Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)

Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET):feasibility of a new imaging concept using a clinical PET/MRI scanner

In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO(2) ((13)C-HCO(3)) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well

Dissimilar responses of fungal and bacterial communities to soil transplantation simulating abrupt climate changes.

Both fungi and bacteria play essential roles in regulating soil carbon cycling. To predict future carbon stability, it is imperative to understand their responses to environmental changes, which is subject to large uncertainty. As current global warming is causing range shifts toward higher latitudes, we conducted three reciprocal soil transplantation experiments over large transects in 2005 to simulate abrupt climate changes. Six years after soil transplantation, fungal biomass of transplanted soils showed a general pattern of changes from donor sites to destination, which were more obvious in bare fallow soils than in maize cropped soils. Strikingly, fungal community compositions were clustered by sites, demonstrating that fungi of transplanted soils acclimatized to the destination environment. Several fungal taxa displayed sharp changes in relative abundance, including Podospora, Chaetomium, Mortierella and Phialemonium. In contrast, bacterial communities remained largely unchanged. Consistent with the important role of fungi in affecting soil carbon cycling, 8.1%-10.0% of fungal genes encoding carbon-decomposing enzymes were significantly (p &lt; 0.01) increased as compared with those from bacteria (5.7%-8.4%). To explain these observations, we found that fungal occupancy across samples was mainly determined by annual average air temperature and rainfall, whereas bacterial occupancy was more closely related to soil conditions, which remained stable 6 years after soil transplantation. Together, these results demonstrate dissimilar response patterns and resource partitioning between fungi and bacteria, which may have considerable consequences for ecosystem-scale carbon cycling

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms

Tree diversity and species identity effects on soil fungi, protists and animals are context dependent

Plant species richness and the presence of certain influential species (sampling effect) drive the stability and functionality of ecosystems as well as primary production and biomass of consumers. However, little is known about these floristic effects on richness and community composition of soil biota in forest habitats owing to methodological constraints. We developed a DNA metabarcoding approach to identify the major eukaryote groups directly from soil with roughly species-level resolution. Using this method, we examined the effects of tree diversity and individual tree species on soil microbial biomass and taxonomic richness of soil biota in two experimental study systems in Finland and Estonia and accounted for edaphic variables and spatial autocorrelation. Our analyses revealed that the effects of tree diversity and individual species on soil biota are largely context dependent. Multiple regression and structural equation modelling suggested that biomass, soil pH, nutrients and tree species directly affect richness of different taxonomic groups. The community composition of most soil organisms was strongly correlated due to similar response to environmental predictors rather than causal relationships. On a local scale, soil resources and tree species have stronger effect on diversity of soil biota than tree species richness per se

Holocene sea level fluctuations and coastal evolution in the central Algarve (southern Portugal)

In Armação de Pêra Bay, southern Portugal, environmental changes during the Holocene can be interpreted based on the morphological and sedimentological similarities between older geomorphic features (cemented beach and dune rocks) and present coastal features. Using knowledge of the present beach and dune processes, we propose a two-step model for the evolution of Armação de Pêra Bay. First, during the rapid sea level rise between about 8800 and 6600 yr cal BP, the bay changed from a positive to a negative budget littoral cell and transgressive dunes formed, favoured by drought conditions. At about 5000 yr cal BP, during a sea level maximum, beach width was less than the critical fetch and dunes stabilized and underwent cementation during the wetter Atlantic climatic event. The second phase of dune accumulation started at about 3200 yr cal BP, due to a regression of sea level during which the bay changed back to a positive budget littoral cell in which beach width was greater than the critical fetch. Currently, the beach width is less than the critical fetch, dunes are inactive, and the sedimentary budget is negative due to sediment storage in local river systems.Fundação para a Ciência e a Tecnologia. FEDER, and OE (Project POCTI/CTA/34162/2000

Plant and microbial uptake and allocation of organic and inorganic nitrogen related to plant growth forms and soil conditions at two subarctic tundra sites in Sweden

In order to follow the uptake and allocation of N in different plant functional types and microbes in two tundra ecosystems differing in nutrient availability, we performed a 15N-labeling experiment with three N forms and followed the partitioning of 15N label among plants, microorganisms and soil organic matter. At both sites the deciduous dwarf shrub Betula nana and the evergreen Empetrum hermaphroditum absorbed added 15N at rates in the order: NH4+ > NO3− > glycine, in contrast to the graminoid Carex species which took up added 15N at rates in the order NO3− > NH4+ > glycine. Carex transported a high proportion of 15N to aboveground parts, whereas the dwarf shrubs allocated most 15N to underground storage. Enhanced 13C in Betula nana roots represents the first field evidence of uptake of intact glycine by this important circumpolar plant. Plant and microbial uptake of label was complementary as plants took up more inorganic than organic N, while microbes preferred organic N. Microbes initially took up a large part of the added label, but over the following four weeks microbial 15N decreased by 50% and most 15N was recovered in soil organic matter, while a smaller but slowly increasing proportion was retained in plant biomass

Long-lasting effects of land use history on soil fungal communities in second-growth tropical rain forests

Our understanding of the long-lasting effects of human land use on soil fungal communities in tropical forests is limited. Yet, over 70% of all remaining tropical forests are growing in former agricultural or logged areas. We investigated the relationship among land use history, biotic and abiotic factors, and soil fungal community composition and diversity in a second-growth tropical forest in Puerto Rico. We coupled high-throughput DNA sequencing with tree community and environmental data to determine whether land use history had an effect on soil fungal community descriptors. We also investigated the biotic and abiotic factors that underlie such differences and asked whether the relative importance of biotic (tree diversity, basal tree area, and litterfall biomass) and abiotic (soil type, pH, iron, and total carbon, water flow, and canopy openness) factors in structuring soil fungal communities differed according to land use history. We demonstrated long-lasting effects of land use history on soil fungal communities. At our research site, most of the explained variation in soil fungal composition (R2 = 18.6%), richness (R2 = 11.4%), and evenness (R2 = 10%) was associated with edaphic factors. Areas previously subject to both logging and farming had a soil fungal community with lower beta diversity and greater evenness of fungal operational taxonomic units (OTUs) than areas subject to light logging. Yet, fungal richness was similar between the two areas of historical land use. Together, these results suggest that fungal communities in disturbed areas are more homogeneous and diverse than in areas subject to light logging. Edaphic factors were the most strongly correlated with soil fungal composition, especially in areas subject to light logging, where soils are more heterogenous. High functional tree diversity in areas subject to both logging and farming led to stronger correlations between biotic factors and fungal composition than in areas subject to light logging. In contrast, fungal richness and evenness were more strongly correlated with biotic factors in areas of light logging, suggesting that these metrics might reflect long-term associations in old-growth forests. The large amount of unexplained variance in fungal composition suggests that these communities are structured by both stochastic and niche assemblage processes