Corticospinal tract integrity and lesion volume play different roles in chronic hemiparesis and its improvement through motor practice

Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.

Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects

Our data highlight the role of SP in reparative neovascularization. Nociceptive signaling may represent a novel target of regenerative medicine.

Targeting stem cell niches and trafficking for cardiovascular therapy.

Regenerative cardiovascular medicine is the frontline of 21st-century health care. Cell therapy trials using bone marrow progenitor cells documented that the approach is feasible, safe and potentially beneficial in patients with ischemic disease. However, cardiovascular prevention and rehabilitation strategies should aim to conserve the pristine healing capacity of a healthy organism as well as reactivate it under disease conditions. This requires an increased understanding of stem cell microenvironment and trafficking mechanisms. Engagement and disengagement of stem cells of the osteoblastic niche is a dynamic process, finely tuned to allow low amounts of cells move out of the bone marrow and into the circulation on a regular basis. The balance is altered under stress situations, like tissue injury or ischemia, leading to remarkably increased cell egression. Individual populations of circulating progenitor cells could give rise to mature tissue cells (e.g. endothelial cells or cardiomyocytes), while the majority may differentiate to leukocytes, affecting the environment of homing sites in a paracrine way, e.g. promoting endothelial survival, proliferation and function, as well as attenuating or enhancing inflammation. This review focuses on the dynamics of the stem cell niche in healthy and disease conditions and on therapeutic means to direct stem cell/progenitor cell mobilization and recruitment into improved tissue repair.

Northern winter climate change: assessment of uncertainty in CMIP5 projections related to stratosphere–troposphere coupling

Future changes in the stratospheric circulation could have an important impact on Northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric circulation variations but also to vertically coherent variations in troposphere-stratosphere circulation. Here we assess Northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project – phase 5 (CMIP5) multi-model ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a significant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification and the stratospheric wind change on SLP. We find that the inter-model spread in stratospheric wind change contributes substantially to the inter-model spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes.

An investigation into the relationship between values and commitment: a study of staff in the UK charity sector

Abstract The concept of values “fit” has been a significant theme in the management literature for many years. It is argued that where there is alignment of staff and organizational values a range of positive outcomes are encountered. What is unclear is how this translates into the charity sector. This study explores the phenomenon of values alignment in two UK charities. Questionnaires were used to measure staff values, perceptions of organization values and staff commitment. Drawing on the work of Finegan (2000), an interaction term is used as a proxy for fit. Analyses of data from 286 participants indicated that it was the perceptions of organization values that had the greatest impact on staff commitment. The alignment of staff values and perceptions of organization values only had a degree of effect within one of the charities. This challenges the dominant view on such alignment and the implications of this are discussed. Keywords staff, values fit, commitment, organizational identification

Representation errors and retrievals in linear and nonlinear data assimilation

This article shows how one can formulate the representation problem starting from Bayes’ theorem. The purpose of this article is to raise awareness of the formal solutions,so that approximations can be placed in a proper context. The representation errors appear in the likelihood, and the different possibilities for the representation of reality in model and observations are discussed, including nonlinear representation probability density functions. Specifically, the assumptions needed in the usual procedure to add a representation error covariance to the error covariance of the observations are discussed,and it is shown that, when several sub-grid observations are present, their mean still has a representation error ; socalled ‘superobbing’ does not resolve the issue. Connection is made to the off-line or on-line retrieval problem, providing a new simple proof of the equivalence of assimilating linear retrievals and original observations. Furthermore, it is shown how nonlinear retrievals can be assimilated without loss of information. Finally we discuss how errors in the observation operator model can be treated consistently in the Bayesian framework, connecting to previous work in this area.

Phosphorescence quantum yield enhanced by intermolecular hydrogen bonds in Cu4I4 clusters in the solid state

Organo-copper(I) halide complexes with a Cu4I4 cubane core and cyclic amines as ligands have been synthesized and their crystal structures have been defined. Their solid state photophysical properties have been measured and correlated with the crystal structure and packing. A unique and remarkably high luminescence quantum yield (76%) has been measured for one of the complexes having the cubane clusters arranged in a columnar structure and held together by N–HI hydrogen bonds. This high luminescence quantum yield is correlated with a slow radiationless deactivation rate of the excited state and suggests a rather strong enhancement of the cubane core rigidity bestowed by the hydrogen bond pattern. Some preliminary thin film deposition experiments show that these compounds could be considered to be good candidates for applications in electroluminescent devices because of their bright luminescence, low cost and relatively easy synthesis processes

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Label-free enrichment of avian Leucocytozoon using flow cytometric sorting

The group of haemosporidian parasites is of general interest to basic and applied science, since several species infect mammals, leading to malaria and associated disease symptoms. Although the great majority of haemosporidian parasites appear in bird hosts, as in the case of Leucocytozoon buteonis, there is little genomic information about genetic aspects of their co-evolution with hosts. Consequently, there is a high need for parasite-enrichment strategies enabling further analyses of the genomes, namely without exposure to DNA-intercalating dyes. Here, we used flow cytometry without an additional labelling step to enrich L. buteonis from infected buzzard blood. A specific, defined area of two-dimensional scattergramms was sorted and the fraction was further analysed. The successful enrichment of L. buteonis in the sorted fraction was demonstrated by Giemsa-staining and qPCR revealing a clear increase of parasite-specific genes, while host-specific genes were significantly decreased. This is the first report describing a labelling-free enrichment approach of L. buteonis from infected buzzard blood. The enrichment of parasites presented here is free of nucleic acid-intercalating dyes which may interfere with fluorescence-based methods or subsequent sequencing approaches.

Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

Comparative analysis of performance and stability among composite cross populations, variety mixtures and pure lines of winter wheat in organic and conventional cropping systems

This study investigated the effects of increased genetic diversity in winter wheat (Triticum aestivum L.), either from hybridization across genotypes or from physical mixing of lines, on grain yield, grain quality, and yield stability in different cropping environments. Sets of pure lines (no diversity), chosen for high yielding ability or high quality, were compared with line mixtures (intermediate level of diversity), and lines crossed with each other in composite cross populations (CCPn, high diversity). Additional populations containing male sterility genes (CCPms) to increase outcrossing rates were also tested. Grain yield, grain protein content, and protein yield were measured at four sites (two organically-managed and two conventionally-managed) over three years, using seed harvested locally in each preceding year. CCPn and mixtures out-yielded the mean of the parents by 2.4% and 3.6%, respectively. These yield differences were consistent across genetic backgrounds but partly inconsistent across cropping environments and years. Yield stability measured by environmental variance was higher in CCPn and CCPms than the mean of the parents. An index of yield reliability tended to be higher in CCPn, CCPms and mixtures than the mean of the parents. Lin and Binns’ superiority values of yield and protein yield were consistently and significantly lower (i.e. better) in the CCPs than in the mean of the parents, but not different between CCPs and mixtures. However, CCPs showed greater early ground cover and plant height than mixtures. When compared with the (locally non-predictable) best-yielding pure line, CCPs and mixtures exhibited lower mean yield and somewhat lower yield reliability but comparable superiority values. Thus, establishing CCPs from smaller sets of high-performing parent lines might optimize their yielding ability. On the whole, the results demonstrate that using increased within-crop genetic diversity can produce wheat crops with improved yield stability and good yield reliability across variable and unpredictable cropping environments.

Unwriting food labels: discursive challenges in the regulation of package claims

This article examines the challenges resulting from the regulation of written discourse on food packages. It uses as a case study Hong Kong’s strict new food-labeling law that requires distributers and retailers to remove certain nutritional claims from packages of imported food before they sell them. This practice of redacting unlawful text on packages requires that distributers and retailers engage in complex processes of discursive reasoning, and it some- times results in packages that are difficult for customers to interpret. The case study highlights important issues in the regulation of commercial texts concerning collaboration, intertextuality, and the conflicts that can arise when the principals, authors, and animators of such texts have different agendas.

Concepts for a geostationary-like polar missions

An evidence-led scientific case for development of a space-based polar remote sensing platform at geostationary-like (GEO-like) altitudes is developed through methods including a data user survey. Whilst a GEO platform provides a nearstatic perspective, multiple platforms are required to provide circumferential coverage. Systems for achieving GEO-like polar observation likewise require multiple platforms however the perspective is non-stationery. A key choice is between designs that provide complete polar view from a single platform at any given instant, and designs where this is obtained by compositing partial views from multiple sensors. Users foresee an increased challenge in extracting geophysical information from composite images and consider the use of non-composited images advantageous. Users also find the placement of apogee over the pole to be preferable to the alternative scenarios. Thus, a clear majority of data users find the “Taranis” orbit concept to be better than a critical inclination orbit, due to the improved perspective offered. The geophysical products that would benefit from a GEO-like polar platform are mainly estimated from radiances in the visible/near infrared and thermal parts of the electromagnetic spectrum, which is consistent with currently proven technologies from GEO. Based on the survey results, needs analysis, and current technology proven from GEO, scientific and observation requirements are developed along with two instrument concepts with eight and four channels, based on Flexible Combined Imager heritage. It is found that an operational system could, mostly likely, be deployed from an Ariane 5 ES to a 16-hour orbit, while a proof-of-concept system could be deployed from a Soyuz launch to the same orbit.