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Search Results: 1 - 10 of 12678 matches for " Christopher Lord "
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The aggregating function of political parties in EU decision-making
Christopher Lord
Living Reviews in European Governance , 2006,
Abstract: This Living Review uses concepts of aggregation to analyse what we do and do not know about the contribution of political parties to the politics and democratic performance of the European Union. It suggests that present representative structures are better at aggregating ‘choices of policies’ than ‘choices of leaders’. Much more, however, needs to be done to analyse the causal contribution of party actors to those patterns of aggregation, and to understand why European Union parties do not develop further where aggregation seems to be deficient in the EU arena.
The aggregating function of political parties in EU decision-making
Christopher J. Lord
Living Reviews in European Governance , 2010,
Abstract: This Living Review uses concepts of aggregation to analyse what we do and do not know about the contribution of political parties to the politics and democratic performance of the European Union. It suggests that present representative structures are better at aggregating ‘choices of policies’ than ‘choices of leaders’. Much more, however, needs to be done to analyse the causal contribution of party actors to those patterns of aggregation, and to understand why European Union parties do not develop further where aggregation seems to be deficient in the EU arena.
Biology-driven cancer drug development: back to the future
Christopher J Lord, Alan Ashworth
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-38
Abstract: In the past 100 years our grasp of the biology of cancer has come a very long way. We now have a working knowledge of how tumors initially form, grow and spread. Importantly, vast amounts of information about features distinguishing tumor from normal cells is being accumulated, resulting in frequent, major new insights into cancer biology.The bad news is that translating this information into the development of new treatments, or even refining the use of the ones we already have, has been much less impressive. Clinicians will attest that cytotoxic chemotherapy regimens, developed with the limited biological information available at the time of their development, remain the mainstay of treatment for most cancers. There are a few high-profile examples of rationally and molecularly targeted therapies, but we need to do much better if we are to shift the entire pattern of treatment to drugs that have high potency but mild side effects.Several articles have extensively reviewed the history of cancer drug development [1] and so here we will only pick out the salient points. It is widely accepted, although clouded by the secrecy of war [2], that the first tentative steps to treating cancer with drugs emanated from the observation that exposure to chemical warfare agents ('poison gases'), such as nitrogen mustards, could limit the proliferative nature of rapidly dividing lymphoid cells. Goodman and Gilman reasoned that this could translate into a therapeutic context and used the nitrogen mustard mustine to treat a patient with non-Hodgkin's lymphoma [3]. Around the same time, and building on the observation that the vitamin folic acid could stimulate acute lymphoblastic leukemia (ALL) cells, Farber used folate analogs such as aminopterin and then amethopterin (methotrexate) to treat ALL, in what is often heralded as the first 'rational' drug development approach [4]. Burchenal, Hitchings and Elion used a similar approach to assess the potential of purine analogs, identifyin
NLK Is a Novel Therapeutic Target for PTEN Deficient Tumour Cells
Ana M. Mendes-Pereira, Christopher J. Lord, Alan Ashworth
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047249
Abstract: PTEN (Phosphatase and tensin homolog) is a tumour suppressor gene commonly defective in human cancer, and is thus a potentially important therapeutic target. Targeting tumour suppressor loss-of-function is possible by exploiting the genetic concept of synthetic lethality (SL). By combining the use of isogenic models of PTEN deficiency with high-throughput RNA interference (RNAi) screening, we have identified Nemo-Like Kinase (NLK) inhibition as being synthetically lethal with PTEN deficiency. This SL is likely mediated by the transcription factor FOXO1 (Forkhead box O1), an NLK substrate, as the selectivity of NLK gene silencing for PTEN deficient cells can be reversed by FOXO1 knockdown. In addition, we provide evidence that PTEN defective cells targeted by NLK gene depletion undergo senescence, suggesting that NLK function is critical for the continued proliferation of PTEN deficient cells. Taken together, these data provide new insight into the potential of targeting of NLK to treat a range of tumourigenic conditions characterised by PTEN deficiency.
A Rediscovered Ancient History of Motivational Interviewing and its Measurement
Christopher W. Dunn,Sarah Peregrine Lord,Jessica Lowe,Jutta Joesch
Motivational Interviewing : Training, Research, Implementation, Practice , 2012, DOI: 10.5195/mitrip.2012.20
Abstract: We wrote this piece for coding teams around the world, hoping to raise some measurement issues, to inspire, and to entertain (perhaps not in that order). This one’s for you, coders and for you, trainers of coders, you who work so hard to measure Motivational Interviewing using the standardized coding systems such as the MISC, MITI, and SCOPE.
An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence
Emilie Rovillain, Louise Mansfield, Christopher J Lord, Alan Ashworth, Parmjit S Jat
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-355
Abstract: To identify the downstream effectors of the p53-p21 and p16-pRB tumour suppressor pathways crucial for mediating entry into senescence, we have carried out a loss-of-function RNA interference screen in conditionally immortalised human fibroblasts that can be induced to rapidly undergo senescence, whereas in primary cultures senescence is stochastic and occurs asynchronously. These cells are immortal but undergo a rapid irreversible arrest upon activation of the p53-p21 and p16-pRB pathways that can be readily bypassed upon their inactivation. The primary screen identified 112 known genes including p53 and another 29 shRNAmirs targetting as yet unidentified loci. Comparison of these known targets with genes known to be up-regulated upon senescence in these cells, by micro-array expression profiling, identified 4 common genes TMEM9B, ATXN10, LAYN and LTBP2/3. Direct silencing of these common genes, using lentiviral shRNAmirs, bypassed senescence in the conditionally immortalised cells.The senescence bypass screen identified TMEM9B, ATXN10, LAYN and LTBP2/3 as novel downstream effectors of the p53-p21 and p16-pRB tumour suppressor pathways. Although none of them has previously been linked to cellular senescence, TMEM9B has been suggested to be an upstream activator of NF-κB signalling which has been found to have a causal role in promoting senescence. Future studies will focus on determining on how many of the other primary hits also have a casual role in senescence and what is the mechanism of action.Normal somatic cells undergo a finite number of divisions before entering a state of irreversible growth arrest termed cellular senescence [1]. This is triggered in response to a variety of intrinsic and extrinsic stimuli including progressive telomere shortening or changes in telomeric structure at the ends of chromosomes or other forms of genotoxic stress such as oncogene activation, or DNA damage or oxidative stress, resulting in a DNA damage response and growth arrest
Effect of wearing a dorsiflexion assist orthosis on mobility, perceived fatigue and exertion during the six-minute walk test in people with multiple sclerosis: a randomised cross-over protocol
James V McLoughlin, Christopher J Barr, Daina Sturnieks, Stephen R Lord, Maria Crotty
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-27
Abstract: A randomised cross-over trial will be conducted with 40 community dwelling PWMS with mild to moderate mobility disability. Participants will initially be screened for disease severity, balance, strength, depression and fatigue at the South Australian Motion Analysis Centre. On two non-consecutive occasions, within two weeks, participants will undergo either the 6-minute walk test (6MWT) or the 6MWT while wearing a dorsiflexion ankle orthosis (with a randomised condition order). Distance walked, perceived exertion, perceived fatigue and the physiological cost of walking (the primary outcome measures) will be compared between the two walking conditions. Additional pre- and post-6MWT assessments for the two conditions will include tests of strength, reaction time, gait and balance.This study will increase our understanding of motor fatigue on gait and balance control in PWMS and elucidate the effect of a Dynamic Ankle Orthosis on fatigue-related balance and gait in PWMS. It will also examine relationships between mobility and balance performance with perceived fatigue levels in this group.ACTRN12612000218897
Paramedic assessment of pain in the cognitively impaired adult patient
Bill Lord
BMC Emergency Medicine , 2009, DOI: 10.1186/1471-227x-9-20
Abstract: A systematic search of health databases for evidence relating to the use of pain assessment tools that have been validated for use with cognitively impaired adults was undertaken using specific search criteria. An extended search included position statements and clinical practice guidelines developed by health agencies to identify evidence-based recommendations regarding pain assessment in older adults.Two systematic reviews met study inclusion criteria. Weaknesses in tools evaluated by these studies limited their application in assessing pain in the population of interest. Only one tool was designed to assess pain in acute care settings. No tools were located that are designed for paramedic use.The reviews of pain assessment tools found that the majority were developed to assess chronic pain in aged care, hospital or hospice settings. An analysis of the characteristics of these pain assessment tools identified attributes that may limit their use in paramedic practice. One tool - the Abbey Pain Scale - may have application in paramedic assessment of pain, but clinical evaluation is required to validate this tool in the paramedic practice setting. Further research is recommended to evaluate the Abbey Pain Scale and to evaluate the effectiveness of paramedic pain management practice in older adults to ensure that the care of all patients is unaffected by age or disability.Although pain is a commonly encountered complaint in prehospital and emergency medicine settings, evidence of inadequate analgesia has been widely documented. Poor pain management practice has been described in the emergency department (ED)[1], and variations in pain management practice in this setting have been associated with ethnicity[2], gender[3], and extremes of age[4].Reasons for inadequacies in pain management practice are likely to be multifactorial. Failure to assess for the presence and severity of pain may be one factor, as efforts to make pain measurement mandatory in the ED have been sh
Fire, flood and ice: Search and rescue missions of the South African Air Force
D Lord
Scientia Militaria: South African Journal of Military Studies , 1999,
Abstract:
Bridging Nature and Nurture: A Look at Epigenetic Effects of Stressful Social Environments on Childhood Development
Sarah Lord
University of Toronto Medical Journal , 2009, DOI: 10.5015/utmj.v87i1.1224
Abstract:
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