| 1. |
- Agerström, Jens, 1976-, et al.
(författare)
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Discriminatory cardiac arrest care? : Patients with low socioeconomic status receive delayed cardiopulmonary resuscitation and are less likely to survive an in-hospital cardiac arrest
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:8, s. 861-869
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Individuals with low socioeconomic status (SES) face widespread prejudice in society. Whether SES disparities exist in treatment and survival following in-hospital cardiac arrest (IHCA) is unclear. The aim of the current retrospective registry study was to examine SES disparities in IHCA treatment and survival, assessing SES at the patient level, and adjusting for major demographic, clinical, and contextual factors.Methods and results: In total, 24 217 IHCAs from the Swedish Register of Cardiopulmonary Resuscitation were analysed. Education and income constituted SES proxies. Controlling for age, gender, ethnicity, comorbidity, heart rhythm, aetiology, hospital, and year, primary analyses showed that high (vs. low) SES patients were significantly less likely to receive delayed cardiopulmonary resuscitation (CPR) (highly educated: OR = 0.89, and high income: OR = 0.98). Furthermore, patients with high SES were significantly more likely to survive CPR (high income: OR = 1.02), to survive to hospital discharge with good neurological outcome (highly educated: OR = 1.27; high income: OR = 1.06), and to survive to 30 days (highly educated: OR = 1.21; and high income: OR = 1.05). Secondary analyses showed that patients with high SES were also significantly more likely to receive prophylactic heart rhythm monitoring (highly educated: OR = 1.16; high income: OR = 1.02), and this seems to partially explain the observed SES differences in CPR delay.Conclusion: There are clear SES differences in IHCA treatment and survival, even when controlling for major sociodemographic, clinical, and contextual factors. This suggests that patients with low SES could be subject to discrimination when suffering IHCA.
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| 2. |
- Agerström, Jens, 1976-, et al.
(författare)
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Intersected groups and discriminatory everyday behavior : Evidence from a lost email experiment
- 2021
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Ingår i: Social Psychology. - : Hogrefe & Huber Publishers. - 1864-9335 .- 2151-2590. ; 52:6, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- De-racialization research suggests that depicting members of ethnic minority groups as gay leads to less stereotypic perceptions oftheir ethnic group. However, whether the consequences of de-racialization translate into real-world behavior is unclear. In a large “lost letter” field experiment (N = 6,654) where an email was ostensibly sent to the wrong recipient by mistake, we investigate whether the relative impact of signaling gayness (vs. heterosexuality) differs for Arab (minority) versus Swedish (majority) senders. The results show clear evidence of ethnic discrimination where Arab (minority) senders receive fewer replies (prosocial response) than Swedish (majority) senders. However, there is no evidence indicating that Arab senders would receive a lower penalty for revealing gayness. Implications for multiple categorization research are discussed.
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| 3. |
- Agerström, Jens, 1976-, et al.
(författare)
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The effect of social gender norms on parental leave uptake intentions : Evidence from two survey experiments on prospective fathers and mothers
- 2023
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Ingår i: Applied Economics. - : Taylor & Francis. - 0003-6846 .- 1466-4283. ; 55:53, s. 6277-6293
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how social gender norms influence parental leave uptake intentions by conducting two separate survey experiments on prospective fathers (N = 877) and mothers (N = 882) in the UK. In a between-subjects design, we manipulate social gender norms by varying information on the average number of days that other fathers and mothers stay at home to take care of a child during the first year after childbirth. We find that when prospective parents (both genders) are exposed to the low staying-home-with-children norm, they plan less parental leave uptake compared to the control (no norm) group. When exposed to the high staying-home-with-children norm, men (but not women) plan more parental leave uptake compared to the control group. We discuss policy implications and suggest directions for future studies.
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| 4. |
- Agerström, Jens, 1976-, et al.
(författare)
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Treatment and survival following in-hospital cardiac arrest : does patient ethnicity matter?
- 2021
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Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953.
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Tidskriftsartikel (refereegranskat)abstract
- AIMS : Previous research on racial/ethnic disparities in relation to cardiac arrest has mainly focused on black vs. white disparities in the USA. The great majority of these studies concerns out-of-hospital cardiac arrest (OHCA). The current nationwide registry study aims to explore whether there are ethnic differences in treatment and survival following in-hospital cardiac arrest (IHCA), examining possible disparities towards Middle Eastern and African minorities in a European context.METHODS AND RESULTS: In this retrospective registry study, 24 217 patients from the IHCA part of the Swedish Registry of Cardiopulmonary Resuscitation were included. Data on patient ethnicity were obtained from Statistics Sweden. Regression analysis was performed to assess the impact of ethnicity on cardiopulmonary resuscitation (CPR) delay, CPR duration, survival immediately after CPR, and the medical team's reported satisfaction with the treatment. Middle Eastern and African patients were not treated significantly different compared to Nordic patients when controlling for hospital, year, age, sex, socioeconomic status, comorbidity, aetiology, and initial heart rhythm. Interestingly, we find that Middle Eastern patients were more likely to survive than Nordic patients (odds ratio = 1.52).CONCLUSION: Overall, hospital staff do not appear to treat IHCA patients differently based on their ethnicity. Nevertheless, Middle Eastern patients are more likely to survive IHCA.
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| 5. |
- Ballante, Flavio, et al.
(författare)
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Docking Finds GPCR Ligands in Dark Chemical Matter
- 2020
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:2, s. 613-620
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput screening has revealed dark chemical matter, a set of drug-like compounds that has never shown bioactivity despite being extensively assayed. If dark molecules are found active at a therapeutic target, their extraordinary selectivity profiles make excellent starting points for drug development. We explored if ligands of therapeutically relevant G-protein-coupled receptors could be discovered by structure-based virtual screening of the dark chemical matter. Molecular docking screens against crystal structures of the A(2A) adenosine and the D-4 dopamine receptors were carried out, and 53 top-ranked molecules were evaluated experimentally. Two ligands of each receptor were discovered, and the most potent had sub-micromolar affinities. Analysis of bioactivity data showed that the ligands lacked activity at hundreds of off-targets, including several that are associated with adverse effects. Our results demonstrate that virtual screening provides an efficient means to mine the dark chemical space, which could contribute to development of drugs with improved safety profiles.
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| 6. |
- Ballante, Flavio, et al.
(författare)
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Structure-Based Virtual Screening for Ligands of G Protein-Coupled Receptors : What Can Molecular Docking Do for You?
- 2021
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Ingår i: Pharmacological Reviews. - : AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS. - 0031-6997 .- 1521-0081. ; 73:4, s. 527-565
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Forskningsöversikt (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome and are important therapeutic targets. During the last decade, the number of atomic -resolution structures of GPCRs has increased rapidly, providing insights into drug binding at the molecular level. These breakthroughs have created excitement regarding the potential of using structural information in ligand design and initiated a new era of rational drug discovery for GPCRs. The molecular docking method is now widely applied to model the threedimensional structures of GPCR-ligand complexes and screen for chemical probes in large compound libraries. In this review article, we first summarize the current structural coverage of the GPCR superfamily and the understanding of receptor-ligand interactions at atomic resolution. We then present the general workflow of structure-based virtual screening and strategies to discover GPCR ligands in chemical libraries. We assess the state of the art of this research field by summarizing prospective applications of virtual screening based on experimental structures. Strategies to identify compounds with specific efficacy and selectivity profiles are discussed, illustrating the opportunities and limitations of the molecular docking method. Our overview shows that structure-based virtual screening can discover novel leads and will be essential in pursuing the next generation of GPCR drugs. Significance Statement--Extraordinary advances in the structural biology of G protein-coupled receptors have revealed the molecular details of ligand recognition by this large family of therapeutic targets, providing novel avenues for rational drug design. Structure-based docking is an efficient computational approach to identify novel chemical probes from large compound libraries, which has the potential to accelerate the development of drug candidates.
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| 7. |
- Begnini, Fabio, et al.
(författare)
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Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction
- 2022
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:4, s. 3473-3517
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Tidskriftsartikel (refereegranskat)abstract
- Upregulation of the transcription factor Nrf2 by inhibition of the interaction with its negative regulator Keap1 constitutes an opportunity for the treatment of disease caused by oxidative stress. We report a structurally unique series of nanomolar Keap1 inhibitors obtained from a natural product-derived macrocyclic lead. Initial exploration of the structure-derived macrocyclic lead. Initial exploration of the structure-activity relationship of the lead, followed by structure-guided optimization, resulted in a 100-fold improvement in inhibitory potency. The macrocyclic core of the nanomolar inhibitors positions three pharmacophore units for productive interactions with key residues of Keap1, including R415, R483, and Y572. Ligand optimization resulted in the displacement of a coordinated water molecule from the Keap1 binding site and a significantly altered thermodynamic profile. In addition, minor reorganizations of R415 and R483 were accompanied by major differences in affinity between ligands. This study therefore indicates the importance of accounting both for the hydration and flexibility of the Keap1 binding site when designing high-affinity ligands.
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| 8. |
- Bender, Brian J., et al.
(författare)
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A practical guide to large-scale docking
- 2021
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Ingår i: Nature Protocols. - : Springer Nature. - 1754-2189 .- 1750-2799. ; 16:10, s. 4799-4832
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Tidskriftsartikel (refereegranskat)abstract
- Structure-based docking screens of large compound libraries have become common in early drug and probe discovery. As computer efficiency has improved and compound libraries have grown, the ability to screen hundreds of millions, and even billions, of compounds has become feasible for modest-sized computer clusters. This allows the rapid and cost-effective exploration and categorization of vast chemical space into a subset enriched with potential hits for a given target. To accomplish this goal at speed, approximations are used that result in undersampling of possible configurations and inaccurate predictions of absolute binding energies. Accordingly, it is important to establish controls, as are common in other fields, to enhance the likelihood of success in spite of these challenges. Here we outline best practices and control docking calculations that help evaluate docking parameters for a given target prior to undertaking a large-scale prospective screen, with exemplification in one particular target, the melatonin receptor, where following this procedure led to direct docking hits with activities in the subnanomolar range. Additional controls are suggested to ensure specific activity for experimentally validated hit compounds. These guidelines should be useful regardless of the docking software used. Docking software described in the outlined protocol (DOCK3.7) is made freely available for academic research to explore new hits for a range of targets. Structure-based docking screens of compound libraries are common in early drug and probe discovery. This protocol outlines best practices and control calculations to evaluate docking parameters prior to undertaking a large-scale prospective screen.
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| 9. |
- Carlsson, Eric, 1972-, et al.
(författare)
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Teknografi
- 2021
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Ingår i: Digitala metoder i humaniora och samhällsvetenskap. - Lund : Studentlitteratur AB. - 9789144140551 ; , s. 45-69
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Bokkapitel (refereegranskat)abstract
- Teknografiska studier undersöker förhållandet mellan teknik, kultur och sociala relationer. Ett sådant perspektiv kan användas för att synliggöra hur teknologier villkorar hur människor agerar, hur deras identiteter formas och hur de blir till som subjekt. I kapitlet exemplifieras hur olika material, såsom digitala vårdappar, innehåll från sociala medier samt intervjuer, kan användas i teknografiskt inspirerade kvalitativa analyser.
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| 10. |
- Carlsson, Ing-Marie, 1961-, et al.
(författare)
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Creating a communication space in the healthcare context : Children’s perspective of using the eHealth service, Sisom
- 2021
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Ingår i: Journal of Child Health Care. - London : Sage Publications. - 1367-4935 .- 1741-2889. ; 25:1, s. 31-43
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Tidskriftsartikel (refereegranskat)abstract
- According to the United Nation’s Convention of the Rights of the Child, children have the right to participate in their own healthcare and make their opinions heard. The aim of this study was thus to explore the impact of using an eHealth service, Sisom, to gain the children’s perspectives during their healthcare appointments. Data were gathered through individual interviews with a purposeful sample of 16 children, aged 6–13 years old, treated for different diseases and using the eHealth service, Sisom, during their healthcare appointments. The interviews were analysed using a constructivist grounded theory. The results showed that using Sisom made children’s voice heard by creating a communication space in the healthcare setting. This meant that the children got involved in the communication, were acknowledged as an important person who could give the answers to questions and were given time. Implementing the use of Sisom is a way to make children’s needs and preferences explicitly visible for decision-making in practice and thereby supporting the further development of child-centred care in practice. © The Author(s) 2020.
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