The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

is given to the source. Deciphering the Liquidity and Credit Crunch 2007-08

Goodwin, Martin Schmalz, and Hao Wu provided excellent research assistance. I am grateful for financial support from the Alfred P. Sloan Foundation. The views expressed herein are those of the author(s

Evaluating the predictability of terrestrial ecosystem carbon fluxes integrating long term eddy-covariance and biometric observations with multi-model ensembles

Discrepancies between future projections of land carbon fluxes originate from different process representations, but also from differences in model parameterization. Model parameters are typically drawn from disparate literature sources, individual site measurements, or expert judgment, allowing for large variability in the actual parameters used and thus model functional responses. In addition, differences in meteorological forcing datasets and modeling setups may contribute strongly to differences at inter-annual and longer time scales. Along with the known differences in the mean model behavior under future climate scenarios, there are likely also differences in model responses to increased climate variability, and extreme events, which have yet to be assessed. In this study we developed an in situ model data fusion experiment to explore the contribution of diverse long-term observations in addressing the divergence of modeled projections of ecosystem water and carbon fluxes until 2100, along with responses to climate variability and extreme events. We focus on two forest sites in France – Hesse and Le Bray – for which carbon and water fluxes have been observed for more than ten years using eddy covariance methodology. The consolidated set of eddy covariance observations and respective uncertainties is complemented with biometric information on aboveground biomass, biomass increments and soil carbon stocks. These datasets are simultaneously used as constraints in the inverse parameter optimization of an ensemble of terrestrial biogeochemical models ranging from specific forest models to generic land surface schemes, namely: BASFOR, FöBAAR, JSBACH, LPJ and ORCHIDEE. The experimental setup includes the harmonization of the optimization by forcing and constraining the models with the same observations, and through a common cost function. The set of multiple constraints ensures that the models simulate the responses of ecosystem fluxes to environmental conditions in agreement with ecosystem pools. In all models we observe significant improvements in modeling performance but modest improvements in estimating the interannual variability in carbon fluxes and pools. The divergence in long-term trends until 2100 between models is reduced in the carbon fluxes and pools after optimization. However, an increase in the variability of net ecosystem fluxes is observed, which results from the higher interannual variability in the climate scenarios, as well as the growing ecosystem carbon pools. These results suggest more frequent and amplified responses of ecosystem carbon cycle as present-day extreme conditions become more frequent. Overall, this study emphasizes the importance of long-term observations in assessing inter-model divergence and in addressing the future sensitivities of ecosystem carbon fluxes to changes in climate variability

Stage-Adapted Treatment of HIV-Associated Hodgkin Lymphoma: Results of a Prospective Multicenter Study

Purpose Although the outcome of patients with HIV-related Hodgkin lymphoma (HIV-HL) has markedly improved since the introduction of combined antiretroviral therapy, standard therapy is still poorly defined. This prospective study investigates a stage- and risk-adapted treatment strategy in patients with HIV-HL. Patients and Methods Patients with early favorable HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of involved-field (IF) radiation. In patients with early unfavorable HIV-HL, four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP baseline) or four cycles of ABVD + 30 Gy of IF radiation were administered. Six to eight cycles of BEACOPP baseline were given in patients with advanced-stage HIV-HL. In patients with advanced HIV infection, BEACOPP was replaced with ABVD. Results Of 108 patients (including eight female patients) included in the study, 23 (21%) had early favorable HL, 14 (13%) had early unfavorable HL, and 71 (66%) had advanced-stage HL. The median CD4 count at HL diagnosis was 240/mu L. The complete remission rates for patients with early favorable, early unfavorable, and advanced-stage HL were 96%, 100%, and 86%, respectively. The 2-year progression-free survival of the entire study population was 91.7%. Eleven patients (11%) have died, and treatment-related mortality was 5.6%. The 2-year overall survival rate was 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%), and advanced-stage HL (86.8%). Conclusion In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL