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Tidligere studier viser at jobbsøkere med innvandrerbakgrunn diskrimineres i ansettelsesprosesser. Denne kvalitative studien undersøker om erfaringer med og forventninger om diskriminering har betydning for hvordan minoriteter fremstiller seg selv i en jobbsøkerprosess. Studien er basert på semistrukturerte intervjuer med nordmenn med innvandrerbakgrunn. Med utgangspunkt i Goffmans teori om stigmabevissthet og inntrykkshåndtering illustrerer studien hvordan etniske minoriteter forsøker å unngå diskriminering gjennom å spille på norskhet og nedtone sin minoritetsbakgrunn. Artikkelen bidrar til den voksende litteraturen om responser på diskriminering og viser at minoriteter bruker stigmahåndterende strategier for å bli gitt en sjanse i det norske arbeidsmarkedet.

Introduction: In the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes. Methods: Patients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors. Results: On-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP. Conclusions: Factors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.

Background: Left atrial (LA) function contributes to the augmentation of cardiac output during exercise. However, LA response to exercise in patients with atrial fibrillation (AF) is unknown. We explored the LA mechanical response to exercise and the association between LA dysfunction and exercise intolerance. Methods: We recruited consecutive patients with symptomatic AF and preserved left ventricular ejection fraction (LVEF). Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET). Two-dimensional and speckle-tracking echocardiography were performed to assess LA function at rest and during exercise. Participants were grouped according to presenting rhythm (AF vs sinus rhythm). The relationship between LA function and cardiorespiratory fitness in patients maintaining SR was assessed using linear regression. Results: Of 177 consecutive symptomatic AF patients awaiting AF ablation, 105 met inclusion criteria; 31 (29.5 %) presented in AF whilst 74 (70.5 %) presented in SR. Patients in SR augmented LA function from rest to exercise, increasing LA emptying fraction (LAEF) and LA reservoir strain. In contrast, patients in AF demonstrated reduced LAEF and reservoir strain at rest, with failure to augment either parameter during exercise. This was associated with reduced VO2Peak compared to those in SR (18.4 ± 5.6 vs 22.5 ± 7.7 ml/kg/min, p = 0.003). In patients maintaining SR, LAEF and reservoir strain at rest and during exercise were associated with VO2Peak, independent of LV function. Conclusion: The maintenance of SR in patients with AF is associated with greater LA reservoir function at rest and greater augmentation with exercise compared to patients in AF. In patients in SR, reduced LA function is associated with reduced exercise tolerance, independent of LV function.

Cabergoline-associated valvulopathy (CAV) is defined by the echocardiographic triad of moderate or severe regurgitation, valvular thickening and restricted valvular motion. While it is a well-described complication of dopamine agonist therapy in Parkinson’s disease, only three convincing cases of CAV have previously been described in the treatment of prolactinoma, with none involving the tricuspid valve. We describe a case of CAV affecting the tricuspid valve, ultimately resulting in the patient’s death. The novel finding of CAV affecting the tricuspid valve suggests a possible link between confirmed cases of CAV and the echocardiographic surveillance studies of cabergoline-treated prolactinoma patients which have mostly demonstrated subclinical tricuspid valve changes. The risk of CAV, although small, prompts a mindful prescription of dopamine agonist therapy for prolactinomas and consideration of measures to minimise cabergoline exposure. The cumulative cabergoline doses and duration of therapy associated with CAV in published cases exceed what has been evaluated in case series and surveillance studies, underscoring the importance of case reports in understanding CAV.

Abstract Background Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease. Aim To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. Method Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947–June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively. Results For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] −1.45 [−1.83, −1.06], p85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias. Conclusion Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

Background Methods Results Conclusions The hepatitis B e antigen (HBeAg)‐negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood.Genotype A, B and D HBeAg‐negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg‐positive rescue mutant and HBeAg‐positive wild‐type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF‐E2‐related factor 2 (Nrf2)/antioxidant response element (ARE)‐dependent gene expression and cellular kinome.In comparison with reference genomes, the patient isolates are characterized by a lower intra‐ and extracellular hepatitis B surface antigen (HBsAg)‐amount, and HBsAg‐retention in the endoplasmic reticulum. Rescue of HBeAg expression increased HBsAg‐amount but not its release. Expression of the isolated genomes is associated with a higher Nrf2/ARE‐dependent gene expression as compared to reference genomes independent of HBeAg expression. Kinome analyses revealed a decreased activity of receptors involved in regulation of proliferative pathways for all patient isolates compared to the reference genomes. No specific conserved mutations could be found between all genomes from Phase 3.HBeAg‐negative genomes from Phase 3 exhibit distinct molecular characteristics leading to lower HBsAg synthesis and release, enhanced oxidative stress protection and decreased activity of key kinases, triggering an antiproliferative stage, which might contribute to the lower probability of hepatocellular carcinoma. The observed differences cannot be associated with loss of HBeAg or specific mutations common to all analysed isolates, indicating the phenotype of Phase 3 derived genomes to be the result of a multifactorial process likely reflecting a conserved natural selection process. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein, the hepatitis delta antigen (HDAg), which exists in two forms acting as nucleoproteins. HDV depends on the envelope proteins of the hepatitis B virus as a helper virus for packaging its ribonucleoprotein complex (RNP). HDV is considered the causative agent for the most severe form of viral hepatitis leading to liver fibrosis/cirrhosis and hepatocellular carcinoma. Many steps of the life cycle of HDV are still enigmatic. This review gives an overview of the complete life cycle of HDV and identifies gaps in knowledge. The focus is on the description of cellular factors being involved in the life cycle of HDV and the deregulation of cellular pathways by HDV with respect to their relevance for viral replication, morphogenesis and HDV-associated pathogenesis. Moreover, recent progress in antiviral strategies targeting cellular structures is summarized in this article.

Abstract Background Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. Results We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis-regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14, RpS24, and Rpn8 are associated with heart phenotypes. Conclusions Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis-regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.

This study examines the causal nexus between Foreign Direct Investment (FDI) and the economic growth of seven (7) regions encompassing 117 countries. A more recent panel dataset over the period 2010-2020 was analysed using the Granger causality approach and panel VAR/block exogeneity test to conduct predictive analysis among the panel series. Wavelet coherence techniques too were adapted in bringing novelty and further justifications to the research in exploring the interaction effects of the variables, which are yet to be popularised in the studied discipline. The empirical results indicate the presence of bi-directional causality between FDI and economic growth globally and in the Asian region. In contrast, the causality is uni-directional in the American region. A non-directional causality was discovered in European, Oceanian, Mediterranean, and African regions, and the findings were consistent with the outcome of the wavelet coherence technique results. The study further classifies the regions into three cross-market categories such as developed, emerging and frontier markets. The results imply no causality for most developed and emerging economies in the regional analysis. Findings also provide insights for governments and policymakers worldwide to formulate policies on directing FDI flows and propositions for a host country to become a more conducive destination for FDI and accelerate economic growth.