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This paper addresses the development of performance-based assessment items for ICT skills, skills in dealing with information and communication technologies, a construct which is rather broadly and only operationally defined. Item development followed a construct-driven approach to ensure that test scores could be interpreted as intended. Specifically, ICT-specific knowledge as well as problem-solving and the comprehension of text and graphics were defined as components of ICT skills and cognitive ICT tasks (i.e., accessing, managing, integrating, evaluating, creating). In order to capture the construct in a valid way, design principles for constructing the simulation environment and response format were formulated. To empirically evaluate the very heterogeneous items and detect malfunctioning items, item difficulties were analyzed and behavior-related indicators with item-specific thresholds were developed and applied. The 69 item’s difficulty scores from the Rasch model fell within a comparable range for each cognitive task. Process indicators addressing time use and test-taker interactions were used to analyze whether most test-takers executed the intended processes, exhibited disengagement, or got lost among the items. Most items were capable of eliciting the intended behavior; for the few exceptions, conclusions for item revisions were drawn. The results affirm the utility of the proposed framework for developing and implementing performance-based items to assess ICT skills.
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.
Sublinear circuits are generalizations of the affine circuits in matroid theory, and they arise as the convex-combinatorial core underlying constrained non-negativity certificates of exponential sums and of polynomials based on the arithmetic-geometric inequality. Here, we study the polyhedral combinatorics of sublinear circuits for polyhedral constraint sets. We give results on the relation between the sublinear circuits and their supports and provide necessary as well as sufficient criteria for sublinear circuits. Based on these characterizations, we provide some explicit results and enumerations for two prominent polyhedral cases, namely the non-negative orthant and the cube [− 1,1]n.
The problem of unconstrained or constrained optimization occurs in many branches of mathematics and various fields of application. It is, however, an NP-hard problem in general. In this thesis, we examine an approximation approach based on the class of SAGE exponentials, which are nonnegative exponential sums. We examine this SAGE-cone, its geometry, and generalizations. The thesis consists of three main parts:
1. In the first part, we focus purely on the cone of sums of globally nonnegative exponential sums with at most one negative term, the SAGE-cone. We ex- amine the duality theory, extreme rays of the cone, and provide two efficient optimization approaches over the SAGE-cone and its dual.
2. In the second part, we introduce and study the so-called S-cone, which pro- vides a uniform framework for SAGE exponentials and SONC polynomials. In particular, we focus on second-order representations of the S-cone and its dual using extremality results from the first part.
3. In the third and last part of this thesis, we turn towards examining the con- ditional SAGE-cone. We develop a notion of sublinear circuits leading to new duality results and a partial characterization of extremality. In the case of poly- hedral constraint sets, this examination is simplified and allows us to classify sublinear circuits and extremality for some cases completely. For constraint sets with certain conditions such as sets with symmetries, conic, or polyhedral sets, various optimization and representation results from the unconstrained setting can be applied to the constrained case.
In this letter we report the first multi-differential measurement of correlated pion-proton pairs from 2 billion Au+Au collisions at sNN=2.42 GeV collected with HADES. In this energy regime the population of Δ(1232) resonances plays an important role in the way energy is distributed between intrinsic excitation energy and kinetic energy of the hadrons in the fireball. The triple differential d3N/dMπ±pdpTdy distributions of correlated π±p pairs have been determined by subtracting the πp combinatorial background using an iterative method. The invariant-mass distributions in the Δ(1232) mass region show strong deviations from a Breit-Wigner function with vacuum width and mass. The yield of correlated pion-proton pairs exhibits a complex isospin, rapidity and transverse-momentum dependence. In the invariant mass range 1.1<Minv(GeV/c2)<1.4, the yield is found to be similar for π+p and π−p pairs, and to follow a power law 〈Apart〉α, where 〈Apart〉 is the mean number of participating nucleons. The exponent α depends strongly on the pair transverse momentum (pT) while its pT-integrated and charge-averaged value is α=1.5±0.08st±0.2sy.
This software demonstration presents the possibilities for the construction, administration, and evaluation of criterion- referenced, computerized adaptive and nonadaptive tests with the R-based open-source KAT-HS app. This app enables users to apply the continuous item calibration strategy of Fink, Born, Spoden, and Frey (2018).
Simple Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation.
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
umanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T-cell differentiation remains inefficient. We generated mice expressing human interleukin-7 (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T-cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.