First measurements of an imaging heavy ion beam probe at the ASDEX Upgrade tokamak.

The imaging heavy ion beam probe (i-HIBP) diagnostic has been successfully commissioned at ASDEX Upgrade. The i-HIBP injects a primary neutral beam into the plasma, where it is ionized, leading to a fan of secondary (charged) beams. These are deflected by the magnetic field of the tokamak and collected by a scintillator detector, generating a strike-line light pattern that encodes information on the density, electrostatic potential, and magnetic field of the plasma edge. The first measurements have been made, demonstrating the proof-of-principle of this diagnostic technique. A primary beam of 85/87Rb has been used with energies ranging between 60 and 72 keV and extracted currents up to 1.5 mA. The first signals have been obtained in experiments covering a wide range of parameter spaces, with plasma currents (Ip) between 0.2 and 0.8 MA and on-axis toroidal magnetic field (Bt) between 1.9 and 2.7 T. Low densities appear to be critical for the performance of the diagnostic, as signals are typically observed only when the line integrated density is below 2.0-3.0 × 1019 m-2 in the central interferometer chord, depending on the plasma shape. The strike line moves as expected when Ip is ramped, indicating that current measurements are possible. Additionally, clear dynamics in the intensity of the strike line are often observed, which might be linked to changes in the edge profile structure. However, the signal-to-background ratio of the signals is hampered by stray light, and the image guide degradation is due to neutron irradiation. Finally, simulations have been carried out to investigate the sensitivity of the expected signals to plasma density and temperature. The results are in qualitative agreement with the experimental observations, suggesting that the diagnostic is almost insensitive to fluctuations in the temperature profile, while the signal level is highly determined by the density profile due to the beam attenuation.

Helium line ratio spectroscopy for high spatiotemporal resolution plasma edge profile measurements at ASDEX Upgrade (invited).

The thermal helium beam edge diagnostic has recently been upgraded at the ASDEX Upgrade (AUG) tokamak experiment. Line ratio spectroscopy on neutral helium is a valuable tool for simultaneous determination of the electron temperature and density of plasmas. The diagnostic now offers a temporal resolution of 900 kHz with a spatial resolution of up to 3 mm at 32 lines of sight (LOS) simultaneously. The LOS covers a radial region of 8.5 cm, starting at the limiter radius and reaching into the confined region beyond the separatrix. Two components are of particular importance for the aforementioned hardware improvements. The first is the optical head, which collects the light from the experiment. Equipped with an innovative clamping system for optical fiber ends, an arbitrary distribution pattern of LOS can be achieved to gain radial and poloidal profiles. The second major development is a new polychromator system that measures the intensity of the 587 nm, 667 nm, 706 nm, and 728 nm helium lines simultaneously for 32 channels with filter-photomultiplier tube arrays. Thus, the thermal helium beam diagnostic supplements the AUG edge diagnostics, offering fast and spatially highly resolved electron temperature and density profile measurements that cover the plasma edge and scrape-off layer region. Plasma fluctuations, edge localized modes, filaments, and other turbulent structures are resolved, allowing analysis of their frequency and localization or their propagation velocity.

Fast piezoelectric valve offering controlled gas injection in magnetically confined fusion plasmas for diagnostic and fuelling purposes.

In magnetically confined fusion plasmas controlled gas injection is crucial for plasma fuelling as well as for various diagnostic applications such as active spectroscopy. We present a new, versatile system for the injection of collimated thermal gas beams into a vacuum chamber. This system consists of a gas pressure chamber, sealed by a custom made piezo valve towards a small capillary for gas injection. The setup can directly be placed inside of the vacuum chamber of fusion devices as it is small and immune against high magnetic fields. This enables gas injection close to the plasma periphery with high duty cycles and fast switch on/off times ≲ 0.5 ms. In this work, we present the design details of this new injection system and a systematic characterization of the beam properties as well as the gas flowrates which can be accomplished. The thin and relatively short capillary yields a small divergence of the injected beam with a half opening angle of 20°. The gas box is designed for pre-fill pressures of 10 mbar up to 100 bars and makes a flowrate accessible from 1018 part/s up to 1023 part/s. It hence is a versatile system for both diagnostic as well as fuelling applications. The implementation of this system in ASDEX Upgrade will be described and its application for line ratio spectroscopy on helium will be demonstrated on a selected example.

[Enzalutamide and Abiraterone in the Treatment of Metastatic Castration-resistant Prostate Cancer after Chemotherapy]. / Enzalutamid a abirateron v lécbe metastatického kastracne refrakterního karcinomu prostaty po predchozí chemoterapii.

AIM: Enzalutamide and abiraterone represent new therapeutical options in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the presented study was retrospective analysis of clinical experience and efficacy of enzalutamide or abiraterone in the postchemo indication in patients with mCRPC. PATIENTS AND METHODS: A total of 32 mCRPC patients were evaluated. All patients received one or more lines of chemotherapy. Twenty-three patients were treated by enzalutamide, nine patients were treated by abiraterone. We defined two parameters: over all survival and progression-free survival. RESULTS: The median follow-up was 6.5 months. A total of 10 patients treated by enzalutamide progressed (43.47%) and eight patients died (34.78%). A total of five patients treated by abiraterone progressed (55.56%) and one patient died (11.11%). We did not observe any statistical difference in over all survival (HR 0.2362, 95% CI 0.0295- 1.8942; p = 0.102) and in progression-free survival (HR 0.9853, 95% CI 0.2934- 3.308; p = 0.939) between enzalutamide and abirateron. CONCLUSION: Our retrospective study demonstrated similar efficacy of enzalutamide and abiraterone in mCRPC patients previously treated by chemotherapy.

[Early Integration of Palliative Care into Standard Oncology Care -  Benefits, Limitations, Barriers and Types of Palliative Care]. / Casná integrace paliativní péce do standardní onkologické péce -  benefit, limitace, bariéry a druhy paliativní péce.

Patients with advanced cancer experience a significant number of physical symptoms and psychological distress, which worsen their quality of life (QOL). Palliative care is oriented to prevent and relieve suffering and promote QOL of patients with advanced cancer. In oncology, the role of palliative care is traditionally perceived to be the treatment after the antineoplastic therapy is finished. A concept of early integration of palliative care into standard oncology practice has been recently introduced. There is a lot of data supporting this concept of parallel application of both oncology care and palliative care. Early palliative care has been shown to provide benefits in QOL, mood, symptoms, health care utilization and survival. In this review, we summarize published data about benefits and difficulties of early palliative care. We also discuss the model of general and specialized palliative care integrated into oncological practice, their differences and consequences.

[Management of chronic and acute pain in patients with cancer diseases]. / Management chronické a akutní bolesti u pacientu s nádorovými chorobami.

Pain is one of the most important and most frequent symptoms of malignancy. Its intensity and prevalence is growing with disease status. Pain should be present in early stage cancer patients also. Pain is, together with other symptoms (anorexia, nausea, depression, anxiety, sleep disturbances), factor of patients quality-of-life and proper therapy is responsible for overall patient satisfaction and activity. Right pain management is always multidimensional and pain should be assessed at each contact. In review article we would like to bring some alerts of pain context in complexity of cancer and we would like to stress some forms of acute pain management.

[Management of infections in palliative and terminal cancer care]. / Lécba infekcí u pacientu v paliativní symptomatické a terminální fázi onkologického onemocnení

BACKGROUND: Patients with cancer are highly susceptible to infections. There is a lack of evidencebased guidelines or protocols for their management in palliative and endoflife care. PURPOSE: To define an optimal dia-gnostic approach and therapeutic management of infections in patients with palliative and terminal cancer care. Along with thromboembolic disease and cancer progression, infections are the most frequent causes of death in oncology. Besides the impact on mortality, they are accompanied with a myriad of symptoms decreasing the quality of life. High incidence of infectons is due to a malignancy itself, the oncolgical therapy and host factors. There is a lack of evidencebased guidelines and protocols for the therapy of infections in palliative and terminal cancer care. Most of available studies are retrospective in nature, with diverse methods and cohorts. Incidence of infections in these patient oscillates between 16- 55% in specialized palliative units, and rises up to 83% in acute care hospitals. From the epidemiologic viewpoint, urinary (39- 42%) and respiratory infections (22- 36%) are the most frequent cases, followed by soft tissue and skin infections (6- 12%) and bacteremias (5- 14%). At present, the antibio-tic treatment does not seem to have a positive impact on the survival rate. Symptom control antibio-tic therapy as a means of symptom control still remains controversial, since it meets this purpose only in a few percents of studies. The most successful is the symtom control in urinary tract infections (60- 79%), in contrast to other sites of infection (30- 43%). In the last week of life there the symptom control is achieved only in 10% of patient. One should always consider the prognosis, actual preformance status and patients preferences when it comes to the management of dia-gnostics and therapy of infections. If the prognosis counts in weeks or months the dia-gnostics and therapy should not differ from the approach to any other oncological patient. In terminal cancer care the antibio-tics should be spared strictly for the purpose of symptom control and with a palliative intent. This article reviews current knowledge of dia-gnostics and therapy of infections in palliative cancer care and includes an algorithm for their management.

[Antiangiogenic biotherapy and chemotherapy in breast cancer: review of literature and case report]. / Antiangiogenní bioterapie a chemoterapie v terapii karcinomu prsu: prehled literatury a kazuistika.

Breast cancer incidence is 120/100,000 women and thus, it is the most frequent malignant disease in women. Despite the ever-increasing incidence, mortality has stayed stable; this is due to screening with detection of early breast cancers, adjuvant treatment and advances in targeted therapy. Currently, we perceive breast cancer as a phenotypically different subunits, influenced by genetic and epigenetic changes. All 5 basic subgroups (luminal A, B, basal-like, HER-2 positive and claudin-low) vary significantly in their prognosis and therapeutic options. The subgroup of basal-like tumors without hormone receptors positivity and HER-2 antigen (triple-negative breast cancer) is prognostically and therapeutically a very unfavorable group. Hormonal and anti-HER-2 therapy is excluded, and the effect of chemotherapy is limited and short-lived. Research for this sub-group of breast tumors in recent years focused on the influence of angiogenesis and DNA repair systems. Therapeutic manipulation of angiogenesis is based on the concept of its influence in the development and maintenance of the malignant process. The longest used and in terms of studies and clinical practice explored treatment is the main path of angiogenesis, the vascular endothelial growth factor. In the last few years, the real effect in the metastatic breast cancer is discussed. The initial positive results of pilot clinical trials showing a significant extension of the progression free survival bring disappointment since they were not translated into prolongation of overall survival. The following case-report presents a patient with metastatic triple-negative breast cancer with combined chemobiotherapy (capecitabine + bevacizumab). In the second part of the article, we discuss possible causes of inconsistent outcomes with antiangiogenic therapy in breast cancer, new directions in scientific research and today knowledge of prediction of its therapeutic effect.

Thoracic response to shoulder belt loading: comparison of tabletop and frontal sled tests with PMHS.

OBJECTIVE: The recent refinement of high-rate optical tracking allows dramatically detailed thoracic deformation measurements to be taken during postmortem human subject (PMHS) sled tests. These data allow analysis of restraint belt geometry and the 3-dimensional thoracic deformations generated by belt impingement. One consequence of this new capability is a better understanding of complementary thoracic characterization experiments such as tabletop tests and how the thoracic response can be interpreted for applications involving more complex loading mechanisms. METHODS: This article reports a detailed evaluation of the timing, magnitude, and direction of the applied belt forces and the resulting thoracic deformations in 2 previously performed tests series involving frontal sled tests and tabletop belt-loading tests. RESULTS: In the sled tests, the posteriorly directed component (SAE x) of the belt tension (F(B)) was F(Bx) = 0.70 F(B) at the shoulder but only F(Bx) = 0.14 F(B) where the belt engaged the anterolateral torso inferiorly. The corresponding components on the tabletop were F(Bx) = 0.60 F(B) (shoulder) and F(Bx) = 0.48 F(B) (lower). CONCLUSIONS: When these components are cross-plotted with chest deflection, pronounced consequences of thoracic anterior wall deformation patterns due to flexion of the thoracic spine and the internal viscera's inertia can be seen in the effective thoracic stiffness. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.

[Bloodstream infections of the intravascular access devices - case reports and review of the literature]. / Septické komplikace intravenózních portových systému - kazuistiky a prehled literatury.

Long-term access devices (VAD) in oncology patients are the elemental procedure of contemporary treatment. Apart from their indisputable benefit they are linked with an increased risk of infectious complications, ranging between simple colonisation of a device to catheter related bloodstream infections. The decision to salvage or extract the VAD in case of bloodstream infection depends on patient's clinical state, localisation of infection (site of insertion, catheter or pocket), casual agent and complications (e.g. endocarditis, septic embolization, osteomyelitis and so on). Authors present 5 case reports of portacath sepsis in their oncology department in 2011 (i.e. 4.46% of 112 inserted ports). In the second part of the article they review current literature data about prevention and treatment of infectious complications of vascular devices in cancer patients.

The simplification of the muscle force prediction using sensitivity analyses.

Today artificial neural networks can be trained to solve problems that are difficult for conventional computers or human beings. The big advantage of an artificial neural network is results obtained without knowledge of the algorithm procedure or without full and exact information. Therefore an artificial neural network was used to predict the muscle forces. The aim of the study was to simplify prediction of muscle forces which are difficult to determine, because many muscles act cooperatively. However, orthopeadists, biomechanical engineers and physical therapists need to take muscle forces into consideration because joint contact forces, as well as muscle forces, need to be estimated in order to understand the joint and bone loading. In terms of sensitivity of the muscle parameters to the results from the proposed neural network object, the muscle force prediction was simplified.

Biological properties of the intervertebral cages made of titanium containing a carbon-carbon composite covered with different polymers.

Intervertebral cages are used in orthopaedics for stabilization of injured lumbar parts of vertebral columns. Our study provides preliminary results of tests of the biological properties of titanium cages with a variously modified carbon/carbon composite (C/C) core. This core was produced from a C/C composite modified by hydrogel materials based on poly(2-hydroxyethyl methacrylate) (HEMA) enriched with 1% collagen or 35% methylmethacrylate or 30% terc-butylmethacrylamide. We evaluated the adhesion of the cells to the tested material coating using an in vitro study of the metabolic activity and cytokine production of the cells (TNF-alpha, IL-8). We studied the biocompatibility of intervertebral cages coated with different copolymers under in vivo condition and in an implantation experiment in the porcine femurs. Both in vitro and in vivo results revealed favourable biotolerance of the use system. Modification of the composite HEMA with the use of collagen seems to have a more positive effect on the new bone tissue formed around the implanted devices than HEMA copolymerized with methylmethacrylate or terc-butylmethacrylamide.

Pseudomembraneous clostridium after autologous bone marrow transplantation.

Clostridium difficile (C. difficile) pseudomembraneous colitis was diagnosed in a 13-year-old boy with Hodgkin's disease 3 months after autologous bone marrow transplantation. Hematopoiesis was fully reconstituted at the time. C. difficile infection occurred after gall bladder empyema had been treated conservatively with i.v. antibiotics and prophylactic 4-week administration of oral amoxicillin. C. difficile colitis was diagnosed early and intensive supportive therapy combined with administration of i.v. and subsequently oral vancomycin therapy failed. It is a phenomenon rarely seen and successful eradication of the clostridium infection was only achieved by a combination of higher dose vancomycin with metronidazole. During the post-colitis recovery the patient experienced a relapse of Hodgkin's disease and died following further surgical intervention 137 days post-transplantation.

Residual stresses in the human aorta and their influences by growth and remodelling.

The aim of the present work is to demonstrate of the influence of the adventitia on distribution of residual stresses in the human aorta. The biomaterial increase in media as well as in adventitia in the course of the aorta's growth is formed by an intussusceptive mechanism of growth. In children's aortas, formative elastin lamellae are wavy with high amplitude perpendicular to the aortic surface. In adults' aortas the waves become smoother (stepwise) towards the adventitia. Also introduced is the growth function, which characterizes the biomaterial growth and the interference between the media and adventitial layers. It is possible to expect an extraordinary variability in the formation of the aortic wall tissue in the course of its growth as a result of metabolic and humoral influences and magnitude of the residual stresses in the course of growth.

Effect of oestradiol on the carbohydrate metabolism of immature rat uterus: the role of fructose-2, 6-bis-phosphate and of phosphoribosyl pyrophosphate.

Enzymes and metabolic intermediates of glycolysis, pentose phosphate pathway and the tricarboxylic acid cycle were measured in immature rat uterus after treatment with oestradiol. The flux of glucose through alternative pathways was examined. Fructose-2,6-bis-phosphate, the well known regulator of glycolytic pathway, increased after the injection of oestradiol and remained elevated. This increase was accompanied by raised levels of most of glycolytic intermediates and by increase in glycolytic flux. The key enzymes of glycolysis and all the enzymes of pentose phosphate pathway showed a gradual increase in the activity with administration of oestradiol up to 48 hours. Phosphoribosyl pyrophosphate, the metabolite required in nucleotide synthesis, was also elevated. Marked changes in the levels of key metabolic intermediates and the enzyme activities are correlated with the increased nucleic acid, protein and lipid synthesis occurring following oestradiol treatment.

Aspects of the regulation of hepatic phosphoribosyl pyrophosphate formation in the obese (ob/ob) mouse: relationship to the pentose phosphate pathway.

The content of phosphoribosyl pyrophosphate (PPRibP) and of intermediates involved in its synthesis has been measured in the livers of obese (ob/ob) mice 2 months and 3-4 months of age, a period of dynamic growth and marked hepatic hypertrophy and hyperplasia, and comparison made with the values found in the lean age-matched control groups. The total hepatic PPRibP content and PPRibP/mg DNA was significantly increased in the 3- to 4-month-old obese mice relative to both the lean control groups and the 2-month-old obese mice, illustrating the significant changes occurring in the obese mouse liver in this transition period. The change in hepatic PPRibP/mg DNA in the obese mice is positively correlated with age (up to 4 months, body weight 60 g) and with parameters linked to the activity of the pentose phosphate pathway. There is no apparent correlation between PPRibP concentration and inorganic phosphate, the energy status of the cell, or the hepatic PPRibP synthetase (EC 2.7.6.1.) activity. The increase in the bioavailability of PPRibP, which is both a substrate and activator of the de novo and salvage pathways of purine and pyrimidine synthesis, is considered in relation to the increased nucleotide requirement associated with the rise in total hepatic RNA, DNA, and adenine nucleotide in the obese mouse.

Pyrimidine nucleotide synthesis in the rat mammary gland: changes in the lactation cycle and effects of diabetes.

Measurements have been made of the activities of the enzymes of the de novo and salvage pathways of pyrimidine synthesis (carbamoyl phosphate synthetase II (glutamine) (EC 6.3.5.5); dihydroorotate dehydrogenase (EC 1.3.99.11); the overall activity of Complex II (orotate phosphoribosyl pyrophosphate transferase (EC 2.4.2.10) and orotidine 5-phosphate decarboxylase (EC 4.1.1.23); uracil phosphoribosyltransferase (EC 2.4.2.9)) in the mammary gland of rats at different stages of the lactation cycle and the effects of diabetes on the activity of these enzymes in lactation have been studied. From a consideration of the changes in enzyme activities and the changes in the tissue concentration of phosphoribosyl pyrophosphate, an activator of the de novo pathway and substrate for both the de novo and salvage routes, it is concluded that the de novo pathway is the major route of pyrimidine synthesis in mammary tissue. Diabetes decreases the activity of the enzymes of the de novo pathway; the effects are particularly marked for Complex II. The present results on pyrimidine synthesis are compared to the pattern for purine synthesis previously published.

Vanadate treatment increases the activity of glycolytic enzymes and raises fructose 2,6-bisphosphate concentration in hearts from diabetic rats.

The present study examined the effect of vanadate on the activity of key enzymes of glycolysis and the level of fructose 2,6-bisphosphate (F-2, 6-P2) in the hearts of diabetic rats. A 20% decrease in the total hexokinase activity and 66% decrease in the type II isoenzyme was found in diabetic rat hearts. Vanadate treatment doubled the activity of type II hexokinase. Pyruvate kinase and phosphofructokinase 1 activity was reduced by 20% in diabetes, vanadate treatment restored the activity of the enzymes to normal. A 43% decrease in the cardiac F-2, 6-P2 level was found in diabetes of four weeks duration. A significant inverse correlation between blood glucose of experimental animals and the level of heart F-2, 6-P2 was observed. Vanadate treatment doubled the amount of F-2, 6-P2 in diabetic rat hearts.