Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis

This study describes a new method for analyzing microcirculatory videos. It introduces algorithms for quantitative assessment of vessel length, diameter, the functional microcirculatory density distribution and red blood-cell (RBC) velocity in individual vessels as well as its distribution. The technique was validated and compared to commercial software. The method was applied to the sublingual microcirculation in a healthy volunteer and in a patient during cardiac surgery. Analysis time was reduced from hours to minutes compared to previous methods requiring manual vessel identification. Vessel diameter was detected with high accuracy (>80%, d > 3 pixels). Capillary length was estimated within 5 pixels accuracy. Velocity estimation was very accurate (>95%) in the range [2.5, 1,000] pixels/s. RBC velocity was reduced by 70% during the first 10 s of cardiac luxation. The present method has been shown to be fast and accurate and provides increased insight into the functional properties of the microcirculation

Rapid automatic assessment of microvascular density in sidestream dark field images

The purpose of this study was to develop a rapid and fully automatic method for the assessment of microvascular density and perfusion in sidestream dark field (SDF) images. We modified algorithms previously developed by our group for microvascular density assessment and introduced a new method for microvascular perfusion assessment. To validate the new algorithm for microvascular density assessment, we reanalyzed a selection of SDF video clips (n = 325) from a study in intensive care patients and compared the results to (semi-)manually found microvascular densities. The method for microvascular perfusion assessment (temporal SDF image contrast analysis, tSICA) was tested in several video simulations and in one high quality SDF video clip where the microcirculation was imaged before and during circulatory arrest in a cardiac surgery patient. We found that the new method for microvascular density assessment was very rapid (<30 s/clip) and correlated excellently with (semi-)manually measured microvascular density. The new method for microvascular perfusion assessment (tSICA) was shown to be limited by high cell densities and velocities, which severely impedes the applicability of this method in real SDF images. Hence, here we present a validated method for rapid and fully automatic assessment of microvascular density in SDF images. The new method was shown to be much faster than the conventional (semi-)manual method. Due to current SDF imaging hardware limitations, we were not able to automatically detect microvascular perfusion

How contemporary bioclimatic and human controls change global fire regimes

Anthropogenically driven declines in tropical savannah burnt area have recently received attention due to their effect on trends in global burnt area. Large-scale trends in ecosystems where vegetation has adapted to infrequent fire, especially in cooler and wetter forested areas, are less well understood. Here, small changes in fire regimes can have a substantial impact on local biogeochemistry. To investigate trends in fire across a wide range of ecosystems, we used Bayesian inference to quantify four primary controls on burnt area: fuel continuity, fuel moisture, ignitions and anthropogenic suppression. We found that fuel continuity and moisture are the dominant limiting factors of burnt area globally. Suppression is most important in cropland areas, whereas savannahs and boreal forests are most sensitive to ignitions. We quantify fire regime shifts in areas with more than one, and often counteracting, trends in these controls. Forests are of particular concern, where we show average shifts in controls of 2.3–2.6% of their potential maximum per year, mainly driven by trends in fuel continuity and moisture. This study gives added importance to understanding long-term future changes in the controls on fire and the effect of fire trends on ecosystem function

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

Phase II drugs that are currently in development for the treatment of cachexia

Cachexia is a syndrome presenting with progressive unintentional weight loss and wasting and weakness of skeletal muscle. Cachexia is prevalent in cancer and in chronic diseases including chronic obstructive pulmonary disease (COPD). Areas covered: The authors searched trial registers for current Phase II clinical trials on cachexia. Twelve studies were found with 11 compounds, including the anti-inflammatory drugs thalidomide, OHR/AVR118, celecoxib, VT-122, omega-3 supplements, and anabolic agents such as ghrelin analogues, MT-102, BYM338 and ruxolotinib. The authors note that one of the studies related to COPD while the others were related to different cancers. Herein, the authors describe the mechanisms of action and their Phase II study design. Expert opinion: The compounds under study affect several pathways involved in cachexia by modulating inflammatory activity, anabolic potential, digestion and direct interaction with the muscle. Due to the multifactorial aspects of cachexia syndrome, combinations of these new drugs with nutritional intervention is probably the most promising approach. Furthermore, future studies should include interventions in pre-cachetic patients, as this stage might be more responsive to treatment. Future studies will benefit from well-defined end points and improved measures of cachexia, providing new insight into the disease. This insight, in combination with the elucidation of cachexia's underlying mechanism, will yield new treatment strategies in the near future