Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

PURPOSE Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y-DOTA]-TOC or [(177)Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. RESULTS Overall, 910 patients underwent 1,804 cycles of [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu-DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(90)Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95% confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [(177)Lu-DOTA]-TOC over [(90)Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [(177)Lu-DOTA]-TOC treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32). CONCLUSION The present results revealed no difference in median overall survival after [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC was less haematotoxic than [(90)Y-DOTA]-TOC.

Holocene climate, fire and vegetation dynamics at the treeline in the Northwestern Swiss Alps

Treelines are expected to rise to higher elevations with climate warming; the rate and extent however are still largely unknown. Here we present the first multi-proxy palaeoecological study from the treeline in the Northwestern Swiss Alps that covers the entire Holocene. We reconstructed climate, fire and vegetation dynamics at Iffigsee, an alpine lake at 2,065 m a.s.l., by using seismic sedimentary surveys, loss on ignition, visible spectrum reflectance spectroscopy, pollen, spore, macrofossil and charcoal analyses. Afforestation with Larix decidua and tree Betula (probably B. pendula) started at ~9,800 cal. b.p., more than 1,000 years later than at similar elevations in the Central and Southern Alps, indicating cooler temperatures and/or a high seasonality. Highest biomass production and forest position of ~2,100–2,300 m a.s.l. are inferred during the Holocene Thermal Maximum from 7,000 to 5,000 cal. b.p. With the onset of pastoralism and transhumance at 6,800–6,500 cal. b.p., human impact became an important factor in the vegetation dynamics at Iffigsee. This early evidence of pastoralism is documented by the presence of grazing indicators (pollen, spores), as well as a wealth of archaeological finds at the nearby mountain pass of Schnidejoch. Human and fire impact during the Neolithic and Bronze Ages led to the establishment of pastures and facilitated the expansion of Picea abies and Alnus viridis. We expect that in mountain areas with land abandonment, the treeline will react quickly to future climate warming by shifting to higher elevations, causing drastic changes in species distribution and composition as well as severe biodiversity losses.

On the counter-radiation of the atmosphere

This paper is the edited translation of the paper by ANDERS ANGSTRÖM ‘‘Über die Gegenstrahlung der Atmosphäre’’ (On the counter-radiation of the atmosphere) that was published 1916 in the Meteorologische Zeitschrift 33, 529–538.

Tree growth response along an elevational gradient: climate or genetics?

Environment and genetics combine to influence tree growth and should therefore be jointly considered when evaluating forest responses in a warming climate. Here, we combine dendroclimatology and population genetic approaches with the aim of attributing climatic influences on growth of European larch (Larix decidua) and Norway spruce (Picea abies). Increment cores and genomic DNA samples were collected from populations along a ~900-m elevational transect where the air temperature gradient encompasses a ~4 °C temperature difference. We found that low genetic differentiation among populations indicates gene flow is high, suggesting that migration rate is high enough to counteract the selective pressures of local environmental variation. We observed lower growth rates towards higher elevations and a transition from negative to positive correlations with growing season temperature upward along the elevational transect. With increasing elevation there was also a clear increase in the explained variance of growth due to summer temperatures. Comparisons between climate sensitivity patterns observed along this elevational transect with those from Larix and Picea sites distributed across the Alps reveal good agreement, and suggest that tree-ring width (TRW) variations are more climate-driven than genetics-driven at regional and larger scales. We conclude that elevational transects are an extremely valuable platform for understanding climatic-driven changes over time and can be especially powerful when working within an assessed genetic framework.

A meta-analysis of cambium phenology and growth: linear and non-linear patterns in conifers of the northern hemisphere

Background and Aims Ongoing global warming has been implicated in shifting phenological patterns such as the timing and duration of the growing season across a wide variety of ecosystems. Linear models are routinely used to extrapolate these observed shifts in phenology into the future and to estimate changes in associated ecosystem properties such as net primary productivity. Yet, in nature, linear relationships may be special cases. Biological processes frequently follow more complex, non-linear patterns according to limiting factors that generate shifts and discontinuities, or contain thresholds beyond which responses change abruptly. This study investigates to what extent cambium phenology is associated with xylem growth and differentiation across conifer species of the northern hemisphere. Methods Xylem cell production is compared with the periods of cambial activity and cell differentiation assessed on a weekly time scale on histological sections of cambium and wood tissue collected from the stems of nine species in Canada and Europe over 1–9 years per site from 1998 to 2011. Key Results The dynamics of xylogenesis were surprisingly homogeneous among conifer species, although dispersions from the average were obviously observed. Within the range analysed, the relationships between the phenological timings were linear, with several slopes showing values close to or not statistically different from 1. The relationships between the phenological timings and cell production were distinctly non-linear, and involved an exponential pattern. Conclusions The trees adjust their phenological timings according to linear patterns. Thus, shifts of one phenological phase are associated with synchronous and comparable shifts of the successive phases. However, small increases in the duration of xylogenesis could correspond to a substantial increase in cell production. The findings suggest that the length of the growing season and the resulting amount of growth could respond differently to changes in environmental conditions.

LiLa-Klassifikation für Frakturen der langen Röhrenknochen im Wachstumsalter

Background. There are two child-specific fracture classification systems for long bone fractures: the AO classification of pediatric long-bone fractures (PCCF) and the LiLa classification of pediatric fractures of long bones (LiLa classification). Both are still not widely established in comparison to the adult AO classification for long bone fractures. Methods. During a period of 12 months all long bone fractures in children were documented and classified according to the LiLa classification by experts and non-experts. Intraobserver and interobserver reliability were calculated according to Cohen (kappa). Results. A total of 408 fractures were classified. The intraobserver reliability for location in the skeletal and bone segment showed an almost perfect agreement (K=0.91-0.95) and also the morphology (joint/shaft fracture) (K=0.87-0.93). Due to different judgment of the fracture displacement in the second classification round, the intraobserver reliability of the whole classification revealed moderate agreement (K=0.53-0.58). Interobserver reliability showed moderate agreement (K=0.55) often due to the low quality of the X-rays. Further differences occurred due to difficulties in assigning the precise transition from metaphysis to diaphysis. Conclusions. The LiLa classification is suitable and in most cases user-friendly for classifying long bone fractures in children. Reliability is higher than in established fracture specific classifications and comparable to the AO classification of pediatric long bone fractures. Some mistakes were due to a low quality of the X-rays and some due to difficulties to classify the fractures themselves. Improvements include a more precise definition of the metaphysis and the kind of displacement. Overall the LiLa classification should still be considered as an alternative for classifying pediatric long bone fractures.

New evidence for the symbiosis between Tuber aestivum and Picea abies

The Burgundy truffle (Tuber aestivum Vittad.), an ectomycorrhizal fungus living in association with host plants, is one of the most exclusive delicacies. The symbiosis with deciduous oak, beech, and hazel dominates our concept of truffle ecophysiology, whereas potential conifer hosts have rarely been reported. Here, we present morphological and molecular evidence of a wildlife T. aestivum symbiosis with Norway spruce (Picea abies Karst.) and an independent greenhouse inoculation experiment, to confirm our field observation in southwest Germany. A total of 27 out of 50 P. abies seedlings developed T. aestivum ectomycorrhizae with a mean mycorrhization rate of 19.6 %. These findings not only suggest P. abies to be a productive host species under suitable biogeographic conditions but also emphasize the broad ecological amplitude and great symbiotic range of T. aestivum. While challenging common knowledge, this study demonstrates a significant expansion of the species' cultivation potential to the central European regions, where P. abies forests occur on calcareous soils.

Recent trends in Inner Asian forest dynamics to temperature and precipitation indicate high sensitivity to climate change

Semi-arid ecosystems play an important role in regulating global climate with the fate of these ecosystems in the Anthropocene depending upon interactions among temperature, precipitation, and CO2. However, in cool-arid environments, precipitation is not the only limitation to forest productivity. Interactions between changes in precipitation and air temperature may enhance soil moisture stress while simultaneously extending growing season length, with unclear consequences for net carbon uptake. This study evaluates recent trends in productivity and phenology of Inner Asian forests (in Mongolia and Northern China) using satellite remote sensing, dendrochronology, and dynamic global vegetation model (DGVM) simulations to quantify the sensitivity of forest dynamics to decadal climate variability and trends. Trends in photosynthetically active radiation fraction (FPAR) between 1982 and 2010 show a greening of about 7% of the region in spring (March, April, May), and 3% of the area ‘browning’ during summertime (June, July, August). These satellite observations of FPAR are corroborated by trends in NPP simulated by the LPJ DGVM. Spring greening trends in FPAR are mainly explained by long-term trends in precipitation whereas summer browning trends are correlated with decreasing precipitation. Tree ring data from 25 sites confirm annual growth increments are mainly limited by summer precipitation (June, July, August) in Mongolia, and spring precipitation in northern China (March, April, May), with relatively weak prior-year lag effects. An ensemble of climate projections from the IPCC CMIP3 models indicates that warming temperatures (spring, summer) are expected to be associated with higher summer precipitation, which combined with CO2 causes large increases in NPP and possibly even greater forest cover in the Mongolian steppe. In the absence of a strong direct CO2 fertilization effect on plant growth (e.g., due to nutrient limitation), water stress or decreased carbon gain from higher autotrophic respiration results in decreased productivity and loss of forest cover. The fate of these semi-arid ecosystems thus appears to hinge upon the magnitude and subtleties of CO2 fertilization effects, for which experimental observations in arid systems are needed to test and refine vegetation models.

Intra-annual dynamics of non-structural carbohydrates in the cambium of mature conifer trees reflects radial growth demands

The presence of soluble carbohydrates in the cambial zone, either from sugars recently produced during photosynthesis or from starch remobilized from storage organs, is necessary for radial tree growth. However, considerable uncertainties on carbohydrate dynamics and the consequences on tree productivity exist. This study aims to better understand the variation in different carbon pools at intra-annual resolution by quantifying how cambial zone sugar and starch concentrations fluctuate over the season and in relation to cambial phenology. A comparison between two physiologically different species growing at the same site, i.e., the evergreen Picea abies Karst. and the deciduous Larix decidua Mill., and between L. decidua from two contrasting elevations, is presented to identify mechanisms of growth limitation. Results indicate that the annual cycle of sugar concentration within the cambial zone is coupled to the process of wood formation. The highest sugar concentration is observed when the number of cells in secondary wall formation and lignification stages is at a maximum, subsequent to most radial growth. Starch disappears in winter, while other freeze-resistant non-structural carbohydrates (NSCs) increase. Slight differences in NSC concentration between species are consistent with the differing climate sensitivity of the evergreen and deciduous species investigated. The general absence of differences between elevations suggests that the cambial activity of trees growing at the treeline was not limited by the availability of carbohydrates at the cambial zone but instead by environmental controls on the growing season duration.

Unraveling environmental drivers of a recent increase in Swiss fungi fruiting

Disentangling biotic and abiotic drivers of wild mushroom fruiting is fraught with difficulties because mycelial growth is hidden belowground, symbiotic and saprotrophic supply strategies may interact, and myco-ecological observations are often either discontinuous or too short. Here, we compiled and analyzed 115 417 weekly fungal fruit body counts from permanent Swiss inventories between 1975 and 2006. Mushroom fruiting exhibited an average autumnal delay of 12 days after 1991 compared with before, the annual number of fruit bodies increased from 1801 to 5414 and the mean species richness doubled from 10 to 20. Intra- and interannual coherency of symbiotic and saprotrophic mushroom fruiting, together with little agreement between mycorrhizal yield and tree growth suggests direct climate controls on fruit body formation of both nutritional modes. Our results contradict a previously reported declining of mushroom harvests and propose rethinking the conceptual role of symbiotic pathways in fungi-host interaction. Moreover, this conceptual advancement may foster new cross-disciplinary research avenues, and stimulate questions about possible amplifications of the global carbon cycle, as enhanced fungal production in moist mid-latitude forests rises carbon cycling and thus increases greenhouse gas exchanges between terrestrial ecosystems and the atmosphere.

Climate extremes and the carbon cycle

The terrestrial biosphere is a key component of the global carbon cycle and its carbon balance is strongly influenced by climate. Continuing environmental changes are thought to increase global terrestrial carbon uptake. But evidence is mounting that climate extremes such as droughts or storms can lead to a decrease in regional ecosystem carbon stocks and therefore have the potential to negate an expected increase in terrestrial carbon uptake. Here we explore the mechanisms and impacts of climate extremes on the terrestrial carbon cycle, and propose a pathway to improve our understanding of present and future impacts of climate extremes on the terrestrial carbon budget.