bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of peripheral nerve function in humans: novel insights from motor nerve excitability
Authors: Farrar Michelle A. , Park Susanna B. , Lin Cindy S.‐Y. , Kiernan Matthew C. 
Published: September 2012

Key points
The evolution of human peripheral nerve function after birth to facilitate more complex neural tasks has not been fully elucidated.
The present study has established the changes that occur in nerve function in developing humans using specialized non‐invasive excitability techniques in infants, children, adolescents and young adults for the first time.
The activity of axonal K+ conductances reduces with formation of the axo‐glial junction. This occurs simultaneously with alterations in passive membrane properties and conductance (axonal diameter and myelination).
These functional alterations serve to enhance the efficiency and speed of impulse conduction, whilst maintaining membrane stability, concurrent with the acquisition of motor skills in childhood.
Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development.
Abstract  While substantial alterations in myelination and axonal growth have been described during maturation, their interactions with the configuration and activity of axonal membrane ion channels to achieve impulse conduction have not been fully elucidated. The present study utilized axonal excitability techniques to compare the changes in nerve function across healthy infants, children, adolescents and adults. Multiple excitability indices (stimulus–response curve, strength–duration time constant, threshold electrotonus, current–threshold relationship and recovery cycle) combined with conventional neurophysiological measures were investigated in 57 subjects (22 males, 35 females; age range 0.46–24 years), stimulating the median motor nerve at the wrist. Maturational changes in conduction velocity were paralleled by significant alterations in multiple excitability parameters, similarly reaching steady values in adolescence. Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P= 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P < 0.001), or ‘fanned‐in’; resting current–threshold slope increased (P < 0.0001); accommodation to depolarizing currents prolonged (P < 0.0001); while greater threshold changes in refractoriness (P= 0.001) and subexcitability (P < 0.01) emerged. Taken together, the present findings suggest that passive membrane conductances and the activity of K+ conductances decrease with formation of the axo‐glial junction and myelination. In turn, these functional alterations serve to enhance the efficiency and speed of impulse conduction concurrent with the acquisition of motor skills during childhood, and provide unique insight into the evolution of postnatal human peripheral nerve function. Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development.
Quantification of arterial flow using digital subtraction angiography
Authors: Bonnefous Odile , Pereira Vitor Mendes , Ouared Rafik , Brina Olivier , Aerts Hans , Hermans Roel , van Nijnatten Fred , Stawiaski Jean , Ruijters Daniel 
Published: September 2012

Purpose:In this paper, a method for the estimation of arterial hemodynamic flow from x‐ray video densitometry data is proposed and validated using anin vitro setup.Methods:The method is based on the acquisition of three‐dimensional rotational angiography and digital subtraction angiography sequences. A modest contrast injection rate (between 1 and 4 ml/s) leads to a contrast density that is modulated by the cardiac cycle, which can be measured in the x‐ray signal. An optical flow based approach is used to estimate the blood flow velocities from the cyclic phases in the x‐ray signal.Results:The authors have validated this methodin vitro, and present three clinical cases. The in vitro experiments compared the x‐ray video densitometry results with the gold standard delivered by a flow meter. Linear correlation analysis and regression fitting showed that the ideal slope of 1 and intercept of 0 were contained within the 95 percentile confidence interval. The results show that a frame rate higher than 50 Hz allows measuring flows in the range of 2 ml/s to 6 ml/s within an accuracy of 5%.Conclusions:Thein vitro and clinical results indicate that it is feasible to estimate blood flow in routine interventional procedures. The availability of an x‐ray based method for quantitative flow estimation is particularly clinically useful for intra‐cranial applications, where other methods, such as ultrasound Doppler, are not available.
Patient radiation doses in interventional cardiology in the U.S.: Advisory data sets and possible initial values for U.S. reference levels
Authors: Miller Donald L. , Hilohi C. Michael , Spelic David C. 
Published: September 2012

Purpose:To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)].Methods:Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X‐ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnostic cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling.Results:Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (Ka,r), cumulative air kerma‐area product (PKA), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but PKA is higher in the U.S.Conclusions:Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.
Positional accuracy of novel x‐ray‐image‐based dynamic tumor‐tracking irradiation using a gimbaled MV x‐ray head of a Vero4DRT (MHI‐TM2000)
Authors: Mukumoto Nobutaka , Nakamura Mitsuhiro , Sawada Akira , Takahashi Kunio , Miyabe Yuki , Takayama Kenji , Mizowaki Takashi , Kokubo Masaki , Hiraoka Masahiro 
Published: September 2012

Purpose:To verify the positional accuracy of a novel x‐ray‐image‐based dynamic tumor‐tracking (DTT) irradiation technique using the gimbaled MV x‐ray head of a Vero4DRT (MHI‐TM2000).Methods:Verification of the x‐ray‐image‐based DTT was performed using three components: a three‐dimensional moving phantom with a steel ball target, a laser displacement gauge, and an orthogonal kV x‐ray imaging subsystem with a gimbaled MV x‐ray head and the system controller of the Vero4DRT. The moving phantom was driven based on seven periodic patterns [peak‐to‐peak amplitude (A): 20–40 mm, breathing period (T): 2–5 s] and 15 patients’ aperiodic respiratory patterns (A: 6.5–22.9 mm, T: 1.9–5.8 s). The target position was detected in real time with the orthogonal kV x‐ray imaging subsystem using the stereo vision technique. Subsequently, the Vero4DRT predicted the next position of the target, and then the gimbaled MV x‐ray head tracked the corresponding orientation of the target. The displacements of the target were measured synchronously using the laser displacement gauge. The difference between the target positions predicted by the Vero4DRT and those measured by the laser displacement gauge was computed as the prediction error (EP), and the difference between the target positions tracked by the gimbaled MV x‐ray head and predicted target positions was computed as the mechanical error (EM). Total tracking system error (ET) was defined as the difference between the tracked and measured target positions.Results:The root mean squares (RMSs) of EP, EM, and ET were up to 0.8, 0.3, and 0.7 mm, respectively, for the periodic patterns. Regarding the aperiodic patterns, the median RMSs of EP, EM, and ET were 1.2 (range, 0.9–1.8) mm, 0.1 (range, 0.1–0.5) mm, and 1.2 (range, 0.9–1.8) mm, respectively. From the results of principal component analysis, tracking efficiency, defined as the ratio of twice the RMS of ET to A, was improved for patients with high respiratory function (R = 0.91; p < 0.01).Conclusions:The present study demonstrated that the Vero4DRT is capable of high‐accuracy x‐ray‐image‐based DTT. ET was caused primarily by EP, and EM was negligible. Furthermore, principal component analysis showed that tracking efficiency could be improved with this system, especially for patients with high respiratory function.
SlicerRT: Radiation therapy research toolkit for 3D Slicer
Authors: Pinter Csaba , Lasso Andras , Wang An , Jaffray David , Fichtinger Gabor 
Published: September 2012

Purpose:Interest in adaptive radiation therapy research is constantly growing, but software tools available for researchers are mostly either expensive, closed proprietary applications, or free open‐source packages with limited scope, extensibility, reliability, or user support. To address these limitations, we propose SlicerRT, a customizable, free, and open‐source radiation therapy research toolkit. SlicerRT aspires to be an open‐source toolkit for RT research, providing fast computations, convenient workflows for researchers, and a general image‐guided therapy infrastructure to assist clinical translation of experimental therapeutic approaches. It is a medium into which RT researchers can integrate their methods and algorithms, and conduct comparative testing.Methods:SlicerRT was implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. SlicerRT provides functionality specifically designed for radiation therapy research, in addition to the powerful tools that 3D Slicer offers for visualization, registration, segmentation, and data management. The feature set of SlicerRT was defined through consensus discussions with a large pool of RT researchers, including both radiation oncologists and medical physicists. The development processes used were similar to those of 3D Slicer to ensure software quality. Standardized mechanisms of 3D Slicer were applied for documentation, distribution, and user support. The testing and validation environment was configured to automatically launch a regression test upon each software change and to perform comparison with ground truth results provided by other RT applications.Results:Modules have been created for importing and loading DICOM‐RT data, computing and displaying dose volume histograms, creating accumulated dose volumes, comparing dose volumes, and visualizing isodose lines and surfaces. The effectiveness of using 3D Slicer with the proposed SlicerRT extension for radiation therapy research was demonstrated on multiple use cases.Conclusions:A new open‐source software toolkit has been developed for radiation therapy research. SlicerRT can import treatment plans from various sources into 3D Slicer for visualization, analysis, comparison, and processing. The provided algorithms are extensively tested and they are accessible through a convenient graphical user interface as well as a flexible application programming interface.
An efficient protocol for radiochromic film dosimetry combining calibration and measurement in a single scan
Authors: Lewis David , Micke Andre , Yu Xiang , Chan Maria F. 
Published: September 2012

Purpose:Radiochromic film provides dose measurement at high spatial resolution, but often is not preferred for routine evaluation of patient‐specific intensity modulated radiation therapy (IMRT) plans owing to ease‐of‐use factors. The authors have established an efficient protocol that combines calibration and measurement in a single scan and enables measurement results to be obtained in less than 30 min. This avoids complications due to postexposure changes in radiochromic film that delay the completion of a measurement, often for up to 24 h, in commonly used methods. In addition, the protocol addresses the accuracy and integrity of the measurement by eliminating environmental and interscan variability issues.Methods:The authors collected dose–response data from six production lots of Gafchromic EBT3 film and three production lots of EBT2 film at doses up to 480 cGy. In this work, the authors used seven different scanners of two different models—Epson 10000XL and V700; postexposure times before scanning from 30 min to 9 days; ambient temperatures for scanning spanning 11 °C; and two film orientations. Scanning was in 48‐bit RGB format at 72 dpi resolution. Dose evaluation was conducted using a triple‐channel dosimetry method. To evaluate the measurement protocol, patient specific IMRT and volumetric modulated arc therapy (VMAT) plans were exposed onto EBT3 films on a Varian Trilogy Linac. Film scanning was done following the protocol under a number of different conditions and the dose maps were analyzed to demonstrate the equivalence of results.Results:The results indicated that the dose–response data could be fit by a set of related rational functions leading to the description of a generic calibration curve. A simplified dosimetry protocol was established where dose–response data for a specific film lot, scanner, and scanning conditions could be derived from two films exposed to known doses. In most cases only one calibrated exposure was required since the dose for one of the films could be zero. Using the Gamma test criterion of 2%/2 mm to evaluate the measurements, similar passing rates ranging between about 95% and 99% for the fields studied were obtained from application films digitized under a variety of conditions all of them different than the conditions under which the calibration films were scanned.Conclusions:The authors have developed a simplified and efficient protocol to measure doses delivered by an IMRT or VMAT plan using only the patient film, one calibration film, one unexposed film, and applying a single scan to acquire a digital image for calculation and analysis. The simplification and timesaving offer a potential practical solution for using radiochromic film for routine treatment plan quality assurance without sacrificing spatial resolution for convenience.
Supporting network evolution and incremental deployment with XIA
Authors: Grandl Robert , Han Dongsu , Lee Suk-Bok , Lim Hyeontaek , Machado Michel , Mukerjee Matthew , Naylor David 
Published: September 2012

eXpressive Internet Architecture (XIA) [1] is an architecture that natively supports multiple communication types and allows networks to evolve their abstractions and functionality to accommodate new styles of communication over time. XIA embeds an elegant mechanism for handling unforeseen communication types for legacy routers.
In this demonstration, we show that XIA overcomes three key barriers in network evolution (outlined below) by (1) allowing end-hosts and applications to start using new communication types (e.g., service and content) before the network supports them, (2) ensuring that upgrading a subset of routers to support new functionalities immediately benefits applications, and (3) using the same mechanisms we employ for 1 and 2 to incrementally deploy XIA in IP networks.
The Thr715Pro variant impairs terminal glycosylation of P-selectin
Authors: Subramanian Hariharan , Gambaryan Stepan , Panzer Simon , Gremmel Thomas , Walter Ulrich , Mannhalter Christine 
Published: September 2012

SummaryP-selectin variant 715Pro is associated with lower concentrations of plasma P-selectin and reduced risk for thrombosis. We examined the influence of 715Pro on P-selectin synthesis, post-translational processing, surface expression and function using HEK293 cells, which do not express endogenous P-selectin. Mass spectrometry revealed that HEK293 cells produced recombinant P-selectin which has a glycosylation pattern comparable to platelet P-selectin. Compared to wild-type transfectants, 715Pro transfectants have ~50% less terminally glycosylated P-selectin and accumulate more immature P-selectin in Golgi. Following Brefeldin A treatment, the majority of 715Pro P-selectin is not modified by Golgi enzymes, while wild-type P-selectin undergoes complete modification. Flow cytometry revealed that 715Pro transfectants have ~20% less P-selectin on the cell surface compared to wild-type transfectants. Secretion of P-selectin by 715Pro transfectants was about 38% lower compared to wild-type transfectants. Binding of HL-60 cells to 715Pro transfectants was ~29% lower than to wild-type transfectants. This observation was confirmed by the presence of fewer platelet-monocyte aggregates (PMA) in the blood of healthy individuals and patients with angiographically proven atherosclerosis, carrying 715Pro P-selectin compared to individuals with wild-type P-selectin. We conclude that the 715Pro variant impairs terminal glycosylation of P-selectin in Golgi, leading to reduced amounts of mature P-selectin and subsequently less surface expression and secretion of P-selectin. The reduced surface expression of 715Pro P-selectin contributes to inefficient adhesion to HL-60 cells or monocytes.
Efficacy and safety of prophylaxis with once-weekly BAY 79–4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients
Authors: Martinowitz Uri , Windyga Jerzy , Di Minno Giovanni , Hellmann Andrzej , Pabinger Ingrid , Enriquez Monika , Schwartz Lawrence , Ingerslev Jørgen , Powell Jerry ,   the LipLong Study Investigators
Published: September 2012

SummaryThe benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79–4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79–4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79–4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79–4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79–4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79–4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79–4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.
Management consensus guidance for the use of rivaroxaban – an oral, direct factor Xa inhibitor
Authors: Kreutz Reinhold , Llau Juan , Norrving Bo , Haas Sylvia , Turpie Alexander 
Published: September 2012

SummaryA number of novel oral anticoagulants that directly target factor Xa or thrombin have been developed in recent years. Rivaroxaban and apixaban (direct factor Xa inhibitors) and dabigatran etexilate (a direct thrombin inhibitor) have shown considerable promise in large-scale, randomised clinical studies for the management of thromboembolic disorders, and have been approved for clinical use in specific indications. Rivaroxaban is licensed for the prevention of venous thromboembolism in patients undergoing elective hip or knee replacement surgery, the treatment of deep-vein thrombosis and prevention of recurrent venous thromboembolism, and for stroke prevention in patients with non-valvular atrial fibrillation. Based on the clinical trial data for rivaroxaban, feedback on its use in clinical practice and the authors’ experience with the use of rivaroxaban, practical guidance for the use of rivaroxaban in special patient populations and specific clinical situations is provided. Although most recommendations are in line with the European summary of product characteristics for the approved indications, additional and, in several areas, different recommendations are given based on review of the literature and the authors’ clinical experience.
A novel D235Y mutation in the GP1BA gene enhances platelet interaction with von Willebrand factor in an Iranian family with platelet-type von Willebrand disease
Authors: Enayat Said , Ravanbod Shirin , Rassoulzadegan Maryam , Jazebi Mohammad , Tarighat Shirin , Ala Fereydoun , Emsley Jonas , Othman Maha 
Published: September 2012

SummaryPlatelet-type von Willebrand disease (PT-VWD) is a rare bleeding disorder with an intrinsic defect in platelets rather than von Willebrand factor (VWF), but has clinical and laboratory features similar to the more common type 2B VWD. The intriguing nature of the pathophysiology and molecular genetics of PT-VWD has created lengthy debate in literature regarding its discrimination from type 2B VWD, and essentially confirming DNA analysis as the gold standard in diagnosis and revealing pathologic mutations. In this report we identify a novel Asp235Tyr mutation in the GP1BA gene of two Iranian patients showing the PT-VWD phenotype who were originally misdiagnosed as type 2B VWD. By structural modelling of the mutant by introducing Tyr235 into the available crystal structure of the glycoprotein (GP)Ibα N-terminal domain, we observed the mutant Tyr235 generates a hydrophobic tip to the extended β-switch loop of GPIbα. Further modelling of the resulting complex with VWFA1 indicates this could result in an enhanced interface compared to wild-type Asp235. This data provides an update to the present knowledge about this rare disorder, and confirms the necessity of genetic testing for accurate diagnosis, and the importance of studying natural mutations to better understand molecular aspects of GPIbα-VWFA1 interaction.