The effect of rs2910686 on ERAP2 expression in IBD and epithelial inflammatory response.

BACKGROUND: ERAP2 is an aminopeptidase involved in antigen processing and presentation, and harbor genetic variants linked to several inflammatory diseases such as Inflammatory Bowel Disease (IBD). The lack of an ERAP2 gene homologue in mice has hampered functional studies, and most human studies have focused on cells of hematopoietic origin. Using an IBD biobank as vantage point, this study explores how genetic variation in ERAP2 affects gene expression in human-derived epithelial organoids upon proinflammatory stimulation. METHODS: An IBD patient cohort was genotyped with regards to two single nucleotide polymorphisms (SNP) (rs2910686/rs2248374) associated with ERAP2 expression levels, and we examined the correlation between colon gene expression and genotype, specifically aiming to establish a relationship with ERAP2 expression proficiency. Human-derived colon organoids (colonoids) with known ERAP2 genotype were established and used to explore differences in whole genome gene expression between ERAP2-deficient (n = 4) and -proficient (n = 4) donors upon pro-inflammatory encounter. RESULTS: When taking rs2910686 genotype into account, ERAP2 gene expression is upregulated in the inflamed colon of IBD patients. Colonoids upregulate ERAP2 upon IFNÉ£ stimulation, and ERAP2 expression proficiency is dependent on rs2910686 genotype. Colonoid genotyping confirms that mechanisms independent of the frequently studied SNP rs2248374 can cause ERAP2-deficiency. A total of 586 genes involved in various molecular mechanisms are differentially expressed between ERAP2 proficient- and deficient colonoids upon proinflammatory stimulation, including genes encoding proteins with the following molecular function: catalytic activity (AOC1, CPE, ANPEP and MEP1A), regulator activity (TNFSF9, MDK, GDF15, ILR6A, LGALS3 and FLNA), transmembrane transporter activity (SLC40A1 and SLC5A1), and extracellular matrix structural constituents (FGL2, HMCN2, and MUC17). CONCLUSIONS: ERAP2 is upregulated in the inflamed IBD colon mucosa, and expression proficiency is highly correlated with genotype of rs2910686. While the SNP rs2248374 is commonly used to determine ERAP2 expressional proficiency, our data confirms that mechanisms independent of this SNP can lead to ERAP2 deficiency. Our data demonstrates that epithelial ERAP2 presence affects the inflammatory response in colonoids, suggesting a pleiotropic role of ERAP2 beyond MHC class I antigen processing.

Health Technology Readiness amongst Patients with Suspected Breast Cancer Using the READHY-tool - a Cross-sectional Study.

Information technologies are increasingly used when informing patients about their disease, treatment and prognosis. These digital platforms have many advantages compared to traditional education interventions. However, there are concerns that some patients may have difficulty with this mode of information delivery. Newly diagnosed breast cancer patients are dependent on understanding their treatment options to make informed treatment decisions. Yet, there is a lack of published material on breast cancer patients and their relationship with technology. We aimed to assess health technology readiness profiles amongst women with a suspected breast cancer diagnosis. Secondly, we wanted to investigate the potential differences between these profiles according to sociodemographic factors and the patients´ current use of technology. This cross-sectional study used the Readiness and Enablement Index for Health Technology (READHY) questionnaire. We included all patients (n = 92) referred to our department with suspected breast cancer. Cluster analysis revealed three distinct profiles: medium (n = 54), high (n = 18), and low (n = 20) health technology readiness. The third profile showed difficulties in health literacy, eHealth literacy, and health insights, along with higher emotional stress. Our study found that most patients had medium to high health technology readiness, but we also identified a group with lower health technology readiness. Based on our results, healthcare personnel dealing with women with suspected breast cancer should be aware of patients struggling with health technology. Age and technology familiarity may indicate vulnerable patients. Future studies should explore optimal methods for information delivery to these distinct profiles and evaluate the long-term impacts.

Comprehensive protocols for culturing and molecular biological analysis of IBD patient-derived colon epithelial organoids.

There are many unanswered questions regarding responses to proinflammatory signals in intestinal epithelial cells (IECs). For example, chemokines secreted by IECs upon external stimuli play multifunctional roles in both homeostasis and during inflammation. Several chemokines are upregulated during active inflammatory bowel disease (IBD), which is associated with an increased influx of immune cells into the gut mucosa. Therefore, studies on how chemokines are regulated in the intestinal epithelium may identify putative treatment targets in IBD. More recently, patient-derived ex vivo models such as intestinal organoids have facilitated molecular analysis of epithelial alterations in IBD patients own cells. Here, we describe refined experimental protocols and methods for the generation and maintenance of IBD patient-derived colonic organoids (colonoids) culture. We also give detailed description of medium, and supplements needed for colonoid establishment, growth, and differentiation, including production of Wnt-3A and Rspondin1 enriched media. Further, we present protocols for RNA and protein isolation from human colonoids, and subsequent gene expression analysis and Western blotting for e.g., signal transduction studies. We also describe how to process colonoids for chemokine protein expression analysis such as immunostaining, confocal imaging, and detection of secreted chemokines by e.g., enzyme-linked immunosorbent assay (ELISA). As proof of principle, we give examples of how the chemoattractant CCL20 can be regulated and expressed in colonoids derived from IBD-patients and healthy controls upon ligands-driven inflammation.

Tofacitinib Downregulates TNF and Poly(I:C)-Dependent MHC-II Expression in the Colonic Epithelium.

Major Histocompatibility Complex (MHC)-I and -II genes are upregulated in intestinal epithelial cells (IECs) during active inflammatory bowel diseases (IBD), but little is known about how IBD-relevant pro-inflammatory signals and IBD drugs can regulate their expression. We have previously shown that the synthetic analog of double-stranded RNA (dsRNA) Polyinosinic:polycytidylic acid (Poly(I:C)), induces interferon stimulated genes (ISGs) in colon organoids (colonoids). These ISGs may be involved in the induction of antigen presentation. In the present study, we applied colonoids derived from non-IBD controls and ulcerative colitis patients to identify induction and effects of IBD-drugs on antigen presentation in IECs in the context of Tumor Necrosis Factor (TNF)-driven inflammation. By RNA sequencing, we show that a combination of TNF and Poly(I:C) strongly induced antigen-presentation gene signatures in colonoids, including expression of MHC-II genes. MHC-I and -II protein expression was confirmed by immunoblotting and immunofluorescence. TNF+Poly(I:C)-dependent upregulation of MHC-II expression was associated with increased expression of Janus Kinases JAK1/2 as well as increased activation of transcription factor Signal transducer and activator of transcription 1 (STAT1). Accordingly, pre-treatment of colonoids with IBD-approved pan-Janus Kinase (JAK) inhibitor Tofacitinib led to the downregulation of TNF+Poly(I:C)-dependent MHC-II expression associated with the abrogation of STAT1 activation. Pre-treatment with corticosteroid Budesonide, commonly used in IBD, did not alter MHC-II expression. Collectively, our results identify a regulatory role for IBD-relevant pro-inflammatory signals on MHC-II expression that is influenced by Tofacitinib.

Dynastic cores and the borrowed time of newcomers. Wealth accumulation and the Norwegian one percent.

This paper explores the trajectories of Norwegians who, in their late-thirties, possessed financial assets, such as securities, company shares and stocks, qualifying them as the wealthiest one percent nationally. We describe the accumulation of financial wealth over a 25-year period in adulthood and study how different wealth sequences are linked to family origins and kinship ties. Although some Norwegians manage to build up large fortunes from relatively modest starting points over their life courses, we find that the value of the assets possessed by self-made individuals, and their ability to retain wealth over time, differ significantly to those based on dynastic lineage. Among the latter group, profound wealth early in adulthood and strategic positions in the economy add to propel exponential ownership of financial wealth from a young age and throughout adulthood. This chimes with C. Wright Mills' suggestion that the amassing of great fortunes is driven by two mechanisms of the big jump that enables initial asset build-up, and the accumulation of advantages that flows from advantageous economic and social ties. Kinship seems of key importance to ensure the efficacy of both mechanisms. Differences in the relationship of wealth accumulation and class origin seem to have little to do with educational strategies. We draw attention to direct wealth transfers and the institution of marriage as two little explored dimensions involved in dynastic closure.

The Impact of a Workplace Terrorist Attack on the Psychosocial Work Environment: A Longitudinal Study From Pre- to Post-disaster.

The psychosocial work environment is of great importance for regaining health and productivity after a workplace disaster. Still, there is a lack of knowledge about the impact of a disaster on the psychosocial work environment. The purpose of this study was to examine whether employees' perceptions of role clarity, role conflicts, and predictability in their work situation changed from before to after a workplace terrorist attack. We combined data from two prospective work environment surveys of employees in three governmental ministries that were the target of the 2011 Oslo terrorist attack. A first two-wave survey was conducted 4-5 years and 2-3 years before the attack, and a second three-wave survey took place 10 months, 2 years, and 3 years after the attack. Of 504 individuals who were employed at the time of the bombing, 220 were employed in both pre- and post-disaster periods, participated in both the first and the second survey, and consented to the linking of data from the two surveys. We found no significant changes in levels of role clarity, role conflict, and predictability from before to after the terrorist attack. Adjusting for sex, age and education had no effect on the results. The findings suggest that perceptions of the psychosocial working environment are likely to be maintained at previous levels in the aftermath of a workplace disaster. Considering the importance of the psychosocial work environment for regaining health and productivity, the findings are important for the preparation for, and management of, future crises.

Host-Viral Interactions in the Pathogenesis of Ulcerative Colitis.

Ulcerative colitis is characterized by relapsing and remitting colonic mucosal inflammation. During the early stages of viral infection, innate immune defenses are activated, leading to the rapid release of cytokines and the subsequent initiation of downstream responses including inflammation. Previously, intestinal viruses were thought to be either detrimental or neutral to the host. However, persisting viruses may have a role as resident commensals and confer protective immunity during inflammation. On the other hand, the dysregulation of gut mucosal immune responses to viruses can trigger excessive, pathogenic inflammation. The purpose of this review is to discuss virus-induced innate immune responses that are at play in ulcerative colitis.

General self-efficacy in individuals with visual impairment compared with the general population.

BACKGROUND: Knowledge about self-efficacy and its significance for the quality of life of people with visual impairment is lacking. The aims of the study were to compare general self-efficacy in individuals with visual impairment with the general population, and to investigate the association between self-efficacy and life satisfaction. METHODS: A telephone-based cross-sectional survey was conducted between January and May 2017 in a probability sample of adults who were members of the Norwegian Association of the Blind and Partially Sighted. Participants were asked questions about their sociodemographic characteristics, characteristics of vision loss, general self-efficacy (General Self-efficacy Scale), and life satisfaction (Cantril's Ladder of Life Satisfaction). We obtained norm data from a representative survey of the general Norwegian population (N = 1792; mean age 53.2 years; 52.5% females). RESULTS: People with visual impairment had higher levels of general self-efficacy than people in the general population (Mean: 31.5 versus 29.0, p < .001). Results from linear regression analyses of the visual impairment population showed that higher education and residential in an urban municipality were associated with higher self-efficacy. Having additional impairments and a previous history of physical or sexual assaults were associated with lower self-efficacy. A linear dose-response relationship was found between self-efficacy and life satisfaction, in the visual impairment population as well as in the general population. CONCLUSIONS: People with visual impairment have higher self-efficacy than people in the general population, possibly due to extensive mastery experience in how to handle life as visually impaired. Self-efficacy seems to be important in achieving the best possible life.

Historical change in an elite profession-Class origins and grades among law graduates over 200 years.

This article explores the relationship between social class and educational achievement measured by grades among Norwegian law graduates over a span of 200 years. We argue that class inequalities may arise due to mechanisms favouring 'insiders', meaning students whose families have legal backgrounds. Alternatively, a broader category of students with origins in educated or elite families could also enjoy special advantages. Our results indicate that there were insignificant class inequalities in grades before the beginning of the 20th century, when they first appeared, and that class inequalities increased to some extent subsequently. Graduates with origins from families with legal backgrounds or origins in the cultural upper class tend to be awarded the highest grades and those with farming or working-class origins tend to be awarded the lowest grades. Inequalities according to class origin can be explained only to a limited extent by performance at secondary school. Unlike class origin, however, the impact of grades at secondary school appears to be highly stable over time. We ask whether mechanisms favouring legal 'insiders' may have become less important over time, whereas the impact of cultural capital may have increased.

The Inflammasome Components NLRP3 and ASC Act in Concert with IRGM To Rearrange the Golgi Apparatus during Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli.IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling.

How and Why to Involve Patients in Drug Development: Perspectives From the Pharmaceutical Industry, Regulatory Authorities, and Patient Organizations.

BACKGROUND: Despite increasing interest and focus on patient-centric approaches to drug development, there might still be divergent views between key stakeholders in how to perceive patient involvement and how possibly divergent views influence the role of patients in the drug development process. The objective of this study is to explore how the perception of patient organizations, pharmaceutical companies, and regulatory agencies influence the role of patients in drug development. METHOD: A qualitative interview study based on 12 semi-structured interviews with representatives from the 3 stakeholders. Interviews were transcribed, and data were analyzed using a social constructivist approach in the form of systematic text condensation. RESULTS: Three main perceptions of patient involvement were identified: "a way to improve quality of life," "a way to avoid business failure," and "a way to foster a faster drug approval process." Transparency, trust, and clarification of expectations and roles were factors perceived as prerequisites for a valuable collaboration. Furthermore, a required cultural mindset change in the pharmaceutical industry, the lack of a common framework, patient organizations having limited resources available, and concerns about what to do with patient responsibility were perceived as the most important barriers for patient involvement. CONCLUSION: Based on the findings, the pharmaceutical industry, patient organizations, and regulatory authorities were labeled as "pioneer/dominant," "unaware/quiet," and "hesitant," respectively. The 3 behavioural descriptors reflect a limited negotiation of the role patients have in drug development. Thus, the pharmaceutical industry appears to be the largest influencer with regard to patients' role in drug development.

Oxidative Chemical Stressors Alter the Physiological State of the Nasal Olfactory Mucosa of Atlantic Salmon.

The olfactory organs of fish have vital functions for chemosensory and defence. Though there have been some ground-breaking discoveries of their involvement in immunity against pathogens in recent years, little is known about how they respond to non-infectious agents, such as exogenous oxidants, which fish encounter regularly. To this end, we employed Atlantic salmon (Salmo salar) as a model to study the molecular responses at the nasal olfactory mucosa of a teleost fish when challenged with oxidants. Microarray analysis was employed to unravel the transcriptional changes at the nasal olfactory mucosa following two types of in vivo exposure to peracetic acid (PAA), a highly potent oxidative agent commonly used in aquaculture: Trial 1: periodic and low dose (1 ppm, every 3 days over 45 days) to simulate a routine disinfection; and Trial 2: less frequent and high dose (10 ppm for 30 min, every 15 days, 3 times) to mimic a bath treatment. Furthermore, leukocytes from the olfactory organ were isolated and exposed to PAA, as well as to hydrogen peroxide (H2O2) and acetic acid (AA)-the two other components of PAA trade products-to perform targeted cellular and molecular response profiling. In the first trial, microarrays identified 32 differentially expressed genes (DEG) after a 45-day oxidant exposure. Erythrocyte-specific genes were overly represented and substantially upregulated following exogenous oxidant exposure. In Trial 2, in which a higher dose was administered, 62 DEGs were identified, over 80% of which were significantly upregulated after exposure. Genes involved in immune response, redox balance and stress, maintenance of cellular integrity and extracellular matrix were markedly affected by the oxidant. All chemical stimuli (i.e., PAA, H2O2, AA) significantly affected the proliferation of nasal leukocytes, with indications of recovery observed in PAA- and H2O2-exposed cells. The migration of nasal leukocytes was promoted by H2O2, but not much by PAA and AA. The three chemical oxidative stressors triggered oxidative stress in nasal leukocytes as indicated by an increase in the intracellular reactive oxygen species level. This resulted in the mobilisation of antioxidant defences in the nasal leukocytes as shown by the upregulation of crucial genes for this response network. Though qPCR revealed changes in the expression of selected cytokines and heat shock protein genes following in vitro challenge, the responses were stochastic. The results from the study advance our understanding of the role that the nasal olfactory mucosa plays in host defence, particularly towards oxidative chemical stressors.

Is perceived safety and threat after workplace terrorism linked to employee sick-leave? A registry-based longitudinal study of governmental employees in Norway.

BACKGROUND: A large body of research has shown that terrorism enhances fears and undermines perceived safety in a high proportion of both directly exposed individuals and individuals without any form of direct exposure (i.e. no geographical proximity to an attack). Some studies have further suggested that fear of terrorism may adversely affect health in those without direct exposure and that this may constitute an important public health burden because of the number who are indirectly exposed. Limited studies have investigated threat and safety perception after workplace terrorism and the possible consequences for employee health. OBJECTIVE: To explore whether perceived safety and threat in employees whose workplace was subjected to a terrorist attack are associated with subsequent sick-leave. METHOD: A longitudinal questionnaire survey on governmental employees' perceived safety and threat at work one (T1) and two (T2) years after the 2011 terrorist attack on the Norwegian ministries was linked to registry data on doctor-certified sick-leave for two 9-month periods following T1 and T2 (N = 1703). RESULTS: There was fairly strong evidence (0.004 < p < 0.034) that higher perceived safety was associated with a close to 30% reduction in sick-leave in fully adjusted models which included terror exposure and symptom-based PTSD. There was inconclusive evidence that lower perceived threat was associated with reduced sick-leave in the full models. CONCLUSIONS: Reduced perceived safety in employees following workplace terrorism may have adverse health consequences of public health significance given how prevalent this perception seems to be. The study supports that post-terrorism response plans should include strategies on how to address the potentially large number of individuals suffering ill health after terror even if they were not directly exposed and do not meet criteria for PTSD.

Antecedentes: Una gran cuerpo de investigación ha mostrado que el terrorismo incrementa el miedo y disminuye la percepción de seguridad en gran proporción tanto en individuos directamente expuestos como también en individuos sin ninguna forma de exposición directa (es decir, sin ninguna proximidad geográfica al ataque). Algunos estudios han sugerido que el miedo al terrorismo puede afectar en forma negativa la salud de aquellos sin exposición directa y que esto puede constituir una importante carga en la salud pública, debido al número de personas expuestas indirectamente. Un limitado número de estudios han investigado la percepción de amenaza y seguridad después de terrorismo en el lugar de trabajo y sus posibles consecuencias para la salud de los empleados.Objetivo: Explorar si es que la seguridad y amenaza percibida en empleados en los cuales su lugar de trabajo fue sujeto a un acto terrorista están asociadas con permiso de ausencia por enfermedad.Método: Se conectaron los resultados de un cuestionario longitudinal sobre la seguridad y amenaza percibida en empleados gubernamentales al primer (T1) y segundo (T2) año posterior al ataque terrorista de los ministerios noruegos del año 2011 con los datos registrados de permiso de ausencia por enfermedad certificados por un médico en dos períodos de nueve meses posteriores a T1 y T2 (N=1703)Resultados: Se encontró evidencia bastante fuerte (0.004< p < 0.034) que mayor seguridad percibida se asoció con una reducción cercana al 30 por ciento en permiso por enfermedad en modelos completamente ajustados que incluían exposición al terror y TEPT basado en síntomas. Hubo evidencia poco concluyente de que menos percepción de la amenaza fue asociada con disminución en permiso por enfermedad en los modelos completos.Conclusiones: La percepción reducida de seguridad en empleados posterior a terrorismo en el lugar de trabajo puede tener consecuencias de salud adversas de relevancia para la salud pública, debido a lo prevalente que es esta percepción. Este estudio apoya la tesis de que los planes de respuesta post-terrorista debiesen incluir estrategias sobre cómo lidiar con el número potencialmente grande de personas que sufren problemas de salud después del terror, incluso si no estuvieron expuestos directamente y no cumplen con los criterios para TEPT.

Effects of exposure to workplace terrorism on subsequent doctor certified sickness absence, and the modifying role of psychological and social work factors: a combined survey and register study.

BACKGROUND: Studies have shown that terrorist attacks affect the mental and physical health of persons exposed to terrorism. When terror strikes at the workplace where people spend much time, and should feel safe, the health consequences for those affected might be severe. The aim of the study was to determine whether psychological and social work factors moderates effects of exposure to a workplace terrorist attack on subsequent doctor-certified sickness absence. METHODS: The study design combined survey data with register data on sickness absence. Data on exposure to the attack, and psychosocial working conditions were collected by a web-based questionnaire 10 months after the attack. Survey data was linked to registry data on doctor-certified sickness absence over the one-year time period following baseline. The survey response rate was 56% (n = 1974), where 80.6% (1591) gave consent to link survey data to data on sickness absence. Exposure to the attack was assessed as "Directly-", or "Indirectly exposed". Psychological and social work factors were measured by the General Questionnaire for Psychological and Social factors at Work (QPSNordic). Data were analyzed with negative binominal hurdle regressions. RESULTS: Direct exposure to the attack increased the odds of becoming sick-listed if role clarity was average (OR = 1.50) or high (OR = 2.13), but not if low (OR = 1.17). Direct exposure was associated with higher sickness absence rates if control over work pace was low (RR = 1.61). Role conflict, support from co-workers, and -superior showed weaker evidence of moderating effects of exposure on sickness absence. CONCLUSIONS: Exposure to the bomb explosion, as well as psychosocial working conditions affect the risk of employee sickness absence. Psychosocial working conditions seems to moderate effects of exposure to workplace terrorism on subsequent sickness absence. Organizations would benefit from striving for good psychological and social working conditions both as preventions against illness and sickness absence, and as measures in the aftermath of a workplace terrorist attack.

Translation and cross-cultural adaptation of the Chelsea Critical Care Physical Assessment tool into Danish.

PURPOSE: The aim of the study was to validate the Chelsea Critical Care Physical Assessment Tool (CPAx) in Danish, including translation, cross-cultural adaptation and evaluation of clinemetric properties. METHOD: International recommendations for translation and cross-cultural adaptation of outcome measures were followed. Physiotherapists with ICU experience investigated the clinemetric properties of the Danish CPAx version among 30 critically ill patients at three different ICUs. Furthermore, a focus group interview was carried out to examine cross-cultural adaptation of the CPAx tool. RESULTS: Translation and pre-test of the Danish version of CPAx resulted in a measurement tool with good clinemetric properties. Few adaptations were made with consideration of comparability between the Danish and the English version. The author of the original version of CPAx, Eve Corner, approved the Danish translation. CONCLUSION: The Danish version of the CPAx seems to be an appropriate measurement instrument for evaluation of physical function in ICU patients. This study is the first step toward a validation of a Danish version of the CPAx tool. However, further research is needed to investigate reliability and responsiveness among patients in the ICU.

How and Why to Involve Patients in Drug Development: Perspectives From the Pharmaceutical Industry, Regulatory Authorities, and Patient Organizations.

BACKGROUND: Despite increasing interest and focus on patient-centric approaches to drug development, there might still be divergent views between key stakeholders in how to perceive patient involvement and how possibly divergent views influence the role of patients in the drug development process. The objective of this study is to explore how the perception of patient organizations, pharmaceutical companies, and regulatory agencies influence the role of patients in drug development. METHOD: A qualitative interview study based on 12 semi-structured interviews with representatives from the 3 stakeholders. Interviews were transcribed, and data were analyzed using a social constructivist approach in the form of systematic text condensation. RESULTS: Three main perceptions of patient involvement were identified: "a way to improve quality of life," "a way to avoid business failure," and "a way to foster a faster drug approval process." Transparency, trust, and clarification of expectations and roles were factors perceived as prerequisites for a valuable collaboration. Furthermore, a required cultural mindset change in the pharmaceutical industry, the lack of a common framework, patient organizations having limited resources available, and concerns about what to do with patient responsibility were perceived as the most important barriers for patient involvement. CONCLUSION: Based on the findings, the pharmaceutical industry, patient organizations, and regulatory authorities were labeled as "pioneer/dominant," "unaware/quiet," and "hesitant," respectively. The 3 behavioural descriptors reflect a limited negotiation of the role patients have in drug development. Thus, the pharmaceutical industry appears to be the largest influencer with regard to patients' role in drug development.

Loneliness among adults with visual impairment: prevalence, associated factors, and relationship to life satisfaction.

BACKGROUND: Little is known about whether and to what extent loneliness impacts the lives of people with visual impairment (VI). Thus, the aim of this study was to examine the prevalence of and factors associated with loneliness in adults with VI, and to examine its association with life satisfaction. METHODS: This cross-sectional interview study included a probability sample of 736 adults (≥18 years old) with VI who were members of the Norwegian Association of the Blind and Partially Sighted. The interviews took place from January to May 2017, collecting information about sociodemographics, VI characteristics, adverse life events, loneliness (Three Item Loneliness Scale), and life satisfaction (Cantril's Ladder of Life Satisfaction). The prevalence of loneliness was compared to data obtained from the general Norwegian population (N = 14,884; mean age 46.4 years; 50.7% females). RESULTS: The prevalence of moderate and severe loneliness in the VI population was 28.7% (95% CI: 25.4, 32.1) and 19.7% (95% CI: 16.9, 22.8), respectively. The rates were consistently higher across age groups compared to the general population. Loneliness was associated with younger age, blindness, having other impairments, unemployment, and a history of bullying or abuse. In addition, higher scores on loneliness were associated with lower levels of life satisfaction (fully adjusted ß = - 0.48, 95% CI: - 0.55, - 0.41). CONCLUSIONS: Loneliness is common in adults with VI. Strategies capable of reducing loneliness could improve life satisfaction among people who are blind or visually impaired.

Employee safety perception following workplace terrorism: a longitudinal study.

Terrorism at the workplace represents an extreme form of workplace violence potentially affecting large numbers of individuals. Evidence suggests that workplace violence adversely affects employees' health and work functioning by increasing perceived threat and decreasing perceived safety. The objective of this study was to explore longitudinal associations between perceived safety at work among employees exposed to a workplace terrorist attack and their views on security measures and emergency preparedness. The study comprised a three-wave follow-up of earlier cross-sectional studies on perceived safety at work in ministerial employees exposed to a terrorist attack in Oslo, Norway, in 2011 (N = 3065). Linear mixed-effects modelling was used to explore how perceived safety at work was associated with employees' perceptions on the prioritization of security measures at work, their knowledge of evacuation procedures, and the extent of escape and evacuation training. The more employees believed security measures were sufficiently prioritized at work and the better their knowledge of evacuation procedures, the higher they rated perceived safety at work. These findings applied both across employees (between-subject effects) and within employees across time (within-subject effects). Employees' views on the extent of escape and evacuation training were not strongly associated with perceived safety at work. Secondary analysis showed that post-traumatic stress reactions were negatively associated with perceived safety at work, and that the positive association between knowledge of evacuation procedures and perceived safety at work was weaker in women and more educated employees. In conclusion, following terrorism at the workplace, employees' perceived safety at work might be increased if employers prioritize security measures and provide good information on evacuation procedures. For employees with high levels of post-traumatic stress reactions, adequate treatment of these reactions will be likely to lead to enhanced perceived safety at work.

Antecedentes: El terrorismo en el lugar de trabajo representa una forma extrema de violencia en el lugar de trabajo y puede, potencialmente, afectar a un gran número de personas. La evidencia sugiere que la violencia en el lugar de trabajo afecta negativamente la salud y el funcionamiento laboral de los empleados al aumentar la amenaza percibida y disminuir la seguridad percibida.Objetivo: Explorar las asociaciones longitudinales entre la seguridad percibida en el trabajo de los empleados expuestos a un ataque terrorista en el lugar de trabajo y sus puntos de vista sobre las medidas de seguridad y la preparación para emergencias.Método: Seguimiento de tres momentos de estudios transversales anteriores sobre la seguridad percibida en el trabajo en empleados ministeriales expuestos a un ataque terrorista en Oslo, Noruega, 2011 (N = 3065). El modelado lineal de efectos mixtos se utilizó para explorar cómo la seguridad percibida en el trabajo estaba asociada con las percepciones de los empleados sobre (i) la priorización de las medidas de seguridad en el trabajo; (ii) sus conocimientos de los procedimientos de evacuación; y (iii) el grado de entrenamiento de escape y evacuación.Resultados: Cuanto más los empleados creyeron que las medidas de seguridad se priorizaron suficientemente en el trabajo y cuanto mejor conocían los procedimientos de evacuación, más alto calificaban la seguridad percibida en el trabajo. Estos hallazgos se aplicaron tanto entre los empleados (efectos entre sujetos) como dentro de los mismos empleados a lo largo del tiempo (efectos dentro del sujeto). Los puntos de vista de los empleados sobre el alcance del entrenamiento de escape y evacuación no estaban fuertemente asociados con la percepción de seguridad en el trabajo. El análisis secundario mostró que las reacciones de estrés postraumático se asociaron negativamente con la percepción de seguridad en el trabajo, y que la asociación positiva entre el conocimiento de los procedimientos de evacuación y la seguridad percibida en el trabajo fue más débil en las mujeres y los empleados con más educación.Conclusión: Tras el terrorismo en el lugar de trabajo, la seguridad percibida de los empleados en el trabajo podría aumentar si los empleadores priorizan las medidas de seguridad y aseguran buena información sobre los procedimientos de evacuación. Para empleados con altos niveles de reacciones de estrés postraumático, el tratamiento adecuado de estas reacciones probablemente conducirá a una mayor seguridad percibida en el trabajo.

Sick leave before and after a work-place targeted terror attack.

OBJECTIVES: To estimate the rate of sick leave and sick leave diagnosis among employees before and after a work-place targeted terror attack, and to compare sick leave in subgroups of employees based on gender and trauma exposure. METHODS: Data on sick leave and diagnosis in ministerial employees from the period 3 years before to 3 years after the 2011 bombing in the governmental district of Oslo was retrieved from the Norwegian Social Insurance Administration Registries. RESULTS: Prior to the attack, sick leave was twice as high in women as in men. Compared to the period prior to the attack, sick leave increased the first year after the attack, for both women and men that were directly exposed to the event. Sick leave stabilized to the initial level 3 years after the incident. For indirectly exposed employees, i.e., those who were not present at the site of the attack, there was no significant increase in sick leave from before to after the attack. There were no statistical significant changes in diagnoses applied before and after the terrorist attack. However, there was a tendency towards an increase in sick leave due to psychological diagnoses among the directly exposed women. CONCLUSIONS: After a work-place terrorist attack a transient increase in sick leave may occur among employees who were present at the site of the attack. The increase may seem relatively modest and last for 1-3 years.

Post-traumatic stress reactions among individuals with visual impairments: a systematic review.

Purpose: To conduct a systematic review of post-traumatic stress reactions among individuals with visual impairment (VI). Materials and methods: Qualitative and quantitative studies were identified through searches in MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, and Cochrane Libraries. The literature search was limited to humans, of English and Scandinavian languages and publication year between 1980 and 2017. Study quality was assessed for all the included studies and extracted data were synthesized using narrative analysis. Results: Of 4235 records identified through literature search, eleven were included in the analyses. Results from the qualitative studies illustrated multiple physical, behavioral, emotional, and cognitive manifestations of trauma. Four out of five quantitative studies showed that various types of potentially traumatic events were significantly associated with mental health adversities (p < 0.05). The prevalence of post-traumatic mental disorders was 4-21.2% for depression, 0.9% for dysthymia, and 32% for substance misuse. The quality of the reviewed studies was considered low to moderate. Conclusion: Traumatic experiences appear to have a great impact on the mental health in people with visual impairment (VI) and these results highlight their need for mental health care. Future studies with higher methodological rigor are recommended. Implications for rehabilitation Visual impairment entails a greater susceptibility to some types of potentially traumatic events, especially threats in everyday life. This calls for a greater emphasis on safe community environments and universal design in public spaces. In rehabilitation after serious accidents or potentially traumatic events, professionals working with people with vision impairment should be aware of the different manifestations of post-traumatic stress responses and that some stress responses may cause additional disability. The high prevalence of traumatic events and their impact on mental health in individuals with visual impairments highlights a need of mental health care.