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Ongoing Challenge (ongoing + challenge)
Selected AbstractsIssues with recruitment to randomised controlled trials in the drug and alcohol field: a literature review and Australian case studyDRUG AND ALCOHOL REVIEW, Issue 2 2008CLARE L. THOMSON Abstract Issues. The randomised control trial (RCT) is a widely used tool for measuring the effectiveness of health treatments and services. However, subject recruitment is an ongoing challenge for those conducting RCTs and may have a serious impact on the success of the study and the reliability of the outcomes. Approach. In this review we present an examination of the problems and strategies associated with recruitment to RCTs, with particular reference to studies conducted in the drug and alcohol field. A case study of recruitment to an RCT for the treatment of alcohol dependence is presented, supplemented by PubMed, Current Contents and Medline searches to identify relevant publications. Key Findings. The literature suggests that the most common barriers to patient participation involve fears of assignment to placebo treatment, insufficient compensation and poor attendance at initial appointments. Moreover, subject referrals from staff may be a greater problem than reluctance of patients. Referrals are inhibited by complicated entry criteria, time constraints due to busy work schedules or a limited research culture. Implications. Subject recruitment may be promoted by financial reimbursement, close partnerships between research and referral staff; increasing the treatment group ratio in multi-drug trials to minimise randomisation to placebo; addressing negative staff attitudes; and simplifying the referral process. Conclusion. The need for multi-centre sites in Australian drug and alcohol treatment studies is highlighted. [source] Diverse developmental mechanisms contribute to different levels of diversity in horned beetlesEVOLUTION AND DEVELOPMENT, Issue 3 2005Armin P. Moczek Summary An ongoing challenge to evolutionary developmental biology is to understand how developmental evolution on the level of populations and closely related species relates to macroevolutionary transformations and the origin of morphological novelties. Here we explore the developmental basis of beetle horns, a morphological novelty that exhibits remarkable diversity on a variety of levels. In this study, we examined two congeneric Onthophagus species in which males develop into alternative horned and hornless morphs and different sexes express marked sexual dimorphism. In addition, both species differ in the body region (head vs. thorax) that develops the horn. Using a comparative morphological approach we show that prepupal growth of horn primordia during late larval development, as well as reabsorption of horn primordia during the pupal stage, contribute to horn expression in adults. We also show that variable combinations of both mechanisms are employed during development to modify horn expression of different horns in the same individual, the same horn in different sexes, and different horns in different species. We then examine expression patterns of two transcription factors, Distal-less (Dll) and aristaless (al), in the context of prepupal horn growth in alternative male morphs and sexual dimorphisms in the same two species. Expression patterns are qualitatively consistent with the hypothesis that both transcription factors function in the context of horn development similar to their known roles in patterning a wide variety of arthropod appendages. Our results suggest that the origin of morphological novelties, such as beetle horns, rests, at least in part, on the redeployment of already existing developmental mechanisms, such as appendage patterning processes. Our results also suggest, however, that little to no phylogenetic distance is needed for the evolution of very different modifier mechanisms that allow for substantial modulation of trait expression at different time points during development in different species, sexes, or tissue regions of the same individual. We discuss the implications of our results for our understanding of the evolution of horned beetle diversity and the origin and diversification of morphological novelties. [source] Whole ecosystem metabolic pulses following precipitation eventsFUNCTIONAL ECOLOGY, Issue 5 2008G. D. Jenerette Summary 1Ecosystem respiration varies substantially at short temporal intervals and identifying the role of coupled temperature- and precipitation-induced changes has been an ongoing challenge. To address this challenge we applied a metabolic ecological theory to identify pulses in ecosystem respiration following rain events. Using this metabolic framework, precipitation-induced pulses were described as a reduction in metabolic activation energy after individual precipitation events. 2We used this approach to estimate the responses of 237 individual events recorded over 2 years at four eddy-covariance sites in southern AZ, USA. The sites varied in both community type (woody and grass dominated) and landscape position (riparian and upland). We used a nonlinear inversion procedure to identify both the parameters for the pre-event temperature sensitivity and the predicted response of the temperature sensitivity to precipitation. By examining multiple events we evaluated the consistency of pulses between sites and discriminated between hypotheses regarding landscape position, event distributions, and pre-event ecosystem metabolism rates. 3Over the 5-day post-event period across all sites the mean precipitation effect was attributed to 6·1 g CO2 m,2 of carbon release, which represented a 21% increase in respiration over the pre-event steady state trajectory of carbon loss. Differences in vegetation community were associated with differences in the integrated magnitude of pulse responses, while differences in topographic position were associated with the initial peak pulse rate. In conjunction with the differences between sites, the individual total pulse response was positively related to the drying time interval and metabolic rates prior to the event. The quantitative theory presented provides an approach for understanding ecosystem pulse dynamics and helps characterized the dependence of ecosystem metabolism on both temperature and precipitation. [source] A cognitive aid for neonatal resuscitation: a randomized controlled trialPEDIATRIC ANESTHESIA, Issue 7 2009M.D. Bould Introduction:, Anaesthetists are among several health care practitioners responsible for neonatal resuscitation in Canada. The Neonatal resuscitation program (NRP) courses are the North American educational standard. NRP has been shown to be an effective way of learning skills and knowledge but retention has been found to be problematic [1]. The use of cognitive aids is mandatory in industries such as aviation, to avoid dependence on memory when decision making in critical situations. Visual cognitive aids have been studied retrospectively in resuscitation and performance was found to correlate to the frequency of use of the aid [2]. Cognitive aids have been found to be of benefit in an unblinded prospective study [3]. We aimed to conduct the first blinded study on the effect of a cognitive aid on the performance of simulated resuscitation. Methods:, We conducted a single-blind randomized controlled trial to investigate whether the presence of a cognitive aid improved performance in a simulated neonatal resuscitation. After ethics board approval we recruited 32 anaesthesia residents who had previously passed the NRP. Subjects were randomized to an intervention group that had a poster detailing the NRP algorithm and a control group without the poster. The cognitive aid was positioned so that it could not be seen on the video recordings of the simulation that was used to assess performance. The scenario was piloted to confirm adequate blinding. Both groups had their performance in a simulated neonatal resuscitation recorded and subsequently analyzed by a peer, an expert anaesthetist and an expert neonatologist, using a previously validated checklist. A further rater observed the scenario in real time to examine frequency of use of the cognitive aid. Results:, The inter-rater reliability of the checklist was excellent with an intraclass correlation coefficient of 0.88. Consequently the mean of the scores assigned by all three raters was used for analysis. The median checklist score in the control group 18.2 [15.0,20.5 (10.7,25.3)] was not significantly different from that in the intervention group 20.3 [18.3,21.3 (15.0,24.3)] (P = 0.08). Retention of NRP skills and knowledge of was poor: when evaluated by the neonatologist none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. Although only one subject in the intervention group did not use the aid at all, only 26.7% used the aid frequently and none used it extensively. Discussion:, Retention of skills after NRP training was poor. Our study confirms previous findings of poor retention of skills after NRP training: Kaczorowski et al. investigated family medicine trainees and found that none of 44 residents that were retested 6,8 months after an NRP course would have passed the course due to errors in life-saving interventions [1]. Previous research has shown that the presence of a cognitive aid can improve performance in the simulated management of a rare, high stakes scenario: malignant hyperthermia [3]. Our negative findings contrast with this and another previous study [2]. A potential reason for this discrepancy is that the raters in the previous studies were not blinded to group allocation, nor were the rating scales used validated. The infrequent use of the cognitive aid may be the reason that it did not improve performance in. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into NRP training. Conclusion:, A randomized single-blinded trial found that a cognitive aid did not improve performance at simulated resuscitation, in contrast to previous retrospective and unblended studies. Retention of skills and knowledge after resuscitation training remains an ongoing challenge for medical educators. [source] ,All-in-One' analysis for metabolite identification using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision energy switchingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2005Mark Wrona The removal of bottlenecks in discovery stage metabolite identification studies is an ongoing challenge for the pharmaceutical industry. We describe the use of an ,All-in-One' approach to metabolite characterization that leverages the fast scanning and high mass accuracy of hybrid quadrupole time-of-flight mass spectrometry (QqToFMS) instruments. Full-scan MS and MS/MS data is acquired using collision energy switching without the preselection, either manually or in a data-dependent manner, of precursor ions. The acquisition of ,clean' MS/MS data is assisted by the use of ultrahigh-performance chromatography. Data acquired using this method can then be mined post-acquisition in a number of ways. These include using narrow window extracted ion chromatograms (nwXICs) for expected biotransformations, XICs for the product ions of the parent compound and/or expected modification of these product ions, and neutral loss chromatograms. This approach has the potential to be truly comprehensive for the determination of in vitro biotransformations in a drug discovery environment. Copyright © 2005 John Wiley & Sons, Ltd. [source] Technical considerations for RNA-based stable isotope probing: an approach to associating microbial diversity with microbial community function,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2002Mike Manefield An ongoing challenge within microbial ecology is the development of methodologies that attribute microbial community functions to microbial diversity. One approach, involving the incorporation of stable isotopes from labelled tracer compounds into biological signature molecules (biomarkers), may overcome this current limitation. To examine the potential of RNA as the biomarker in stable isotope probing we have generated a series of atom % 13C-enriched RNA samples through exploitation of the anabolic abilities of a phenol-degrading environmental isolate. Isotope ratio mass spectrometry was used to determine the atom % 13C of each RNA sample (ca. 1,100%). The corresponding buoyant density (1.755,1.795,g,mL,1) was determined by equilibrium density gradient centrifugation and agarose gel electrophoresis. This empirically defined relationship between the atom % 13C of RNA and its buoyant density suggests ribonucleic acids with atom % 13C enrichments greater than 10% can be isolated by equilibrium density centrifugation. The processing and analysis of isolated RNA by reverse transcription polymerase chain reaction, denaturing gradient gel electrophoresis, cloning and sequencing are discussed. The RNA-based stable isotope probing protocol presented here will find particular utility in assessing the roles of microbial community members in the biodegradation of natural and anthropogenic xenobiotic compounds. Copyright © 2002 John Wiley & Sons, Ltd. [source] Dionaea muscipula (Venus Flytrap) Establishment, Release, and Response of Associated Species in Mowed Patches on the Rims of Carolina BaysRESTORATION ECOLOGY, Issue 4 2005James O Luken Abstract Carolina bays are depression wetlands of high conservation value that occur across the Southeastern Coastal Plain of the United States. Venus flytrap (Dionaea muscipula) is one rare carnivorous plant that grows in open habitats on the rims of Carolina bays. Without frequent burning, vegetation on bay rims becomes dominated by evergreen shrubs and Venus flytrap populations decline. This project examined the utility of mechanical mowing, soil clearing, transplanting, and seeding as an approach to restoring populations of Venus flytraps when fire is precluded. Mowing of patches on bay rims produced open sites with little ground-layer vegetation. After two growing seasons, adult Venus flytraps transplanted to mowed patches showed high survivorship and relatively high leaf number/plant. Suppressed Venus flytraps existing on-site quickly initiated growth in response to mowing. These volunteers and the transplants had higher flowering percentages than plants in reference populations. Seeds of Venus flytraps were scattered in mowed and cleared plots. Seedling establishment was low, but seedlings persisted into the second growing season. Mowing created suitable habitat for growth and flowering of adult Venus flytraps and facilitated establishment of two other carnivorous species, Sundew (Drosera capillaris) and Bladderwort (Utricularia subulata). But, mowing and clearing also facilitated invasion by four species of grasses and rushes; evergreen shrubs resprouted quickly after mowing. Maintaining persistent openings by mowing the rims of Carolina bays will be an ongoing challenge due to availability of potential invaders and rapid regrowth of shrubs. [source] Proteomics: Recent Applications and New TechnologiesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Mollisa M. Elrick Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models and man. In addition, several recent studies have attempted to integrate proteomics data with genomics and/or metabonomics data in a systems biology approach. The translation of proteomic technology and bioinformatics tools to clinical samples, such as in the areas of disease and toxicity biomarkers, represents one of the major opportunities and challenges facing this field. An ongoing challenge in proteomics continues to be the analysis of the serum proteome due to the vast number and complexity of proteins estimated to be present in this biofluid. Aside from the removal of the most abundant proteins, a number of interesting approaches have recently been suggested that may help reduce the overall complexity of serum analysis. In keeping with the increasing interest in applications of proteomics, the tools available for proteomic analyses continue to improve and expand. For example, enhanced tools (such as software and labeling procedures) continue to be developed for the analysis of 2D gels and protein quantification. In addition, activity-based probes are now being used to tag, enrich and isolate distinct sets of proteins based on enzymatic activity. One of the most active areas of development involves microarrays. Antibody-based microarrays have recently been released as commercial products while numerous additional capture agents (e.g. aptamers) and many additional types of microarrays are being explored. [source] High-Dimensional Cox Models: The Choice of Penalty as Part of the Model Building ProcessBIOMETRICAL JOURNAL, Issue 1 2010Axel Benner Abstract The Cox proportional hazards regression model is the most popular approach to model covariate information for survival times. In this context, the development of high-dimensional models where the number of covariates is much larger than the number of observations ( ) is an ongoing challenge. A practicable approach is to use ridge penalized Cox regression in such situations. Beside focussing on finding the best prediction rule, one is often interested in determining a subset of covariates that are the most important ones for prognosis. This could be a gene set in the biostatistical analysis of microarray data. Covariate selection can then, for example, be done by L1 -penalized Cox regression using the lasso (Tibshirani (1997). Statistics in Medicine16, 385,395). Several approaches beyond the lasso, that incorporate covariate selection, have been developed in recent years. This includes modifications of the lasso as well as nonconvex variants such as smoothly clipped absolute deviation (SCAD) (Fan and Li (2001). Journal of the American Statistical Association96, 1348,1360; Fan and Li (2002). The Annals of Statistics30, 74,99). The purpose of this article is to implement them practically into the model building process when analyzing high-dimensional data with the Cox proportional hazards model. To evaluate penalized regression models beyond the lasso, we included SCAD variants and the adaptive lasso (Zou (2006). Journal of the American Statistical Association101, 1418,1429). We compare them with "standard" applications such as ridge regression, the lasso, and the elastic net. Predictive accuracy, features of variable selection, and estimation bias will be studied to assess the practical use of these methods. We observed that the performance of SCAD and adaptive lasso is highly dependent on nontrivial preselection procedures. A practical solution to this problem does not yet exist. Since there is high risk of missing relevant covariates when using SCAD or adaptive lasso applied after an inappropriate initial selection step, we recommend to stay with lasso or the elastic net in actual data applications. But with respect to the promising results for truly sparse models, we see some advantage of SCAD and adaptive lasso, if better preselection procedures would be available. This requires further methodological research. [source] Recent progress in engineering ,/, hydrolase-fold family membersBIOTECHNOLOGY JOURNAL, Issue 2 2007Zhen Qian Abstract The members of the ,/, hydrolase-fold family represent a functionally versatile group of enzymes with many important applications in biocatalysis. Given the technical significance of ,/, hydrolases in processes ranging from the kinetic resolution of enantiomeric precursors for pharmaceutical compounds to bulk products such as laundry detergent, optimizing and tailoring enzymes for these applications presents an ongoing challenge to chemists, biochemists, and engineers alike. A review of the recent literature on ,/, hydrolase engineering suggests that the early successes of "random processes" such as directed evolution are now being slowly replaced by more hypothesis-driven, focused library approaches. These developments reflect a better understanding of the enzymes' structure-function relationship and improved computational resources, which allow for more sophisticated search and prediction algorithms, as well as, in a very practical sense, the realization that bigger is not always better. [source] Ureterocele: an ongoing challenge in infancy and childhoodBJU INTERNATIONAL, Issue 8 2002A.A. Shokeir First page of article [source] New Templating Strategies with Salen Scaffolds (Salen=N,N,-Bis(salicylidene)ethylenediamine Dianion)CHEMISTRY - A EUROPEAN JOURNAL, Issue 34 2008Arjan Abstract Templated approaches towards selective organic synthesis is a common feature in nature in which nucleic acid templated synthesis plays a crucial role in various fundamental biological processes. The key feature that allows control over the amazing selectivity found in natural processes is evidently the effective molarity of the reaction partners that is mediated by the macromolecular templation event. An ongoing challenge within many chemical sciences is to exploit similar templating principles and make use of synthetic systems that are designed for specific chemical conversions. Here, we describe the recent developments that involve (metallo)salen scaffolds that are used for diverse templating events (salen=N,N,-bis(salicylidene)ethylenediamine dianion). [source] Age-related macular disease: an ongoing challengeCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2003Alan C Bird MD FRCOphth No abstract is available for this article. [source] Ventilation threshold as a measure of impaired physical performance in adults with growth hormone excessCLINICAL ENDOCRINOLOGY, Issue 3 2002Scott G. Thomas Summary objective Fatigue is a prominent symptom among patients with GH excess and acromegaly. Identifying the physiological basis of such complaints and obtaining objective measures to quantify their severity remains an ongoing challenge. We investigated whether submaximal measures of aerobic performance can be used to assess GH excess-associated fatigue objectively. design and patients To investigate this possibility we examined the relation between physical function and physical capacity in 12 patients with active acromegaly and persistent fatigue before and after 3 and 6 months of treatment with the long-acting somatostatin analogue octreotide (LAR®). measurements Heart rate (HR) and rating of perceived exertion (RPE using Borg's 10-point scale) were measured during a 160-metre self-paced walk test (SPW). Maximum oxygen uptake (VO2max) and ventilation threshold (VeT: a measure of work rate when breathlessness develops) were measured during a progressive treadmill test to fatigue or symptom-limited maximum. The Profile Of Mood States questionnaire (POMS) was used to quantify subjective feelings of fatigue and vigour. Morning fasting levels of GH and IGF-I were measured using immunoassay of serum samples. results SPW speed at a fast pace of 1·69 ± 0·18 m/s was achieved with higher than normal HR (112 ± 15/min; normal = 102) and RPE (2·4 ± 1·2). Similar to GH-deficient adults, VO2max (22·6 ± 6·4 ml.kg,1.min,1; normal ~30 ml.kg,1.min,1) and VeT (13·1 ± 2·9 ml.kg,1.min,1; predicted normal ~16 ml.kg,1(min,1) were low. However, VeT occurred at a normal fraction of VO2max (VeT/VO2max = 0·58). VeT was significantly increased and plasma IGF-I levels reduced following 3 and 6 months of octreotide LAR® treatment. Reduction in circulating IGF-I levels was correlated with improvement in reported vigour (r = 0·85) and VeT (r = 0·65) (P < 0·05). conclusions Our findings demonstrate impairment in physical function and physical capacity consistent with the perception of increased fatigue among acromegalic patients. These objective measures of compromised physical function are similar to the changes that we have reported previously in adults with GH deficiency. Taken together, these data suggest that a narrow window for GH/IGF-I levels is required to maintain optimal physical function. [source] MANDATORY HIV TESTING IN PREGNANCY: IS THERE EVER A TIME?DEVELOPING WORLD BIOETHICS, Issue 1 2008RUSSELL ARMSTRONG ABSTRACT Despite recent advances in ways to prevent transmission of HIV from a mother to her child during pregnancy, infants continue to be born and become infected with HIV, particularly in southern Africa where HIV prevalence is the highest in the world. In this region, emphasis has shifted from voluntary HIV counselling and testing to routine testing of women during pregnancy. There have also been proposals for mandatory testing. Could mandatory testing ever be an option, even in high-prevalence settings? Many previous examinations of mandatory testing have dealt with it in the context of low HIV prevalence and a well-resourced health care system. In this discussion, different assumptions are made. Within this context, where mandatory testing may be a strategy of last resort, the objections to it are reviewed. Special attention is paid in the discussion to the entrenched vulnerability of women in much of southern Africa and how this contributes to both HIV prevalence and ongoing challenges for preventing HIV transmission during pregnancy. While mandatory testing is ethically plausible, particularly when coupled with guaranteed access to treatment and care, the discussion argues that the moment to employ this strategy has not yet come. Many barriers remain for pregnant women in terms of access to testing, treatment and care, most acutely in the southern African setting, despite the presence of national and international human rights instruments aimed at empowering women and removing such barriers. While this situation persists, mandatory HIV testing during pregnancy cannot be justified. [source] Patients' recovery after critical illness at early follow-upJOURNAL OF CLINICAL NURSING, Issue 5-6 2010Michelle A Kelly Aim., To determine the quality of life, particularly physical function, of intensive care survivors during the early recovery process. Background., Survivors of critical illness face ongoing challenges after discharge from the intensive care unit and on returning home. Knowledge about health issues during early phases of recovery after hospital discharge is emerging, yet still limited. Design., Descriptive study where the former critically ill patients completed instruments on general health and quality of life (SF-36) in the first six months of recovery. Methods., Participants responded to the SF-36 questionnaire and questions about problems, one to six months after intensive care, either face-to-face or by telephone. Results., Thirty-nine participants had a mean age of 60 years; of them, 59% were men and had been in intensive care for 1,69 days (median = 5). Most participants (69%) rated their health as good or fair, but 54% rated general health as worse than a year ago. Mean quality of life scores for all scales ranged from 25,65·5%, with particularly low scores for Role-Physical (25) and Pain (45·1). Half the participants reported difficulty with mobility, sleep and concentration, and 72% that their responsibilities at home had changed. No relationships were found between SF-36 scores and admission diagnosis, gender, age or length of intensive care stay. Conclusions., These survivors of critical illness and hospitalisation in an intensive care unit perceive their general health to be good despite experiencing significant physical limitations and disturbed sleep during recovery. Relevance to clinical practice., Knowledge of issues in these early phases of recovery and discussion and resolution of patient problems could normalise the experience for the patient and help to facilitate better quality of life. [source] Dementia and Driving: Autonomy Versus SafetyJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 10 2005Article first published online: 23 SEP 200, Charlene Hoffman Snyder MSN, NP-BC Purpose This article reviews the effects of various types of dementia on driving skills, the available assessment measures, legal considerations, and the important role played by the nurse practitioner (NP) in the process of recommending driving cessation. It provides strategies and resources that may offer guidance to NPs who are attempting to balance the continued independence of patients with dementia, as represented by driving, with the safety not only of such patients but also of the public at large. Data sources A review of the biomedical literature, resources available on the World Wide Web, and illustrative case studies were used. Conclusions The diagnosis of dementia alone is often insufficient to determine driver competence because the topographic losses of dementia are complex. Recognizing when cessation should occur is made more difficult because objective assessment tools do not exist to predict impaired driving skills. Recommending driving cessation at the appropriate time can be a challenge for NPs, who must balance such a significant impact on the driver's autonomy with concerns about public safety if the patient continues to drive despite progressive impairment. Implications for practice The progressive loss of cognitive abilities in dementia presents a series of ongoing challenges for the patient throughout the disease continuum. Unfortunately, the recommendation to stop driving can present one of the more immediate issues confronting the patient, the family, and the healthcare provider. Failure to assess diminished driving skill can lead either to premature or to delayed driving cessation. Either outcome can have adverse effects on the patient, the patient's family, and public safety. [source] Legislating Against Climate Change: A UK Perspective on a Sisyphean ChallengeTHE MODERN LAW REVIEW, Issue 3 2009Article first published online: 1 MAY 200, Mark Stallworthy The UK's Climate Change Act offers a framework for civil society to achieve ,low carbon' realignment through to 2050. The Act is reviewed for its coherence as a mechanism for directing future policy. The legislation establishes a carbon budgetary process, mandates greenhouse gas reduction targets and strategies, and imposes a novel range of duties supported by processes for ensuring transparency concerning progress. Following an overview of climate change risks and likely economic consequences, the analysis identifies selected regulatory strategies. It explores the main statutory features, with an emphasis upon the implications of imposing mandatory duties on decision makers. An evaluation of the key policy choice of emissions trading is informed by perspectives of environmental justice, in particular as to questions of equitable burden-sharing in relation to impacts of climate change and related policies. A concluding section summarises reasonable expectations and ongoing challenges. [source] | ||||||||||||||||