An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma

Background Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. Patients and methods Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. Results With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). Conclusions In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. Clinical trials The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT0000256

Investigating the representation of heatwaves from an ensemble of km-scale regional climate simulations within CORDEX-FPS convection

Heatwaves (HWs) are high-impact phenomena stressing both societies and ecosystems. Their intensity and frequency are expected to increase in a warmer climate over many regions of the world. While these impacts can be wide-ranging, they are potentially influenced by local to regional features such as topography, land cover, and urbanization. Here, we leverage recent advances in the very high-resolution modelling required to elucidate the impacts of heatwaves at these fine scales. Further, we aim to understand how the new generation of km-scale regional climate models (RCMs) modulates the representation of heatwaves over a well-known climate change hot spot. We analyze an ensemble of 15 convection-permitting regional climate model (CPRCM, ~ 2–4 km grid spacing) simulations and their driving, convection-parameterized regional climate model (RCM, ~ 12–15 km grid spacing) simulations from the CORDEX Flagship Pilot Study on Convection. The focus is on the evaluation experiments (2000–2009) and three subdomains with a range of climatic characteristics. During HWs, and generally in the summer season, CPRCMs exhibit warmer and drier conditions than their driving RCMs. Higher maximum temperatures arise due to an altered heat flux partitioning, with daily peaks up to ~ 150 W/m$^{2}$ larger latent heat in RCMs compared to the CPRCMs. This is driven by a 5–25% lower soil moisture content in the CPRCMs, which is in turn related to longer dry spell length (up to double). It is challenging to ascertain whether these differences represent an improvement. However, a point-scale distribution-based maximum temperature evaluation, suggests that this CPRCMs warmer/drier tendency is likely more realistic compared to the RCMs, with ~ 70% of reference sites indicating an added value compared to the driving RCMs, increasing to 95% when only the distribution right tail is considered. Conversely, a CPRCMs slight detrimental effect is found according to the upscaled grid-to-grid approach over flat areas. Certainly, CPRCMs enhance dry conditions, with knock-on implications for summer season temperature overestimation. Whether this improved physical representation of HWs also has implications for future changes is under investigation

Precipitation frequency in Med-CORDEX and EURO-CORDEX ensembles from 0.44° to convection-permitting resolution: impact of model resolution and convection representation

Recent studies using convection-permitting (CP) climate simulations have demonstrated a step-change in the representation of heavy rainfall and rainfall characteristics (frequency-intensity) compared to coarser resolution Global and Regional climate models. The goal of this study is to better understand what explains the weaker frequency of precipitation in the CP ensemble by assessing the triggering process of precipitation in the different ensembles of regional climate simulations available over Europe. We focus on the statistical relationship between tropospheric temperature, humidity and precipitation to understand how the frequency of precipitation over Europe and the Mediterranean is impacted by model resolution and the representation of convection (parameterized vs. explicit). We employ a multi-model data-set with three different resolutions (0.44°, 0.11° and 0.0275°) produced in the context of the MED-CORDEX, EURO-CORDEX and the CORDEX Flagship Pilot Study "Convective Phenomena over Europe and the Mediterranean" (FPSCONV). The multi-variate approach is applied to all model ensembles, and to several surface stations where the integrated water vapor (IWV) is derived from Global Positioning System (GPS) measurements. The results show that all model ensembles capture the temperature dependence of the critical value of IWV (IWVcv), above which an increase in precipitation frequency occurs, but the differences between the models in terms of the value of IWVcv, and the probability of its being exceeded, can be large at higher temperatures. The lower frequency of precipitation in convection-permitting simulations is not only explained by higher temperatures but also by a higher IWVcv necessary to trigger precipitation at similar temperatures, and a lower probability to exceed this critical value. The spread between models in simulating IWVcv and the probability of exceeding IWVcv is reduced over land in the ensemble of models with explicit convection, especially at high temperatures, when the convective fraction of total precipitation becomes more important and the influence of the representation of entrainment in models thus becomes more important. Over lowlands, both model resolution and convection representation affect precipitation triggering while over mountainous areas, resolution has the highest impact due to orography-induced triggering processes. Over the sea, since lifting is produced by large-scale convergence, the probability to exceed IWVcv does not depend on temperature, and the model resolution does not have a clear impact on the results

The first multi-model ensemble of regional climate simulations at kilometer-scale resolution. Part I: Evaluation of precipitation

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼ 3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40 at 12 km to ∼ −3 at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales. © 2021, The Author(s)

The first multi-model ensemble of regional climate simulations at kilometer-scale resolution, part I: evaluation of precipitation

Here we present the first multi-model ensemble of regional climate simulations at kilometer-scale horizontal grid spacing over a decade long period. A total of 23 simulations run with a horizontal grid spacing of ∼3 km, driven by ERA-Interim reanalysis, and performed by 22 European research groups are analysed. Six different regional climate models (RCMs) are represented in the ensemble. The simulations are compared against available high-resolution precipitation observations and coarse resolution (∼ 12 km) RCMs with parameterized convection. The model simulations and observations are compared with respect to mean precipitation, precipitation intensity and frequency, and heavy precipitation on daily and hourly timescales in different seasons. The results show that kilometer-scale models produce a more realistic representation of precipitation than the coarse resolution RCMs. The most significant improvements are found for heavy precipitation and precipitation frequency on both daily and hourly time scales in the summer season. In general, kilometer-scale models tend to produce more intense precipitation and reduced wet-hour frequency compared to coarse resolution models. On average, the multi-model mean shows a reduction of bias from ∼ −40% at 12 km to ∼ −3% at 3 km for heavy hourly precipitation in summer. Furthermore, the uncertainty ranges i.e. the variability between the models for wet hour frequency is reduced by half with the use of kilometer-scale models. Although differences between the model simulations at the kilometer-scale and observations still exist, it is evident that these simulations are superior to the coarse-resolution RCM simulations in the representing precipitation in the present-day climate, and thus offer a promising way forward for investigations of climate and climate change at local to regional scales

The effects of market economy and foreign MNE subsidiaries on the convergence and divergence of HRM

This study explores patterns of human resource management (HRM) practices across market economies, and between indigenous firms and foreign MNE subsidiary operations, offering a novel perspective on convergence and divergence. Applying institutional theorizing to improve our understanding of convergence/ divergence as a process and an outcome, data collected from nine countries at three points in time over a decade confirm that convergence and divergence occur to different extents in a non-linear fashion, and vary depending on the area of HRM practice observed. Patterns of adoption and convergence/ divergence are explained through the effect of institutional constraints, which vary between liberal and coordinated market economies, and between indigenous firms and foreign MNE subsidiaries. The study contributes a more graded conceptualization of convergence/ divergence, which reflects the complex dynamic reality of international business

Aortic root dimension changes during systole and diastole: evaluation with ECG-gated multidetector row computed tomography

Cardiac pulsatility and aortic compliance may result in aortic area and diameter changes throughout the cardiac cycle in the entire aorta. Until this moment these dynamic changes could never be established in the aortic root (aortic annulus, sinuses of Valsalva and sinotubular junction). The aim of this study was to visualize and characterize the changes in aortic root dimensions during systole and diastole with ECG-gated multidetector row computed tomography (MDCT). MDCT scans of subjects without aortic root disease were analyzed. Retrospectively, ECG-gated reconstructions at each 10% of the cardiac cycle were made and analyzed during systole (30–40%) and diastole (70–75%). Axial planes were reconstructed at three different levels of the aortic root. At each level the maximal and its perpendicular luminal dimension were measured. The mean dimensions of the total study group (n = 108, mean age 56 ± 13 years) do not show any significant difference between systole and diastole. The individual dimensions vary up to 5 mm. However, the differences range between minus 5 mm (diastolic dimension is greater than systolic dimensions) and 5 mm (vice versa). This variability is independent of gender, age, height and weight. This study demonstrated a significant individual dynamic change in the dimensions of the aortic root. These results are highly unpredictable. Most of the healthy subjects have larger systolic dimensions, however, some do have larger diastolic dimensions

Management earnings forecasts and IPO performance: evidence of a regime change

Companies undertaking initial public offerings (IPOs) in Greece were obliged to include next-year profit forecast in their prospectuses, until the regulation changed in 2001 to voluntary forecasting. Drawing evidence from IPOs issued in the period 1993–2015, this is the first study to investigate the effect of disclosure regime on management earnings forecasts and IPO long-term performance. The findings show mainly positive forecast errors (forecasts are lower than actual earnings) and higher long-term returns during the mandatory period, suggesting that the mandatory disclosure requirement causes issuers to systematically bias profit forecasts downwards as they opt for the safety of accounting conservatism. The mandatory disclosure requirement artificially improves IPO share performance. Overall, our results show that mandatory disclosure of earnings forecasts can impede capital market efficiency once it goes beyond historical financial information to involve compulsory projections of future performance