| 51. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 52. |
- Baldo, B., et al.
(author)
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SIRT1 is increased in affected brain regions and hypothalamic metabolic pathways are altered in Huntington disease
- 2019
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In: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 45:4, s. 361-379
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Journal article (peer-reviewed)abstract
- Aims: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. Methods: Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. Results: We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin-concentrating hormone (MCH) in the LHA and of brain-derived neurotrophic factor (BDNF) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT. Conclusions: We show that SIRT1 expression is increased in HD-affected brain regions and that metabolic pathways are altered in the HD hypothalamus.
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| 53. |
- Bykov, I., et al.
(author)
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Modification of adhered dust on plasma-facing surfaces due to exposure to ELMy H-mode plasma in DIII-D
- 2017
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In: NUCLEAR MATERIALS AND ENERGY. - : Elsevier BV. - 2352-1791. ; 12, s. 379-385
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Journal article (peer-reviewed)abstract
- Transient heat load tests have been conducted in the lower divertor of DIII-D using DiMES manipulator in order to study the behavior of dust on tungsten Plasma Facing Components (PFCs) during ELMy H-mode discharges. Samples with pre- adhered, pre- characterized dust have been exposed at the outer strike point (OSP) in a series of discharges with varied intra-(inter-) ELM heat fluxes. We used C dust because of its high sublimation temperature and non-metal properties. Al dust as a surrogate for Be and W dust were employed as relevant to that in the ITER divertor. The poor initial thermal contact between the substrate and the particles led to overheating, sublimation and shrinking of the carbon dust, and wetting induced coagulation of Al dust. Little modification of the W dust was observed. An enhanced surface adhesion and improvement of the thermal contact of C and Al dust were the result of exposure. A post mortem "adhesive tape" sampling showed that 70% of Al, <5% of W and C particles could not be removed from the surface owing to the improved adhesion. Al and C but not W particles that could be lifted had W inclusions indicating damage to the substrate. This suggests that non destructive methods may be inefficient for removal of dust in ITER.
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| 54. |
- Labbé, Catherine, et al.
(author)
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Role for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies.
- 2015
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In: Neurology. - 1526-632X. ; 85:19, s. 1680-1686
-
Journal article (peer-reviewed)abstract
- Objective:To assess the importance of MAPT variant p.A152T in the risk of synucleinopathies. Methods:In this case-control study, we screened a large global series of patients and controls, and assessed associations between p.A152T and disease risk. We included 3,229 patients with clinical Parkinson disease (PD), 442 with clinical dementia with Lewy bodies (DLB), 181 with multiple system atrophy (MSA), 832 with pathologically confirmed Lewy body disease (LBD), and 2,456 healthy controls. Results:The minor allele frequencies (MAF) in clinical PD cases (0.28%) and in controls (0.2%) were not found to be significantly different (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.63-2.98, p = 0.42). However, a significant association was observed with clinical DLB (MAF 0.68%, OR 5.76, 95% CI 1.62-20.51, p = 0.007) and LBD (MAF 0.42%, OR 3.55, 95% CI 1.04-12.17, p = 0.04). Additionally, p.A152T was more common in patients with MSA compared to controls (MAF 0.55%, OR 4.68, 95% CI 0.85-25.72, p = 0.08) but this was not statistically significant and therefore should be interpreted with caution. Conclusions:Overall, our findings suggest that MAPT p.A152T is a rare low penetrance variant likely associated with DLB that may be influenced by coexisting LBD and AD pathology. Given the rare nature of the variant, further studies with greater sample size are warranted and will help to fully explain the role of p.A152T in the pathogenesis of the synucleinopathies
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| 55. |
- Loeffen, Erik A. H., et al.
(author)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Journal article (peer-reviewed)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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| 56. |
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| 57. |
- McLean, A. P., et al.
(author)
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Rat choice in rapidly changing concurrent schedules
- 2018
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In: Journal of the Experimental Analysis of Behavior. - : Wiley. - 0022-5002. ; 109:2, s. 313-335
-
Journal article (peer-reviewed)abstract
- In two experiments, experimentally naïve rats were trained in concurrent variable-interval schedules in which the reinforcer ratios changed daily according to a pseudorandom binary sequence. In Experiment 1, relative response rates showed clear sensitivity to current-session reinforcer ratios, but not to previous sessions' reinforcer ratios. Within sessions, sensitivity to the current session's reinforcement rates increased steadily, and by session end, response ratios approached matching to the current-session reinforcer ratios. Across sessions, sensitivity to the current session's reinforcer ratio decreased with continued exposure to the pseudorandom binary sequence, contrary to expectations based on previous studies demonstrating learning sets. Using a second group of naïve rats, Experiment 2 replicated the main results from Experiment 1 and showed that although there were increases over sessions in both changeover rate and response rate during the changeover delay, neither could explain the accompanying reductions in sensitivity. We consider the role of reinforcement history, showing that our results can be simulated using two separate representations, one local and one nonlocal, but a more complex approach will be needed to bring together these results and other history effects such as learning sets and spontaneous recovery. © 2018 Society for the Experimental Analysis of Behavior
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| 58. |
- McLean, Angela R., et al.
(author)
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A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation
- 2017
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1862
-
Research review (peer-reviewed)abstract
- Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entree into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.
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