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Summary: Thrombopoietin receptor agonists (TPO‐RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first‐line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end‐points included the sustained remission off‐treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)‐4, IL‐9 and IL‐17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor‐β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation. [ABSTRACT FROM AUTHOR]

Stable hydrogen and carbon isotope ratios of wood lignin methoxy groups (δ13CLM and δ2HLM values) have been shown to be reliable proxies of past temperature variations. Previous studies showed that δ2HLM values even work in temperate environments where classical tree-ring width and maximum latewood density measurements are less successful for climate reconstructions. Here, we analyse the annually resolved δ13CLM values from 1916–2015 of four beech trees (Fagus sylvatica) from a temperate site near Hohenpeißenberg in southern Germany and compare these data with regional- to continental-scale climate observations. Initial δ13CLM values were corrected for the Suess effect (a decrease of δ13C in atmospheric CO 2) and physiological tree responses to increasing atmospheric CO 2 concentrations considering a range of published discrimination factors. The calibration of δ13CLM chronologies against instrumental data reveals the highest correlations with regional summer (r=0.68) and mean annual temperatures (r=0.66), as well as previous-year September to current-year August temperatures (r=0.61), all calculated from 1916–2015 and reaching p<0.001. Additional calibration trials using detrended δ13CLM values and climate data (to constrain effects of autocorrelation on significance levels) returned rsummer=0.46 (p<0.001), rannual=0.25 (p<0.05) and rprev.September-August=0.18 (p>0.05). The new δ13CLM chronologies were finally compared with the previously produced δ2HLM values of the same trees in order to evaluate the additional gain of assessing past climate variability using a dual-isotope approach. Compared to δ13CLM , δ2HLM values correlate substantially more strongly with large-scale temperatures averaged over western Europe (rprev.September-August=0.69), whereas only weak and mainly insignificant correlations are obtained between precipitation and both isotope chronologies (δ13CLM and δ2HLM values). Our results indicate the great potential of using δ13CLM values from temperate environments as a proxy for local temperatures and, in combination with δ2HLM values, to assess regional- to sub-continental scale temperature patterns. [ABSTRACT FROM AUTHOR]

Stable hydrogen and carbon isotope ratios of wood lignin methoxy groups (d13CLM and d²HLM values) have been shown to be reliable proxies of past temperature variations. Previous studies showed that ²HLM values even work in temperate environments where classical tree-ring width and maximum latewood density measurements are less skilful. Here, we analyse annually resolved d13CLM values from 1916-2015 of four beech trees (Fagus sylvatica) from a temperate site near Hohenpeißenberg in southern Germany and compare these data with regional to continental scale climate observations. Initial d13CLM values were corrected for the Suess effect (a decrease of d13C in atmospheric CO2) and physiological tree responses to increasing atmospheric CO2 concentrations considering a range of published discrimination factors. The calibration of d13CLM chronologies against instrumental data reveals highest correlations with regional summer (r = 0.68) and mean annual temperatures (r = 0.66), as well as previous-year September to current-year August temperatures (r = 0.61), all calculated from 1916-2015 and reaching p < 0.001. Additional calibration trials using detrended d13CLM values and climate data, to constrain effects of autocorrelation on significance levels, returned rsummer = 0.46 (p < 0.001), rannual = 0.25 (p < 0.05) and rprev.Sep-Aug = 0.18 (p > 0.05). The new d13CLM chronologies were finally compared with previously produced d²HLM values of the same trees to evaluate the additional gain of assessing past climate variability using a dual-isotope approach. Compared to d13CLM, d²HLM values correlates substantially stronger with large-scale temperatures averaged over western Europe (rprev.Sep-Aug = 0.69), whereas only weak and mainly insignificant correlations are obtained between precipitation and both isotope chronologies (d13CLM and d²HLM values). Our results indicate great potential of using d13CLM values from temperate environments as a proxy for local temperatures, and in combination with d²HLM values, to assess regional to sub-continental scale temperature patterns. [ABSTRACT FROM AUTHOR]

Methane (CH4) production within the oceanic mixed layer is a widespread phenomenon, but the underlying mechanisms are still under debate. Marine algae might contribute to the observed CH4 oversaturation in oxic waters, but so far direct evidence for CH4 production by marine algae has only been provided for the coccolithophore Emiliania huxleyi. In the present study we investigated, next to E. huxleyi , other widespread haptophytes, i.e., Phaeocystis globosa and Chrysochromulina sp. We performed CH4 production and stable carbon isotope measurements and provide unambiguous evidence that all three investigated marine algae are involved in the production of CH4 under oxic conditions. Rates ranged from 1.9±0.6 to 3.1±0.4 µ g of CH4 per gram of POC (particulate organic carbon) per day, with Chrysochromulina sp. and E. huxleyi showing the lowest and highest rates, respectively. Cellular CH4 production rates ranged from 16.8±6.5 (P. globosa) to 62.3±6.4 ag CH4 cell -1 d -1 (E. huxleyi ; ag = 10 -18 g). In cultures that were treated with 13C -labeled hydrogen carbonate, δ13CH4 values increased with incubation time, resulting from the conversion of 13C –hydrogen carbonate to 13CH4. The addition of 13C -labeled dimethyl sulfide, dimethyl sulfoxide, and methionine sulfoxide – known algal metabolites that are ubiquitous in marine surface layers – resulted in the occurrence of 13C -enriched CH4 in cultures of E. huxleyi , clearly indicating that methylated sulfur compounds are also precursors of CH4. By comparing the algal CH4 production rates from our laboratory experiments with results previously reported in two field studies of the Pacific Ocean and the Baltic Sea, we might conclude that algae-mediated CH4 release is contributing to CH4 oversaturation in oxic waters. Therefore, we propose that haptophyte mediated CH4 production could be a common and important process in marine surface waters. [ABSTRACT FROM AUTHOR]

Background: Financial incentives are effective in moderating physician and patient behaviour, but they have not been studied in the context of medical education. Aim: This study assessed whether financial incentives can motivate students to acquire electrocardiogram (ECG) interpretation skills. Methods: Students enrolled for a cardio-respiratory teaching module ( n = 121) were randomised to an intervention (financial incentive) or a control (book voucher raffle) condition. All students took three validated exams of ECG interpretation skills (at module entry, module exit and seven weeks later). Only the exit exam was financially incentivised in the intervention group. The primary outcome was the proportion of students who correctly identified ≥60% of clinically important diagnoses in the exit exam. Results: Financial incentives more than doubled the odds of correctly identifying ≥60% of diagnoses in the exit exam (adjusted odds ratio 2.44, 95% confidence interval 1.05-5.67) and significantly increased student learning time. However, there was no significant effect on performance levels in the retention exam. Conclusions: Financial incentives increase reported learning time and examination results in the short-term. The lack of a sustained effect on performance suggests that financial incentives may foster a superficial or strategic rather than a deep approach to learning. [ABSTRACT FROM AUTHOR]