British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 1: compensated cirrhosis

\ua9 2023 BMJ Publishing Group. All rights reserved.The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Here, in part one, we focus on outpatient management of compensated cirrhosis, encompassing hepatocellular cancer surveillance, screening for varices and osteoporosis, vaccination and lifestyle measures. We also introduce a compensated cirrhosis care bundle for use in the outpatient setting. Part two concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. The third part of the guidance covers special circumstances encountered in managing people with cirrhosis: surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis

Prodigious submarine landslides during the inception and early growth of volcanic islands

Volcanic island inception applies large stresses as the ocean crust domes in response to magma ascension and is loaded by eruption of lavas. There is currently limited information on when volcanic islands are initiated on the seafloor, and no information regarding the seafloor instabilities island inception may cause. The deep sea Madeira Abyssal Plain contains a 43 million year history of turbidites among which many originate from mass movements in the Canary Islands. Here, we investigate the composition and timing of a distinctive group of turbidites that we suggest represent a new unique record of large-volume submarine landslides triggered during the inception, submarine shield growth, and final subaerial emergence of the Canary Islands. These slides are predominantly multi-stage and yet represent among the largest mass movements on the Earth’s surface up to three or more-times larger than subaerial Canary Islands flank collapses. Thus whilst these deposits provide invaluable information on ocean island geodynamics they also represent a significant, and as yet unaccounted, marine geohazard

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

Selecting CMIP5 GCMs for downscaling over multiple regions

The unprecedented availability of 6-hourly data from a multi-model GCM ensemble in the CMIP5 data archive presents the new opportunity to dynamically downscale multiple GCMs to develop high-resolution climate projections relevant to detailed assessment of climate vulnerability and climate change impacts. This enables the development of high resolution projections derived from the same set of models that are used to characterise the range of future climate changes at the global and large-scale, and as assessed in the IPCC AR5. However, the technical and human resource required to dynamically-downscale the full CMIP5 ensemble are significant and not necessary if the aim is to develop scenarios covering a representative range of future climate conditions relevant to a climate change risk assessment. This paper illustrates a methodology for selecting from the available CMIP5 models in order to identify a set of 8–10 GCMs for use in regional climate change assessments. The selection focuses on their suitability across multiple regions—Southeast Asia, Europe and Africa. The selection (a) avoids the inclusion of the least realistic models for each region and (b) simultaneously captures the maximum possible range of changes in surface temperature and precipitation for three continental-scale regions. We find that, of the CMIP5 GCMs with 6-hourly fields available, three simulate the key regional aspects of climate sufficiently poorly that we consider the projections from those models ‘implausible’ (MIROC-ESM, MIROC-ESM-CHEM, and IPSL-CM5B-LR). From the remaining models, we demonstrate a selection methodology which avoids the poorest models by including them in the set only if their exclusion would significantly reduce the range of projections sampled. The result of this process is a set of models suitable for using to generate downscaled climate change information for a consistent multi-regional assessment of climate change impacts and adaptation

Harmonized gap-filled datasets from 20 urban flux tower sites

A total of 20 urban neighbourhood-scale eddy covariance flux tower datasets are made openly available after being harmonized to create a 50 site-year collection with broad diversity in climate and urban surface characteristics. Variables needed as inputs for land surface models (incoming radiation, temperature, humidity, air pressure, wind and precipitation) are quality controlled, gap-filled and prepended with 10 years of reanalysis-derived local data, enabling an extended spin up to equilibrate models with local climate conditions. For both gap filling and spin up, ERA5 reanalysis meteorological data are bias corrected using tower-based observations, accounting for diurnal, seasonal and local urban effects not modelled in ERA5. The bias correction methods developed perform well compared to methods used in other datasets (e.g. WFDE5 or FLUXNET2015). Other variables (turbulent and upwelling radiation fluxes) are harmonized and quality controlled without gap filling Site description metadata include local land cover fractions (buildings, roads, trees, grass etc.), building height and morphology, aerodynamic roughness estimates, population density and satellite imagery. This open collection can help extend our understanding of urban environmental processes through observational synthesis studies or in the evaluation of land surface environmental models in a wide range of urban settings. These data can be accessed from https://doi.org/10.5281/zenodo.7104984 (Lipson et al., 2022).Peer reviewe

Induction of sustained clinical remission in early axial spondyloarthritis following certolizumab pegol treatment: 48-week outcomes from C-OPTIMISE

INTRODUCTION: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. METHODS: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48). RESULTS: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious. CONCLUSIONS: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified. TRIAL REGISTRATION: NCT02505542

Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders

<p>Abstract</p> <p>Background</p> <p>Few studies exist on the validity of food frequency questionnaires (FFQs) administered to elderly people. The aim of this study was to assess the validity of a short FFQ on present dietary intake, developed specially for the AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the validity of FFQs is essential before they are used in studies on diet-related disease risk and health outcomes.</p> <p>Method</p> <p>128 healthy elderly participants (74 y ± 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day weighed food record. Validity of the AGES-FFQ was assessed by comparing its answers to the dietary data obtained from the weighed food records, using Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra test for trend.</p> <p>Result</p> <p>For men a correlation ≥ 0.4 was found for potatoes, fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71). A lower, but acceptable, correlation was also found for raw vegetables (r = 0.33). The highest correlation for women was found for consumption of rye bread, oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals, cooked vegetables and soft drinks did not show a significant correlation to the reference method. Pearson Chi-Square and Kendall's tau showed similar results, as did the Jonckheere-Terpstra trend test.</p> <p>Conclusion</p> <p>A majority of the questions in the AGES-FFQ had an acceptable correlation and may be used to rank individuals according to their level of intake of several important foods/food groups. The AGES-FFQ on present diet may therefore be used to study the relationship between consumption of several specific foods/food groups and various health-related endpoints gathered in the AGES-Reykjavik Study.</p

Hydrostatic and osmotic pressure study of the RNA hydration

The tertiary structure of nucleic acids results from an equilibrium between electrostatic interactions of phosphates, stacking interactions of bases, hydrogen bonds between polar atoms and water molecules. Water interactions with ribonucleic acid play a key role in its structure formation, stabilization and dynamics. We used high hydrostatic pressure and osmotic pressure to analyze changes in RNA hydration. We analyzed the lead catalyzed hydrolysis of tRNAPhe from S. cerevisiae as well as hydrolytic activity of leadzyme. Pb(II) induced hydrolysis of the single phosphodiester bond in tRNAPhe is accompanied by release of 98 water molecules, while other molecule, leadzyme releases 86

Identification and Characterization of Antifungal Compounds Using a Saccharomyces cerevisiae Reporter Bioassay

New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces cerevisiae reporter bioassay in which S. cerevisiae heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida spp., Cryptococcus spp. and molds such as Aspergillus fumigatus and Rhizopus oryzae. Drug-resistant Candida albicans from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against C. albicans biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, S. cerevisiae reporter bioassay