Chapter 2 Getting everyone on the same page

In designing, implementing, and evaluating organizational interventions, program logic plays a central role as it outlines the core components of the intervention and links them to both proximal and distal outcomes. Also, central in the design, implementation, and evaluation of organizational interventions is the engagement of stakeholders across the organization (employees, managers, and specialists). Concrete tools are lacking for stakeholders to be engaged in the design of interventions and in defining criteria that can guide evaluation. This chapter outlines a structured process – the cocreated program logic (COP) process – for how organizational stakeholders can be involved in defining intervention goals and activities and thus forming the program logic together with interventionists (researchers or consultants). The program logic can then be used to guide the evaluation of the organizational intervention. The authors present two cases illustrating how the COP process has been used in their reserach. The chapter ends with lessons learned

Biased and g protein-independent signaling of chemokine receptors

Biased signaling or functional selectivity occurs when a 7TM receptor preferentially activates one of several available pathways. It can be divided into three distinct forms: ligand bias, receptor bias, and tissue or cell bias, where it is mediated by different ligands (on the same receptor), different receptors (with the same ligand) or different tissues or cells (for the same ligand-receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may not be absolute, i.e. full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of classic redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where a single chemokine may bind to several receptors – in both cases with the same functional outcome. The ubiquitous biased signaling confer a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles and different functional outcomes in a ligand-, receptor- or cell/tissue-defined manner. As the low number of successful drug development plans implies, there are great difficulties in targeting chemokine receptors; in particular with regard to receptor antagonists as anti-inflammatory drugs. Un-defined and putative non-selective targeting of the complete cellular signaling system could be the underlying cause of lack of success. Therefore, biased ligands could be the solution

Basin level ecological regions of the upper Grande Ronde River

Ecological regionalization is a form of spatial classification, where boundaries are drawn around areas relatively homogeneous in landscape characteristics. In the delineation of ecological regions, or ecoregions, the process includes the analysis of ecosystem structure and function. Ecoregions have been developed at national and state scales for research and resource management. Stream classification is another method to order the variability of aquatic habitats, that spans spatial scales from microhabitat to valley segment. In this study, ecoregions are developed at the scale of a large watershed (3000 square kilometers), the upper Grande Ronde River basin in northeastern Oregon. The ecoregion framework presented here is proposed to bridge the gap between stream and ecoregions classification. The classification at this scale is meant to address issues of management at local scales: to aid in sample design, extrapolation of the results of site-specific studies and the development of best management practices that are predictive of ecosystem response

All by myself: How perceiving organizational constraints when others do not hampers work engagement

Organizational constraints (OCs) represent work conditions that interfere with employees’ performance. Although employees share the same work environment, perceptions of OCs may vary among team members. In this study, we examined employee–teammate perceptual congruence and incongruence regarding three types of OCs (i.e., social, structural, and infrastructure) and the associated consequences for employee work engagement among health care employees from two Spanish hospitals (N = 141). Multilevel polynomial regression with response surface analyses revealed that the perceptual congruence and incongruence effects depended on the type of OCs. Congruence in perceptions was linked with greater work engagement only for social OCs. Incongruence had an effect in cases of social and structural OCs, but not infrastructure OCs: work engagement was worse when an employee rated OCs as higher (i.e., more problematic) than their teammates did. Our findings suggest that the negative effects of OCs are additionally exacerbated by perceptual incongruence with teammates and indicate the need to include social contexts in the study of work environment perceptions

Beyond the individual: A systematic review of the effects of unit-level demands and resources on employee productivity, health, and well-being

Creating sustainable employment—that is, a condition in which employees remain productive but also enjoy good health and well-being—is a challenge for many organizations. Work environment factors are major contributors to these employee outcomes. The job demands–resources model categorizes work environment factors into demands versus resources, which are, respectively, detrimental versus beneficial to employee outcomes. Although conceptualized as workplace factors, these job characteristics have been studied mostly at an individual level. Therefore, their roles at the supraindividual level (i.e., any work-unit level above an individual, such as group or organization) for employee productivity, health, and well-being remains unclear. The aim of this systematic review is to synthesize evidence concerning job resources and job demands at the supraindividual level and their relationships to productivity, health, and work-related well-being. The review covers articles published through December 2018. In total, 202 papers met the inclusion criteria. We found stronger support for the beneficial roles of supraindividual job resources than for the detrimental roles of job demands for productivity and work-related well-being. Regarding health, most of the relationships were found to be nonsignificant. To conclude, this review demonstrates that, at the supraindividual level, the motivational path has received more support than the health impairment path. Based on these findings, we provide recommendations for further research and practice

Prognostic Impact of Active Mechanical Circulatory Support in Cardiogenic Shock Complicating Acute Myocardial Infarction, Results from the Culprit-Shock Trial

Objectives: To analyze the use and prognostic impact of active mechanical circulatory support (MCS) devices in a large prospective contemporary cohort of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Background: Although increasingly used in clinical practice, data on the efficacy and safety of active MCS devices in patients with CS complicating AMI are limited. Methods: This is a predefined subanalysis of the CULPRIT-SHOCK randomized trial and prospective registry. Patients with CS, AMI and multivessel coronary artery disease were categorized in two groups: (1) use of at least one active MCS device vs. (2) no active MCS or use of intra-aortic balloon pump (IABP) only. The primary endpoint was a composite of all-cause death or renal replacement therapy at 30 days. Results: Two hundred of 1055 (19%) patients received at least one active MCS device (n = 112 Impella®; n = 95 extracorporeal membrane oxygenation (ECMO); n = 6 other devices). The primary endpoint occurred significantly more often in patients treated with active MCS devices compared with those without active MCS devices (142 of 197, 72% vs. 374 of 827, 45%; p < 0.001). All-cause mortality and bleeding rates were significantly higher in the active MCS group (all p < 0.001). After multivariable adjustment, the use of active MCS was significantly associated with the primary endpoint (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.7–5.9; p < 0.001). Conclusions: In the CULPRIT-SHOCK trial, active MCS devices were used in approximately one fifth of patients. Patients treated with active MCS devices showed worse outcome at 30 days and 1 year

Release of extracellular membrane vesicles from microvilli of epithelial cells is enhanced by depleting membrane cholesterol

AbstractWe previously reported on the occurrence of prominin-1-carrying membrane vesicles that are released into body fluids from microvilli of epithelial cells. This release has been implicated in cell differentiation. Here we have characterized these vesicles released from the differentiated Caco-2 cells. We find that in these vesicles, prominin-1 directly interacts with membrane cholesterol and is associated with a membrane microdomain. The cholesterol depletion using methyl-β-cyclodextrin resulted in a marked increase in their release, and a dramatic change in the microvillar ultrastructure from a tubular shape to a “pearling” state, with multiple membrane constrictions, suggesting a role of membrane cholesterol in vesicle release from microvilli

Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study

Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies

The natural history of epilepsy in tuberous sclerosis complex

Background: Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease. Methods: A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox-Gastaut syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment, and genetic mutation. Results: Two hundred ninety-one patients were included. Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure; 54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset in the first year of life; and 12.1% of adults without a seizure history developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and 33.5% achieved epilepsy remission; 37.5% of these patients achieved medication freedom. IS was a risk factor for refractory epilepsy (p<0.0001) and LGS (p<0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy each correlated with poor cognitive outcome (p<0.0001). Epilepsy remission correlated with better cognitive outcome (p<0.0001). TSC2 was a risk factor for IS and epilepsy; patients without an identified mutation were more likely to achieve remission. Conclusion: Most patients with TSC develop epilepsy and most develop multiple seizure types. Onset typically occurs in the first year of life; however, adults remain at risk. Although refractory epilepsy is common, many patients achieve seizure control. Many features of seizure history are predictive of cognitive and epilepsy outcome