Use of the out-of-hours emergency dental service at two south-east London hospitals

Abstract Background Prior to the introduction of the 2006 NHS dental contract in England and Wales, general dental practitioners (GDPs) were responsible for the provision of out-of-hours (OOH) emergency dental services (EDS); however there was great national variation in service provision. Under the contractual arrangements introduced 1st April 2006, local commissioning agencies became formally responsible for the provision of out-of-hours emergency dental services. This study aimed to examine patients' use of an out-of-hours emergency dental service and to determine whether the introduction of the 2006 national NHS dental contract had resulted in a change in service use, with a view to informing future planning and commissioning of care. Methods A questionnaire was administered to people attending the out-of-hours emergency dental service at two inner city London hospitals over two time periods; four weeks before and six months after the introduction of the dental contract in April 2006. The questionnaire explored: reasons for attending; dental registration status and attendance; method of access; knowledge and use of NHS Direct; satisfaction with the service; future preferences for access and use of out-of-hours dental services. Data were compared to determine any impact of the new contract on how and why people accessed the emergency dental service. Results The response rate was 73% of attendees with 981 respondents for the first time period and 546 for the second. There were no significant differences between the two time periods in the gender, age, ethnic distribution or main language of service users accessing the service. Overall, the main dental problem was toothache (72%) and the main reason for choosing this service was due to the inability to access another emergency dental service (42%). Significantly fewer service users attended the out-of-hours emergency dental service during the second period because they could not get an appointment with their own dentist (p = 0.002 from 28% to 20%) and significantly more service users in the second period felt the emergency dental service was easier to get to than their own dentist (P = 0.003 from 8% to 14%). Service users found out about the service from multiple sources, of which family and friends were the most common source (30%). In the second period fewer service users were obtaining information about the service from dental receptionists (P = 0.002 from 14% to 9%) and increased use of NHS Direct for a dental problem was reported (P = 0.002 from 16% to 22%) along with more service users being referred to the service by NHS Direct (P = 0.02 from 19% to 24%). The most common preference for future emergency dental care was face-to-face with a dentist (79%). Conclusion This study has provided an insight into how and why people use an out-of-hours emergency dental service and has helped to guide future commissioning of these services. Overall, the service was being used in much the same way both before and after the 2006 dental contract. Significantly more use was being made of NHS Direct after April 2006; however, informal information networks such as friends and family remain an important source of information about accessing emergency dental services.</p

Selection of antigenically advanced variants of seasonal influenza viruses.

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.This work was supported by the Bill & Melinda Gates Foundation Global Health Grant OPPGH5383; National Institute of Allergy and Infectious Diseases (NIAID) Public Health Service research grants (USA); ERATO (Japan Science and Technology Agency); the Center for Research on Influenza Pathogenesis (CRIP) funded by the NIAID Contracts HHSN266200700010C and HHSN27 2201400008C; the Japan Initiative for Global Research Network on Infectious Diseases; Grants-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; Grants-in-Aid from the Ministry of Health, Labour and Welfare, Japan; grants from the Strategic Basic Research Program of the Japan Science and Technology Agency; and by the Advanced Research & Development Programs for Medical Innovation from the Japan Agency for Medical Research and Development (AMED). C.A.R. was supported by a University Research Fellowship from the Royal Society. The authors acknowledge a Netherlands Organisation for Scientific Research (NWO) VICI grant, European Union (EU) FP7 programs EMPERIE (223498) and ANTIGONE (278976); Human Frontier Science Program (HFSP) program grant P0050/2008; Wellcome 087982AIA; and NIH Director's Pioneer Award DP1-OD000490-01. D.F.B and D.J.S. acknowledge CamGrid, the University of Cambridge distributed computer system. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nmicrobiol.2016.5

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

Relative contribution of biomedical, demographic, and socioeconomic factors to COVID-19 vaccine receipt in rural India

Background: In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease 2019 (COVID-19). Yet, little is known about the factors influencing access to vaccination at the individual level within rural poor settings of low-income countries. The aim of this study was to examine determinants of vaccine receipt in rural India. Methods: A census of a rural village in Tamil Nadu was undertaken from June 2021 to September 2022. We surveyed 775 participants from 262 households. Household-level data on socioeconomic status (SES), water, sanitation, and hygiene practices, and individual-level demographic information, travel history, and biomedical data, including anthropometry, vital signs, and comorbidities, were collected. Logistic regression models with 5-fold cross-validation were used to identify the biomedical, demographic, and socioeconomic determinants of vaccine receipt and the timing of receipt within the first 30 days of eligibility. Vaccine ineligible participants were excluded leaving 659 eligible participants. There were 650 eligible participants with complete biomedical, demographic, and socioeconomic data. Results: There were 68.0% and 34.0% of individuals (N = 650) who had received one and two vaccine doses, respectively. Participants with household ownership of a permanent account number (PAN) or ration card were 2.15 (95% CI:1.32–3.52) or 3.02 (95% CI:1.72–5.29) times more likely to receive at least one vaccine dose compared to households with no ownership of such cards. Participants employed as housewives or self-employed non-agricultural workers were 65% (95% CI:0.19–0.67) or 59% (95% CI:0.22–0.76) less likely to receive at least one vaccine dose compared to salaried workers. Household PAN card ownership, occupation and age were linked to the timing of vaccine receipt. Participants aged ≤18 and 45–60 years were 17.74 (95% CI:5.07–62.03) and 5.51 (95% CI:2.74–11.10) times more likely to receive a vaccine within 30 days of eligibility compared to 19-44-year-olds. Biomedical factors including BMI, vital signs, comorbidities, and COVID-19 specific symptoms were not consistently associated with vaccine receipt or timing of receipt. No support was found that travel history, contact with COVID-19 cases, and hospital admissions influenced vaccine receipt or timing of receipt. Conclusion: Factors linked to SES were linked to vaccine receipt, more so than biomedical factors which were targeted by vaccine policies. Future research should explore if government interventions including vaccine mandates, barriers to vaccine access, or peer influence linked to workplace or targeted vaccine promotion campaigns underpin these findings

Performance of a Modular Ton-Scale Pixel-Readout Liquid Argon Time Projection Chamber

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations

Entanglement demonstration on board a nano-satellite

Global quantum networks for secure communication can be realized using large fleets of satellites distributing entangled photon pairs between ground-based nodes. Because the cost of a satellite depends on its size, the smallest satellites will be most cost-effective. This Letter describes a miniaturized, polarization entangled, photon-pair source operating on board a nano-satellite. The source violates Bell’s inequality with a Clauser–Horne–Shimony–Holt parameter of 2.60±0.06. This source can be combined with optical link technologies to enable future quantum communication nano-satellite missions

SpooQy-1: The First Nano-Satellite to Demonstrate Quantum Entanglement in Space

SpooQy-1 is a 3-unit nanosatellite that was launched into a Low Earth Orbit from the International Space Station on the 17th of June 2019. The spacecraft hosts a scientific payload capable of producing entangled photon-pairs and measuring their polarization in orthogonal bases to perform a Bell test. Since launch, SpooQy-1 has routinely demonstrated the generation and detection of polarization entangled photon-pairs in Space, something that has previously only been demonstrated by the 630kg Micius mission by the Chinese Academy of Sciences. The measured entanglement correlations can violate Bell\u27s inequality with a CHSH parameter value of 2.60±0.06, over operating temperatures of 16 °C to 21.5 °C. These results demonstrate that quantum entanglement can be generated in space on highly resource-constrained platforms. A follow-on 12U mission, developed in partnership with RAL space,will build on this to demonstrate space-to-ground entanglement distribution, which is required for space-based nodes to support global quantum communication networks

Toll-Like Receptor- and Filarial Antigen-Mediated, Mitogen-Activated Protein Kinase- and NF-κB-Dependent Regulation of Angiogenic Growth Factors in Filarial Lymphatic Pathology

Filarial lymphatic pathology is of multifactorial origin, with inflammation, lymphangiogenesis, and innate immune responses all playing important roles. The role of Toll-like receptors (TLRs) in the development of filarial pathology is well characterized. Similarly, the association of pathology with elevated levels of plasma angiogenic factors has also been documented. To examine the association between TLR function and the development of lymphangiogenesis in filarial infections, we examined TLR- and filarial antigen-induced expression and production of various angiogenic growth factors. We demonstrate that TLR ligands (specifically TLR2, -3, and -5 ligands) induce significantly increased expression/production of vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (Ang-1) in the peripheral blood mononuclear cells of individuals with lymphatic pathology (CP individuals) compared to that in cells of asymptomatic infected (INF) individuals. Similarly, filarial antigens induce significantly enhanced production of VEGF-C in CP compared with INF individuals. TLR2-mediated enhancement of angiogenic growth factor production in CP individuals was shown to be dependent on mitogen-activated protein kinase (MAPK) and NF-κB signaling, as pharmacologic inhibition of either extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, or NF-κB signaling resulted in significantly diminished production of VEGF-A and Ang-1. Our data therefore strongly suggest an important association between TLR signaling and lymphangiogenesis in the development of pathology in human lymphatic filariasis