COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals.

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

Two-dimensional type-II Dirac fermions in layered oxides.

Relativistic massless Dirac fermions can be probed with high-energy physics experiments, but appear also as low-energy quasi-particle excitations in electronic band structures. In condensed matter systems, their massless nature can be protected by crystal symmetries. Classification of such symmetry-protected relativistic band degeneracies has been fruitful, although many of the predicted quasi-particles still await their experimental discovery. Here we reveal, using angle-resolved photoemission spectroscopy, the existence of two-dimensional type-II Dirac fermions in the high-temperature superconductor La1.77Sr0.23CuO4. The Dirac point, constituting the crossing of [Formula: see text] and [Formula: see text] bands, is found approximately one electronvolt below the Fermi level (EF) and is protected by mirror symmetry. If spin-orbit coupling is considered, the Dirac point degeneracy is lifted and the bands acquire a topologically non-trivial character. In certain nickelate systems, band structure calculations suggest that the same type-II Dirac fermions can be realised near EF.

Direct observation of orbital hybridisation in a cuprate superconductor.

The minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper-oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital ([Formula: see text] and [Formula: see text]) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.

A trans-Atlantic examination of haddock Melanogrammus aeglefinus food habits.

The food habits of Melanogrammus aeglefinus were explored and contrasted across multiple north-eastern and north-western Atlantic Ocean ecosystems, using databases that span multiple decades. The results show that among all ecosystems, echinoderms are a consistent part of M. aeglefinus diet, but patterns emerge regarding where and when M. aeglefinus primarily eat fishes v. echinoderms. Melanogrammus aeglefinus does not regularly exhibit the increase in piscivory with ontogeny that other gadoids often show, and in several ecosystems there is a lower occurrence of piscivory. There is an apparent inverse relationship between the consumption of fishes and echinoderms in M. aeglefinus over time, where certain years show high levels of one prey item and low levels of the other. This apparent binary choice can be viewed as part of a gradient of prey options, contingent upon a suite of factors external to M. aeglefinus dynamics. The energetic consequences of this prey choice are discussed, noting that in some instances it may not be a choice at all.

Lunar atmosphere. How surface composition and meteoroid impacts mediate sodium and potassium in the lunar exosphere.

Despite being trace constituents of the lunar exosphere, sodium and potassium are the most readily observed species due to their bright line emission. Measurements of these species by the Ultraviolet and Visible Spectrometer (UVS) on the Lunar Atmosphere and Dust Environment Explorer (LADEE) have revealed unambiguous temporal and spatial variations indicative of a strong role for meteoroid bombardment and surface composition in determining the composition and local time dependence of the Moon's exosphere. Observations show distinct lunar day (monthly) cycles for both species as well as an annual cycle for sodium. The first continuous measurements for potassium show a more repeatable variation across lunations and an enhancement over KREEP (Potassium Rare Earth Elements and Phosphorus) surface regions, revealing a strong dependence on surface composition.

A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.

BACKGROUND: Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry. RESULTS: Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P < 0.001) with a concomitant increase in the proportion of CD27+ memory B cells (P < 0.001) and activated CD86+CD27+ memory B cells (P < 0.001), as an immunopharmacodynamic marker of CD40 activation. CONCLUSIONS: CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY NUMBER: ACTRN12609000294257.

Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels.

BACKGROUND: Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations. OBJECTIVE: To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect. METHODS: Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values. RESULTS: The therapeutic range was 27-411 ng mL(-1) . The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. CONCLUSIONS: The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327).

Tc99m-hepatobiliary iminodiacetic acid (HIDA) scintigraphy in clinical practice.

There have been evolutionary changes in the management of pathological conditions of the hepatobiliary system over recent years, particularly with an increasing emphasis on modern hepatobiliary surgical techniques. Concurrent advances have occurred in imaging technology and availability, leading to a greater use of ultrasound, multidetector computed tomography (CT), and magnetic resonance imaging (MRI) in the primary evaluation of hepatobiliary disease. Radionuclide imaging using technetium(99m) (Tc(99m)) hepatobiliary iminodiacetic acid (HIDA) derivatives is an established technique that complements morphological imaging, providing valuable functional information in both pre- and postoperative evaluation of patients with suspected or known hepatobiliary disease. This review discusses the current clinical indications for Tc(99m) HIDA scintigraphy using clinical cases to demonstrate how this technique continues to play a valuable diagnostic role in the assessment of the functional integrity of the hepatobiliary system.

You are what you eat, whenever or wherever you eat it: an integrative analysis of fish food habits in Canadian and U.S.A. waters.

The degree to which fish diet differs by season and area, particularly over broad scales, was examined for the first time in temperate, contiguous north-west Atlantic Ocean waters by comparing food habit data for 10 species of fishes collected concurrently during the spring and autumn surveys in the U.S.A. (Gulf of Maine proper and Georges Bank) and in the summer survey in Canada (western Scotian Shelf and Bay of Fundy). For most species, there was a general concurrence among the three seasons and four areas: summer diets had the same dominant prey items as spring and autumn diets. Although a suite of multivariate analyses did elucidate some differences in specific proportions of the diet for these species across seasons and areas, the main prey did not substantially change for most of these species. These results suggest that there are (1) minimal differences in diet across season for these species at these taxonomic resolutions, (2) there are minimal differences in diet geographically for these species and (3) differences across species, as expected, are important. Many fisheries ecosystem and multispecies models are dependent on food habit data, where resolving seasonal and spatial differences in diet remains an important consideration; however, the present work implies that amalgamated estimates of diet from seasonal surveys may be a reasonable approach when no finer seasonal resolution exists, as long as due diligence is exercised.

Observation of narrow-band terahertz coherent Cherenkov radiation from a cylindrical dielectric-lined waveguide.

We report experimental observation of narrow-band coherent Cherenkov radiation driven by a subpicosecond electron bunch traveling along the axis of a hollow cylindrical dielectric-lined waveguide. For an appropriate choice of dielectric wall thickness, a short-pulse beam current profile excites only the fundamental mode of the structure, producing energetic pulses in the terahertz range. We present detailed measurements showing a narrow emission spectrum peaked at 367 + or - 3 GHz from a 1 cm long fused silica capillary tube with submillimeter transverse dimensions, closely matching predictions. We demonstrate a 100 GHz shift in the emitted central frequency when the tube wall thickness is changed by 50 microm. Calibrated measurements of the radiated energy indicate up to 10 microJ per 60 ps pulse for an incident beam charge of 200 pC, corresponding to a peak power of approximately 150 kW.

Breakdown limits on Gigavolt-per-meter electron-beam-driven wakefields in dielectric structures.

First measurements of the breakdown threshold in a dielectric subjected to GV/m wakefields produced by short (30-330 fs), 28.5 GeV electron bunches have been made. Fused silica tubes of 100 microm inner diameter were exposed to a range of bunch lengths, allowing surface dielectric fields up to 27 GV/m to be generated. The onset of breakdown, detected through light emission from the tube ends, is observed to occur when the peak electric field at the dielectric surface reaches 13.8+/-0.7 GV/m. The correlation of structure damage to beam-induced breakdown is established using an array of postexposure inspection techniques.

Therapeutic frontiers: preventing and treating infectious diseases by inhibiting bacterial quorum sensing.

Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.

Castellaniella gen. nov., to accommodate the phylogenetic lineage of Alcaligenes defragrans, and proposal of Castellaniella defragrans gen. nov., comb. nov. and Castellaniella denitrificans sp. nov.

Comparative 16S rRNA gene sequence analysis indicates that two distinct sublineages exist within the genus Alcaligenes: the Alcaligenes faecalis lineage, comprising Alcaligenes aquatilis and A. faecalis (with the three subspecies A. faecalis subsp. faecalis, A. faecalis subsp. parafaecalis and A. faecalis subsp. phenolicus), and the Alcaligenes defragrans lineage, comprising A. defragrans. This phylogenetic discrimination is supported by phenotypic and chemotaxonomic differences. It is proposed that the A. defragrans lineage constitutes a distinct genus, for which the name Castellaniella gen. nov. is proposed. The type strain for Castellaniella defragrans gen. nov., comb. nov. is 54PinT (=CCUG 39790T = CIP 105602T = DSM 12141T). Finally, on the basis of data from the literature and new DNA-DNA hybridization and phenotypic data, the novel species Castellaniella denitrificans sp. nov. (type strain NKNTAUT = DSM 11046T = CCUG 39541T) is proposed for two strains previously identified as strains of A. defragrans.

Effects of ion motion in intense beam-driven plasma wakefield accelerators.

Recent proposals for using plasma wakefield accelerators (PWFA) as a component of a linear collider have included intense electron beams with densities many times in excess of the plasma density. The beam's electric fields expel the plasma electrons from the beam path to many beam radii in this regime. We analyze here the motion of plasma ions under the beam fields, and find for a proposed PWFA collider scenario that the ions completely collapse inside of the beam. Simulations of ion collapse are presented. Implications of ion motion on the feasibility of the PWFA-based colliders are discussed.

Parvibaculum lavamentivorans converts linear alkylbenzenesulphonate surfactant to sulphophenylcarboxylates, alpha,beta-unsaturated sulphophenylcarboxylates and sulphophenyldicarboxylates, which are degraded in communities.

AIMS: The aims were to test whether Parvibaculum lavamentivoransT degraded commercial linear alkylbenzenesulphonate (LAS) surfactant via omega-oxygenation and beta-oxidation to sulphophenylcarboxylates (SPCs), whether the organism was widespread and reisolable, and whether the degradative community used the 4-sulphocatechol 1,2-dioxygenase to cleave the aromatic ring from LAS. METHODS AND RESULTS: Heterotrophic P. lavamentivoransT converted LAS (side chain length C10-C13) to SPCs (C4-C13), alpha,beta-unsaturated SPCs (C4-C13) and sulphophenyldicarboxylates (SPdCs) (at least C8-C12). Identifications came from high performance liquid chromatography (HPLC) separation, an electrospray interface and mass spectrometry. No evidence for other paths was found. The degradation of LAS in trickling filters inoculated with environmental samples always showed transient SPC intermediates (HPLC) and the presence of the P. lavamentivorans morphotype in the community. One new isolate was obtained. A community able to mineralize LAS contained 4-sulphocatechol-1,2-dioxygenase at high specific activity. CONCLUSIONS: Parvibaculum lavamentivoransT degrades commercial LAS via omega-oxygenation, oxidation and chain shortening through beta-oxidation to yield a wide range of SPCs. The latter are degraded in bacterial communities which contain organisms like P. lavamentivorans, and which utilize sulphocatechol dioxygenase for ring cleavage. SIGNIFICANCE AND IMPACT OF THE STUDY: There is one widespread pathway to degrade LAS. Any traces of LAS and larger amounts of SPCs in the effluent from sewage works are exposed to degradative organisms in acclimated and pristine environments. These degradative reactions can now be studied in pure cultures.

The prevalence of avascular necrosis in patients treated with chemotherapy for testicular tumours.

To study the prevalence of avascular necrosis in patients receiving chemotherapy for testicular cancer we invited 103 consecutive patients treated by chemotherapy to attend for MRI scan of the hips. Four of 47 (9% (CI 2-20%)) patients scanned and 4/103 (3.8% (CI 1-10%)) of patients invited to participate in the study had evidence of avascular necrosis. As not all patients in the study had completed the at risk period this equates to a 3-year actuarial risk of 6.3% (95% confidence limits (CI) 2.4-16.1). These data suggest that avascular necrosis is an uncommon but significant complication of chemotherapy including steroids as anti-emetics.

Efficiency of searching the grey literature in palliative care.

A systematic review into palliative care team effectiveness was undertaken which has, inherent in its methodology, grey literature searching. Over 100 letters were written to a systematically chosen range of service providers, commissioners, and experts in combination with requests for information in six UK national cancer/palliative care organization newsletters. In addition, the System for Information on Grey Literature (SIGLE ) database was searched. As a result, 25 document hard copies were received. The documents were, in all but one case (this one study was also highlighted by the SIGLE search), not relevant as they were predominated by annual reports, service descriptions, and needs assessments. In terms of obtaining unpublished studies for possible inclusion in the review, this comprehensive search was unsuccessful and, therefore, it would appear that grey literature searching is not a useful tool in palliative care systematic reviews.