Cavity-enhanced Ramsey spectroscopy at a Rydberg-atom–superconducting-circuit interface

The coherent interaction of Rydberg helium atoms with microwave fields in a λ/4 superconducting coplanar waveguide resonator has been exploited to probe the spectral characteristics of an individual resonator mode. This was achieved by preparing the atoms in the 1s55s 3S1 Rydberg level by resonance enhanced two-color two-photon excitation from the metastable 1s2s 3S1 level. The atoms then traveled over the resonator in which the third harmonic microwave field, at a frequency of ωres=2π×19.556 GHz, drove the two-photon 1s55s 3S1 → 1s56s 3S1 transition. By injecting a sequence of Ramsey pulses into the resonator and monitoring the coherent evolution of the Rydberg state population by state-selective pulsed electric field ionization as the frequency of the microwave field was tuned, spectra were recorded that allowed the resonator resonance frequency and quality factor to be determined with the atoms acting as microscopic quantum sensors

Metatalk and metalinguistic knowledge: the interplay of procedural and declarative knowledge in the classroom discourse of first-language grammar teaching

This is the author accepted manuscript. The final version is available from Routledge via the DOI in this record'High-quality talk' is a fundamental principle of many approaches to teaching grammar. However, relatively few studies have attempted to characterize this talk with attention to the ways in which classroom dialogue might engender metalinguistic thinking. This paper explores how the concepts of procedural and declarative metalinguistic knowledge may be applied to classroom discourse in order to identify the problems and potentials of grammatical 'Metatalk'. The data is drawn from observations of grammar for writing lessons in 17 classrooms across England. This opportunity sample was drawn from the intervention group of a randomized control trial funded by the Education Endowment Foundation all of whom were working within a pedagogical model which embeds attention to grammar as a resource for meaning-making within the teaching of writing. Given the impact of effective teacher-student dialogue on student learning, studies such as this are valuable for illuminating how classroom talk operates within the teaching of grammar for writing. The findings particularly reveal the role of teacherguided talk during collaborative writing activities in facilitating transfer between declarative and procedural metalinguistic knowledge.Education Endowment Foundatio

Preparation of circular Rydberg states in helium with n ≥ 70 using a modified version of the crossed-fields method

Circular Rydberg states with n = 70 have been prepared in helium using a modified version of the crossed-fields method. This approach to the preparation of high-n circular Rydberg states overcomes limitations of the standard crossed-fields method which arise at this, and higher, values of n. The experiments were performed with atoms traveling in pulsed supersonic beams that were initially laser photoexcited from the metastable 1s2s³S₁ level to the 1s73s³S₁ level by resonance-enhanced two-color two-photon excitation in a magnetic field of 16.154 G. These excited atoms were then polarized using a perpendicular electric field of 0.844 V/cm, and transferred by a pulse of microwave radiation to the state that, when adiabatically depolarized, evolves into the n = 70 circular state in zero electric field. The excited atoms were detected by state-selective electric field ionization. Each step of the circular state preparation process was validated by comparison with the calculated atomic energy-level structure in the perpendicular electric and magnetic fields used. Of the atoms initially excited to the 1s73s³S₁ level, ∼ 80% were transferred to the n = 70 circular state. At these high values of n, Δn = 1circular-to-circular Rydberg state transitions occur at frequencies below 20 GHz. Consequently, atoms in these states, and the circular state preparation process presented here, are well suited to hybrid cavity QED experiments with Rydberg atoms and superconducting microwave circuits

Ab initio study of magnetism at the TiO2/LaAlO3 interface

In this paper we study the possible relation between the electronic and magnetic structure of the TiO2/LaAlO3 interface and the unexpected magnetism found in undoped TiO2 films grown on LaAlO$_3$. We concentrate on the role played by structural relaxation and interfacial oxygen vacancies. LaAlO3 has a layered structure along the (001) direction with alternating LaO and AlO2 planes, with nominal charges of +1 and -1, respectively. As a consequence of that, an oxygen deficient TiO2 film with anatase structure will grow preferently on the AlO2 surface layer. We have therefore performed ab-initio calculations for superlattices with TiO2/AlO2 interfaces with interfacial oxygen vacancies. Our main results are that vacancies lead to a change in the valence state of neighbour Ti atoms but not necessarily to a magnetic solution and that the appearance of magnetism depends also on structural details, such as second neighbor positions. These results are obtained using both the LSDA and LSDA+U approximations.Comment: Accepted for publication in Journal of Materials Scienc

Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018

BACKGROUNDS AND AIMS: Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. METHODS: The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. RESULTS: Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. CONCLUSIONS: The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing

Procedural confidence in hospital based practitioners: implications for the training and practice of doctors at all grades

<p>Abstract</p> <p>Background</p> <p>Medical doctors routinely undertake a number of practical procedures and these should be performed competently. The UK Postgraduate Medical Education and Training Board (PMETB) curriculum lists the procedures trainees should be competent in. We aimed to describe medical practitioner's confidence in their procedural skills, and to define which practical procedures are important in current medical practice.</p> <p>Methods</p> <p>A cross sectional observational study was performed measuring procedural confidence in 181 hospital practitioners at all grades from 2 centres in East Anglia, England.</p> <p>Results</p> <p>Both trainees and consultants provide significant service provision. SpR level doctors perform the widest range and the highest median number of procedures per year. Most consultants perform few if any procedures, however some perform a narrow range at high volume. Cumulative confidence for the procedures tested peaks in the SpR grade. Five key procedures (central line insertion, lumbar puncture, pleural aspiration, ascitic aspiration, and intercostal drain insertion) are the most commonly performed, are seen as important generic skills, and correspond to the total number of procedures for which confidence can be maintained. Key determinants of confidence are gender, number of procedures performed in the previous year and total number of procedures performed.</p> <p>Conclusion</p> <p>The highest volume of service requirement is for six procedures. The procedural confidence is dependent upon gender, number of procedures performed in the previous year and total number of procedures performed. This has implications for those designing the training curriculum and with regards the move to shorten the duration of training.</p

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14&nbsp;weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48&nbsp;weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Multiple signalling modalities mediated by dendritic exocytosis of oxytocin and vasopressin

The mammalian hypothalamic magnocellular neurons of the supraoptic and paraventricular nuclei are among the best understood of all peptidergic neurons. Through their anatomical features, vasopressin- and oxytocin-containing neurons have revealed many important aspects of dendritic functions. Here, we review our understanding of the mechanisms of somato-dendritic peptide release, and the effects of autocrine, paracrine and hormone-like signalling on neuronal networks and behaviour