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.

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.

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.

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.

Microbial metabolism of sulfur- and phosphorus-containing xenobiotics.

The enzymes involved in the microbial metabolism of many important phosphorus- or sulfur-containing xenobiotics, including organophosphate insecticides and precursors to organosulfate and organosulfonate detergents and dyestuffs have been characterized. In several instances their genes have been cloned and analysed. For phosphonate xenobiotics, the enzyme system responsible for the cleavage of the carbon-phosphorus bond has not yet been observed in vitro, though much is understood on a genetic level about phosphonate degradation. Phosphonate metabolism is regulated as part of the Pho regulon, under phosphate starvation control. For organophosphorothionate pesticides the situation is not so clear, and the mode of regulation appears to depend on whether the compounds are utilized to provide phosphorus, carbon or sulfur for cell growth. The same is true for organosulfonate metabolism, where different (and differently regulated) enzymatic pathways are involved in the utilization of sulfonates as carbon and as sulfur sources, respectively. Observations at the protein level in a number of bacteria suggest that a regulatory system is present which responds to sulfate limitation and controls the synthesis of proteins involved in providing sulfur to the cell and which may reveal analogies between the regulation of phosphorus and sulfur metabolism.

Microbial desulfonation.

Organosulfonates are widespread compounds, be they natural products of low or high molecular weight, or xenobiotics. Many commonly found compounds are subject to desulfonation, even if it is not certain whether all the corresponding enzymes are widely expressed in nature. Sulfonates require transport systems to cross the cell membrane, but few physiological data and no biochemical data on this topic are available, though the sequences of some of the appropriate genes are known. Desulfonative enzymes in aerobic bacteria are generally regulated by induction, if the sulfonate is serving as a carbon and energy source, or by a global network for sulfur scavenging (sulfate-starvation-induced (SSI) stimulon) if the sulfonate is serving as a source of sulfur. It is unclear whether an SSI regulation is found in anaerobes. The anaerobic bacteria examined can express the degradative enzymes constitutively, if the sulfonate is being utilized as a carbon source, but enzyme induction has also been observed. At least three general mechanisms of desulfonation are recognisable or postulated in the aerobic catabolism of sulfonates: (1) activate the carbon neighboring the C-SO3- bond and release of sulfite assisted by a thiamine pyrophosphate cofactor; (2) destabilize the C-SO3- bond by addition of an oxygen atom to the same carbon, usually directly by oxygenation, and loss of the good leaving group, sulfite; (3) an unidentified, formally reductive reaction. Under SSIS control, different variants of mechanism (2) can be seen. Catabolism of sulfonates by anaerobes was discovered recently, and the degradation of taurine involves mechanism (1). When anaerobes assimilate sulfonate sulfur, there is one common, unknown mechanism to desulfonate the inert aromatic compounds and another to desulfonate inert aliphatic compounds; taurine seems to be desulfonated by mechanism (1).

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.

Aeromonas spp as a potential cause of diarrhoea in children.

AIMS: To determine the prevalence of Aeromonas spp in the faeces of children and the association with symptoms of gastroenteritis. METHODS: Faecal specimens (n = 1026) were cultured for Aeromonas spp using three selective media and an enrichment broth at both 30 degrees C and 37 degrees C. The isolation of Aeromonas spp was correlated with symptoms of gastroenteritis, previous antibiotic use, and environmental temperature. RESULTS: Aeromonas spp (n = 28) from 26 (2.5%) patients were recovered. Bile salt, Irgasan, and brilliant green agar was the most efficient selective culture medium. Eleven of the patients had symptoms of gastroenteritis, usually mild diarrhoea of two to three days' duration, in the absence of other recognised enteropathogens. A caviae was a particularly frequent isolate (nine out of 11 cases) in symptomatic individuals. Only one out of seven Aeromonas spp recovered by enrichment culture alone was possibly associated with symptoms of gastroenteritis. There was a close correlation between the environmental temperature and isolation of Aeromonas spp. CONCLUSIONS: Aeromonas spp and particularly A caviae may cause gastroenteritis in children, most often during warmer months of the year. Culture for these potential enteropathogens could be confined to summer and autumn months. Bile salt, Irgasan, and brilliant green selective agar, but not alkaline peptone water enrichment, is an efficient culture medium for recovering possibly clinically important isolates.

Phenotypic methods for speciating clinical Aeromonas isolates.

AIMS: To establish the suitability of currently available phenotypic methods for speciation of clinical Aeromonas isolates in diagnostic microbiology laboratories. METHODS: Using 62 Aeromonas spp, three schemes based on biochemical reactions were compared: a series of conventional tests; a system based on the suicide phenomenon, comprising two tubes in total; and a commercially available test, API 20 NE, augmented with a plate assay for beta haemolysin production. The whole cell and outer membrane protein (OMP) profiles of strains were examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE), according to the results of the above schemes, to determine the intra-species homogeneity. RESULTS: Ninety per cent of strains were identified satisfactorily according to conventional criteria. For these strains, agreement was obtained using the suicide phenomenon and API schemes in 93% and 88% of cases, respectively. The three schemes concurred for 82% of strains. Whole cell protein profiles were unsuitable for comparing strains within a species. However, OMP patterns were similar for 89% of A caviae and 63% of A hydrophila. CONCLUSION: Phenospeciation of clinical Aeromonas isolates by the scheme based on the suicide phenomenon is simple to perform and accurate, and suitable for use in the diagnostic laboratory. OMP profiles are potentially useful for confirming the identity of A caviae and most A hydrophila, but not A sobria.

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.

Squamous cell carcinoma of the thyroid: outcome of treatment in 16 patients.

AIMS AND METHODS: Squamous cell carcinoma of the thyroid is very rare and has a poor prognosis. Treatment and outcome were retrospectively analysed in a consecutive series of 16 patients treated at the Royal Marsden Hospital, with the aim of establishing guidelines for management. RESULTS: Twelve of the 16 patients had locoregional disease only at presentation and four had distant metastases. Eight of the 16 underwent surgery and four were given post-operative radiotherapy. Radiotherapy alone was used in six patients unsuitable for surgery. Median survival was 16 months. There were three long-term survivors; each had localized disease treated with surgery and post-operative radiotherapy. Patients treated with surgery alone all developed local recurrence. Two of six patients treated with radiotherapy alone had a partial response but all subsequently developed progressive local disease. Chemotherapy was used in two patients with no response. CONCLUSIONS: Long-term survival is possible if disease is diagnosed early and is completely resected. Surgery should be followed by radical dose radiotherapy.

Stage IV endometrial carcinoma: a 10 year review of patients.

Stage IV endometrial cancer is uncommon, often occurs in elderly patients and has a poor prognosis, which makes the choice of treatment difficult. 18 patients with stage IV endometrial cancer presenting over a 10 year period, between 1987 and 1997, were reviewed with regard to mode of treatment and response. The mean age was 65 years. Five had disease confined to the pelvis and 13 had extra pelvic disease. 15 of 18 patients had a total abdominal hysterectomy (TAH). One patient received radiotherapy alone and five received post-operative radiotherapy. Overall freedom from pelvic symptoms was achieved in seven of 18 patients. All seven had undergone TAH and two had received post-operative radiotherapy. Progestogens were given to 13 patients. Six received progestogens alone, without radiotherapy or chemotherapy. Of these, two responded, one for 9 months and one with verified lung metastases, who had a complete response, is still alive at 6.5 years. Eight patients received chemotherapy, with single agent cisplatin or carboplatin AUC 6. Three patients responded, one for 4.5 years. The overall median survival was 12 months from diagnosis. Actuarial 5 year survival was 15% (CI 3-36). There was no significant survival difference for, hormone therapy or chemotherapy. Stage IV endometrial cancer has a poor prognosis but durable response can be achieved in some patients.

Audit in action: significant reduction of double-contrast barium enema screening time with no loss of examination quality.

The double-contrast barium enema is an examination of high radiation exposure to the patient. As part of a departmental audit, our own fluoroscopic screening times were being recorded. A study was undertaken to see if a determined effort could reduce the screening time without having a detrimental effect on the quality of the examinations. Methods of screening time reduction were identified and then implemented by two radiologists. In the period before the study the average screening time for radiologists A and B was 2.6 min and 3.2 min, respectively (over 56 examinations). After implementation of the changes, the average screening time for both was 0.9 min (over 50 examinations). This is a statistically significant reduction (p less than 0.01). The examinations were assessed independently by a gastroradiologist. No difference in the quality of the examinations was identified. We conclude that a significant reduction of screening time for the double-contrast barium enema can be achieved without loss of examination quality.

Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

Reproducibility of bone ages when performed by radiology registrars: an audit of Tanner and Whitehouse II versus Greulich and Pyle methods.

This audit analysed the Tanner and Whitehouse II twenty bone (TW2) method of bone age assessment which was used in our department, and compared it with the Greulich and Pyle (GP) method. 50 previous bone ages were independently re-calculated by each of three registrars using both techniques, with the time taken to perform each assessment being recorded. For each method the interobserver variation was analysed in terms of the spread of results. The intraobserver variation in TW2 was determined by comparing the bone age originally reported with that subsequently calculated on the same film by the same registrar. The average spread of results was 0.74 years for TW2 method, and 0.96 years for the GP method and this difference is not statistically significant at the 5% level. The average intraobserver variation to TW2 was 0.33 years, but with 95% confidence limits of -0.87 to +1.53 years. The average time taken was 7.9 min for TW2 and 1.4 min for GP assessments. It was concluded that the GP method gave similar reproducibility and was faster than the TW2 method. Following clinical discussion the routine departmental bone age assessment method was changed from the TW2 to the GP method.

Avascular necrosis in patients treated with BEP chemotherapy for testicular tumours.

Avascular necrosis (AVN) is known to occur after combination chemotherapy for lymphomas and leukaemias that includes high dose corticosteroids, but it has been reported rarely in patients with solid tumours. We describe five recent cases in young men with testicular tumours (three of which were of good prognosis), who had been treated with chemotherapy using dexamethasone as an antiemetic. Dexamethasone is a low cost and effective antiemetic, but it may be responsible for inducing AVN in patients receiving chemotherapy for solid tumours. A prospective survey of the frequency of AVN is justified to quantify the extent of the problem.