Site formation and chronology of the new Paleolithic site Sima de Las Palomas de Teba, southern Spain

The newly identified Paleolithic site Sima de Las Palomas de Teba hosts an almost seven -m-thick sediment profile investigated here to elucidate the rock shelter's chronostratigraphy and formation processes. At its base, the sediment sequence contains rich archeological deposits recording intensive occupation by Neanderthals. Luminescence provides a terminus ante quem of 39.4 ± 2.6 ka or 44.9 ± 4.1 ka (OSL) and 51.4 ± 8.4 ka (TL). This occupation ended with a rockfall event followed by accumulation of archeologically sterile sediments. These were covered by sediments containing few Middle Paleolithic artifacts, which either indicate ephemeral occupation by Neanderthals or reworking as suggested by micromorphological features. Above this unit, scattered lithic artifacts of undiagnostic character may represent undefined Paleolithic occupations. Sediment burialagesbetweenabout23.0±1.5ka(OSL)and40.5±3.4ka(pIRIR)provideanUpperPaleolithicchronology for sediments deposited above the rockfall. Finally, a dung-bearing Holocene layer in the upper most part of the sequence contains a fragment of a human mandible dated to 4032 ± 39 14C yr BP. Overall, the sequence represents an important new site for studying the end of Neanderthal occupation in southern Spain

Spatiotemporal distribution and speciation of silver nanoparticles in the healing wound

Funding: This research was supported by funds from the MIUR-FIRB project number RBFR08M6W8. Acknowledgments: ELGA LabWater is acknowledged for providing the PURELAB Option-Q and Ultra Analytic systems, which produced the ultra-pure water used for Ag determinations. Adam Douglas and Dhinesh Asogan are acknowledged for their technical support during LA-ICP-MS analysis at the University of Venice, and the authors gratefully acknowledge Bill Spence and Teledyne Cetac Technologies for the loan of the laser ablation instrumentation. Laura Molin and ISTM-CNR are acknowledged for MALDI-TOF-MS analysis. The synchrotron experiments were performed on beamline ID21 at the European Synchrotron Radiation Facility (ESRF), Grenoble, France (proposal #CH4121).Peer reviewedPostprin

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

A novel demand forecasting model for radical innovation

This work presents a novel simulation-based forecasting approach combining concepts from the Bass Diffusion Model and the Discrete Choice Model from a System Dynamics perspective. The proposed approach allows for the forecasting of the adoption rate and the timing of adoption by examining the underlying preferences of individual customers and the social forces that influence these underlying preferences. A real-scale preliminary application to the German market for electric cars, parameterized through a conjoint analysis, is provided. Simulation results show the potential of the proposed approach, which provides evidence for the main factors that influence the electric vehicle adoption process in Germany.Este trabalho apresenta um novo modelo para a previsão de demanda de inovações radicais baseada em simulação de Dinâmica de Sistemas que combina conceitos do modelo de difusão de Bass e do modelo de escolha discreta. Diferentemente de outras abordagens existentes, esta proposta permite estimar não somente a fatia de mercado do produto, mas também seu comportamento no tempo (timing), a partir das preferências individuais do consumidor e das forças que as influenciam. O modelo proposto pode ser facilmente parametrizado através da Conjoint Analysis e foi testado em escala real no mercado alemão de carros elétricos. Os resultados obtidos colocam em evidência o potencial da abordagem proposta, auxiliando na compreensão dos principais fatores na escolha desse produto.0

Impact of liver fibrosis on survival of patients with intrahepatic cholangiocarcinoma receiving gemcitabine-based chemotherapy

Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively analyzed the cases of 70 patients diagnosed with iCCA between 2007 and 2020 in our tertiary hospital. Histopathological assessment of fibrosis was performed by an expert hepatobiliary pathologist. Additionally, the fibrosis-4 score (FIB-4) was calculated as a non-invasive surrogate marker for liver fibrosis. For overall survival (OS) and progression-free survival (PFS), Kaplan–Meier curves and Cox-regression analyses were performed. Subgroup analyses revealed a median OS of 21 months (95% CI = 16.7–25.2 months) and 16 months (95% CI = 7.6–24.4 months) for low and high fibrosis, respectively (p = 0.152). In non-cirrhotic patients, the median OS was 21.8 months (95% CI = 17.1–26.4 months), compared with 9.5 months (95% CI = 4.6–14.3 months) in cirrhotic patients (p = 0.007). In conclusion, patients with iCCA and cirrhosis receiving palliative chemotherapy have decreased OS rates, while fibrosis has no significant impact on OS or PFS. These patients should not be prevented from state-of-the-art first-line chemotherapy

Impact of Liver Fibrosis on Survival of Patients with Intrahepatic Cholangiocarcinoma Receiving Gemcitabine-Based Chemotherapy

Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively analyzed the cases of 70 patients diagnosed with iCCA between 2007 and 2020 in our tertiary hospital. Histopathological assessment of fibrosis was performed by an expert hepatobiliary pathologist. Additionally, the fibrosis-4 score (FIB-4) was calculated as a non-invasive surrogate marker for liver fibrosis. For overall survival (OS) and progression-free survival (PFS), Kaplan–Meier curves and Cox-regression analyses were performed. Subgroup analyses revealed a median OS of 21 months (95% CI = 16.7–25.2 months) and 16 months (95% CI = 7.6–24.4 months) for low and high fibrosis, respectively (p = 0.152). In non-cirrhotic patients, the median OS was 21.8 months (95% CI = 17.1–26.4 months), compared with 9.5 months (95% CI = 4.6–14.3 months) in cirrhotic patients (p = 0.007). In conclusion, patients with iCCA and cirrhosis receiving palliative chemotherapy have decreased OS rates, while fibrosis has no significant impact on OS or PFS. These patients should not be prevented from state-of-the-art first-line chemotherapy

OSL chronologies of paleoenvironmental dynamics recorded by loess-paleosol sequences from Europe: Case studies from the Rhine-Meuse area and the Neckar Basin

Loess-paleosol sequences (LPS) represent an important terrestrial archive for the reconstruction of the paleoenvironmental evolution during the Last Glacial cycle in Europe. In the Rhine-Meuse area and the south-western Germany, there are only few numerical ages determined with state-of-the-art luminescence methods, which limits the robustness of established chronostratigraphies. This study presents a comparative dating approach using quartz and feldspar post-infrared (pIRIR(290)) optically stimulated luminescence (OSL) from fine- and medium-grained samples of five loess-paleosol sequences. Paleoenvironmental dynamics are reconstructed by high-resolution grain-size analysis. The OSL ages are evaluated as being robust and consistent with other records. Furthermore, we show that ages for hillslope deposits are sometimes overestimated due to low-frequency high-magnitude erosive processes. The integration of OSL ages, stratigraphy and high-resolution grain-size data contributes to a temporal more complete data record from Western and Central Europe. Secondly, we propose a combined stratigraphic model for LPS of the Last Glacial cycle, which is developed and discussed in the context of other key sites such as Havrincourt, Schwalbenberg II, Tonchesberg, Nussloch and Dolni Vestonice. Comparable chronologies and patterns in proxy data between sites with a large spatial distance suggest a possible semi-synchronous response to climatic changes in Europe. By combining our data with the Eifel-Laminated-Sediment-Archive (ELSA) and the NGRIP ice core, a relationship of loess archives and large-scale climatic signals is discussed and a proxydata based event-stratigraphy is developed. This model refines existing chronostratigraphic models and contributes to solve open discussion concerning the timing and demarcation of sedimentary units and sequences from for Western and Central Europe. (C) 2017 Elsevier B.V. All rights reserved