2,266 research outputs found
The Increment of Short-term Variability of Repolarisation Determines the Severity of the Imminent Arrhythmic Outcome
Risk, precaution and science: towards a more constructive policy debate. Talking point on the precautionary principle
Few issues in contemporary risk policy are as momentous or contentious as the precautionary principle. Since it first emerged in German environmental policy, it has been championed by environmentalists and consumer protection groups, and resisted by the industries they oppose (Raffensperger & Tickner, 1999). Various versions of the principle now proliferate across different national and international jurisdictions and policy areas (Fisher, 2002). From a guiding theme in European Commission (EC) environmental policy, it has become a general principle of EC law (CEC, 2000; Vos & Wendler, 2006). Its influence has extended from the regulation of environmental, technological and health risks to the wider governance of science, innovation and trade (O'Riordan & Cameron, 1994)
Hybridization between wild and cultivated potato species in the Peruvian Andes and biosafety implications for deployment of GM potatoes
The nature and extent of past and current hybridization between cultivated potato and wild relatives in nature is of interest to crop evolutionists, taxonomists, breeders and recently to molecular biologists because of the possibilities of inverse gene flow in the deployment of genetically-modified (GM) crops. This research proves that natural hybridization occurs in areas of potato diversity in the Andes, the possibilities for survival of these new hybrids, and shows a possible way forward in case of GM potatoes should prove advantageous in such areas
Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve
Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-
inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle.
Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials
were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was
investigated in an anaesthetized rabbit proarrhythmia model.
Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac
(20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was
observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong
while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac
following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades
de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of
diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased
the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium
current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not
influenced.
Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and
does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen
repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve
What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools
Background - The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on the following assumptions: (i) accessions that may exchange genetic material can be analyzed as if they are part of one gene pool, and (ii) genetic differentiation among species is expected to be higher than within species. Results - A dataset of 566 South-American accessions (encompassing 89 species and subspecies) was analyzed in two steps. First, with the program STRUCTURE 2.2 in an 'unsupervised' procedure, individual accessions were assigned to inferred clusters based on genetic similarity. The results showed that the South American members of section Petota could be arranged in 16 clusters of various size and composition. Next, the accessions within the clusters were grouped by maximizing the partitioning of genetic diversity among subgroups (i.e., maximizing Fst values) for all available individuals of the accessions (2767 genotypes). This two-step approach produced an optimal partitioning into 44 groups. Some of the species clustered as genetically distinct groups, either on their own, or combined with one or more other species. However, accessions of other species were distributed over more than one cluster, and did not form genetically distinct units. Conclusions - We could not find any support for 43 species (almost half of our dataset). For 28 species some level of support could be found varying from good to weak. For 18 species no conclusions could be drawn as the number of accessions included in our dataset was too low. These molecular data should be combined with data from morphological surveys, with geographical distribution data, and with information from crossing experiments to identify natural units at the species level. However, the data do indicate which taxa or combinations of taxa are clearly supported by a distinct set of molecular marker data, leaving other taxa unsupported. Therefore, the approach taken provides a general method to evaluate the taxonomic system in any species complex for which molecular data are available
The effect of fluid resuscitation on the effective circulating volume in patients undergoing liver surgery: a post-hoc analysis of a randomized controlled trial
To assess the significance of an analogue of the mean systemic filling pressure (Pmsa) and its derived variables, in providing a physiology based discrimination between responders and non-responders to fluid resuscitation during liver surgery. A post-hoc analysis of data from 30 patients undergoing major hepatic surgery was performed. Patients received 15 ml kg(-1) fluid in 30 min. Fluid responsiveness (FR) was defined as an increase of 20% or greater in cardiac index, measured by FloTrac-Vigileo((R)). Dynamic preload variables (pulse pressure variation and stroke volume variation: PPV, SVV) were recorded additionally. Pvr, the driving pressure for venous return (=Pmsa-central venous pressure) and heart performance (EH; Pvr/Pmsa) were calculated according to standard formula. Pmsa increased following fluid administration in responders (n = 18; from 13 +/- 3 to 17 +/- 4 mmHg, p < 0.01) and in non-responders (n = 12; from 14 +/- 4 to 17 +/- 4 mmHg, p < 0.01). Pvr, which was lower in responders before fluid administration (6 +/- 1 vs. 7 +/- 1 mmHg; p = 0.02), increased after fluid administration only in responders (from 6 +/- 1 to 8 +/- 1 mmHg; p < 0.01). EH only decreased in non-responders (from 0.56 +/- 0.17 to 0.45 +/- 0.12; p < 0.05). The area under the receiver operating characteristics curve of Pvr, PPV and SVV for predicting FR was 0.75, 0.73 and 0.72, respectively. Changes in Pmsa, Pvr and EH reflect changes in effective circulating volume and heart performance following fluid resuscitation, providing a physiologic discrimination between responders and non-responders. Also, Pvr predicts FR equivalently compared to PPV and SVV, and might therefore aid in predicting FR in case dynamic preload variables cannot be used
Evaluating the effectiveness of a tailored multifaceted performance feedback intervention to improve the quality of care: protocol for a cluster randomized trial in intensive care
Contains fulltext :
95871.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Feedback is potentially effective in improving the quality of care. However, merely sending reports is no guarantee that performance data are used as input for systematic quality improvement (QI). Therefore, we developed a multifaceted intervention tailored to prospectively analyzed barriers to using indicators: the Information Feedback on Quality Indicators (InFoQI) program. This program aims to promote the use of performance indicator data as input for local systematic QI. We will conduct a study to assess the impact of the InFoQI program on patient outcome and organizational process measures of care, and to gain insight into barriers and success factors that affected the program's impact. The study will be executed in the context of intensive care. This paper presents the study's protocol. METHODS/DESIGN: We will conduct a cluster randomized controlled trial with intensive care units (ICUs) in the Netherlands. We will include ICUs that submit indicator data to the Dutch National Intensive Care Evaluation (NICE) quality registry and that agree to allocate at least one intensivist and one ICU nurse for implementation of the intervention. Eligible ICUs (clusters) will be randomized to receive basic NICE registry feedback (control arm) or to participate in the InFoQI program (intervention arm). The InFoQI program consists of comprehensive feedback, establishing a local, multidisciplinary QI team, and educational outreach visits. The primary outcome measures will be length of ICU stay and the proportion of shifts with a bed occupancy rate above 80%. We will also conduct a process evaluation involving ICUs in the intervention arm to investigate their actual exposure to and experiences with the InFoQI program. DISCUSSION: The results of this study will inform those involved in providing ICU care on the feasibility of a tailored multifaceted performance feedback intervention and its ability to accelerate systematic and local quality improvement. Although our study will be conducted within the domain of intensive care, we believe our conclusions will be generalizable to other settings that have a quality registry including an indicator set available. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50542146
Use of genetically modified bacteria for drug delivery in humans: Revisiting the safety aspect
The use of live, genetically modified bacteria as delivery vehicles for biologics is of considerable interest scientifically and has attracted significant commercial investment. We have pioneered the use of the commensal gut bacterium Bacteroides ovatus for the oral delivery of therapeutics to the gastrointestinal tract. Here we report on our investigations of the biological safety of engineered B. ovatus bacteria that includes the use of thymineless death as a containment strategy and the potential for the spread of transgenes in vivo in the mammalian gastrointestinal tract. We demonstrate the ability of GM-strains of Bacteroides to survive thymine starvation and overcome it through the exchange of genetic material. We also provide evidence for horizontal gene transfer in the mammalian gastrointestinal tract resulting in transgene-carrying wild type bacteria. These findings sound a strong note of caution on the employment of live genetically modified bacteria for the delivery of biologics
Thin-section Computed Tomography findings before and after azithromycin treatment of neutrophilic reversible lung allograft dysfunction
Recently a novel subgroup of bronchiolitis obliterans syndrome (BOS) has been described in patients after lung transplantation with high neutrophil counts in broncho-alveolar lavage and recovery of lung functional decline with azithromycin treatment. We aimed to describe the thin-section computed tomography (CT) findings of these neutrophilic reversible allograft dysfunction (NRAD) patients before and after azithromycin.status: publishe
Options for early breast cancer follow-up in primary and secondary care : a systematic review
Background
Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer.
Method
A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions.
Results
Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival.
Conclusions
Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed
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