A compact von Hámos spectrometer for parallel X-ray Raman scattering and X-ray emission spectroscopy at ID20 of the European Synchrotron Radiation Facility.

A compact spectrometer for medium-resolution resonant and non-resonant X-ray emission spectroscopy in von Hámos geometry is described. The main motivation for the design and construction of the spectrometer is to allow for acquisition of non-resonant X-ray emission spectra while measuring non-resonant X-ray Raman scattering spectra at beamline ID20 of the European Synchrotron Radiation Facility. Technical details are provided and the performance and possible use of the spectrometer are demonstrated by presenting results of several X-ray spectroscopic methods on various compounds.

Experimental capabilities for liquid jet samples at sub-MHz rates at the FXE Instrument at European XFEL.

The Femtosecond X-ray Experiments (FXE) instrument at the European X-ray Free-Electron Laser (EuXFEL) provides an optimized platform for investigations of ultrafast physical, chemical and biological processes. It operates in the energy range 4.7-20 keV accommodating flexible and versatile environments for a wide range of samples using diverse ultrafast X-ray spectroscopic, scattering and diffraction techniques. FXE is particularly suitable for experiments taking advantage of the sub-MHz repetition rates provided by the EuXFEL. In this paper a dedicated setup for studies on ultrafast biological and chemical dynamics in solution phase at sub-MHz rates at FXE is presented. Particular emphasis on the different liquid jet sample delivery options and their performance is given. Our portfolio of high-speed jets compatible with sub-MHz experiments includes cylindrical jets, gas dynamic virtual nozzles and flat jets. The capability to perform multi-color X-ray emission spectroscopy (XES) experiments is illustrated by a set of measurements using the dispersive X-ray spectrometer in von Hamos geometry. Static XES data collected using a multi-crystal scanning Johann-type spectrometer are also presented. A few examples of experimental results on ultrafast time-resolved X-ray emission spectroscopy and wide-angle X-ray scattering at sub-MHz pulse repetition rates are given.

Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

PEACE V - Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial.

BACKGROUND: Pelvic nodal recurrences are being increasingly diagnosed with the introduction of new molecular imaging techniques, like choline and PSMA PET-CT, in the restaging of recurrent prostate cancer (PCa). At this moment, there are no specific treatment recommendations for patients with limited nodal recurrences and different locoregional treatment approaches are currently being used, mostly by means of metastasis-directed therapies (MDT): salvage lymph node dissection (sLND) or stereotactic body radiotherapy (SBRT). Since the majority of patients treated with MDT relapse within 2 years in adjacent lymph node regions, with an estimated median time to progression of 12-18 months, combining MDT with whole pelvic radiotherapy (WPRT) may improve oncological outcomes in these patients. The aim of this prospective multicentre randomized controlled phase II trial is to assess the impact of the addition of WPRT to MDT and short-term androgen deprivation therapy (ADT) on metastasis-free survival (MFS) in the setting of oligorecurrent pelvic nodal recurrence. METHODS & DESIGN: Patients diagnosed with PET-detected pelvic nodal oligorecurrence (≤5 nodes) following radical local treatment for PCa, will be randomized in a 1:1 ratio between arm A: MDT and 6 months of ADT, or arm B: WPRT added to MDT and 6 months of ADT. Patients will be stratified by type of PET-tracer (choline, FACBC or PSMA) and by type of MDT (sLND or SBRT). The primary endpoint is MFS and the secondary endpoints include clinical and biochemical progression-free survival (PFS), prostate cancer specific survival, quality of life (QoL), toxicity and time to castration-resistant prostate cancer (CRPC) and to palliative ADT. Estimated study completion: December 31, 2023. DISCUSSION: This is the first prospective multicentre randomized phase II trial assessing the potential of combined WPRT and MDT as compared to MDT alone on MFS for patients with nodal oligorecurrent PCa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03569241, registered June 14, 2018, ; Identifier on Swiss National Clinical Trials Portal (SNCTP): SNCTP000002947, registered June 14, 2018.

68Ga-PSMA PET/CT-based metastasis-directed radiotherapy for oligometastatic prostate cancer recurrence after radical prostatectomy.

PURPOSE: The aim of this communication was to assess the efficacy of directed oligometastatic radiotherapy (RT) based on 68Ga-PSMA PET/CT in patients with prostate cancer (PCa) biochemical relapse (BCR) after primary treatment with curative intent. METHODS: This is a retrospective analysis of a monocentric cohort of PCa patients diagnosed with oligometastatic disease on 68Ga-PSMA PET/CT and treated with metastasis-directed RT. Inclusion criteria were: histologically proven PCa, BCR after primary treatment with curative intent, oligometastatic disease defined as ≤ 3 metastatic lesions. To evaluate the efficacy of the therapy, biochemical response defined as a decrease of > 50% of PSA (PSA50) was measured at 1 and 4 months. Patients were followed up until progression and start of androgen deprivation therapy (ADT). BCR-free survival and ADT-free survival were calculated. RESULTS: 20 patients met the inclusion criteria. Median PSA value: 1.4 ng/ml (IQR, 0.3-2.3 ng/ml). A total of 30 PSMA-positive lesions were treated: 18 lymph nodes (60%), nine bone (30%) and three visceral lesions (10%). Median follow-up was 15 months (range 4-33 months). Biochemical response at 1 and 4 months was found in 3/20 patients (15%) and 14/20 (70%), respectively. BCR-free survival rate at 1 year was 79% and 53% at 2 years. ADT-free survival at 2 years was 74%. CONCLUSION: This retrospective study suggests that metastasis-directed RT based on 68Ga-PSMA PET/CT may be a valuable treatment in patients with PCa oligometastatic disease, providing promising BCR-free survival rates and potentially postponing ADT for at least 2 years in 74% of the patients. Response assessment should not be measured before 4 months after treatment.

Ballistic Anisotropic Magnetoresistance of Single-Atom Contacts.

Anisotropic magnetoresistance, that is, the sensitivity of the electrical resistance of magnetic materials on the magnetization direction, is expected to be strongly enhanced in ballistic transport through nanoscale junctions. However, unambiguous experimental evidence of this effect is difficult to achieve. We utilize single-atom junctions to measure this ballistic anisotropic magnetoresistance (AMR). Single Co and Ir atoms are deposited on domains and domain walls of ferromagnetic Fe layers on W(110) to control their magnetization directions. They are contacted with nonmagnetic tips in a low-temperature scanning tunneling microscope to measure the junction conductances. Large changes of the magnetoresistance occur from the tunneling to the ballistic regime due to the competition of localized and delocalized d-orbitals, which are differently affected by spin-orbit coupling. This work shows that engineering the AMR at the single atom level is feasible.

[The future of pediatric intensive care]. / Le futur des soins intensifs pédiatriques.

Paediatric intensive care is born 40 years ago. It has been shown that admission of critically ill children in intensive care (ICU) where no paediatric intensivists worked increased significantly the mortality and the length of stay. The recognition of Paediatric Intensive Care (PICU) does not exist in Belgium and children are admitted in both adult and paediatric intensive care units. It is mandatory to recognise the PICU specificity and the usefulness of a fellowship in paediatric intensive care. Development of molecular biology and genetics will permit in the near future to understand reversible and irreversible cellular processes of the majority of problems responsible for mortality in critical care and to allow the development of new diagnostic and therapeutic techniques. Rapid development of information will permit the creation of multicenter databases including all PICU's data. The final goal is an intelligent tool for making decision process. Telemedecine is born which permits a virtual consultation of the patient. Technological progress must not impair the wellbeing of the child and its family. The PICU of the future must be "parents admitted". PICU profile is progressively changing, the way of taking care of the critically ill child and its family is also changing and improving. An ethical reflexion among the health care providers' team and a dialogue with parents will blossom.

[Non-invasive bi-level ventilation in paediatric status asthmaticus]. / Ventilation non invasive chez un nourrisson en état de mal asthmatique.

Invasive ventilation in status asthmaticus is associated with an increased mortality and morbidity. To avoid intubation associated complications, non-invasive bi-level ventilation is often used in adults and children. We report the clinical history of an 11-month old infant, which encountered intubation criteria but was treated successfully by full-face mask non-invasive bi-level ventilation. Despite difficulties in application due to young age and lack of age related material, non-invasive bi-level ventilation is a good tool in the treatment of children with status asthmaticus.

Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk.

Bronchogenic carcinoma is closely associated with cigarette smoking although additional environmental or individual factors might regulate a person's susceptibility to that disease. To further define such risk factors, the prevalence of the genetic debrisoquine 4-hydroxylation deficiency was determined before therapeutic intervention in 270 lung cancer patients. Nineteen homozygous carriers of this defect (poor metabolizers) were found (7.0%, 95% confidence limits 4.3%-10.8%), a number being lower than 30 out of 270 reference patients (11.1%, 95% confidence limits 7.6%-15.5%). The odds ratio of 0.61 was of marginal statistical significance (P = 0.067). Subdividing the collective according to histology revealed a trend towards underrepresentation of poor metabolizers especially among patients with adenocarcinoma (1 out of 37, P = 0.086) and among young patients not older than 50 years (none out of 32, P = 0.028). All poor metabolizers (PMs) in the cancer group were smokers. In 18 patients the phenotype assignment was confirmed by a second test several weeks after surgical or other treatment. In 220 of the lung cancer patients the N-acetyltransferase polymorphism was evaluated by means of the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after ingestion of caffeine (coffee). There were 111 (50.5%) slow acetylators and 109 (49.5%) fast acetylators. A statistically significant clustering of either phenotype after stratification according to histology, or debrisoquine hydroxilator status was lacking. Moreover, there was no difference in the ratio of both phenotypes as compared to the reference collective of 245 patients (53.5% slow and 46.5% fast acetylators). As a third genetic host factor the AB0 blood group frequencies were evaluated in 263 lung cancer patients. The frequency ratio of A/O was significantly higher as compared to 41,423 blood donors (odds ratio 1.37, 95% confidence limits 1.02-1.84, P less than 0.05). A/O tended to be especially high in young patients not older than 50 years. The ratio B/O in bronchial cancer was significantly higher than expected. The results suggest that the debrisoquine hydroxilator status might have an impact on an individual's susceptibility to lung cancer. This association is either a weak one and/or is restricted to certain histological cancer types or to patients with certain characteristics. The acetylator phenotype could not be established as a risk factor, whereas AB0 blood groups seem to influence lung cancer susceptibility.