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A central question in conservation is how best to manage biodiversity, despite human domination of global processes (= Anthropocene). Common responses (i.e. translocations, genetic rescue) forestall potential extirpations, yet have an uncertain duration. A textbook example is the greater prairie chicken (GRPC: Tympanuchus cupido pinnatus ), where translocations (1992-1998) seemingly rescued genetically depauperate Illinois populations. We re-evaluated this situation after two decades by genotyping 21 microsatellite loci from 1831 shed feathers across six leks in two counties over 4 years (2010-2013). Low migration rates (less than 1%) established each county as demographically independent, but with declining-population estimates (4 year average N  = 79). Leks were genetically similar and significantly bottlenecked, with low effective population sizes (average N e  = 13.1; 4 year N e / N  = 0.166). Genetic structure was defined by 12 significantly different family groups, with relatedness r  = 0.31 > half-sib r  = 0.25. Average heterozygosity, indicating short-term survival, did not differ among contemporary, pre- and post-translocated populations, whereas allelic diversity did. Our results, the natural history of GRPC (i.e. few leks, male dominance hierarchies) and its controlled immigration suggest demographic expansion rather than genetic rescue. Legal protection under the endangered species act (ESA) may enhance recovery, but could exacerbate political-economic concerns on how best to manage 'conservation-reliant' species, for which GRPC is now an exemplar.

Background: Unconventional natural gas (UNG) extraction (fracking) is ongoing in 29 North American shale basins (20 states), with ~6000 wells found within the Fayetteville shale (north-central Arkansas). If the chemical signature of fracking is detectable in streams, it can be employed to bookmark potential impacts. We evaluated benthic biofilm community composition as a proxy for stream chemistry so as to segregate anthropogenic signatures in eight Arkansas River catchments. In doing so, we tested the hypothesis that fracking characteristics in study streams are statistically distinguishable from those produced by agriculture or urbanization., Results: Four tributary catchments had UNG-wells significantly more dense and near to our sampling sites and were grouped as 'potentially-impacted catchment zones' (PICZ). Four others were characterized by significantly larger forested area with greater slope and elevation but reduced pasture, and were classified as 'minimally-impacted' (MICZ). Overall, 46 bacterial phyla/141 classes were identified, with 24 phyla (52%) and 54 classes (38%) across all samples. PICZ-sites were ecologically more variable than MICZ-sites, with significantly greater nutrient levels (total nitrogen, total phosphorous), and elevated Cyanobacteria as bioindicators that tracked these conditions. PICZ-sites also exhibited elevated conductance (a correlate of increased ion concentration) and depressed salt-intolerant Spartobacteria, suggesting the presence of brine as a fracking effect. Biofilm communities at PICZ-sites were significantly less variable than those at MICZ-sites., Conclusions: Study streams differed by Group according to morphology, land use, and water chemistry but not in biofilm community structure. Those at PICZ-sites covaried according to anthropogenic impact, and were qualitatively similar to communities found at sites disturbed by fracking. The hypothesis that fracking signatures in study streams are distinguishable from those produced by other anthropogenic effects was statistically rejected. Instead, alterations in biofilm community composition, as induced by fracking, may be less specific than initially predicted, and thus more easily confounded by agriculture and urbanization effects (among others). Study streams must be carefully categorized with regard to the magnitude and extent of anthropogenic impacts. They must also be segregated with statistical confidence (as herein) before fracking impacts are monitored.

Objective: This study characterized telemedicine utilization among Medicaid enrollees by patients' demographic characteristics, geographic location, enrollment type, eligibility category, and clinical conditions., Methods: This study used 2008-2009 Medicaid claims data from 28 states and the District of Columbia to characterize telemedicine claims (indicated by GT for professional fee claims or Q3014 for facility fees) on the basis of patients' demographic characteristics, geographic location, enrollment type, eligibility category, and clinical condition as indicated by ICD-9 codes. States lacking Medicaid telemedicine reimbursement policies were excluded. Chi-square tests were used to compare telemedicine utilization rates and one-way analysis of variance was used to estimate mean differences in number of telemedicine encounters among subgroups., Results: A total of 45,233,602 Medicaid enrollees from the 22 states with telemedicine reimbursement policies were included in the study, and .1% were telemedicine users. Individuals ages 45 to 64 (16.4%), whites (11.3%), males (8.5%), rural residents (26.0%), those with managed care plans (7.9%), and those categorized as aged, blind, and disabled (28.1%) were more likely to receive telemedicine (p<.001). Nearly 95% of telemedicine claims were associated with a behavioral health diagnosis, of which over 50% were for bipolar disorder and attention-deficit disorder or attention-deficit hyperactivity disorder (29.3% and 23.4%, respectively). State-level variation was high, ranging from .0 to 59.91 claims per 10,000 enrollees (Arkansas and Arizona, respectively)., Conclusions: Despite the touted potential for telemedicine to improve health care access, actual utilization of telemedicine in Medicaid programs was low. It was predominantly used to treat behavioral health diagnoses. Reimbursement alone is insufficient to support broad utilization for Medicaid enrollees.

Background: Seed-applied neonicotinoids are widely used in agriculture, yet their effects on non-target species remain incompletely understood. One important group of non-target species is arthropod natural enemies (predators and parasitoids), which contribute considerably to suppression of crop pests. We hypothesized that seed-applied neonicotinoids reduce natural-enemy abundance, but not as strongly as alternative insecticide options such as soil- and foliar-applied pyrethroids. Furthermore we hypothesized that seed-applied neonicotinoids affect natural enemies through a combination of toxin exposure and prey scarcity., Methods: To test our hypotheses, we compiled datasets comprising observations from randomized field studies in North America and Europe that compared natural-enemy abundance in plots that were planted with seed-applied neonicotinoids to control plots that were either (1) managed without insecticides (20 studies, 56 site-years, 607 observations) or (2) managed with pyrethroid insecticides (eight studies, 15 site-years, 384 observations). Using the effect size Hedge's d as the response variable, we used meta-regression to estimate the overall effect of seed-applied neonicotinoids on natural-enemy abundance and to test the influence of potential moderating factors., Results: Seed-applied neonicotinoids reduced the abundance of arthropod natural enemies compared to untreated controls ( d = -0.30 ± 0.10 [95% confidence interval]), and as predicted under toxin exposure this effect was stronger for insect than for non-insect taxa ( Q M = 8.70, df = 1, P = 0.003). Moreover, seed-applied neonicotinoids affected the abundance of arthropod natural enemies similarly to soil- or foliar-applied pyrethroids ( d = 0.16 ± 0.42 or -0.02 ± 0.12; with or without one outlying study). Effect sizes were surprisingly consistent across both datasets ( I 2  = 2.7% for no-insecticide controls; I 2  = 0% for pyrethroid controls), suggesting little moderating influence of crop species, neonicotinoid active ingredients, or methodological choices., Discussion: Our meta-analysis of nearly 1,000 observations from North American and European field studies revealed that seed-applied neonicotinoids reduced the abundance of arthropod natural enemies similarly to broadcast applications of pyrethroid insecticides. These findings suggest that substituting pyrethroids for seed-applied neonicotinoids, or vice versa, will have little net affect on natural enemy abundance. Consistent with previous lab work, our results also suggest that seed-applied neonicotinoids are less toxic to spiders and mites, which can contribute substantially to biological control in many agricultural systems. Finally, our ability to interpret the negative effect of neonicotinoids on natural enemies is constrained by difficulty relating natural-enemy abundance to biological control function; this is an important area for future study., Competing Interests: The authors declare there are no competing interests.

Ecosystems transition quickly in the Anthropocene, whereas biodiversity adapts more slowly. Here we simulated a shifting woodland ecosystem on the Colorado Plateau of western North America by using as its proxy over space and time the fundamental niche of the Arizona black rattlesnake (Crotalus cerberus). We found an expansive (= end-of-Pleistocene) range that contracted sharply (= present), but is blocked topographically by Grand Canyon/Colorado River as it shifts predictably northwestward under moderate climate change (= 2080). Vulnerability to contemporary wildfire was quantified from available records, with forested area reduced more than 27% over 13 years. Both 'ecosystem metrics' underscore how climate and wildfire are rapidly converting the Plateau ecosystem into novel habitat. To gauge potential effects on C. cerberus, we derived a series of relevant 'conservation metrics' (i.e. genetic variability, dispersal capacity, effective population size) by sequencing 118 individuals across 846 bp of mitochondrial (mt)DNA-ATPase8/6. We identified five significantly different clades (net sequence divergence = 2.2%) isolated by drainage/topography, with low dispersal (F ST = 0.82) and small sizes (2N ef = 5.2). Our compiled metrics (i.e. small-populations, topographic-isolation, low-dispersal versus conserved-niche, vulnerable-ecosystem, dispersal barriers) underscore the susceptibility of this woodland specialist to a climate and wildfire tandem. We offer adaptive management scenarios that may counterbalance these metrics and avoid the extirpation of this and other highly specialized, relictual woodland clades.

Morphological data are a conduit for the recognition and description of species, and their acquisition has recently been broadened by geometric morphometric (GM) approaches that co-join the collection of digital data with exploratory 'big data' analytics. We employed this approach to dissect the Western Rattlesnake (Crotalus viridis) species-complex in North America, currently partitioned by mitochondrial (mt)DNA analyses into eastern and western lineages (two and seven subspecies, respectively). The GM data (i.e., 33 dorsal and 50 lateral head landmarks) were gleaned from 2,824 individuals located in 10 museum collections. We also downloaded and concatenated sequences for six mtDNA genes from the NCBI GenBank database. GM analyses revealed significant head shape differences attributable to size and subspecies-designation (but not their interactions). Pairwise shape distances among subspecies were significantly greater than those derived from ancestral character states via squared-change parsimony, with the greatest differences separating those most closely related. This, in turn, suggests the potential for historic character displacement as a diversifying force in the complex. All subspecies, save one, were significantly differentiated in a Bayesian discriminant function analysis (DFA), regardless of whether our priors were uniform or informative (i.e., mtDNA data). Finally, shape differences among sister-clades were significantly greater than expected by chance alone under a Brownian model of evolution, promoting the hypothesis that selection rather than drift was the driving force in the evolution of the complex. Lastly, we combine head shape and mtDNA data so as to derived an integrative taxonomy that produced robust boundaries for six OTUs (operational taxonomic units) of the C. viridis complex. We suggest these boundaries are concomitant with species-status and subsequently provide a relevant nomenclature for its recognition and representation.

Businesses changing their practices in ways that support tobacco control efforts recently have gained interest, as demonstrated by CVS Health's voluntary policy to end tobacco sales. Point-of-sale (POS) advertisements are associated with youth smoking initiation, increased tobacco consumption, and reduced quit attempts among smokers. There is interest in encouraging retailers to limit tobacco POS advertisements voluntarily. This qualitative exploratory study describes Oklahoma tobacco retailers' perspectives on a mutual benefit exchange approach, and preferred message and messenger qualities that would entice them to take voluntary action to limit tobacco POS advertisements. This study found that mutual benefit exchange could be a viable option along with education and law as strategies to create behavior change among tobacco retailers. Many retailers stated that they would be willing to remove noncontractual POS advertisements for a 6-month commitment period when presented with mutual exchange benefit, tailored message, and appropriate messenger. Mutual benefit exchange, as a behavior change strategy to encourage voluntary removal of POS tobacco advertisements, was acceptable to retailers, could enhance local tobacco control in states with preemption, and may contribute to setting the foundation for broader legislative efforts., (© 2015 Society for Public Health Education.)

Biodiversity elements with narrow niches and restricted distributions (i.e., 'short range endemics,' SREs) are particularly vulnerable to climate change. The New Mexico Ridge-nosed Rattlesnake (Crotalus willardi obscurus, CWO), an SRE listed under the U.S. Endangered Species Act within three sky islands of southwestern North America, is constrained at low elevation by drought and at high elevation by wildfire. We combined long-term recapture and molecular data with demographic and niche modeling to gauge its climate-driven status, distribution, and projected longevity. The largest population (Animas) is numerically constricted (N = 151), with few breeding adults (Nb = 24) and an elevated inbreeding coefficient (ΔF = 0.77; 100 years). Mean home range (0.07 km2) is significantly smaller compared to other North American rattlesnakes, and movements are within, not among sky islands. Demographic values, when gauged against those displayed by other endangered/Red-Listed reptiles [e.g., Loggerhead Sea Turtle (Caretta caretta)], are either comparable or markedly lower. Survival rate differs significantly between genders (female

Neonicotinoids are the most widely used class of insecticides worldwide, but patterns of their use in the U.S. are poorly documented, constraining attempts to understand their role in pest management and potential nontarget effects. We synthesized publicly available data to estimate and interpret trends in neonicotinoid use since their introduction in 1994, with a special focus on seed treatments, a major use not captured by the national pesticide-use survey. Neonicotinoid use increased rapidly between 2003 and 2011, as seed-applied products were introduced in field crops, marking an unprecedented shift toward large-scale, preemptive insecticide use: 34-44% of soybeans and 79-100% of maize hectares were treated in 2011. This finding contradicts recent analyses, which concluded that insecticides are used today on fewer maize hectares than a decade or two ago. If current trends continue, neonicotinoid use will increase further through application to more hectares of soybean and other crop species and escalation of per-seed rates. Alternatively, our results, and other recent analyses, suggest that carefully targeted efforts could considerably reduce neonicotinoid use in field crops without yield declines or economic harm to farmers, reducing the potential for pest resistance, nontarget pest outbreaks, environmental contamination, and harm to wildlife, including pollinator species.

This paper studies the origin and the genetic and morphological diversity of the pumpkinseed sunfish, a North American invader that is actively expanding its range in the Northern Black Sea Coast. Based on an analysis of variability of the nucleotide sequence of the mtDNA cyt b locus, it was found that all populations of the Northern Black Sea Coast (basins of Dnieper, Dniester, and Danube rivers) are represented by one haplotype. Intraspecific variability is absent. Phylogeographic analysis revealed that the most related haplotype is in a population of pumpkinseed sunfish from New Germany Lake in the Potomac Riverbasin (Maryland, United States), which makes it possible to consider it a parent of the investigated populations. Morphological variation oin countable traits was highly homogeneous. Significant differentiation of a sample from the population of the Dnieper Reservoir from the populations of the Danube and Dniester was found for plastic traits of both the body and cranium. Analysis of the trajectories of development showed that the Dnieper is inhabited by a "pelagic" morpho-ecological form of pumpkinseed sunfish, while the Dniester and Danube is inhabited by a "littoral" form. It is suggested that the success of the settlement of this North American species in the Northern Black Sea Coast does not depend on the origin or the level of its genetic diversity but is instead likely to be ensured by the realization of its available discrete morpho-ecological variability.

Policies that shield people from the harm of tobacco exposure are essential to protect the health of the population. Coalitions have often led the way in safeguarding community health by promoting social norm change though policy adoption. In some states, tobacco control laws are weak, in part because of a tobacco industry tactic of prohibiting or pre-empting communities from enacting ordinances that are more protective. In spite of strong state-level preemptions, local coalitions in Oklahoma have implemented hundreds of voluntary policies in tobacco control that have improved the protection and health of their communities while not violating preemption. Three case studies of policy change are presented that exemplify the key approach of local coalitions working with strong allies and informed decision makers to establish tobacco-free businesses, schools, and outdoor recreational areas. In each of the cases, the policy changes surpassed the protection provided by the state laws and inspired additional policy changes. The key strategies and lessons learned may help tobacco control coalitions in other states limited by preemption to garner more support and momentum for important policy changes within their communities and states., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Research in tobacco control demonstrating best practices is widely disseminated; however, application at the local level is often difficult. Translating research into practice requires a concerted effort to develop an understanding of the evidence and how it can be applied within diverse contexts., Purpose: A strategic planning infrastructure was developed to support the translation of evidence-based interventions into community practice. This paper highlights the strategic process of turning "know-what" into "know-how" to facilitate the strategic planning and implementation of tobacco control best practices at the local level., Design: The purpose, people, process, and product strategies of knowledge management and translation provided a framework for the strategic planning infrastructure. The knowledge translation concepts of audience, motivations, and mechanisms were synergized in the neo-strategic planning component design., Setting/participants: The participants were 20 community coalitions funded to implement local tobacco control programs., Intervention: From 2004 to 2011, the strategic planners facilitated a cyclical process to translate research into practice using a trio of integrated tools, skill-building workshops on strategic planning, and grantee-driven technical assistance and consultation., Main Outcome Measures: In the short term, the usefulness of the strategic planning components to the programs was measured. The intermediate outcome was the successful movement of the community programs from the planning stage to the implementation stage. The achievement of community-level changes in planned tobacco control efforts was the overall outcome measure for the success of the local coalitions., Results: Seventeen of 20 communities that began the planning process implemented strategic plans. All 17 of the programs implemented evidence-based practices, resulting in numerous tobacco-free policies, increased cessation, and increased support from the media and community., Conclusions: Bridging the gap between research and practice can enhance the practicality, efficiency, and effectiveness of tobacco control programs at the local level, maximizing the potential positive health impact., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin on lymphatic endothelial cells initiates platelet signaling events that are necessary for prevention of blood-lymph mixing during development. In the present study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases promotes platelet adhesion to primary mouse lymphatic endothelial cells at low shear. Using supported lipid bilayers containing mobile Podoplanin, we further show that activation of Src and Syk in platelets promotes clustering of CLEC-2 and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center of the platelet to form a single structure. Fluorescence lifetime imaging demonstrates that molecules within these clusters are within 10 nm of one another and that the clusters are disrupted by inhibition of Src and Syk family kinases. CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin using direct stochastic optical reconstruction microscopy. These findings provide mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature development., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Cerebrospinal fluid (CSF) analysis is routinely used in the diagnostic work-up of multiple sclerosis (MS), by detecting CSF-specific oligoclonal bands (OCB). More recently, several studies have reported CSF free light chains (FLC) as an alternative. We show that absolute CSF κFLC concentrations were highly sensitive - more than OCB testing - and specific for clinically isolated syndrome, relapsing remitting and primary progressive MS. Measurement of κFLC alone was sufficient. Our results suggest that CSF κFLC levels measured by nephelometry, if validated in a larger series, are a preferred test to OCB analysis in the diagnostic work-up of patients suspected of having MS., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The C-type lectin-like receptor CLEC-2 mediates platelet activation through a hem-immunoreceptor tyrosine-based activation motif (hemITAM). CLEC-2 initiates a Src- and Syk-dependent signaling cascade that is closely related to that of the 2 platelet ITAM receptors: glycoprotein (GP)VI and FcγRIIa. Activation of either of the ITAM receptors induces shedding of GPVI and proteolysis of the ITAM domain in FcγRIIa. In the present study, we generated monoclonal antibodies against human CLEC-2 and used these to measure CLEC-2 expression on resting and stimulated platelets and on other hematopoietic cells. We show that CLEC-2 is restricted to platelets with an average copy number of ∼2000 per cell and that activation of CLEC-2 induces proteolytic cleavage of GPVI and FcγRIIa but not of itself. We further show that CLEC-2 and GPVI are expressed on CD41+ microparticles in megakaryocyte cultures and in platelet-rich plasma, which are predominantly derived from megakaryocytes in healthy donors, whereas microparticles derived from activated platelets only express CLEC-2. Patients with rheumatoid arthritis, an inflammatory disease associated with increased microparticle production, had raised plasma levels of microparticles that expressed CLEC-2 but not GPVI. Thus, CLEC-2, unlike platelet ITAM receptors, is not regulated by proteolysis and can be used to monitor platelet-derived microparticles., (© 2014 by The American Society of Hematology.)

Pharmacological and surgical treatments offer symptomatic benefits to patients with Parkinson's disease; however, as the condition progresses, patients experience gradual worsening in symptom control, with the development of a range of disabling complications. In addition, none of the currently available therapies have convincingly shown disease-modifying effects - either in slowing or reversing the disease. These problems have led to extensive research into the possible use of gene therapy as a treatment for Parkinson's disease. Several treatments have reached human clinical trial stages, providing important information on the risks and benefits of this novel therapeutic approach, and the tantalizing promise of improved control of this currently incurable neurodegenerative disorder.

Axon regeneration in the injured adult CNS is reportedly inhibited by myelin-derived inhibitory molecules, after binding to a receptor complex comprised of the Nogo-66 receptor (NgR1) and two transmembrane co-receptors p75/TROY and LINGO-1. However, the post-injury expression pattern for LINGO-1 is inconsistent with its proposed function. We demonstrated that AMIGO3 levels were significantly higher acutely than those of LINGO-1 in dorsal column lesions and reduced in models of dorsal root ganglion neuron (DRGN) axon regeneration. Similarly, AMIGO3 levels were raised in the retina immediately after optic nerve crush, whilst levels were suppressed in regenerating optic nerves, induced by intravitreal peripheral nerve implantation. AMIGO3 interacted functionally with NgR1-p75/TROY in non-neuronal cells and in brain lysates, mediating RhoA activation in response to CNS myelin. Knockdown of AMIGO3 in myelin-inhibited adult primary DRG and retinal cultures promoted disinhibited neurite growth when cells were stimulated with appropriate neurotrophic factors. These findings demonstrate that AMIGO3 substitutes for LINGO-1 in the NgR1-p75/TROY inhibitory signalling complex and suggests that the NgR1-p75/TROY-AMIGO3 receptor complex mediates myelin-induced inhibition of axon growth acutely in the CNS. Thus, antagonizing AMIGO3 rather than LINGO-1 immediately after CNS injury is likely to be a more effective therapeutic strategy for promoting CNS axon regeneration when combined with neurotrophic factor administration.

Global climate change is apparent within the Arctic and the south-western deserts of North America, with record drought in the latter reflected within 640,000 km(2) of the Colorado River Basin. To discern the manner by which natural and anthropogenic drivers have compressed Basin-wide fish biodiversity, and to establish a baseline for future climate effects, the Stream Hierarchy Model (SHM) was employed to juxtapose fluvial topography against molecular diversities of 1092 Bluehead Sucker (Catostomus discobolus). MtDNA revealed three geomorphically defined evolutionarily significant units (ESUs): Bonneville Basin, upper Little Colorado River and the remaining Colorado River Basin. Microsatellite analyses (16 loci) reinforced distinctiveness of the Bonneville Basin and upper Little Colorado River, but subdivided the Colorado River Basin into seven management units (MUs). One represents a cline of three admixed gene pools comprising the mainstem and its lower-gradient tributaries. Six others are not only distinct genetically but also demographically (i.e. migrants/generation <9.7%). Two of these (i.e. Grand Canyon and Canyon de Chelly) are defined by geomorphology, two others (i.e. Fremont-Muddy and San Raphael rivers) are isolated by sharp declivities as they drop precipitously from the west slope into the mainstem Colorado/Green rivers, another represents an isolated impoundment (i.e. Ringdahl Reservoir), while the last corresponds to a recognized subspecies (i.e. Zuni River, NM). Historical legacies of endemic fishes (ESUs) and their evolutionary potential (MUs) are clearly represented in our data, yet their arbiter will be the unrelenting natural and anthropogenic water depletions that will precipitate yet another conservation conflict within this unique but arid region., (© 2012 Blackwell Publishing Ltd.)

Multichannel omnivory by generalist predators, especially the use of both grazing and epigeic prey, has the potential to increase predator abundance and decrease herbivore populations. However, predator use of the epigeic web (soil surface detritus/microbe/algae consumers) varies considerably for reasons that are poorly understood. We therefore used a stable isotope approach to determine whether prey availability and predator hunting style (active hunting vs. passive web-building) impacted the degree of multichannel omnivory by the two most abundant predators on an intertidal salt marsh, both spiders. We found that carbon isotopic values of herbivores remained constant during the growing season, while values for epigeic feeders became dramatically more enriched such that values for the two webs converged in August. Carbon isotopic values for both spider species remained midway between the two webs as values for epigeic feeders shifted, indicating substantial use of prey from both food webs by both spider species. As the season progressed, prey abundance in the grazing food web increased while prey abundance in the epigeic web remained constant or declined. In response, prey consumption by the web-building spider shifted toward the grazing web to a much greater extent than did consumption by the hunting spider, possibly because passive web-capture is more responsive to changes in prey availability. Although both generalist predator species engaged in multichannel omnivory, hunting mode influenced the extent to which these predators used prey from the grazing and epigeic food webs, and could thereby influence the strength of trophic cascades in both food webs.

Platelets are highly reactive cell fragments that adhere to exposed extracellular matrix (ECM) and prevent excessive blood loss by forming clots. Paradoxically, megakaryocytes, which produce platelets in the bone marrow, remain relatively refractory to the ECM-rich environment of the bone marrow despite having the same repertoire of receptors as platelets. These include the ITAM (immunoreceptor tyrosine-based activation motif)-containing collagen receptor complex, which consists of glycoprotein VI (GPVI) and the Fc receptor γ-chain, and the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing receptor G6b-B. We showed that mice lacking G6b-B exhibited macrothrombocytopenia (reduced platelet numbers and the presence of enlarged platelets) and a susceptibility to bleeding as a result of aberrant platelet production and function. Platelet numbers were markedly reduced in G6b-B-deficient mice compared to those in wild-type mice because of increased platelet turnover. Furthermore, megakaryocytes in G6b-B-deficient mice showed enhanced metalloproteinase production, which led to increased shedding of cell-surface receptors, including GPVI and GPIbα. In addition, G6b-B-deficient megakaryocytes exhibited reduced integrin-mediated functions and defective formation of proplatelets, the long filamentous projections from which platelets bud off. Together, these findings establish G6b-B as a major inhibitory receptor regulating megakaryocyte activation, function, and platelet production.

Metabolomic analysis has the potential to generate disease-specific metabolite signatures unique to individuals. Autoimmune illnesses, such as inflammatory uveitis, have highlighted the discriminative power of metabolomics by allowing disease sub-classification. Elucidating surrogate markers for neurological disease is particularly important, given the constraints in accessing central nervous system tissue in vivo. Metabolomic analysis, using either (1)H NMR spectroscopy or mass spectroscopy can be performed using biofluids such as urine, blood or cerebrospinal fluid and may permit the identification of disease specific metabolite signatures which may be useful as disease biomarkers. This is particularly relevant to complex diseases such as multiple sclerosis where promising preliminary work has been carried out. Future work in this field may well generate metabolite profiles to monitor disease evolution, prognosticate and guide therapeutic decisions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Theory predicts that founder effects have a primary role in determining metapopulation genetic structure. However, ecological factors that affect extinction-colonization dynamics may also create spatial variation in the strength of genetic drift and migration. We tested the hypothesis that ecological factors underlying extinction-colonization dynamics influenced the genetic structure of a tiger salamander (Ambystoma tigrinum) metapopulation. We used empirical data on metapopulation dynamics to make a priori predictions about the effects of population age and ecological factors on genetic diversity and divergence among 41 populations. Metapopulation dynamics of A. tigrinum depended on wetland area, connectivity and presence of predatory fish. We found that newly colonized populations were more genetically differentiated than established populations, suggesting that founder effects influenced genetic structure. However, ecological drivers of metapopulation dynamics were more important than age in predicting genetic structure. Consistent with demographic predictions from metapopulation theory, genetic diversity and divergence depended on wetland area and connectivity. Divergence was greatest in small, isolated wetlands where genetic diversity was low. Our results show that ecological factors underlying metapopulation dynamics can be key determinants of spatial genetic structure, and that habitat area and isolation may mediate the contributions of drift and migration to divergence and evolution in local populations.

Adeno-associated viral vectors (AAV) are increasingly used to deliver therapeutic genes to the central nervous system (CNS) where they promote transgene expression in post mitotic neurones for long periods with little or no toxicity. In adult rat dorsal root ganglia (DRG), we investigated the cellular tropism of AAV8 containing the green fluorescent protein gene (gfp) after either intra-lumbar DRG or intrathecal injection and showed that transduced DRG neurones (DRGN) expressed GFP irrespective of the delivery route, while non-neuronal cells were GFP(-). After intra-DRG delivery of AAV8(gfp), the mean DRGN transduction rate was 11%, while intrathecal delivery transduced a mean of 1.5% DRGN. After intra-DRG injection, 2% of small DRGN (<30 μm in diameter) were GFP(+) compared with 32% of large DRGN (>60 μm in diameter). Axons of transduced DRGN were also GFP(+); no intra-spinal neurones were transduced. A small number of contralateral DRGN were transduced after intra-DRG injection, suggesting that AAV8 may diffuse from injected DRG into the spinal canal. Microglia and astrocytes were highly ramified with increased GFAP(+) immunoreactivity (i.e. activated) in the neuropil around GFP(+) DRG axon projections within the cord after intra-DRG injection. This study showed that after both intra-DRG and intrathecal delivery, strong preferential AAV8 tropism exists for large DRGN unassociated with cell death, but GFP(+) axons projecting in the spinal cord induced local glial activation. These results open up opportunities for targeted delivery of therapeutics such as neurotrophic factors to the injured spinal cord., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

Multiple sclerosis is a common disease of the CNS. The first of these articles (Hassan-Smith and Douglas, 2011) examined its epidemiology and diagnosis. This article explores the management and prognosis of multiple sclerosis, including the rapidly evolving field of disease-modifying therapeutics. However, equally important is the management of problems related to chronic multiple sclerosis and knowledge of which symptomatic treatments may be helpful. Finally, the prognosis is discussed; vital when counselling newly diagnosed patients.

Multiple sclerosis is an inflammatory disease of the CNS. The disease is predominantly diagnosed in young adults, with long-term implications for both their personal and professional lives. The economic impact of the condition is particularly significant as the majority of patients are of working age, costing the UK economy approximately £1.4 billion (McCrone et al, 2008).

The reasons for the failure of central nervous system (CNS) axons to regenerate include the presence of myelin- and non-myelin derived inhibitory molecules, neuronal apoptosis and the absence of a potent neurotrophic stimulus. Transactivation of the epidermal growth factor receptor (EGFR) has been implicated in signalling inhibition of axon growth in the CNS. Small molecule EGFR inhibitors such as AG1478 and PD168393 promote CNS axon growth after optic nerve transection despite the presence of inhibitory molecules in the environment of the regenerating axon. However, our results demonstrate that phosphorylated EGFR (pEGFR) is not present on regenerating axons and that the majority of pEGFR is present in glia, suggesting that EGFR cannot play a direct intra-axonal role in signalling inhibition and thus disinhibited CNS axon growth must be indirectly mediated by glia. We argue that EGFR may not have a role in signalling axon growth inhibition since AG1478 and PD168393 promotes neuronal neurite outgrowth in CNS myelin-inhibited cultures after EGFR knockdown. This review discusses the current evidences for and against the involvement of EGFR in signalling myelin inhibition., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Axon regeneration in the adult central nervous system (CNS) is prevented by inhibitory molecules present in myelin, which bind to a receptor complex that leads to downstream RhoGTP activation and axon growth cone collapse. Here, we compared expression of Citron kinase (Citron-K), a target molecule of RhoGTP in non-regenerating dorsal root ganglion neurons (DRGN) after dorsal column (DC) injury, and in regenerating DRGN after either sciatic nerve (SN) injury or preconditioning SN+DC lesion models. We show by microarray that Citron-K mRNA levels in DRGN of a non-regenerating DC injury model were elevated 2-fold compared to those of intact control DRGN. Conversely, Citron-K levels were reduced by 2 and 2.4-fold at 10 days post lesion in the regenerating SN and preconditioning SN+DC lesion models, respectively, compared to levels in control intact DRGN. Western blotting and immunohistochemistry confirmed these observations and localised Citron-K immunostaining to both DRGN and satellite glia. In dissociated, adult rat DRG cell cultures, 80% knockdown of Citron-K, in the presence of inhibitory concentrations of CNS myelin extract (CME), promoted significant disinhibited DRGN neurite outgrowth, only when cells were stimulated with neurotrophic factors. The levels of RhoGTP remained unchanged after Citron-K knockdown in the presence of CME while enhanced cofilin levels correlated with disinhibited DRGN neurite outgrowth. This observation suggests that Citron-K plays a role in axon growth downstream of Rho activation. We conclude that Citron-K regulates actin polymerisation downstream of RhoA and may offer a potentially novel therapeutic approach for promoting CNS axon regeneration., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This article documents the addition of 229 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acacia auriculiformis × Acacia mangium hybrid, Alabama argillacea, Anoplopoma fimbria, Aplochiton zebra, Brevicoryne brassicae, Bruguiera gymnorhiza, Bucorvus leadbeateri, Delphacodes detecta, Tumidagena minuta, Dictyostelium giganteum, Echinogammarus berilloni, Epimedium sagittatum, Fraxinus excelsior, Labeo chrysophekadion, Oncorhynchus clarki lewisi, Paratrechina longicornis, Phaeocystis antarctica, Pinus roxburghii and Potamilus capax. These loci were cross-tested on the following species: Acacia peregrinalis, Acacia crassicarpa, Bruguiera cylindrica, Delphacodes detecta, Tumidagena minuta, Dictyostelium macrocephalum, Dictyostelium discoideum, Dictyostelium purpureum, Dictyostelium mucoroides, Dictyostelium rosarium, Polysphondylium pallidum, Epimedium brevicornum, Epimedium koreanum, Epimedium pubescens, Epimedium wushanese and Fraxinus angustifolia., (© 2010 Blackwell Publishing Ltd.)

CD248 is a cell surface receptor that specifically identifies fibroblasts and pericytes during development and in association with cancer and inflammation. However, its function is poorly defined and its role in lymphoid organs not studied. Here, we used (4-hydroxy-3-nitrophenyl)acetyl chicken gamma-globulin immunisation and mice lacking CD248 to study whether CD248 modulates popliteal LN (pLN) expansion and subsequent immune responses. We have found that CD248 is required for complete pLN expansion but not for co-ordination of B and T cell compartmentalisation or antibody production following (4-hydroxy-3-nitrophenyl)acetyl chicken gamma-globulin immunisation. In vitro, we show that CD248 expression in human MG63 stromal cells and mouse embryonic fibroblasts leads to a pro-proliferative and pro-migratory phenotype. This correlates with a proliferating CD248(+) population observed in vivo during pLN expansion. Taken together, these data highlight a role for CD248 in secondary lymphoid organ remodelling during adaptive immune responses.

We analyzed both mitochondrial (mt-) and nuclear (n) DNAs in a conservation phylogenetic framework to examine deep and shallow histories of the Beaded Lizard (Heloderma horridum) and Gila Monster (H. suspectum) throughout their geographic ranges in North and Central America. Both mtDNA and intron markers clearly partitioned each species. One intron and mtDNA further subdivided H. horridum into its four recognized subspecies (H. n. alvarezi, charlesbogerti,exasperatum, and horridum). However, the two subspecies of H. suspectum (H. s. suspectum and H. s. cinctum) were undefined. A supertree approach sustained these relationships. Overall, the Helodermatidae is reaffirmed as an ancient and conserved group. Its most recent common ancestor (MRCA) was Lower Eocene [35.4 million years ago (mya)], with a approximately 25 my period of stasis before the MRCA of H. horridum diversified in Lower Miocene. Another approximately 5 my passed before H. h. exasperatum and H. h. horridum diverged, followed by approximately 1.5 my before H. h. alvarezi and H. h. charlesbogerti separated. Heloderma suspectum reflects an even longer period of stasis (approximately 30 my) before diversifying from its MRCA. Both H. suspectum (México) and H. h. alvarezi also revealed evidence of historic range expansion following a recent bottleneck. Our conservation phylogenetic approach emphasizes the origin and diversification of this group, yields information on the manner by which past environmental variance may have impacted its populations and, in turn, allows us to disentangle historic from contemporary impacts that might threaten its long-term persistence. The value of helodermatid conservation resides in natural services and medicinal products, particularly venom constituents, and these are only now being realized., ((c) 2009 Elsevier Inc. All rights reserved.)

Inhibition of central nervous system axon growth is reportedly mediated in part by calcium-dependent phosphorylation of axonal epidermal growth factor receptor, with local administration of the epidermal growth factor receptor kinase inhibitors AG1478 and PD168393 to an optic nerve lesion site promoting adult retinal ganglion cell axon regeneration. Here, we show that epidermal growth factor receptor was neither constitutively expressed, nor activated in optic nerve axons in our non-regenerating and regenerating optic nerve injury models, a finding that is inconsistent with phosphorylated epidermal growth factor receptor-dependent intra-axonal signalling of central nervous system myelin-related axon growth inhibitory ligands. However, epidermal growth factor receptor was localized and activated within most glia in the retina and optic nerve post-injury, and thus an indirect glial-dependent mechanism for stimulated retinal ganglion cell axon growth by epidermal growth factor receptor inhibitors seemed plausible. Using primary retinal cultures with added central nervous system myelin extracts, we confirmed previous reports that AG1478/PD168393 blocks epidermal growth factor receptor activation and promotes disinhibited neurite outgrowth. Paradoxically, neurites did not grow in central nervous system myelin extract-containing cultures after short interfering ribonucleic acid-mediated knockdown of epidermal growth factor receptor. However, addition of AG1478 restored neurite outgrowth to short interfering ribonucleic acid-treated cultures, implying that epidermal growth factor receptor does not mediate AG1478-dependent effects. TrkA-/B-/C-Fc fusion proteins and the kinase blocker K252a abrogated the neuritogenic activity in these cultures, correlating with the presence of the neurotrophins brain derived neurotrophic factor, nerve growth factor and neurotrophin-3 in the supernatant and increased intracellular cyclic adenosine monophosphate activity. Neurotrophins released by AG1478 stimulated disinhibited retinal ganglion cell axon growth in central nervous system myelin-treated cultures by the induction of regulated intramembraneous proteolysis of p75(NTR) and Rho inactivation. Retinal astrocytes/Müller cells and retinal ganglion cells were the source of neurotrophins, with neurite outgrowth halved in the presence of glial inhibitors. We attribute AG1478-stimulated neuritogenesis to the induced release of neurotrophins together with raised cyclic adenosine monophosphate levels in treated cultures, leading to axon growth and disinhibition by neurotrophin-induced regulated intramembraneous proteolysis of p75(NTR). These off-target effects of epidermal growth factor receptor kinase inhibition suggest a novel therapeutic approach for designing treatments to promote central nervous system axon regeneration.

In the present study, we investigated the role and mechanism through which activated retinal glia stimulate retinal ganglion cell (RGC) neurite outgrowth. We have found that the level of retinal glial activation correlates directly with enhanced RGC neurite outgrowth after a preconditioning intravitreal Zymosan injection. Reduction in the number of activated glia in primary rat retinal cultures led to significantly reduced RGC neurite outgrowth. Glial-related neurite outgrowth appears to be, at least in part, mediated via apolipoprotein E (ApoE), which is expressed by activated retinal astrocytes and Müller glia. ApoE-deficient mice showed significantly reduced RGC neurite outgrowth potential after intravitreal Zymosan injection compared with age-matched wild-type animals. These observations suggest that ApoE, expressed by activated retinal glia, stimulates RGC neurite outgrowth after intravitreal Zymosan injection.

Background: Chronic communicating hydrocephalus is a common sequela of subarachnoid haemorrhage and develops when the flow and drainage of CSF are impaired after fibrosis in the subarachnoid space. Released by platelets into the CSF after subarachnoid haemorrhage, transforming growth factor (TGF)beta1/beta2 are potent fibrogenic agents that may promote post-haemorrhagic fibrosis and chronic communicating hydrocephalus., Methods: Temporal changes in total (latent plus active) TGFbeta1/beta2 CSF levels of post-haemorrhage patients developing acute hydrocephalus were measured using ELISA to discover if titres were higher in patients that subsequently developed chronic communicating hydrocephalus, compared with those that did not., Results: Mean (SD) CSF levels of total TGFbeta1 were 97 (42) pg/ml and total TGFbeta2 were 395 (39) pg/ml in control patients with (non-haemorrhagic) hydrocephalus. For days 1-5 post-subarachnoid haemorrhage (dph), levels of 1427 (242) pg/ml and 976 (191) pg/ml were seen for total TGFbeta1 and TGFbeta2, respectively. Beyond 5 dph, total TGFbeta1/beta2 levels declined but remained significantly elevated (p<0.01) above control patient values for at least 19 dph. Haemorrhagic patients that went on to develop chronic communicating hydrocephalus had significantly higher levels of total TGFbeta1 (p<0.01) and TGFbeta2 (p<0.05) between 1 and 9 dph, compared with those of haemorrhagic patients that did not., Conclusions: Acutely measured levels of TGFbeta1/beta2 in the CSF of patients with subarachnoid haemorrhage are thus potential prognostic biomarkers for the subsequent development of chronic communicating hydrocephalus, indicating likely dependency on CSF shunting.

In investigating the consequences of gene silencing in axon growth disinhibition strategies in cultured retinal ganglion cells (RGC), we conducted experiments designed to silence RhoA signalling in PC12 and primary adult rat retinal cell cultures (containing RGC) by siRNA-mediated RhoA mRNA knockdown. We demonstrate wide differences in the levels of RhoA mRNA knockdown, dose-dependent cell toxicity, and induction of endogenous inflammatory cytokine and interferon responses to siRNA therapy. Toxicity effects observed with RhoA-siRNA was significantly reduced with "Stealth" chemical modification of the sequence, promoting approximately 50% and 70% knockdown of RhoA mRNA and protein in retinal cells, respectively, while promoting significant disinhibited RGC neurite outgrowth in the presence of inhibitory CNS myelin. Our results highlight differential responsiveness of cell lines compared to primary cultured cells, and demonstrate the efficacy of the "Stealth" modification to reduce siRNA-induced interferon responses, thereby increasing target cell viability and reducing off-target effects of the delivered nucleic acids.

The literature supports that unique rabies virus (RABV) variants are often compartmentalized in different species of bats. In Colorado, two divergent mtDNA lineages of big brown bats (Eptesicus fuscus) co-occur. RABV associated with this species also segregates into two clades. We hypothesized that unique RABV variants might be associated with mtDNA lineages of Colorado big brown bats. DNA was extracted from brain tissue of rabid big brown bats, the ND2 gene was amplified to determine mtDNA lineage, and the lineage was compared to a previously derived phylogenetic analysis of the RABV N gene. No correspondence was found between host bat lineage and RABV variant.

The past 10 years has seen a shift in our etiological concepts of Parkinson's disease, moving from a nearly exclusively environmentally mediated disease towards a complex disorder with important genetic contributors. The identification of responsible mutations in certain genes, particularly alpha-synuclein, Parkin, PINK1, DJ-1 and LRRK2, has increased our understanding of the clinical and pathological changes underlying Parkinson's disease, with implications for patient diagnosis, management and future research. This review will outline the specific genetic advances, discuss their implications for clinical practice and hint at future directions for research into this common and disabling disease.

Guillain-Barré syndrome typically presents with an acute ascending areflexic weakness, progressing over 4 weeks or less. The most common form of the disease is an acute inflammatory demyelinating polyneuropathy, but other forms with primarily axonal pathologies are well documented. The association of Guillain-Barré syndrome with a range of antecedent infections, particularly Campylobacter jejuni enteritis, is also established. A range of serological and neurophysiological investigations can assist in making an accurate diagnosis. Background information about the syndrome and the evidence base for such treatments are discussed herein.

During Pleistocene, the Laurentide ice sheet rearranged and diversified biotic distributions in eastern North America, yet had minimal physical impact in western North America where lineage diversification is instead hypothesized to result from climatic changes. If Pleistocene climatic fluctuations impacted desert species, the latter would reflect patterns of restricted gene flow concomitant with indications of demographic bottlenecks. Accordingly, molecular evidence for refugia should be present within these distributions and for subsequent range expansions as conditions improved. We sought answers to these questions by evaluating mitochondrial DNA (mtDNA) sequences from four species of rattlesnakes [Crotalus mitchellii (speckled rattlesnake), Crotalus cerastes (sidewinder), Crotalus tigris (tiger rattlesnake), Crotalus ruber (red diamond rattlesnake)] with distributions restricted to desert regions of southwestern North America. We inferred relationships using parsimony and maximum likelihood, tested intraspecific clades for population expansions, applied an isolation-with-migration model to determine bi-directional migration rates (m) among regions, and inferred divergence times for species and clades by applying a semiparametric penalized likelihood approach to our molecular data. Evidence for significant range expansion was present in two of eight regions in two species (Crotalus mitchellii pyrrhus, C. tigris region north). Two species (C. cerastes, C. mitchellii) showed a distribution concomitant with northward displacement of Baja California from mainland México, followed by vicariant separation into subclades. Effects of Pleistocene climate fluctuations were found in the distributions of all four species. Three regional diversification patterns were identified: (i) shallow genetic diversity that resulted from Pleistocene climatic events (C. tigris, C. ruber); (ii) deep Pleistocene divisions indicating allopatric segregation of subclades within refugia (C. mitchellii, C. cerastes); and (iii) lineage diversifications that extended to Pliocene or Late Miocene (C. mitchellii, C. cerastes). Clade-diversifying and clade-constraining effects impacted the four species of rattlesnakes unequally. We found relatively high levels of molecular diversification in the two most broadly distributed species (C. mitchellii, C. cerastes), and lower levels of genetic diversification in the two species (C. tigris, C. ruber) whose ranges are relatively more restricted. Furthermore, in several cases, the distributions of subspecies were not congruent with our molecular information. We suggest regional conservation perspectives for southwestern deserts cannot rely upon subspecies as biodiversity surrogates, but must instead employ a molecular and deep historical perspective as a primary mechanism to frame biodiversity reserves within this region.

According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-beta and provided an additive, increased delay in apoptosis when given in combination with IFN-beta. VCAM-1 delivered its antiapoptotic effect through binding the integrin alpha9beta1. The alpha9beta1 signaling pathway shares significant features with the IFN-beta survival signaling pathway, requiring PI3 kinase, NF-kappaB activation, as well as de novo protein synthesis, but the kinetics of NF-kappaB activation by VCAM-1 were slower and more sustained compared with IFN-beta. This study demonstrates a novel functional role for alpha9beta1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.

Objective: To explore patients' perceptions of health-care built environments, to assess how they perceived health-care built facilities and designs. To develop a set of patient-centred indicators by which to appraise future health-care designs., Design: Qualitative and quantitative methodologies, including futures group conferencing, autophotographic study, novice-expert exchanges and a questionnaire survey of a representative sample of past patients., Setting and Participants: The research was carried out at Salford Royal Hospitals NHS Trust (SRHT), Greater Manchester, UK, selected for the study because of planned comprehensive redevelopment based on the new NHS vision for hospital care and service delivery for the 21st century. Participants included 35 patients who took part in an autophotographic study, eight focus groups engaged in futures conferencing, a sample of past inpatients from the previous 12 months that returned 785 completed postal questionnaires., Results: The futures group provided suggestions for radical improvements which were categorized into transport issues; accessibility and mobility; ground and landscape designs; social and public spaces; homeliness and assurance; cultural diversity; safety and security; personal space and access to outside. Patients' autophotographic study centred on: the quality of the ward design, human interactions, the state and quality of personal space, and facilities for recreation and leisure. The novices' suggestions were organized into categories of elemental factors representing patient-friendly designs. Experts from the architectural and surveying professions and staff at SRHT in turn considered these categories and respective subsets of factors. They agreed with the novices in terms of the headings but differed in prioritizing the elemental factors. The questionnaire survey of past patients provided opinions about ward designs that varied according to where they stayed, single room, bay ward or long open ward. The main concerns were limitation of private space around the bed area, supportive of privacy and dignity, ward noise and other disturbances., Conclusions: Patients perceived sustainable health-care environments to be supportive of their health and recovery. The design indicators developed from their perspectives and from their considerations for improvements to the health-care built environment were based on their visions of the role of the health-care facilities. These were homely environments that supported normal lifestyle and family functioning and designs that were supportive of accessibility and travel movements through transitional spaces.

In an effort to provide effective and efficient care to patients with chronic health conditions, the U.S. healthcare system is in the process of redesigning its delivery system. One approach to meet the high demands of patients and to best utilize resources is the use of a multidisciplinary team approach to provide better care when compared to an individual patient - physician care. When properly implemented, this team approach provides positive measurable outcomes. With a diverse group of healthcare professionals, such as physicians, nurses, pharmacists, dieticians, and health educators with the patient at the center of the team, the team can ensure treatment goals are maintained for chronic diseases. The team approach implements: patient satisfaction and self-management, development of a community support network, team coordination, team communication, patient follow-up, use of protocols and other tools, use of computerized information systems, and outcome evaluations. The goal of this paper is to demonstrate the benefits of utilizing this multidisciplinary approach with Type II diabetes through the improvement of glycemic control and improved quality of life. Cost effectiveness is also discussed.

Biotic homogenization, the gradual replacement of native biotas by locally expanding non-natives, is a global process that diminishes floral and faunal distinctions among regions. Although patterns of homogenization have been well studied, their specific ecological and evolutionary consequences remain unexplored. We argue that our current perspective on biotic homogenization should be expanded beyond a simple recognition of species diversity loss, towards a synthesis of higher order effects. Here, we explore three distinct forms of homogenization (genetic, taxonomic and functional), and discuss their immediate and future impacts on ecological and evolutionary processes. Our goal is to initiate future research that investigates the broader conservation implications of homogenization and to promote a proactive style of adaptive management that engages the human component of the anthropogenic blender that is currently mixing the biota on Earth.

Inflammatory responses occur within tissue microenvironments, with functional contributions from both haematopoietic (lymphocytic) cells and stromal cells (including macrophages and fibroblasts). These environments are complex--a compound of many different cell types at different stages of activation and differentiation. Traditional models of inflammatory disease highlight the role of antigen-specific lymphocyte responses and attempt to identify causative agents. However, recent studies have indicated the importance of tissue microenvironments and the innate immune response in perpetuating the inflammatory process. The prominent role of stromal cells in the generation and maintenance of these environments has begun to challenge the primacy of the lymphocyte in regulating chronic inflammatory processes. Sensible enquiries into factors regulating the persistence of inflammatory disease necessitate an understanding of the mechanisms regulating tissue homeostasis and remodelling during inflammation. This article highlights recent insights into the factors regulating dynamic aspects of inflammation, focusing particularly on mononuclear cell infiltrates, their interactions with stromal cells in tissues and the relevance of these interactions to existing and possible future therapies. A key feature of current research has been a growing appreciation that disordered spatial and temporal interactions between infiltrating immune cells and resident stromal cells lie at the heart of disease persistence.

Absorption spectroscopy measurements of the time-dependent heating of thin foils exposed to intense z-pinch radiation sources are presented. These measurements and their analysis provide valuable benchmarks for, and insights into, the radiative heating of matter by x-ray sources. Z-pinch radiation sources with peak powers of up to 160 TW radiatively heated thin plastic-tamped aluminum foils to temperatures approximately 60 eV. The foils were located in open slots at the boundary of z-pinch hohlraums surrounding the pinch. Time-resolved Kalpha satellite absorption spectroscopy was used to measure the evolution of the Al ionization distribution, using a geometry in which the pinch served as the backlighter. The time-dependent pinch radius and x-ray power were monitored using framing camera, x-ray diode array, and bolometer measurements. A three-dimensional view factor code, within which one-dimensional (1D) radiation-hydrodynamics calculations were performed for each surface element in the view factor grid, was used to compute the incident and reemitted radiation flux distribution throughout the hohlraum and across the foil surface. Simulated absorption spectra were then generated by postprocessing radiation-hydrodynamics results for the foil heating using a 1D collisional-radiative code. Our simulated results were found to be in good general agreement with experimental x-ray spectra, indicating that the spectral measurements are consistent with independent measurements of the pinch power. We also discuss the sensitivity of our results to the spectrum of the radiation field incident on the foil, and the role of nonlocal thermodynamic equilibrium atomic kinetics in affecting the spectra.

Programmed cell death (apoptosis) is critical for the normal development and homeostasis of the immune system. There is emerging evidence that failure of apoptosis to eliminate potentially pathogenic, autoreactive T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). This failure is related to multiple abnormalities of apoptosis-regulatory molecules that involve survivin, a recently described cell cycle-regulated anti-apoptosis protein. In this study, we investigated the relationship between survivin expression in peripheral T lymphocytes and clinical features of MS. We detected a significant over-expression of survivin in mitogen stimulated T lymphocytes from patients with active MS when compared with corresponding expression in patients with stable MS or those with inflammatory and non-inflammatory neurologic disorders. This over-expression of survivin in patients with active MS correlated with cellular resistance to apoptosis and with features of disease activity, such as disease duration and the number of enhanced lesions on cranial magnetic resonance imaging. There was no correlation between cellular survivin levels and the expression of other apoptosis-inhibitory proteins, such as Bcl-2 and Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP). Our findings indicate that cellular over-expression of the novel anti-apoptosis protein survivin is a feature of clinically active MS.

Experiments performed on the 8-MA Saturn accelerator to investigate the effects of interwire gap spacing on long-implosion-time Z pinches have resulted in the observation of a regime of optimal wire number. The experiments varied the wire number of 40 and 32 mm diam arrays, resulting in interwire gaps from 3.9 to 0.36 mm, with fixed mass and length. aluminum K-shell powers up to 3.4 TW were measured, with long, slow rising, lower power x-ray pulses for interwire gaps greater than 2.2 mm and less than 0.7 mm, and short, fast rising, higher power pulses for interwire gaps in the range 0.7-2.2 mm.