Joint-Angle Coordination Patterns Ensure Stabilization of a Body-Plus-Tool System in Point-to-Point Movements with a Rod

When performing a goal-directed action with a tool, it is generally assumed that the point of control of the action system is displaced from the hand to the tool, implying that body and tool function as one system. Studies of how actions with tools are performed have been limited to studying either end-effector kinematics or joint-angle coordination patterns. Because joint-angle coordination patterns affect end-effector kinematics, the current study examined them together, with the aim of revealing how body and tool function as one system. Seated participants made point-to-point movements with their index finger, and with rods of 10, 20, and 30 cm attached to their index finger. Start point and target were presented on a table in front of them, and in half of the conditions a participant displacement compensated for rod length. Results revealed that the kinematics of the rod’s tip showed higher peak velocity, longer deceleration time, and more curvature with longer rods. End-effector movements were more curved in the horizontal plane when participants were not displaced. Joint-angle trajectories were similar across rod lengths when participants were displaced, whereas more extreme joint-angles were used with longer rods when participants were not displaced. Furthermore, in every condition the end-effector was stabilized to a similar extent; both variability in joint-angle coordination patterns that affected end-effector position and variability that did not affect end-effector position increased in a similar way vis-à-vis rod length. Moreover, the increase was higher in those conditions, in which participants were not displaced. This suggests that during tool use, body and tool are united in a single system so as to stabilize the end-effector kinematics in a similar way that is independent of tool length. In addition, the properties of the actual trajectory of the end-effector, as well as the actual joint-angles used, depend on the length of the tool and the specifics of the task

Synergies reciprocally relate end-effector and joint-angles in rhythmic pointing movements

During rhythmic pointing movements, degrees of freedom (DOF) in the human action system-such as joint-angles in the arm-are assumed to covary to stabilise end-effector movement, e.g. index finger. In this paper, it is suggested that the end-effector movement and the coordination of DOF are reciprocally related in synergies that link DOF so as to produce the end-effector movement. The coordination of DOF in synergies and the relation between end-effector movement and DOF coordination received little attention, though essential to understand the principles of synergy formation. Therefore, the current study assessed how the end-effector movement related to the coordination of joint-angles during rhythmic pointing across target widths and distances. Results demonstrated that joint-angles were linked in different synergies when end-effector movements differed across conditions. Furthermore, in every condition, three joint-angles (shoulder plane of elevation, shoulder inward-outward rotation, elbow flexion-extension) largely drove the end-effector, and all joint-angles contributed to covariation that stabilised the end-effector. Together, results demonstrated synergies that produced the end-effector movement, constrained joint-angles so that they covaried to stabilise the end-effector, and differed when end-effector movement differed. Hence, end-effector and joint-angles were reciprocally related in synergies-indicating that the action system was organised as a complex dynamical system

Выявление понятий и их взаимосвязей в рамках технологии контент-мониторинга

Приведены подходы к решению проблемы выявления фактографической информации из неструктурированных текстовых потоков. Описаны технологические решения, позволяющие извлекать из полнотекстовых документов такие понятия как фирмы, фамилии, географические названия и т.п., а также выявлять силу их взаимосвязей на основе применения двух алгоритмов. Первый из этих алгоритмов основывается на учете совместного вхождения понятий в одни и те же документы, а второй на учете общего для рассматриваемых понятий контекста.Наведено підходи до вирішення проблеми виявлення фактографічної інформації з неструктурованих текстових потоків. Описано технологічні рішення, що дозволяють добути з повнотекстових документів такі поняття як фірми, прізвища, географічні назви тощо, а також виявляти силу їхніх взаємозв’язків на базі застосування двох алгоритмів. Перший з цих алгоритмів базується на врахуванні спільного входження понять до одних і тих самих документів, а другий — на врахуванні загального для понять, що розглядаються, контексту.Approaches to the solution of a problem of revealing factual information from unstructured text flows are given. The technological solutions, allowing to take from text-through documents such concepts as a firm, a surname, place names, etc., and also to reveal force of their interrelations on the basis of application of two algorithms are described. The first of these algorithms is based on the account of joint concepts occurrence in the same documents, and the second one on the account of the context common for considered concepts

Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome

Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival. TP53 mutations were detected in 230 (10.5%) patients with AML/MDS-EB with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was observed in 174 (76%) patients. Multiple TP53 mutations were found in 49 (21%) patients. Concurrent mutations were detected in 113 (49%) patients. No significant difference in any of the aforementioned molecular characteristics of mutant TP53 was detected between AML and MDS-EB. Patients with mutant TP53 have a poor outcome (2-year overall survival, 12.8%); however, no survival difference between AML and MDS-EB was observed. Importantly, none of the molecular characteristics were significantly associated with survival in mutant TP53 AML/MDS-EB. In most patients, TP53 mutations remained detectable in complete remission by deep sequencing (73%). Detection of residual mutant TP53 was not associated with survival. Mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity

Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia

PURPOSE The applicability of FLT3-internal tandem duplications (FLT3-ITD) for assessing measurable residual disease (MRD) in acute myeloid leukemia (AML) in complete remission (CR) has been hampered by patient-specific duplications and potential instability of FLT3-ITD during relapse. Here, we comprehensively investigated the impact of next-generation sequencing (NGS)-based FLT3-ITD MRD detection on treatment outcome in a cohort of patients with newly diagnosed AML in relation to established prognostic factors at diagnosis and other MRD measurements, ie, mutant NPM1 and multiparameter flow cytometry. METHODS In 161 patients with de novo FLT3-ITD AML, NGS was performed at diagnosis and in CR after intensive remission induction treatment. FLT3-ITD MRD status was correlated with the cumulative incidence of relapse and overall survival (OS). RESULTS NGS-based FLT3-ITD MRD was present in 47 of 161 (29%) patients with AML. Presence of FLT3-ITD MRD was associated with increased risk of relapse (4-year cumulative incidence of relapse, 75% FLT3-ITD MRD v 33% no FLT3-ITD MRD; P < .001) and inferior OS (4-year OS, 31% FLT3-ITD MRD v 57% no FLT3-ITD MRD; P < .001). In multivariate analysis, detection of FLT3-ITD MRD in CR confers independent prognostic significance for relapse (hazard ratio, 3.55; P < .001) and OS (hazard ratio 2.51; P = .002). Strikingly, FLT3-ITD MRD exceeds the prognostic value of most generally accepted clinical and molecular prognostic factors, including the FLT3-ITD allelic ratio at diagnosis and MRD assessment by NGS-based mutant NPM1 detection or multiparameter flow cytometry. CONCLUSION NGS-based detection of FLT3-ITD MRD in CR identifies patients with AML with profound risk of relapse and death that outcompetes the significance of most established prognostic factors at diagnosis and during therapy, and furnishes support for FLT3-ITD as a clinically relevant biomarker for dynamic disease risk assessment in AML

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019.

BACKGROUND Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). METHODS We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. FINDINGS Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). INTERPRETATION Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. FUNDING This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902)

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer:A Population-Based Cross-sectional Study with Standardized Radiological Evaluation after Dedicated Training

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located ≤8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and (ipsi) lateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p &lt;.001) and lateral local recurrence (14.7%, 4.4%, 0%; p &lt; 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract.</p

Supporting the high schools students with dyslexia

Tato diplomová práce se zabývá studenty s diagnostikovanou dyslexií, kteří studují na středních školách. V první části jsou teoreticky nastíněná východiska této problematiky. Tato část se zaměřuje na diagnostiku, poradenství, možnosti a formy podpory studentů s dyslexií na středních školách. Ve výzkumné části jsou prezentovány výsledky šetření. Za účelem splnění cílů této diplomové práce byla použita kombinace kvalitativního a kvantitativního přístupu konkrétně - rozhovory se studenty, dotazníkové šetření a pozorování. V hlavní části jsou prezentované názory studentů s dyslexií na jejich znevýhodnění, průběh studia a možnosti volby profesního zaměření po ukončení střední školy. Následně jsou uvedeny názory jejich rodičů na danou problematiku a názory učitelů na téma formy podpory studentů s dyslexií a jejich aplikace v praxi. V poslední části jsou uvedena doporučení pro praxi v oblasti poradenství, učitelství a také doporučení pro rodiče.This thesis pursues the high school students with diagnosed dyslexia. In the first part the outlets of this dilemma are outlined by theory. It includes diagnostics, counseling, options and forms of supporting the high schools students with dyslexia. In the exploratory part the results of my research are presented. To achieve the thesis targets I used combination of qualitative and quantitative approach. In specific - interviews with students, question-form research and observations. Main part presents the attitudes of students to their handicap, studies progressions and options of their profession specialization after graduating from a high school. Sequentially the attitudes of parents to this dilemma as well as opinions of pedagogues about form of supporting the students and its application in practice are presented. Conclusion states the recommendations for counseling practice, pedagoguism and also references for parents.Katedra speciální pedagogikyFaculty of EducationPedagogická fakult

Comparing Different Methods to Create a Linear Model for Uncontrolled Manifold Analysis

An essential step in uncontrolled manifold analysis is creating a linear model that relates changes in elemental variables to changes in performance variables. Such linear models are usually created by means of an analytical method. However, a multiple regression analysis is also suggested. Whereas the analytical method includes only averages of joint angles, the regression method uses the distribution of all joint angles. We examined whether the latter model is more suitable to describe manual reaching movements. The relation between estimated and measured fingertip-position deviations from the mean of individual trials, the relation between fingertip variability and nongoal-equivalent variability, goal-equivalent variability, and nongoal-equivalent variability indicated that the linear model created with the regression method gives a more accurate description of the reaching data. Therefore, we suggest the usage of the regression method to create the linear model for uncontrolled manifold analysis in tasks that require the approximation of the linear model