'Immunising' physicians against availability bias in diagnostic reasoning: A randomised controlled experiment

Background: Diagnostic errors have often been attributed to biases in physicians' reasoning. Interventions to 'immunise' physicians against bias have focused on improving reasoning processes and have largely failed. Objective: To investigate the effect of increasing physicians' relevant knowledge on their susceptibility to availability bias. Design, settings and participants: Three-phase multicentre randomised experiment with second-year internal medicine residents from eight teaching hospitals in Brazil. Interventions: Immunisation: Physicians diagnosed one of two sets of vignettes (either diseases associated with chronic diarrhoea or with jaundice) and compared/contrasted alternative diagnoses with feedback. Biasing phase (1 week later): Physicians were biased towards either inflammatory bowel disease or viral hepatitis. Diagnostic performance test: All physicians diagnosed three vignettes resembling inflammatory bowel disease, three resembling hepatitis (however, all with different diagnoses). Physicians who increased their knowledge of either chronic diarrhoea or jaundice 1 week earlier were expected to resist the bias attempt. Main outcome measurements: Diagnostic accuracy, measured by test score (range 0-1), computed for subjected-to-bias and not-subjected-to-bias vignettes diagnosed by immunised and not-immunised physicians. Results: Ninety-one residents participated in the experiment. Diagnostic accuracy differed on subjected-to-bias vignettes, with immunised physicians performing better than non-immunised physicians (0.40 vs 0.24; difference in accuracy 0.16 (95% CI 0.05 to 0.27); p=0.004), but not on not-subjected-to-bias vignettes (0.36 vs 0.41; difference -0.05 (95% CI -0.17 to 0.08); p=0.45). Bias only hampered non-immunised physicians, who performed worse on subjected-to-bias than not-subjected-to-bias vignettes (difference -0.17 (95% CI -0.28 to -0.05); p=0.005); immunised physicians' accuracy did not differ (p=0.56). Conclusions: An intervention directed at increasing knowledge of clinical findings that discriminate between similar-looking diseases decreased physicians' susceptibility to availability bias, reducing diagnostic errors, in a simulated setting. Future research needs to examine the degree to which the intervention benefits other disease clusters and performance in clinical practice. Trial registration number: 68745917.1.1001.0068

New Multicomponent Forms of the Antiretroviral Nevirapine with Improved Dissolution Performance

In the pharmaceutical area, some drugs exhibit physicochemical properties that adversely affect the formulation processes for bioavailability and effectiveness. Nevirapine (NVP) is an antiretroviral drug that presents low aqueous solubility, which directly impacts its bioavailability. Among all possible modifications, multicomponent crystals, such as cocrystals and eutectic compositions, have been successfully used to improve the solubility of drugs. In this work, the propensity of the formation of multicomponent systems of NVP with seven possible coformers were predicted and tested: salicylic acid (SA), 3-hydroxybenzoic acid (3HBZC), 4-hydroxybenzoic acid (4HBZC), saccharin (SAC), theophylline (THEO), caffeine (CAF), and urea (URE). Results indicate that NVP-SA, NVP-SAC, NVP-3HBZC, and NVP-4HBZC are cocrystals, whereas NVP-THEO and NVP-CAF are eutectic materials, and NVP-URE is a solid physical mixture. A temperature-dependent disorder behavior was identified for NVP-SA cocrystal. Dissolution studies for the eutectic materials are reported, evidencing that these materials exhibit a significant increase in NVP dissolution kinetics.Fil: Costa, Rogeria Nunes. Universidade Federal de Sao Paulo; BrasilFil: Reviglio, Ana Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Siedler, Sana. Universidade Federal de Santa Catarina; BrasilFil: Cardoso, Simone G.. Universidade Federal de Santa Catarina; BrasilFil: Garro Linck, Yamila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Monti, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Carvalho, Alexandre Magnus G.. Centro Nacional de Pesquisa em Energia e Materiais; BrasilFil: Resende, Jackson A. L. C.. Universidade Federal do Mato Grosso do Sul; BrasilFil: Chaves, Marcelo H. C.. Fundación Oswaldo Cruz; BrasilFil: Rocha, Helvético Vinícius Antunes. Fundación Oswaldo Cruz; BrasilFil: Choquesillo Lazarte, Duane. Consejo Superior de Investigaciones Científicas; España. Universidad de Granada; EspañaFil: Infantes, Lourdes. Consejo Superior de Investigaciones Científicas; España. Instituto de Química Física Rocasolano; EspañaFil: Cuffini, Silvia Lucia. Universidade de Sao Paulo; Brasi

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Assessing the performance of analytical methods for propolis – A collaborative trial by the international honey commission

Propolis is a resinous beehive product with extraordinary bioactivity and chemical richness, linked with the botanical sources of the resin. The potential of this product keeps captivating the scientific community, conducting to continuous and growing research on plant sources, composition, or applications in agriculture, cosmetics, pharmacy, odontology, etc. In all cases, the quality assessment is a requirement and relies on methods to extract the bioactive substances from the raw propolis and quantify different components. Unfortunately, besides the absence of international quality requirements, there is also a lack of standardized analytical procedures, despite the presence of several methodologies with unknown reliability, often not comparable. To overcome the current status, the International Honey Commission established an inter-laboratory study, with propolis samples from around the globe, to harmonize analytical methods and evaluate their accuracy. A common set of protocols was matched between twelve laboratories from nine countries, for quantification of ash, wax, and balsamic content in raw propolis, and spectrophotometric evaluation of total phenolics, flavone/flavonol, and flavanone/ dihydroflavonol in the extract. A total of 3428 results (97% valid data), were used to assess the methods’ accuracy following ISO-5725 guidelines. The within-laboratory precision, revealed good agreement levels for the majority of the methods, with relative variance below 5%. As expected, the between-laboratory variance increased, but, with exception of the flavanone method that revealed a clear lack of consistency, all the others maintained acceptable variability levels, below 30%. Because the performance of ultrasounds procedures was low, they cannot be recommended until further improvements are made.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020). Thanks to the Programa Apíıcola Nacional 2020-2022 (National Beekeeping Program) for funding the project "Standardization of production procedures and quality parameters of bee products" and to Project PDR2020-1.0.1- FEADER-031734: “DivInA-Diversification and Innovation on Beekeeping Production”. National funding by FCT – Foundation for Science and Technology, through the institutional scientific employment program-contract with Soraia I. Falcão. A special thanks is given to Hartmut Scheiter and Allwex Food Trading GmbH, Bremen, Germany, for providing, handling and delivering the propolis blind samples.info:eu-repo/semantics/publishedVersio

ICES. 2020. Working Group on Acoustic and Egg Surveys for Sardine and Anchovy in ICES areas 7, 8 and 9

he Working Group on Acoustic and Egg Surveys (WGACEGG) coordinates pelagic surveys for a number of stocks and provides monitoring for the two major sardine and anchovy stocks in ICES areas 6, 7, 8, and 9. The group evaluated small pelagic fish biomass indices derived from acoustic and Daily Egg Production Method (DEPM) surveys in ICES areas 6, 7, 8 and 9. These indices have been provided to the ICES Working Group on Southern Horse Mackerel, Anchovy and Sardine (WGHANSA), the Working Group on Widely Distributed Stocks (WGWIDE) and the Herring Assessment Working Group for the Area South of 62ºN (HAWG) stock assessment group, to serve as fishery-independent input for analytical assessment purposes. DEPM and acoustic indices were derived based on data collected using independent methods. Acoustic- and DEPM-derived biomass indices from quasi-synoptic surveys conducted in the Bay of Biscay in spring were compared, to assess the presence of potential bias and to improve the precision of fish stock biomass estimates. The DEPM-based anchovy biomass index was 22% higher than the acoustic index in 2019. Unusual concentrations of anchovy in Eastern Cantabrian Sea, an area not covered by the acoustic survey, and the presence near the sea surface of actively spawning individuals possibly under-sampled by acoustics in central Bay of Bay had been postulated as potential causes of this discrepancy. No significant difference was found between sardine biomass indices derived from DEPM and acoustics in 2019. The group has updated its database of standard gridded maps covering the European Atlantic area. This initiative continues to inform on the spatial dynamics of various parameters collected during the surveys coordinated under the auspices of the group (fish acoustic densities, anchovy and sardine egg abundance, surface temperature and salinity). Results of an analysis of the time series of gridded maps (anchovy and sardine acoustic density, surface salinity and temperature) showed quantitative changes in the spatial and temporal distribution of anchovy and sardine over the last 15 years, and further define their habitats in European Atlantic waters in spring. The timing and spatial coverage of DEPM and acoustic surveys that will be conducted by group members in 2020 were planned to optimise the monitoring of anchovy and sardine populations and their pelagic environment in the European Atlantic area. The synoptic nature of the survey components has been assessed for each target species. A manual describing the protocols used during the DEPM surveys coordinated by the WGACEGG group was reviewed, and writing of a manual of WGACEGG acoustic surveys continued. Both manuals will be available in 2020. The final results of the 2017 sardine DEPM assessment were endorsed by the group

Preliminary results from the ECOCADIZ 2020-07 Spanish acoustic survey (01 – 14 August 2020)

The present working document summarises a part of the main results obtained from the Spanish (pelagic ecosystem-) acoustic survey conducted by IEO between 01st and 14th August 2020 in the Portuguese and Spanish shelf waters (20-200 m isobaths) off the Gulf of Cadiz (GoC) onboard the R/V Miguel Oliver. The 21 foreseen acoustic transects were sampled. A total of 26 valid fishing hauls were carried out for echo-trace ground-truthing purposes. Four additional night trawls were conducted to collect anchovy hydrated females (DEPM). This working document only provides abundance and biomass estimates for anchovy, sardine and chub mackerel, which are presented without age structure. The distribution of all the mid-sized and small pelagic fish species susceptible of being acoustically assessed is also shown from the mapping of their back-scattering energies. GoC anchovy acoustic estimates in summer 2020 were of 5153 million fish and 44 877 tones, with the bulk of the population occurring in the Spanish waters. The current biomass estimate becomes in the second historical maximum within the time-series. The estimates of sardine abundance and biomass in summer 2020 were 1923 million fish and 50 721 t, estimates close to the historical average, but lower than the values estimated last year and the most recent maxima reached in 2018. A total of 32 854 t and 448 million fish were estimated for Chub mackerel, estimates similar to the most recent ones and very close to the time-series average

Community structure of woody plants on islands along a bioclimatic gradient

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