ferential operator is demonstrated. The suffi cient conditions for existence of the solutions of one class of the nonlinear second order diff erential equations on the real axis are obtained.

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We prove two-sided inequalities between the integral moduli of smoothness of a function on R d[superscript] / T d[superscript] and the weighted tail-type integrals of its Fourier transform/series. Sharpness of obtained results in particular is given by the equivalence results for functions satisfying certain regular conditions. Applications include a quantitative form of the Riemann-Lebesgue lemma as well as several other questions in approximation theory and the theory of function spaces.

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Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes.

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BACKGROUND: Surgical site infection after stoma reversal is common. The optimal skin closure technique after stoma reversal has been widely debated in the literature. OBJECTIVE: We hypothesized that pursestring near-complete closure of the stoma site would lead to fewer surgical site infections compared with conventional primary closure. DESIGN: This study was a parallel prospective multicenter randomized controlled trial. SETTINGS: This study was conducted at 2 university medical centers. PATIENTS: Patients (N = 122) presenting for elective colostomy or ileostomy reversal were selected. INTERVENTIONS: Pursestring versus conventional primary closure of stoma sites were compared. MAIN OUTCOME MEASURES: Stoma site surgical site infection within 30 days of surgery, overall surgical site infection, delayed healing (open wound for >30 days), time to wound epithelialization, and patient satisfaction were the primary outcomes measured. RESULTS: The pursestring group had a significantly lower stoma site infection rate (2% vs 15%, p = 0.01). There was no difference in delayed healing or patient satisfaction between groups. Time to epithelialization was measured in only 51 patients but was significantly longer in the pursestring group (34.6 ± 20 days vs 24.1 ± 17 days, p = 0.02). LIMITATIONS: This study was limited by the variability in procedures and surgeons, the limited follow-up after 30 days, and the inability to perform blinding. CONCLUSION: Pursestring closure after stoma reversal has a lower risk of stoma site surgical site infection than conventional primary closure, although wounds may take longer to heal with the use of this approach. REGISTRATION NUMBER: NCT01713452 (www.clinicaltrials.gov).

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In these challenging financial times the use of research as a basis for effective health and social care cannot be overstated. 'Shaping the Future', a joint Public Health Agency and University of Ulster workshop (27 January) takes a fresh look at research within the Allied Health Professions (AHPs) to improve the care and experiences of people across Northern Ireland.The AHPs provide a wide range of services including physiotherapy, occupational therapy, radiography, podiatry, speech and language therapy and orthoptics.The nature of their work enables AHPs to carry out research that can rapidly benefit patient care and experience. 'Shaping the Future' will look at priorities for new AHP research and consider how existing research can be more effectively shared and used in health and social care development, rather than perhaps being limited to the academic world.Speaking at the event, Professor Bernie Hannigan, Director of Health and Social Care Research and Development (HSC R&D), aDivision of the PHA, said: "A sound base of evidence from research is vital for effective health and social care practice. I welcome this study as an important resource that will help generate new evidence and highlight the potential for existing evidence to be applied in practice. The evidence base points to beneficial innovations that use the most up-to-date knowledge and keep the service user at the centre of care practices. At this event, health and social care policy makers, commissioners, academics and researchers will be able to consider how they can do and use research to ensure our AHP services deliver the best outcomes for patients and are sufficiently cost-effective to be sustained."A recent study funded by HSC R&D was carried out by the University of Ulster working closely with leading AHPs, key stakeholders and service users* from throughout Northern Irealnd. Presenting the results of this study at the 'Shaping the Future' event will help to identify ways to gather evidence and contribute to innovative projects and programmes.Professor Suzanne McDonough, of the Health and Rehabilitation Sciences Research Centre at the University of Ulster, said: "In our study we used the Delphi technique, which is a structured process using a series of questionnaires, to gather information and gain consensus from AHP groups, stakeholders and service users."The results identified seven major priority areas for research. These ranged from: the need for more practice evaluation particularly in the areas of mental health, cancer, obesity; diabetes; chronic disease management (especially stroke and brain injury); the role of AHPs in health promotion; service delivery issues such as access to services and waiting times. This study provides an important road map for AHP research priorities. It is the first step in the process of identifying what research still needs to be undertaken, what research already exists but needs to be translated, and some of the processes that need to be in place to ensure that research is an integral part of the day-to-day practice of AHPs and of service delivery."

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This report gives a comprehensive and up-to-date review of Alzheimer's disease biomarkers. Recent years have seen significant advances in this field. Whilst considerable effort has focused on A�_ and tau related markers, a substantial number of other molecules have been identified, that may offer new opportunities.This Report : Identifies 60 candidate Alzheimer's (AD) biomarkers and their associated studies. Of these, 49 are single species or single parameters, 7 are combinations or panels and 4 involve the measurement of two species or parameters or their ratios. These include proteins (n=34), genes (n=11), image-based parameters (n=7), small molecules (n=3), proteins + genes (n=2) and others (n=3). Of these, 30 (50%) relate to species identified in CSF and 19 (32%) were found in the blood. These candidate may be classified on the basis of their diagnostic utility, namely those which i) may allow AD to be detected when the disease has developed (48 of 75†= 64%), ii) may allow early detection of AD (18 of 75† = 24%) and iii) may allow AD to be predicted before the disease has begun to develop (9 of 75†= 12%). † Note: Of these, 11 were linked to two or more of these capabilities (e.g. allowed both early-stage detection as well as diagnosis after the disease has developed).Biomarkers: AD biomarkers identified in this report show significant diversity, however of the 60 described, 18 (30%) are associated with amyloid beta (A�_) and 9 (15%) relate to Tau. The remainder of the biomarkers (just over half) fall into a number of different groups. Of these, some are associated with other hypotheses on the pathogenesis of AD however the vast majority are individually unique and not obviously linked with other markers. Analysis and discussion presented in this report includes summaries of the studies and clinical trials that have lead to the identification of these markers. Where it has been calculated, diagnostic sensitivity, specificity and the capacity of these markers to differentiate patients with suspected AD from healthy controls and individuals believed to be suffering from other neurodegenerative conditions, have been indicated. These findings are discussed in relation to existing hypotheses on the pathogenesis of the AD and the current drug development pipeline. Many uncertainties remain in relation to the pathogenesis of AD, in diagnosing and treating the disease and many of the studies carried out to identify disease markers are at an early stage and will require confirmation through larger and longer investigations. Nevertheless, significant advances in the identification of AD biomarkers have now been made. Moreover, whilst much of the research on AD biomarkers has focused on amyloid and tau related species, it is evident that a substantial number of other species may provide important opportunities.Purpose of Report: To provide a comprehensive review of important and recently discovered candidate biomarkers of AD, in particular those with potential to reliably detect the disease or with utility in clinical development, drug repurposing, in studies of the pathogenesis and in monitoring drug response and the course of the disease. Other key goals were to identify markers that support current pipeline developments, indicate new potential drug targets or which advance understanding of the pathogenesis of this disease.Drug Repurposing: Studies of the pathogenesis of AD have identified aberrant changes in a number of other disease areas including inflammation, diabetes, oxidative stress, lipid metabolism and others. These findings have prompted studies to evaluate some existing approved drugs to treat AD. This report identifies studies of 9 established drug classes currently being investigated for potential repurposing.Alzheimer’s Disease: In 2005, the global prevalence of dementia was estimated at 25 million, with more than 4 million new cases occurring each year. It is also calculated that the number of people affected will double every 20 years, to 80 million by 2040, if a cure is not found. More than 50% of dementia cases are due to AD. Today, approximately 5 million individuals in the US suffer from AD, representing one in eight people over the age of 65. Direct and indirect costs of AD and other forms of dementia in the US are around $150 billion annually. Worldwide, costs for dementia care are estimated at $315 billion annually. Despite significant research into this debilitating and ultimately fatal disease, advances in the development of diagnostic tests for AD and moreover, effective treatments, remain elusive.Background: Alzheimer's disease is the most common cause of dementia, yet its clinical diagnosis remains uncertain until an eventual post-mortem histopathology examination is carried out. Currently, therapy for patients with Alzheimer disease only treats the symptoms; however, it is anticipated that new disease-modifying drugs will soon become available. The urgency for new and effective treatments for AD is matched by the need for new tests to detect and diagnose the condition. Uncertainties in the diagnosis of AD mean that the disease is often undiagnosed and under treated. Moreover, it is clear that clinical confirmation of AD, using cognitive tests, can only be made after substantial neuronal cell loss has occurred; a process that may have taken place over many years. Poor response to current therapies may therefore, in part, reflect the fact that such treatments are generally commenced only after neuronal damage has occurred. The absence of tests to detect or diagnose presymptomatic AD also means that there is no standard that can be applied to validate experimental findings (e.g. in drug discovery) without performing lengthy studies, and eventual confirmation by autopsy.These limitations are focusing considerable effort on the identification of biomarkers that advance understanding of the pathogenesis of AD and how the disease can be diagnosed in its early stages and treated. It is hoped that developments in these areas will help physicians to detect AD and guide therapy before the first signs of neuronal damage appears. The last 5-10 years have seen substantial research into the pathogenesis of AD and this has lead to the identification of a substantial number of AD biomarkers, which offer important insights into this disease. This report brings together the latest advances in the identification of AD biomarkers and analyses the opportunities they offer in drug R&D and diagnostics.��

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Introduction: Apoptosis plays a central role in chronic hepatitis C virus (HCV) infection. Although the activation of cell death signals has been reported, HCV infection persists in most patients suggesting a pro-survival adaptation, eventually developing hepatocellular carcinoma. This study focused on the role of mitochondria in the activation of pro- and antiapoptotic response in cells expressing HCV proteins. Materials and Methods: Human Osteosarcoma U2-OS cells inducibly expressing the HCV polyprotein; huh7.5 hepatoma cells transfected with full length HCV genome. Results: Long term induction of viral proteins in U2-OS cells induced a cyclosporine A-sensitive cytochrome c partial release from mitochondria, revealed by immunofluorescence, western blot and spectral analysis. In HCV-transfected Huh7.5 cells, release of the apoptosis inducing factor (AIF) with no apparent nuclear translocation was also observed. HCV positive cells displayed an HIF-dependent enhanced glycolysis, charachterized by up-regulation of the mitochondria-bound Hexokinase II (HKII); preliminary data on signal transduction pathway revealed the iperphosphorylation of Glycogen synthase kinase 3b(GSK3b). Conclusion: HCV causes a cell stress activating an early apoptotic response, the entity of which likely depends on the cell type. Nevertheless a wide series of cell survival mechanisms are also triggered resulting in a metabolic adaptation possibly favouring carcinogenesis. Based on our results, we propose a pro-survival mechanism linking HCV infection to inhibition of GSK-3b, stabilization of HIF1a and up-regulation of HKII, the last events causing a glycolytic shift and protecting from apoptosis.

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The Bamford review of mental health and learning disabilities identified the need for research to help with service and policy development in a number of areas. We worked with key stakeholders, gaining significant input from service users and carers along with professionals and researchers, to agree five top priorities. Research reviews were funded by HSC R&D Division, Public Health Agency (PHA) to set out current knowledge about policies and care services relevant to Children and Young People; Patient Outcomes; Intellectual Disability; Psychological Therapies and Primary Care.The reviews which can be accessed below will serve as accessible, high quality sources of up-to-date knowledge for commissioners, policy-makers, academics and providers of health or social care services as well as service users. We hope that the reviews will help to inform future development and delivery of Mental Health and Intellectual Disability services and so achieve the best outcomes for service users and their families. The reviews have also identified a number of important areas for further research.A Call for research proposals�to these areas is announced today. Further information on this Call can be found by clicking hereA further Rapid review in personality disorders has been commissioned in conjunction with HSCB and DHSSPS and is now available to download here.

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Local and national policy increasingly emphasises the central role of service users and the public in shaping Health and Social Care (HSC). This is the second edition of the HSC R&D Division��'s Personal and Public Involvement (PPI) Strategy, which highlights the importance of involving patients and the public in research and outlines the progress already made in implementing PPI in research in Northern Ireland.