Monoclonal antibodies to a membrane glycoprotein induce the phosphorylation of histone H1 in sea urchin spermatozoa.

Two groups of mAbs reacting with external domains of a major sea urchin sperm membrane glycoprotein of 210 kD were isolated. Previous studies have shown that group I mAbs inhibit the acrosome reaction induced by egg jelly and also cause large increases in intracellular Ca2+ [( Ca2+]i). Group II mAbs, at comparable levels of cell surface binding, neither inhibit the egg jelly-induced acrosome reaction nor cause increases in [Ca2+]i. In this paper, we investigate the ability of these mAbs to induce the cAMP-dependent phosphorylation of sperm histone H1. Group I mAbs induce H1 phosphorylation to the same level and on the same peptide, as occurs upon treatment of sperm with egg jelly. These mAbs also activate adenylate cyclase to the same extent as egg jelly. Group II mAbs do not induce H1 phosphorylation and are only poor activators of adenylate cyclase. Group I mAbs compete with each other, but not with group II mAbs, for binding to the cell surface. These data indicate that the activation of adenylate cyclase is an initial event in the pathway leading from the binding of mAbs to a specific domain of the 210-kD protein at the cell surface, to the discrete phosphorylation of histone H1 in highly condensed sperm chromatin. The domain on the 210-kD protein recognized by group I mAbs plays a critical role in signal transduction during the early events of fertilization

Exploring the use of strategic frameworks in dental practice

This paper explores the use of strategic frameworks in NHS and private dental practice. It reviews the policy context of dentistry and suggests the challenges in this context will require dental practices to prioritise understanding and engagement with a strategic approach. A strategic approach will be required in order to enhance and improve performance. Two specific strategic frameworks will be explored in terms of their relevance to NHS and private dental practic

A comparison of the cost-effectiveness of treatment of prolonged acute convulsive epileptic seizures in children across Europe

In the majority of children and adolescents with epilepsy, optimal drug therapy adequately controls their condition. However, among the remaining patients who are still uncontrolled despite mono-, bi- or tri-therapy with chronic anti-epileptic treatment, a rescue medication is required. In Western Europe, the licensed medications available for first-line treatment of prolonged acute convulsive seizures (PACS) vary widely, and so comparators for clinical and economic evaluation are not consistent. No European guidelines currently exist for the treatment of PACS in children and adolescents and limited evidence is available for the effectiveness of treatments in the community setting. The authors present cost-effectiveness data for BUCCOLAM® (midazolam oromucosal solution) for the treatment of PACS in children and adolescents in the context of the treatment pathway in seven European countries in patients from 6 months to 18 years. For each country, the health economic model consisted of a decision tree, with decision nodes informed by clinical data and expert opinion obtained via a Delphi methodology. The events modelled are those associated with a patient experiencing a seizure in the community setting. The model assessed the likelihood of medication being administered successfully and of seizure cessation. The associated resource use was also modelled, and ambulance call-outs and hospitalisations were considered. The patient's quality of life was estimated by clinicians, who completed a five-level EuroQol five dimensions questionnaire from the perspective of a child or adolescent suffering a seizure. Despite differences in current therapy, treatment patterns and healthcare costs in all countries assessed, BUCCOLAM was shown to be cost saving and offered increased health-related benefits for patients in the treatment of PACS compared with the current local standard of care

Chromosomal instability and lack of cyclin E regulation in hCdc4 mutant human breast cancer cells

INTRODUCTION: Cyclin E, a G(1 )cyclin essential for G(1)–S phase transition, is known to have a profound effect on tumorigenesis. Elevated levels of cyclin E have been associated with breast cancer, and chromosomal instability observed in breast cancer is suggested to be associated with constitutive expression of cyclin E. It was previously demonstrated that SUM149PT human breast cancer cells show very high levels of cyclin E expression by western analysis and that they express a nonfunctional cyclin E ubiquitin ligase due to a mutation in the F-box protein hCdc4. METHODS: We examined cyclin E expression in both MCF10A and SUM149PT cells using western blot analysis and flow cytometry. Immunofluorescence was utilized for the localization of cyclin E in both normal and breast cancer cells. In addition, array comparative genomic hybridization analysis was performed to compare chromosome copy number alterations with levels of cyclin E expression among a panel of breast cancer cell lines. RESULTS: SUM149PT cells overexpress cyclin E on a cell per cell basis for the duration of the cell cycle. High cyclin E levels are maintained throughout the S phase, and SUM149PT cells exhibit an S phase delay or arrest probably due to cyclin E overexpression. In addition, comparative genomic hybridization indicated that SUM149PT cells exhibit many chromosome copy number alterations, which may reflect prior or ongoing genomic instability. However, no direct correlation was observed between cyclin E levels and genomic copy number alteration in a panel of human breast cancer cell lines. CONCLUSIONS: Cyclin E is overexpressed at high levels throughout the cell cycle in SUM149PT cells, which is in stark contrast to cyclin E degradation observed in the mid to late S phase of normal cells. SUM149PT cells are unable to regulate cyclin E and also exhibit many copy number alterations. However, there was a lack of direct correlation between cyclin E overexpression and chromosomal instability across a panel of other breast cancer cell lines examined

A survey of task-oriented crowdsourcing

Since the advent of artificial intelligence, researchers have been trying to create machines that emulate human behaviour. Back in the 1960s however, Licklider (IRE Trans Hum Factors Electron 4-11, 1960) believed that machines and computers were just part of a scale in which computers were on one side and humans on the other (human computation). After almost a decade of active research into human computation and crowdsourcing, this paper presents a survey of crowdsourcing human computation systems, with the focus being on solving micro-tasks and complex tasks. An analysis of the current state of the art is performed from a technical standpoint, which includes a systematized description of the terminologies used by crowdsourcing platforms and the relationships between each term. Furthermore, the similarities between task-oriented crowdsourcing platforms are described and presented in a process diagram according to a proposed classification. Using this analysis as a stepping stone, this paper concludes with a discussion of challenges and possible future research directions.This work is part-funded by ERDF-European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through the FCT-Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) within the Ph.D. Grant SFRH/BD/70302/2010 and by the Projects AAL4ALL (QREN11495), World Search (QREN 13852) and FCOMP-01-0124-FEDER-028980 (PTDC/EEI-SII/1386/2012). The authors also thank Jane Boardman for her assistance proof reading the document.info:eu-repo/semantics/publishedVersio

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry

This is an Author's Accepted Manuscript of an article published in "The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry" version of the article as published in the Entrepreneurship and Regional Development, 2012 september,[copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/08985626.2012.710260"[EN] Recent research into the clustering effect on firms has moved away from a simplistic view to a more complex approach. More realistic and complex causal relationships are now considered when analysing these territorial networks. Specifically, this paper attempts to analyse how cluster connect- edness moderates the relationship of a firm's innovation effort and the results obtained from this effort. We want to question the commonly accepted direct and positive impact of R&D effort, and moreover, we suggest the existence of a saturation effect and that the level of cluster's inter-connectedness in the cluster moderates this effect. We have developed our empirical study focusing on the Spanish textile industrial cluster. This is a complex manufacturing industry that uses relatively low-technology manufacturing and R&D. Our findings suggest that the degree to which a firm is involved with, or connected to, other firms in the cluster can moderate the effect of the R&D effort on its innovation results. More generally, we aim to contribute to the discussion on the degree to which firms should be involved in the cluster network in order to operate efficiently and gain the maximum competitive advantages. Our findings have implications both in recent cluster and network literature as well for institutional policy.Molina Morales, FX.; Expósito Langa, M. (2012). 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Routine provision of information on patient-reported outcome measures to healthcare providers and patients in clinical practice

This is the final version. Available from Cochrane Collaboration via the DOI in this record.This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the impact of the routine use of patient-reported outcomes (PROs) in clinical practice on the process of care (including patient-physician communication, professionals awareness of patients' quality of life, diagnosis and recognition rates, treatment rates, health services and resource use, as well as patient behaviour); patients' and professionals' experiences of care; and health outcomes (both generic and disease-specific, using both routinely-used clinical measures and PROs).Spanish Ministry of ScienceInnovation and the European commissionNational Institutes of Health Research (NIHR

Climate change adaptation, flood risks and policy coherence in integrated water resources management in England

Integrated water resources management (IWRM) assumes coherence between cognate aspects of water governance at the river basin scale, for example water quality, energy production and agriculture objectives. But critics argue that IWRM is often less ‘integrated’ in practice, raising concerns over inter-sectoral coherence between implementing institutions. One increasingly significant aspect of IWRM is adaptation to climate change-related risks, including threats from flooding, which are particularly salient in England. Although multiple institutional mechanisms exist for flood risk management (FRM), their coherence remains a critical question for national adaptation. This paper therefore (1) maps the multi-level institutional frameworks determining both IWRM and FRM in England; (2) examines their interaction via various inter-institutional coordinating mechanisms; and (3) assesses the degree of coherence. The analysis suggests that cognate EU strategic objectives for flood risk assessment demonstrate relatively high vertical and horizontal coherence with river basin planning. However, there is less coherence with flood risk requirements for land-use planning and national flood protection objectives. Overall, this complex governance arrangement actually demonstrates de-coherence over time due to ongoing institutional fragmentation. Recommendations for increasing IWRM coherence in England or re-coherence based on greater spatial planning and coordination of water-use and land-use strategies are proposed