Showing papers by "Newcastle University published in 2006"
Oregon Health & Science University1, Newcastle University2, Novartis3, University of Texas MD Anderson Cancer Center4, University of Düsseldorf5, Leipzig University6, Cornell University7, National Institutes of Health8, Harvard University9, University of Barcelona10, Heidelberg University11, Wake Forest University12, Icahn School of Medicine at Mount Sinai13, University of Paris14, University of Bordeaux15, Erasmus University Rotterdam16, Royal Adelaide Hospital17, Medical University of Vienna18, University of Mainz19, Katholieke Universiteit Leuven20, University of British Columbia21, University of Basel22, Aarhus University23, Fred Hutchinson Cancer Research Center24, Uppsala University25, Mater Health Services26, University of Bologna27, University of Chicago28
TL;DR: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients.
Abstract: BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...
3,351 citations
1,463 citations
TL;DR: It is shown that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA, suggesting that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.
Abstract: Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% ± 9.3%; individuals with Parkinson disease, 52.3% ± 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.
1,362 citations
TL;DR: In this paper, the authors synthesize the existing evidence that addresses the question: "What are the effects of faculty development interventions on the knowledge, attitudes and skills of teachers in medical education, and on the institutions in which they work?"
Abstract: Background: Preparing healthcare professionals for teaching is regarded as essential to enhancing teaching effectiveness. Although many reports describe various faculty development interventions, there is a paucity of research demonstrating their effectiveness.Objective: To synthesize the existing evidence that addresses the question: “What are the effects of faculty development interventions on the knowledge, attitudes and skills of teachers in medical education, and on the institutions in which they work?”Methods: The search, covering the period 1980–2002, included three databases (Medline, ERIC and EMBASE) and used the keywords: staff development; in-service training; medical faculty; faculty training/development; continuing medical education. Manual searches were also conducted.Articles with a focus on faculty development to improve teaching effectiveness, targeting basic and clinical scientists, were reviewed. All study designs that included outcome data beyond participant satisfaction were accepted....
1,091 citations
Journal Article•
TL;DR: In this article, the authors synthesize the existing evidence that addresses the question: "What are the effects of faculty development interventions on the knowledge, attitudes and skills of teachers in medical education, and on the institutions in which they work?"
Abstract: Background: Preparing healthcare professionals for teaching is regarded as essential to enhancing teaching effectiveness. Although many reports describe various faculty development interventions, there is a paucity of research demonstrating their effectiveness.Objective: To synthesize the existing evidence that addresses the question: “What are the effects of faculty development interventions on the knowledge, attitudes and skills of teachers in medical education, and on the institutions in which they work?”Methods: The search, covering the period 1980–2002, included three databases (Medline, ERIC and EMBASE) and used the keywords: staff development; in-service training; medical faculty; faculty training/development; continuing medical education. Manual searches were also conducted.Articles with a focus on faculty development to improve teaching effectiveness, targeting basic and clinical scientists, were reviewed. All study designs that included outcome data beyond participant satisfaction were accepted....
1,080 citations
TL;DR: This paper examined the effect of an image of a pair of eyes on contributions to an honesty box used to collect money for drinks in a university coffee room and found that people paid nearly three times more for their drinks when eyes were displayed rather than a control image.
Abstract: We examined the effect of an image of a pair of eyes on contributions to an honesty box used to collect money for drinks in a university coffee room. People paid nearly three times as much for their drinks when eyes were displayed rather than a control image. This finding provides the first evidence from a naturalistic setting of the importance of cues of being watched, and hence reputational concerns, on human cooperative behaviour.
1,062 citations
TL;DR: This review considers the basic principles of mitochondrial genetics which govern both the behaviour and investigation of pathogenic mtDNA mutations summarizing recent advances, and an assessment of the ongoing debate into the role of somatic mt DNA mutations in neurodegenerative disease, ageing and cancer.
Abstract: Since their first association with human disease in 1988, more than 250 pathogenic point mutations and rearrangements of the 16.6 kb mitochondrial genome (mtDNA) have been reported in a spectrum of clinical disorders which exhibit prominent muscle and central nervous system involvement. With novel mutations and disease phenotypes still being described, mtDNA disorders are recognized collectively as common, inherited genetic diseases although relatively little is still known concerning the precise pathophysiological mechanisms that lead to cell dysfunction and pathology. This review considers the basic principles of mitochondrial genetics which govern both the behaviour and investigation of pathogenic mtDNA mutations summarizing recent advances in this area, and an assessment of the ongoing debate into the role of somatic mtDNA mutations in neurodegenerative disease, ageing and cancer.
1,011 citations
TL;DR: That the globe is not swamped with oil is testament to the efficiency and versatility of the networks of microorganisms that degrade hydrocarbons, some of which have recently begun to reveal the secrets of when and how they exploit Hydrocarbons as a source of carbon and energy.
Abstract: Hundreds of millions of litres of petroleum enter the environment from both natural and anthropogenic sources every year. The input from natural marine oil seeps alone would be enough to cover all of the world's oceans in a layer of oil 20 molecules thick. That the globe is not swamped with oil is testament to the efficiency and versatility of the networks of microorganisms that degrade hydrocarbons, some of which have recently begun to reveal the secrets of when and how they exploit hydrocarbons as a source of carbon and energy.
993 citations
TL;DR: It is indicated that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication.
Abstract: Background Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. Methods We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel–Haenszel test. Results Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 p...
988 citations
Johns Hopkins University1, Université libre de Bruxelles2, Columbia University3, Newcastle University4, University College Dublin5, University of North Carolina at Chapel Hill6, University of Toronto7, University of Pennsylvania8, University of Michigan9, Inova Fairfax Hospital10, Duke University11, Washington University in St. Louis12, Alfred Hospital13, University of Pittsburgh14, St. Vincent's Health System15
TL;DR: This update to the international guidelines is based primarily on a consensus of opinion rendered by experts in the field and should not be considered to be hard and fast rules.
Abstract: Since the writing of the 1998 guidelines for the selection of candidates for lung transplantation, there has been an increased understanding of the natural history of various lung diseases as well as new treatment strategies developed that may forestall the need for transplantation for certain disorders. This has resulted in several changes to the current strategy for selecting patients for this procedure. The primary goal of this document is to provide up-to-date guidelines to help physicians in the referral and selection process of candidates for lung transplantation. With limited prospective randomized studies to support the recommendations outlined in this document, this update to the international guidelines is based primarily on a consensus of opinion rendered by experts in the field. The bulleted guidelines should therefore not be considered to be hard and fast rules. Because of the potential for long waiting times to transplantation, physicians should err on the side of early referral of their patients to a lung transplant center. © 2006 International Society for Heart and Lung Transplantation.
983 citations
TL;DR: Euthymic bipolar patients demonstrate relatively marked impairment in aspects of executive function and verbal memory, and it is not yet clear whether these are two discrete areas of impairment or are related to one another.
TL;DR: It is shown that the relative abundance and frequency with which different taxa are observed in samples can be explained by a neutral community model (NCM), which suggests that chance and immigration are important forces in shaping the patterns seen in prokaryotic communities.
Abstract: Summary
Naturally occurring populations of bacteria and archaea are vital to life on the earth and are of enormous practical significance in medicine, engineering and agriculture. However, the rules governing the formation of such communities are still poorly understood, and there is a need for a usable mathematical description of this process. Typically, microbial community structure is thought to be shaped mainly by deterministic factors such as competition and niche differentiation. Here we show, for a wide range of prokaryotic communities, that the relative abundance and frequency with which different taxa are observed in samples can be explained by a neutral community model (NCM). The NCM, which is a stochastic, birth–death immigration process, does not explicitly represent the deterministic factors and therefore cannot be a complete or literal description of community assembly. However, its success suggests that chance and immigration are important forces in shaping the patterns seen in prokaryotic communities.
TL;DR: In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life and the survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy.
Abstract: Summary Background Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. Methods 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T i MCS and T i sym) and mean improvement (μMCS and μsym) were measured. Findings NIV improved T i MCS, T i sym, μMCS, μsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0·006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including μsym (p=0·018), but conferred no survival benefit. Interpretation In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.
TL;DR: It is shown that climate change-driven loss of live coral, and ultimately structural complexity, in the Seychelles results in local extinctions, substantial reductions in species richness, reduced taxonomic distinctness, and a loss of species within key functional groups of reef fish.
Abstract: As one of the most diverse and productive ecosystems known, and one of the first ecosystems to exhibit major climate-warming impacts (coral bleaching), coral reefs have drawn much scientific attention to what may prove to be their Achilles heel, the thermal sensitivity of reef-building corals. Here we show that climate change-driven loss of live coral, and ultimately structural complexity, in the Seychelles results in local extinctions, substantial reductions in species richness, reduced taxonomic distinctness, and a loss of species within key functional groups of reef fish. The importance of deteriorating physical structure to these patterns demonstrates the longer-term impacts of bleaching on reefs and raises questions over the potential for recovery. We suggest that isolated reef systems may be more susceptible to climate change, despite escaping many of the stressors impacting continental reefs.
TL;DR: Patients with elevated blood pressure should follow a weight-reducing diet, take regular exercise, and restrict alcohol and salt intake, as available evidence does not support relaxation therapies, calcium, magnesium or potassium supplements to reduce blood pressure.
Abstract: PurposeTo quantify effectiveness of lifestyle interventions for hypertension.Data sourcesElectronic bibliographic databases from 1998 onwards, existing guidelines, systematic reviews.Study selection and data abstractionWe included randomized, controlled trials with at least 8 weeks' follow-up, compa
TL;DR: A novel ELISA method is developed that detects only oligomeric “soluble aggregates” of α‐syn in human plasma as a potential biomarker for Parkinson's disease and offers new opportunities for developing diagnostic tests for PD and related diseases.
Abstract: To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analysis of blood or cerebrospinal fluid (CSF). alpha-Synuclein (alpha-syn) protein has been linked to the pathogenesis of PD with the discovery of mutations in the gene encoding alpha-syn in familial cases with early-onset PD. Lewy bodies and Lewy neurites, which constitute the main pathological features in the brains of patients with sporadic PD and dementia with Lewy bodies, are formed by the conversion of soluble monomers of alpha-syn into insoluble aggregates. We recently reported the presence of alpha-syn in normal human blood plasma and in postmortem CSF. Here, we investigated whether alpha-syn can be used as a biomarker for PD. We have developed a novel ELISA method that detects only oligomeric "soluble aggregates" of alpha-syn. Using this ELISA, we report the presence of significantly elevated (P=0.002) levels of oligomeric forms of alpha-syn in plasma samples obtained from 34 PD patients compared with 27 controls; 52% (95% confidence intervals 0.353-0.687) of the PD patients displayed signals >0.5 OD with our ELISA assay in comparison to only 14.8% (95% confidence intervals 0.014-0.281) for the control cases. An analysis of the test's diagnostic value revealed a specificity of 0.852 (95% confidence intervals 0.662-0.958), sensitivity of 0.529 (95% confidence intervals 0.351-0.702) and a positive predictive value of 0.818 (95% confidence intervals 0.597-0.948). These observations offer new opportunities for developing diagnostic tests for PD and related diseases and for testing therapeutic agents aimed at preventing or reversing the aggregation of alpha-syn.
TL;DR: In order to develop effective environmental interventions, in relation to obesity, it needs to understand how individuals, and different groups of individuals, interact with their environments in terms of physical activity and food intake.
Abstract: Obesity is a significant health and social problem which has reached pandemic levels. The obesogenicity of an environment has been defined as ‘the sum of influences that the surroundings, opportunities, or conditions of life have on promoting obesity in individuals or populations’.1 Prevention and treatment of obesity has focused on pharmacological, educational and behavioural interventions, with limited overall success. A novel and a longer-term approach would be to investigate the environments that promote high energy intake and sedentary behaviour; this has not yet been fully understood. The obesity epidemic has attracted attention at all levels, from general media interest to policy and practice from health and other professions including urban designers and planners. Shaping the environment to better support healthful decisions has the potential to be a key aspect of a successful obesity prevention intervention. Thus in order to develop effective environmental interventions, in relation to obesity, w...
University of Michigan1, Newcastle University2, University of Cologne3, Simon Fraser University4, Harvard University5, University of Hyogo6, Max Planck Society7, Peking University8, University of California, San Diego9, University of Zurich10, University of Washington11, Hannover Medical School12, University of Freiburg13
TL;DR: These findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development.
Abstract: The molecular basis of nephronophthisis, the most frequent genetic cause of renal failure in children and young adults, and its association with retinal degeneration and cerebellar vermis aplasia in Joubert syndrome are poorly understood. Using positional cloning, we here identify mutations in the gene CEP290 as causing nephronophthisis. It encodes a protein with several domains also present in CENPF, a protein involved in chromosome segregation. CEP290 (also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formation. NPHP6 is found at centrosomes and in the nucleus of renal epithelial cells in a cell cycle-dependent manner and in connecting cilia of photoreceptors. Abrogation of its function in zebrafish recapitulates the renal, retinal and cerebellar phenotypes of Joubert syndrome. Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development.
TL;DR: In this paper, the authors compared the performance of Data Envelopment Analysis (DEA) and Stochastic Frontier Analysis (SFA) on the same set of container port data for the world's largest container ports and compared the results obtained.
Abstract: The efficiency of the container port industry has been variously studied utilising either Data Envelopment Analysis (DEA) or Stochastic Frontier Analysis (SFA). Given the strengths and weaknesses associated with these two approaches, the efficiency estimates and scale properties derived from these analyses are not always convincing. This paper applies both approaches to the same set of container port data for the world’s largest container ports and compares the results obtained. A high degree of correlation is found between the efficiency estimates derived from all the models applied, suggesting that results are relatively robust to the DEA models applied or the distributional assumptions under SFA. High levels of technical efficiency are associated with scale, greater private-sector participation and with transhipment as opposed to gateway ports. In analysing the implications of the results for management and policy makers, a number of shortcomings of applying a cross-sectional approach to an industry characterised by significant, lumpy and risky investments are identified and the potential benefits of a dynamic analysis, based on panel data, are enumerated.
TL;DR: The weight of evidence suggests that greater neuropsychological dysfunction in bipolar disorder is associated with a worse prior course of illness, particularly the number of manic episodes, hospitalizations and length of illness.
Abstract: Objectives The notion that sufferers of bipolar disorder achieve complete syndromal and functional recovery between illness episodes has been brought into question by evidence that a large proportion of patients fail to regain premorbid levels of functioning after the resolution of major affective symptoms. A growing body of evidence suggests that bipolar patients exhibit neuropsychological impairment that persists even during the euthymic state, which may be a contributory factor to poor psychosocial outcome. However, the aetiology of such impairment and its relation to progression of illness are not well understood. This review aims to consider evidence from studies investigating both the relationship between cognitive impairment and clinical outcome and studies of neurocognitive function in unaffected first-degree relatives (FDRs) of bipolar sufferers to address issues of the temporal evolution of cognitive impairment in bipolar disorder. Methods Systematic literature review. Results The weight of evidence suggests that greater neuropsychological dysfunction in bipolar disorder is associated with a worse prior course of illness, particularly the number of manic episodes, hospitalizations and length of illness. The most consistent finding was a negative relationship between the number of manic episodes and verbal declarative memory performance. Impairment in unaffected FDRs was reported in verbal declarative memory and some facets of executive function. Conclusions Cognitive impairment may be a trait vulnerability factor for bipolar disorder that is present before illness onset and worsens as the illness progresses. Further investigation into the causal relationship between cognitive impairment and illness course is essential.
TL;DR: This approach provides an accessible in vitro model system for studies of mammalian gametogenesis, as well as for the development of new strategies for the generation of transgenic mice and treatment of infertility.
TL;DR: Protocolized fluid administration using oesophageal Doppler monitoring may improve the postoperative outcome in patients undergoing surgery.
Abstract: Background: Protocolized fluid administration using oesophageal Doppler monitoring may improve the postoperative outcome in patients undergoing surgery. Methods: A total of 108 patients undergoing elective colorectal resection were recruited into a doubleblind prospective randomized controlled trial. An oesophageal Doppler probe was placed in all patients. The control group received perioperative fluid at the discretion of the anaesthetist, whereas the intervention group received additional colloid boluses based on Doppler assessment. Primary outcome was length of postoperative hospital stay. Secondary outcomes were morbidity, return of gastrointestinal function and cytokine markers of the systemic inflammatory response. Standard preoperative and postoperative management was used in all patients. Results: Demographic and surgical details were similar in the two groups. Aortic flow time, stroke volume, cardiac output and cardiac index during the intraoperative period were higher in the intervention group (P < 0·050). The intervention group had a reduced postoperative hospital stay (7 versus 9d ays in the control group; P = 0·005), fewer intermediate or major postoperative complications (2 versus 15 per cent; P = 0·043) and tolerated diet earlier (2 versus 4d ays;P = 0·029). There was a reduced rise in perioperative level of the cytokine interleukin 6 in the intervention group (P = 0·039). Conclusion: A protocol-based fluid optimization programme using intraoperative oesophageal Doppler monitoring leads to a shorter hospital stay and decreased morbidity in patients undergoing elective colorectal resection.
TL;DR: Genotyping polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 found a common haplotype associated with decreased risk of AMD that carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes.
Abstract: Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years. It is a complex disease in which genetic and environmental factors contribute to susceptibility. Complement factor H (CFH) has recently been identified as a major AMD susceptibility gene, and the Y402H polymorphism has been proposed as the likely causative factor. We genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 individuals with severe neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis showed a common haplotype associated with decreased risk of AMD that was present on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with Y402H and was replicated in an independent sample.
TL;DR: New longitudinal data derived from a histological analysis of tooth enamel suggest fewer differences between samples and smaller ranges of variation than in many radiographic studies and present a more realistic picture of worldwide variation in enamel formation times.
TL;DR: This article defines and illustrates sociophonetic variation within speech, highlighting both its pervasiveness and also the relatively minor role it has played in the development of phonetic and phonological theory.
TL;DR: NU7441 shows sufficient proof of principle through in vitro and in vivo chemos Sensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use.
Abstract: DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by ionizing radiation and topoisomerase II poisons, such as etoposide and doxorubicin. A major pathway for the repair of DSB is nonhomologous end joining, which requires DNA-dependent protein kinase (DNA-PK) activity. We investigated the therapeutic use of a potent, specific DNA-PK inhibitor (NU7441) in models of human cancer. We measured chemosensitization by NU7441 of topoisomerase II poisons and radiosensitization in cells deficient and proficient in DNA-PK(CS) (V3 and V3-YAC) and p53 wild type (LoVo) and p53 mutant (SW620) human colon cancer cell lines by clonogenic survival assay. Effects of NU7441 on DSB repair and cell cycle arrest were measured by gammaH2AX foci and flow cytometry. Tissue distribution of NU7441 and potentiation of etoposide activity were determined in mice bearing SW620 tumors. NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB. NU7441 appreciably increased G(2)-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells. In mice bearing SW620 xenografts, NU7441 concentrations in the tumor necessary for chemopotentiation in vitro were maintained for at least 4 hours at nontoxic doses. NU7441 increased etoposide-induced tumor growth delay 2-fold without exacerbating etoposide toxicity to unacceptable levels. In conclusion, NU7441 shows sufficient proof of principle through in vitro and in vivo chemosensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use.
TL;DR: The normalization process model has face validity in assessing the potential for complex interventions to become routinely embedded in everyday clinical work, and evaluating the factors that promote or inhibit their success and failure in practice.
Abstract: Understanding how new clinical techniques, technologies and other complex interventions become normalized in practice is important to researchers, clinicians, health service managers and policy-makers. This paper presents a model of the normalization of complex interventions. Between 1995 and 2005 multiple qualitative studies were undertaken. These examined: professional-patient relationships; changing patterns of care; the development, evaluation and implementation of telemedicine and related informatics systems; and the production and utilization of evidence for practice. Data from these studies were subjected to (i) formative re-analysis, leading to sets of analytic propositions; and to (ii) a summative analysis that aimed to build a robust conceptual model of the normalization of complex interventions in health care. A normalization process model that enables analysis of the conditions necessary to support the introduction of complex interventions is presented. The model is defined by four constructs: interactional workability; relational integration; skill set workability and contextual integration. This model can be used to understand the normalization potential of new techniques and technologies in healthcare settings The normalization process model has face validity in (i) assessing the potential for complex interventions to become routinely embedded in everyday clinical work, and (ii) evaluating the factors that promote or inhibit their success and failure in practice.
TL;DR: It is shown that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic "P bodies," including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression pathways.