Sharing information across patient subgroups to draw conclusions from sparse treatment networks.

Network meta-analysis (NMA) usually provides estimates of the relative effects with the highest possible precision. However, sparse networks with few available studies and limited direct evidence can arise, threatening the robustness and reliability of NMA estimates. In these cases, the limited amount of available information can hamper the formal evaluation of the underlying NMA assumptions of transitivity and consistency. In addition, NMA estimates from sparse networks are expected to be imprecise and possibly biased as they rely on large-sample approximations that are invalid in the absence of sufficient data. We propose a Bayesian framework that allows sharing of information between two networks that pertain to different population subgroups. Specifically, we use the results from a subgroup with a lot of direct evidence (a dense network) to construct informative priors for the relative effects in the target subgroup (a sparse network). This is a two-stage approach where at the first stage, we extrapolate the results of the dense network to those expected from the sparse network. This takes place by using a modified hierarchical NMA model where we add a location parameter that shifts the distribution of the relative effects to make them applicable to the target population. At the second stage, these extrapolated results are used as prior information for the sparse network. We illustrate our approach through a motivating example of psychiatric patients. Our approach results in more precise and robust estimates of the relative effects and can adequately inform clinical practice in presence of sparse networks.

Spin-polarized proton beam generation from gas-jet targets by intense laser pulses.

A method of generating spin-polarized proton beams from a gas jet by using a multipetawatt laser is put forward. With currently available techniques of producing prepolarized monatomic gases from photodissociated hydrogen halide molecules and petawatt lasers, proton beams with energy ≳50 MeV and ≈80% polarization are proved to be obtained. Two-stage acceleration and spin dynamics of protons are investigated theoretically and by means of fully self-consistent three-dimensional particle-in-cell simulations. Our results predict the dependence of the beam polarization on the intensity of the driving laser pulse. Generation of bright energetic polarized proton beams would open a domain of polarization studies with laser driven accelerators and have potential application to enable effective detection in explorations of quantum chromodynamics.

Teaching and Learning Process of Decision-Making Units in Talented Young Players From U-10 to U-14.

There are multiple factors that have been studied for talent identification (TI) with regard to sport performance, such as physical and physiological parameters; psychological, social, and contextual parameters; and technical-tactical parameters. However, despite the importance of these indicators for reaching the elite, new trends seem to assure that one of the key elements in a young player is decision making (DM). Thus, in the last decades, research DM in young players has increased. Nevertheless, very little has been done in relation with DM and talented players. The purpose of this study was to analyze and compare the effectiveness, number, and duration of DM units (DMUs) of three groups of talented young players in U-10, U-12, and U-14 levels. Ninety-seven youth players participated in the study. A total of 1,087 actions were analyzed. The Nomination Scale for Identifying Football Talent was utilized to screen the talent pool (N = 18), and the Game Performance Evaluation Tool was used for analyzing the 1,087 actions completed. The results showed that the effectiveness has to be more than 80% for children to be considered talented. Moreover, a greater effectiveness of DMUs was shown in older age groups. The game speed also increased with age. It was revealed that U-12 did not follow the progression in the decisional demands in the formative stages. It is highlighted, therefore, the necessity of reviewing the organizational aspects in the U-12 age group, related mainly to the size of the pitch and the number of players, because it does not follow the same progression in regard to decisional demands. Future studies should follow this study with the U-16, U-18, and U-23 age groups, with the purpose of knowing the effectiveness, duration, and number of DMUs in older age groups. Furthermore, policy makers and teachers/coaches from both educational and soccer context must take these results into account, with the purpose of adjusting the teaching and learning process of talented children in sport.

Polarized electron acceleration in beam-driven plasma wakefield based on density down-ramp injection.

We investigate the precession of electron spins during beam-driven plasma-wakefield acceleration based on density down-ramp injection by means of full three-dimensional (3D) particle-in-cell (PIC) simulations. A relativistic electron beam generated via, e.g., laser wakefield acceleration, serves as the driving source. It traverses the prepolarized gas target and accelerates polarized electrons via the excited wakefield. We derive the criteria for the driving beam parameters and the limitation on the injected beam flux to preserve a high degree of polarization for the accelerated electrons, which are confirmed by our 3D PIC simulations and single-particle modeling. The electron-beam driver is free of the prepulse issue associated with a laser driver, thus eliminating possible depolarization of the prepolarized gas due to ionization by the prepulse. These results provide guidance for future experiments towards generating a source of polarized electrons based on wakefield acceleration.

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma.

BACKGROUND: Rearrangements of RET are drivers of oncogenesis, traceable in different cancer types as papillary thyroid carcinoma (PTC), non-small cell lung cancer, colorectal or breast cancer. Anchored multiplex PCR based next-generation sequencing (NGS) can detect RET rearrangements involving previously unknown partner genes. METHODS: A sample of PTC underwent NGS, following detection of RET rearrangement by fluorescence in situ hybridization. Expression analysis of ANKRD26 and RET was performed for the tumor harboring ANKRD26-RET, for corresponding normal thyroid tissue and PTC tumors with representative genetic alterations (BRAFV600E, CCDC6-RET), complemented by a comparative search in the "UniProt" database. RESULTS: NGS analysis resulted in the discovery of the fusion ANKRD26-RET. ANKRD26 mRNA was expressed in all PTC tumors (ANKRD26-RET, BRAFV600E, CCDC6-RET) and in normal thyroid tissue, whereas RET mRNA was detected only in the tumors with RET rearrangement. On protein level, ANKRD26-RET combines the RET tyrosine kinase to ankyrin repeat and coiled-coil domains. CONCLUSIONS: ANKRD26-RET is a novel rearrangement of the RET gene, associated with RET expression in thyroid tissue. The result is a fusion of the RET tyrosine kinase to prominent protein-protein interaction motifs. Further studies are required to investigate the influence of different RET rearrangements on metastasis and disease-free survival in PTC.

Vitamin D Supplementation and Physical Activity of Young Soccer Players during High-Intensity Training.

The aim of this study was to confirm that vitamin D supplementation of young soccer players during eight-week high-intensity training would have a significant effect on their motion activity. The subjects were divided into two groups: the experimental one, which was supplemented with vitamin D (SG, n = 20), and the placebo group (PG, n = 16), which was not supplemented with vitamin D. All the players were subjected to the same soccer training, described as High-Intensity Interval Training (HIIT). The data of the vitamin D status, time motion parameters and heart rate were collected just before and after the intervention. A significant increase in 25(OH)D concentration (119%) was observed in the supplemented group, while the non-supplemented group showed a decrease of 8.4%. Based on the obtained results, it was found that physical activity indicators in the players were significantly improved during small-sided games at the last stage of the experiment. However, taking into account the effect of supplementation with vitamin D, there were no statistically significant differences between the placebo and the supplemented groups; thus, the effect size of the conducted experiment was trivial.

Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques - A molecular and clinical analysis.

INTRODUCTION: Oncogenic BRAF and RAS mutations as well as multiple known (and yet unknown) RET fusion oncogenes comprise the majority of causative molecular alterations in papillary thyroid carcinoma (PTC). Apparently "mutation-negative" PTCs encompass a heterogenous group impeding analysis of prognostic significance of underlying genetics. MATERIAL AND METHODS: BRAF wild type PTC tissue of 56 patients was analyzed using two established methods: hybrid-specific RT-PCR for the predominant rearrangement RET/PTC1 and fluorescent in situ hybridization (FISH). Clinical features of the cases with and without RET rearrangement were compared (patient age, gender, tumor size, focality, lymph node affection, and iodine avidity). RESULTS: RT-PCR revealed RET/PTC1 rearrangements in five of 56 tumors (9%). FISH confirmed these, and identified four additional RET rearrangements (9/56; 16%). Loss of the iodine avidity only occurred in cases of RET/PTC hybrids (7/9 tumors), but not in RET/PTC-negative PTCs (0/41 tumors with available uptake information; p = 0.029). The risk to develop lymph node metastases was eight times higher in presence of RET rearrangements (p = 0.010). CONCLUSIONS: FISH analysis, in contrast to hybrid-specific RT-PCR, revealed infrequent and unknown RET fusion genes. The presence of RET rearrangements was associated with a significantly elevated risk to develop iodine refractory disease and lymph node metastases. Of note, significant clinical discrimination was only achievable when taking the FISH results into account; differences would have been missed when using the RT-PCR method only. Increasing evidence of the clinical impact of RET/PTC-positivity may influence the decision on the extent of surgical resection, especially on lymph node dissection, in PTCs.

Novel rearrangements involving the RET gene in papillary thyroid carcinoma.

BACKGROUND: In the field of gene fusions driving tumorigenesis in papillary thyroid carcinoma (PTC), rearrangement of the proto-oncogene RET is the most frequent alteration. Apart from the most common rearrangement of RET to CCDC6, more than 15 partner genes are yet reported. The landscape of RET rearrangements in PTC ("RET-PTC") can notably be enlarged by modern targeted next-generation sequencing, indicating similarities between oncogenic pathways in other cancer types with identical genetic alterations. METHODS: Targeted next-generation sequencing was performed for two cases of BRAF-wild type PTC with confirmation of the results by Sanger sequencing. A "UniProt" database research was performed to assess protein alterations resulting from RET rearrangements. RESULTS: RUFY2-RET and KIAA1468-RET were detected. The fusion genes were not present in normal tissue of the index patients. The rearrangement RUFY2-RET lead to a fusion of the RET tyrosine kinase domain to a RUN domain and a coiled-coil domain. For KIAA1468-RET, a fusion to a LisH domain and two coiled-coil domains resulted. CONCLUSIONS: RUFY2-RET and KIAA1468-RET are novel RET/PTC rearrangements. The fusions were previously described in non-small cell lung cancer. The rearrangement results in a fusion of the RET tyrosine kinase to regulatory domains of RUFY2 and KIAA1468.

Two-dimensional structures of electron bunches in relativistic plasma cavities.

The spatial structure of an ultralow-emittance electron bunch in a plasma wakefield blowout regime is studied. The full Liénard-Wiechert potentials are considered for mutual interparticle interactions in the framework of the equilibrium slice model. This model uses the quasistatic theory which allows one to solve the Liénard-Wiechert potentials without knowledge of the electrons' history. The equilibrium structure we find is similar to already observed hexagonal lattices but shows topological defects. Scaling laws for interparticle distances are obtained from numerical simulations and analytical estimations.

Time-dependent behavior of porcine periodontal ligament: A combined experimental, numeric in-vitro study.

INTRODUCTION: The aim of this study was to analyze the time-dependent in-vitro behavior of the periodontal ligament (PDL) by determining the material parameters using specimens of porcine jawbone. Time-dependent material parameters to be determined were expected to complement the results from earlier biomechanical studies. METHODS: Five mandibular deciduous porcine premolars were analyzed in a combined experimental-numeric study. After selecting suitable specimens (excluding root resorption) and preparing the measurement system, the specimens were deflected by a distance of 0.2 mm at loading times of 0.2, 0.5, 1, 2, 5, 10, and 60 seconds. The deflection of the teeth was determined via a laser optical system, and the resulting forces and torques were measured. To create the finite element models, a microcomputed tomography scanner was used to create 3-dimensional x-ray images of the samples. The individual structures (tooth, PDL, bone) of the jaw segments were reconstructed using a self-developed reconstruction program. A comparison between experiment and simulation was conducted using the results from finite element simulations. Via iterative parameter adjustments, the material parameters (Young's modulus and Poisson's ratio) of the PDL were assessed at different loading velocities. RESULTS: The clinically observed effect of a distinct increase in force during very short periods of loading was confirmed. Thus, a force of 2.6 N (±1.5 N) was measured at the shortest stress duration of 0.2 seconds, and a force of 1.0 N (±0.5 N) was measured at the longest stress duration of 60 seconds. The numeric determination of the material parameters showed bilinear behavior with a median value of the first Young's modulus between 0.06 MPa (2 seconds) and 0.04 MPa (60 seconds), and the second Young's modulus between 0.30 MPa (10 seconds) and 0.20 MPa (60 seconds). The ultimate strain marking the transition from the first to the second Young's modulus remained almost unchanged with a median value of 6.0% for all loading times. CONCLUSION: A combined experimental-numeric analysis is suitable for determining the material properties of the PDL. Microcomputed tomography allows high-precision recordings with only minimum effort. This study confirms the assumption of time dependency and nonlinearity of previous studies.

Plasma copeptin in children and adolescents with type 1 diabetes mellitus in comparison to healthy controls.

UNLABELLED: In a cohort of children and adolescents with type 1 diabetes mellitus the trial tested the hypothesis that copeptin levels are associated with kidney function, biometrical data and quality of diabetes control. PATIENTS AND METHODS: A total of 141 subjects were recruited to participate in the trial: 80 patients with type 1 diabetes (13.0±3.4years, HbA1c 7.85±1.42%) and 61 healthy controls (12.4±2.8years). Clinical and socio-economic data were assessed. A sandwich immunoassay (B.R.A.H.M.S. GmbH/Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany) was used for measuring plasma copeptin levels. RESULTS: The mean concentration of copeptin in the diabetic patients was 4.75±3.46pmol/l. There was a strong inverse correlation between copeptin and GFR (r=-0.86, p=0.021), as well as with total cholesterol (r=-0.23, p=0.041), LDL-cholesterol (r=-0.24, p=0.036), but not with serum creatinine, albuminuria, HbA1c, blood glucose, MAGE, CRP, systolic or diastolic blood pressure or age, diabetes duration, weight, height and BMI. Comparing patients with a diabetes duration of ⩾7years (n=45) with those with a diabetes duration <7years (n=35), patients with a longer duration of diabetes had higher copeptin levels (5.24±2.26 vs 4.13±2.86, p=0.045). Performing multivariate analyses only GFR could be identified as a parameter associated with copeptin (R-square=0.05, ß=-0.23, p=0.032). In the healthy controls mean copeptin concentration was 5.56±3.15pmol/l. The copeptin concentration and GFR were inversely correlated as well (r=-0.61, p=0.034). However, other correlation and multivariate analyses revealed no further significant results. Comparing patients with type 1 diabetes mellitus with the healthy controls, the diabetes patients revealed no significant difference with respect to copeptin (p=0.24), serum creatinine (49.8±11.9 vs 50.4±11.0µmol/l, p=0.53) or GFR (102.4±23.3 vs 104.5±19.1ml/min, p=0.47). On the other hand, patients with type 1 diabetes had lower concentrations of CRP (1.66±3.91 vs 3.21±3.04µg/ml, p=0,013), triglycerides (0.88±0.53 vs 1.13±0.60mmol/l, p=0.010), and a lower ratio of LDL-/HLD-cholesterol (1.73±0.69 vs 2.32±0.80, p<0.001), as well as lower body weight (51.3±18.0 vs 60.3±15.7kg, p=0.002) and BMI (19.7±3.8 vs 23.2±2.9kg/m(2), p<0.001). In contrast to the controls, the diabetes patients had higher blood glucose levels at the time of examination (8.2±3.8 vs 4.7±0.5mmol/l, p<0.001), higher HDL-cholesterol levels (1.59±0.34 vs 1.26±0.24mmol/l, p<0.001), as well as higher education and higher educational levels of the mothers. CONCLUSIONS: The present trial revealed a clear association between GFR and copeptin in children and adolescents with type 1 diabetes mellitus. Hence, copeptin can be considered as a marker of renal function.

Group 4 metallocene catalysed full dehydrogenation of hydrazine borane.

A study of the full dehydrogenation of hydrazine borane (H2N-NH2·BH3) to give H2 and N2 as gaseous products catalysed by a variety of group 4 metallocene alkyne complexes of the type CpM(L)(η(2)-Me3SiC2SiMe3) (Cp' = substituted or unsubstituted η(5)-cyclopentadienyl; M = Ti, no L; M = Zr, L = pyridine) and group 4 metallocene hydrides is presented. Volumetric data show that the amount of hydrogen released is strongly dependent on both, the metal and the cyclopentadienyl ligand.

Preparation and characterization of [CF3SO3(SiMe3)2]+[B(C6F5)4]-.

Using tetrakis(pentafluorophenyl)borate, [B(C(6)F(5))(4)](-), as weakly coordinating counterion, the bis(trimethylsilyl)trifluoromethylsulfonium cation, [CF(3)SO(3)(Me(3)Si)(2)](+), is readily isolated for X-ray, NMR and IR structural characterization.