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Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
The aim of this study was to identify good practice principles for health technology assessment (HTA) that are the most relevant and of highest priority for application in Latin America and to identify potential barriers to their implementation in the region.
HTA good practice principles proposed at the international level were identified and then explored during a deliberative process in a forum of assessors, funders, and product manufacturers.
Forty-two representatives from ten Latin American countries participated. Good practice principles proposed at the international level were considered valid and potentially relevant to Latin America. Five principles were identified as priority and with the greatest potential to be strengthened at this time: transparency in the production of HTA, involvement of relevant stakeholders in the HTA process, mechanisms to appeal decisions, clear priority-setting processes in HTA, and a clear link between HTA and decision making. The main challenge identified was to find a balance between the application of these principles and the available resources in a way that would not detract from the production of reports and adaptation to the needs of decision makers.
The main recommendation was to progress gradually in strengthening HTA and its link to decision making by developing appropriate processes for each country, without trying to impose, in the short-term, standards taken from examples at the international level without adequate adaptation of these to local contexts.
Introduction: Research supports the role of mentors in the personal development and career advancement of medical trainees. Compared to non-mentored peers, mentored residents are nearly twice as likely to describe excellent career preparation and demonstrate objective career success. In prior research, only 65% of training programs in Canada had a mentorship program, and 40% indicated a need for more formal mentorship models. Methods: A needs assessment survey was distributed to RCPSC Emergency Medicine (EM) Program Directors across Canada regarding mentorship available to resident physicians training at their centers. Additionally, all EM resident and staff physicians involved in mentorship were surveyed on their perceptions of current models at their institutions. Both surveys were comprised of binary, open ended, and 5 point likert scale questions. Responses were analyzed using Fisher’s exact test. Results: Eleven Program Directors responded to the survey. Formal mentorship programs were found in 82% of training centers, with 77% of programs instituted within the past 5 years. Half of resident/mentor pairings were based on a combination of identified career goals, participant personality traits, or resident request. Other pairing methods included perceived resident needs or attending physician request. Most meetings are face-to-face, with one program requiring mutual scheduled shifts. Residents identified that mentorship was significantly associated with benefits to career (p=0.0016) and niche (p=0.0019) development. Formal mentorship was felt to have a significant association with resident academic development (p=0.05) and lower rates of burnout (p=0.0018) by staff physicians. Staff mentors also associated a personal development benefit related to involvement in a mentorship relationship (p=0.0355). Conclusion: The majority of EM programs have adopted formal mentorship programs within the past 5 years. Residents and staff identify that mentorship relationships are associated with improved career and niche development as well as academic advancement. Future research will include a before and after study of the implementation of a formal mentorship program within the RCPSC-EM program at the University of Manitoba.
A participatory plant breeding (PPB) program involving the French farmers' association ‘Réseau Semences Paysannes’ and the French National Agricultural Research Institute (INRA) at Le Moulon was initiated in 2005. In the process of designing the breeding scheme, we evaluated the impact of farmer selection at an early stage (F2) on bread wheat cross progeny populations. The objectives were to characterize the effect of farmer selection, to evaluate the impact of farmer selection on intra-varietal diversity, to provide farmers with relevant information that they can use to improve their selection practices. Early selection was found efficient for some traits and for some of the 35 F2-derived F3 families. For traits of interest such as thousand kernel weight or grain weight per spike, when the response was significant, it was always positive. For most of the traits studied, the among-family genetic variance increased after selection while the average within-family genetic variance decreased. This study provides the first quantitative results for this PPB program and information that will help optimize it in the future.
The safety of the food supply is a subject of intense interest to consumers, particularly as a result of large-scale outbreaks that involve hundreds and sometimes thousands of consumers. During the last decade, this concern about food safety has expanded to include the diets of companion animals as a result of several incidences of chemical toxicities and infectious disease transmission. This has led to increased research into the causes and controls for these hazards for both companion animals and their owners. The following summary provides an introduction to the issues, challenges and new tools being developed to ensure that commercial pet foods are both nutritious and safe.
A new approach is developed, employing “in situ” electrical resistivity measurements, as a tool to study ion beam mixing of evaporated metal-metal multi or bilayers. The electrical resistivity variations measured continuously during the ion bombardment exhibit a monotonical increase and a tendency toward a saturation process allowing to detect precisely the total mixing of the film. The volume fraction of intermixed atoms can be determined within the framework of a simple conduction model. Experimental results are given in the case of Fe-Al and Al-Ag multilayers.
Evaporated bilayers and multilayers of Fe and Al have been studied during ion beam mixing with Xe ions using in-situ electrical resistivity measurements. Experiments have been performed in the composition range 40 – 58 at.% Al and at both temperatures 77 K and 300 K. A semi-empirical model is proposed to explain the observed kinetics. At low doses, a square root dependence of the mixed volume fraction on dose is found at 77 K but not at 300 K. The results are discussed by comparison with the different models proposed for ion beam mixing.
The effect of γ-ray and electron irradiation on the adhesion of gold films to PTFE has been ascertained. The film adhesion has been found to undergo a sharp increase at a γ-ray dose of 5 × 106 to 1 × 107 rads. Qualitative ‘Scotch tape’ tests also show an increase in adhesion when the films are irradiated with electrons (250 eV - 3 keV).
Examination of the interface region of very thin (∼ 20 Å) gold films on PTFE by X-ray photo-electron spectroscopy indicates the increase in adhesion results from radiolytic processes and consequent chemical interaction with the gold.
La mesure de la radioactivité atmosphérique constitue une difficulté métrologique majeure. En fonction des mécanismes de prélèvement sur filtre et des paramètres de mesure, l'activité alpha des aérosols est sous estimée. L’énergie cinétique des particules alpha est atténuée dans la matière qu’elles traversent, et une partie de cette énergie ne parvient plus au détecteur. Le rendement de mesure est alors dégradé et nécessite une correction. Pour répondre aux conditions de mesures usuelles, le laboratoire a développé un modèle empirique pour l'évaluation des corrections de l’activité alpha en fonction de la masse des aérosols déposés sur le filtre. Le modèle a été validé expérimentalement et a permis une meilleure estimation de l'incertitude sur la mesure de l'activité alpha des aérosols. L'étude a contribué à une première évaluation du facteur de correction pour des filtres peu encrassés provenant de la région parisienne : Fαlabo= 1,6 ± 0,5.
Plasma-assisted nitriding is an attractive surface treatment for
metallurgical surface modification to improve wear, hardness and fatigue
resistance of austenitic stainless steels. However, this technique requires
low temperature processing in order to avoid chromium nitride precipitation
and hence the degradation of corrosion properties. This paper presents a low
temperature high rate plasma nitriding process and will emphasis on the
consequences of nitrogen incorporation on the metallographic and
crystallographic properties of the sample surface.
The lectin-inhibitory sugars D-glucosamine (GlcN) and N-acetyl D-glucosamine (GlcNAc) are known to enhance susceptibility of the tsetse fly vector to infection with Trypanosoma brucei. GlcNAc also stimulates trypanosome growth in vitro in the absence of any factor derived from the fly. Here, we show that GlcNAc cannot be used as a direct energy source, nor is it internalized by trypanosomes. It does, however, inhibit glucose uptake by binding to the hexose transporter. Deprivation of D-glucose leads to a switch from a metabolism based predominantly on substrate level phosphorylation of D-glucose to a more efficient one based mainly on oxidative phosphorylation using L-proline. Procyclic form trypanosomes grow faster and to higher density in D-glucose-depleted medium than in D-glucose-rich medium. The ability of trypanosomes to use L-proline as an energy source can be regulated depending upon the availability of D-glucose and here we show that this regulation is a graded response to D-glucose availability and determined by the overall metabolic state of the cell. It appears, therefore, that the growth stimulatory effect of GlcNAc in vitro relates to the switch from D-glucose to L-proline metabolism. In tsetse flies, however, it seems probable that the effect of GlcNAc is independent of this switch as pre-adaptation to growth in proline had no effect on tsetse infection rate.
Growth, tolerance and zinc and cadmium hyperaccumulation of Thlaspi caerulescens populations from three metal
contaminated soils and three normal soils were compared under controlled conditions. Individuals of six
populations were cultivated on five soils with increasing concentrations of zinc (50–25000 μg g−1) and cadmium
(1–170 μg g−1). There was no mortality of normal soil populations in the four metal-contaminated soils, but plant
growth was reduced to half that of populations from metal-contaminated soils. However, in noncontaminated soil,
the growth of individuals from normal soils was greater than that of individuals from metal-contaminated soils.
Individuals from normal soils concentrated three times more zinc in the aboveground biomass than those from
metal-contaminated soils, but the latter accumulated twice as much cadmium. We conclude that populations of
T. caerulescens from both normal and metal-contaminated soils are interesting material for phytoextraction of zinc
and cadmium, but to optimize the process of phytoextraction it is necessary to combine the extraction potentials
of both type of populations.
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