While systematic literature reviews (SLRs) have contributed substantially to developing knowledge in fields such as medicine, they have made limited contributions to developing knowledge in the ...supply chain management domain. This is due to the ontological and epistemological idiosyncrasies of research in supply chain management, which need to be accounted for when retrieving, selecting, and synthesizing studies in an SLR. Therefore, we propose a new paradigm for SLRs in the supply chain domain that is based on both best practice and the unique attributes of doing supply chain management research. This approach involves exploring existing studies with attention to theoretical boundaries, units of analysis, sources of data, study contexts, and definitions and the operationalization of constructs, as well as research methods, with the goal of refining or revising existing theory. This new paradigm will push supply chain management research to the frontier of current methodological standards and build a foundation for improving the contribution of future SLRs in the supply chain and adjacent management disciplines.
Purpose
– The purpose of this research is to explore the resilience domain, which is important in the field of supply chain management; it investigates the effects relational competencies have for ...resilience and the effect resilience, in turn, has on a supply chain
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s customer value.
Design/methodology/approach
– The research is empirical in nature and employs a confirmatory approach that builds on the relational view as a primary theoretical foundation. It utilizes survey data collected from manufacturing firms from three countries, which is analyzed using structural equation modeling.
Findings
– It is found that communicative and cooperative relationships have a positive effect on resilience, while integration does not have a significant effect. It is also found that improved resilience, obtained by investing in agility and robustness, enhances a supply chain
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s customer value.
Practical implications
– Some findings contrast the expectations derived from theory. Particularly, practitioners can learn that integration has a limited role in enhancing resilience.
Originality/value
– The study distinguishes between a proactive and reactive dimension of resilience: robustness and agility. The relational view serves as the theoretical basis to explain the effects between three types of relational competencies (communication, cooperation, and integration) and the above-mentioned two dimensions of resilience.
Most of the theories that have dominated supply chain management (SCM) take a reductionist and static view on the supply chain and its management, promoting a global hunt for cheap labor and ...resources. As a result, supply chains tend to be operated without much concern for their broader contextual environment. This perspective overlooks that supply chains have become both vulnerable and harmful systems. Recent and ongoing crises have emphasized that the structures and processes of supply chains are fluid and interwoven with political‐economic and planetary phenomena. Building on panarchy theory, this article reinterprets the supply chain as a social–ecological system and leaves behind a modernist view of SCM, replacing it with a more contemporary vision of “dancing the supply chain.” A panarchy is a structure of adaptive cycles that are linked across different levels on scales of time, space, and meaning. It represents the world’s complexities more effectively than reductionist and static theories ever could, providing the basis for transformative SCM.
Purpose
This study aims to enhance the understanding of competency requirements of supply chain planners and analysts (SCP&As) and identify different personal preferences of hiring managers toward ...job candidates’ competency profiles.
Design/methodology/approach
A total of 243 supply chain managers with hiring experience participated in an adaptive choice-based conjoint experiment to uncover the relative importance of six competency attributes, namely, analytical and problem-solving ability, interpersonal skills, general management skills, computer/IT skills, supply chain management (SCM) knowledge and industry experience.
Findings
SCM knowledge and analytical and problem-solving ability were identified as the most important competencies and were considered three times more important than general management skills. Based on convergent cluster and ensemble analysis, two types of hiring managers were identified. The first group is characterized by a pronounced preference for job candidates with extensive SCM knowledge. In contrast, the second group’s members prefer candidates with a more balanced competency profile.
Originality/value
The authors’ findings help companies to facilitate a better person–job fit, a key determinant of employee performance and job satisfaction.
Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help ...to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
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•Integrative analysis of orthogonal data on response to vaccination•Strong association between plasma metabolomics and PBMC transcriptomics•Sterol metabolism integrates cellular and humoral responses•Metabolic phenotype, such as inositol phosphate metabolism, influences immune outcome
An integrated metabolic response underlies the immune response to shingles vaccine in humans.
Human papillomaviruses (HPVs) are the causative agent of several anogenital cancers as well as head and neck cancers, with HPV+ head and neck squamous cell carcinoma (HNSCC) becoming a rapidly ...growing public health issue in the Western world. Due its viral etiology and potentially its subanatomical location, HPV+ HNSCC exhibits an immune microenvironment which is more inflamed and thus distinct from HPV-negative HNSCC. Notably, the antigenic landscape in most HPV+ HNSCC tumors extends beyond the classical HPV oncoproteins E6/7 and is extensively targeted by both the humoral and cellular arms of the adaptive immune system. Here, we provide a comprehensive overview of HPV-specific immune responses in patients with HPV+ HNSCC. We highlight the localization, antigen specificity, and differentiation states of humoral and cellular immune responses, and discuss their similarities and differences. Finally, we review currently pursued immunotherapeutic treatment modalities that attempt to harness HPV-specific immune responses for improving clinical outcomes in patients with HPV+ HNSCC.
Purpose
– The purpose of this paper is to provide groundwork for an emerging theory of supply chain robustness – which has been conceptualized as a dimension of supply chain resilience – through ...reviewing and synthesizing related yet disconnected studies. The paper develops a formal definition of supply chain robustness to build a framework that captures the dimensions, antecedents and moderators of the construct as discussed in the literature.
Design/methodology/approach
– The authors apply a systematic literature review approach. In order to reduce researcher bias, they involve a team of academics, librarians and managers.
Findings
– The paper first, provides a formal definition of supply chain robustness; second, builds a theoretical framework of supply chain robustness that augments both causal and descriptive knowledge; third,shows how findings in this review support practice; and fourth,reveals methodological insights on the use of journal rankings in reviews.
Research limitations/implications
– At this stage, managers may benefit from seeing these relationships as clues derived from the literature. The paper is fundamentally a call for researchers to conduct quantitative testing of such relationships to derive more reliable understanding and practical applications.
Practical implications
– Rather than presenting empirical findings, this paper reveals to managers that visibility, risk management orientation and reduced network complexity have been the main predictive antecedents of supply chain robustness (as discussed in the academic literature). This provides a potentially important signal as to where to invest resources.
Originality/value
– The study is the first to develop a formal definition of supply chain robustness and to establish a comprehensive theoretical framework for understanding the construct.
T cell exhaustion is a state of T cell dysfunction associated with expression of programmed death 1 (PD-1). Exhausted CD8+ T cells are maintained by self-renewing stem-like T cells that provide ...differentiated TIM3+ cells, a part of which possesses effector-like properties. PD-1-targeted therapies enhance T cell response by promoting differentiation of stem-like T cells toward TIM3+ cells, but the role of mTOR during T cell exhaustion remains elusive. Here, we showed that mTOR inhibition has distinct outcomes during the beginning of and after the establishment of chronic viral infection. Blocking mTOR during the T cell expansion phase enhanced the T cell response by causing accumulation of stem-like T cells, leading to improved efficacy of PD-1 immunotherapy; whereas, after exhaustion progressed, mTOR inhibition caused immunosuppression, characterized by decreased TIM3+ cells and increased viral load with minimal changes in stem-like T cells. Mechanistically, a cell-intrinsic mTOR signal was vital for differentiation of stem-like T cells into the TIM3+ state in the early and late phases of chronic infection as well as during PD-1 immunotherapy. Thus, PD-1 blockade worked after cessation of mTOR inhibition, but simultaneous treatment failed to induce functional TIM3+ cells, reducing efficacy of PD-1 immunotherapy. Our data demonstrate that mTOR regulates T cell exhaustion and have important implications for combination cancer therapies with PD-1 blockade.
BackgroundRadiotherapy (RT) has been shown to stimulate an antitumor immune response in irradiated tumors as well as unirradiated distant sites (abscopal effect). Previous studies have demonstrated a ...role for the tumor-draining lymph node (LN) in mediating an anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) stimulated antitumor immune response. Here, we investigated whether the LN is also important in mediating a RT alone stimulated abscopal response.MethodsWe used a subcutaneous modified B16F10 flank tumor model injected bilaterally. Our B16F10 cell line has an inserted viral glycoprotein which facilitated identification of tumor-specific T-cells. RT was directed at one flank tumor alone or one flank tumor and the tumor-draining LN. We evaluated response by tumor growth measurements and flow cytometry of both tumor-infiltrating and LN T-cells.ResultsWe show that local tumor irradiation improves distant tumor control (abscopal effect). Depletion of CD8+ T-cells significantly reduced this abscopal response. We have previously shown, in a chronic lymphocytic choriomeningitis virus (LCMV) infection, that the T-cell proliferative burst following blockade of PD-1/L1 is provided by a ‘stem-like’ CD8+ T-cell subset which then differentiate into terminally differentiated effectors. These terminally differentiated effectors have the potential to kill virally infected or tumor cells following PD-1/L1 blockade. In the chronic LCMV infection, stem-like CD8+ T-cells were found exclusively in secondary lymphoid organs. Similarly, here we found these cells at high frequencies in the tumor-draining LN, but at low frequencies within the tumor. The effect of RT on this T-cell subset in unknown. Interestingly, tumor irradiation stimulated total CD8+ and stem-like CD8+ T-cell proliferation in the LN. When the LN and the tumor were then targeted with RT, the abscopal effect was reduced, and we found a concomitant reduction in the number of total tumor-specific CD8+ T-cells and stem-like CD8+ T-cells in both the irradiated and unirradiated tumor.ConclusionsThese correlative results suggest the tumor-draining LN may be an important mediator of the abscopal effect by serving as a stem-like CD8+ T-cell reservoir, a site for stem-like T-cell expansion, and a site from which they can populate the tumor.
MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8 ⁺ T-cell response are not well understood. Using an acute viral infection ...model, we show that microRNAs of the miR-17-92 cluster are strongly induced after T-cell activation, down-regulated after clonal expansion, and further silenced during memory development. miR-17-92 promotes cell-cycle progression of effector CD8 ⁺ T cells, and its expression is critical to the rapid expansion of these cells. However, excessive miR-17-92 expression enhances mammalian target of rapamycin (mTOR) signaling and strongly skews the differentiation toward short-lived terminal effector cells. Failure to down-regulate miR-17-92 leads to a gradual loss of memory cells and defective central memory cell development. Therefore, our results reveal a temporal expression pattern of miR-17-92 by antigen-specific CD8 ⁺ T cells during viral infection, the precise control of which is critical to the effector expansion and memory differentiation of CD8 ⁺ T cells.
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