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Little evidence exists to support pharmacotherapeutic strategies for heart failure management in paediatrics. A recent Europe-wide survey suggests that this translates into substantial variability in clinical practice.
To conduct a formal discussion among an expert group of paediatric cardiology physicians on controversial aspects regarding the pharmacotherapy of children heart failure, facilitate consensus, and highlight areas of agreement and disagreement.
A two-round modified Delphi process was conducted between July and August 2015. Topics addressed were predominantly selected from the results of a previous Europe-wide survey. Fourteen statements were presented for discussion grouped under three categories; Angiotensin-converting-enzyme-inhibitors: Considerations for optimal dosage; Angiotensin-converting-enzyme-inhibitors for the management of CHDs; Neurohumoral antagonists for the management of dilated cardiomyopathy-related heart failure.
A total of 13 paediatricians dedicated to cardiology from across Europe and the United States of America completed the study; of them, 92% had a working experience in the field of more than 10 years and were working in a specific paediatric cardiology unit. Agreement on the acceptance/rejection of 11 statements was achieved. Results show agreement on the importance of a set of topics relevant to the standardisation of the therapy as well as consensus upon specific therapeutic attitudes.
We have found areas of common thinking and motivation, which can provide a means of triggering scientific collaboration. Our results might also contribute to disseminate available paediatric evidence and promote reducing unjustified variability in everyday practice. Until solid evidence is available, other research methods can contribute to advancing the goal of safe and effective paediatric heart failure pharmacotherapy.
Introduction: Alcohol use disorder (AUD) is a chronic relapsing and highly comorbid disease. Patients suffering from AUD are frequently seen in the emergency department (ED) presenting intoxicated or in withdrawal. Brief interactions in the ED are often the only portal of entry to the healthcare system for many of these patients. Oral naltrexone and long acting injectable naltrexone are effective treatment options for AUD associated with decreased cravings, shorter length of hospital stay, and lower cost of healthcare utilization. This study's objective was to perform a systematic review of the literature evaluating initiation of naltrexone in the ED. Methods: Electronic searches of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and CINAHL were conducted and reference lists were hand-searched. Randomized controlled trials (RCTs) comparing initiation of naltrexone in patients (≥18 years) to standard care in the ED were included. Two reviewers independently screened titles and abstracts, reviewed full text articles for inclusion, assessed quality of the studies, and extracted data. Results: The search strategy yielded 183 potentially relevant citations. After eliminating duplicate citations and studies that did not meet eligibility criteria, 10 articles were retrieved for full text review. There were no published RCTs that examined naltrexone initiation in the ED. There is one ongoing study being conducted in New York, which aims to assess naltrexone initiation in the ED and measure health outcomes and quality of life of study participants, as well as potential healthcare cost savings. Conclusion: The lack of published research in this area demonstrates a significant gap in knowledge. It is clear that well-designed RCTs are needed to evaluate the effectiveness of initiating naltrexone for those with AUD at the ED visit.
Introduction: There is increasing evidence to support the integration of simulation into medical training; however, no national emergency medicine (EM) simulation curriculum currently exists. Using Delphi methodology, we aimed to identify and establish content validity evidence for EM curricular content best suited for simulation-based training to inform national postgraduate EM training. Methods: A national panel of experts in EM simulation-related education iteratively rated potential curricular topics, on a 4-point scale, to determine those best suited for simulation-based training. After each round, responses were analyzed and topics scoring <2/4 were removed. Remaining topics were resent to the panel for further ratings until consensus was achieved, defined as Cronbach α ≥ 0.95. At conclusion of the Delphi process, topics that were rated ≥3.5/4 were considered core curricular topics, while those rated 3.0-3.5 were considered extended curricular topics. Results: Forty-four experts from 13 Canadian centres participated. Two hundred and eighty potential curricular topics, in 29 domains, were generated from a systematic review of the literature, analysis of relevant educational documents and a survey of Delphi panelists. Three rounds of Delphi surveys were completed before consensus was achieved, with response rates ranging from 93-100%. Twenty-eight topics, in 8 domains, reached consensus as core curricular topics. An additional 35 topics, in 14 domains, reached consensus as extended curricular topics. Conclusion: Delphi methodology allowed for achievement of expert consensus and content validation of EM curricular content best suited for simulation-based training. These results provide a foundation for improved integration of simulation into postgraduate EM training and can be used to inform a national simulation curriculum to supplement clinical training and optimize learning.
A total of eight ileal and caecal cannulated Yorkshire barrows were used to determine the interactions of dietary fibre (DF) and lipid types on apparent digestibility of DM and fatty acids (FA) and FA flows in gastrointestinal segments. Pigs were offered four diets that contained either pectin or cellulose with or without beef tallow or maize oil in two Youden square designs (n 6). Each period lasted 15 d. Faeces, ileal and caecal contents were collected to determine apparent ileal digestibility (AID), apparent caecal digestibility and apparent total tract digestibility (ATTD) of dietary components. The interactions between DF and lipid types influenced (P <0·05) the digestibility of DM and FA flows. The addition of maize oil decreased (P <0·05) AID of DM in pectin diets, and the addition of beef tallow depressed (P <0·001) ATTD of DM in cellulose diets. Dietary supplementation with beef tallow decreased (P <0·05) the AID of FA in pectin-containing diets but had no effects in cellulose-containing diets. Dietary supplementation with beef tallow increased (P <0·05) AID of SFA and PUFA and the flow of ileal oleic, vaccenic, linolenic and eicosadienoic acids and reduced the flow of faecal lauric, docosatetraenoic and docosapentaenoic acids in pectin- and cellulose-containing diets. In conclusion, the interaction between DF type and lipid saturation modulates digestibility of DM and lipids and FA flows but differs for soluble and insoluble fibre sources, SFA and unsaturated fatty acids and varies in different gastrointestinal segments.
Harvest weed seed control (HWSC) is an Australian innovation, developed to target high proportions of weed seed retained at crop maturity by many major weed species. There is the potential, however, that a reduction in the average height of retained seed is an adaptation to the long-term use of HWSC practices. With the aim of examining the distribution of rigid ryegrass (Lolium rigidum Gaudin) seed through crop canopies, a survey of Australian wheat (Triticum aestivum L.) fields was conducted at crop maturity. Nine sites with medium to long-term HWSC use were specifically included to examine the influence of HWSC use on seed retention height. During the 2013 wheat harvest, L. rigidum and wheat plant samples were collected at five heights downward through the crop canopy (40, 30, 20, 10, and 0 cm above ground level) in 71 wheat fields. Increased crop competition resulted in higher proportions of L. rigidum seed in the upper crop canopy (>40 cm). The increase in plant height is likely a shade-intolerance response of L. rigidum plants attempting to capture more light. This plant attribute creates the opportunity to use crop competition to improve HWSC efficacy by increasing the average height of seed retention. Crop competition can, therefore, have a double impact by reducing overall L. rigidum seed production and increasing seed retention height. Examining the distribution of wheat biomass and L. rigidum seed through the crop canopy, we determined that reducing harvest height for HWSC considerably increased the collection of L. rigidum seed (25%) but to a lesser extent wheat crop biomass (14%). Comparison of + and − HWSC use at nine locations found no evidence of adaptation to this form of weed control following 5 to 10 yr of use. Although the potential for resistance to HWSC remains, these results indicate that this will not readily occur in the field.
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
B. Sicardy, Observatoire de Paris and University Pierre et Marie Curie Paris, FRANCE,
M. El Moutamid, Cornell University Ithaca, New York, USA,
A. C. Quillen, University of Rochester Rochester, New York, USA,
P. M. Schenk, Lunar and Planetary Institute Houston, Texas, USA,
M. R. Showalter, SETI Institute Mountain View, California, USA,
K. Walsh, Southwest Research Institute Boulder, Colorado, USA
HESS J1614–518 and HESS J1616–508 are two tera-electron volt γ-ray sources that are not firmly associated with any known counterparts at other wavelengths. We investigate the distribution of interstellar medium towards the tera-electron volt γ-ray sources using results from a 7-mm-wavelength Mopra study, the Mopra Southern Galactic Plane CO Survey, the Millimetre Astronomer’s Legacy Team-45 GHz survey and [C i] data from the HEAT telescope. Data in the CO(1–0) transition lines reveal diffuse gas overlapping the two tera-electron volt sources at several velocities along the line of sight, while observations in the CS(1–0) transition line reveal several interesting dense gas features. To account for the diffuse atomic gas, archival H i data was taken from the Southern Galactic Plane Survey. The observations reveal gas components with masses ~103 to 105 M⊙ and with densities ~102 to 103 cm−3 overlapping the two tera-electron volt sources. Several origin scenarios potentially associated with the tera-electron volt γ-ray sources are discussed in light of the distribution of the local interstellar medium. We find no strong convincing evidence linking any counterpart with HESS J1614–518 or HESS J1616–508.
Most studies on digestion in the equine have been carried out with animals confined to stables with little or no exercise. An increased rate of digesta passage has been reported in exercised versus non exercise horses with an associated decrease in digestibility (Pagan et al., 1998). Microbial degradation makes an important contribution to diet digestibility in the equine. It is not clear however, if exercise has any effect on the composition and activity of the microbial population within hindgut which may impact on the digestion. The aim of this experiment was to assess the impact of exercise on microbial fermentation within the hindgut of the horse.
In Australia, widespread evolution of multi-resistant weed populations has driven the development and adoption of harvest weed seed control (HWSC). However, due to incompatibility of commonly used HWSC systems with highly productive conservation cropping systems, better HWSC systems are in demand. This study aimed to evaluate the efficacy of the integrated Harrington Seed Destructor (iHSD) mill on the seeds of Australia’s major crop weeds during wheat chaff processing. Also examined were the impacts of chaff type and moisture content on weed seed destruction efficacy. Initially, the iHSD mill speed of 3,000 rpm was identified as the most effective at destroying rigid ryegrass seeds present in wheat chaff. Subsequent testing determined that the iHSD mill was highly effective (>95% seed kill) on all Australian crop weeds examined. Rigid ryegrass seed kill was found to be highest for lupin chaff and lowest in barley, with wheat and canola chaff intermediate. Similarly, wheat chaff moisture reduced rigid ryegrass seed kill when moisture level exceeded 12%. The broad potential of the iHSD mill was evident, in that the reductions in efficacy due to wide-ranging differences in chaff type and moisture content were relatively small (≤10%). The results from these studies confirm the high efficacy and widespread suitability of the iHSD for use in Australian crop production systems. Additionally, as this system allows the conservation of all harvest residues, it is the best HWSC technique for conservation cropping systems.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
Over the period of modern satellite observations, Arctic sea-ice extent at the end of the melt season (September) has declined at a rate of >11% per decade, and there is evidence that the rate of decline has accelerated during the last decade. While climate models project further decreases in sea- ice mass and extent through the 21st century, the model ensemble mean trend over the period of instrumental records is smaller than observed. Possible reasons for the apparent discrepancy between observations and model simulations include observational uncertainties, vigorous unforced climate variability in the high latitudes, and limitations and shortcomings of the models stemming in particular from gaps in understanding physical process. The economic significance of a seasonally sea-ice-free future Arctic, the increased connectivity of a warmer Arctic with changes in global climate, and large uncertainties in magnitude and timing of these impacts make the problem of rapid sea-ice loss in the Arctic a grand challenge of climate science. Meaningful prediction/projection of the Arctic sea-ice conditions for the coming decades and beyond requires determining priorities for observations and model development, evaluation of the ability of climate models to reproduce the observed sea-ice behavior as a part of the broader climate system, improved attribution of the causes of Arctic sea-ice change, and improved understanding of the predictability of sea-ice conditions on seasonal through centennial timescales in the wider context of the polar climate predictability.
Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. Especially, saturated, hydrogen-rich molecules are formed through surface chemistry. Astrochemical models have developed over the decades to understand the molecular processes in the interstellar medium, taking into account grain surface chemistry. However, essential input information for gas-grain models, such as binding energies of molecules to the surface, have been derived experimentally only for a handful of species, leaving hundreds of species with highly uncertain estimates. Moreover, some fundamental processes are not well enough constrained to implement these into the models.
The proceedings gives three examples how computational chemistry techniques can help answer fundamental questions regarding grain surface chemistry.
Functional neurological disorders (FNDs), also known as conversion disorder, are unexplained neurological symptoms unrelated to a neurological cause. The disorder is common, yet poorly understood. The symptoms are experienced as involuntary but have similarities to voluntary processes. Here we studied intention awareness in FND.
A total of 26 FND patients and 25 healthy volunteers participated in this functional magnetic resonance study using Libet's clock.
FND is characterized by delayed awareness of the intention to move relative to the movement itself. The reporting of intention was more precise, suggesting that these findings are reliable and unrelated to non-specific attentional deficits. That these findings were more prominent with aberrant positive functional movement symptoms rather than negative symptoms may be relevant to impairments in timing for an inhibitory veto process. Attention towards intention relative to movement was associated with lower right inferior parietal cortex activity in FND, a region early in the processing of intention. During rest, aberrant functional connectivity was observed with the right inferior parietal cortex and other motor intention regions.
The results converge with observations of low inferior parietal activity comparing involuntary with voluntary movement in FND, emphasizing core deficiencies in intention. Heightened precision of this impaired intention is consistent with Bayesian theories of impaired top-down priors that might influence the sense of involuntariness. A primary impairment in voluntary motor intention at an early processing stage might explain clinical observations of slowed effortful voluntary movement, heightened self-directed attention and underlie functional movements. These findings further suggest novel therapeutic targets.
Open-water swimming is increasingly popular, often in water not considered safe for bathing. Limited evidence exists on the associated health risks. We investigated gastrointestinal illness in 1100 swimmers in a River Thames event in London, UK, to describe the outbreak and identify risk factors. We conducted a retrospective cohort study. Our case definition was swimmers with any: diarrhoea, vomiting, abdominal cramps lasting ⩾48 h, nausea lasting ⩾48 h, with onset within 9 days after the event. We used an online survey to collect information on symptoms, demographics, pre- and post-swim behaviours and open-water experience. We tested associations using robust Poisson regression. We followed up case microbiological results. Survey response was 61%, and attack rate 53% (338 cases). Median incubation period was 34 h and median symptom duration 4 days. Five cases had confirmed microbiological diagnoses (four Giardia, one Cryptosporidium). Wearing a wetsuit [adjusted relative risk (aRR) 6·96, 95% confidence interval (CI) 1·04–46·72] and swallowing water (aRR 1·42, 95% CI 1·03–1·97) were risk factors. Recent river-swimming (aRR 0·78, 95% CI 0·67–0·92) and age >40 years (aRR 0·83, 95% CI 0·70–0·98) were protective. Action to reduce risk of illness in future events is recommended, including clarification of oversight arrangements for future swims to ensure appropriate risk assessment and advice is provided.
It is postulated that knowledge of genotype may be more powerful than other types of personalised information in terms of motivating behaviour change. However, there is also a danger that disclosure of genetic risk may promote a fatalistic attitude and demotivate individuals. The original concept of personalised nutrition (PN) focused on genotype-based tailored dietary advice; however, PN can also be delivered based on assessment of dietary intake and phenotypic measures. Whilst dietitians currently provide PN advice based on diet and phenotype, genotype-based PN advice is not so readily available. The aim of this review is to examine the evidence for genotype-based personalised information on motivating behaviour change, and factors which may affect the impact of genotype-based personalised advice. Recent findings in PN will also be discussed, with respect to a large European study, Food4Me, which investigated the impact of varying levels of PN advice on motivating behaviour change. The researchers reported that PN advice resulted in greater dietary changes compared with general healthy eating advice, but no additional benefit was observed for PN advice based on phenotype and genotype information. Within Food4Me, work from our group revealed that knowledge of MTHFR genotype did not significantly improve intakes of dietary folate. In general, evidence is weak with regard to genotype-based PN advice. For future work, studies should test the impact of PN advice developed on a strong nutrigenetic evidence base, ensure an appropriate study design for the research question asked, and incorporate behaviour change techniques into the intervention.
Data from a rawinsonde network are used to provide aerological estimates of monthly precipitation minus evaporation (P – E) averaged over the region north of 70° N. Using published climatological estimates of E, area-averaged P is obtained for each month and year as a residual. Using surface temperatures from the rawinsonde network, the fraction of precipitation falling as snow is then estimated. Over the 1974–91 study period, precipitation and snowfall (water equivalent) have annual means of 26.6 and 19.0 cm. respectively. Assuming a representative aged snowpack density of 330 kg m−3 yields a total snow depth of 57.5 cm. The mean annual cycles of both variables display an autumn maximum, but because of the temperature dependency, nearly all precipitation falls as rain during July and August. Composite analyses reveal that increased precipitation for all seasons and increased snowfall for winter and autumn are favored by a “winter-type” circulation pattern, characterized by stronger troughs over the Atlantic and Eurasian sectors of the Arctic, associated with increased cyclonic activity over the Arctic peripheral seas.