Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Piebaldism, Multiple Café‐au‐lait Macules, and Intertriginous Freckling: Clinical Evidence of a Common Pathway between KIT and Sprouty‐Related, Ena/Vasodilator‐Stimulated Phosphoprotein Homology‐1 Domain Containing Protein 1 (SPRED1)

Abstract: Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5‐year‐old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café‐au‐lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty‐related, Ena/vasodilator‐stimulated phosphoprotein homology‐1 domain containing protein 1 (SPRED1) mutations that also has multiple café‐au‐lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café‐au‐lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.
Left-Sided Predominance of Hypodontia Irrespective of Cleft Sidedness in a French Population

Objective Individuals with oral clefts exhibit considerably more dental anomalies than do individuals without clefts. Our aim was to evaluate the prevalence of tooth agenesis in a sample composed of 124 children (81 boys and 43 girls, mean age 12.5 years) with clefts registered with the Cleft Palate Center in Strasbourg (France). Design Cleft types and dental agenesis were assessed by clinical and radiographic examination. Cleft types were divided into four groups according to the clinical extent of the cleft (cleft lip only [CL, 12.9%], cleft lip and alveolus [CLA, 4%], cleft lip and palate [CLP, 49.2%], and cleft palate only [CP, 33.9%]). Results Of the subjects 63% had evidence of hypodontia: maxillary lateral incisors (54%) and upper and lower premolars (32%) were the most common missing teeth. The number of dental ageneses associated with CP (54%) and CLP (79%) was significantly higher than that with CL (33%). All these anomalies were found in proportionately higher frequencies as the severity of the cleft increased, and we found left side predominance for hypodontia (p < .01) irrespective of cleft sidedness. Conclusions Both right-sided and left-sided clefts were more frequently correlated with left-sided dental agenesis. This left-sided prevalence suggests that common signaling malfunctions might be involved, both in dental development anomalies and cleft genesis.
Development of an Integrated Subspecialist Multidisciplinary Neuro-oncology Service

Abstract Traditionally, the poor outcome for patients with malignant brain tumours led to therapeutic nihilism. In turn, this resulted in lack of interest in neurosurgical oncology subspecialisation, and less than ideal patient pathways. One problem of concern was the low rate of tumour resection. Between 1997 and 2006, 685 treated glioblastomas were identified. In the first four years only 40% of patients underwent tumour resection, rising to 55% in the last four years. Before revision of the pathway, the median length of hospital stay was 8 days, and 35% of patients received the results of their histology outside of a clinic setting. A pathway of care was established, in which all patients were discussed pre-operatively in an MDT meeting and then directed into a new surgical neuro-oncology clinic providing first point of contact. This limited the number of surgeons operating on adult glioma patients and aided recruitment into research studies. Now, three consultant neurosurgeons run this service, easily fulfilling IOG requirement to spend >50% of programmed activities in neuro-oncology. Nursing support has been critical to provide an integrated service. This model has allowed increased recruitment to clinical trials. The introduction of this service led to an increase in patients discussed pre-operatively in an MDT (66% rising to 87%; P=0.027), an increase in the rate of surgical resection (from 40% to 80%) and more patients being admitted electively (from 25% to 80%; P<0.001). There was a reduction in the median length of stay (8 days reduced to 4.5 days; P<0.001). For the cohort of GBM patients that went on to have chemoradiotherapy we improved median survival to 18 months, with 35% of patients alive at two years, comparable to international outcomes. Implementing a specialist neurosurgical oncology service begins with understanding the patient care pathway. Our patients have benefitted from the culture of subspecialisation and the excellent inter-disciplinary working relationships that have been developed.
Numerical Simulations of Heat Transfer and Fluid Flow Problems Using an Immersed-Boundary Finite-Volume Method on NonStaggered Grids

ABSTRACT This article describes the application of the immersed boundary technique for simulating fluid flow and heat transfer problems over or inside complex geometries. The methodology is based on a fractional step method to integrate in time. The governing equations are discretized and solved on a regular mesh with a finite-volume nonstaggered grid technique. Implementations of Dirichlet and Neumann types of boundary conditions are developed and completely validated. Several phenomenologically different fluid flow and heat transfer problems are simulated using the technique considered in this study. The accuracy of the method is second-order, and the efficiency is verified by favorable comparison with previous results from numerical simulations and laboratory experiments.
Measures of Partisan Bias for Legislating Fair Elections

Several measures of partisan bias are reviewed for single member districts with two dominant parties. These include variants of the simple bias that considers only deviation of seats from 50% at statewide 50% vote. Also included are equalization of losing votes and equalization of wasted votes, both of which apply directly when the statewide vote is not 50% and which require, not just partisan symmetry, but specific forms of the seats-votes curve. A new measure of bias is introduced, based on the geometric area between the seats-vote curve and the symmetrically inverted seats-votes curve. These measures are applied to recent Pennsylvania congressional elections and to abstract models of the seats-votes curves. The numerical values obtained from the various measures of bias are compared and contrasted. Each bias measure has merits for different seats-votes curves and for different elections, but all essentially agree for most cases when applied to measure only partisan bias, not conflated with competitiveness. This supports the inclusion of partisan fairness as a fundamental element for election law reform, and some options are discussed.
A Probabilistic Methodology for Integrating Knowledge and Experiments on Biological Networks

Biological systems are traditionally studied by focusing on a specific subsystem, building an intuitive model for it, and refining the model using results from carefully designed experiments. Modern experimental techniques provide massive data on the global behavior of biological systems, and systematically using these large datasets for refining existing knowledge is a major challenge. Here we introduce an extended computational framework that combines formalization of existing qualitative models, probabilistic modeling, and integration of high-throughput experimental data. Using our methods, it is possible to interpret genomewide measurements in the context of prior knowledge on the system, to assign statistical meaning to the accuracy of such knowledge, and to learn refined models with improved fit to the experiments. Our model is represented as a probabilistic factor graph, and the framework accommodates partial measurements of diverse biological elements. We study the performance of several probabilistic inference algorithms and show that hidden model variables can be reliably inferred even in the presence of feedback loops and complex logic. We show how to refine prior knowledge on combinatorial regulatory relations using hypothesis testing and derive p-values for learned model features. We test our methodology and algorithms on a simulated model and on two real yeast models. In particular, we use our method to explore uncharacterized relations among regulators in the yeast response to hyper-osmotic shock and in the yeast lysine biosynthesis system. Our integrative approach to the analysis of biological regulation is demonstrated to synergistically combine qualitative and quantitative evidence into concrete biological predictions.
Microwave Ablation of Symptomatic Benign Thyroid Nodules: Energy Requirement per ml Volume Reduction

Abstract Purpose: Microwave ablation (MWA) represents a novel thermal ablative treatment of benign thyroid nodules. The aim was to determine the energy required per ml volume reduction in order to match the required energy to the volume-of-interest (VOI). Materials and Methods: 25 patients with 25 nodules (6 solid, 13 complex and 6 cystic) were treated by microwave ablation (MWA). The transmitted energy (E) was correlated with the volume change (∆ V) after 3 months. The energy required per ml volume reduction after 3 months was calculated by E/∆ V. Results: MWA resulted in a significant (p < 0.0001) volume reduction (∆ V) with a mean of 12.4 ± 13.0 ml (range: 1.5 – 63.2 ml) and relative reduction of 52 ± 16 % (range: 22 – 77 %). There was a positive correlation between E and ∆ V (r = 0.82; p < 0.05). The mean E/∆ V was 1.52 ± 1.08 (range: 0.4 – 4.6) kJ/ml for all nodules and 2.30 ± 1.5 (0.9 – 4.6), 1.5 ± 0.9 (0.4 – 3.6), 0.75 ± 0.25 (0.4 – 1.2) kJ/ml, respectively, for solid, complex and cystic nodules with a significant difference in E/∆ V for solid and cystic (p < 0.03). Conclusion: The energy required per volume depends on the nodule consistency. Solid nodules require more energy than cystic ones. The estimation of the energy needed per volume-of-interest as an additional parameter should help to avoid under- or overtreatment. Key Points: • The estimated required energy for a volume-of-interest depends on the nodule consistency • In solid nodules a higher energy transmission than in cystic nodules is recommended • The energy transmission as an additional marker to ultrasound is helpful for improving periprocedural monitoring Citation Format: • Korkusuz Y, Kohlhase K, Gröner D et al. Microwave Ablation of Symptomatic Benign Thyroid Nodules: Energy Requirement per ml Volume Reduction. Fortschr Röntgenstr 2016; 188: 1054 – 1060
Effects of Exercise Therapy on Balance Capacity in Chronic Stroke: Systematic Review and Meta-Analysis

Background and Purpose— The purpose of this systematic review and meta-analysis was to investigate the effects of exercise training on balance capacity in people in the chronic phase after stroke. Furthermore, we aimed to identify which training regimen was most effective. Methods— Electronic databases were searched for randomized controlled trials evaluating the effects of exercise therapy on balance capacity in the chronic phase after stroke. Studies were included if they were of moderate or high methodological quality (PEDro score ≥4). Data were pooled if a specific outcome measure was reported in at least 3 randomized controlled trials. A sensitivity analysis and consequent subgroup analyses were performed for the different types of experimental training (balance and/or weight-shifting training, gait training, multisensory training, high-intensity aerobic exercise training, and other training programs). Results— Forty-three randomized controlled trials out of 369 unique hits were included. A meta-analysis could be conducted for the Berg Balance Scale (28 studies, n=985), Functional Reach Test (5 studies, n=153), Sensory Organization Test (4 studies, n=173), and mean postural sway velocity (3 studies, n=89). A significant overall difference in favor of the intervention group was found for the Berg Balance Scale (mean difference 2.22 points (+3.9%); 95% confidence interval [CI], 1.26–3.17; P<0.01; I2=52%), Functional Reach Test (mean difference=3.12 cm; 95% CI, 0.90–5.35; P<0.01; I2=74%), and Sensory Organization Test (mean difference=6.77 (+7%) points; 95% CI, 0.83–12.7; P=0.03; I2=0%). Subgroup analyses of the studies that included Berg Balance Scale outcomes demonstrated a significant improvement after balance and/or weight-shifting training of 3.75 points (+6.7%; 95% CI, 1.71–5.78; P<0.01; I2=52%) and after gait training of 2.26 points (+4.0%; 95% CI, 0.94–3.58; P<0.01; I2=21, whereas no significant effects were found for other training regimens. Conclusions— This systematic review and meta-analysis showed that balance capacities can be improved by well-targeted exercise therapy programs in the chronic phase after stroke. Specifically, balance and/or weight-shifting and gait training were identified as successful training regimens.
Genetic Algorithms for Finite Mixture Model Based Voxel Classification in Neuroimaging

Finite mixture models (FMMs) are an indispensable tool for unsupervised classification in brain imaging. Fitting an FMM to the data leads to a complex optimization problem. This optimization problem is difficult to solve by standard local optimization methods, such as the expectation-maximization (EM) algorithm, if a principled initialization is not available. In this paper, we propose a new global optimization algorithm for the FMM parameter estimation problem, which is based on real coded genetic algorithms. Our specific contributions are two-fold: 1) we propose to use blended crossover in order to reduce the premature convergence problem to its minimum and 2) we introduce a completely new permutation operator specifically meant for the FMM parameter estimation. In addition to improving the optimization results, the permutation operator allows for imposing biologically meaningful constraints to the FMM parameter values. We also introduce a hybrid of the genetic algorithm and the EM algorithm for efficient solution of multidimensional FMM fitting problems. We compare our algorithm to the self-annealing EM-algorithm and a standard real coded genetic algorithm with the voxel classification tasks within the brain imaging. The algorithms are tested on synthetic data as well as real three-dimensional image data from human magnetic resonance imaging, positron emission tomography, and mouse brain MRI. The tissue classification results by our method are shown to be consistently more reliable and accurate than with the competing parameter estimation methods
Interval Estimation for Reinforcement-Learning Algorithms in Continuous-State Domains

The reinforcement learning community has explored many approaches to obtaining value estimates and models to guide decision making; these approaches, however, do not usually provide a measure of confidence in the estimate. Accurate estimates of an agent's confidence are useful for many applications, such as biasing exploration and automatically adjusting parameters to reduce dependence on parameter-tuning. Computing confidence intervals on reinforcement learning value estimates, however, is challenging because data generated by the agent-environment interaction rarely satisfies traditional assumptions. Samples of value-estimates are dependent, likely non-normally distributed and often limited, particularly in early learning when confidence estimates are pivotal. In this work, we investigate how to compute robust confidences for value estimates in continuous Markov decision processes. We illustrate how to use bootstrapping to compute confidence intervals online under a changing policy (previously not possible) and prove validity under a few reasonable assumptions. We demonstrate the applicability of our confidence estimation algorithms with experiments on exploration, parameter estimation and tracking.
A variation on CSMA/CD that yields movable TDM slots in integrated voice/data local networks

A variation on the carrier-sense, multiple-access/collision-detection (CSMA/CD) protocol for local-area, random-access broadcast networks is presented. The new protocol supports any mix of voice and data traffic, and has an upper bound on the delay of periodic traffic. In conventional CSMA/CD systems, statistical fluctuations in the transmission delay may cause disruptions in reconstructed voice waveforms. This does not occur with the new protocol. With this protocol, data sources use conventional CSMA/CD techniques to access the channel, while voice sources use a subset of these protocols, and appear to acquire a time-division multiplexed (TDM) slot. As in TDM systems, the entire system capacity can be used by the periodic sources. Unlike TDM systems, periodic slots are repositioned when other transmissions interfere with them, timing discrepancies between sources can be tolerated, and a centralized controller is not required to assign slots. Simulations are used to compare the delays in this system with those in conventional CSMA/CD systems. It is shown that at link utilizations of 0.9, voice sources can operate in a time-assignment, speech-interpolation mode. The effect of periodic traffic on conventional CSMA/CD protocols is also determined.
Discrete Pattern of Burst Stimulation in the Ventrobasal Thalamus for Anti-Nociception

The thalamus has been proposed to play a role in sensory modulation via switching between tonic and burst dual firing of individual neurons. Of the two firing modes, altered burst firing has been repeatedly implicated with pathological pain conditions, which suggests that maintaining a certain form of thalamic burst could be crucial for controlling pain. However, specific elements of burst firing that may contribute to pain control have not yet been actively investigated. Utilizing the deep brain stimulation (DBS) technique, we explored the effects of bursting properties in pain control by electrically stimulating the ventrobasal (VB) thalamus in forms of burst patterned to test different aspects of bursts during the formalin induced nociception in mice. Our results demonstrated that electrical stimulations mimicking specific burst firing properties are important in producing an anti-nociceptive effect and found that the ≤3 ms interval between burst pluses (intra-burst-interval: IntraBI) and ≥3 pulses per burst were required to reliably reduce formalin induced nociceptive responses in mice. Periodicity of IntraBI was also suggested to contribute to anti-nociception to a limited extent.
Profiling of Temperature-Induced Changes in Borrelia burgdorferi Gene Expression by Using Whole Genome Arrays

ABSTRACT Borrelia burgdorferi is the etiologic agent of Lyme disease, the most prevalent arthropod-borne disease in the United States. The genome of the type strain, B31, consists of a 910,725-bp linear chromosome and 21 linear and circular plasmids comprising 610,694 bp. During its life cycle, the spirochete exists in distinctly different environments, cycling between a tick vector and a mammalian host. Temperature is one environmental factor known to affect B. burgdorferi gene expression. To identify temperature-responsive genes, genome arrays containing 1,662 putative B. burgdorferi open reading frames (ORFs) were prepared on nylon membranes and employed to assess gene expression in B. burgdorferi B31 grown at 23 and 35°C. Differences in expression of more than 3.5 orders of magnitude could be readily discerned and quantitated. At least minimal expression from 91% of the arrayed ORFs could be detected. A total of 215 ORFs were differentially expressed at the two temperatures; 133 were expressed at significantly greater levels at 35°C, and 82 were more significantly expressed at 23°C. Of these 215 ORFs, 134 are characterized as genes of unknown function. One hundred thirty-six (63%) of the differentially expressed genes are plasmid encoded. Of particular interest is plasmid lp54 which contains 76 annotated putative genes; 31 of these exhibit temperature-regulated expression. These findings underscore the important role plasmid-encoded genes may play in adjustment of B. burgdorferi to growth under diverse environmental conditions.
Use of Carbon Fiber Reinforced Polymer (CFRP) with CFRP Anchors for Shear-Strengthening and Design Recommendations/Quality Control Procedures for CFRP Anchors

The objective of the study was to demonstrate the feasibility of using bi-directional layouts of CFRP for shear strengthening of bridge girders. In a previous project (0-6306), it was demonstrated that uni-directional CFRP strips and CFRP anchors could be used to improve the shear strength of reinforced concrete elements. Tests of I-beams with both uni-directional and bi-directional CFRP strips indicated that the use of bi-directional strips led to improved shear capacity. Because the data on the bi-directional layout of CFRP was limited, additional work was needed to understand the behavior and design of CFRP strips and anchors for bridge elements subjected to large shear forces. Since the anchor installation is a key element of the strengthening technique, there is a need for quality control procedures to make sure that the materials are used properly and the installation meets the design requirements. The information obtained from this project provides needed guidance that will enable TxDOT to design strengthening projects using CFRP materials and to develop quality control procedures to assess workmanship in the ield.
Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial.

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; -1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco. it as EudraCT 2006-004205-26.
Heterogeneous firing rate response of mouse layer V pyramidal neurons in the fluctuation‐driven regime

We recreated in vitro the fluctuation‐driven regime observed at the soma during asynchronous network activity in vivo and we studied the firing rate response as a function of the properties of the membrane potential fluctuations. We provide a simple analytical template that captures the firing response of both pyramidal neurons and various theoretical models. We found a strong heterogeneity in the firing rate response of layer V pyramidal neurons: in particular, individual neurons differ not only in their mean excitability level, but also in their sensitivity to fluctuations. Theoretical modelling suggest that this observed heterogeneity might arise from various expression levels of the following biophysical properties: sodium inactivation, density of sodium channels and spike frequency adaptation.