The early impact of the UK's new alcohol taxation system on product strength and price: an exploratory comparative descriptive study.

OBJECTIVES: We explored the early impact of changes to the UK alcohol tax system, implemented in August 2023, on the strength and price of alcoholic products available for sale on the website of the largest supermarket in England. STUDY DESIGN: Our comparative descriptive study using longitudinal brand-level data was not preregistered and should be considered exploratory. METHODS: Data were collected weekly (May to October 2023) using automated web scraping tools. Outcomes were product strength (% alcohol by volume [ABV]) and price (per 10 mL of pure alcohol and per litre of product). We undertook paired t-tests, two-sample Kolmogorov-Smirnov tests, and quantile regression to compare outcomes before and after the tax changes. Beer, cider, spirits, and ready-to-drinks (RTDs) were analysed separately. RESULTS: There was a reduction in the mean strength of beer, driven by manufacturers reformulating a small number of weaker beers, moving them into a lower tax band (<3.5%ABV). The mean price per 10 mL of alcohol and per litre of product was significantly higher after the new tax system for beer, cider, and spirits and significantly lower for RTDs. Increases in the price of beer tended to occur across the entire distribution, whereas increases in the price of cider occurred among more expensive products. CONCLUSIONS: Changes to product strength tended to occur among weaker products near the new lowest tax band, suggesting tax bands may be a potential stimulus for change. Reformulation of stronger products would have better public health potential. Longer term monitoring, including data on purchasing/consumption, is required.

The independent and joint risks of alcohol consumption, smoking, and excess weight on morbidity and mortality: a systematic review and meta-analysis exploring synergistic associations.

OBJECTIVE: Alcohol consumption, smoking, and excess weight independently increase the risk of morbidity/mortality. Less is known about how they interact. This research aims to quantify the independent and joint associations of these exposures across health outcomes and identify whether these associations are synergistic. STUDY DESIGN: The protocol for this systematic review and meta-analysis was pre-registered (PROSPERO CRD42021231443). METHODS: Medline and Embase were searched between 1 January 2010 and 9 February 2022. Eligible peer-reviewed observational studies had to include adult participants from Organisation for Co-Operation and Development countries and report independent and joint associations between at least two eligible exposures (alcohol, smoking, and excess weight) and an ICD-10 outcome (or equivalent). For all estimates, we calculated the synergy index (SI) to identify whether joint associations were synergistic. Meta-analyses were conducted for outcomes with sufficiently homogenous data. RESULTS: The search returned 26,290 studies, of which 98 were included. Based on 138,130 participants, the combined effect (SI) of alcohol and smoking on head and neck cancer death/disease was 3.78 times greater than the additive effect of each exposure (95% confidence interval [CI] = 2.61, 5.48). Based on 2,603,939 participants, the combined effect of alcohol and excess weight on liver disease/death was 1.55 times greater than the additive effect of each exposure (95% CI = 1.33, 1.82). CONCLUSION: Synergistic associations suggest the true population-level risk may be underestimated. In the absence of bias, individuals with multiple risks would experience a greater absolute risk reduction from an intervention that targets a single exposure than individuals with a single risk.

High dietary fat and the development of osteoarthritis in a rabbit model.

OBJECTIVE: Osteoarthritis (OA) is associated with obesity, although this relationship remains unclear. Proposed etiologies of OA in obesity include mechanical loading of malaligned joints and possible toxicity of dietary fat. The hypothesis tested in the present study was that increased dietary fat worsens OA in both malaligned and normal joints, detected by biochemical and histological cartilage markers. METHOD: 83 New Zealand white rabbits were divided among two conditions related to OA: bowing of the knee and a 14%kcal vs 47.8%kcal fat diet. Rabbit weights and knee angles were compared throughout the experiment. At 28 and 38 weeks, intra-articular forces were measured, animals sacrificed, and knee cartilage examined for histological changes, glycosaminoglycan content, 35S uptake, and aggrecanase-1 expression. RESULTS: There were no differences in animal weights or intra-articular forces between the two diets. Despite increased fat content in their diet, animals on the 47.8%kcal fat diet did not gain excess weight. Representative histology showed atypical shearing of articular cartilage among animals on the high fat diet. Animals on the 47.8%kcal fat diet had suppression of protein synthesis compared to the 14%kcal fat diet: lower glycosaminoglycan content and aggrecanase-1 expression in all knee compartments at both times, and lower 35S uptake at 38 weeks. CONCLUSION: These results suggest dietary fat, independent of animal weight, results in altered chondrocyte function. Increased dietary fat was associated with changes in rabbit cartilage in vivo and appears to be a risk factor for the development of OA.

Intra-operative recurrent laryngeal nerve stimulation during anterior cervical discectomy: a simple and effective technique.

Recurrent laryngeal nerve (RLN) palsy is a recognised complication of anterior cervical discectomy (ACD) surgery. We report our experience of intra-operative neuromonitoring using RLN stimulation in 19 patients undergoing ACD surgery. This simple and safe technique has the potential to reduce the incidence of RLN palsy in this patient group.

Native Escherichia coli OmpF porin surfaces probed by atomic force microscopy.

Topographs of two-dimensional porin OmpF crystals reconstituted in the presence of lipids were recorded in solution by atomic force microscopy (AFM) to a lateral resolution of 10 angstroms and a vertical resolution of 1 angstrom. Protein-protein interactions were demonstrated on the basis of the AFM results and earlier crystallographic findings. To assess protein-lipid interactions, the bilayer was modeled with kinked lipids by fitting the head groups to contours determined with AFM. Finally, two conformations of the extracellular porin surface were detected at forces of 0.1 nanonewton, demonstrating the potential of AFM to monitor conformational changes with high resolution.

Effect of pre-operative expectations on the outcomes following total shoulder arthroplasty.

AIMS: Few studies have evaluated the relationship between patients' pre-operative expectations and the outcome of orthopaedic procedures. Our aim was to determine the effect of expectations on the outcome after primary anatomical total shoulder arthroplasty (TSA). We hypothesised that patients with greater expectations would have better outcomes. PATIENTS AND METHODS: Patients undergoing primary anatomical TSA completed the Hospital for Special Surgery's Shoulder Expectations Survey pre-operatively. The American Shoulder and Elbow Surgeons (ASES), Shoulder Activity Scale (SAS), Short-Form-36 (SF-36), and visual analogue scale (VAS) for pain, fatigue, and general health scores were also collected pre-operatively and two years post-operatively. Pearson correlations were used to assess the relationship between the number of expectations and the outcomes. Differences in outcomes between those with higher and lower levels of expectations for each expectation were assessed by independent samples t-test. Multivariable linear regression analysis was used to control for potential confounding factors. RESULTS: A total of 67 patients were evaluated two years post-operatively. Most parameters of outcome improved significantly from baseline and most patients were satisfied. A greater number of expectations was associated with a significantly greater improvement in the ASES score (p = 0.02). In the multivariable analysis, a greater number of expectations was an independent predictor of better ASES, VAS and SF-36 scores, as well as improvements in ASES and VAS pain scores (p < 0.05). Greater expectations for many specific expectation questions were significantly associated with better outcomes (p < 0.05). CONCLUSION: TSA is a successful procedure with significant improvements in outcome, and greater pre-operative expectations are associated with better outcomes. Cite this article: Bone Joint J 2017;99-B:1190-6.

Towards the molecular architecture of the asymmetric unit membrane of the mammalian urinary bladder epithelium: a closed "twisted ribbon" structure.

The asymmetric unit membrane (AUM) forms numerous plaques covering the apical surface of mammalian urinary bladder epithelium. These plaques contain four major integral membrane proteins called uroplakins Ia, Ib, II and III, which form particles arranged in a well-ordered hexagonal lattice with p6 symmetry and a lattice constant of 16.5 nm. Bovine AUM plaques negatively stained with anionic sodium silicotungstate revealed structural detail to 3.1 nm resolution. Correlation averaging resolved each particle into 12 stain-excluding domains arranged in two concentric rings (inner ring radius (rm) = 3.7 nm, outer ring radius (rout) = 6.6 nm), each with six domains which were rotated by roughly 30 degrees relative to each other. Negative staining with cationic uranyl formate increased the resolution to 2.2 nm and unveiled distinct connections between adjacent AUM particles. These connections may provide a molecular basis for the observed insolubility of the plaques in many detergents. Examination of the luminal face of freeze-dried/unidirectionally metal-shadowed AUM plaques established a left-handed vorticity of the 16 nm protein particles, whereas the cytoplasmic face exhibited no significant surface corrugations. Three-dimensional reconstruction from sodium silicotungstate-stained specimens revealed the AUM particles to be built of six "V-shaped" subunits anchored upright in the membrane. The mass density distribution within uranyl formate-stained AUM particles was similar except that the inner tip of each V was bridged to the outer tip of an adjacent V, so that the 16 nm AUM particle appeared as a continuous, "twisted ribbon" embracing a central cavity. Finally, mass measurements of unstained/freeze-dried plaques by scanning transmission electron microscopy yielded a total mass of 1,120 kDa per membrane-bound AUM particle. By imposing constraints on the possible uroplakin stoichiometries within AUM plaques, these data provide a first glimpse of the molecular architecture of the 16 nm particles constituting the plaques.

Towards atomic interpretation of F-actin filament three-dimensional reconstructions.

We have recorded dark field images of negatively stained F-actin filaments polymerized with 2 mM MgCl2 and 50 mM KCl with a scanning transmission electron microscope and computed 3-D reconstructions using a helical parameter search to optimize simultaneously the helical repeat length, the radial position of the filament axis, and the helical selection rule. The resulting optimized averaged filament 3-D reconstruction at 2.5 nm resolution is remarkably similar to an atomic model of the F-actin filament. By comparison, several structural features of the reconstruction can be interpreted at the level of distinct secondary structure elements, and predictions made by the atomic model could be verified: for instance, the density connecting the two long-pitch helical strands in our reconstruction co-localizes with an extended beta-hairpin, the "hydrophobic loop" (i.e. residues 262 to 274), which according to the atomic model establishes the major intersubunit contact between the two long-pitch helical strands. The most pronounced structural variations among individual filament 3-D reconstructions were observed in (1) the details of the intersubunit contact pattern between the two long-pitch helical strands, and (2) the exact size and shape of subdomain 2 of the F-actin molecule, which appears rather flexible and easily deformed. In addition, we found that all phenotypes of F-actin filament 3-D reconstructions that arise from small deviations from the optimal helical parameters or from lowering the nominal resolution exhibited stronger intersubunit contacts between than along the two long-pitch helical strands, a structural feature that has been emphasized for a number of F-actin filament 3-D reconstructions in the past. Since this is clearly at variance with the relative strength of the intersubunit contacts as predicted by the atomic model, it may represent an artifactual structural feature arising from low-resolution data or suboptimal helical data processing, and should therefore be interpreted with caution in terms of indicating chemical, mechanical or conformational states of the F-actin filament.

Stimulatory and inhibitory effects of ethanol on hippocampal acetylcholine release.

Using the microdialysis technique and sensitive HPLC procedures for the determination of acetylcholine (ACh) and ethanol, we investigated the release of ACh in rat hippocampus after acute ethanol administration. Systemic administration of ethanol (0.8 and 2.4 g/kg i.p.) led to peak ethanol concentrations of 21 and 42 mM in the hippocampus, respectively. The high dose caused a long-lasting inhibition of basal ACh release by up to 33%. Local infusion of scopolamine (1 microM) enhanced hippocampal ACh release up to eightfold in the presence of neostigmine (10 microM), and this stimulated release was also inhibited after systemic ethanol administration (by up to 45%). The low dose of ethanol (0.8 g/kg) led to a delayed stimulation of hippocampal ACh release. A stimulatory effect on ACh release was also observed when ethanol (50-100 mM) was infused directly into the hippocampus or into the septal area, i.e. to the origin of the cholinergic septohippocampal pathway; thus, the stimulatory effect may be mediated by a direct effect on cholinergic fibres. We conclude that ethanol exerts dual modulatory effects on the activity of the septohippocampal cholinergic fibres, depending on the dose and the site of administration. It is suggested that the inhibition of hippocampal ACh release by intoxicating doses of ethanol may contribute to the well-known cognitive and amnesic effects of ethanol intake.

Has negative staining still a place in biomacromolecular electron microscopy?

Transmission electron microscopy of proteins has provided molecular- and in a few cases near-atomic-resolution structural information. In this review, we critically evaluate the potential and the limitations in obtaining molecular resolution, particularly with negatively stained specimens, and put these into perspective with cryomicroscopy of unstained frozen-hydrated and sugar-embedded preparations.

Interactive realtime Doppler-ultrasound visualization of the heart.

Heart valve insufficiencies can optimally be assessed using transesophageal, triggered, three-dimensional ultrasound imaging. The dynamic ultrasound data contain morphological as well as functional components which are recorded and displayed simultaneously. It allows the visualization of intracardiac motion which is an important parameter to detect abnormal flow caused by defect valves. A realtime reconstruction is desired to get a spatial impression on the one hand and to interactively clip parts of the volume on the other hand. Therefore, we use the OpenGL Volumizer API. Scalability of the visualization was tested with respect to different workstations and graphics resources using a Multipipe Utility library. The combination of both APIs enables a visualization of volumetric and functional data with frame rates up to 10 frames per second. By using the proposed method, it is possible to visualize the jet in the original color-coding which is employed during a conventional two-dimensional examination for displaying the velocity values. The morphological and the functional data are handled as two independent data channels. A good scalability from low cost up to high end graphic workstations is given by the use of the MPU. The quality of the resulting 3D images allows exact differentiation of heart valve insufficiencies to support the diagnostic procedure.

Self-expanding nitinol renal artery stents: comparison of safety and efficacy of bare versus Polyzene-F nanocoated stents in a porcine model.

OBJECTIVE: To investigate the safety and efficacy of a Polyzene-F nanocoat on new low-profile self-expandable nitinol stents in minipig renal arteries. MATERIALS AND METHODS: Ten bare nitinol stents (BNS) and 10 stents coated with a 50 nm-thin Polyzene-F coating were randomly implanted into renal arteries of 10 minipigs (4- and 12-week follow-up, 5 animals/group). Thrombogenicity, on-stent surface endothelialization, vessel wall injury, late in-stent stenosis, and peristrut vessel wall inflammation were determined by quantitative angiography and postmortem histomorphometry. RESULTS: In 6 of 10 BNS, >50% stenosis was found, but no stenosis was found in stents with a nanothin Polyzene-F coating. Histomorphometry showed a statistically significant (p < 0.05) different average maximum luminal loss of 55.16% ± 8.43% at 12 weeks in BNS versus 39.77% ± 7.41% in stents with a nanothin Polyzene-F coating. Stents with a nanothin Polyzene-F coating had a significantly (p < 0.05) lower inflammation score after 12 weeks, 1.31 ± 1.17 versus 2.17 ± 0.85 in BNS. The results for vessel wall injury (0.6 ± 0.58 for Polyzene-F-coated stents; 0.72 ± 0.98 for BNS) and re-endothelialization, (1.16 ± 0.43 and 1.23 ± 0.54, respectively) were not statistically significant at 12-week follow-up. No thrombus deposition was observed on the stents at either follow-up time point. CONCLUSION: Nitinol stents with a nanothin Polyzene-F coating successfully decreased in-stent stenosis and vessel wall inflammation compared with BNS. Endothelialization and vessel wall injury were found to be equal. These studies warrant long-term pig studies (≥120 days) because 12 weeks may not be sufficient time for complete healing; thereafter, human studies may be warranted.

Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part I: kidney.

PURPOSE: Using a pig model: (1) to evaluate the vascular distribution pattern, including the homogeneity and completeness of the intra-arterial microsphere distribution, of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in acute whole-kidney embolization; (2) to evaluate the durability and biocompatibility of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in chronic partial kidney embolization. METHODS: Twenty-two animals were divided into four groups: group 1 (n = 4) underwent total arterial renal occlusion with immediate euthanasia. Groups 2-4 had chronic superselective and partial renal embolization with increasing follow-up times: group 2 (n = 2), 1 week; group 3 (n = 7), 4 weeks; and group 4 (n = 9), 14 weeks. Key endpoints in group 1 were homogeneity and completeness of acute embolizations. In groups 2-4 the key endpoints were durability of embolization and particle-related inflammation in chronic partial embolizations as assessed by quantitative angiography or histomorphometry. A numerical angiographic occlusion score (0.0 to 4.0, where 3.0 is optimal) was developed to assess and quantify the angiographic durability of superselective embolizations (groups 2-4). RESULTS: In group 1, a relatively homogeneous distribution of the particles from segmental arteries to the precapillary level was shown by histomorphometry. Some particles reached the glomerular vas afferens (10 microm diameter). In groups 2-4, a mild recanalization appeared during follow-up. The immediate average postembolization occlusion score of 3.18 +/- 0.73 was reduced to 1.44 +/- 0.73 (statistically significant). Microscopy revealed subtotal necrosis but no foreign body granuloma formation. The intra-arterial appearance of giant cells closely attaching to the surface of the embolic spheres inside the vessel lumen was noted. Vessel walls showed major ischemic reactions. CONCLUSION: Microspheres 40-120 microm in diameter might achieve total occlusion of the arterial kidney vasculature when injected centrally as a result of their fairly homogeneous distribution. Segmental renal infarction occurs after chronic partial embolization despite recanalizations during follow-up. Only mild specific intra-arterial foreign body reactions were found.

Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part II: liver.

PURPOSE: To evaluate trisacryl-gelatin microspheres (40-120 microm) for acute and chronic tissue embolization in mini-pig livers. METHODS: Thirteen animals were divided into four groups: group 1 (n = 3), total arterial bed occlusion with acute procedure; groups 2 to 4, chronic superselective embolization with follow-up of 1 week (group 2, n = 1), 4 weeks (group 3, n = 4) or 14 weeks (group 4, n = 5). Key endpoints were homogeneity and particle distribution in acute embolizations (group 1) and necrosis and inflammation in chronic embolizations (groups 2-4) as assessed microscopically and angiographically. RESULTS: After liver embolization, parenchymal necrosis did not occur; only signs of vessel wall disintegration were evident. The bile ducts remained intact. A distinct foreign body reaction with sparse leukocytic infiltration and giant cells was found at 14 weeks, but no signs of major inflammation were found. Particles were seen at the presinusoidal level, but no particle transportation into the sinusoids was observed. CONCLUSIONS: Embolization in mini-pig livers, using small trisacryl-gelatin microspheres, results in vessel fibrosis without parenchymal or bile duct necrosis. The most likely explanation for preservation of the parenchyma is portal inflow. Small trisacryl-gelatin microspheres may be ideal as an adjunct for chemoembolization.

[Status of postoperative pain therapy in West Germany. Results of a representative survey]. / Zur Lage der postoperativen Schmerztherapie in der Bundesrepublik Deutschland. Ergebnisse einer Repräsentativumfrage.

To determine how pain is assessed and managed in the early postoperative period, what the prescribing habits and general opinions on postoperative pain are, and what suggestions for future improvement could be made, questionnaires were sent to 430 anesthesia departments in the FRG. Of these, 188 were returned (38% response). Systemic treatment (opiates, major and minor tranquilizers, peripherally acting analgesics and spasmolytics) was preferred in most cases, although regional anesthesia/analgesia seems to be rather popular. Data are given not only for analgesic techniques, but also for the most frequently used drugs. The study highlighted deficiencies in communication between the anesthetic staff and the patients that resulted in poor assessment of acute pain problems. The findings indicate a need to document pain and pain relief more often and more precisely in order to improve postoperative pain control.

Pure-tone increment detection in harmonic and inharmonic backgrounds.

The present study investigated the effect of increasing the number and frequency range of background components upon the detection of an increment to the intensity of the center component. Previous studies [e.g., Green et al., J. Acoust. Soc. Am. 75, 1163-1167 (1984)] have demonstrated that, for background stimuli consisting of logarithmically spaced pure-tone components, as the number of background components is increased, the threshold for detection of an increment to the center component is decreased. The present study investigated this effect using harmonically spaced, as well as logarithmically spaced, backgrounds, because many natural sounds, including voiced speech sounds, consist of harmonically spaced components. Two conditions were employed for both types of backgrounds, fixed-level and roving-level within a trial. Group results revealed a small decrease in threshold with increasing number of components only for the fixed-level, logarithmically spaced backgrounds. No decrease in threshold was observed for the other three conditions, including the roving-level, logarithmically spaced backgrounds which were the same as those used by Green et al. (1984). The present results suggest that the decrease in signal threshold with increasing number of background components exists only under limited conditions and that it is a highly individual phenomenon. The present results also suggest that the effect does not occur for harmonically spaced complexes such as most natural sounds including voiced speech.

The relation between vowel recognition and measures of frequency resolution.

The purpose of this study was to employ measures of frequency resolution obtained from individual subjects to predict each subject's vowel recognition performance. Input filter patterns at six test frequencies were obtained from normal-hearing and hearing-impaired subjects. These patterns were used to correlate frequency resolution with vowel recognition in those same subjects. Vowels were presented at levels at which the entire spectrum was fully audible to each subject. Using each subject's measured filter characteristics (and interpolated values for intermediate frequencies), an "internal spectrum" of each vowel was calculated by determining the outputs of all filter channels for the vowel as the input signal. It was speculated that the more similar two internal spectra for a subject were, the more often they would be confused in the vowel recognition task. This expectation received some support when the measure of similarity was a point-by-point Euclidean distance between the two internal spectra. Stronger support was obtained when the measure of similarity was based upon Klatt's (1982) "weighted slope metric" that emphasizes similarities of spectral peak locations. The present study demonstrates a relation between impairments of frequency resolution and vowel recognition. The described filter-bank model of vowel recognition suggests that measures of frequency resolution along with the acoustic spectra of vowel stimuli may be useful in predicting the recognition of vowels by individuals.

Real-time isocontouring and texture mapping meet new challenges in interactive molecular graphics applications.

A technique to extract solid isosurfaces from three-dimensional electron density data at high speed is presented. The ability to change the contouring threshold in real time renders the method a powerful tool for interactive analysis of proteins and their supramolecular assemblies, in order to compare and combine structural information gathered by different data acquisition methods. Chemical properties can effectively be mapped onto these isosurfaces by the use of texture mapping. The implications of these methods in combination with other visualization techniques are discussed, and a framework for their integration into a general-purpose molecular graphics toolkit is proposed.

Virtual reality modeling language in chemistry.

A new concept in the field of molecular modeling using the information transfer mechanism of the World Wide Web (WWW) is presented. The Virtual Reality Modeling Language (VRML) provides an object-oriented method for the description of molecular models. The structure and capabilities of this new language are introduced. It is shown that the transport of molecular models over the WWW using VRML is a very efficient and powerful method for the exchange of molecular information.

Hybrid scanning transmission electron/scanning tunneling microscope system for the preparation and investigation of biomolecules.

A hybrid scanning transmission electron/scanning tunneling microscope vacuum system is introduced, which allows freeze drying and metal coating of biological samples and their simultaneous observation by scanning transmission electron microscopy and scanning tunnelling microscopy (STM). Different metal coatings and STM tips were analysed to obtain the highest possible resolution for such a system. Bovine liver catalase was used as a test sample and the STM results are compared to a molecular scale model.