Separability of neural responses to standardised mechanical stimulation of limbs

Abstract Considerable scientific and technological efforts are currently being made towards the development of neural prostheses. Understanding how the peripheral nervous system responds to electro-mechanical stimulation of the limb, will help to inform the design of prostheses that can restore function or accelerate recovery from injury to the sensory motor system. However, due to differences in experimental protocols, it is difficult, if not impossible, to make meaningful comparisons between different peripheral nerve interfaces. Therefore, we developed a low-cost electronic system to standardise the mechanical stimulation of a rat’s hindpaw. Three types of mechanical stimulations, namely, proprioception, touch and nociception were delivered to the limb and the electroneurogram signals were recorded simultaneously from the sciatic nerve with a 16-contact cuff electrode. For the first time, results indicate separability of neural responses according to stimulus type as well as intensity. Statistical analysis reveal that cuff contacts placed circumferentially, rather than longitudinally, are more likely to lead to higher classification rates. This flexible setup may be readily adapted for systematic comparison of various electrodes and mechanical stimuli in rodents. Hence, we have made its electro-mechanical design and computer programme available onlin

Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA

Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of 64Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of 64Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that 64Cu-NOTA-TRC105 exhibited better stability than 64Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with 64Cu-labeled TRC105

A second generation human haplotype map of over 3.1 million SNPs

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r(2) of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r(2) of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62863/1/nature06258.pd

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Reviewing the use of resilience concepts in forest sciences

Purpose of the review Resilience is a key concept to deal with an uncertain future in forestry. In recent years, it has received increasing attention from both research and practice. However, a common understanding of what resilience means in a forestry context, and how to operationalise it is lacking. Here, we conducted a systematic review of the recent forest science literature on resilience in the forestry context, synthesising how resilience is defined and assessed. Recent findings Based on a detailed review of 255 studies, we analysed how the concepts of engineering resilience, ecological resilience, and social-ecological resilience are used in forest sciences. A clear majority of the studies applied the concept of engineering resilience, quantifying resilience as the recovery time after a disturbance. The two most used indicators for engineering resilience were basal area increment and vegetation cover, whereas ecological resilience studies frequently focus on vegetation cover and tree density. In contrast, important social-ecological resilience indicators used in the literature are socio-economic diversity and stock of natural resources. In the context of global change, we expected an increase in studies adopting the more holistic social-ecological resilience concept, but this was not the observed trend. Summary Our analysis points to the nestedness of these three resilience concepts, suggesting that they are complementary rather than contradictory. It also means that the variety of resilience approaches does not need to be an obstacle for operationalisation of the concept. We provide guidance for choosing the most suitable resilience concept and indicators based on the management, disturbance and application context