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Argues that operations strategy research should integrate recent theories from the resource-based view of strategic management. Going beyond the model of Hayes and Wheelwright, this would call for the end of the market-based view, where operations strategy merely follows the directions set by the marketing function. It would emphasize the dynamic development and leveraging of competencies and capabilities in order to set new business diversification strategies. A new paradigm of operations strategy could emerge, where "management fundamentals" such as learning and culture would be actively integrated within operations, in order to become key sources of competitive advantage. Accordingly, the operations function could progressively: take the leadership of strategy formulation; create "portfolios" of optional capabilities for strategies of organizational agility; and implement world-class practices more effectively through evolutionary strategic frameworks.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Human umbilical cord mesenchymal stromal cells possess considerable therapeutic promise for acute respiratory distress syndrome. Umbilical cord mesenchymal stromal cells may exert therapeutic effects via extracellular vesicles, while priming umbilical cord mesenchymal stromal cells may further enhance their effect. The authors investigated whether interferon-γ–primed umbilical cord mesenchymal stromal cells would generate mesenchymal stromal cell–derived extracellular vesicles with enhanced effects in Escherichia coli (E. coli) pneumonia. Methods In a university laboratory, anesthetized adult male Sprague–Dawley rats (n = 8 to 18 per group) underwent intrapulmonary E. coli instillation (5 × 109 colony forming units per kilogram), and were randomized to receive (a) primed mesenchymal stromal cell–derived extracellular vesicles, (b) naïve mesenchymal stromal cell–derived extracellular vesicles (both 100 million mesenchymal stromal cell–derived extracellular vesicles per kilogram), or (c) vehicle. Injury severity and bacterial load were assessed at 48 h. In vitro studies assessed the potential for primed and naïve mesenchymal stromal cell–derived extracellular vesicles to enhance macrophage bacterial phagocytosis and killing. Results Survival increased with primed (10 of 11 [91%]) and naïve (8 of 8 [100%]) mesenchymal stromal cell–derived extracellular vesicles compared with vehicle (12 of 18 [66.7%], P = 0.038). Primed—but not naïve—mesenchymal stromal cell–derived extracellular vesicles reduced alveolar–arterial oxygen gradient (422 ± 104, 536 ± 58, 523 ± 68 mm Hg, respectively; P = 0.008), reduced alveolar protein leak (0.7 ± 0.3, 1.4 ± 0.4, 1.5 ± 0.7 mg/ml, respectively; P = 0.003), increased lung mononuclear phagocytes (23.2 ± 6.3, 21.7 ± 5, 16.7 ± 5 respectively; P = 0.025), and reduced alveolar tumor necrosis factor alpha concentrations (29 ± 14.5, 35 ± 12.3, 47.2 ± 6.3 pg/ml, respectively; P = 0.026) compared with vehicle. Primed—but not naïve—mesenchymal stromal cell–derived extracellular vesicles enhanced endothelial nitric oxide synthase production in the injured lung (endothelial nitric oxide synthase/β-actin = 0.77 ± 0.34, 0.25 ± 0.29, 0.21 ± 0.33, respectively; P = 0.005). Both primed and naïve mesenchymal stromal cell–derived extracellular vesicles enhanced E. coli phagocytosis and bacterial killing in human acute monocytic leukemia cell line (THP-1) in vitro (36.9 ± 4, 13.3 ± 8, 0.1 ± 0.01%, respectively; P = 0.0004) compared with vehicle. Conclusions Extracellular vesicles from interferon-γ–primed human umbilical cord mesenchymal stromal cells more effectively attenuated E. coli–induced lung injury compared with extracellular vesicles from naïve mesenchymal stromal cells, potentially via enhanced macrophage phagocytosis and killing of E. coli.

BackgroundAmong patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P. aeruginosa by a Th17-mediated mechanism.ResultsExogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro.ConclusionsOur data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with P. aeruginosa in the CF lung.

Cardiography is an indispensable element of health care. However, the accessibility of at-home cardiac monitoring is limited by device complexity, accuracy, and cost. We have developed a real-time algorithm for heart rate monitoring and beat detection implemented in a custom-built, affordable system. These measurements were processed from seismocardiography (SCG) and gyrocardiography (GCG) signals recorded at the sternum, with concurrent electrocardiography (ECG) used as a reference. Our system demonstrated the feasibility of non-invasive electro-mechanical cardiac monitoring on supine, stationary subjects at a cost of $100, and with the SCG–GCG and ECG algorithms decoupled as standalone measurements. Testing was performed on 25 subjects in the supine position when relaxed, and when recovering from physical exercise, to record 23,984 cardiac cycles at heart rates in the range of 36–140 bpm. The correlation between the two measurements had r2 coefficients of 0.9783 and 0.9982 for normal (averaged) and instantaneous (beat identification) heart rates, respectively. At a sampling frequency of 250 Hz, the average computational time required was 0.088 s per measurement cycle, indicating the maximum refresh rate. A combined SCG and GCG measurement was found to improve accuracy due to fundamentally different noise rejection criteria in the mutually orthogonal signals. The speed, accuracy, and simplicity of our system validated its potential as a real-time, non-invasive, and affordable solution for outpatient cardiac monitoring in situations with negligible motion artifact.

We used differential display-PCR (DD-PCR) to identify glucocorticoid-inducible genes that regulate lung development in late gestation. DD-PCR, a method to screen for differentially expressed genes, is based on a comparison of mRNAs isolated from a subset of two or more cell populations by analysis of RT-PCR products on DNA-sequencing gels. We isolated cDNA probes representing mRNAs expressed in primary cultures of rat lung fibroblasts, but not in epithelial cells, on fetal day 20. A day 20 glucocorticoid-treated fibroblast cDNA library was screened with a single probe to isolate the 3.1-kb cDNA late-gestation lung 1( LGL1; GenBank accession no. AF109674 ) encoding a deduced polypeptide of 188 amino acids. Northern analysis confirmed that LGL1is expressed in human, rat, and mouse fetal lungs, induced by glucocorticoid, developmentally regulated in fibroblasts but not detectable in epithelium. In situ hybridization confirmed LGL1 expression in the mesenchyme, but not in the epithelium, of fetal rat lung, kidney, and gut. The predicted LGL1 gene product (lgl1) showed 81% homology to P25TI, a polypeptide trypsin inhibitor recently identified in human glioblastoma and neuroblastoma cells but not detected in normal human tissues. Both lgl1 and P25TI belong to the CRISP family of cysteine-rich extracellular proteins. Trypsin is produced by both normal bronchial epithelial and lung adenocarcinoma cells. Although additional studies will be necessary to clearly establish a functional role for lgl1, we propose that lgl1 has a role in normal lung development that is likely to be via regulation of extracellular matrix degradation.

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The glucocorticoids (GC) and retinoids (RA) modulate branching morphogenesis and cytodifferentiation in the developing lung. We investigated downstream target genes that link glucocorticoid stimulation to the achievement of a mature lung in glucocorticoid receptor (GR) knockout mice. All GR(null) mice and approximately 80% of mice homozygous for a hypomorphic allele (GR(hypo)) die shortly after birth of respiratory failure. cDNA microarray analysis showed organ-specific upregulation of the retinoic acid responsive gene midkine (MK) and its chondroitin-sulfate binding partner PG-M/versican at fetal day 18 and at neonatal day 1 in lungs of GR(hypo) mice, and at neonatal day 1 in lungs of GR(null) mice. By contrast, lung MK and PG-M/versican were downregulated in these mice at fetal day 16.5. In situ hybridization studies showed a dramatic decrease in MK and PG-M/versican RNA between days 16.5 and 17.5 in GR(WT) but not in GR(null) mice. Continued diffuse and robust expression of MK protein was observed in GR(null) mice at neonatal day 1. These findings suggest that MK may contribute to the dysmature lung phenotype in GR-deficient mice. Exposure of cultured day 21 fetal rat lung cells to GC downregulated MK, whereas RA enhanced MK expression. Our findings demonstrate the coincident modulation of expression of MK at the same developmental time point by both GC and RA, providing a potential mechanism for the integration of GC and RA effects on fetal lung development.