Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

Fine-Structure Qubit Encoded in Metastable Strontium Trapped in an Optical Lattice.

We demonstrate coherent control of the fine-structure qubit in neutral strontium atoms. This qubit is encoded in the metastable ^{3}P_{2} and ^{3}P_{0} states, coupled by a Raman transition. Using a magnetic quadrupole transition, we demonstrate coherent state initialization of this THz qubit. We show Rabi oscillations with more than 60 coherent cycles and single-qubit rotations on the µs scale. With spin echo, we demonstrate coherence times of tens of ms. Our results pave the way for fast quantum information processors and highly tunable quantum simulators with two-electron atoms.

Tumor mimicking gastric ulcer penetrating asymptomatically into the pancreas.

Gastroduodenal ulcer disease is characterized by ulceration of the stomach or duodenum, with ulcer lesions occurring more frequently in the duodenum. Serious complications of this disease include bleeding, perforation of the ulcer and penetration into surrounding organ. Our report presents the case of an older man who had a gastric ulcer penetrating into the pancreas. This was not diagnosed at the time of the penetration. The patient came to our care for recurrent hematemesis without a proven source of bleeding. During the diagnostic process, the presence of an intramural gastric tumor was suspected. An excision of the suspected lesion was successfully performed at our clinic, followed by histological confirmation of perforated ulcer. The postoperative course was complicated by the development of a pancreatic fistula. However, conservative treatment resulted in complete recovery of the patient.

Deep learning for diagnosis and survival prediction in soft tissue sarcoma.

BACKGROUND: Clinical management of soft tissue sarcoma (STS) is particularly challenging. Here, we used digital pathology and deep learning (DL) for diagnosis and prognosis prediction of STS. PATIENTS AND METHODS: Our retrospective, multicenter study included a total of 506 histopathological slides from 291 patients with STS. The Cancer Genome Atlas cohort (240 patients) served as training and validation set. A second, multicenter cohort (51 patients) served as an additional test set. The use of the DL model (DLM) as a clinical decision support system was evaluated by nine pathologists with different levels of expertise. For prognosis prediction, 139 slides from 85 patients with leiomyosarcoma (LMS) were used. Area under the receiver operating characteristic (AUROC) and accuracy served as main outcome measures. RESULTS: The DLM achieved a mean AUROC of 0.97 (±0.01) and an accuracy of 79.9% (±6.1%) in diagnosing the five most common STS subtypes. The DLM significantly improved the accuracy of the pathologists from 46.3% (±15.5%) to 87.1% (±11.1%). Furthermore, they were significantly faster and more certain in their diagnosis. In LMS, the mean AUROC in predicting the disease-specific survival status was 0.91 (±0.1) and the accuracy was 88.9% (±9.9%). Cox regression showed the DLM's prediction to be a significant independent prognostic factor (P = 0.008, hazard ratio 5.5, 95% confidence interval 1.56-19.7) in these patients, outperforming other risk factors. CONCLUSIONS: DL can be used to accurately diagnose frequent subtypes of STS from conventional histopathological slides. It might be used for prognosis prediction in LMS, the most prevalent STS subtype in our cohort. It can also help pathologists to make faster and more accurate diagnoses. This could substantially improve the clinical management of STS patients.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Clinical application of ultrashort echo-time MRI for lung pathologies in children.

Lung magnetic resonance imaging (MRI) is considered to be challenging, because the low proton density of the tissue, fast signal decay, and respiratory artefacts hamper adequate image quality. MRI of the lungs and thorax is increasingly used in the paediatric population, because it is a radiation-free alternative to chest CT. Recently, ultrashort echo-time (UTE) sequences have been introduced into clinical MRI protocols, in order to improve the contrast-to-noise ratio due to reduced susceptibility artefacts and to depict structural alterations comparable to CT. The purpose of this review is to provide an overview of various clinical conditions and pathologies in the paediatric chest depicted by an UTE sequence, the so-called three-dimensional (3D) Cones sequence, in comparison with conventional MRI sequences. Besides describing typical features of cystic fibrosis, we present UTE application in other more or less common paediatric lung pathologies, for instance, interstitial pneumopathies, pulmonary infections, and congenital pulmonary malformations.

Turbulence Mechanisms of Enhanced Performance Stellarator Plasmas.

We theoretically assess two mechanisms thought to be responsible for the enhanced performance observed in plasma discharges of the Wendelstein 7-X stellarator experiment fueled by pellet injection. The effects of the ambipolar radial electric field and the electron density peaking on the turbulent ion heat transport are separately evaluated using large-scale gyrokinetic simulations. The essential role of the stellarator magnetic geometry is demonstrated, by comparison with a tokamak.

Morgagni hernia - case reports.

Morgagni hernia is a rare form of diaphragmatic hernia. It is a congenital defect of the diaphragm, often asymptomatic in adulthood and thus usually found only incidentally. Its treatment is predominantly surgical. This article presents three case reports of patients operated in our department.

Stellarators Resist Turbulent Transport on the Electron Larmor Scale.

Electron temperature gradient (ETG)-driven turbulence, despite its ultrafine scale, is thought to drive significant thermal losses in magnetic fusion devices-but what role does it play in stellarators? The first numerical simulations of ETG turbulence for the Wendelstein 7-X stellarator, together with power balance analysis from its initial experimental operation phase, suggest that the associated transport should be negligible compared to other channels. The effect, we argue, originates essentially from the geometric constraint of multiple field periods, a generic feature of stellarators.

Dentist-Perceived Barriers and Attractors to Cognitive-Behavioral Treatment Provided by Mental Health Providers in Dental Practices.

Over 1 in 5 dental patients report moderate to severe dental fear. Although the efficacy of cognitive-behavioral treatment (CBT) for dental fear has been examined in over 20 randomized controlled trials-with 2 meta-analyses finding strong average effect sizes ( d > 1)-CBT has received almost no dissemination beyond the specialty clinics that tested it. The challenge, then, is not how to treat dental fear but how to disseminate and implement such an evidence-based treatment in a way that recognizes the rewards and barriers in the US health care system. This mixed-method study investigated the potential of disseminating CBT through care from a mental health provider from within the dental home, a practice known as evidence-based collaborative care (EBCC). Two preadoption studies were conducted with practicing dentists drawn from a self-organized Practice-Based Research Network in the New York City metropolitan area. The first comprised 3 focus groups ( N = 17), and the second involved the administration of a survey ( N = 46). Focus group participants agreed that CBT for dental fear is worthy of consideration but identified several concerns regarding its appeal, feasibility, and application in community dental practices. Survey participants indicated endorsement of factors promoting the use of EBCC as a mechanism for CBT dissemination, with no factors receiving less than 50% support. Taken together, these findings indicate that EBCC may be a useful framework through which an evidence-based treatment for dental fear treatment can be delivered.

Tendon healing induced by chemically modified mRNAs.

Tendon disorders are frequent both in human and veterinary medicine with high re-injury rates and unsatisfactory therapeutic treatments. Application of naked, chemically-modified mRNA (cmRNA), encoding for therapeutic proteins, is an innovative approach to address tendon healing. In the current study, we demonstrated that injection of naked cmRNA, diluted in a glucose-containing solution, into tendons resulted in high protein expression in healthy and experimentally-injured tendons. Injection of bone morphogenetic protein 7 (BMP-7)-encoding cmRNA resulted in a significantly higher expression of BMP-7 protein and reduced formation of collagen type III, compared to vehicle control. Moreover, in a large animal model, reporter protein expression was detectable not only in healthy, but also in experimentally-injured, severely inflamed tendons. Summarising, these results demonstrated the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders.

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer.

BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). CONCLUSIONS: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted. REGISTERED CLINICAL TRIAL NUMBER: NCT00798655.

[Diagnosis and treatment of billiary ileus]. / Diagnostika a lécba biliárního ileu.

INTRODUCTION: Biliary ileus represents only 14% of mechanical obstructions of the gastrointestinal tract. However, the rate of non-strangulated small bowel obstructions reaches as much as 25% in patients over 65 years of age. Usually, a pressure necrosis is created by a large gallstone that passes through the developed biliodigestive fistula, subsequently obturating the gastrointestinal tract. CASE REPORTS: 35 patients underwent a surgical procedure at the Department of Surgery, Teaching Hospital Pilsen for biliary ileus from January 1, 2000 to January 31, 2015. Mean age was 79 years (median 78 years; min. 58 years; max. 92 years). Aerobilia was visible in abdominal X-ray scans in 7 cases (26%) of 27 acquired images. Preoperatively, colonoscopy was done 2 times and esophagogastroduodenoscopy 9 times. Regarding surgical procedures, enterolithotomy was done in 21 cases, extraction of the gallstone from gastrotomy was done 3 times, small bowel resection 7 times, Hartmann resection 1 time, resection of ileoascendentoanastomosis 1 time, and extraction of the gallstone from duodenotomy with duodenojejunoanastomosis and cholecystectomy was done in 1 case. Ileotransversoanastomosis was performed in 1 case. Postoperative 30-day mortality was 14.3%. Postoperative morbidity according Clavien-Dindo was 22.8% for grade 1, 5.7% for grade 2, 11.5% for grade 3, and 11.5% for grade 4. A recurrence was observed in 8.8%. Primary treatment of the fistula and cholecystectomy were done in 1 case. CONCLUSION: The indication of primary biliodigestive fistula treatment always depends on the general condition of the patient and on the local finding in the gallbladder area. Residual fistula increases the risk of reccurence, but primary treatment is associated with higher mortality. It is also important to duly revise the entire bowel to avoid an early reccurence due to multiple gallstones. KEY WORDS: biliary ileus diagnosis treatment.

[Coincidence of colonic lymphoma and gallstone ileus - case report]. / Koincidence lymfomu tracníku a biliárního ileu - kazuistika.

INTRODUCTION: Primary colonic lymphoma is a very rare malignant disease of the gastrointestinal tract, accounting for 14% of all malignant diseases in this location. It is classified in the group of extranodal lymphomas; its long-term asymptomatic progression makes it different from common colorectal carcinomas making its diagnosis very difficult, more often accidental. Gallstone ileus is quite an uncommon complication of cholecystolithiasis diagnosed with difficulty. Up to 50% of cases are diagnosed during surgery. The obturated location depends on the size of the stone, location of the conjunction between the biliary and gastrointestinal tracts, and also on any preexisting stenosis due to another unknown pathology. CASE REPORT: We present a case of an 86-year-old man treated for acute diverticulitis with typical clinical symptoms. Following further examination (colonoscopy, computed tomography) revealed a tumour-like infiltration in the sigmoid colon wall and a voluminous polyp was suspected according to the colonoscopy. Computed tomography described an obstruction by a biliary stone tumbling through the cholecystocolonic fistula. Subsequent biopsy supported the suspected malignant etiology. The patient underwent resection of the sigmoid colon sec. Hartmann; an infiltration was found in the subhepatic space, which corresponded to the described fistulisation between the biliary tract and the colon. A large 40 mm gallstone was found in the resected sigmoid colon over the stenosis and the bowel wall showed diffuse thickening with several polyps; final histopathological assessment confirmed malignant lymphoma of the plasmocytoma type. No serious complications occurred in the postoperative period; after healing, the patient was transferred to hematooncology care. CONCLUSION: The article describes the presence of two rare diseases - colonic lymphoma and gallstone ileus. Clearly, without the biliary stone obstruction in the preexisting tumorous stenosis in the sigmoid colon, the malignant hematooncology disease would not have been diagnosed. KEY WORDS: primary colonic lymphoma - gallstone ileus - complication of the cholecystolithiasis - extranodal lymphoma - acute diverticulitis.

[Mediastinitis after esophageal perforation]. / Mediastinitida po perforaci jícnu.

INTRODUCTION: Assessment of therapy in patients with mediastinal infection resulting from esophageal perforation. MATERIAL AND METHODS: Retrospective (2008-2012) processing of a group of surgically treated patients. The aspects assessed were aetiology, the surgical methods applied and the length of therapy. RESULTS: The total number of patients treated was 16. In 8 cases, the aetiology was iatrogenic (3 cases of leaking esophageal anastomosis in consequence of resection of the esophagus, 2 cases of perforation after fundoplication, 1 case of esophageal cardiomyotomy, and 2 cases of perforation during endoscopy). In 4 patients, the aetiology was spontaneous perforation, impacted foreign bodies caused difficulties to 3 patients, and the last cause was acid corrosive esophagitis. A stent was applied in all the patients at the site of the defect. The mediastinitis was drained through the access from thoracotomy or left thoracolaparotomy, respectively (8 cases), or by combination of laparotomy/laparostomy and pleural drainage (5 cases). Pleural (in 3 cases) and neck (1 case) drainage meant minimum intervention. Esophagectomy was not carried out in any of the patients. 4 patients died. The average period of time for which the stent was left in situ was 53.7 days; the average time of hospitalization in surviving patients was 53.4 days. CONCLUSION: Stent application does not show any difference regarding patients' survival (25% mortality), but enables shortening the total therapy time and, predominantly, preserving the native esophagus.

Substantially improved gene transfer to interneurons with second-generation glutamate receptor-targeted DART-AAV vectors.

BACKGROUND: Adeno-associated viral vectors (AAVs) are a widely used gene transfer platform in neuroscience. Although naturally AAV serotypes can have preferences for certain tissues, selectivity for particular cell types in the CNS does not exist. Towards interneuron targeting, capsid engineering of AAV2 including display of the designed ankyrin repeat protein (DARPin) 2K19 specific for the glutamate receptor subunit 4 (GluA4) at the N-terminus of the VP2 capsid protein has been established. The resulting AAV-VP2N is highly specific for interneurons, but exhibits rather moderate transduction efficiencies. METHODS: Two alternative insertion sites for 2K19 in the GH2/GH3 loop of capsid proteins VP1 (AAV-VP1L) or VP2 (AAV-VP2L) were exploited to yield second generation GluA4-AAVs. Having packaged reporter genes under ubiquitous promoters, the vectors were characterized for biochemical properties as well as gene delivery into cell lines and rat hippocampal slice cultures. Electrophysiological recordings monitored the functional properties of transduced cells. RESULTS: Compared to AAV-VP2N, the second-generation vectors, especially AAV-VP1L, achieved about 2-fold higher genomic titers as well as a substantially improved GluA4 binding. Improvements in gene transfer activities were 18-fold on GluA4-overexpressing A549 cells and five-fold on rat hippocampal organotypic slice cultures reaching approximately 60 % of all parvalbumin positive interneurons upon a single administration. The spiking behaviour of transduced cells was unaltered and characteristic for a heterogeneous group of interneurons. CONCLUSION: The substantially improved gene transfer activity of the second generation GluA4-targeted AAV combined with low toxicity makes this vector an attractive tool for interneuron-directed gene transfer with unrestricted promotor and transgene choice.

4D-MR flow analysis in patients after repair for tetralogy of Fallot.

OBJECTIVES: Comprehensive analysis of haemodynamics by 3D flow visualisation and retrospective flow quantification in patients after repair of tetralogy of Fallot (TOF). METHODS: Time-resolved flow-sensitive 4D MRI (spatial resolution ~ 2.5 mm, temporal resolution = 38.4 ms) was acquired in ten patients after repair of TOF and in four healthy controls. Data analysis included the evaluation of haemodynamics in the aorta, the pulmonary trunk (TP) and left (lPA) and right (rPA) pulmonary arteries by 3D blood flow visualisation using particle traces, and quantitative measurements of flow velocity. RESULTS: 3D visualisation of whole heart haemodynamics provided a comprehensive overview on flow pattern changes in TOF patients, mainly alterations in flow velocity, retrograde flow and pathological vortices. There was consistently higher blood flow in the rPA of the patients (rPA/lPA flow ratio: 2.6 ± 2.5 vs. 1.1 ± 0.1 in controls). Systolic peak velocity in the TP was higher in patients (1.9 m/s ± 0.7 m/s) than controls (0.9 m/s ± 0.1 m/s). CONCLUSIONS: 4D flow-sensitive MRI permits the comprehensive evaluation of blood flow characteristics in patients after repair of TOF. Altered flow patterns for different surgical techniques in the small patient cohort may indicate its value for patient monitoring and potentially identifying optimal surgical strategies.

[Skeletal trauma during the growing period. Radiological diagnostics]. / Skeletttraumatologie im Wachstumsalter: Radiologische Diagnostik.

Bone fractures in childhood are a common occurrence. A differentiated assessment of fractures is of great importance for the diagnostics, therapy planning and estimation of the prognosis. This review article explains the most important characteristics of skeletal trauma in childhood. Skeletal development, the mechanisms of fracture healing and growth disorders after injury to the epiphyseal plates and classification of fractures will be discussed and typical bone fractures in children and the pitfalls in X-ray diagnostics are demonstrated.

In situ labeling of non-accommodating interneurons based on metabolic rates.

Maintaining high frequency firing of narrow action potentials puts a large metabolic load on fast spiking (FS), perisomatic-inhibitory interneurons compared to their slow-spiking, dendrite targeting counterparts. Although the relationship of action potential (AP) firing and metabolism is firmly established, there is no single method to differentiate interneurons in situ based on their firing properties. In this study, we explore a novel strategy to easily identify the metabolically active FS cells among different classes of interneurons. We found that the oxidation of the fluorescent free radical marker 2,7-dichlorodihydrofluorescein (H2DCF) preferentially occurs in interneurons both in slice cultures and acute brain slices. Despite their morphological heterogeneity, almost all DCF-positive (DCF+) neurons belonged to the cluster of non-accommodating FS interneurons. Furthermore, all FS interneurons expressing parvalbumin (PV) both in slice cultures and in acute slices from tdTomato-PVCre transgenic mice were also DCF+. However, only half of the recorded DCF + cells were also PV+, indicating that H2DCF-oxidation occurs in different interneuron classes characterized by non-accomodating AP-firing. Comprehensively enhancing spontaneous neuronal activity led to mitochondrial oxidation of DCF in pyramidal cells as well as interneurons, suggesting that the apparent selectivity towards interneurons represents differences in the underlying metabolic load. While radical-scavenging, inhibition of APs or NO-synthesis, and iron chelation had no effect on the staining pattern, exposure to the complex-I inhibitor, rotenone, prevented interneuronal DCF accumulation. We conclude that H2DCF oxidation is independent of free radicals but correlates with the intensive oxidative energy metabolism and high mitochondrial mass in interneurons sharing the non-accommodating FS phenotype.