The association between albuminuria and long-term renal risk:How to improve the precision of drug effect estimates

The worldwide increase in the number of patients with diabetic kidney disease needs to be tackled due to the consequences of the disease. Improving the quality of life and survival of this growing number of patients requires timely access to novel and effective treatments. Timely access to novel treatments can be achieved by decreasing the duration of clinical studies aiming to prove the efficacy of a new drug in preventing dialysis or the requirement of a kidney transplantation. The amount of urinary protein (albuminuria) and its changes are associated with the future risk for dialysis or a kidney transplantation. Changes in albuminuria occur early in the course of the diabetic kidney disease. Hence, using changes in albuminuria levels as a measurement of drug efficacy can decrease the duration of studies in diabetic kidney disease. This thesis examines the use of albuminuria as a measurement of drug efficacy. Part one of this thesis shows that more frequent measurements of albuminuria should be used to monitor the fluctuations in albuminuria levels after treatment initiation. These albuminuria fluctuations need to be taken into account when planning patient treatment aimed at preventing dialysis or the requirement of kidney transplantation. The second part of this thesis describes an optimized way of using albuminuria measurements in efficacy analysis for improving the precision of clinical trial outcomes. In conclusion, the findings presented in this thesis support the use of albuminuria as a measurement of drug efficacy in diabetic kidney disease clinical trials

Quantifying Asthenospheric and Lithospheric Controls on Mafic Magmatism Across North Africa

African basin‐and‐swell morphology is often attributed to the planform of sub‐plate mantle convection. Across North Africa, the coincidence of Neogene and Quaternary (i.e. <23 Ma) magmatism, topographic swells, long wavelength gravity anomalies, and slow shear wave velocity anomalies within the asthenosphere provides observational constraints for this hypothesis. Admittance analysis of topographic and gravity fields corroborates the existence of sub‐plate support. To investigate quantitative relationships between intraplate magmatism, shear wave velocity, and asthenospheric temperature, we collected and analyzed a suite of 224 lava samples from Tibesti, Jabal Eghei, Haruj, Sawda/Hasawinah and Gharyan volcanic centers of Libya and Chad. Forward and inverse modeling of major, trace, and Rare Earth elements were used for thermobarometric studies and to determine melt fraction as a function of depth. At each center, mafic magmatism is modeled by assuming adiabatic decompression of dry peridotite with asthenospheric potential temperatures of 1300–1360°C. Surprisingly, the highest temperatures are associated with the low‐lying Haruj volcanic center rather than with the more prominent Tibesti swell. Our results are consistent with earthquake tomographic models which show that the slowest shear wave anomalies within the upper mantle occur directly beneath the Haruj center. This inference is corroborated by converting observed velocities into potential temperatures, which are in good agreement with those determined by geochemical inverse modeling. Our results suggest that North African volcanic swells are primarily generated by thermal anomalies located beneath thinned lithosphere.Shell Research National Aeronautics and space administration National environmental research council ForschungsGermeinsChaf

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541–750)

The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium’s spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic. © 2019 National Academy of Sciences. All rights reserved

Fuelling in front of the barrier—are there age based behavioral differences in Garden Warblers Sylvia borin?

Garden Warblers Sylvia borin were studied during autumn stopover in Crete before crossing the barrier of the Mediterranean Sea and the Sahara Desert. Birds followed with transmitters show extensive stopover periods, which were longer in first-year birds, 16 days, compared with adult birds, 14 days. The distribution of body masses from birds trapped in fig trees were used to estimate the departure body mass and the results found indicate that both age categories on average depart with a fuel load close to 100% of lean body mass. The movement of transmitter birds shows differences between first-year and adult birds. Adult birds move further away from the release site and many also left the study area. Several were found settled outside the study area, up to 17 km away, indicating that they regularly make longer stopover movements. It is suggested that this might be a result of that they return to a place where they stayed during an earlier migration. It was shown that stopover site fidelity exists and nine garden warblers were recaptured in the area during a following autumn. The results found highlights the importance of stopover areas close to the Sahara Desert

Mauritius since the last glacial:environmental and climatic reconstruction of the last 38 000 years from Kanaka Crater

A 10 m long peat core from the Kanaka Crater (20° 25′ S, 57° 31′ E), located at 560 m elevation in Mauritius, was analyzed for microfossils. Eight radiocarbon ages show the pollen record reflects environmental and climatic change of the last ca. 38 cal ka BP. The record shows that the island was continuously covered by forest with Erica heath (Philippia) in the uplands. Cyperaceous reedswamp with Pandanus trees was abundant in the coastal lowlands as well as locally in the waterlogged crater. The record shows changes in climatic humidity (wet from 38.0 to 22.7 cal ka BP, drier from 22.7 to 10.6 cal ka BP, and wetter again from 10.6 cal ka BP to recent) as the main response to climate change. A high turnover in montane forest species is evidenced at 22.7 cal ka BP and at the start of the Holocene. The limited altitudinal ranges in the mountains of Mauritius (maximum altitude 828 m), and changing humidity being more important than changing temperature, suggests that in response to climate change a reassortment in taxonomic composition of montane forests might be equally important as displacement of forest types to new altitudinal intervals. We found weak impact of the latitudinal migration of the Intertropical Convergence Zone and data suggest that the Indian Ocean Dipole is a more important driver for climatic change in the southwest Indian Ocean

Dune ages in the sand deserts of the southern Sahara and Sahel

In this paper we aim to document the history of aeolian processes within the southern Sahara as part of the INQUA Dune Atlas. We review available luminescence ages for sand dunes across the southern Sahara to develop an improved understanding of the dune chronology on a regional basis and attempt to correlate periods of sand accumulation. This was achieved by analysing dune age by country, as well as by latitude and longitude. The results show a very patchy spatial distribution of dune ages with large gaps that encompass some of the largest sand seas. Despite these gaps, some related patterns in dune morphology and stratigraphy appear to be consistent between northern Nigeria and southern Mali where older linear dunes are distinct from younger Late Holocene transverse and barchanoid dunes. Elsewhere in Mauretania linear dunes with different orientations appear to have accumulated at different times, most likely in response to changes in atmospheric circulation. Regional climatic changes are identified where dunes are transgressed by lake deposits within endorehic basins. We identify four locations where dune accumulation is terminated by lacustrine transgressions, two of which, in Lake Chad and the Bodélé Depression, occur shortly after the last glacial maximum (LGM). The third example at Gobiero in Niger occurred later, in the early Holocene, around 8.4 ka and a fourth marks a later transgression of Palaeolake MegaChad after 4.7 ka. Larger-scale latitudinal and longitudinal distributions in dune ages across the southern Sahara do not show any consistent patterns, though this may be due to the small sample size relative to the study area. In addition, local variations in external controls such as wind regime, rainfall, vegetation and sand supply need to be considered, sometimes on a site by site basis. Limiting the analysis to dune ages determined using the single-aliquot regenerative-dose (SAR) protocol indicates a lack of dune preservation during the LGM and the Younger Dryas, times associated with increased dust input to the oceans which is assumed to indicate increased aeolian activity. The SAR dune dates suggest that preservation of dunes at the onset of succeeding humid intervals is an important component of the dune record. The most striking examples of this phenomenon occur where dunes are preserved within endorehic basins by lacustrine transgressions

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund