Computational modelling in disorders of consciousness: closing the gap towards personalised models for restoring consciousness

Disorders of consciousness are complex conditions characterised by persistent loss of responsiveness due to brain injury. They present diagnostic challenges and limited options for treatment, and highlight the urgent need for a more thorough understanding of how human consciousness arises from coordinated neural activity. The increasing availability of multimodal neuroimaging data has given rise to a wide range of clinically- and scientifically-motivated modelling efforts, seeking to improve data-driven stratification of patients, to identify causal mechanisms for patient pathophysiology and loss of consciousness more broadly, and to develop simulations as a means of testing in silico potential treatment avenues to restore consciousness. As a dedicated Working Group of clinicians and neuroscientists of the international Curing Coma Campaign, here we provide our framework and vision to understand the diverse statistical and generative computational modelling approaches that are being employed in this fast-growing field. We identify the gaps that exist between the current state-of-the-art in statistical and biophysical computational modelling in human neuroscience, and the aspirational goal of a mature field of modelling disorders of consciousness; which might drive improved treatments and outcomes in the clinic. Finally, we make several recommendations for how the field as a whole can work together to address these challenges

3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors.

Dynamic alterations in the unique brain extracellular matrix (ECM) are involved in malignant brain tumors. Yet studies of brain ECM roles in tumor cell behavior have been difficult due to lack of access to the human brain. We present a tunable 3D bioengineered brain tissue platform by integrating microenvironmental cues of native brain-derived ECMs and live imaging to systematically evaluate patient-derived brain tumor responses. Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain ECM-containing microenvironment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells\u27 transcriptomic and release profiles. Label-free metabolic imaging of the composite model structure identifies metabolically distinct sub-populations within a tumor type and captures extracellular lipid-containing droplets with potential implications in drug response. The versatile bioengineered 3D tumor tissue system sets the stage for mechanistic studies deciphering microenvironmental role in brain tumor progression

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council–Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA’s objectives is to ‘Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function’—in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during ‘normal’ ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing

How far from harmonization are sanitary, phytosanitary and quality-related standards? An exporter's perception approach

Reprint Address: Engler, A (reprint author), Univ Talca, Dept Econ Agr, Fac Ciencias Agr, 2 Norte 685, Talca, Chile.Harmonization of trade regulations and standards is perhaps the most contentious issue regarding export markets due to the impacts that it can have on trade. We determine the extent of harmonization as perceived by exporters with respect to the major Sanitary and Phytosanitary Standards (SPSs) and quality measures which Chile faces in 16 international fresh fruit markets. The methodology combined qualitative and quantitative techniques. First, the most relevant safety and quality standards and regulations were identified and ranked. Second, a representative sample of exporters was interviewed to assess their perceptions regarding the level of stringency across markets and time for selected regulations. Perceptions were ranked on a likert scale and based on this scale a stringency index was constructed. The results show that Chile faces regulations which can be grouped into the following categories: (i) phytosanitary measures; (ii) tolerance limits for pesticide residues and contaminants; (iii) hygiene requirements; (iv) labeling, marking and packaging; (v) product and process standards; and (vi) registration procedures and other import requirements. The number of regulations varied among countries, ranging from 13 to 3 out of the 14 considered in the study. The most stringent country among the sample as perceived by exporters was Mexico, whereas the least stringent was Saudi Arabia. Additionally, exporters agreed that stringency has increased over time with an average of 15% between 2005 and 2009. (C) 2012 Elsevier Ltd. All rights reserved

Heterogeneity of farms entering export supply chains: the case of fruit growers from central-south Chile

Engler, A (Engler, A.)[ 2 ]; Cofre, G (Cofre, G.). Univ Talca, Fac Ciencias Agr, Dept Agr Econ, Talca, ChileThe increasing stringency of world food markets requires farmers to adjust farm structure and commercial strategies to remain integrated in export supply chains. The goal of this study was to identify and characterize different types of fresh fruit farms with regard to farm structural and commercial strategies for a representative sample of fresh fruit growers from central-south Chile exporting to world markets. A typology of farms was constructed based on multivariate analysis, according to which five types of farms were differentiated from five distinct factors. Cluster I comprised the smallest and uncertified farms (14.3% of the sample). The remaining four clusters comprised certified farms, but with different farm structural and commercial characteristics. Cluster II (15.1%) was composed of farms located further from market connections. Cluster III (23.9%) comprised farms with the highest number of fruit species, and consequently, more diversified in fruit production. Cluster IV (8.8%) was the smallest group, and comprised the largest firms. Finally, Cluster V (37.8%) was composed of highly specialized fruit farms, with the highest proportion of hectares dedicated to the production of a single fruit species. The results show the heterogeneity among fresh fruit farms and support the need for differentiated incentives and technological transfer schemes from the public sector and fruit companies in order to successfully keep farmers within export supply chains

Growth performance and expression of immune-regulatory genes in rainbow trout (Oncorhynchus mykiss) juveniles fed extruded diets with varying levels of lupin (Lupinus albus), peas (Pisum sativum) and rapeseed (Brassica napus)

Varying levels of lupin (Lupinus albus), peas (Pisum sativum) and rapeseed (Brassica napus) meals were evaluated as partial replacements for fishmeal in extruded diets for rainbow trout, with particular emphasis on the effect on growth performance and the expression of three genes associated with immune response. A series of 10 isonitrogenous (450gkg1 crude protein) and isolipidic (17gkg1 crude lipid) diets were formulated to contain different levels of lupin (150gkg1, 250gkg1 and 350gkg1), rapeseed cake (100gkg1, 200gkg1 and 300gkg1) and pea (50gkg1, 150gkg1 and 250gkg1) meals. The control diet was prepared with fish meal as the sole source of protein. Triplicate groups of fish (37.08 +/- 3.58g) were assigned to each experimental diet. The feeding experiment was conducted for 9weeks at 14.3 +/- 0.4 degrees C. The fish were hand fed three times per day, 6days per week to apparent satiation level. Growth performance, feed utilization and immunological response were significantly affected by the type of plant protein as well as level of inclusion. Hepatosomatic index (HSI) increased in all groups of fish fed diets with pea and rapeseed cake meal. Dietary inclusion of lupin did not affect the expression of Mx-1 gene. Our results suggest that fish meal can be replaced by lupin in the diet of rainbow trout without any apparent adverse effects on key innate immunological genes

La Facultad va a la Escuela del Barrio

Fil: Pernici, M. P.. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina