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The CorWave LVAD uses a unique wave membrane technology for low shear blood propulsion, operating in a pulsatile mode, synchronized with the native ventricle. Preclinical testing suggests this new LVAD could overcome several limitations of continuous flow LVADs. The device will be evaluated in a multicenter feasibility study in Australia, Europe, and Asia. Patients, Clinicians, and Device Developers share a mutual interest to confirm device safety and performance as early as possible. Up to 15 patients will be enrolled using typical LVAD inclusion/exclusion criteria: patients with worsening heart failure despite optimal medical management. As in other LVAD trials, the primary endpoint will be survival. Secondary endpoints include freedom from adverse events (AEs), (e.g. stroke, bleeding, infection, and pump replacement), quality of life and neurocognitive measures. Given that this is a feasibility study, not powered to demonstrate clinical benefit, we also plan to collect data predictive of AEs, validating preclinical data where applicable. These will include von Willebrand Factor assays, arterial pulse pressure and aortic valve opening, which are factors implicated in bleeding and aortic insufficiency. Increased aorta stiffness post-LVAD, correlated with increased AEs, will be measured. The synchronous, pulsatile flow of the CorWave LVAD is hypothesized to improve patient exercise capacity and possibly native ventricular recovery. Thus, patients will undergo exercise testing and evaluation of ventricular size and ejection fraction while on pump support. Potential outcomes include 1) Low AEs and favorable biomarker and functional test data, permitting judicious initiation of a pivotal trial, 2) Equivocal AEs and/or inconclusive biomarker and functional results, enabling Clinicians and Device Developers to collaborate to identify improvements prior to a pivotal trial, or 3) Increased AEs with negative biomarker and functional data, requiring device design and/or management revisions prior to re-commencing clinical studies. Survival rates achieved with current LVADs create a challenging standard, but the high AE rates offer opportunities for new technologies to prevent stagnation in the field. New approaches to cost-effective early LVAD trial design are required to sustain innovation and safely transition into pivotal trials. [ABSTRACT FROM AUTHOR]

1. Populations of Metrosideros polymorpha establish across a broad range of precipitation in Hawai‘i – from <400 to >10000 mm per year. To determine whether adjustment of hydraulic and photosynthetic traits could contribute to this success in both high and low rainfall, we sampled populations on the wet and the dry sides of Hawai‘i Island, replicated on two different-aged lava flows at similar elevation and mean annual temperature. 2. We quantified 24 stem and leaf traits in an integrated study of hydraulics, gas exchange, leaf chemistry and anatomy. 3. Values for traits associated with capacity for water transport through the plant and gas exchange per leaf area were higher at dry sites, including photosynthetic capacity, nitrogen per leaf area and hydraulic conductivity on both sapwood area and leaf area basis. These adjustments, due to plastic and/or heritable differentiation, would partially compensate for generally lower water availability. 4. Specific leaf area shifted towards lower values at the dry sites. However, several other traits associated directly with drought tolerance were inflexible across sites, including stem vulnerability to embolism and leaf cuticular conductance, indicating that the ability to persist through dry periods is sustained across the species’ range. 5. The ability of M. polymorpha to establish across a wide range of habitats is associated with, on one hand, adjustments in traits that would enable sustained growth across a dramatic range of moisture supply while simultaneously maintaining as fixed other traits that would contribute to survival through extended drought. [ABSTRACT FROM AUTHOR]

Plant functional traits vary both along environmental gradients and among species occupying similar conditions, creating a challenge for the synthesis of functional and community ecology. We present a trait-based approach that provides an additive decomposition of species’ trait values into alpha and beta components: beta values refer to a species’ position along a gradient defined by community-level mean trait values; alpha values are the difference between a species’ trait values and the mean of co-occurring taxa. In woody plant communities of coastal California, beta trait values for specific leaf area, leaf size, wood density and maximum height all covary strongly, reflecting species distributions across a gradient of soil moisture availability. Alpha values, on the other hand, are generally not significantly correlated, suggesting several independent axes of differentiation within communities. This trait-based framework provides a novel approach to integrate functional ecology and gradient analysis with community ecology and coexistence theory. [ABSTRACT FROM AUTHOR]

T-cell anergy is a state of immunological tolerance characterized by unresponsiveness to antigenic stimulation. Previous studies have shown that anergy is induced in T cells following stimulation in the absence of adequate costimulatory signals. These cells fail to respond to stimulation via the T-cell receptor (TCR), and fail to produce normal levels of interleukin-2 (IL-2). We present results here which show that low concentrations of the superantigen staphylococcal enterotoxin A (SEA) in the absence of antigen-presenting cells induced both proliferation and anergy in the A.E7 T-cell clone. Furthermore, under these conditions, the A.E7 clone remained responsive to exogenous IL-2. Fluorescence-activated cellular cytometry analysis revealed unaltered expression of the TCR/CD3 complex in the anergized clone; however, both CD4 and CD25 expression increased after 24 hr of stimulation by SEA under these conditions. Interestingly, a low level of IL-2 production was measured during the induction of anergy. Most strikingly, stimulation of the A.E7 clone by SEA in combination with exogenous IL-2 resulted in a more pronounced state of anergy. These results suggest that the induction of anergy is a process that is essentially independent of the production of IL-2. [ABSTRACT FROM AUTHOR]

Purpose Implantation of a left ventricular assist device (LVAD) is associated with a significant change in cardiac output for patients with severe heart failure. We hypothesized that this abrupt change circulatory flow would be associated with acute metabolic changes related to tissue oxygen delivery. Methods We enrolled 32 patients in a prospective observational cohort study undergoing elective LVAD placement at the University of Colorado from 2013 to 2017 and collected blood immediately before surgery and 24 hours post-operatively and performed clinical follow up for a minimum of 1 year. We performed UHPLC-MS based metabolomics to quantify 24 metabolites with heavy isotope labelled standards and measured an additional 91,413 features with a minimum signal to noise ratio of 3 and minimum relative ion intensity of 1000. We performed the statistical analysis with JMP v14 and for the metabolomics analysis we report false discovery rate corrected p values. Results Subsequent heart transplantation significantly increased survival in patients undergoing elective LVAD placement (Table 1). After surgery, we noted significant changes in patients' metabolomic profile with glutamate decreasing and kynurenine and leucine/isoleucine increasing. We also identified 6941 out of 91,413 features with an FDR corrected p value less 0.05 that were significantly different between the pre-surgery and post-surgery samples (Figure 1) Conclusion LVAD placement resulted in significant metabolomic changes after 24 hours. Subsequent analyses have the potential to identify metabolomic profiles that predict clinical outcomes or guide therapies. [ABSTRACT FROM AUTHOR]

The presence of phylogenetic signal is assumed to be ubiquitous. However, for microorganisms, this may not be true given that they display high physiological flexibility and have fast regeneration. This may result in fundamentally different patterns of resemblance, that is, in variable strength of phylogenetic signal. However, in microbiological inferences, trait similarities and therewith microbial interactions with its environment are mostly assumed to follow evolutionary relatedness. Here, we tested whether indeed a straightforward relationship between relatedness and physiological traits exists for aerobic methane-oxidizing bacteria (MOB). We generated a comprehensive data set that included 30 MOB strains with quantitative physiological trait information. Phylogenetic trees were built from the 16S rRNA gene, a common phylogenetic marker, and the pmoA gene which encodes a subunit of the key enzyme involved in the first step of methane oxidation. We used a Blomberg's K from comparative biology to quantify the strength of phylogenetic signal of physiological traits. Phylogenetic signal was strongest for physiological traits associated with optimal growth pH and temperature indicating that adaptations to habitat are very strongly conserved in MOB. However, those physiological traits that are associated with kinetics of methane oxidation had only weak phylogenetic signals and were more pronounced with the pmoA than with the 16S rRNA gene phylogeny. In conclusion, our results give evidence that approaches based solely on taxonomical information will not yield further advancement on microbial eco-evolutionary interactions with its environment. This is a novel insight on the connection between function and phylogeny within microbes and adds new understanding on the evolution of physiological traits across microbes, plants and animals. [ABSTRACT FROM AUTHOR]

Understanding plant trait responses to elevated temperatures in the Arctic is critical in light of recent and continuing climate change, especially because these traits act as key mechanisms in climate-vegetation feedbacks. Since 1992, we have artificially warmed three plant communities at Alexandra Fiord, Nunavut, Canada (79°N). In each of the communities, we used open-top chambers (OTCs) to passively warm vegetation by 1-2 °C. In the summer of 2008, we investigated the intraspecific trait responses of five key species to 16 years of continuous warming. We examined eight traits that quantify different aspects of plant performance: leaf size, specific leaf area (SLA), leaf dry matter content (LDMC), plant height, leaf carbon concentration, leaf nitrogen concentration, leaf carbon isotope discrimination (LCID), and leaf δN. Long-term artificial warming affected five traits, including at least one trait in every species studied. The evergreen shrub Cassiope tetragona responded most frequently (increased leaf size and plant height/decreased SLA, leaf carbon concentration, and LCID), followed by the deciduous shrub Salix arctica (increased leaf size and plant height/decreased SLA) and the evergreen shrub Dryas integrifolia (increased leaf size and plant height/decreased LCID), the forb Oxyria digyna (increased leaf size and plant height), and the sedge Eriophorum angustifolium spp. triste (decreased leaf carbon concentration). Warming did not affect δN, leaf nitrogen concentration, or LDMC. Overall, growth traits were more sensitive to warming than leaf chemistry traits. Notably, we found that responses to warming were sustained, even after many years of treatment. Our work suggests that tundra plants in the High Arctic will show a multifaceted response to warming, often including taller shoots with larger leaves. [ABSTRACT FROM AUTHOR]

Aim Climate change poses significant threats to biodiversity, including impacts on species distributions, abundance and ecological interactions. At a landscape scale, these impacts, and biotic responses such as adaptation and migration, will be mediated by spatial heterogeneity in climate and climate change. We examine several aspects of the geography of climate change and their significance for biodiversity conservation. Location California and Nevada, USA. Methods Using current climate surfaces (PRISM) and two scenarios of future climate (A1b, 2070–2099, warmer-drier and warmer-wetter), we mapped disappearing, declining, expanding and novel climates, and the velocity and direction of climate change in California and Nevada. We also examined fine-scale spatial heterogeneity in protected areas of the San Francisco Bay Area in relation to reserve size, topographic complexity and distance from the ocean. Results Under the two climate change scenarios, current climates across most of California and Nevada will shrink greatly in extent, and the climates of the highest peaks will disappear from this region. Expanding and novel climates are projected for the Central Valley. Current temperature isoclines are projected to move up to 4.9 km year−1 in flatter regions, but substantially slower in mountainous areas because of steep local topoclimate gradients. In the San Francisco Bay Area, climate diversity within currently protected areas increases with reserve size and proximity to the ocean (the latter because of strong coastal climate gradients). However, by 2100 of almost 500 protected areas (>100 ha), only eight of the largest are projected to experience temperatures within their currently observed range. Topoclimate variability will further increase the range of conditions experienced and needs to be incorporated in future analyses. Main Conclusions Spatial heterogeneity in climate, from mesoclimate to topoclimate scales, represents an important spatial buffer in response to climate change, and merits increased attention in conservation planning. [ABSTRACT FROM AUTHOR]

Aim: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. Location: Tundra biome. Time period: Data collected between 1964 and 2016. Major taxa studied: 295 tundra vascular plant species. Methods: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species‐level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species‐level traits. Results: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species‐level trait expression. Main conclusions: Traditional functional groups only coarsely represent variation in well‐measured traits within tundra plant communities, and better explain resource economic traits than size‐related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease ( COPD) is characterized by an abnormal regulatory T cell ( Treg) response and increases in T helper type 1 ( Th1) and Th17 cell responses. It is unclear if dysregulation of micro RNAs (mi RNA) within Treg cells contributes to the abnormal inflammatory response in COPD. In this study, we aimed to compare the mi RNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed mi RNAs. We first obtained Treg and T effector cells (Teff) from peripheral blood of non-smokers, unaffected current smokers and COPD current smokers. Then, we assessed their mi RNA expression by microarray analysis followed by real-time reverse transcription-polymerase chain reaction ( RT- PCR) validation of particular mi RNAs. Six and 96 mi RNAs were expressed differentially in COPD Treg cells versus Treg cells of healthy non-smokers and healthy smokers, whereas no differences were found in mi RNA expression in Teff cells. We found that mi R-199a-5p was repressed by approximately fourfold in Treg cells of COPD patients compared to healthy smokers ( P < 0·05). In addition, mi R-199a-5p was over-expressed in Treg cells compared to Teff cells ( P < 0·001) and had significant over-representation of its target genes in the Treg transcriptome, being associated with the transforming growth factor ( TGF)-β activation pathway ( P < 0·01). We also confirmed the function of mi R-199a5p in an in-vitro loss-of-function cell model running TaqMan® arrays of the human TGF-β pathway. These findings suggest that the abnormal repression of mi R-199a-5p in patients with COPD compared to unaffected smokers may be involved in modulating the adaptive immune balance in favour of a Th1 and Th17 response. [ABSTRACT FROM AUTHOR]

The conservation implications of large-scale rainforest clearing and fragmentation on the persistence of functional and taxonomic diversity remain poorly understood. If traits represent adaptive strategies of plant species to particular circumstances, the expectation is that the effect of forest clearing and fragmentation will be affected by species functional traits, particularly those related to dispersal. We used species occurrence data for woody plants in 46 rainforest patches across 75,000 ha largely cleared of forest by the early 1900s to determine the combined effects of area reduction, fragmentation, and patch size on the taxonomic structure and functional diversity of subtropical rainforest. We compiled species trait values for leaf area, seed dry mass, wood density, and maximum height and calculated species niche breadths. Taxonomic structure, trait values (means, ranges), and the functional diversity of assemblages of climbing and free-standing plants in remnant patches were quantified. Larger rainforest patches had higher species richness. Species in smaller patches were taxonomically less related than species in larger patches. Free-standing plants had a high percentage of frugivore dispersed seeds; climbers had a high proportion of small wind-dispersed seeds. Connections between the patchy spatial distribution of free-standing species, larger seed sizes, and dispersal syndrome were weak. Assemblages of free-standing plants in patches showed more taxonomic and spatial structuring than climbing plants. Smaller isolated patches retained relatively high functional diversity and similar taxonomic structure to larger tracts of forest despite lower species richness. The response of woody plants to clearing and fragmentation of subtropical rainforest differed between climbers and slow-growing mature-phase forest trees but not between climbers and pioneer trees. Quantifying taxonomic structure and functional diversity provides an improved basis for conservation planning and management by elucidating the effects of forest-area reduction and fragmentation. Efectos de la Forma de Crecimiento y Atributos Funcionales en la Respuesta de Plantas Leñosas al Desmonte y Fragmentación de Bosque Lluvioso Subtropical [ABSTRACT FROM AUTHOR]

Purpose To characterize cardiovascular and cerebrovascular responses to exercise among individuals with continuous-flow left ventricular assist devices (CF-LVAD). Methods 9 CF-LVAD subjects, 11 patients with advanced heart failure with reduced ejection fraction (HFrEF, all New York Heart Association IIIB-IV with left ventricular ejection fraction <35%), and 11 Healthy controls (HC) underwent invasive hemodynamic assessment during two submaximal levels of exercise (to simulate real-world activities of daily living) and symptom-limited cardiopulmonary exercise testing. Cardiac output (Qc) was measured by Swan-Ganz catheterization, oxygen uptake (VO2) by indirect calorimetry, mean arterial pressure (MAP) by arterial line and Middle Cerebral Artery Velocity (MCAV) by transcranial Doppler. All hemodynamic parameters were continuously recorded throughout all stages of exercise. Results Demographics are reported in Table 1. As demonstrated in Figure 1 , workload and VO2 were similar between HFrEF and CF-LVAD groups, and significantly less than levels observed among HCs. Similarly, the increase in MAP and Qc throughout exercise was blunted among HFrEF and CF-LVAD groups in comparison to HCs. MCAV increased throughout exercise among HCs, but was relatively unchanged among HFrEF and CF-LVAD groups. Conclusion Despite restoration of resting Qc, CF-LVAD implantation is associated with a blunted cardiovascular and cerebrovascular response to exercise compared to healthy individuals, with exertional hemodynamics that are similar to individuals with advanced HFrEF. [ABSTRACT FROM AUTHOR]