Theorizing with managers: how to achieve both academic rigor and practical relevance?

Purpose. There are heightened concerns that the theory-praxis gap is widening, despite decades of academic literature addressing the issue. We propose that one viable solution to this challenge is involving practitioners in research processes as active, reflective and empowered participants. Most extant discussions addressing the inclusion of managers as partners in theorizing restrain themselves to an ‘if’ question, arguing whether or not it is possible to create sufficiently rigorous knowledge in collaboration with practitioners. This leaves the ‘how’ question unanswered, i.e., how should such gap-bridging research be conducted in practice. Thus, the aim of this paper is to investigate how academic researchers in management and marketing can theorize with managers in order to generate results that are both academically rigorous and managerially relevant. Design/methodology/approach. Based on a literature review of collaborative theorizing processes, we develop a conceptual framework highlighting the main research design decisions when theorizing with managers. The use of the framework is illustrated with four research program examples. Findings. Most accounts of theorizing with managers use – explicitly or implicitly – abduction as the main mode of inference. In addition to this philosophical commonality, our literature review identified twelve themes that should be considered when designing collaborative research processes. The four illustrative examples indicate that theorizing with managers is an effective way of producing and socializing both academically sound and managerially relevant knowledge. On the other hand, collaborative theorizing processes are time-consuming and studies using abductive reasoning may be more challenging to publish in top-tier journals. Originality/value. This paper makes two contributions. First, we go beyond the extensive academic literature which provides a plethora of explanations and ideas for potential remedies for bridging the theory-praxis gap by offering a detailed description how one particular solution, theorizing with managers, unfolds in practice. Second, we ground collaborative theorizing processes in the philosophy of science and put abduction forward as a common nominator for such studies

New directions for service research: refreshing the process of theorizing to increase contribution

Purpose – For service research to develop as an applied social science there is the need to refresh the process of theorizing so it focuses not only on increasing new academic knowledge but also on knowledge that is managerially relevant. Guidelines are provided to achieve this.Design/methodology/approach – A theorizing process that integrates general theoretic perspectives and contextual research to develop midrange theory is developed. The process is based on the philosophical foundations of pragmatism and abductive reasoning, which has their origins in the 1950s when the management sciences were being established.Findings –A recent research stream that develops midrange theory about customer and actor engagement is used to illustrate the theorizing process.Practical Implications – Practicing managers, customers and other stakeholders in a service system use theory, so there is a need to focus on how theory is used in specific service contexts and how this research leads to academic knowledge that is managerially relevant. Thus, as applied social science, service research needs to explicitly focus on bridging the theory-praxis gap with midrange theory byincorporating a general theoretic perspective and contextual research.Originality/value - The contribution comes from providing a broader framework to guide the theorizing process that integrates general theoretic perspectives and applied research to develop midrange theory. While general theories operate at the most abstract level of conceptualization midrange theories are context-specific, and applied theory (theories-in-use) embedded in empirical researc

Theorizing with managers to bridge the theory-praxis gap: foundations for a research tradition

Purpose –To refine an agenda concerning the theory-praxis gap in order to develop a foundation for a research tradition. Approach – We synthesize and build on the suggestions the suggestions in commentary articles by Kohli (2017), Leeflang (2017) and Möller (2017). Findings – We develop a research agenda consisting of issues. 1. The need for a systemic view of business practice 2. The need for innovative and meaningful theoretical understanding 3. The need to identify conditions and approaches for collaborative theorizing 4. To further define and instruct the abductive approach 5. To explore pragmatic realism to ensure both practical outcomes and truthful theories Originality/value – The five issues are a step towards developing a theory-praxis research tradition

Phosphodiesterase 1b (PDE1B) Regulates Spatial and Contextual Memory in Hippocampus

Augmentation of cyclic nucleotide signaling through inhibition of phosphodiesterase (PDE) activity has long been understood to enhance memory. Efforts in this domain have focused predominantly on PDE4, a cAMP-specific phosphodiesterase implicated in consolidation. But less is known about the function of other PDEs expressed in neuroanatomical regions critical to memory. The PDE1 isoforms are the only PDEs to regulate neuronal cAMP and cGMP levels in a Ca2+/Calmodulin (CaM) dependent manner. Here, we show that knock-down of PDE1B in hippocampus of adult mice enhances contextual and spatial memory without effect on non-cognitive behaviors. Pharmacological augmentation of memory in rats was observed with a selective inhibitor of PDE1 dosed before and immediately after training, but not with drug dosed either 1 h after training or before recall. Our data clearly demonstrate a role for the PDE1B isoforms as negative regulators of memory, and they implicate PDE1 in an early phase of consolidation, but not retrieval. Inhibition of PDE1B is a promising therapeutic mechanism for treating memory impairment

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Theorizing about resource integration through service-dominant logic

Resource integration, as it relates to value creation, has recently been a key aspect of the discussions about service-dominant (S-D) logic. However, the majority of research pays relatively little explicit attention to the process of theorizing and the epistomological and ontological assumptions upon which the theorizing process is based. This article addresses these issues. The processes that relate to theorizing and developing strong theory are discussed. We then examine how to conceptualize ‘resources’ and ‘resource integration’ following differing ontological and epistemological assumptions that guide the theorizing process. Research recommendations to help navigate through the finer details underlying the theorizing process and to advance a general theory of resource integration are developed

Baseline and early digital [¹⁸F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients:a pilot study

Objective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. Methods Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [18F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected. Results Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. Conclusion Both multiparametric MRI and [18F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.</p

Differentially expressed alternatively spliced genes in Malignant Pleural Mesothelioma identified using massively parallel transcriptome sequencing

<p>Abstract</p> <p>Background</p> <p>Analyses of Expressed Sequence Tags (ESTs) databases suggest that most human genes have multiple alternative splice variants. The alternative splicing of pre-mRNA is tightly regulated during development and in different tissue types. Changes in splicing patterns have been described in disease states. Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4 malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal lung. We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples.</p> <p>Methods</p> <p>We developed a software pipeline to map the transcriptome read sequences of the 4 MPM samples and 1 normal lung sample onto known exon junction sequences in the comprehensive AceView database of expressed sequences and to count how many reads map to each junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing platform for 5 samples were compared with 151,486 exon junctions from the AceView database. The exon junction expression index (EJEI) was calculated for each exon junction in each sample to measure the differential expression of alternative splicing events. Top ten exon junctions with the largest EJEI difference between the 4 mesothelioma and the normal lung sample were then examined for differential expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples. Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05) were further examined with qRT-PCR in additional 18 MPM and 18 normal lung specimens.</p> <p>Results</p> <p>We found 70,953 exon junctions covered by at least one sequence read in at least one of the 5 samples. All 10 identified most differentially expressed exon junctions were validated as present by RT-PCR, and 8 were differentially expressed exactly as predicted by the sequence analysis. The differential expression of the AceView exon junctions for the ACTG2 and CDK4 genes were also observed to be statistically significant in an additional 18 MPM and 18 normal lung samples examined using qRT-PCR. The differential expression of these two junctions was shown to successfully classify these mesothelioma and normal lung specimens with high sensitivity (89% and 78%, respectively).</p> <p>Conclusion</p> <p>Whole-transcriptome shotgun sequencing, combined with a downstream bioinformatics pipeline, provides powerful tools for the identification of differentially expressed exon junctions resulting from alternative splice variants. The alternatively spliced genes discovered in the study could serve as useful diagnostic markers as well as potential therapeutic targets for MPM.</p

VASP: A Volumetric Analysis of Surface Properties Yields Insights into Protein-Ligand Binding Specificity

Many algorithms that compare protein structures can reveal similarities that suggest related biological functions, even at great evolutionary distances. Proteins with related function often exhibit differences in binding specificity, but few algorithms identify structural variations that effect specificity. To address this problem, we describe the Volumetric Analysis of Surface Properties (VASP), a novel volumetric analysis tool for the comparison of binding sites in aligned protein structures. VASP uses solid volumes to represent protein shape and the shape of surface cavities, clefts and tunnels that are defined with other methods. Our approach, inspired by techniques from constructive solid geometry, enables the isolation of volumetrically conserved and variable regions within three dimensionally superposed volumes. We applied VASP to compute a comparative volumetric analysis of the ligand binding sites formed by members of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains and the serine proteases. Within both families, VASP isolated individual amino acids that create structural differences between ligand binding cavities that are known to influence differences in binding specificity. Also, VASP isolated cavity subregions that differ between ligand binding cavities which are essential for differences in binding specificity. As such, VASP should prove a valuable tool in the study of protein-ligand binding specificity

Intraplaque haemorrhage quantification and molecular characterisation using attention based multiple instance learning

Intraplaque haemorrhage (IPH) represents a critical feature of plaque vulnerability as it is robustly associated with adverse cardiovascular events, including stroke and myocardial infarction. How IPH drives plaque instability is unknown. However, its identification and quantification in atherosclerotic plaques is currently performed manually, with high inter-observer variability, limiting its accurate assessment in large cohorts. Leveraging the Athero-Express biobank, an ongoing study comprising a comprehensive dataset of histological, transcriptional, and clinical information from 2,595 carotid endarterectomy patients, we developed an attention-based additive multiple instance learning (MIL) framework to automate the detection and quantification of IPH across whole-slide images of nine distinct histological stains. We demonstrate that routinely available Haematoxylin and Eosin (H&E) staining outperformed all other plaque relevant Immunohistochemistry (IHC) stains tested (AUROC = 0.86), underscoring its utility in quantifying IPH. When combining stains through ensemble models, we see that H&E + CD68 (a macrophage marker) as well as H&E + Verhoeff-Van Gieson elastic fibers staining (EVG) leads to a substantial improvement (AUROC = 0.92). Using our model, we could derive IPH area from the MIL-derived patch-level attention scores, enabling not only classification but precise localisation and quantification of IPH area in each plaque, facilitating downstream analyses of its association and cellular composition with clinical outcomes. By doing so, we demonstrate that IPH presence and area are the most significant predictors of both preoperative symptom presentation and major adverse cardiovascular events (MACE), outperforming manual scoring methods. Automating IPH detection also allowed us to characterise IPH on a molecular level at scale. Pairing IPH measurements with single-cell transcriptomic analyses revealed key molecular pathways involved in IPH, including TNF-α signalling, extracellular matrix remodelling and the presence of foam cells. This study represents the largest effort in the cardiovascular field to integrate digital pathology, machine learning, and molecular data to predict and characterize IPH which leads to better understanding how it drives symptoms and MACE. Our model provides a scalable, interpretable, and reproducible method for plaque phenotyping, enabling the derivation of plaque phenotypes for predictive modelling of MACE outcomes