Time spent at home poststroke: “home-time” a meaningful and robust outcome measure for stroke trials

<p><b>Background and Purpose:</b> Stroke outcome assessment requires some measure of functional recovery. Several instruments are in common use but all have recognized limitations. We examined duration of stay in the patient’s own home over the first 90 days since stroke—"home-time"—as an alternative outcome likely to show graded response with improved reliability.</p> <p><b>Methods:</b> We examined prospectively collected data from the GAIN International trial using analysis of variance with Bonferroni contrasts of adjacent modified Rankin scale score categories.</p> <p><b>Results:</b> We had full outcome data from 1717 of 1788 patients. Increasing home-time was associated with improved modified Rankin scale scores (P<0.0001). The relationship held across all modified Rankin scale grades except 4 to 5.</p> <p><b>Conclusions:</b> Home-time offers a robust, useful, and easily validated outcome measure for stroke, particularly across better recovery levels.</p&gt

Rational design of a (S)-selective-transaminase for asymmetric synthesis of (1S)-1-(1,1′-biphenyl-2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production of pure chiral amines. However, their catalytic efficiency toward bulky ketone substrates is greatly limited by steric hindrance and therefore presents a great challenge for industrial synthetic applications. We hereby report an example of rational transaminase enzyme design to help alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has no detectable catalytic activity toward the bulky aromatic ketone 2-acetylbiphenyl, we employed a rational design strategy combining in silico and in vitro studies to engineer the transaminase enzyme with a minimal number of mutations, achieving an high catalytic activity and high enantioselectivity. We found that, by introducing two mutations W57G/R415A, detectable enzyme activity was achieved. The rationally designed variant, W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rate by more than 1716-fold toward the bulky ketone under study, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of >99%)

A polymorphic transcriptional regulatory domain in the amyotrophic lateral sclerosis risk gene CFAP410 correlates with differential isoform expression

We describe the characterisation of a variable number tandem repeat (VNTR) domain within intron 1 of the amyotrophic lateral sclerosis (ALS) risk gene CFAP410 (Cilia and flagella associated protein 410) (previously known as C21orf2), providing insight into how this domain could support differential gene expression and thus be a modulator of ALS progression or risk. We demonstrated the VNTR was functional in a reporter gene assay in the HEK293 cell line, exhibiting both the properties of an activator domain and a transcriptional start site, and that the differential expression was directed by distinct repeat number in the VNTR. These properties embedded in the VNTR demonstrated the potential for this VNTR to modulate CFAP410 expression. We extrapolated these findings in silico by utilisation of tagging SNPs for the two most common VNTR alleles to establish a correlation with endogenous gene expression. Consistent with in vitro data, CFAP410 isoform expression was found to be variable in the brain. Furthermore, although the number of matched controls was low, there was evidence for one specific isoform being correlated with lower expression in those with ALS. To address if the genotype of the VNTR was associated with ALS risk, we characterised the variation of the CFAP410 VNTR in ALS cases and matched controls by PCR analysis of the VNTR length, defining eight alleles of the VNTR. No significant difference was observed between cases and controls, we noted, however, the cohort was unlikely to contain sufficient power to enable any firm conclusion to be drawn from this analysis. This data demonstrated that the VNTR domain has the potential to modulate CFAP410 expression as a regulatory element that could play a role in its tissue-specific and stimulus-inducible regulation that could impact the mechanism by which CFAP410 is involved in ALS

Continental-scale variation in otolith geochemistry of juvenile American shad (Alosa sapidissima)

Author Posting. © NRC Research Press, 2008. This article is posted here by permission of NRC Research Press for personal use, not for redistribution. The definitive version was published in Canadian Journal of Fisheries and Aquatic Sciences 65 (2008): 2623-2635, doi:10.1139/F08-164.We assembled a comprehensive atlas of geochemical signatures in juvenile American shad (Alosa sapidissima) to discriminate natal river origins on a large spatial scale and at a high spatial resolution. Otoliths and (or) water samples were collected from 20 major spawning rivers from Florida to Quebec and were analyzed for elemental (Mg:Ca, Mn:Ca, Sr:Ca, and Ba:Ca) and isotope (87Sr:86Sr and δ18O) ratios. We examined correlations between water chemistry and otolith composition for five rivers where both were sampled. While Sr:Ca, Ba:Ca, 87Sr:86Sr, and δ18O values in otoliths reflected those ratios in ambient waters, Mg:Ca and Mn:Ca ratios in otoliths varied independently of water chemistry. Geochemical signatures were highly distinct among rivers, with an average classification accuracy of 93% using only those variables where otolith values were accurately predicted from water chemistry data. The study represents the largest assembled database of otolith signatures from the entire native range of a species, encompassing approximately 2700 km of coastline and 19 degrees of latitude and including all major extant spawning populations. This database will allow reliable estimates of natal origins of migrating ocean-phase American shad from the 2004 annual cohort in the future.This work was funded by National Science Foundation (NSF) grants OCE-0215905 and OCE-0134998 to SRT and by an American Museum of Natural History Lerner–Gray Grant for Marine Research and a scholarship from SEASPACE, Inc., to BDW

Limited diversity in natal origins of immature anadromous fish during ocean residency

Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of NRC Research Press for personal use, not for redistribution. The definitive version was published in Canadian Journal of Fisheries and Aquatic Sciences. 67 (2010): 1699-1707, doi:10.1139/F10-086.Variable migration patterns can play a significant role in promoting diverse life history traits among populations. However, population and stage specific movement patterns are generally unknown yet crucial aspects of life history strategies in many highly migratory species. We used a natural tag approach using geochemical signatures in otoliths to identify natal origins of one-year-old anadromous American shad (Alosa sapidissima) during ocean residency. Otolith signatures of migrants were compared to a database of baseline signatures from 20 source populations throughout their spawning range. Samples were dominated by fish from only two rivers, while all other potential source populations were nearly or completely absent. These data support the hypothesis that American shad exhibit diverse migratory behaviors and immature individuals from populations throughout the native range do not all mix on northern summer feeding grounds. Rather, our results suggest populations of anadromous fish are distributed heterogeneously at sea in the first year of life and thus may encounter different ocean conditions at a critical early life history stage.This work was funded by National Science Foundation grants OCE-0215905 and OCE-0134998 to SRT and by a WHOI Ocean Life Institute grant to BDW

A precision six-load-component transducer: A design incorporating finite-length measurement paths

The design of an instrument is described that measures three resultant force components and three resultant moment components acting on a surface. Within the framework of linear elastostatics of an isotropic homogeneous material the device separates to a given precision the six resultant load components. Sensor paths of finite length are employed. Moreover if fiber-optic differential displacement sensors are used rather than traditional electrical resistance strain gages, the range and sensitivity of the instrument can in principle be improved without sacrificing the device stiffness. The primary reason for these improvements is that a complete solution to the equations of elasticity allows certain displacements to be measured over large distances and be combined to yield all of the resultant load components. These displacement measurements over a long distance accommodates the use of fiber-optic interferometric sensors. The use of optical sensors in contrast with electrical-resistance gages, has the potential to allow the measurement precision and range to scale with the geometry of the device rather than the maximum strain in the instrument. It becomes possible by virtue of these features to produce a better instrument.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43934/1/11340_2006_Article_BF02322149.pd

Size-selective mortality during freshwater and marine life stages of steelhead related to freshwater growth in the Skagit River, Washington

Wild steelhead trout, Oncorhynchus mykiss, in the Puget Sound are currently in decline, and very little is known about the early life history of these threatened fish. This study evaluated consequences of early growth and survival to smolt or adult stages in different precipitation zones of the Skagit River Basin, Washington. The objectives of this study were to determine whether significant size-selective mortality (SSM) in wild steelhead could be detected between freshwater stages and returning adults; and if so, how the magnitude of SSM varied among juveniles rearing in different precipitation zones (snow and mixed rain-snow). Wild steelhead were sampled as juveniles, smolts, and adults, and scales were measured to compare back-calculated size distributions and growth rates of rearing juveniles with individuals that survived from an earlier life stage to the smolt and adult stages. Back-calculated size-at-annulus comparisons indicated that steelhead in the snow zone were significantly larger at annulus-1 than those in the mixed zone. Steelhead sampled as adults were significantly larger than those sampled as juveniles at annuli-1, -2, and -3, and larger than those sampled as smolts at annuli-2 and -3, Steelhead sampled as smolts were larger than those sampled as juveniles at annuli-1 and -2, but smolts and juveniles were the same size at annulus-3. The disparity in size-at-age-2 and -3 between steelhead sampled at earlier and later life stages suggested that fast growth during the second or third freshwater growing seasons was vitally important for survival to adulthood, and that both freshwater and marine survival could be attributed, in part, to size attained at earlier life stages in freshwater. Efforts for recovery of threatened Puget Sound steelhead could benefit by considering SSM in freshwater environments, and identifying factors that limit growth during early life stages

Gendering the careers of young professionals: some early findings from a longitudinal study. in Organizing/theorizing: developments in organization theory and practice

Wonders whether companies actually have employees best interests at heart across physical, mental and spiritual spheres. Posits that most organizations ignore their workforce – not even, in many cases, describing workers as assets! Describes many studies to back up this claim in theis work based on the 2002 Employment Research Unit Annual Conference, in Cardiff, Wales

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele