Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Challenge and hindrance appraisals of job demands: one man’s meat, another man’s poison?

Background and objectives: Many job stress models assume that all workers experience a particular job demand in the same way–an assumption that may or may not be warranted and that has rarely been tested. Building on appraisal theory, we explore (a) how individuals appraise particular job demands (i.e., as a challenge or as a hindrance) and (b) how these appraisals affect the relationship between job demands and engagement/burnout. Design and Methods: A multi-occupation cross-sectional study was conducted among 527 Chinese workers (321 females, 60.9%; Mage = 32.74, SD = 6.70). The data were analyzed using hierarchical multiple regression analysis. Results: We found that the appraisal of job demands (time urgency, role conflict, and emotional demands) as a challenge moderated the associations between these demands and burnout/engagement. Generally, the results indicate that the presence of high job demands was associated with negative outcomes. However, these detrimental effects were weaker if workers appraised these characteristics as being high-challenge. Conclusions: This study extends research on job demands within the challenge–hindrance framework by focusing on the moderating effects of appraisals. Given the important role of appraisal, we conclude that researchers should include appraisal more systematically in their theorizing and research on the effects of job demands on well-being

The fun and frustration of modern working life: Contributions from an occupational health psychology perspective

Festschrift for prof.dr. Wilmat Schaufel

Feeling vital or fatigued? Relations with demands and resources in a university context

This study examines whether specific (matching) combinations of demands and resources exist in the prediction of both positive and negative outcomes (i.e., vitality and fatigue) in a university context. In addition, we test the Demand-Induced Strain Compensation (DISC) Model's key principles in this context to study its relevance, validity, and generalizability. A cross-sectional survey study was conducted among 397 employees and 497 students at a Dutch university. Hierarchical multiple regression analyses among both employees and students showed matching combinations of demands and resources in the prediction of vitality and fatigue. Specifically, an increase in cognitive demands was particularly associated with more student cognitive vitality when cognitive resources were high. Furthermore, results showed that an increase in cognitive demands was related to less cognitive fatigue in both employees and students when cognitive resources were high. Findings partly confirm our hypotheses in showing the important role of matching resources in the relation between demands and vitality and fatigue in university staff and students. Our study reveals that a sustainable work environment is about maintaining a healthy balance between sufficient, matching resources and demands at work or study

Employee sustainable performance (E-super): Theoretical conceptualization, scale development, and psychometric properties

Although the concept of employee sustainable performance has received considerable attention in the practitioner literature, academic research still lacks a clear conceptualization and empirical operationalization of this concept. Defining employee sustainable performance as a regulatory process in which an individual worker enduringly and efficiently achieves particular desired work goals while maintaining a satisfactory level of well-being, this paper describes a corresponding instrument called E-SuPer, and examines its psychometric properties. The E-SuPer instrument was tested and cross-validated using two cross-sectional survey studies (n = 153 and n = 160), focusing on factorial validity, internal consistency, and discriminant and concurrent validity. Psychometric findings across the two samples revealed that the E-SuPer instrument consists of one general factor of ten items with good internal consistency. Discriminant validity and concurrent validity with other relevant constructs (task performance, counterproductive work behavior, and employee vitality) were also confirmed, showing promising results. Finally, theoretical and practical implications, as well as suggestions for future research, are outlined

Country differences in the relationship between leadership and employee engagement: A meta-analysis

Leadership is frequently related to important organizational outcomes such as follower engagement. However, to date we have little insight into the degree to which this relation is contingent upon (a) types of leadership style and (b) national culture. These two issues are addressed in a meta-analysis of 209 independent (257 effect sizes), mainly cross-sectional studies (79%), involving 82,386 participants from 45 countries. The findings show that whereas abusive supervision was negatively associated with work engagement, several leadership styles (e.g., servant, empowering, ethical, and charismatic leadership) have positive correlations with subordinate engagement; some dimensions of national culture (e.g., gender egalitarianism, human orientation, performance orientation, future orientation, and power distance) moderate the leadership–employee engagement relationship. However, the correlations between servant, ethical, and transactional leadership and subordinate engagement are less likely to vary across national cultural characteristics. Notwithstanding the proliferation of leadership–employee engagement literature with more than 200 published articles, a strong reliance on cross-sectional designs have impeded it to gain any solid conclusions about causality due to endogeneity biases. We conclude by providing a detailed future research agenda and discussing how our results can stimulate future leadership research and inform practices with regards to leader development

Walking the Tightrope between Work and Home: The Role of Job/Home Resources in the Relation between Job/Home Demands and Employee Health and Well-being

The present study investigated the role of job/home resources in the relation between job/home demands and exhaustion, job satisfaction, work-home interference, and home-work interference during the COVID-19 pandemic. We explored the prevalence of job/home demands and resources during the COVID-19 pandemic, and examined whether working at different locations (i.e., working from home or at the office) affects how both job/home demands and resources are associated with employees' health and well-being. An online cross-sectional survey study using self-report questionnaires was carried out among the networks of the International Commission on Occupational Health (ICOH) association (N=153). The findings of this study illustrated that (1) cognitive job demands/resources and emotional home demands/resources were crucial in predicting employee health and well-being; (2) a conceptual match was detected between corresponding demands and resources; (3) subgroup analysis showed that employees were not heavily affected by the different working locations during the pandemic. In conclusion, this study confirms the positive role of job/home resources. We suggest that cultivating specific job/home resources and establishing an appropriate match between specific job/home resources and corresponding job/home demands is necessary to ensure employees' health and well-being in times of a pandemic

Authenticity at Work : A Matter of Fit?

Authenticity at work refers to the extent to which a worker feels in touch with their true self while at work. At first sight this concept seems to overlap with the concept of person-environment (P-E) fit, that is, the degree to which an individual experiences good fit with their work environment. Drawing on a sample of 867 Dutch gifted workers, structural equation modeling was used to investigate (i) whether authenticity at work and P-E fit can be distinguished, and (ii) how authenticity at work and P-E fit were associated with employee well-being. As expected, confirmatory factor analysis revealed that authenticity at work and P-E fit were distinct from each other. Moreover, the mediated effect of authenticity at work was stronger for two negative forms of well-being (burnout and boredom) than for two positive forms of well-being (work engagement and job satisfaction). The theoretical and practical implications of these findings are discussed, especially focusing on the distinction between authenticity and P-E fit