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Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% +/- 0.9% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6 mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P <.0001). The placebo-adjusted gMean for time-weighted average of percentage change in UACR from baseline was -6.0% (95% CI, -15.0 to 3.0; P =.1954). The adverse-event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.
One of the major challenges in understanding the evolution of our own species is identifying the role climate change has played in the evolution of hominin species. To clarify the influence of climate, we need long and continuous high-resolution paleoclimate records, preferably obtained from hominin-bearing sediments, that are well-dated by tephro- and magnetostratigraphy and other methods. This is hindered, however, by the fact that fossil-bearing outcrop sediments are often discontinuous, and subject to weathering, which may lead to oxidation and remagnetization. To obtain fresh, unweathered sediments, the Hominin Sites and Paleolakes Drilling Project (HSPDP) collected a ∼216-meter core (WTK13) in 2013 from Early Pleistocene Paleolake Lorenyang deposits in the western Turkana Basin (Kenya). Here, we present the magnetostratigraphy of the WTK13 core, providing a first age model for upcoming HSPDP paleoclimate and paleoenvrionmental studies on the core sediments. Rock magnetic analyses reveal the presence of iron sulfides carrying the remanent magnetizations. To recover polarity orientation from the near-equatorial WTK13 core drilled at 5°N, we developed and successfully applied two independent drill-core reorientation methods taking advantage of (1) the sedimentary fabric as expressed in the Anisotropy of Magnetic Susceptibility (AMS) and (2) the occurrence of a viscous component oriented in the present day field. The reoriented directions reveal a normal to reversed polarity reversal identified as the top of the Olduvai Subchron. From this excellent record, we find no evidence for the ‘Vrica Subchron’ previously reported in the area. We suggest that outcrop-based interpretations supporting the presence of the Vrica Subchron have been affected by the oxidation of iron sulfides initially present in the sediments -as evident in the core record- and by subsequent remagnetization. We discuss the implications of the observed geomagnetic record for human evolution studies.
In this Letter, we study the role of the donor:acceptor interface nanostructure upon charge separation and recombination in organic photovoltaic devices and blend films, using mixtures of PBTTT and two different fullerene derivatives (PC70BM and ICTA) as models for intercalated and nonintercalated morphologies, respectively. Thermodynamic simulations show that while the completely intercalated system exhibits a large free-energy barrier for charge separation, this barrier is significantly lower in the nonintercalated system and almost vanishes when energetic disorder is included in the model. Despite these differences, both femtosecond-resolved transient absorption spectroscopy (TAS) and time-delayed collection field (TDCF) exhibit extensive first-order losses in both systems, suggesting that geminate pairs are the primary product of photoexcitation. In contrast, the system that comprises a combination of fully intercalated polymer:fullerene areas and fullerene-aggregated domains (1:4 PBTTT:PC70BM) is the only one that shows slow, second-order recombination of free charges, resulting in devices with an overall higher short-circuit current and fill factor. This study therefore provides a novel consideration of the role of the interfacial nanostructure and the nature of bound charges and their impact upon charge generation and recombination.
One of the most significant Late Holocene climate shifts occurred around 2800 years ago, when cooler and wetter climate conditions established in western Europe. This shift coincided with an abrupt change in regional atmospheric circulation between 2760 and 2560 cal years BP, which has been linked to a grand solar minimum with the same duration (the Homeric Minimum). We investigated the temporal sequence of hydroclimatic and vegetation changes across this interval of climatic change (Homeric climate oscillation) by using lipid biomarker stable hydrogen isotope ratios (ED values) and pollen assemblages from the annually-laminated sediment record from lake Meerfelder Maar (Germany). Over the investigated interval (3200-2000 varve years BP), terrestrial lipid biomarker ED showed a gradual trend to more negative values, consistent with the western Europe long-term climate trend of the Late Holocene. At ca. 2640 varve years BP we identified a strong increase in aquatic plants and algal remains, indicating a rapid change in the aquatic ecosystem superimposed on this long-term trend. Interestingly, this aquatic ecosystem change was accompanied by large changes in ED values of aquatic lipid biomarkers, such as nC(21) and nC(23) (by between 22 and 30%(0)). As these variations cannot solely be explained by hydroclimate changes, we suggest that these changes in the Wag value were influenced by changes in n-alkane source organisms. Our results illustrate that if ubiquitous aquatic lipid biomarkers are derived from a limited pool of organisms, changes in lake ecology can be a driving factor for variations on sedimentary lipid MN values, which then could be easily misinterpreted in terms of hydro climatic changes. (C) 2017 Elsevier Ltd. All rights reserved.
Reaching the Sustainable Development Goals requires a fundamental socio-economic transformation accompanied by substantial investment in low-carbon infrastructure. Such a sustainability transition represents a non-marginal change, driven by behavioral factors and systemic interactions. However, typical economic models used to assess a sustainability transition focus on marginal changes around a local optimum, whichby constructionlead to negative effects. Thus, these models do not allow evaluating a sustainability transition that might have substantial positive effects. This paper examines which mechanisms need to be included in a standard computable general equilibrium model to overcome these limitations and to give a more comprehensive view of the effects of climate change mitigation. Simulation results show that, given an ambitious greenhouse gas emission constraint and a price of carbon, positive economic effects are possible if (1) technical progress results (partly) endogenously from the model and (2) a policy intervention triggering an increase of investment is introduced. Additionally, if (3) the investment behavior of firms is influenced by their sales expectations, the effects are amplified. The results provide suggestions for policy-makers, because the outcome indicates that investment-oriented climate policies can lead to more desirable outcomes in economic, social and environmental terms.
The Cotentin Peninsula (Normandy, France) displays sequences of marine terraces and rasas, the latter being wide Late Cenozoic coastal erosion surfaces, that are typical of Western European coasts in Portugal, Spain, France and southern England. Remote sensing imagery and field mapping enabled reappraisal of the Cotentin coastal sequences. From bottom to top, the N Cotentin sequence includes four previously recognized Pleistocene marine terraces (T1 to T4) at elevations <40 m as well as four higher and older rasas (R1 to R4) reaching 200 +/- 5 m in elevation. Low-standing marine terraces are not observed in the central part of the Peninsula and a limited number of terraces are described to the south. The high-standing rasas are widespread all over the peninsula. Such strandline distributions reveal major changes during the Late Cenozoic. Progressive uplift of an irregular sea-floor led to subaerial exposure of bathymetric highs that were carved into rocky platforms, rasas and marine terraces. Eventually, five main islands coalesced and connected to the mainland to the south to form the Cotentin Peninsula. On the basis of previous dating of the last interglacial maximum terrace (i.e. Marine Isotopic Stage, MIS 5e), sequential morphostratigraphy and modelling, we have reappraised uplift rates and derived: (i) mean Upper Pleistocene (i.e. since MIS 5e similar to 122 +/- 6 ka, i.e. kilo annum) apparent uplift rates of 0.04 +/- 0.01 mm/yr, (ii) mean Middle Pleistocene eustasy-corrected uplift rates of 0.09 +/- 0.03 mm/yr, and (iii) low mean Pleistocene uplift rates of 0.01 mm/yr. Extrapolations of these slow rates combined with geological evidence implies that the formation of the sequences from the Cotentin Peninsula occurred between 3 Ma (Pliocene) and 15 Ma (Miocene), which cannot be narrowed down further without additional research. Along the coasts of Western Europe, sequences of marine terraces and rasas are widespread (169 preserve the MIS Se benchmark). In Spain, Portugal, S England and other parts of western France, the sequences morphostratigraphy is very similar to that of Cotentin. The onset of such Western European sequences occurred during the Miocene (e.g. Spain) or Pliocene (e.g. Portugal). We interpret this Neogene-Quaternary coastal uplift as a symptom of the increasing lithospheric compression that accompanies Cenozoic orogenies. (C) 2017 Elsevier B.V. All rights reserved.
The phylogenetic structure of communities (PSC) reveals how evolutionary history affects community assembly processes. However, there are important knowledge gaps on PSC patterns for annual communities and there is a need for studies along environmental gradients in dry ecosystems where several processes shape PSC. Here, we investigated the PSC of annual plants along an aridity gradient in Israel, including eight years, two spatial scales, the effects of shrubs on understory, and the phylogenetic signal of important traits. Increasing drought stress led to overdispersed PSC at the drier end of the gradient, indicating that species were less related than expected by chance. This was supported at a smaller spatial scale, where within the drier sites, communities in open- more arid- habitats were more overdispersed than those under nurse shrubs. Interestingly, some key traits related to drought resistance were not conserved in the phylogeny. Together, our findings suggested that while habitat filtering selected for drought resistance strategies, these strategies evolved independently along multiple contrasting evolutionary lineages. Our comprehensive PSC study provides strong evidence for the interacting effects of habitat filtering and plant- plant interactions, particularly highlighting that the conservative evolution of traits should not be assumed in future interpretations of PSC patterns.
Reaching the Sustainable Development Goals requires a fundamental socio-economic transformation accompanied by substantial investment in low-carbon infrastructure. Such a sustainability transition represents a non-marginal change, driven by behavioral factors and systemic interactions. However, typical economic models used to assess a sustainability transition focus on marginal changes around a local optimum, whichby constructionlead to negative effects. Thus, these models do not allow evaluating a sustainability transition that might have substantial positive effects. This paper examines which mechanisms need to be included in a standard computable general equilibrium model to overcome these limitations and to give a more comprehensive view of the effects of climate change mitigation. Simulation results show that, given an ambitious greenhouse gas emission constraint and a price of carbon, positive economic effects are possible if (1) technical progress results (partly) endogenously from the model and (2) a policy intervention triggering an increase of investment is introduced. Additionally, if (3) the investment behavior of firms is influenced by their sales expectations, the effects are amplified. The results provide suggestions for policy-makers, because the outcome indicates that investment-oriented climate policies can lead to more desirable outcomes in economic, social and environmental terms.