838 research outputs found

    You’re either with us or against us! Moral conviction determines how the politicized distinguish friend from foe

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    This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this recordThree studies investigated how politicized collective identification affects individuals’ reactions towards others. We hypothesized that a strong politicized identity tends to be accompanied by a moral conviction about the politicized cause, which in turn determines how the politicized respond to those less committed to their cause. Consistent with this, Study 1 showed that politicized (feminist) identification is associated with lower identification with women who place moderate (vs. high) moral value on gender equality. Study 2 showed that politicized identification was associated with negative emotions towards people who disagree with this cause and this was mediated by the extent to which participants saw supporting the activist goal as morally obligatory. Study 3 showed that politicized identification, to the extent to which it implied holding a moral conviction about the activist cause, is associated with a desire for more social distance to an attitudinally dissimilar other, but not from an attitudinally similar other.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research reported in this article was partially funded by a Marie Curie Intra-European Fellowship (328485) awarded to Maarten Zaal

    MANdatory - why men need (and are needed for) gender equality progress

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    While much progress has been made towards gender equality, diversity and inclusion in the workplace, education and society, recent years have also revealed continuing challenges that slow or halt this progress. To date, the majority of gender equality action has tended to approach gender equality from one side: being focused on the need to remove barriers for girls and women. We argue that this is only half the battle, and that a focus on men is MANdatory, highlighting three key areas: First, we review men’s privileged status as being potentially threatened by progress in gender equality, and the effects of these threats for how men engage in gender-equality progress. Second, we highlight how men themselves are victims of restrictive gender roles, and the consequences of this for men’s physical and mental health, and for their engagement at work and at home. Third, we review the role of men as allies in the fight for gender equality, and on the factors that impede and may aid in increasing men’s involvement. We end with recommendations for work organizations, educational institutions and society at large to reach and involve men as positive agents of social change

    Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions:a cross sectional in silico study: Potential novel binding interactions with resins

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    Background Sevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness. Aim The aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. Method In this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 were extracted from the University Groningen IADB.nl database. Drugs dispensed to  2.0 were identified as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identified as potential interacting drug. Results Of the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identified for sevelamer and polystyrene sulfonate respectively. Conclusion Several potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identified based on dispensing data and assessment of chemical properties for which further interaction research is warranted

    Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

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    BACKGROUND AND OBJECTIVE: Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone.METHODS: A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.RESULTS: Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC 0-8 h and C max of oxycodone with, respectively, 44.7% (p &lt; 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC 0-8 h and C max of the active metabolite oxymorphone were 74.2% (p &lt; 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC 0-8 h and C max of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. CONCLUSION: Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.</p

    Glucocorticoid sensitivity in Behcet's disease

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    WOS: 000209773300007PubMed ID: 23781311Objective: Glucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-) inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behcet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity. Methods: Healthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-alpha and GR-beta) were measured. Results: Healthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9 beta minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals. At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-alpha/GR-beta mRNA expression levels was significantly lower in BD. Conclusions: Polymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-b splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.The Dutch Arthritis AssociationThis work was supported by a grant from The Dutch Arthritis Association

    Resonant X-Ray Magnetic Scattering from CoO

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    We analyze the recent experiment [W. Neubeck {\em et al.}, Phys. Rev. B \vol(60,1999,R9912)] for the resonant x-ray magnetic scattering (RXMS) around the K edge of Co in the antiferromagnet CoO. We propose a mechanism of the RXMS to make the 4p4p states couple to the magnetic order: the intraatomic exchange interaction between the 4p4p and the 3d3d states and the pp-dd mixing to the 3d3d states of neighboring Co atoms. These couplings induce the orbital moment in the 4p4p states and make the scattering tensor antisymmetric. Using a cluster model, we demonstrate that this modification gives rise to a large RXMS intensity in the dipole process, in good agreement with the experiment. We also find that the pre-edge peak is generated by the transition to the 3d3d states in the quadrupole process, with negligible contribution of the dipole process. We also discuss the azimuthal angle dependence of the intensity.Comment: 15 pages, 8 figure

    Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behçet Disease

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    Introduction: The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genomewide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended metaanalysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our

    Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension:a randomized controlled trial

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    Background:Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.Methods:We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.Results:Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P &lt; 0.001, n = 40) and 59.5% in the SoC arm (P &lt; 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).Conclusion:Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.</p
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