Susceptibility of Thymocytes for Infection by Chicken Anemia Virus is Related to Pre- and Posthatching Development

To investigate the age-dependent mechanism of susceptibility for chicken anemia virus (CAV) infection, we inoculated embryos and chickens of ages between day 9 of embryonic development and day 28 after hatching with CAV. Chicken embryos inoculated at days 9 and 11 of development showed no CAV-infected cells in the thymus, nor in other lymphoid organs. Many CAV-infected cells were detected in the thymic cortex of all chicken embryos inoculated at days 13 and 16 of development and of all chickens inoculated 1, 3, and 7 days after hatching. All embryos and chickens that contained CAV-infected cells in the thymus also contained CAV-infected cells in the bone marrow, but not in the bursa of Fabricius or the spleen. In chickens inoculated at days 14 and 21, only few CAV-infected cells were detected in the thymus, whereas these cells were not detected in thymi of 28-day-old inoculated chickens. Depletion of the thymic cortex was only detected in chickens inoculated from day 16 of embryonic development till day 21 after hatching. Only hematocrit values of the chickens inoculated 1 and 3 days after hatching were below normal. The rationale for the simultaneous susceptibility of cells of the T-cell lineage and cells of the erythrocyte lineage is discussed. As far as the thymus is concerned, the absence of clinical and microscopical signs of CAV infection in older chickens and the inability of CAV to infect embryos at days 9 and 11 of embryonic development may be caused by a lack of susceptible thymocytes. In view of the three waves of thymic precursor cells that populate the thymus during ontogeny, as described by Le Douarin and colleagues, we hypothesize that CAV only infects thymocytes derived from the second wave of precursor cells

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

DeepTract: A Probabilistic Deep Learning Framework for White Matter Fiber Tractography

We present DeepTract, a deep-learning framework for estimating white matter fibers orientation and streamline tractography. We adopt a data-driven approach for fiber reconstruction from diffusion weighted images (DWI), which does not assume a specific diffusion model. We use a recurrent neural network for mapping sequences of DWI values into probabilistic fiber orientation distributions. Based on these estimations, our model facilitates both deterministic and probabilistic streamline tractography. We quantitatively evaluate our method using the Tractometer tool, demonstrating competitive performance with state-of-the art classical and machine learning based tractography algorithms. We further present qualitative results of bundle-specific probabilistic tractography obtained using our method. The code is publicly available at: https://github.com/itaybenou/DeepTract.git

Pre-service teachers linking their metalinguistic knowledge to their practice: A functional approach

Existing work in Anglophone countries has raised concerns regarding teachers’ knowledge about language (KAL); this may well be an issue in other countries also, with notable exceptions such as Finland. In Australia, with the introduction of the new Australian Curriculum, the question of teacher KAL has become crucial. Teachers, both practising and pre-service, generally have some knowledge about language as an object, usually including the text structures of particular school genres and information about sentence structure and word classes. This knowledge may be based on traditional grammar and may not be well applied above the sentence level. Teachers may also have an intuitive knowledge of discourse structures and are beginning to reflect on their own discourse using understandings of dialogic teaching. This paper provides an example of how first-year pre-service teachers (PSTs) were introduced to KAL at both the grammatical and the discourse levels, as part of an introductory unit on spoken language. A range of approaches was used, including a functional view of discourse. The PSTs then applied their KAL by putting it into a context that was meaningful for them: discussing their own practice. The paper gives an illustration of some of the work they produced that demonstrates their emerging understandings

Mesures visant à freiner la hausse des coûts dans l’assurance obligatoire des soins : rapport du groupe d'experts

La santé est un des ingrédients fondamentaux du bien-être humain. On peut escompter que l’élévation du niveau de vie, la multiplication des maladies chroniques et le risque croissant de multimorbidité dû à l’évolution démographique entraînent une hausse des coûts de la santé imputable à plusieurs facteurs. Au total, ces coûts sont passés de 37,5 milliards de francs en 1996 à 77,8 milliards en 2015, tandis que ceux de l'AOS ont grimpé de 10,8 à 27,5 milliards de francs. Notons qu'au cours de cette période en question, l’importance économique a augmenté non seulement en termes absolus mais également rapporté au produit intérieur brut (PIB), indice qui mesure la performance économique d’un pays. Alors que les coûts globaux de la santé représentaient, en 1996, 9,2 % du PIB par année, ce pourcentage était supérieur à 12 en 2015. En comparaison avec la croissance démographique, les coûts des soins de santé ont également augmenté de façon disproportionnée: la progression des prestations nettes dans l’AOS est en effet de 4 % environ par assuré en moyenne, soit 3,5 % déduction faite de l’inflation. Certes, les bases de données ne sont pas parfaites, mais le faisceau d’indices pointant une tendance à l’accélération de la hausse des coûts est incontestable. Pour tenter de la freiner, une intervention politique s’impose de plus en plus, si bien que les mesures de nature à permettre au système de santé de rester financièrement viable sur la durée, tant pour les payeurs de primes que les pouvoirs publics, gagnent en importance. Les mesures envisagées dans le présent rapport visent en particulier à éviter que des prestations médicales inutiles et évitables soient fournies et, partant, à contribuer à freiner la hausse des coûts. (Contexte

Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside <i>DPYD</i>

Background: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G &gt; A/rs75017182, c.2846A &gt; T/rs67376798 and c.1679 T &gt; G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. The goal of this study was to identify additional genetic variants, both inside and outside DPYD, that may contribute to fluoropyrimidine toxicity. Methods: Biospecimens and data from the Alpe-DPD study were used. Exon sequencing was performed to identify risk variants inside DPYD. In silico and in vitro analyses were used to classify DPYD variants. A genome-wide association study (GWAS) with severe fluoropyrimidine-related toxicity was performed to identify variants outside DPYD. Association with severe toxicity was assessed using matched-pair analyses for the exon sequencing and logistic, Cox, and ordinal regression analyses for GWAS. Results: Twenty-four non-synonymous, frameshift, and splice site DPYD variants were detected in ten of 986 patients. Seven of these variants (c.1670C &gt; T, c.1913 T &gt; C, c.1925 T &gt; C, c.506delC, c.731A &gt; C, c.1740 + 1G &gt; T, c.763 − 2A &gt; G) were predicted to be deleterious. The carriers of either of these variants showed a trend towards a 2.14-fold (95% CI, 0.41–11.3, P = 0.388) increased risk of severe toxicity compared to matched controls (N = 30). After GWAS of 942 patients, no individual single nucleotide polymorphisms achieved genome-wide significance (P ≤ 5 × 10−8), however, five variants were suggestive of association (P &lt; 5 × 10−6) with severe toxicity. Conclusions: Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity.</p

Herbal supplements in the print media: communicating benefits and risks

Background The rise in use of food supplements based on botanical ingredients (herbal supplements) is depicted as part of a trend empowering consumers to manage their day-to-day health needs, which presupposes access to clear and accurate information to make effective choices. Evidence regarding herbal supplement efficacy is extremely variable so recent regulations eliminating unsubstantiated claims about potential effects leave producers able to provide very little information about their products. Medical practitioners are rarely educated about herbal supplements and most users learn about them via word-of-mouth, allowing dangerous misconceptions to thrive, chief among them the assumption that natural products are inherently safe. Print media is prolific among the information channels still able to freely discuss herbal supplements. Method This study thematically analyses how 76 newspaper/magazine articles from the UK, Romania and Italy portray the potential risks and benefits of herbal supplements. Results Most articles referenced both risks and benefits and were factually accurate but often lacked context and impartiality. More telling was how the risks and benefits were framed in service of a chosen narrative, the paucity of authoritative information allowing journalists leeway to recontextualise herbal supplements in ways that serviced the goals and values of their specific publications and readerships. Conclusion Providing sufficient information to empower consumers should not be the responsibility of print media, instead an accessible source of objective information is required.</p