Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout

Objective. To determine whether prospective testing forHLA-B*58:01, as a strategy to prevent seriousadverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the NationalHealth Service in the UK. Methods. A systematic review and meta-analysis for the association ofHLA-B*58:01with cutaneous andhypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetimecosts and outcomes associated with testingvsstandard care (with febuxostat prescribed for patients whotest positive). Scenario analyses assessed alternative treatment assumptions and patient populations. Results. The number of patients needed to test to prevent one case of adverse drug reaction was 11 286(95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103(95% CR: £98, £106) and 0.0023 (95% CR: 0.0006, 0.0055), respectively, resulting in an incrementalcost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effectiveat a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICERbelow £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 perQALY gained. Conclusion. Routine testing forHLA-B*58:01in order to reduce the incidence of adverse drug reactions inpatients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing isexpected to become cost-effective with reductions in the cost of genotyping, and with the future avail-ability of cheaper, generic febuxosta

Azorean freshwater invertebrates : status, threats and biogeographic notes

This paper presents an updated catalogue of the freshwater invertebrates of the Azores archipelago and reviews the published records to account for the current taxonomic status and changes in the nomenclature of the listed taxa. The number of freshwater invertebrate species that has been recorded in the Azores has risen sharply throughout the 20th century to 241 species based on field collections and the identification by several generations of local and foreign researchers. The freshwater fauna has been described as the following: (i) being "disharmonic", i.e., lacking taxa commonly found in continental freshwater systems such as the Plecoptera, and (ii) possessing a relatively high degree of endemism in selected groups. As expected, most recorded invertebrates are primarily of Palaearctic origin. However, endemic species make up 11 % of the freshwater invertebrate fauna, which emphasises the unique character of Azorean freshwater habitats, the importance of conservation measures and the need to continue the study of these systems.Este artículo presenta un catalogo actualizado de los invertebrados acuáticos presentes en el Archipiélago de las Azores. La revisión de los registros publicados de estos animales dulceacuícolas se ha realizado teniendo en cuenta el estado taxonómico actual y los cambios en las nomenclaturas de las taxones listados. De todas las maneras la lista no pretende ser un catalogo definitivo, dado que nuevos registros continúan apareciendo, en particular, aquellos que pertenecen a habitats poco estudiados, como es el caso de los sistemas acuáticos dulceacuícolas de las Azores. El número de registros de especies de invertebrados de agua dulce en Azores ha sufrido un incremento importante a lo largo del siglo XX alcanzando 241 especies, que refleja los esfuerzos realizados en la recolección e identificación por parte de varias generaciones de investigadores. La fauna acuática es inarmónica faltando taxones comunes que si existen en los sistemas dulceacuícolas continentales, tal es el caso de los Plecoptera, y abundam los endemismos en otros grupos. La mayoría de invertebrados catalogados son primordialmente de origen Paleártico. Sin embargo, el porcentaje de especies endémicas es de 11 % lo que enfatiza el carácter único de estas especies de Las Azores, la importancia de su conservación y la necesidad de proseguir con un trabajo continuado

A simple method to determine soil–water retention curves of compacted active clays

Determining the Soil Water Retention Curve (SWRC) of an active clay constitutes a challenge due to the significant, and sometimes irreversible, volume changes that occur during wetting and drying cycles. A novel yet simple method of experimentally determining the evolution of the SWRCs with moisture cycles is presented based on the results of a rigorous experimental study. Its purpose is to support the modelling of water flux in earthworks exposed to weather cycles that cause deterioration. Firstly, three SWRC branches (the primary drying, a scanning drying, and a scanning wetting branch) are measured and used to fit the proposed generic SWRC semi-empirical model in terms of water ratio, that, in the adsorptive region, is independent of the compaction conditions (void ratio and water content at compaction). Soil Shrink-Swell Curves (SSSCs) in terms of water ratio versus void ratio, that are easy to measure, can be determined for different compaction conditions over several drying and wetting cycles. Finally, the SSSCs are combined with the generic SWRC model to determine the evolution of the SWRCs with moisture cycles for the compaction conditions of interest. This method is demonstrated for two London clays of high and very high plasticity. Samples were compacted in five different conditions, varying in gravimetric water content and dry density, and were cycled six times between 1 and 80 MPa of total suction. The generic SWRC model was fitted to the experimental data. The model was able to estimate the SWRC in terms of degree of saturation over the six drying-wetting cycles without propagation of error. The significance of the research is that SWRC can now be determined over a range of wetting and drying cycles quickly and simply and enable modelling of deterioration of clays fills due to the action of weather to be accurate

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

Early diabetic retinopathy is characterized by changes in subtle visual functions such as contrast sensitivity and dark adaptation. The outcome of several studies suggests that glutamate is involved in retinal neurodegeneration during diabetes. We hypothesized that the protein levels of ionotropic glutamate receptor subunits are altered in the retina during diabetes. Therefore, we investigated whether human diabetic patients have altered immunoreactivity of ionotropic glutamate receptor subunits in the retina.http://www.sciencedirect.com/science/article/B6SYR-4RS9SS1-1/1/232d6ae7147919a2286326863ee69f1

Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs

Background: Mammalian transcriptomes contain thousands of long noncoding RNAs (lncRNAs). Some lncRNAs originate from intragenic enhancers which, when active, behave as alternative promoters producing transcripts that are processed using the canonical signals of their host gene. We have followed up this observation by analyzing intergenic lncRNAs to determine the extent to which they might also originate from intergenic enhancers. Results: We integrated high-resolution maps of transcriptional initiation and transcription to annotate a conservative set of intergenic lncRNAs expressed in mouse erythroblasts. We subclassified intergenic lncRNAs according to chromatin status at transcriptional initiation regions, defined by relative levels of histone H3K4 mono- and trimethylation. These transcripts are almost evenly divided between those arising from enhancer-associated (elncRNA) or promoter-associated (plncRNA) elements. These two classes of 5′ capped and polyadenylated RNA transcripts are indistinguishable with regard to their length, number of exons or transcriptional orientation relative to their closest neighboring gene. Nevertheless, elncRNAs are more tissue-restricted, less highly expressed and less well conserved during evolution. Of considerable interest, we found that expression of elncRNAs, but not plncRNAs, is associated with enhanced expression of neighboring protein-coding genes during erythropoiesis. Conclusions: We have determined globally the sites of initiation of intergenic lncRNAs in erythroid cells, allowing us to distinguish two similarly abundant classes of transcripts. Different correlations between the levels of elncRNAs, plncRNAs and expression of neighboring genes suggest that functional lncRNAs from the two classes may play contrasting roles in regulating the transcript abundance of local or distal loci

Extrafloral nectaries in Leguminosae: phylogenetic distribution, morphological diversity and evolution

Extrafloral nectaries (EFNs) mediating ecologically important ant-plant protection mutualisms are especially common and unusually diverse in the Leguminosae. We present the first comprehensively curated list of legume genera with EFNs, detailing and illustrating their systematic and phylogenetic distributions, locations on the plant, morphology and anatomy, based on a unified classification of EFN categories and a time-calibrated phylogeny incorporating 710 of the 768 genera. This new synthesis, the first since McKey (1989)?s seminal paper, increases the number of genera with EFNs to 152 (20% of legumes), distributed across subfamilies Cercidoideae (1), Detarioideae (19), Caesalpinioideae (87) and Papilionoideae (45). EFNs occur at nine locations, and are most prevalent on vegetative plant parts, especially leaves (74%) and inflorescence axes (26%). Four main categories (with eight subcategories) are recognized: formless, trichomatic (exposed, hollow), parenchymatic (embedded, pit, flat, elevated) and abscission zone EFNs (non-differentiated, swollen scars). Phylogenetic reconstruction of EFNs suggests independent evolutionary trajectories of different EFN types, with elevated EFNs restricted almost exclusively to Caesalpinioideae (where they underwent spectacular morphological disparification), flat EFNs in Detarioideae, swollen scar EFNs in Papilionoideae, and Cercidoideae is the only subfamily bearing intrastipular EFNs. We discuss the complex evolutionary history of EFNs and highlight future research directions.Fil: Marazzi, Brigitte. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina. Natural History Museum Of Canton Ticino; SuizaFil: González, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Delgado Salinas, Alfonso. Universidad Nacional Autónoma de México; MéxicoFil: Luckow, Melissa A.. Cornell University; Estados UnidosFil: Ringelberg, Jens J.. Universitat Zurich; SuizaFil: Hughes, Colin E.. Universitat Zurich; Suiz

Can warning labels communicating the environmental impact of meat reduce meat consumption? Evidence from two multiple treatment reversal experiments in college dining halls

Meat consumption has an adverse impact on both human and planetary health. To date, very few studies have examined the effectiveness of interventions tackling the overconsumption of meat in field settings. The present research addresses this gap by examining the impact of gain-framed labelling interventions communicating the adverse environmental consequences of meat consumption, using a multiple treatment reversal design across two university college dining halls over a period of five weeks. In College A the intervention weeks consisted of text-only or text-and-image labels communicating the adverse environmental consequences of meat consumption, and in College B patrons were exposed to either environmental or health labels (gain-framed; combining images and text). In total 13,869 (6,577 in College A and 7,292 in College B) meals (dishes) were analysed over the period of interest. Beta-binomial regressions found no statistically significant impact of the intervention periods compared to baseline on meat consumption in both College A and College B. The number of meal type options emerged as the only consistent predictor of meat consumption across models and across both colleges: meat consumption decreased with an increase in non-meat meal options. A post-study survey (College A: n = 88; College B: n = 53) revealed that patrons in both dining halls perceived environmental labels bearing both text and images as more informative and influential at changing behaviour compared to the other labelling interventions, although this did not translate into a change in behaviour. We discuss the implications of these findings for research, policy, and practice

A Review of the Applicability of Current Green Practices in Healthcare Facilities

Background: Circular economy (CE) has raised great interest as a concept and as a development model worldwide. This concept aims to provide a substitute for the linear economic model, which was based on production and consumption, continuous growth, and resources depletion. CE allows a greener economy with sustainable development and promotes more balanced societies. The healthcare sector is a major contributor to the climate crisis, with a carbon footprint representing 4.4% of global net emissions. It is thus essential to rethink the applicability of CE in healthcare. Methods: We conducted a scoping review guided by the Arksey and O’Malley methodological framework and utilised PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist. A systematic search from MEDLINE complete, SCOPUS, and Web of Science databases published between 1992 and 2022. Results: Through database searching a total of 1018 records were identified and 475 duplicates were removed. From the total search, 543 articles were screened by title/abstract according to the inclusion and exclusion criteria. After screening, 38 full-text articles were selected and assessed for eligibility. Forty-seven additional records were also identified through other sources and screened for eligibility. Other sources included: 12 articles from snowballing of previous papers; 9 articles following peer-reviewers suggestions; 19 reports from relevant organisations in CE and healthcare; two webpage, and one book. Conclusion: Specific areas were identified where hospitals could reduce their greenhouse gas (GHG) emissions and consequently their negative environmental impact, namely through waste management, energy, water, transportation/travel, hospital design, food optimisation, green procurement, and behaviour. Also, lack of staff awareness and knowledge of the environmental impact of healthcare, and hospitals sustainability were identified as major contributors.peer-reviewe