Letteratura scientifica selezionata sul tema "HR-TKD"

Heart Rate Responses and Training Load During Nonspecific and Specific Aerobic Training in Adolescent Taekwondo AthletesThe efficacy of replacing generic running with Taekwondo (TKD) specific technical skills during interval training at an intensity corresponding to 90-95% of maximum heart rate (HRmax) has not yet been demonstrated. Therefore, the purpose of this study was to compare the HR responses and perceived exertion between controlled running and high-intensity TKD technical interval training in adolescent TKD athletes. Eighteen adolescent, male TKD athletes performed short-duration interval running and TKD specific technical skills (i.e. 10-20 [10-s of exercise interspersed with 20 s of passive recovery]) in a counterbalanced design. In both training methods, HR was measured and expressed as the percentage of HR reserve (%HRres). Rating of perceived exertion (RPE, Borg's category rating-10 scale), Banister's training impulse (TRIMP) and Edwards' training load (TL) were used to quantify the internal training load. Recorded cardiovascular responses expressed in %HRresin the two training methods were not significantly different (p > 0.05). Furthermore, the two training methods induced similar training loads as calculated by Banister and Edwards' methods. Perceived exertion ranged between "hard" and "very hard" during all interval training sessions. These findings showed that performing repeated TKD specific skills increased HR to the same level, and were perceived as producing the same training intensity as did short-duration interval running in adolescent TKD athletes. Therefore, using specific TKD kicking exercises in high-intensity interval training can be applied to bring more variety during training, mixing physical and technical aspects of the sport, while reaching the same intensity as interval running.

Purpose:The session rating of perceived exertion (RPE) is a practical and non-invasive method that allows a quantification of the internal training load (TL) in individual and team sports, but no study has investigated its construct validity in martial arts. Therefore, the purpose of this study was to examine the convergent validity between the session-RPE method and two objective HR-based methods for quantifying the similar TL during a high-TL camp in young Taekwondo (TKD) athletes.Methods:Ten young TKD athletes (mean ± SD: age, 13.1 ± 2.4 y; body mass, 46.1 ± 12.7 kg; height, 1.53 ± 0.15 m; maximum heart rate (HRmax), 201.0 ± 8.2 bpm) participated in this study. During the training period, subjects performed 35 TKD training sessions, including two formal competitions during which RPE and HR were recorded and analyzed (308 individual training sessions). Correlation analysis was used to evaluate the convergent validity between session-RPE method and the two commonly used HR-based methods for assessing TL in a variety of training modes.Results:Significant relationships were found between individual session-RPE and all the HR-based TLs (r values from 0.55 to 0.90; P < .001). Significant correlations were observed in all mode of exercises practiced in TKD.Conclusions:This study shows that session-RPE can be considered as a valid method to assess TL in TKD.

Introduction: Next-generation sequencing (NGS) represents a promising modality for measurable residual disease (MRD) testing in patients with acute myeloid leukemia (AML), but systematic efforts are required to define the appropriate targets, test characteristics, and clinical implications. We recently reported that detection of persistent NPM1 or FLT3 internal tandem duplication (ITD) mutations in adults with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplantation (alloHCT) is associated with increased relapse and death compared with those testing negative (JAMA 2023, PMID: 36881031). FLT3 tyrosine kinase domain (TKD) variants are present in 7-10% of adult patients with AML but the utility of this target for AML MRD testing in CR1 prior to alloHCT was previously unknown. Methods: Patients aged 18 or older who underwent alloHCT for AML in CR1 between 2013 and 2019 reported to have a FLT3-TKD variant at diagnosis and a pre-conditioning remission blood sample available in the CIBMTR biorepository were eligible for this study. Single-amplicon NGS (SA-NGS) library generation utilizing UMI-tagged primers targeting the D835 and I836 codons of FLT3 was performed on 400ng genomic DNA sequenced with unique dual indices, with error-corrected variant calling. Primary outcomes were overall survival (OS) and cumulative incidence of relapse (CIR). Secondary outcomes were relapse-free survival (RFS) and non-relapse mortality (NRM), with NRM being considered as a competing risk. Results: A total of351 patients met inclusion criteria for this study, and 342 (97.4%) had sufficient DNA for SA-NGS and were analyzed for clinical outcomes. Of these patients, 81 (23.7%) experienced relapse at a median of 5 months post-alloHCT. Using the current ELN-recommended variant allele fraction (VAF) threshold of 0.1% for NGS-based AML MRD, 14 patients (4.1%) tested positive. Patients with FLT3-TKD MRD VAF≥0.1% experienced higher rates of relapse (73.8% vs. 20.5%, p &lt; 0.0001) and decreased OS (11.4% vs. 66.8%, p &lt; 0.001) compared to VAF&lt;0.1%. The highly sensitive SA-NGS method allowed for exploration to determine if a deeper VAF threshold of 0.01% (previously validated for NPM1 and FLT3-ITD in the Pre-MEASURE study) was prognostic for FLT3-TKD as an MRD target. This led to an additional 20 patients being reclassified as positive (n = 34 with VAF above 0.01%, =9.9%). However, there was no significant difference in CIR (33.6% vs. 19.7%, p = 0.089) or OS (65.2% vs. 66.9%, p = 0.267) between patients with 0.01%≤VAF&lt;0.1% and VAF&lt;0.01% ( Figure). Out of 28 SA-NGS positive calls, 6 could not be validated by orthogonal digital droplet PCR testing, and interestingly, none of those 6 patients experienced relapse. Site-reported pre-transplant remission multiparametric flow cytometry (MFC) was available for 335 patients (98%). Results of MFC were not associated with differences in CIR (HR 1.2, 95% CI 0.52 - 2.76, p = 0.67) or OS (HR 0.78, 95% CI 0.34 - 1.77, p = 0.551).In multivariable analysis, FLT3-TKD NGS-MRD VAF≥0.1% remained prognostic for CIR (HR 6.1, 95% CI 3.1 - 12.0, p &lt; 0.001) and OS (HR 3.2, 95% CI 1.7 - 5.9, p &lt; 0.001). Conclusions: Detectable persistence of FLT3-TKD variants in blood from AML patients in first remission prior to first alloHCT is rare, but at a VAF level of 0.1% was strongly associated with increased relapse and death after transplant compared to those testing negative. In contrast to FLT3-ITD NGS-MRD, no evidence was found to support lowering the NGS-MRD VAF threshold from 0.1% to 0.01% for FLT3-TKD. Alternative methodology may further improve NGS-MRD test performance. Site-reported MFC prior to alloHCT did not stratify for post-transplant relapse or survival. Optimal NGS-MRD testing for patients with AML will likely require a multi-target approach and testing for persistence of FLT3-TKD MRD is shown here to represent an important component of this strategy.

Abstract Inversion or translocation of chromosome 16 inv(16)/t(16;16) [hereafter abbreviated inv(16)] represent common cytogenetic abnormalities in adult acute myeloid leukemia (AML). At the molecular level inv(16) result in the generation of the CBFb-MYH11 fusion protein that is known to interfere with the heterodimeric transcription factor RUNX1/CBFb and thereby contributes to impaired differentiation of hematopoietic cells. Patients (pts.) with inv(16) are considered to have a favorable outcome, in particular when treated with cytarabine-based consolidation regimens. However, a significant proportion of these pts. relapse and survival after 5 years is about 60%. These findings together with studies from murine models suggest that additional genetic lesions are underlying the clinical heterogeneity of inv(16)-positive AML. The recently described mutations in the signaling molecules FLT3, KIT and RAS represent potential secondary genetic lesions that might contribute to leukemic transformation through constitutive activation. In this study we determined the incidence of KIT (exons 8, 10, 11, and 17), FLT3 (ITD; TKD at D835/I836,) and RAS (NRAS/KRAS exon1, exon2) mutations in 94 adult AML pts. (16 to 60 years; median age 41 years) with inv(16) and evaluated their prognostic impact on clinical outcome. KIT and RAS mutation screening was performed using a sensitive DHPLC-based assay; samples with abnormal profile were confirmed by direct sequencing. FLT3 mutations were identified as previously described. Pts. were entered on 3 AMLSG treatment trials [AML HD93, AML HD98A, AMLSG 07–04]. Postremission therapy implied cytarabine-based (HiDAC n=57) regimens as well as autologous (n=23) or allogeneic (n=13) stem cell transplantation (SCT) in first CR. Mutations were identified in 84% of inv(16) AML with highest frequencies in NRAS (47%) followed by KIT (26%) and FLT3-TKD (15%); 10/24 KIT mutations affected exon17. KRAS and FLT3-ITD mutations were detected in 10% and 3%, respectively. Complete remission (CR) rate was 90% for the whole group. In univariable analyses, FLT3-TKD mutations were associated with a significant inferior relapse-free survival (RFS) (p=0.01). For the other mutations there was no significant difference in RFS when comparing mutated and unmutated pts. Multivariable analysis adjusted for postremission therapy revealed FLT3-TKD (HR 2.39, p=0.04) and in trend KIT exon17 mutations (HR 2.8, p=0.06) as adverse prognostic factors. Therefore, an explorative subgroup analysis was performed for KIT exon17 mutations for the different postremission strategies. In pts. treated with HiDAC, KIT exon17 mutations were associated with a significant inferior RFS (p<0.0001), in contrast to pts. receiving SCT (p=0.70). For overall survival (OS) none of the tested variables were significantly associated with prognosis. KIT, FLT3, or RAS gene mutations can be detected in 84% of inv(16)-positive AML further sustaining the model of cooperating gene mutations. Although the numbers are still quite small, FLT3-TKD and KIT exon17 mutations are of prognostic relevance; the prognostic impact of KIT exon17 mutations seems to be abrogated by SCT strategies. Thus, KIT and FLT3 mutation status might reach clinical importance with regard to the availability of specific inhibitors and the type of postremission therapy.

Abstract In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-/KRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT (37%) and FLT3 (17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04], log10(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).

Abstract Abstract 1616 Poster Board I-642 CD74 is a type II integral membrane protein receptor that binds its ligand MIF to induce phosphorylation of the extracellular signal-regulated kinase-1/2 (ERK-1/2) and drive cellular proliferation via nuclear factor-kappa B (NF-kB) activation. CD74 expression has been identified in human solid tumors, and its expression is associated with adverse prognosis in advanced pancreatic cancer. As CD74 is expressed and NF-kB constitutively activated in myeloblasts, we hypothesized that CD74 expression might also be associated with adverse outcome in AML. To investigate the prognostic impact of CD74 expression in the context of other predictive molecular markers in CN-AML, we assessed CD74 expression levels by Affymetrix HG-U133 Plus 2.0 microarray in 102 younger [<60 years (y)] adults with primary CN-AML, treated on the front-line CALGB 19808 trial with an induction regimen containing daunorubicin, cytarabine, etoposide and, in some cases, the inhibitor of multidrug resistance valspodar, and consolidation with autologous stem cell transplantation. Microarray data were analyzed using the Robust Multichip Average method, making use of a GeneAnnot chip definition file, which resulted in a single probe-set measurement for CD74. At diagnosis, CD74 expression, when assessed as a continuous variable, was significantly associated only with extramedullary disease involvement (P=.006) among clinical features, and with none of the molecular prognostic variables tested, including NPM1, WT1, CEBPA, FLT3 (FLT3-ITD and FLT3-TKD) mutations, MLL partial tandem duplication, or differential BAALC and ERG expression levels. Although CD74 expression levels were not associated with achievement of complete remission (CR; 83% vs 81%), higher levels of CD74 were associated with shorter disease-free survival [DFS; P=.046, hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.12-3.08] and with shorter overall survival (OS; P=.02, HR 1.32, CI 1.04-1.67). In multivariable analyses, higher CD74 expression was independently associated with shorter DFS (P=.045, HR 1.98, CI 1.16-3.40), after adjusting for WT1 mutations (P<.001) and FLT3-TKD (P=.04), and shorter OS (P=.01, HR 1.58, CI 1.11-2.25) after adjusting for FLT3-TKD (P=.02), WT1 mutations (P=.007), BAALC expression levels (P=.02), white blood counts (P=.007), and extramedullary involvement (P=.04). As quartiles 2-4 had similar expression levels distinct from the lowest quartile, to display the impact of CD74 expression levels on clinical outcome only, pts were dichotomized into low (the lowest quartile) and high (the top three quartiles) CD74 expressers. The Kaplan-Meier curves for DFS and OS (Figures 1 and 2) are shown below. In conclusion, our study identifies elevated CD74 expression as associated with adverse prognosis in younger CN-AML pts. Since we previously reported that higher CD74 expression was favorably associated with achievement of CR in AML patients receiving chemotherapy plus bortezomib, an inhibitor of the proteasome and NF-kB (Attar et al., Clin Cancer Res, 2008;14:1446-54), it is possible that in future studies elevated CD74 levels can be used not only for prognostication, but also to stratify CN-AML pts to study of bortezomib-containing chemotherapy regimens. Figure 1 Disease free survival Figure 1. Disease free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 411 The herald of next generation sequencing has ushered an era for the discovery of frequent novel mutations such as DNMT3a, IDH1/2 and ASXL1 in acute myeloid leukaemia with a normal karyotype (AML-NK). The frequency of these mutations has been extensively documented; however, there is inconclusive evidence for their prognostic significance. Furthermore, whilst having a ‘normal' cytogenetic karyotype, AML-NK has been characterized by SNP-A karyotyping revealing multiple cryptic genomic aberrations. To predict prognosis, mutations of FLT3, NPM1 and CEBPA as well as gene expression profiles have been used as biomarkers. Using 454 next generation sequencing (NGS), we sought to determine the prognostic significance of mutations in ASXL1, DNMT3a, FLT3, IDH1/2, NPM1 and TP53 as well as detect cryptic genomic aberrations using 250K SNP microarrays in 92 AML-NK patients (pts) uniformly treated from the UK MRC/NCRI AML clinical trials, excluding pts with induction deaths. We demonstrate the presence of 54 cryptic genomic aberrations in 37 pts consisting of 11 deletions (del) (8 pts), 10 gains (10 pts) and 33 regions of UPD (29 pts). Aberrations were excluded as CNV's if there was >50% overlap with variants from the DGV and an internal cohort of 91 healthy subjects. The median size of del was 1.6Mb(0.18Mb-3.4Mb) with chromosome (chr) 4(q24) and 17(q11.2 and q22.1) deleted in two pts. One pt had micro del on chr12p13.2-p12.3 and 21q22.11-q22.12 affecting the ETV6 and AML1 genes, respectively, that was confirmed by FISH. Gains (median 0.37Mb(0.26–0.71Mb)) were identified on chr8 (4 pts). The median size of UPD's was 83.3Mb(20.5Mb-158Mb) with interstitial UPD <20Mb excluded from the analysis. Chromosome 13 (q12.11-q34) and 6(p25.3-p22.1) were the most frequently affected with UPD observed in 15 and 5 pts, respectively. Of the 15 pts with UPD of chr13, 11 pts had this occurrence in small clones. Additional regions affected by UPD included chromosomes 1, 2, 4, 5, 7 and 11. NPM1, DNMT3a, FLT3-ITD, IDH2, FLT3-TKD, IDH1, TP53 and ASXL1 mutations occurred in 64%, 49%, 22%, 5%, 3%, 2% and 1% of patients, respectively with 13 cases having no detectable mutations. The R882 mutation hotspot of DNMT3a occurred in 33/45 cases with clone size ranging from 34–65% and occurred concurrently with mutations in NPM1 (31 pts), FLT3-ITD/TKD (30 pts) and IDH2 (9 pts). IDH1 (R130H) and IDH2 (R140Q and R172K) mutations were mutually exclusive and occurred in 23 pts, with 4 pts having concurrent FLT3, NPM1 and DNMT3a mutations. Only 1 patient had an ASXL1 mutation with a concurrent IDH2 mutation and 2 cases had mutation of TP53. FLT3-TKD/ITD mutations were exclusive of each other. Not all pts with FLT3-ITD mutation had UPD of chromosome 13. There was no correlation between genomic aberrations and mutations of any other assayed genes. The median duration of follow-up from time of diagnosis of the study group was 44 months (range 2–160). There were no significant correlations between the presence of genomic aberrations and age, sex, WBC, secondary disease or mutations in IDH1/2, FLT3-ITD or DNMT3a. Patients with FLT3-TKD were likely to have gains (2/5) compared to those with wild type (8/85, p=0.04). Patients with genomic aberrations had worse overall survival (OS) compared to pts without aberrations, (5 year OS 12% vs 40%, hazard ratio (HR) adjusted for other prognostic variables 2.56 (1.43–4.60), p=0.001); this was also seen when considering UPD on OS ((8% for those with UPD compared to 37% for those without UPD (adjusted HR 2.52(1.40–4.54) p=0.002) and cumulative incidence of relapse (CIR) (78% in pts with UPD compared to 54% for those without UPD (adjusted HR 4.04(1.84–8.90) p=0.0003). Adjusted analysis showed a dose effect for the number of UPD's on OS (p=0.007) and relapse (p=0.001). In a model building analysis, adjusted for age, WBC, sex, secondary disease, performance status and mutations of IDH1, IDH2, FLT3-ITD/TKD, DNMT3a and NPM1, only UPD proved independently prognostic for relapse and survival. We conclude that cryptic genomic aberrations in uniformly treated AML-NK pts provide better prognostic value and outcome prediction than metaphase cytogenetics and mutation detection, thereby, helping to identify patient groups with poor prognosis and requiring specific therapeutic strategies. Disclosures: No relevant conflicts of interest to declare.

La compréhension des mécanismes de déformation dans les matériaux cristallins passe par la caractérisation fine des microstructures. Dans le cadre de la microscopie électronique à balayage, la mesure précise des gradients d’orientation et des déformations élastiques du cristal est l’objectif des méthodes dites à haute résolution angulaire. Pour cela, elles emploient des techniques de corrélation d’images numériques afin de recaler les clichés de diffraction électronique. Cette thèse propose une méthode de recalage originale. Le champ de déplacement à l’échelle du scintillateur est décrit par une homographie linéaire. Il s’agit d’une transformation géométrique largement utilisée en vision par ordinateur pour modéliser les projections. L’homographie entre deux clichés est mesurée à partir d’une grande et unique région d’intérêt en utilisant un algorithme de Gauss-Newton par composition inverse numériquement efficace. Une correction des distorsions optiques causées par les lentilles de la caméra lui est intégrée et sa convergence est assurée par un pré-recalage des clichés. Ce dernier repose sur des algorithmes de corrélation croisée globale basés sur les transformées de Fourier-Mellin et de Fourier. Il permet de rendre compte des rotations allant jusqu’à une dizaine de degrés avec une précision comprise typiquement entre 0,1 et 0,5°. La détermination de l’homographie est indépendante de la géométrie de projection. Cette dernière n’est considérée qu’à l’issue du recalage pour déduire analytiquement les rotations et les déformations élastiques. La méthode est validée numériquement sur des clichés simulés distordus optiquement, désorientés jusqu’à 14° et présentant des déformations élastiques équivalentes jusqu’à 5×10⁻². Cette étude montre que la mesure précise de déformations élastiques comprises entre 1×10⁻⁴ et 2×10⁻³ nécessite de corriger la distorsion optique radiale, même lorsque la désorientation est faible. Finalement, la méthode est appliquée à des clichés acquis par diffraction des électrons rétrodiffusés (EBSD) et en transmission en utilisant la nouvelle configuration TKD on-axis (transmission Kikuchi diffraction). Des métaux polycristallins déformés plastiquement ainsi que des semi-conducteurs sont caractérisés. La méthode retranscrit des détails fins de la microstructure d’un acier martensitique trempé et revenu et d’un acier sans interstitiels déformé de 15% en traction, malgré la détérioration du contraste de diffraction induit par la déformation plastique. Les structures de déformation sont également analysées dans de l’aluminium nanostructuré obtenu par déformation plastique sévère grâce au couplage de la méthode de recalage et de la configuration TKD on-axis. Ce couplage permet d’atteindre simultanément une haute résolution spatiale (3 à 10 nm) et une haute résolution angulaire (0,01 à 0,05°). Des cartes de déformation élastiques sont obtenues à l’échelle de quelques nanomètres dans une lame mince de SiGe et les densités de dislocations dans un monocristal de GaN sont déterminées avec une résolution voisine de 2,5×10⁻³ µm⁻¹ (soit 8×10¹² m⁻²)
Understanding the deformation mechanisms in crystalline materials requires a fine characterization of microstructures. The precise measurement of lattice rotations and elastic strains in the scanning electron microscope is the aim of the so-called high-angular resolution methods. For this purpose, digital image correlation techniques are used in order to register electron diffraction patterns. In this thesis, an original registration approach is proposed. The displacement field across the whole scintillator is modelled by a linear homography. Such a shape function is often met is the field of computer vision to describe projective transformations. The homography between two patterns is measured from a single and large region of interest using a numerically efficient inverse-compositional Gauss-Newton algorithm. It integrates a correction of optical distortions caused by camera lenses and its convergence is ensured by a pre-alignment step of the patterns. The latter relies on global cross-correlation algorithms based on Fourier-Mellin and Fourier transforms. It fairly accounts for rotations up to approximately ten degrees with an accuracy typically between 0.1 and 0.5°. The homography is measured independently from the projection geometry, which is only considered afterwards to analytically deduce the rotations and elastic strains. The proposed method is validated numerically from simulated and optically distorted patterns showing disorientations up to 14° in the presence of elastic strains up to 5×10⁻². The accurate measurement of elastic strains between 1×10⁻⁴ and 2×10⁻³ requires a correction of radial distortion effects, even when the disorientation angle is small. Finally, the method is applied to patterns acquired by means of electron backscatter diffraction (EBSD) and in transmission using the new on-axis transmission Kikuchi diffraction (TKD) configuration. Plastically deformed polycrystalline metals as well as semiconductors are characterized. The method highlights fine details of the microstructure of a quenched and tempered martensitic steel and of an interstitial free steel deformed by 15% in tension, although plastic deformation deteriorates the diffraction contrast. The deformation structures in a nanostructured aluminium obtained by severe plastic deformation are also analysed by coupling the image registration method to the on-axis TKD configuration. This coupling allows a high spatial resolution (3 to 10 nm) and a high angular resolution (0.01 to 0.05°) to be reached simultaneously. Elastic strain maps are obtained at the nanoscale in a SiGe thin foil. The geometrically necessary dislocation densities in a GaN single crystal are mapped with a resolution of about 2.5×10⁻³ µm⁻¹ (i.e. 8×10¹² m⁻²)