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Investigating out-of-equilibrium dynamics with two-dimensional (2D) systems is of widespread theoretical interest, as these systems are strongly influenced by fluctuations and there exists a superfluid phase transition at a finite temperature. In this work, we realise matter-wave interference for degenerate Bose gases, including the first demonstration of coherent splitting of 2D Bose gases using magnetic trapping potentials. We improve the fringe contrast by imaging only a thin slice of the expanded atom clouds, which will be necessary for subsequent studies on the relaxation of the gas following a quantum quench.

We apply three machine learning strategies to optimize the atomic cooling processes utilized in the production of a Bose-Einstein condensate (BEC). For the first time, we optimize both laser cooling and evaporative cooling mechanisms simultaneously. We present the results of an evolutionary optimization method (differential evolution), a method based on non-parametric inference (Gaussian process regression) and a gradient-based function approximator (artificial neural network). Online optimization is performed using no prior knowledge of the apparatus, and the learner succeeds in creating a BEC from completely randomized initial parameters. Optimizing these cooling processes results in a factor of four increase in BEC atom number compared to our manually-optimized parameters. This automated approach can maintain close-to-optimal performance in long-term operation. Furthermore, we show that machine learning techniques can be used to identify the main sources of instability within the apparatus.

We dress atoms with multiple-radiofrequency (RF) fields and investigate the spectrum of transitions driven by an additional probe field. A complete theoretical description of this rich spectrum is presented, in which we find allowed transitions and determine their amplitudes using the resolvent formalism. Experimentally, we observe transitions up to sixth order in the probe field using RF spectroscopy of Bose-Einstein condensates trapped in single- and multiple-RF-dressed potentials. We find excellent agreement between theory and experiment, including the prediction and verification of previously unobserved transitions, even in the single-RF case.

Techniques to manipulate the individual constituents of an ultracold mixture are key to investigating impurity physics. In this work, we confine a mixture of the hyperfine ground states of Rb-87 in a double-well potential. The potential is produced by dressing the atoms with multiple radiofrequencies. The amplitude and phase of each frequency component of the dressing field are individually controlled to independently manipulate each species. Furthermore, we verify that our mixture of hyperfine states is collisionally stable, with no observable inelastic loss.

Methods to manipulate the individual constituents of an ultracold quantum gas mixture are essential tools for a number of applications, for example the direct quantum simulation of impurity physics. We investigate a scheme in which species-selective control is achieved using magnetic potentials dressed with multiple radiofrequencies, exploiting the different Landé g-factors of the constituent atomic species. We describe a mixture dressed with two frequencies, where atoms are confined in harmonic potentials with a controllable degree of overlap between the two atomic species. This is then extended to a four radiofrequency scheme in which a double well potential for one species is overlaid with a single well for the other. The discussion is framed with parameters that are suitable for a 85Rb and 87Rb mixture, but is readily generalised to other combinations.

Immunotherapy with the chimeric anti-GD2 monoclonal antibody dinutuximab, combined with alternating granulocyte-macrophage colony-stimulating factor and intravenous interleukin-2 (IL-2), improves survival in patients with high-risk neuroblastoma. We aimed to assess event-free survival after treatment with ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2, compared with dinutuximab beta alone in children and young people with high-risk neuroblastoma. We did an international, open-label, phase 3, randomised, controlled trial in patients with high-risk neuroblastoma at 104 institutions in 12 countries. Eligible patients were aged 1–20 years and had MYCN-amplified neuroblastoma with stages 2, 3, or 4S, or stage 4 neuroblastoma of any MYCN status, according to the International Neuroblastoma Staging System. Patients were eligible if they had been enrolled at diagnosis in the HR-NBL1/SIOPEN trial, had completed the multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide, with or without topotecan, vincristine, and doxorubicin), had achieved a disease response that fulfilled prespecified criteria, had received high-dose therapy (busulfan and melphalan or carboplatin, etoposide, and melphalan) and had received radiotherapy to the primary tumour site. In this component of the trial, patients were randomly assigned (1:1) to receive dinutuximab beta (20 mg/m2 per day as an 8 h infusion for 5 consecutive days) or dinutuximab beta plus subcutaneous IL-2 (6 × 106 IU/m2 per day on days 1–5 and days 8–12 of each cycle) with the minimisation method to balance randomisation for national groups and type of high-dose therapy. All participants received oral isotretinoin (160 mg/m2 per day for 2 weeks) before the first immunotherapy cycle and after each immunotherapy cycle, for six cycles. The primary endpoint was 3-year event-free survival, analysed by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01704716, and EudraCT, number 2006-001489-17, and recruitment to this randomisation is closed. Between Oct 22, 2009, and Aug 12, 2013, 422 patients were eligible to participate in the immunotherapy randomisation, of whom 406 (96%) were randomly assigned to a treatment group (n=200 to dinutuximab beta and n=206 to dinutuximab beta with subcutaneous IL-2). Median follow-up was 4·7 years (IQR 3·9–5·3). Because of toxicity, 117 (62%) of 188 patients assigned to dinutuximab beta and subcutaneous IL-2 received their allocated treatment, by contrast with 160 (87%) of 183 patients who received dinutuximab beta alone (p<0·0001). 3-year event-free survival was 56% (95% CI 49–63) with dinutuximab beta (83 patients had an event) and 60% (53–66) with dinutuximab beta and subcutaneous IL-2 (80 patients had an event; p=0·76). Four patients died of toxicity (n=2 in each group); one patient in each group while receiving immunotherapy (n=1 congestive heart failure and pulmonary hypertension due to capillary leak syndrome; n=1 infection-related acute respiratory distress syndrome), and one patient in each group after five cycles of immunotherapy (n=1 fungal infection and multi-organ failure; n=1 pulmonary fibrosis). The most common grade 3–4 adverse events were hypersensitivity reactions (19 [10%] of 185 patients in the dinutuximab beta group vs 39 [20%] of 191 patients in the dinutuximab plus subcutaneous IL-2 group), capillary leak (five [4%] of 119 vs 19 [15%] of 125), fever (25 [14%] of 185 vs 76 [40%] of 190), infection (47 [25%] of 185 vs 64 [33%] of 191), immunotherapy-related pain (19 [16%] of 122 vs 32 [26%] of 124), and impaired general condition (30 [16%] of 185 vs 78 [41%] of 192). There is no evidence that addition of subcutaneous IL-2 to immunotherapy with dinutuximab beta, given as an 8 h infusion, improved outcomes in patients with high-risk neuroblastoma who had responded to standard induction and consolidation treatment. Subcutaneous IL-2 with dinutuximab beta was associated with greater toxicity than dinutuximab beta alone. Dinutuximab beta and isotretinoin without subcutaneous IL-2 should thus be considered the standard of care until results of ongoing randomised trials using a modified schedule of dinutuximab beta and subcutaneous IL-2 are available. European Commission 5th Frame Work Grant, St. Anna Kinderkrebsforschung, Fondation ARC pour la recherche sur le Cancer.

To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepoint of 109 days, resulting from the median time between ASCR and initiation of immunotherapy, was used to define patients’ eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2–8.2 years) for 844 eligible patients balanced for risk factors, such as age, sex, stage 4, MYCN amplification and response prior to HDT. The five-year event-free and overall survival (95% confidence interval (CI) of 466 patients not receiving immunotherapy was 42% (38–47%) and 50% (46–55%) but was 57% (51–62%) and 64% (59–69%) for 378 patients receiving immunotherapy (p < 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (p = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (p = 0.0043, HR 1.494) and >1 metastatic compartment at diagnosis (p < 0.001, HR 2.665) as risk factors for relapse or progression. Results suggest an important role for dinutuximab beta-based immunotherapy within the treatment concepts applied in HR-NBL1/SIOPEN.

Background Classical allergy diagnostic workup “from symptoms to molecules” comprises 1) clinical investigation, 2) skin prick- and IgE- testing, and recently, 3) molecular allergy testing. We aimed to examine the diagnostic fidelity of the alternative approach “from molecules to symptoms”, which was recently suggested in the EAACI Molecular Allergology User’s Guide, in a retrospective clinical study. Methods Records from 202 patients with clinically suspected allergic sensitizations were extracted from files at two sites applying either the “ISAC-first” workup with IgE-testing by immuno-solid phase allergen chip ISAC112 followed by selected skin prick tests (SPT) or the “SPT-first” starting with SPT followed by the microarray test. Results In the ISAC-first procedure significantly less SPTs were performed during allergy diagnosis (median 4 vs. 14). By SPT in 19% of patients in the ISAC-first group and in 34% in the SPT-first group additional respiratory allergens (p = 0.014) were detected not positive in ISAC microarray. By ISAC microarray test 18% additional sensitizations were found in the ISAC-first, and 32% in SPT-first cohort (p = 0.016). For food allergens 13 and 12% additional sensitizations were detected by the microarray not detected by SPT in the two groups (p = 0.800). No additional food allergen was found by SPT in the ISAC-first group, while in 6% of the cases in the SPT-first group detected sensitizations were negative in the microarray. Discussion The ISAC-first approach followed by (fewer) SPTs meets the demands for a patient’s tailored diagnostic work-up and therefore can be considered equivalent to the conventional way using the skin prick test as first screening tool, followed by IgE diagnosis. Conclusions For the diagnostic verification of clinically suspected allergy, the novel concept “from molecules to clinic” offers a reliable diagnostic workup in shorter time. Due to lower skin test numbers it is especially applicable for young children and seniors, in atopic patients, and whenever skin tests get difficult or unreliable.

Background The performance of a primary posterior capsulorhexis (PPC) with and without posterior optic buttonholing (POBH) may significantly influence the intraocular pressure (IOP) after cataract surgery in age-related cataract patients. Methods The prospective randomized clinical study was performed at the department of Ophthalmology, Medical University of Vienna, Austria. Thirty consecutive cataract patients with bilateral same-day cataract surgery (60 eyes) under topical anesthesia were enrolled. In randomized order, cataract surgery with combined PPC/POBH was performed in one eye; in the other eye, cataract surgery was performed with PPC and in-the-bag implantation of the intraocular lens (IOL). Standardized IOP measurements by Goldmann applanation tonometry were performed preoperatively, 1, 2, 4, 6, 8 and 24 hours postoperatively, as well as 1 week and 1 month postoperatively. Results During the first 24 hours after surgery, all IOP measurements were significantly lower in eyes with combined PPC/POBH when compared to eyes with solitary PPC ( p  < 0.001). No IOP peaks of more than 27 mmHg were observed with combined PPC/POBH. In contrast, in eyes with PPC and in-the-bag IOL implantation, seven patients had an IOP peak of more than 27 mmHg and four IOP peaks of more than 30 mmHg. One week and 1 month postoperatively, IOP measurements were statistically comparable, and no significant differences could be observed between the two groups ( p  > 0.05). Conclusion Postoperative IOP peaks after cataract surgery with sole PPC can be effectively prevented by the buttonholing of the IOL through the posterior capsulorhexis.

Aim: To determine the effects of various mixtures of O2 and CO2 on retinal blood flow in healthy subjects. Methods: A randomised, double masked, four way crossover trial was carried out in 12 healthy male non-smoking subjects. Gas mixtures (100% O2, 97.5% O2 + 2.5% CO2, 95% O2 + 5% CO2, and 92% O2 + 8% CO2) were administered for 10 minutes each. Two non-invasive methods were used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the assessment of retinal vessel diameters. Arterial pH, pCO2, and pO2 were determined with an automatic blood gas analysis system. Retinal blood flow through a major temporal vein was calculated. Results: Retinal blood velocity, retinal vessel diameter, and retinal blood flow decreased during all breathing periods (p <0.001 each). Administration of 92% O2 + 8% CO2 significantly increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%, and 8% CO2 to oxygen caused a marked decrease in pH and an increase in pCO2 (p <0.001 versus pure oxygen). Conclusions: Breathing of pure oxygen and oxygen in combination with carbon dioxide significantly decreases retinal blood flow. Based on these data the authors speculate that hyperoxia induced vasoconstriction is not due to changes in intravascular pH and cannot be counteracted by an intravascular increase in pCO2.