Background The lung microbiome’s contribution to IPF pathogenesisis unknown. Using COMET-IPF (Correlating Outcomes with biochemical Markers to Estimate Time-progression in Idiopathic Pulmonary Fibrosis), the goal of this study was to determine whether unique microbial signatures would associate with disease progression. Methods IPF subjects within four years of diagnosis aged 35–80 were eligible for inclusion. Subjects were followed for up to a maximum of 80 weeks. This completed observational study is registered with ClinicalTrials.gov, number NCT01071707. Progression-free survival was defined as death, acute exacerbation, lung transplant, or decline in FVC of 10% or DLCO of 15%.DNA was isolated from 55 bronchoscopic alveolar lavage (BAL) samples. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) based on a 3% sequence divergence. Adjusted Cox models identified OTUs significantly associated with progression-free survival at a p<0·10 level. These OTUs were then used in principal components (PC) analysis. The association between PCs and microbes with high factor loadings from the PC analysis and progression-free survival were examined via Cox regression analyses. Findings Mean FVC was 70·1% and mean DLCO 42·3 %predicted. Significant associations with disease progression were noted with increased % relative abundance of two OTUs identified by PC analysis, a Streptococcus OTU. (p<0·0009) and a Staphylococcus OTU(p=0·01). Strength of associations using PCs versus two OTUs alone was similar. Threshold analysis helped define a cut point for % relative abundance for each OTU associated with progression-free survival, >3·9% for the Streptococcus OTU, HR 10·19 (95% CI 2·94, 35·35; p=0·0002) and >1·8% for the Staphylococcus OTU, HR 5·06 (1·71, 14·93; p=0·003). Interpretation These preliminary data suggest IPF disease progression is associated with presence of specific members within the Staphylococcus and Streptococcus genera.
Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes. MRI scans from the TCGA/TCIA lower grade glioma database ( = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of "T2-FLAIR mismatch" sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate-substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular-radiographic associations. A separate institutional cohort ( = 82) was analyzed to validate the T2-FLAIR mismatch sign. Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [ = 0.234 (0.111-0.358)], T2-FLAIR mismatch sign [ = 0.728 (0.538-0.918)], lesion margins [ = 0.292 (0.135-0.449)], and peritumoral edema [ = 0.173 (0.096-0.250)]. All 15 cases that were positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2-FLAIR mismatch sign [ = 0.747 (0.536-0.958)]; all 10 cases positive for the T2-FLAIR mismatch sign were -mutant, 1p/19q non-codeleted tumors ( < 0.00001; PPV = 100%, NPV = 76%). Among lower-grade gliomas, T2-FLAIR mismatch sign represents a highly specific imaging biomarker for the -mutant, 1p/19q non-codeleted molecular subtype..
Sharing common inputs across business lines can potentially generate synergy that justifies related diversification. The pursuit of such synergy through diversification is, however, fundamentally driven by the indivisibility of inputs between firms. Following Penrose's insight, I argue that to realize this synergy, a firm needs to actively manage the interdependencies between different business lines, which, in turn, increases its coordination costs. The coordination costs may increase faster than synergy and set a limit to related diversification. This is particularly salient when the firm's existing business lines already have complex interdependencies among them. I test these arguments on a dataset of U.S. equipment manufacturers for the period 1993 to 2003. The results show that a firm is more likely to diversify into a new business when its existing business lines can potentially share more inputs with the new business; however, the firm is less likely to diversify into any new business when its existing business lines are complex. Importantly, the firm's likelihood of diversifying into a new business decreases more with the complexity in the firm's existing business lines if they share more inputs with the new business. These results suggest that increasing coordination costs counterbalance the potential synergistic benefits associated with related diversification. Copyright © 2010 John Wiley & Sons, Ltd.
This paper studies the impact of task complexity and decomposability on the degree of organizational divisionalization and hierarchy within firms. Drawing upon the team theory and modularity literature, it argues that the degree of divisionalization is predicated not only on the extent of interdependence (complexity) among tasks but also on the extent to which those interdependent relationships are decomposable. As such, the feasibility and benefits of modularization in organizational design may be overstated when the underlying tasks are not decomposable. In addition, this paper argues that organizational hierarchy serves to mitigate the tension between complexity and decomposability by facilitating a higher degree of divisionalization. These arguments are tested using data on the business activities and organization structures of U.S. equipment manufacturers in 1993–2003. Results show that divisionalization increases with task complexity, suggesting that complex task systems encourage more division of managerial responsibilities. However, divisionalization decreases as task systems become less decomposable. Meanwhile, organizational hierarchy increases with task complexity, and it increases as task systems become less decomposable. These findings highlight the constraints firms face in designing modular organization structures and the role of hierarchy in coordinating complex task systems that are not fully decomposable.
In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.
Research summary: We examine the role of firm strategy in the global effort to combat pollution. We find that U.S. plants release less toxic emissions when their parent firm imports more from low‐wage countries (LWCs). Consistent with the Pollution Haven Hypothesis, goods imported by U.S. firms from LWCs are in more pollution‐intensive industries. U.S. plants shift production to less pollution‐intensive industries, produce less waste, and spend less on pollution abatement when their parent imports more from LWCs. The negative impact of LWC imports on emissions is stronger for U.S. plants located in counties with greater institutional pressure for environmental performance, but weaker for more‐capable U.S. plants and firms. These results highlight the role of local institutions and firm capability in explaining firms' offshoring and environmental strategies. Managerial summary: Using confidential trade, production, and pollution data of more than 8,000 firms and 18,000 plants from the U.S. Census Bureau for years 1992–2009, we find that U.S. plants release less toxic emissions when their parent firm imports more from low‐wage countries (LWCs). In addition, goods imported by U.S. firms from LWCs are in more pollution‐intensive industries. U.S. plants shift production to less pollution‐intensive industries, produce less waste, and spend less on pollution abatement when their parent imports more from LWCs. However, not all U.S. firms choose to “offshore pollution.” U.S. plants located in counties with greater institutional pressure for environmental performance offshore more, but more‐capable U.S. plants and firms offshore less. Copyright © 2017 John Wiley & Sons, Ltd.
This paper examines how multinational corporations (MNCs) selectively assign supervisory responsibilities to units in countries with varying levels of institutional quality. Arbitraging across institutional contexts is an important function of MNCs, but it also creates coordination challenges. The choice of organization structure, such as the differential assignment of supervisory responsibilities, is an important tool for managing these coordination challenges. Using data on the business activities and supervision relationships within U.S. multinational manufacturers in 1996-2008, I find that frontline subsidiaries in countries with weaker institutions are more likely to be supervised by foreign rather than domestic supervisory units. Foreign supervision is even more likely when subsidiaries in weak-institution countries conduct activities that are more central to or interdependent with their parents' global operations. These findings confirm that MNCs use differential supervision to enhance global coordination. The paper highlights one of the most unique features of MNCs: a multinational hierarchy that resides within firm's boundary but across national borders. It also connects MNCs' hierarchical structure with institutional imperfections that give rise to the emergence of the firm in the first place.
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