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Introduction: Prompt and effective hemorrhage control is paramount to improve survival in patients with catastrophic bleeding. In the ever-expanding field of bleeding control techniques, there is a need for a realistic training model to practice these life-saving skills. This study aimed to create a realistic perfused post-mortem human specimen (PMHS) flow model that is suitable for training various bleeding control techniques. Materials and Methods: This laboratory study was conducted in the SkillsLab & Simulation Center of Erasmus MC, University Medical Center Rotterdam, the Netherlands. One fresh frozen and five AnubiFiX® embalmed PMHS were used for the development of the model. Subsequent improvements in the exact preparation and design of the flow model were made based on model performance and challenges that occurred during this study and are described. Results: Circulating arteriovenous flow with hypertonic saline was established throughout the entire body via inflow and outflow cannulas in the carotid artery and jugular vein of embalmed PMHS. We observed full circulation and major hemorrhage could be mimicked. Effective bleeding control was achieved by placing a resuscitative endovascular balloon occlusion of the aorta (REBOA) catheter in the model. Regional perfusion significantly reduced the development of tissue edema. Conclusion: Our perfused PMHS model with circulating arterial and venous flow appears to be a feasible method for the training of multiple bleeding control techniques. Regional arteriovenous flow successfully reduces tissue edema and increases the durability of the model. Further research should focus on reducing edema and enhancing the durability of the model.

Purpose: Use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as adjunct for temporary hemorrhage control in patients with exsanguinating torso hemorrhage is increasing. Characteristics of aortic occlusion balloons (AOB) are diverse and evolving as efforts are made to improve the technology. It is important to select a device that fits the requirements of the medical situation to minimize the risk of failure and complications. The aim of this study is to appraise guidance in the choice of an AOB in a specific situation. Methods: We assessed 29 AOB for differences and outline possible advantages and disadvantages of each. Bending stiffness was measured with a three-point bending device. Results: Diameter of the AOB ranged from 6 (ER-REBOA™) to 10 (Coda®-46) French. However, some need large-bore access sheaths up to 22 French (Fogarty®-45 and LeMaitre®-45) or even insertion via cut-down (Equalizer™-40). Bending stiffness varied from 0.08 N/mm (± 0.008 SD; Coda®-32) to 0.72 N/mm (± 0.024 SD; Russian prototype). Rescue Balloon™ showed kinking of the shaft at low bending pressures. The only non-compliant AOB is REBOA Balloon®. ER-REBOA™, Fogarty®, LeMaitre®, REBOA Balloon®, and Rescue Balloon™ are provided with external length marks to assist blind positioning. Conclusion: In resource-limited settings, a guidewire- and fluoroscopy-free, rather stiff device, such as ER-REBOA™, Fogarty®, and LeMaitre®, is warranted. Of these devices, ER-REBOA™ is the only catheter compatible with seven French sheaths and specifically designed for emergency hemorrhage control. Of the over-the-wire devices, Q50® has several features that facilitate use and reduce the risk of malplacement or vessel damage.

BACKGROUND Hemorrhage from truncal and junctional injuries is responsible for the vast majority of potentially survivable deaths in combat casualties, causing most of its fatalities in the prehospital arena. Optimizing the deployment of the advanced bleeding control modalities required for the management of these injuries is essential to improve the survival of severely injured casualties. This study aimed to establish consensus on the optimal use and implementation of advanced bleeding control modalities in combat casualty care.METHODS A Delphi method consisting of three rounds was used. An international expert panel of military physicians was selected by the researchers to complete the Delphi surveys. Consensus was reached if 70% or greater of respondents agreed and if 70% or greater responded.RESULTS Thirty-two experts from 10 different nations commenced the process and reached consensus on which bleeding control modalities should be part of the standard equipment, that these modalities should be available at all levels of care, that only trained physicians should be allowed to apply invasive bleeding control modalities, but all medical and nonmedical personnel should be allowed to apply noninvasive bleeding control modalities, and on the training requirements for providers. Consensus was also reached on the necessity of international registries and guidelines, and on certain indications and contraindications for resuscitative endovascular balloon occlusion of the aorta (REBOA) in military environments. No consensus was reached on the role of a wound clamp in military settings and the indications for REBOA in patients with chest trauma, penetrating axillary injury or penetrating neck injury in combination with thoracoabdominal injuries.CONCLUSION Consensus was reached on the contents of a standard bleeding control toolbox, where it should be available, providers and training requirements, international registries and guidelines, and potential indications for REBOA in military environments.

Aim: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR © 2022 The Authors

Use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as adjunct for temporary hemorrhage control in patients with exsanguinating torso hemorrhage is increasing. Characteristics of aortic occlusion balloons (AOB) are diverse and evolving as efforts are made to improve the technology. It is important to select a device that fits the requirements of the medical situation to minimize the risk of failure and complications. The aim of this study is to appraise guidance in the choice of an AOB in a specific situation.We assessed 29 AOB for differences and outline possible advantages and disadvantages of each. Bending stiffness was measured with a three-point bending device.Diameter of the AOB ranged from 6 (ER-REBOA™) to 10 (CodaIn resource-limited settings, a guidewire- and fluoroscopy-free, rather stiff device, such as ER-REBOA™, Fogarty

A 63-year old female was referred to our hospital because she had a mass on the right side of the neck. The swelling had slowly progressed in a couple of months. Besides problems with swallowing there were no other complaints. Her previous medical history was unremarkable and she could not remember any family members with similar lesions. Physical examination showed a non-tender mass with a diameter of around 6 cm located just anterior of the sternocleidomastoid muscle in the anterior triangle of the neck. The mass was mobile in a back-forward direction but could not be moved in a cranial-caudal direction. No signs of cranial nerve deficits were detected. An ultrasound examination showed a highly vascularized structure in the bifurcation between the internal and external carotid artery (Fig. 33.1).

Ion Cyclotron Radio Frequency (ICRF) antennas operating under high voltage to couple high power to fusion plasmas are at risk of electrical arcing. The standard Voltage Standing Wave Ratio (VSWR) system does not protect low impedance areas, which are used in antennas to achieve load tolerance to variations in plasma loading during Edge Localised Modes (ELMs). The Scattering Matrix Arc Detection System (SMAD) was designed to create additional protection for these areas, and 4 complete systems were implemented and tested on the ITER-like antenna (ILA) on JET. This paper describes the performance under relevant experimental conditions of load tolerance and/or high voltage and electrical arcing causing generator trip events.

Operating ion cyclotron resonance heating (ICRH) antennas at high power density puts them at risk of arcing which reduces the coupled power to the plasma because the perturbed impedance match triggers the voltage standing wave ratio (VSWR) based generator trip system but even worse might damage the antenna beyond repair because of the arc's localised energy deposition. New antennas are designed to operate in a load tolerant way which creates low impedance zones that are especially at risk since the existing VSWR protection systems are less sensitive to arcs in these areas. To protect these low impedance areas, a new arc protection system referred as scattering matrix arc detection (SMAD) has been proposed. This paper describes the basic operating principle and implementation in hard- and software for the JET ITER-like antenna (ILA), with testbed and preliminary JET commissioning results.

The ion cyclotron resonance frequency (ICRF) heating system on JET is currently being upgraded to validate new matching concepts in view of coupling ICRF power to ITER-like plasmas and to further increase the total additional heating power on JET. The present paper reports on first testbed results from the new JET ITER-like antenna as well as on the first use of the newly installed hybrid couplers between two of the existing A2 antennas. Several other on-going improvements, such as improved trip management system, external conjugate-T matching circuit and arc detection systems are also discussed.

Contains fulltext : 48612.pdf (Publisher’s version ) (Closed access) We aimed to quantify the effects of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) on stance and gait ("axial"motor control), and related this to effects on finger movements ("appendicular" motor control). Fourteen PD patients and 20 matched controls participated. Subjects completed several balance and gait tasks (standing with eyes open or closed, on a normal or foam surface; retropulsion test; walking with eyes closed; walking up and down stairs; Get Up and Go test). Postural control was quantified using trunk sway measurements (angle and angular velocity) in the roll and pitch directions. Subjects further performed a pinch grip reaction time task, where we measured isometric grip forces, as well as movement and reaction times. Patients were examined with STN stimulators switched on or off (order randomised across patients), always after a supramaximal levodopa dosage. STN stimulation improved postural control, as reflected by a reduced trunk sway tremor during stance, a reduced duration for all gait tasks, an increased trunk pitch velocity while rising from a chair, and improved roll stability. STN stimulation also improved finger control, as reflected by a reduced time to reach maximum grip force, without altering reaction times and maximum force levels. Improvements in finger control timing did not correlate with reduced task durations during gait. We conclude that STN stimulation affords improvement of postural control in PD, over and above optimal drug treatment. STN stimulation also provides a simultaneous effect on distal and axial motor control. Because improvements in distal and axial motor control were not correlated, we assume that these effects are mediated by stimulation of different structures within the STN.

The objective of this study was to determine the role of a mortality registration in the quality control of patients who died after peripheral bypass surgery. We developed a mortality registration to classify causes of death, to evaluate shortcomings in treatment, and to determine the extent of agreement between pre- and postmortem findings. In a 10-year period, 28 of the 1,022 patients (2.7%) who underwent peripheral arterial reconstruction died. Fifty-three percent of the patients died owing to postoperative complications, most frequently a myocardial infarction. A shortcoming in the medical treatment was observed in only one patient. Forty-three percent of the relatives gave permission for an autopsy. In only two cases, the autopsy report revealed a myocardial infarction that had remained unnoticed during the clinical course. In this selected group of patients undergoing a peripheral bypass operation, the causes of death and the shortcomings in medical care could usually be identified without the help of autopsy data.

The full spectral electric dyadic Green's function for three dimensional current distributions in planar stratified media can be obtained straight from Maxwell's equations. By following a physical reasoning analogous with the free space case but using general derivative relations for multilayered Green's functions, we derive a "basic" mixed potential form with a simple vector potential kernel but multiple scalar potential kernels, and also obtain the well established single scalar potential formulations with a dyadic vector potential kernel. Mixed potential forms are thus arrived at without the a priori introduction of scalar and vector potential, or choice of gauge condition. The nonuniqueness of the scalar potential kernel and the dyadic nature of the scalar and/or vector potentials are believed to be clarified by the proposed approach. A discussion of the different formulations focuses on physical meaning and numerical consequences for the solution of integral equations.

Planar circuits and antennas in stratified media are efficiently analyzed using an integral-equation formulation with a spectral-domain approach to construct the required Green's functions. This efficiency is largely lost when arbitrary three-dimensional (3-D) structures have to be analyzed. We, therefore, focus attention on "quasi 3-D" structures, which, although not fully 3-D, are still seen to cover most practical problems. The formulation of the electric field is adapted to the geometry as a hybrid dyadic-mixed-potential form. Evaluation of all z, z/sup '/-dependent parts of the reaction integrals is done analytically in the spectral domain. The remaining evaluation is done in the space domain with a mixed-potential formalism. We obtain a combined spectral-space domain approach to solve the integral equation. Numerical results demonstrate the applicability of the method to (most) 3-D problems that occur in planar stratified media.

Objective: To evaluate treatment and complications which is essential for good medical practice. Design: Prospective audit. Setting: City hospital, the Netherlands. Subjects: All the patients who died on the surgical ward between 1994 and 1998 and were classified according to four categories of mortality recording. Interventions: The causes of death, inaccuracies in treatment and the extent of agreement between premortem and postmortem findings were documented. Main outcome measures: Morbidity and mortality. Results: Of the 11 195 patients admitted, 420 (4%) deceased during their hospital stay. Most patients died of the disease with which they presented at admission ( n = 176, 42%) or of complications ( n = 167, 40%). In 20% ( n = 83) of the cases a shortcoming in the clinical course was found. 251 of the 420 patients who died (60%) had a necropsy. 53 of the 251 reports (21%) gave information that could have had an effect on the treatment or the clinical course. Conclusions: Recording mortality is a way o...

Background: A mortality registration system for patients who died after admission to a surgical ward with a hip fracture was developed. The aim of this study was to verify whether performing autopsies is necessary to obtain an accurate picture of the clinical course of these patients. Methods: The mortality registration system was used to classify causes of death, to evaluate shortcomings in treatment, and to determine the extent of agreement between clinical and autopsy findings. Results: Between 1989 and 1998, 101 of the 1,240 patients (8%) admitted with a hip fracture died in hospital. Most of these patients (61%) died of postoperative complications, of which pneumonia was the most common. Shortcomings in medical treatment were observed in 16 of the 101 deaths (16%). Permission to perform an autopsy was given by the relatives of 46 patients (46%); in three patients (7%) there was a disparity between clinical and autopsy findings. Conclusions: The disparity between clinical and autopsy findings depends on the accuracy of the preoperative diagnosis and the complexity of the postoperative events. In this selected group of hip fracture patients, the causes of death and the shortcomings in medical care could be identified without the help of autopsy data.

We constrain the rotation law in Be star circumstellar disks. We show that Keplerian rotation is a valid approximation.

Previous research has revealed that cells contributing to coronary vascular formation are derived from the dorsal mesocardium, however, the fate of these cells during consecutive stages of heart development is still unclear. We have conducted a study regarding the recruitment of vascular components and the subsequent differentiation into mature vessel wall structures with the aid of immunohistochemical markers directed against endothelium, smooth muscle cells, and fibroblasts. The proepicardial organ including an adhering piece of primordial liver of quail embryos (ranging from HH15 to HH18) was transplanted into the pericardial cavity of chicken embryos (ranging from HH15 to HH18). The chicken-quail chimeras (n=16) were harvested from the early stage of endothelial tube formation (HH25) to the late stage of mature vessel wall composition (HH43). Before HH32 endothelial cells have invaded the myocardium to give rise to yet undifferentiated coronary vessels. These endothelial cells are not accompanied by other non-endothelial cells. The superficial epicardial layer changes from a squamous mesothelium into a cuboid epithelium preceding media and adventitia formation. Subsequently, a condensed area of mesenchymal cells delaminates from the cuboidal lining extending toward the vessel plexus. Around the coronary arteries, these mesenchymal cells differentiate into smooth muscle cells or fibroblasts as shown by immunohistochemical markers. We conclude that epithelial-mesenchymal transformation of the epicardial lining delivers the smooth muscle cells and fibroblasts of the coronary arterial vessel wall. Molecules involved in epithelial transformation processes elsewhere in the embryo are also expressed within the subepicardial layer, and are considered to participate in inducing this process.

ITER's Ion Cyclotron Range of Frequencies (ICRF) system [1] comprises two antenna launchers designed by CYCLE (a consortium of European associations listed in the author affiliations above) on behalf F4E for the ITER Organisation (IO), each inserted as a Port Plug (PP) into one of ITER's Vacuum Vessel (VV) ports. Each launcher is an array of 4 toroidal by 6 poloidal RF current straps specified to couple up to 20 MW in total to the plasma in the frequency range of 40 to 55 MHz but limited to a maximum system voltage of 45 kV and limits on RF electric fields depending on their location and direction with respect to respectively the torus vacuum and the toroidal magnetic field. A crucial aspect of coupling ICRF power to plasmas is the knowledge of the plasma density profiles in the Scrape-Off Layer (SOL) and the location of the RF current straps with respect to the SOL. The launcher layout and details were optimized and its performance estimated for a worst case SOL provided by the IO. The paper summarizes the estimated performance obtained within the operational parameter space specified by IO. Aspects of the RF grounding of the whole antenna PP to the VV port and the effect of the voids between the PP and the Blanket Shielding Modules (BSM) surrounding the antenna front are discussed.

Objective: The differentiation of the coronary vasculature was studied to establish in particular the formation of the coronary venous system. Methods: Antibody markers were used to demonstrate endothelial, smooth muscle, and fibroblastic cells in serial sections of embryonic quail hearts. The anti- β myosin heavy chain and the neuronal marker HNK-1 were added to our incubation protocol. Results: In HH32, the coronary vascular network has developed into a circulatory system with connections to the sinus venosus, the aorta and the right atrium. The connections between the aorta and the right atrium allow for direct arteriovenous shunting. Subsequently, differentiation into coronary arteries and veins occurs with an interposed capillary network. The smooth muscle cells of the coronary arterial media derive from the subepicardial layer, whereas the subepicardially located cardiac veins recrute atrial myocardium, as these cells express the β -myosin heavy chain antigen. Ganglia are located in the subepicardium close to the vessels, while nerve fibres tend to colocalize with the formed vessel channels. Conclusions: A new finding is presented in which the subepicardial coronary veins have a media that consists of myocardial cells. The close positional relationship of neural tissue and coronary vessels that penetrate the heart wall is explained as inductive for vessel wall differentiation, but not for invasion into the heart.

Research concerning the em- bryologic development of the coronary plexus has enriched our understanding of anomalous coronary vessel patterning. However, the differen- tiation of the coronary vessel plexus into arteries, veins, and a capillary network is still incomplete. Immunohistochemical techniques have been used for whole mounts and serial sections of quail embryo hearts to demonstrate endothelium, vas- cular smooth muscle cells, and fibroblasts. From HH35 onward, the lumen of the coronary plexus was visualized by injecting India ink into the aorta. In HH17, branches from the sinus venosus plexus expand into the proepicardial organ to reach the dorsal side of the atrioventricular sul- cus. From HH25 onward, vessel formation pro- ceeds toward the ventral side and the apex of the heart. After lumenized connections of the coro- nary vessels with the aorta and right atrium are established, a media composed of smooth muscle cells and an adventitia composed of procollagen- producingfibroblasts are formed around the coro- nary arteries. In the early stage, bloodflow through the coronary plexus is possible, although connections with the aorta have yet to be estab- lished. After the coronary plexus and the aorta and right atrium are interconnected, coronary vessel differentiation proceeds by media and ad- ventitia formation around the proximal coronary arteries. At the same time, the remodeling of the vascular plexus is manifested by disappearance of arteriovenous anastomoses, leaving only capil- laries to connect the arterial and venous system. Dev. Dyn. 208:338-348, 1997. r 1997 Wiley-Liss, Inc.

The ITER Ion Cyclotron Range of Frequencies (ICRF) antenna's capacity to couple power to plasma is determined by the plasma Scrape-Off Layer (SOL) profile, shaping of the front strap array, layout of the Port Plug (PP) and detailed design of its RF components. The first two factors are taken into account by the Torino Polytechnic Ion Cyclotron Antenna (TOPICA) calculated strap array Scattering/Impedance 24-port ( S 24 × 24 −/ Z 24 × 24 −) matrices, while this paper deals with the optimisation of the PP layout and components. The RF modeling techniques are explained and used to maximise the coupled power under a set of constraints on RF quantities inside the PP. The total PP RF surface conductive and volumetric dielectric losses are calculated. The resulting S -parameters at the rear RF PP flanges are evaluated as input for the design of the pre-match, decoupling and matching network outside the PP. A discussion of the effect of errors on the PP excitation on the coupled power is also included.

The ongoing design of the ITER Ion Cyclotron Heating and Current Drive system (20 MW, 40-55 MHz) is rendered challenging by the wide spectrum of requirements and interface constraints to which it is subject, several of which are conflicting and/or still in a high state of flux. These requirements include operation over a broad range of plasma scenarios and magnetic fields (which prompts usage of wide-band phased antenna arrays), high radio-frequency (RF) power density at the first wall (and associated operation close to voltage and current limits), resilience to ELM-induced load variations, intense thermal and mechanical loads, long pulse operation, high system availability, efficient nuclear shielding, high density of antenna services, remote-handling ability, tight installation tolerances, and nuclear safety function as tritium confinement barrier. R&D activities are ongoing or in preparation to validate critical antenna components (plasma-facing Faraday screen, RF sliding contacts, RF vacuum windows), as well as to qualify the RF power sources and the transmission and matching components. Intensive numerical modeling and experimental studies on antenna mock-ups have been conducted to validate and optimize the RF design. The paper highlights progress and outstanding issues for the various system components. (C) 2013 ITER Organization. Published by Elsevier B.V. All rights reserved.

The next step in the Wendelstein stellarator line is the large superconducting device Wendelstein 7-X, currently under construction in Greifswald, Germany. Steady-state operation is an intrinsic feature of stellarators, and one key element of the Wendelstein 7-X mission is to demonstrate steady-state operation under plasma conditions relevant for a fusion power plant. Steady-state operation of a fusion device, on the one hand, requires the implementation of special technologies, giving rise to technical challenges during the design, fabrication and assembly of such a device. On the other hand, also the physics development of steady-state operation at high plasma performance poses a challenge and careful preparation. The electron cyclotron resonance heating system, diagnostics, experiment control and data acquisition are prepared for plasma operation lasting 30 min. This requires many new technological approaches for plasma heating and diagnostics as well as new concepts for experiment control and data acquisition.

When testing the SHAD system on JET ICRF antennas, parasitic signals in the detection band (5–20MHz) were detected. We have identified emission from grid breakdown events in the Neutral Beam injectors, and Ion Cyclotron Emission from the plasma. Spurious signals in the band 4–10 MHz are also often observed at the onset of ELM events. Such parasitic signals could complicate the design and operation of SHAD in ICRF systems for fusion devices.

RF arc detection is a key operational and safety issue for the ICRF system on ITER. Indeed the high voltages inside the antenna put it at risk of arcing, which could cause substantial damage. This paper describes the various possibilities explored by circuit simulation and the strategy now considered to protect the ITER ICRF antenna from RF arcs.

In the past years, one of the focal points of the JET experimental programme was on ion-cyclotron resonance heating (ICRH) studies in view of the design and exploitation of the ICRH system being developed for ITER. In this brief review, some of the main achievements obtained in JET in this field during the last 5 years will be summarized. The results reported here include important aspects of a more engineering nature, such as (i) the appropriate design of the RF feeding circuits for optimal load resilient operation and (ii) the test of a compact high-power density antenna array, as well as RF physics oriented studies aiming at refining the numerical models used for predicting the performance of the ICRH system in ITER. The latter include (i) experiments designed for improving the modelling of the antenna coupling resistance under various plasma conditions and (ii) the assessment of the heating performance of ICRH scenarios to be used in the non-active operation phase of ITER. © 2011 IOP Publishing Ltd.

Over the last decade, endovascular aneurysm repair (EVAR) has been used extensively for the elective treatment of infra-renal abdominal aneurysms. However, it remains unclear how specific devices perform and how they compare to others. We provide an overview of currently used endografts, and discuss the current evidence regarding device-specific outcomes. Published literature confirms differences in results according to endograft selection. These differences were more pronounced with older generations of devices, in comparison to newer models. Contemporary results are generally good and one should remember that no randomized data exist regarding individual device performance. Moreover, by the time there is enough follow-up to draw conclusions, the data is relatively obsolete due to constant improvements in endograft technology and design. Results from EVAR have been steadily improving and individualized device selection has shown to be valuable. It appears that patients with favorable anatomy do well with most modern endografts. Those with challenging anatomies may benefit more from a particular design, delivery and deployment feature requiring greater knowledge and experience for adequate device selection.

Contains fulltext : 80017.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. METHODS: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. FINDINGS: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. INTERPRETATION: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. FUNDING: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.

In this paper, significant results in the heating and current drive domains obtained at JET in the past few years following systems upgrade and dedicated experimental time, will be reviewed. Firstly, an overview of the new Ion Cyclotron Resonance Frequency (ICRF) heating capabilities will be presented i.e. results from the ITER‐Like ICRF antenna (ILA), the use of External Conjugate‐T and 3dB hybrid couplers to increase the ICRF power during ELMy H‐mode. Furthermore, experiments to study the influence of the phasing of the ICRF antenna on power absorption and coupling will be described. Looking at Low Hybrid (LH) issues for ITER, the effect of the location of gas injection on the LH coupling improvement at large launcher‐separatrix distances will be discussed as the possibility to operate at ITER‐relevant power densities. Experiments to characterise the LH power losses in the Scrape‐Off‐Layer (SOL) and to determine the LH wave absorption and current drive using power modulation will be shown. Finally, plas...

The commissioning of the ITER‐Like ICRF Antenna (ILA) [1] on JET plasmas from May 2008 to April 2009 in various conditions (33, 42 and 47 MHz, L‐ and H‐mode, antenna strap‐plasma separatrix distances of ∼9 to 17 cm) has provided relevant information for future antenna design and operation. The maximum power density achieved was 6.2 MW/m2 in L‐mode with strap to plasma separatrix distance of ∼9–10 cm at 42 MHz on the lower half of the ILA extrapolating to 8 MW/m2 if the full generator power had been available. Efficient (trip‐free operation) ELM tolerance was obtained both at 33 and 42 MHz on a large range of ELMs with strap voltages up to 42 kV and a maximum power density of 4.1 MW/m2. The paper reviews these achievements as well as remaining issues.

Following an overview of the ITER Ion Cyclotron Resonance Frequency (ICRF) system, the JET ITER‐like antenna (ILA) will be described. The ILA was designed to test the following ITER issues: (a) reliable operation at power densities of order 8 MW/m2 at voltages up to 45 kV using a close‐packed array of straps; (b) powering through ELMs using an internal (in‐vacuum) conjugate‐T junction; (c) protection from arcing in a conjugate‐T configuration, using both existing and novel systems; and (d) resilience to disruption forces. ITER‐relevant results have been achieved: operation at high coupled power density; control of the antenna matching elements in the presence of high inter‐strap coupling, use of four conjugate‐T systems (as would be used in ITER, should a conjugate‐T approach be used); operation with RF voltages on the antenna structures up to 42 kV; achievement of ELM tolerance with a conjugate‐T configuration by operating at 3Ω real impedance at the conjugate‐T point; and validation of arc detection sys...

The Scattering Matrix Arc Detection System (SMAD) has been fully deployed on all 4 sets of Resonant Double Loop (RDL), Vacuum Transmission Line (VTL) and Antenna Pressurised Transmission Lines (APTL) of the JET ICRF ITER‐Like Antenna (ILA) and this has been indispensable for operating at low (real) T‐point impedance values to investigate ELM tolerance. This paper describes the necessity of the SMAD vs VSWR (Voltage Standing Wave Ratio) protection system, SMAD commissioning, problems and a number of typical events detected by the SMAD system during operation on plasma.

Ion Cyclotron Resonance Frequency (ICRF) antennas achieve maximum power transfer from RF generator to plasma load by establishing an impedance match. The JET ITER‐Like Antenna (ILA) consists of 4 mutually coupled resonators that need to be matched simultaneously and whose resonant states need to be accurately controlled by several available actuators to couple maximum power and to achieve optimal ELM resilience. The operation of the matching system is described. Experimental operation revealed some phenomena and sensitivities that did not surface from simulation alone and that should be taken into account for the design of future ICRF antennae systems.

A set of simulation/interpretation tools based on transmission line theory and on the RF model developed by M. Vrancken [2] has been developed to study the ITER‐like Antenna (ILA) at JET. For given tuning element settings, the unique solution of the equations governing the ILA circuit requires solving a system of coupled linear equations relating the voltages and currents at the antenna straps and other key locations. This computation allows cross‐checking predicted values against measured experimental ones. Further more, a minimization procedure allows improving the correspondence with the quantities measured in the circuit during shots, thus coping with unavoidable errors arising from uncertainties in the measurements or from inaccuracies in the adopted RF model. Typical applications are e.g. fine‐tuning of the second‐stage of the ILA circuit for increased ELM‐resilience, cross‐checking the calibration of the measurements throughout the circuit and predicting the antenna performance and matching conditions in new plasma scenarios.

Objective: To evaluate a modified technique for carotid body tumor (CBT) resection. Background: Resection of CBT can lead to substantial postoperative morbidity because of a rich vascularization and close connection to neurovascular structures. The impact of a modified surgical technique on postoperative outcome was evaluated and compared with a historical group and the literature. Methods: Medical records of patients who underwent CBT surgery at Leiden University Medical Center between 1963 and 2005 were retrospectively reviewed. Before 1992, a standard approach was conducted. After 1992, most tumors were resected using an alternative technique, working in a craniocaudal fashion from skull base to carotid bifurcation. Data were reported as details of the pre, intra-, and postoperative periods. Results: A total of 111 CBT resections (69 standard, 42 craniocaudal) were performed in 94 patients (44 male/50 female, mean age 41). The standard group consisted of 39 Shamblin I (56%), 22 II (32%), and 8 III (12%) tumors. The craniocaudally approached CBT included 12 Shamblin I (29%), 13 II (31%), and 17 III (40%) tumors. The mean blood loss was 901 mL (standard operations) versus 281 mL (craniocaudal approach, P 0.0005). Persistent cranial nerve damage was encountered after 26 (23%) of 111 operations; 21 after the standard operations (30% within this group, including 3 preexistent nonresolved cranial nerve deficits); and 5 (12%, including 2 due to additional vagal body resections) after the craniocaudal operations (P 0.025). Conclusions: The craniocaudal dissection technique of a CBT can be applied with little blood loss, thereby reducing the risk of postoperative morbidity. arotid body tumors (CBT) are neoplasms arising from paraganglionic tissue at the bifurcation of the common carotid artery. The aim of the surgical management is the complete removal of CBT at an early stage to prevent further growth with the risk of local involvement of adjacent neurovascular structures. Resection of the CBT at an early stage reduces the chance of intraoperative blood loss and surgeryinduced morbidity. Control of the internal and external carotid arteries and the smaller supplying vessels is imperative to facilitate a dry operation field. The dissection along the relatively avascular plane should furthermore result in pres

Background The groin incision after arterial reconstructive surgery is most likely at risk for infectious or lymphatic wound complications. Theoretically; sparing lymphatic tissue by a lateral approach to the femoral artery should minimize these. The aim of this study was to assess the incidence of wound complications after the lateral versus the direct approach of the common femoral artery. Methods The study population included all patients who underwent an exploration of the common femoral artery between May 2002 and December 2005. Restults After 6 weeks, no statistical differences in the occurrence of wound complications could be shown. A wound infection was present after 6 weeks in 6.1% in the direct group versus 6.0% in the lateral group. Lymphorrhea was persistent in 3.1% in the direct group versus 5.0% in the lateral group. Conclusions Using a lateral vertical incision for the approach of the common femoral artery did not decrease the incidence of postoperative wound complications.

Rupture of the thoracic aorta after a blunt traumatic accident is a life-threatening event. This injury is instantly fatal in about 80% of the victims, and half of those who initially survive the incident will die during the first day, if left untreated. Before 1997, patients were treated with an open repair, but the conventional surgical approach carries a high mortality and morbidity rate. Graft interposition and cross-clamping of the aorta are responsible for a high paraplegia rate. Despite the fact that active distal perfusion of the aorta lowers the incidence of neurological deficit, the timing of these extensive procedures in the severely injured multi-trauma patient is difficult. The endovascular repair of a traumatic thoracic aortic rupture has gained rapid acceptance as a better alternative. This minimally invasive procedure has a median operating time of1 h, and it can be done during the same session in which other life-threatening injuries are repaired. There is no need for a thoracotomy or single lung ventilation, blood loss is minimal and systemic heparinization is not required. So far, no spinal cord ischemia has been described for the endovascular repair. Besides numerous advantages, a few problems can be expected. The narrow aortic diameter of these young trauma-victims, combined with a steep aortic arch, makes the adaptation of the endograft along the inner curvature sometimes difficult. Because the smallest endograft usually exceeds the narrow aortic diameter, only excessively oversized devices can be used, which explains the high type I endoleak encountered in the published series. No randomized studies are yet available comparing the open with the endovascular technique, but the initial results of the endovascular repair seem promising and lower mortality and morbidity rates are documented. Long-term outcome are lacking so far, but are needed to address the durability of the procedure. Further research and development should concentrate on the problems we have seen with steep and narrow aortic arches, and devices with more flexible curves and smaller diameters should become available in the near future.

The RF characteristics of the JET‐ITER Like (JET‐IL) antenna relevant for operation on plasma have been assessed using full wave three Dimensional (3D) electromagnetic CST® Microwave Studio (MWS) simulations, measurements of the full 8‐port antenna strap array S/Z‐matrix, and RF circuit modeling. These efforts are made in parallel with the high voltage testing of the antenna inside a vacuum tank and the hardware implementation of a RF (Radio Frequency) matching feedback control system prior to installation of the antenna on the JET tokamak.

The paper summarizes the activities carried out and difficulties encountered assembling and testing the JET‐EP ITER‐like ICRH antenna. First results from low power as well as high power testing and commissioning activities are presented.

Successful cryopreservation is essential for a large-scale dispersal of bovine in vitro produced (IVP) embryos that have been shown to be more sensitive to cryopreservation than their in vivo counterparts. On the other hand, the use of animal proteins in freezing media increases sanitary risks. We first replaced animal proteins, such as bovine serum albumin (BSA) in the freezing medium by plant-derived peptides (vegetal peptones). A batch of wheat peptones was selected after a preliminary experiment showing the absence of toxicity of concentrations

To determine the rate of autopsy and the rate of disparity between autopsy results and the clinically determined cause of death in a surgical ward.Descriptive.A total of 12,000 patients were admitted to the surgical ward of the Red Cross Hospital, the Hague, the Netherlands, from January 1999 to December 2002. 305 (3%) died during their stay on the ward. By using our standard mortality registration system, it was possible to classify the causes of death, evaluate shortcomings in treatment, and determine the extent of agreement between pre- and post-mortem findings.Permission for an autopsy was obtained for 136 patients (45%). The autopsy rates in patients who died following abdominal aortic surgery, colonic surgery, peripheral artery bypass surgery, and hip surgery were 55%, 63%, 35% and 30%, respectively. In 37 patients (27%), the autopsy report revealed a disparity with the clinical cause of death. Patients who died after abdominal aortic surgery or colonic surgery had disparity rates of 33% and 21%, respectively. Patients who died after peripheral artery bypass surgery or hip surgery had disparity rates of 13% and 7%, respectively.The overall rate of autopsy was lower (45%) than in the period 1992-1998 (60%), but remained relatively high in patient groups who were previously found to have a high rate of disparity between pre- and post-mortem findings. Post-mortem examination remains an important tool that can be used to verify diagnosis and treatment and therefore assess the quality of care.

To develop a safe and accurate method for the administration in the neonatal intensive care unit of several potent medications as a continuous infusion without overloading the infant, especially the very low birth weight (VLBW) infant by diluents. The method designed is based on a weight-adapted solution limiting the diluent administration and allowing for a versatile modulation of dose administration. As this method was initially designed for VLBW infants, the point of departure of this method is a standard maximal fluid load of 0.3 ml/h for each medication, delivered in a low compliant circuit with a high-precision syringe driver. Solutions are made for 24 h, which is a compromise between drug stability and repeated pressure drops in the circuit when changing the syringe and administration set. To translate a prescription into a solution a conversion factor is calculated. In addition to the calculation principle, this conversion factor is given for a number of commonly used drugs in neonatal care. In our experience, the method described adds to the safety and accuracy of continuous drug administration in neonatal care.

Integral equation modelling of electromagnetic radiation and interference phenomena in planar circuits and antennas offers exact solutions usually at the cost of excessive computation time, especially when arbitrary 3D conducting surfaces are involved. However, for most of these problems, the geometry can be restricted to the 2.5D case, that is, only horizontal (parallel to layer structure) and vertical conducting surfaces (normal to the dielectric layers) are present. This paper reports progress in the full wave analysis of these structures. An alternative but generally valid form for the electric field in the stratified medium is presented. For the 2.5D geometry, but modelling all current components, the availability of analytical expressions for the Green's functions in the spectral domain is then exploited to perform a mixed spectral and spatial calculation of the matrix elements required to solve the integral equation. An overall reduction of computation time is hereby envisaged. Numerical results of actual 2.5D structures are provided.

ITER's Ion Cyclotron Range of Frequencies (ICRF) system [Lamalle et al., Fusion Eng. Des. 88, 517–520 (2013)] comprises two antenna launchers designed by CYCLE (a consortium of European associations listed in the author affiliations above) on behalf of ITER Organisation (IO), each inserted as a Port Plug (PP) into one of ITER's Vacuum Vessel (VV) ports. Each launcher is an array of 4 toroidal by 6 poloidal RF current straps specified to couple up to 20 MW in total to the plasma in the frequency range of 40 to 55 MHz but limited to a maximum system voltage of 45 kV and limits on RF electric fields depending on their location and direction with respect to, respectively, the torus vacuum and the toroidal magnetic field. A crucial aspect of coupling ICRF power to plasmas is the knowledge of the plasma density profiles in the Scrape-Off Layer (SOL) and the location of the RF current straps with respect to the SOL. The launcher layout and details were optimized and its performance estimated for a worst case SOL provided by the IO. The paper summarizes the estimated performance obtained within the operational parameter space specified by IO. Aspects of the RF grounding of the whole antenna PP to the VV port and the effect of the voids between the PP and the Blanket Shielding Modules (BSM) surrounding the antenna front are discussed. These blanket modules, whose dimensions are of the order of the ICRF wavelengths, together with the clearance gaps between them will constitute a corrugated structure which will interact with the electromagnetic waves launched by ICRF antennas. The conditions in which the grooves constituted by the clearance gaps between the blanket modules can become resonant are studied. Simple analytical models and numerical simulations show that mushroom type structures (with larger gaps at the back than at the front) can bring down the resonance frequencies, which could lead to large voltages in the gaps between the blanket modules and perturb the RF properties of the antenna if they are in the ICRF operating range. The effect on the wave propagation along the wall structure, which is acting as a spatially periodic (toroidally and poloidally) corrugated structure, and hence constitutes a slow wave structure modifying the wall boundary condition, is examined.

In early development the epicardium as an extracardiac organ envelops the initially bare myocardial surface. In this way, a three-layered organ is formed consisting of an inner endocardium, the muscular myocardium, and the covering epicardium (Manasek, 1969; Ho and Shimada, 1978; Viragh and Challice, 1981; Hiruma and Hirakow, 1988). The epicardium proved to be the source for novel cell populations migrating into the myocardial wall, which play major, but not yet fully comprehended, roles in heart development. It has been shown in a number of studies, using knockout mice, that when the epicardium is missing, the coronary vessels fail to develop properly (Kwee et al, 1995; Yang et al, 1995), usually leading to embryonic death at a very specific point in development. It must be concluded that the formation of the coronary vasculature is one of the features of heart development depending on epicardial differentiation. Therefore, we describe and discuss first the differentiation of the epicardial-derived cells (EPDCs), followed by the development of the endothelium that does not derive from the epicardial organ proper, and the smooth muscle cells and adventitial fibroblasts of the coronary vessel wall. Finally, we discuss the differentiation of the vascular tree, starting with a plexiform system of sinusoidal vessels, developing into arteries and veins, interconnected by a capillary network.

In the present study, we investigated the modulatory role of the epicardium in myocardial and coronary development. Epicardial cell tracing experiments have shown that epicardium-derived cells are the source of interstitial myocardial fibroblasts, cushion mesenchyme, and smooth muscle cells. Epicardial outgrowth inhibition studies show abnormalities of the compact myocardial layer, myocardialization of cushion tissue, looping, septation, and coronary vascular formation. Lack of epicardial spreading is partly compensated by mesothelial outgrowth over the conotruncal region. Heterospecific epicardial transplant is able to partially rescue the myocardial development, as well as septation and coronary formation.

Abstract —The epicardium and dorsal mesocardium are known to be the source of structures that form the wall of the coronary vessels. Because mouse knockout studies have shown that proper epicardial formation is also essential for myocardial development, we have studied in detail the migration and differentiation of epicardium-derived cells (EPDCs) within the developing heart. We constructed chicken-quail chimeras by grafting the quail epicardial organ, including a piece of primordial liver, at essentially stages 16 and 17. The embryos were studied at stages 25 to 43. To detect quail-derived EPDCs, an anti-quail nucleus antibody was used in combination with several differentiation markers, eg, for muscle actin, for vascular smooth muscle cells, for procollagen-I, for quail endothelium, and for Purkinje fibers. At stages 25 to 31, EPDCs are encountered in the myocardial wall and the subendocardial region. The latter deposition is spatially facilitated as the endocardium protrudes through transient discontinuities in the myocardium to contact the subepicardial layer. Later on, at stages 32 to 43, EPDCs invaded, by way of the atrioventricular sulcus, the atrioventricular cushion tissue. The localization is apparent at the interface with the myocardium, as well as subendocardially, but never within the endocardial lining. The origin of endothelium, smooth muscle cells, and fibroblasts of the coronary vessel wall from the epicardial graft were confirmed in accordance with already published data. The functional role of the novel EPDCs in the subendocardium, myocardium, and atrioventricular cushions remains to be investigated. A close positional relationship is found with the differentiating Purkinje fibers. Furthermore, a regulatory role is postulated in the process of endocardial-mesenchymal transformation. The ultimate fate of EPDCs seems to be a cardiac fibroblast cell line involved in the formation of the fibrous heart skeleton.

We present numerical model calculations (3D, NLTE radiative line transfer) for the cyclic, long-term variations of Be-star emission lines. These variations are believed be formed in quasi-Keplerian disks with single-armed global disk oscillations (Okazaki 1991, PASJ 43, 75). In our recent study (Hummel & Hanuschik 1997, A&A 320, 852), we showed that global disk oscillations in disks with R d = 5 R * can indeed account for both the observed line-profile asymmetries and their cyclic evolution.