The European Commission has recognized the need for more stringent action to manage biological invasions and has committed to develop a dedicated legislative instrument. Under this upcoming ...legislation, European countries and their relevant institutions will have additional obligations and commitments in respect to invasive alien species. In September 2012, the European Commission’s Joint Research Centre (JRC) launched the European Alien Species Information Network (EASIN) to facilitate the exploration of existing alien species information from distributed sources and to assist the implementation of European policies on biological invasions. Subsequent to the launching of EASIN, there was an evident need to define its niche within a complex environment of global, European, regional and national information systems. Herein we propose an organizational chart clearly defining the role of each actor in this framework, and we emphasize the need for collaboration in order to effectively support EU policies.
Background
Huntington’s Disease (HD) is a hereditary neurodegenerative disorder which affects individuals’ ability to walk, talk, think, and reason. Onset is usually in the forties, there are no ...therapies currently available that alter disease course, and life expectancy is 10–20 years from diagnosis. The gene causing HD is fully penetrant, with a 50% probability of passing the disease to offspring. Although the impacts of HD are substantial, there has been little report of the quality of life of people with the condition in a manner that can be used in economic evaluations of treatments for HD. Health state utility values (HSUVs), used to calculate quality-adjusted life-years (QALYs), are the metric commonly used to inform such healthcare policy decision-making.
Objectives
The aim was to report HSUVs for HD, with specific objectives to use European data to: (i) describe HSUVs by demographic and clinical characteristics; (ii) compare HSUVs of people with HD in the UK with population norms; (iii) identify the relative strength of demographic and clinical characteristics in predicting HSUVs.
Methods
European Huntington’s Disease Network REGISTRY study data were used for analysis. This is a multi-centre, multi-national, observational, longitudinal study, which collects six-monthly demographic, clinical, and patient-reported outcome measures, including the SF-36. SF-36 scores were converted to SF-6D HSUVs and described by demographic and clinical characteristics. HSUVs from people with HD in the UK were compared with population norms. Regression analysis was used to estimate the relative strength of age, gender, time since diagnosis, and disease severity (according to the Total Function Capacity (TFC) score, and the UHDRS’s Motor score, Behavioural score, and Cognition score) in predicting HSUVs.
Results
11,328 questionnaires were completed by 5560 respondents with HD in 12 European countries. Women generally had lower HSUVs than men, and HSUVs were consistently lower than population norms for those with HD in the UK, and dropped with increasing disease severity. The regression model significantly accounted for the variance in SF-6D scores (
n
= 1939;
F
7,1931 = 120.05;
p
< 0.001; adjusted R-squared 0.3007), with TFC score, Behavioural score, and male gender significant predictors of SF-6D values (
p
< 0.001).
Conclusion
To our knowledge, this is the first report of HSUVs for HD for countries other than the UK, and the first report of SF-6D HSUVs described for 12 European countries, according to demographic and clinical factors. Our analyses provide new insights into the relationships between HD disease characteristics and assessment of health-related quality of life in a form that can be used in policy-relevant economic evaluations.
Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor ...onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.
Engineering resistance genes to gain effector recognition is emerging as an important step in attaining broad, durable resistance. We engineered potato resistance gene R3a to gain recognition of the ...virulent AVR3aEM effector form of Phytophthora infestans. Random mutagenesis, gene shuffling and site-directed mutagenesis of R3a were conducted to produce R3a* variants with gain of recognition towards AVR3aEM. Programmed cell death following gain of recognition was enhanced in iterative rounds of artificial evolution and neared levels observed for recognition of AVR3aKI by R3a. We demonstrated that R3a*-mediated recognition responses, like for R3a, are dependent on SGT1 and HSP90. In addition, this gain of response is associated with re-localisation of R3a* variants from the cytoplasm to late endosomes when co-expressed with either AVR3aKI or AVR3aEM a mechanism that was previously only seen for R3a upon co-infiltration with AVR3aKI. Similarly, AVR3aEM specifically re-localised to the same vesicles upon recognition by R3a* variants, but not with R3a. R3a and R3a* provide resistance to P. infestans isolates expressing AVR3aKI but not those homozygous for AVR3aEM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the ...first clinicopathological study of a patient with HD in receipt of cell‐suspension striatal allografts who took part in the NEST‐UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade post‐transplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site. Ann Neurol 2018;84:950–956
Structural changes of thin MgAl films during hydrogen desorption Fritzsche, Helmut; Saoudi, Mouna; Haagsma, Julian ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2009, Letnik:
600, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We used neutron reflectometry (NR) to study the structural changes of thin Pd-capped Mg
0.7Al
0.3 and Mg
0.6Al
0.4 alloy films after hydrogen absorption and during hydrogen desorption. NR enabled us ...to determine the hydrogen content and hydrogen distribution in these thin MgAl alloy films along with the structural changes associated with the desorption process. The thin films expand by about 20% during the hydrogen absorption and the hydrogen is stored only in the MgAl layer with no hydrogen content in the Pd layer. The Mg
0.7Al
0.3 films are fully desorbed at 448
K, whereas for the Mg
0.6Al
0.4 films a temperature of 473
K is needed to fully desorb the hydrogen. Our NR measurements show that the higher annealing temperature needed to desorb the hydrogen from the Mg
0.6Al
0.4 films led to an interdiffusion of the Pd layer into the MgAl layer. This Pd interdiffusion was also observed in a Mg
0.7Al
0.3 film after a 9
h annealing at 473
K. So, the Pd interdiffusion into a MgAl film that has been charged with hydrogen is a common feature of the Pd/Mg
0.7Al
0.3 and Pd/Mg
0.6Al
0.4 alloy system. In contrast, for the as-prepared hydrogen-free Pd/Mg
0.7Al
0.3 film the Pd layer stays intact and only a small interdiffusion zone occurs at the Pd/MgAl interface.
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