Real-time surveillance of severe acute respiratory infections in Scottish hospitals: an electronic register-based approach, 2017-2022.

OBJECTIVES: The COVID-19 pandemic highlighted the importance of routine syndromic surveillance of respiratory infections, specifically new cases of severe acute respiratory infection (SARI). This surveillance often relies on questionnaires carried out by research nurses or transcriptions of doctor's notes, but existing, routinely collected electronic healthcare data sets are increasingly being used for such surveillance. We investigated how patient diagnosis codes, recorded within such data sets, could be used to capture SARI trends in Scotland. STUDY DESIGN: We conducted a retrospective observational study using electronic healthcare data sets between 2017 and 2022. METHODS: Sensitive, specific and timely case definition (CDs) based on patient diagnosis codes contained within national registers in Scotland were proposed to identify SARI cases. Representativeness and sensitivity analyses were performed to assess how well SARI cases captured by each definition matched trends in historic influenza and SARS-CoV-2 data. RESULTS: All CDs accurately captured the peaks seen in laboratory-confirmed positive influenza and SARS-CoV-2 data, although the completeness of patient diagnosis records was discovered to vary widely. The timely CD provided the earliest detection of changes in SARI activity, whilst the sensitive CD provided insight into the burden and severity of SARI infections. CONCLUSIONS: A universal SARI surveillance system has been developed and demonstrated to accurately capture seasonal SARI trends. It can be used as an indicator of emerging secondary care burden of emerging SARI outbreaks. The system further strengthens Scotland's existing strategies for respiratory surveillance, and the methods described here can be applied within any country with suitable electronic patient records.

The upgraded Polaris powder diffractometer at the ISIS neutron source.

This paper describes the design and operation of the Polaris time-of-flight powder neutron diffractometer at the ISIS pulsed spallation neutron source, Rutherford Appleton Laboratory, UK. Following a major upgrade to the diffractometer in 2010-2011, its detector provision now comprises five large ZnS scintillator-based banks, covering an angular range of 6° ≤ 2θ ≤ 168°, with only minimal gaps between each bank. These detectors have a substantially increased solid angle coverage (Ω âˆ¼ 5.67 sr) compared to the previous instrument (Ω âˆ¼ 0.82 sr), resulting in increases in count rate of between 2× and 10×, depending on 2θ angle. The benefits arising from the high count rates achieved are illustrated using selected examples of experiments studying small sample volumes and performing rapid, time-resolved investigations. In addition, the enhanced capabilities of the diffractometer in the areas of in situ studies (which are facilitated by the installation of a novel design of radial collimator around the sample position and by a complementary programme of advanced sample environment developments) and in total scattering studies (to probe the nature of short-range atomic correlations within disordered crystalline solids) are demonstrated.

Chronic unpredictable stress promotes cell-specific plasticity in prefrontal cortex D1 and D2 pyramidal neurons.

Exposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure stress-related alterations in intrinsic excitability and synaptic regulation of mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of 'less intense' stress or 2 or 4 weeks of 'more intense' CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1-or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons (D2-PYR) showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1-and D2-PYR exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that D1-and D2-PYR subpopulations differentially undergo stress-induced intrinsic and synaptic plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.

Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target.

Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.

Continental-scale variation in chloride/bromide ratios of wet deposition.

Chlorine and bromine play crucial roles in atmospheric element cycles and are important environmental tracers in catchment investigations, so understanding their distribution at the Earth's near-surface is imperative for deciphering their behaviour. This study presents the first continental-scale analysis of Cl- and Br- concentrations of wet deposition, based on six and half years of weekly samples collected across North America. A recently developed imputation algorithm was applied to estimate the high proportion of censored Br- values, as well as the other eight analytes, based on the multivariate relationships of nine analytes. The results are consistent with previous studies that have found that the concentrations of these two ions in wet deposition, and the Cl-/Br- ratios of wet deposition decrease with distance inland. Close to the coast, Cl-/Br- ratios of wet deposition are similar to the ratio found in seawater (~288 by mass), rapidly decrease to approximately a third of the seawater ratio at ~200km inland, and then decrease at a much lesser rate to reach mass-ratios of 20 to 10 at ~1500km inland, following a logarithmic regression. The Niagara Falls and the Great Salt Lake are identified as localised sources of atmospheric solutes based on elevated Cl-/Br- ratios of wet deposition at proximal sites. Our observations provide further confidence in the findings presented in previous studies that have shown that Cl-/Br- ratios systematically decrease with increasing distance from the coast, despite the potential confounding impact of other processes, such as weather patterns, chemical behaviour and anthropogenic activity. Our results provide improved estimates of Cl-/Br- ratios of wet deposition source water in the absence of site-specific data.

The new high field photoexcitation muon spectrometer at the ISIS pulsed neutron and muon source.

A high power pulsed laser system has been installed on the high magnetic field muon spectrometer (HiFi) at the International Science Information Service pulsed neutron and muon source, situated at the STFC Rutherford Appleton Laboratory in the UK. The upgrade enables one to perform light-pump muon-probe experiments under a high magnetic field, which opens new applications of muon spin spectroscopy. In this report we give an overview of the principle of the HiFi laser system and describe the newly developed techniques and devices that enable precisely controlled photoexcitation of samples in the muon instrument. A demonstration experiment illustrates the potential of this unique combination of the photoexcited system and avoided level crossing technique.

Cotton-wool-like bioactive glasses for bone regeneration.

Inorganic sol-gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol-gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca(2+) ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5-2µm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material.

Evaluation of imperfections in silica and chalcogenide glass microspheres using focussed ion beam milling and imaging.

Microspheres made from optical glasses such as silica and chalcogenide are used as both passive and active optical elements in micro-optics systems and devices. The homogeneity of the microspheres is crucial to their optical quality and performance in such devices and so it is essential, in optimizing such systems, that techniques with nanometer scale resolution are developed to measure the internal structure and homogeneity of such spheres. In this work an analytical protocol based on focussed ion beam milling, combined with secondary ion and secondary electron imaging, has been developed to study the internal homogeneity of glass microspheres. The results have shown that silica microspheres with diameters of three to five microns, fabricated by a sol-gel method, have internal inhomogeneities and voids that will lead to non-uniform optical properties. The FIB milling and imaging technique developed has been found to be a very useful method of studying such inhomogeneities, which have been proposed, but never previously observed, in glass microspheres. The FIB based technique has also been used on larger chalcogenide glass (Ga(2)S(3):La(2)S(3)) microspheres (diameter of order 70 microns) but no inhomogeneities have been observed at the spatial resolution of a few microns so far achieved for these larger microspheres. This study suggests that the FIB based milling and imaging technique may have potential for quantitative use in the measurement of morphological variations in such systems as well as in the study of aging processes in micron-sized glass spheres.

Multi-analytical study of patination methods on steel substrates: a full insight into surface chemistry and morphology.

Patination of metals has been used for decorative or protective purposes, and several methods aimed to create coloured films on metal surfaces have been developed. This work describes a multi-analytical approach to characterize artificial blue patinas created on mild steel substrates by means of traditional recipes and methods for colouring ancient objects and artefacts. We suggest the combined use of secondary ion mass spectrometry, focused ion beam, X-ray diffraction spectroscopy, white light interferometry and reflectance spectroscopy to characterize blue patinas on steel substrates and to investigate the relationship between the developed colour and the patina layer microstructure and composition. Therefore, the analysis of the oxide films produced by either thermal or chemical colouring methods has been successfully performed, providing information about the film morphology, the surface composition and in-depth elemental distribution within the coloured layers, and the origin of the colour developed on the surface.

Biomineralization of gold: biofilms on bacterioform gold.

Bacterial biofilms are associated with secondary gold grains from two sites in Australia. 16S ribosomal DNA clones of the genus Ralstonia that bear 99% similarity to the bacterium Ralstonia metallidurans-shown to precipitate gold from aqueous gold(III) tetrachloride-were present on all DNA-positive gold grains but were not detected in the surrounding soils. These results provide evidence for the bacterial contribution to the authigenic formation of secondary bacterioform gold grains and nuggets.

Liposomes encapsulating polymeric chitosan based vesicles--a vesicle in vesicle system for drug delivery.

Drug delivery systems comprising vesicles prepared from one amphiphile encapsulating vesicles prepared from a second amphiphile have not been prepared previously due to a tendency of the bilayer components of the different vesicles to mix during preparation. Recently we have developed polymeric vesicles using the new polymer-palmitoyl glycol chitosan and cholesterol in a 2:1 weight ratio. These polymeric vesicles have now been encapsulated within egg phosphatidylcholine (egg PC), cholesterol (2:1 weight ratio) liposomes yielding a vesicle in vesicle system. The vesicle in vesicle system was visualised by freeze fracture electron microscopy. The mixing of the different bilayer components was studied by monitoring the excimer fluorescence of pyrene-labelled polymeric vesicles after their encapsulation within egg PC liposomes or hexadecyl diglycerol ether niosomes. A minimum degree of lipid mixing was observed with the polymeric vesicle-egg PC liposome system when compared to the polymeric vesicle-hexadecyl diglycerol ether niosome system. The polymeric vesicle-egg PC vesicle in vesicle system was shown to retard the release of encapsulated solutes. 28% of 5(6)-carboxyfluorescein (CF) encapsulated in the polymeric vesicle compartment of the vesicle in vesicle system was released after 4 h compared to the release of 62% of encapsulated CF from plain polymeric vesicles within the same time period.

Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers.

OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also obtained four hours after consuming the juice. RESULTS: Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects. CONCLUSION: The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice. SPONSORSHIP: Funded by the Scottish Executive Rural Affairs Department and the Danish Government.

Relationship among antioxidant activity, vasodilation capacity, and phenolic content of red wines.

The relationship among antioxidant activity, based on the electron-spin resonance determination of the reduction of Fremy's radical, vasodilation activity, and phenolic content was investigated in 16 red wines. The wines were selected to provide a range of origins, grape varieties, and vinification methods. Sensitive and selective HPLC methods were used for the analysis of the major phenolics in red wine: free and conjugated myricetin, quercetin, kaempferol, and isorhamnetin; (+)-catechin, (-)-epicatechin, gallic acid, p-coumaric acid, caffeic acid, caftaric acid, trans-resveratrol, cis-resveratrol, and trans-resveratrol glucoside. Total anthocyanins were measured using a colorimetric assay. The total phenolic content of the wines was determined according to the Folin-Ciocalteu colorimetric assay and also by the cumulative measurements obtained by HPLC. The 16 wines exhibited a wide range in the values of all parameters investigated. However, the total phenol contents, measured both by HPLC and colorimetrically, correlated very strongly with the antioxidant activity and vasodilation activity. In addition, the antioxidant activity was associated with gallic acid, total resveratrol, and total catechin. In contrast, only the total anthocyanins were correlated with vasodilation activity. The results demonstrate that the different phenolic profiles of wines can produce varying antioxidant and vasodilatant activities, which opens up the possibility that some red wines may provide enhanced health benefits for the consumer.

Assessment of the antioxidant potential of scotch whiskeys by electron spin resonance spectroscopy: relationship to hydroxyl-containing aromatic components.

Electron spin resonance (ESR) spectroscopy has been used to assess the antioxidant capacity of eight Scotch whiskeys by measuring the extent by which the original spirits, or pyridine solutions of their residues, reduced Fremy's radical or galvinoxyl radical. All whiskeys displayed antioxidant activity greater than that of a 0.2 mM solution of Trolox in the Fremy's assay and of a 0.1 mM solution of quercetin in the galvinoxyl assay. The relative antioxidant capacities determined according to the two assays were highly correlated and strongly related to the total phenol content as determined by using the Folin-Ciocalteu method. Activity was a consequence of maturation in oak casks with the "newmake" spirit showing no effect. Of 10 aromatic constituents analyzed, activity was most strongly correlated with ellagic acid and gallic acid in both assays. The reductive capacities of four major phenolics were determined, which, in summation, accounted for 31-53% of the total antioxidant activity of the whiskeys. There was no evidence for synergistic interaction between the phenols investigated.

Crystallization and preliminary X-ray crystallographic analysis of a vancomycin-N-acetyl-D-Ala-D-Ala complex.

A vancomycin-N-acetyl-D-Ala-D-Ala complex has been crystallized by the sitting-drop vapour-diffusion method using imidazole maleic buffer at pH 7.6. The novel crystals obtained belong to the space group P6322 with unit-cell parameters a = b = 73.43 (1), c = 277.17 (4) A, gamma = 120 degrees. The crystal density was determined as 1. 106 g cm-3 which gives a supercell of 24 molecules (12 dimers) per asymmetric unit for an acceptable Matthews number and an estimated solvent content of 42%. Data were collected at room temperature to 2. 8 A.

Antitumor agents. 190. Absolute stereochemistry of the cytotoxic germacranolides, tomenphantins A and B, from Elephantopus tomentosus.

The structures and absolute stereochemistries of tomenphantins A (1) and B (2), cytotoxic germacranolides isolated from Elephantopus tomentosus, are reported herein. 1H and 13C NMR spectroscopic data, chemical transformation, and single-crystal X-ray analysis were used in these determinations.

Antioxidant efficacy of phytoestrogens in chemical and biological model systems.

Phytoestrogens (PEs) are diphenolic compounds from plants which can bind to estrogen receptors and have estrogen and antiestrogen effects in man and animals. Like other plant phenolics, PEs may have antioxidant properties through hydrogen/electron donation via hydroxyl groups. They might therefore act as free radical scavengers and inhibit development of coronary heart disease and cancers. The hydrogen-donating ability of a range of phytoestrogens was assessed using electron spin resonance spectroscopy, the ferric-reducing ability of plasma assay, and the Trolox equivalent antioxidant capacity. In addition, the ability of compounds to inhibit lipid peroxidation was examined in vitamin E-deficient liver microsomes. Genistein had the highest activity of the isoflavones; however, the isoflavones were relatively poor hydrogen donors compared with the other estrogenic compounds examined. Coumestrol and equol were more effective antioxidants than genistein but had relatively limited activity in comparison with Trolox. The only estrogenic compound with significant antioxidant activity was kaempferol which is better known as a dietary antioxidant than a phytoestrogen. As the concentrations of PEs used in this study exceed the estimated serum concentrations, their relatively poor antioxidant ability in vitro may indicate little significance as antioxidants in vivo.

The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers.

OBJECTIVE: To assess whether consumption of 100 ml of whisky or red wine by healthy male subjects increased plasma total phenol content and antioxidant capacity. DESIGN: A Latin square arrangement to eliminate ordering effects whereby, after an overnight fast, nine volunteers consumed 100 ml of red wine, malt whisky or unmatured 'new make' spirit. Each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained from the anticubital vein at intervals up to 4h after consumption of the beverages when a urine sample was also obtained. RESULTS: Within 30 min of consumption of the wine and whisky, there was a similar and significant increase in plasma total phenol content and antioxidant capacity as determined by the ferric reducing capacity of plasma (FRAP). No changes were observed following consumption of 'new make' spirit. CONCLUSIONS: Consumption of phenolic-containing alcoholic beverages transiently raises total phenol concentration and enhances the antioxidant capacity of plasma. This is compatible with suggestions that moderate alcohol usage and increased antioxidant intake decrease the risk of coronary heart disease.

A reappraisal of the diversity and class distribution of aspartate transcarbamoylases in gram-negative bacteria.

Recently, the subunit composition of class A aspartate transcarbamoylases (ATCases) in fluorescent pseudomonads has been clarified. We present evidence that distribution of this type of ATCase may be more widespread than at first suspected. Bacterial ATCases exist in three forms: class A (molecular mass approximately 450-500 kDA); class B, typified by Escherichia coli ATCase (approximately 300 kDa); and class C, typified by Bacillus subtilis ATCase (approximately 100 kDa). Using gradient gel electrophoresis with activity-staining to scan bacterial sonicates, we report the existence of six more class ATCases. We have purified one of these, Acinetobacter calcoaceticus ATACase, and found its subunit composition to be similar to that of the pseudomonad ATCases. Two of these ATCases come from bacteria outside the gamma-subgroup of the Proteobacteria, one from the alpha-subgroup and one from Deinococcus radiophilus, a species phylogenetically remote from the Proteobacteria. Unexpectedly, three bacterial species, closely related to the fluorescent pseudomonads and acinetobacters, have ATCases of 100 kDa (class C). One of these, Stenotrophomonas (formerly Xanthomonas) maltophilia has been purified and found to be a homotrimer of 35 kDa polypeptide chains. We believe this is the first time that class C ATCases have been reported in Gram-negative bacteria. A distinctive cluster in the gamma-3 subgroup of the Proteobacteria is formed by the enteric bacteria and their relatives. So far only class B ATCases have been reported in this group. The evolutionary implications of these findings are discussed.