Evaluación genética caprinos criollos : Informe n°9 (incluye nacimientos 2020)

Este informe tiene como objetivo principal presentar el mérito genético de los caprinos Criollos del Norte Neuquino (CNN) candidatos al próximo servicio del Campo Anexo Pilcaniyeu (CAP) de INTA EEA Bariloche. Con la información contenida en el informe, más la inspección visual de los animales, los responsables del programa de mejoramiento genético podrán decidir los apareamientos según el tipo de progenie deseada. PARÁMETROSProCaprino. Servicio Nacional de evaluación genéticaEstación Experimental Agropecuaria BarilocheFil: Giovannini, Nicolas. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Maurino, Maria Julia. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; Argentin

Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios

Background: In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. Methods: Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET (LETD), RBE-weighted dose (D-RBE) and biological range shift distributions. Results: In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on (alpha/beta)(x) and LET values. The SOBP study emphasizes the variation of LETD and RBE not only as a function of depth but also of lateral distance from the central beam axis. Application to clinical-like scenario shows consistent discrepancies from the values obtained for a constant RBE of 1.1, when using a variable RBE scheme for proton irradiation in tissues with low (alpha/beta)(x), regardless of the model. Biological range shifts of 0.6-2.4 mm (for high (alpha/beta)(x)) and 3.0 -5.4 mm (for low (alpha/beta)(x)) were found from the fall-off analysis of individual profiles of RBE-weighted fraction dose along the beam penetration depth. Conclusions: Although more experimental evidence is needed to validate the accuracy of the investigated models and their input parameters, their consistent trend suggests that their main RBE dependencies (dose, LET and (alpha/beta)(x)) should be included in treatment planning systems. In particular, our results suggest that simpler models based on the linear-quadratic formalism and LETD might already be sufficient to reproduce important RBE dependencies for re-evaluation of plans optimized with the current RBE = 1.1 approximation. This approach would be a first step forward to consider RBE variations in proton therapy, thus enabling a more robust choice of biological dose delivery. The latter could in turn impact clinical outcome, especially in terms of reduced toxicities for tumors adjacent to organs at risk

Using SNP arrays to leverage historic data sets for improved prediction accuracy and estimation of GxE of fruit maturity in sweet cherry (abstract)

Publishe

Core Outcome Set for IgE ‐mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study ‘ COMFA ’

Background: IgE‐mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. Methods: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two‐round online‐modified Delphi process followed by hybrid consensus meeting to finalize the COS. Results: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in‐person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, ‘allergic symptoms’ and ‘quality of life’ achieved consensus for inclusion as ‘core’ outcomes. Conclusion: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Pancreatic metastasis from osteosarcoma and Ewing sarcoma: literature review

International audienc

Editorial: Advances in diagnosing and treating new-onset refractory status epilepticus (NORSE).

info:eu-repo/semantics/publishe

Prediction of genetic value for sweet cherry fruit maturity among environments using a 6K SNP array

The timing of fruit maturity is an important trait in sweet cherry production and breeding. Phenotypic variation for phenology of fruit maturity in sweet cherry appears to be under strong genetic control, but that control might be complicated by phenotypic instability across environments. Although such genotype-by-environment interaction (G × E) is a common phenomenon in crop plants, knowledge about it is lacking for fruit maturity timing and other sweet cherry traits. In this study, 1673 genome-wide SNP markers were used to estimate genomic relationships among 597 weakly pedigree-connected individuals evaluated over two seasons at three locations in Europe and one location in the USA, thus sampling eight ‘environments’. The combined dataset enabled a single meta-analysis to investigate the environmental stability of genomic predictions. Linkage disequilibrium among marker loci declined rapidly with physical distance, and ordination of the relationship matrix suggested no strong structure among germplasm. The most parsimonious G × E model allowed heterogeneous genetic variance and pairwise covariances among environments. Narrow-sense genomic heritability was very high (0.60–0.83), as was accuracy of predicted breeding values (>0.62). Average correlation of additive effects among environments was high (0.96) and breeding values were highly correlated across locations. Results indicated that genomic models can be used in cherry to accurately predict date of fruit maturity for untested individuals in new environments. Limited G × E for this trait indicated that phenotypes of individuals will be stable across similar environments. Equivalent analyses for other sweet cherry traits, for which multiple years of data are commonly available among breeders and cultivar testers, would be informative for predicting performance of elite selections and cultivars in new environments