Gastroesophageal reflux and antacid therapy in IPF: analysis from the Australia IPF Registry

BACKGROUND AND OBJECTIVE:Gastroesophageal reflux disease (GORD) is highly prevalent in idiopathic pulmonary fibrosis (IPF) and may play a role in its pathogenesis. Recent IPF treatment guidelines suggest that all patients with IPF be considered for antacid therapy. However, emerging evidence suggests that antacid therapy does not improve IPF patient outcomes and may increase the risk of pulmonary infection. METHODS:Using prospectively collected data from the Australian IPF Registry including use of antacid therapy, GORD diagnosis and GORD symptoms, the relationship of these GORD variables to survival and disease progression was assessed. The severity of GORD symptoms using the frequency scale for symptoms of GORD (FSSG) and its relationships to outcomes was also assessed for the first time in an IPF cohort. RESULTS:Five hundred eighty-seven (86%) of the 684 patients in the Australian IPF Registry were eligible for inclusion. Patients were mostly male (69%), aged 71.0 ± 8.5 years with moderate disease (FVC 81.7 ± 21.5%; DLco 48.5 ± 16.4%). Most patients were taking antacids (n = 384; 65%), though fewer had a diagnosis of GORD (n = 243, 41.4%) and typical GORD symptoms were even less common (n = 171, 29.1%). The mean FSSG score was 8.39 ± 7.45 with 43% (n = 251) having a score > 8. Overall, there was no difference in survival or disease progression, regardless of antacid treatment, GORD diagnosis or GORD symptoms. CONCLUSIONS:Neither the use of antacid therapy nor the presence of GORD symptoms affects longer term outcomes in IPF patients. This contributes to the increasing evidence that antacid therapy may not be beneficial in IPF patients and that GORD directed therapy should be considered on an individual basis to treat the symptoms of reflux.Helen E. Jo, Tamera J. Corte, Ian Glaspole, Christopher Grainge, Peter M. A. Hopkins ... Peter A. Bampton ... et al

Seismic anisotropy of the upper mantle below Western rift, East Africa

Although the East African rift system formed in cratonic lithosphere above a large‐scale mantle upwelling, some sectors have voluminous magmatism, while others have isolated, small‐volume eruptive centers. We conduct teleseismic shear wave splitting analyses on data from 5 lake‐bottom seismometers and 67 land stations in the Tanganyika‐Rukwa‐Malawi rift zone, including the Rungwe Volcanic Province (RVP), and from 5 seismometers in the Kivu rift and Virunga Volcanic Province, to evaluate rift‐perpendicular strain, rift‐parallel melt intrusion, and regional flow models for seismic anisotropy patterns beneath the largely amagmatic Western rift. Observations from 684 SKS and 305 SKKS phases reveal consistent patterns. Within the Malawi rift south of the RVP, fast splitting directions are oriented northeast with average delays of ~1 s. Directions rotate to N‐S and NNW north of the volcanic province within the reactivated Mesozoic Rukwa and southern Tanganyika rifts. Delay times are largest (~1.25 s) within the Virunga Volcanic Province. Our work combined with earlier studies shows that SKS‐splitting is rift parallel within Western rift magmatic provinces, with a larger percentage of null measurements than in amagmatic areas. The spatial variations in direction and amount of splitting from our results and those of earlier Western rift studies suggest that mantle flow is deflected by the deeply rooted cratons. The resulting flow complexity, and likely stagnation beneath the Rungwe province, may explain the ca. 17 Myr of localized magmatism in the weakly stretched RVP, and it argues against interpretations of a uniform anisotropic layer caused by large‐scale asthenospheric flow or passive rifting

Circulating RNA differences between patients with stable and progressive idiopathic pulmonary fibrosis

Britt Clynick, Helen E. Jo, Tamera J. Corte, Ian N. Glaspole, Christopher Grainge, Peter M.A. Hopkins ... et al

Biomarker signatures for progressive idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). Methods: In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. Results 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. Conclusion: A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.Britt Clynick ... Paul N. Reynolds ... et. a

Industrial Symbiosis: Old Wine in Recycled Bottles? Some Perspective from the History of Economic and Geographical Thought

‘‘Industrial symbiosis’’ (IS) is a central concept in the industrial ecology literature, which describes geographically proximate interfirm relationships involving the exchange of residual materials, water, and energy. Despite its obvious relevance to regional science, economic geography, and urban economics, the issue is only beginning to be addressed in these subdisciplines. This situation is paradoxical as both recovery linkages and the very concept of IS were discussed in some depth by numerous economists and geographers several decades ago. The goals of this article are to document this intellectual history, in the process gaining a better understanding of the phenomenon while shedding additional light on current controversies. In doing so, the authors further hope to restimulate economists, geographers, and regional scientists’ interest in the topic and to illustrate the long-standing importance of geographical co-location in facilitating the ‘‘internalization of externalities’’ of industrial operations