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Aim To compare 6‐month adherence, persistence and treatment patterns among patients initiating once‐weekly glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), dulaglutide versus semaglutide, and dulaglutide versus exenatide BCise, using claims from the HealthCore Integrated Research Database. Materials and methods Patients aged ≥18 years, with type 2 diabetes, ≥1 claim for dulaglutide, semaglutide or exenatide BCise during the index period February 2018 to December 2018 (index date = earliest GLP‐1RA fill date), no claim for GLP‐1RAs in the 6‐month pre‐index period, and continuous enrolment 6 months pre‐ and post‐index were included. Dulaglutide users were propensity‐matched 1:1 to semaglutide users (3852 pairs) or exenatide BCise users (1879 pairs). The proportions of adherent (proportion of days covered ≥80%) patients were compared using chi‐squared tests. Persistence, measured as days to discontinuation, was analysed using a Cox regression model. Results Matched cohorts (dulaglutide:semaglutide and dulagutide:exenatide BCise) were balanced in baseline characteristics and the mean age was 54 and 55 years, respectively, with approximately 51% and 49% women, respectively. At 6 months, significantly more dulaglutide users were adherent than semaglutide (59.7% vs. 42.7%; P

Aim The aim was to decipher Europe‐wide spatio‐temporal patterns of forest growth dynamics and their associations with carbon isotope fractionation processes inferred from tree rings as modulated by climate warming. Location Europe and North Africa (30‒70° N, 10° W‒35° E). Time period 1901‒2003. Major taxa studied Temperate and Euro‐Siberian trees. Methods We characterize changes in the relationship between tree growth and carbon isotope fractionation over the 20th century using a European network consisting of 20 site chronologies. Using indexed tree‐ring widths (TRWi), we assess shifts in the temporal coherence of radial growth across sites (synchrony) for five forest ecosystems (Atlantic, boreal, cold continental, Mediterranean and temperate). We also examine whether TRWi shows variable coupling with leaf‐level gas exchange, inferred from indexed carbon isotope discrimination of tree‐ring cellulose (Δ13Ci). Results We find spatial autocorrelation for TRWi and Δ13Ci extending over a maximum of 1,000 km among forest stands. However, growth synchrony is not uniform across Europe, but increases along a latitudinal gradient concurrent with decreasing temperature and evapotranspiration. Latitudinal relationships between TRWi and Δ13Ci (changing from negative to positive southwards) point to drought impairing carbon uptake via stomatal regulation for water saving occurring at forests below 60° N in continental Europe. An increase in forest growth synchrony over the 20th century together with increasingly positive relationships between TRWi and Δ13Ci indicate intensifying impacts of drought on tree performance. These effects are noticeable in drought‐prone biomes (Mediterranean, temperate and cold continental). Main conclusions At the turn of this century, convergence in growth synchrony across European forest ecosystems is coupled with coordinated warming‐induced effects of drought on leaf physiology and tree growth spreading northwards. Such a tendency towards exacerbated moisture‐sensitive growth and physiology could override positive effects of enhanced leaf intercellular CO2 concentrations, possibly resulting in Europe‐wide declines of forest carbon gain in the coming decades. Spanish Government, Grant/Award Number: AGL2015‐68274 ‐C3 ‐3‐R; Sixth Framework Programme, Grant/AwardNumber: EVK2‐2001 ‐00237; Seventh Framework Programme, Grant/AwardNumber: COST ‐STSM ‐ECOST ‐STSM ‐FP1304‐140915‐066395 and ERANET‐Mundus program (Grant agreement 20112573)

Aims To evaluate adherence, persistence, glycaemic control and costs at 12‐month follow‐up for patients initiating dulaglutide versus liraglutide or exenatide once weekly. Materials and methods The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre‐ and post‐index HbA1c results. Propensity scores were used to match the cohorts. Results The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P

Aims Examine real‐world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral‐only Regimens (INITIATOR) study. Materials and methods Linked insurance claims and medical record data were collected from 2 large US health insurers (April 1, 2010 to March 31, 2012) of T2DM adults initiating treatment with glargine (GLA) or liraglutide (LIRA). Baseline characteristics were examined and changes in 12‐month follow‐up outcomes were described for both treatment groups: HbA1c, weight change, hypoglycaemia, persistence, healthcare utilisation and costs. Results A total of 4490 patients were included (GLA, 2116; LIRA, 2374). At baseline, GLA patients had significantly higher HbA1c vs LIRA patients (9.72% vs 8.19%; P < .001), lower likelihood of having HbA1c < 7% (7.1% vs 23.8%; P < .001), lower bodyweight (100.9 kg vs 110.9 kg, P < .001), higher Charlson Comorbidity Index score (0.88 vs 0.63; P < .001), and higher diabetes‐related costs ($3492 vs $2089; P < .001), respectively. During 12‐months of follow‐up, treatment persistence was 64%, mean HbA1c reduction was −1.24% and weight change was + 1.17 among GLA patients, and was 49%, −0.51% and −2.74 kg, respectively, among LIRA patients. Diabetes‐related costs increased significantly from baseline to follow‐up for LIRA patients ($2089 vs $3258, P < .001) but not for GLA patients ($3492 vs $3550, P = .890). Conclusions There were clinically relevant baseline differences in both groups, suggesting that GLA and LIRA are prescribed for different patient groups, and highlighting that efficacy results from clinical trials do not always translate into real‐world practice. Significant increases in healthcare costs were observed in the LIRA group, warranting further cost‐effectiveness analysis.

Rising atmospheric carbon dioxide [CO₂] can accelerate tree growth by stimulating photosynthesis and increasing intrinsic water-use efficiency (iWUE). Little evidence exists, however, for the long-term growth and gas-exchange responses of mature trees in tropical forests to the combined effects of rising [CO₂] and other global changes such as warming. Using tree rings and stable isotopes of carbon and oxygen, we investigated long-term trends in the iWUE and stem growth (basal area increment, BAI) of three canopy tree species in a tropical monsoon forest in western Thailand (Chukrasia tabularis, Melia azedarach, and Toona ciliata). To do this, we modelled the contribution of ontogenetic effects (tree diameter or age) and calendar year to variation in iWUE, oxygen isotopes, and BAI using mixed-effects models. Although iWUE increased significantly with both tree diameter and calendar year in all species, BAI at a given tree diameter was lower in more recent years. For one species, C. tabularis, differences in crown dominance significantly influence stable isotopes and growth. Tree ring Δ¹⁸O increased with calendar year in all species, suggesting that increasing iWUE may have been driven by relatively greater reductions in stomatal conductance - leading to enrichment in Δ¹⁸O - than increases in photosynthetic capacity. Plausible explanations for the observed declines in growth include water stress resulting from rising temperatures and El Nino events, increased respiration, changes in allocation, or more likely, a combination of these factors.

The validity of optically stimulated luminescence (OSL) has been tested on known-age (historical) fluvial deposits along the rivers Danube (Austria) and Ebro (Spain). As partial bleaching of the OSL signal prior to deposition can interfere with correct age estimates, different approaches to extracting the dose accumulated during burial are compared. Using the finite mixture model gave OSL ages that are internally as well as stratigraphically consistent and in agreement with independent age control. According to these results, fluvial deposition at the Danube River study site can be attributed to different periods ranging from Bronze Age to the 18th century A.D. Fluvial deposits of Roman age and of the late 17th or early 18th century A.D. were found at the Ebro River study site. This is consistent with the morphological subdivision of the valleys and encourages further investigation of the fluvial and archaeological history of the study areas using OSL. © 2009 Wiley Periodicals, Inc.

Aim: To identify the dominant spatial patterns of Fagus sylvatica radial growth in the Eastern Alps, and to understand their relationships to climate variation and bioclimatic gradients. Location: Fourteen beech stands in the Eastern Alps, growing between 200 and 1500 m a.s.l. in Italy, Slovenia and Austria. Methods: At each site, trees were sampled using increment borers or by taking discs from felled trees. Cores and discs were processed by measuring and crossdating ring width. Ring width series were standardized, averaged, and prewhitened to obtain site chronologies. Hierarchical Cluster Analysis (HCA) and Principal Components Analysis of prewhitened site chronologies were used to identify spatial and altitudinal growth patterns, related to the bioclimatic position of each stand. Bootstrap correlation and response functions were computed between monthly climatic variables and either principal component scores or composite chronologies from stands associated by HCA. The stability of dendroclimatic signals was analysed by moving correlation functions (MCF). Correlation analysis (teleconnections) based on a data base of 37 Italian and Slovenian beech tree-ring chronologies revealed the spatial extent of principal component scores. Results: Sampled trees were 200-400 years old, representing the oldest beech trees that have been crossdated for the Alps to date. Maximum age was directly related to altitude and to the presence of historical forms of conservation. Tree-ring parameters varied according to geographic patterns and the age of sampled trees. Stands were bioclimatically organized according to their location, and with reference to their elevation and distance from the Adriatic Sea. A direct response to winter temperature was found at all elevations. The altitudinal gradient ranged from low-elevation stands, characterized by a Mediterranean-type, late spring-summer drought signal, to mountain and high-elevation stands, characterized by a direct response to growing season temperature plus an inverse response to the previous year's July temperature. The mountain and high-elevation signal was evident in Austria, the Central Alps and Slovenia, while the low-elevation signal was confined to mountains adjacent to the Adriatic Sea. MCF revealed trends in the response to climatic factors affecting tree-ring formation in mountain and high-mountain stands linked to climatic warming. Main conclusions: Dendroclimatic networks can be used for bioclimatic studies of tree populations. A biogeographical separation emerged between the Alps and the Apennines at the upper elevations, while different degrees of mediterraneity distinguished sites at lower elevations. This information will be useful in assessing any future climate-related bioclimatic shifts, especially for forests at ecotones and along altitudinal gradients.

We present an extensive new network of ring-width chronologies, comprising data from 100 sites within the Austrian Eastern Alps, made up of multiple tree species. Principal components analysis and cluster analysis were used to identify five separate high-frequency tree-growth signals from these data. Tree-growth variability at these sites is explained by site altitude and species differences that moderate the effects of the annually varying climatic forcing on tree growth. Recently developed, two-century long gridded climate data sets for the Greater Alpine Region were used to assess the relationship between climate and tree growth. Tree growth at low altitudes is controlled mainly by spring-summer moisture availability. At high altitudes precipitation is no longer a limiting factor and growth is mostly determined by summer temperature. In the intermediate altitudinal range, we did not find any direct relationships with specific climatic variables. High-altitude chronologies suitable for reconstructing past temperatures and low-altitude chronologies suitable for reconstructing past precipitation were identified.