| 21. |
- Gomes, Filomena, et al.
(författare)
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ESPEN guidelines on nutritional support for polymorbid internal medicine patients
- 2018
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Ingår i: Clinical Nutrition. - : CHURCHILL LIVINGSTONE. - 0261-5614 .- 1532-1983. ; 37:1, s. 336-353
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Polymorbidity (also known as multimorbidity)-defined as the co-occurrence of at least two chronic health conditions - is highly prevalent, particularly in the hospitalized population. Nonetheless, clinical guidelines largely address individual diseases and rarely account for polymorbidity. The aim of this project was to develop guidelines on nutritional support for polymorbid patients hospitalized in medical wards.Methods: The methodology used for the development of the current project follows the standard operating procedures for ESPEN guidelines. It started with an initial meeting of the Working Group in January 2015, where twelve key clinical questions were developed that encompassed different aspects of nutritional support: indication, route of feeding, energy and protein requirements, micronutrient requirements, disease-specific nutrients, timing, monitoring and procedure of intervention. Systematic literature searches were conducted in three different databases (Medline, Embase and the Cochrane Library), as well as in secondary sources (e.g. published guidelines), until April 2016. Retrieved abstracts were screened to identify relevant studies that were used to develop recommendations, which were followed by submission to Delphi voting rounds.Results: From a total of 4532 retrieved abstracts, 38 relevant studies were analyzed and used to generate a guideline draft that proposed 22 recommendations and four statements. The results of the first online voting showed a strong consensus (agreement of >90%) in 68% of recommendations and 75% of statements, and consensus (agreement of >75-90%) in 32% of recommendations and 25% of statements. At the final consensus conference, a consensus greater than 89% was reached for all of the recommendations.Conclusions: Despite the methodological difficulties in creating non-disease specific guidelines, the evidence behind several important aspects of nutritional support for polymorbid medical inpatients was reviewed and summarized into practical clinical recommendations. Use of these guidelines offer an evidence-based nutritional approach to the polymorbid medical inpatient and may improve their outcomes.
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| 22. |
- Grossmann, Igor, et al.
(författare)
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Insights into the accuracy of social scientists' forecasts of societal change
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
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Tidskriftsartikel (refereegranskat)abstract
- How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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| 23. |
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| 24. |
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| 25. |
- Hagger, Martin S., et al.
(författare)
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A Multilab Preregistered Replication of the Ego-Depletion Effect
- 2016
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 11:4, s. 546-573
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Tidskriftsartikel (refereegranskat)abstract
- Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion. Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control.
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| 26. |
- Kenna, J. Gerry, et al.
(författare)
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Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury
- 2018
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Ingår i: Methods in Pharmacology and Toxicology. - New York, NY : Springer New York. - 1557-2153 .- 1940-6053. ; , s. 627-651
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.
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| 27. |
- Lal, KG, et al.
(författare)
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Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 272-
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Tidskriftsartikel (refereegranskat)abstract
- Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality.
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| 28. |
- Melillo, Nicola, et al.
(författare)
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Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug–Drug Interactions in Rats
- 2023
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (khe), and biliary excretion (kbh). The observed median fold-decreases in gadoxetate liver AUC were 3.8- and 1.5-fold for ciclosporin and rifampicin, respectively. Ketoconazole unexpectedly decreased systemic and liver gadoxetate AUCs; the remaining drugs investigated (asunaprevir, bosentan, and pioglitazone) caused marginal changes. Ciclosporin decreased gadoxetate khe and kbh by 3.78 and 0.09 mL/min/mL, while decreases for rifampicin were 7.20 and 0.07 mL/min/mL, respectively. The relative decrease in khe (e.g., 96% for ciclosporin) was similar to PBPK-predicted inhibition of uptake (97–98%). PBPK modelling correctly predicted changes in gadoxetate systemic AUCR, whereas underprediction of decreases in liver AUCs was evident. The current study illustrates the modelling framework and integration of liver imaging data, PBPK, and tracer-kinetic models for prospective quantification of hepatic transporter-mediated DDI in humans.
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| 29. |
- Paquin-Proulx, D, et al.
(författare)
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Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:46
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that HIV-1 disease progression is determined in the early stages of infection. Here, preinfection invariant natural killer T (iNKT) cell levels were predictive of the peak viral load during acute HIV-1 infection (AHI). Furthermore, iNKT cells were preferentially lost in AHI. This was particularly striking in the colonic mucosa, where iNKT cells were depleted more profoundly than conventional CD4+T cells. The initiation of antiretroviral therapy during AHI-prevented iNKT cell dysregulation in peripheral blood but not in the colonic mucosa. Overall, our results support a model in which iNKT cells are early and preferential targets for HIV-1 infection during AHI.
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| 30. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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