A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts

Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8–20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82–0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P \u3c 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P \u3c 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling

Linking learning with governance in networks and clusters: key issues for analysis and policy

In this paper we analyse the relationship between governance and learning in clusters and networks. In particular, we see these two key elements as interdependent, suggesting that, under particular circumstances, such interdependence may drive clusters and networks towards a dynamic development trajectory. A pure ‘governance perspective’ makes the development of any locality dependent on the system of powers which exists within the locality or across the global value chain. In parallel, a pure ‘competence-based approach’ focuses mainly on the capabilities of actors to learn and undertake activities. In contrast, we open the prospects for an interdependent relation that may change the actual competences of actors as well as the governance settings and dynamics in networks and clusters. When supported by public policies, the learning process may have the potential to modify the governance environment. Simultaneously, the learning process is intrinsically influenced by economic power, which may seriously affect the development prospects of clusters and networks. This is why an intertwined consideration of both aspects is necessary to promote specific approaches to learning and to design appropriate policies. In this paper we offer two preliminary case studies to clarify some of these dynamics: the first taken from the computers cluster in Costa Rica and the second from an Italian bio-pharmaceutical firm and its production network. The first case study refers to the software cluster that was created from scratch in Costa Rica thanks to an enlightened government policy in coordination with new local enterprises and an important foreign direct investor; while the second reflects on the ability of an individual company to create a network of relationships with large transnational companies in order to acquire new competences without falling into a subordinate position with respect to its larger partners

Cheating the locals: invasive mussels steal and benefit from the cooling effect of indigenous mussels

The indigenous South African mussel Perna perna gapes during periods of aerial exposure to maintain aerobic respiration. This behaviour has no effect on the body temperatures of isolated individuals, but when surrounded by conspecifics, beneficial cooling effects of gaping emerge. It is uncertain, however, whether the presence of the invasive mussel Mytilus galloprovincialis limits the ability of P. perna for collective thermoregulation. We investigated whether varying densities of P. perna and M. galloprovincialis influences the thermal properties of both natural and artificial mussel beds during periods of emersion. Using infrared thermography, body temperatures of P. perna within mixed artificial beds were shown to increase faster and reach higher temperatures than individuals in conspecific beds, indicating that the presence of M. galloprovincialis limits the group cooling effects of gaping. In contrast, body temperatures of M. galloprovincialis within mixed artificial mussel beds increased slower and exhibited lower temperatures than for individuals in beds comprised entirely of M. galloprovincialis. Interestingly, differences in bed temperatures and heating rates were largely dependent on the size of mussels, with beds comprised of larger individuals experiencing less thermal stress irrespective of species composition. The small-scale patterns of thermal stress detected within manipulated beds were not observed within naturally occurring mixed mussel beds. We propose that small-scale differences in topography, size-structure, mussel bed size and the presence of organisms encrusting the mussel shells mask the effects of gaping behaviour within natural mussel beds. Nevertheless, the results from our manipulative experiment indicate that the invasive species M. galloprovincialis steals thermal properties as well as resources from the indigenous mussel P. perna. This may have significant implications for predicting how the co-existence of these two species may change as global temperatures continue to rise

Differential Efficacy From the Addition of Bortezomib to R-CHOP in Diffuse Large B-Cell Lymphoma According to the Molecular Subgroup in the REMoDL-B Study With a 5-Year Follow-Up

The REMoDL-B phase III adaptive trial compared rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) versus R-CHOP + bortezomib (RB-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL), stratified by molecular subtype. Primary analysis at a median follow-up of 30 months found no effect of bortezomib on progression-free survival (PFS) or overall survival (OS). Retrospective analysis using a gene expression–based classifier identified a molecular high-grade (MHG) group with worse outcomes. We present an updated analysis for patients successfully classified by the gene expression profile (GEP). Eligible patients were age older than 18 years with untreated DLBCL, fit enough for full-dose chemotherapy, and with adequate biopsies for GEP. Of 1,077 patients registered, 801 were identified with Activated B-Cell (ABC), Germinal Center B-cell, or MHG lymphoma. At a median follow-up of 64 months, there was no overall benefit of bortezomib on PFS or OS (5-year PFS hazard ratio [HR], 0.81; P = .085; OS HR, 0.86; P = .32). However, improved PFS and OS were seen in ABC lymphomas after RB-CHOP: 5-year OS 67% with R-CHOP versus 80% with RB-CHOP (HR, 0.58; 95% CI, 0.35 to 0.95; P = .032). Five-year PFS was higher in MHG lymphomas: 29% versus 55% (HR, 0.46; 95% CI, 0.26 to 0.84). Patients with ABC and MHG DLBCL may benefit from the addition of bortezomib to R-CHOP in initial therapy

Introducing BASE: the Biomes of Australian Soil Environments soil microbial diversity database

Microbial inhabitants of soils are important to ecosystem and planetary functions, yet there are large gaps in our knowledge of their diversity and ecology. The ‘Biomes of Australian Soil Environments’ (BASE) project has generated a database of microbial diversity with associated metadata across extensive environmental gradients at continental scale. As the characterisation of microbes rapidly expands, the BASE database provides an evolving platform for interrogating and integrating microbial diversity and function

Introducing BASE: the Biomes of Australian Soil Environments soil microbial diversity database

Background: Microbial inhabitants of soils are important to ecosystem and planetary functions, yet there are large gaps in our knowledge of their diversity and ecology. The 'Biomes of Australian Soil Environments' (BASE) project has generated a database of microbial diversity with associated metadata across extensive environmental gradients at continental scale. As the characterisation of microbes rapidly expands, the BASE database provides an evolving platform for interrogating and integrating microbial diversity and function. Findings: BASE currently provides amplicon sequences and associated contextual data for over 900 sites encompassing all Australian states and territories, a wide variety of bioregions, vegetation and land-use types. Amplicons target bacteria, archaea and general and fungal-specific eukaryotes. The growing database will soon include metagenomics data. Data are provided in both raw sequence (FASTQ) and analysed OTU table formats and are accessed via the project's data portal, which provides a user-friendly search tool to quickly identify samples of interest. Processed data can be visually interrogated and intersected with other Australian diversity and environmental data using tools developed by the 'Atlas of Living Australia'. Conclusions: Developed within an open data framework, the BASE project is the first Australian soil microbial diversity database. The database will grow and link to other global efforts to explore microbial, plant, animal, and marine biodiversity. Its design and open access nature ensures that BASE will evolve as a valuable tool for documenting an often overlooked component of biodiversity and the many microbe-driven processes that are essential to sustain soil function and ecosystem services

The Reelin Receptors Apoer2 and Vldlr Coordinate the Patterning of Purkinje Cell Topography in the Developing Mouse Cerebellum

The adult cerebellar cortex is comprised of reproducible arrays of transverse zones and parasagittal stripes of Purkinje cells. Adult stripes are created through the perinatal rostrocaudal dispersion of embryonic Purkinje cell clusters, triggered by signaling through the Reelin pathway. Reelin is secreted by neurons in the external granular layer and deep cerebellar nuclei and binds to two high affinity extracellular receptors on Purkinje cells-the Very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer2). In mice null for either Reelin or double null for Vldlr and Apoer2, Purkinje cell clusters fail to disperse. Here we report that animals null for either Vldlr or Apoer2 individually, exhibit specific and parasagittally-restricted Purkinje cell ectopias. For example, in mice lacking Apoer2 function immunostaining reveals ectopic Purkinje cells that are largely restricted to the zebrin II-immunonegative population of the anterior vermis. In contrast, mice null for Vldlr have a much larger population of ectopic Purkinje cells that includes members from both the zebrin II-immunonegative and -immunopositive phenotypes. HSP25 immunoreactivity reveals that in Vldlr null animals a large portion of zebrin II-immunopositive ectopic cells are probably destined to become stripes in the central zone (lobules VI–VII). A small population of ectopic zebrin II-immunonegative Purkinje cells is also observed in animals heterozygous for both receptors (Apoer2+/−: Vldlr+/−), but no ectopia is present in mice heterozygous for either receptor alone. These results indicate that Apoer2 and Vldlr coordinate the dispersal of distinct, but overlapping subsets of Purkinje cells in the developing cerebellum