Shaping quantum pulses of light via coherent atomic memory

We describe a technique for generating pulses of light with controllable photon numbers, propagation direction, timing, and pulse shapes. The technique is based on preparation of an atomic ensemble in a state with a desired number of atomic spin excitations, which is later converted into a photon pulse. Spatio-temporal control over the pulses is obtained by exploiting long-lived coherent memory for photon states and electromagnetically induced transparency (EIT) in an optically dense atomic medium. Using photon counting experiments we observe generation and shaping of few-photon sub-Poissonian light pulses. We discuss prospects for controlled generation of high-purity n-photon Fock states using this technique.Comment: 4 pages, 4 figure

Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1

Background: Methylotrophic microorganisms are playing a key role in biogeochemical processes - especially the global carbon cycle - and have gained interest for biotechnological purposes. Significant progress was made in the recent years in the biochemistry, genetics, genomics, and physiology of methylotrophic bacteria, showing that methylotrophy is much more widespread and versatile than initially assumed. Despite such progress, system-level description of the methylotrophic metabolism is currently lacking, and much remains to understand regarding the network-scale organization and properties of methylotrophy, and how the methylotrophic capacity emerges from this organization, especially in facultative organisms. Results: In this work, we report on the integrated, system-level investigation of the metabolic network of the facultative methylotroph Methylobacterium extorquens AM1, a valuable model of methylotrophic bacteria. The genome-scale metabolic network of the bacterium was reconstructed and contains 1139 reactions and 977 metabolites. The sub-network operating upon methylotrophic growth was identified from both in silico and experimental investigations, and 13C-fluxomics was applied to measure the distribution of metabolic fluxes under such conditions. The core metabolism has a highly unusual topology, in which the unique enzymes that catalyse the key steps of C1 assimilation are tightly connected by several, large metabolic cycles (serine cycle, ethylmalonyl- CoA pathway, TCA cycle, anaplerotic processes). The entire set of reactions must operate as a unique process to achieve C1 assimilation, but was shown to be structurally fragile based on network analysis. This observation suggests that in nature a strong pressure of selection must exist to maintain the methylotrophic capability. Nevertheless, substantial substrate cycling could be measured within C2/C3/C4 inter-conversions, indicating that the metabolic network is highly versatile around a flexible backbone of central reactions that allows rapid switching to multi-carbon sources. Conclusions: This work emphasizes that the metabolism of M. extorquens AM1 is adapted to its lifestyle not only in terms of enzymatic equipment, but also in terms of network-level structure and regulation. It suggests that the metabolism of the bacterium has evolved both structurally and functionally to an efficient but transitory utilization of methanol. Besides, this work provides a basis for metabolic engineering to convert methanol into value-added products

A Highly Tailored Text and Voice Messaging Intervention to Improve Medication Adherence in Patients With Either or Both Hypertension and Type 2 Diabetes in a UK Primary Care Setting: Feasibility Randomized Controlled Trial of Clinical Effectiveness.

BACKGROUND: The efficacy of a highly tailored digital intervention to support medication adherence and feasibility to support clinical effectiveness as an adjunct to the primary care setting has not been evaluated. OBJECTIVE: This trial aimed to assess the behavioral efficacy of a highly tailored digital intervention to support medication adherence and to evaluate the feasibility of its clinical effectiveness, in patients with either or both hypertension and type 2 diabetes. We also examined quality of life and mechanisms of behavior change. Intervention fidelity, engagement, and satisfaction were also explored. METHODS: This was a multicenter, individually randomized controlled trial of 2 parallel groups: an intervention group that received a highly tailored text message and interactive voice response intervention for 12 weeks, and a control group that received usual care. Medication adherence was measured using self-reports and assessor-blinded practice records of a repeat prescription. Systolic blood pressure and glucose levels were assessed by nurses blinded to group allocation during practice visits at 3 months follow-up. Questionnaires obtained data to assess intervention mechanisms of action and satisfaction and digital log files captured data to evaluate fidelity and engagement. RESULTS: A total of 135 nonadherent patients (62/135, 46% female; 122/135, 90.3%; aged above 50 years) were randomly allocated in the intervention (n=79) or in the control group (n=56); of whom 13% (18/135) were lost at follow-up. Medication adherence was significantly improved in the intervention group compared with the control group (t116=2.27; P=.02, 2-tailed). Systolic blood pressure was 0.6 mmHg (95% CI -7.423 to 6.301), and hemoglobin A1c was 4.5 mmol/mol (95% CI -13.099 to 4.710) lower in the intervention group compared with the control group. Changes in intentional nonadherence and nonintentional nonadherence explained the improvements in medication adherence in the intervention group (beta=.074, SE=0.464; P=.04), but not in the control group (beta=.00, SE 1.35; P=.37). The intervention had 100% fidelity, a median of 12 days of engagement, and 76% overall satisfaction. CONCLUSIONS: Our trial is the first that has been conducted in the United Kingdom and showed that among nonadherent patients with either or both hypertension and type 2 diabetes, a highly tailored digital intervention was effective at improving treatment adherence and feasible to obtain clinically meaningful outcomes. Changes in intentional and nonintentional nonadherence predicted the improvements in medication adherence. The intervention had high fidelity, engagement, and satisfaction. Future research using a rigorous design is needed to evaluate the clinical effectiveness and cost-effectiveness of the intervention in primary care. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 10668149; http://www.controlled-trials.com/ISRCTN10668149

Cervical screening attendance and cervical cancer risk among women who have sex with women

Objectives: To describe cervical cancer screening participation among women who have sex exclusively with women (WSEW) and women who have sex with women and men (WSWM) compared with women who have sex exclusively with men (WSEM), and women who have never had sex and compare this with bowel (colorectal) and breast screening participation. To explore whether there is evidence of differential stage 3 cervical intraepithelial neoplasia (CIN3) or cervical cancer risk. Methods: We describe cervical, bowel and breast cancer screening uptake in age groups eligible for the national screening programmes, prevalent CIN3 and cervical cancer at baseline, and incident CIN3 and cervical cancer at five years follow-up, among 218,674 women in UK Biobank, a cohort of healthy volunteers from the UK. Results: Compared with WSEM, in adjusted analysis [odds ratio (95% confidence interval)], WSEW 0.10 (0.08–0.13), WSWM 0.73 (0.58–0.91), and women who have never had sex 0.02 (0.01–0.02) were less likely to report ever having attended cervical screening. There were no differences when considering bowel cancer screening uptake (p = 0.61). For breast cancer screening, attendance was lower among WSWM 0.79 (0.68 to 0.91) and women who have never had sex 0.47 (0.29–0.58), compared with WSEM. There were incident and prevalent cases of both CIN3 and cervical cancer among WSEW and WSWM. Compared with WSEM with a single male partner, among WSEW there was a twofold increase in CIN3 1.91 (1.01 to 3.59); among WSWM with only one male partner, this was 2.25 (1.19 to 4.24). Conclusions: These findings highlight the importance of improving uptake of cervical screening among all women who have sex with women and breast screening among WSWM and women who have never had sex

Attribution of neuropsychiatric symptoms and prioritisation of evidence in the diagnosis of neuropsychiatric lupus:a mixed method study

OBJECTIVE: Neuropsychiatric lupus (NPSLE) is challenging to diagnose. Many neuropsychiatric symptoms, such as headache and hallucinations, cannot be verified by tests or clinician assessment. We investigated prioritisations of methods for diagnosing NPSLE and attributional views.METHODS: Thematic and comparative analyses were used to investigate how clinicians prioritise sources of evidence from a 13-item list, and explore discordances in clinician and patient perspectives on attribution.RESULTS: We identified high levels of variability and uncertainty in clinicians' assessments of neuropsychiatric symptoms in SLE patients. In attributional decisions, clinicians (surveys n = 400, interviews n = 50) ranked clinicians' assessments above diagnostic tests (many of which they reported were often unenlightening in NPSLE). Clinicians ranked patient opinion of disease activity last, and 46% of patients reported never/rarely having been asked if their SLE was flaring, despite experienced patients often having "attributional insight". SLE Patients (surveys n = 676, interviews n = 27) estimated higher attributability of neuropsychiatric symptoms to the direct effects of SLE on the nervous system than clinicians (p &lt; 0.001 for all symptoms excluding mania), and 24% reported that their self-assessment of disease activity was never/rarely concordant with their clinicians. Reports of misattributions were common, particularly of non-verifiable diffuse symptoms. Terminology differed between clinicians and influenced attribution estimates.CONCLUSION: NPSLE diagnostic tests and clinician assessments have numerous limitations, particularly in detecting diffuse neuropsychiatric symptoms that can be directly attributable and benefit from immunosuppression. Our findings suggest that incorporating patient attributional insights-although also subject to limitations-may improve attribution decision-making. Consensus regarding terminology and interpretations of "direct attributability" is required.</p

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices

Background and Aims There are few data on the feasibility of population screening for paroxysmal AF using hand-held ECG devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact (‘remote’) or via in-person appointments in primary care, and explored impact of age on screening outcomes. Methods People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (3 practices). Participants were asked to use a handheld ECG for 1-4 weeks. Screening outcomes included: uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Results Screening was carried out by 2,141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2,429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Conclusion Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact, and in all ages over 64 years, including in people aged 85 and over

Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project

Objective: Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge, and symptom under-reporting contributes to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. Methods: Quantitative and qualitative data analysed included: prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids, and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system. Results: We recruited 2,817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients' quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (p< 0.001) in the comparisons with IA patients for severe headache. Clinician and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritised for discussion and treatment. Conclusion: We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be-currently under-estimated-direct effects on the nervous system in IA and other systemic rheumatological diseases