Concept and benchmark results for Big Data energy forecasting based on Apache Spark

The present article describes a concept for the creation and application of energy forecasting models in a distributed environment. Additionally, a benchmark comparing the time required for the training and application of data-driven forecasting models on a single computer and a computing cluster is presented. This comparison is based on a simulated dataset and both R and Apache Spark are used. Furthermore, the obtained results show certain points in which the utilization of distributed computing based on Spark may be advantageous

Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families

The Implementation of Managed Entry Agreements in Central and Eastern Europe : Findings and Implications

Funding Information: In Bosnia and Herzegovina, both The Federation of Bosnia and Herzegovina and the Republic of Srpska, also have special funds and budgets in place for the financing of expensive medicines, which are innovative and under patent. Similar earmarked funds are available in Scotland (the New Medicines Fund funded by the Pharmaceutical Price Regulation Scheme [PPRS] rebates) [35] and England (the Cancer Drugs Fund) [36]. However, support for such earmarked funds is mixed. While they facilitate access, critics raised issues about fairness towards other disease areas and patient groups that are not eligible for special funding [3, 39]. Further, the views of a Patient and Clinician Engagement meeting in Scotland [37] and the end-of-life criteria in England [38] offer opportunities for special considerations affecting medicines for end-of-life and very rare conditions to be taken into account in the health technology assessment process. Funding Information: The authors would like to acknowledge Dr. Jan Jones from the Scottish Medicines Consortium, Scotland, for contributing to the discussion with information on Scotland, Drs. Lyudmila Bezmelnitsyna and Anastasia Isaeva for contributing to data collection in Russia and Dr. Kate?ina Podrazilov? from SZP ?R for providing information on the Czech Republic. Alessandra Ferrario was a Research Officer at the LSE Health at the time this research was conducted. She is now a postdoctoral Research Fellow at the Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, USA. Email: [email protected] No sources of funding were used for this study. The authors declare they have no conflicts of interest. However, Di?na Ar?ja, Maria Dimitrova, Jurij F?rst, Ieva Grei?i?t?-Kuprijanov, Iris Hoxha, Arianit Jakupi, Erki Laidm?e, Vanda Markovic-Pekovic, Dmitry Meshkov, Guenka Petrova, Maciej Pomorski and Patricia Vella Bonanno work directly for national health authorities or are advisers to them. Alessandra Ferrario, Tomasz Bochenek, Ileana Mardare, Dominik Tomek, Luka Voncina, Alan Haycox, Panos Kanavos,?Olga L?blov?, and Brian Godman are academics and independent researchers also working with national and regional health authorities and others to improve the quality and efficiency of prescribing, and Tarik Catic, D?vid Dank?,and Tanja Novakovic are involved with pharmaceutical, pharmacoeconomics and outcomes research groups in their countries. Olga L?blov? has also carried out remunerated consultancy activities for A&R Partners, Baxter AG and Instytut Arcana and Ileana Mardare has signed a consulting contract with Ewopharma A.G. Romania. The content of the paper and the conclusions are those of each author and may not necessarily reflect those of any organisation that employs them. Publisher Copyright: © 2017, The Author(s).Background: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. Method: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. Results: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). Conclusions: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.publishersversionPeer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Sensitivity of satellite-based methods for deriving solar radiation to different choice of aerosol input and models

This paper presents a sensitivity analysis of satellite-based methods for deriving solar irradiance components for analyzing the impact of the external inputs that are normally associated to the satellite model. Different sensitivity calculations have been performed using as reference site the PSA (Solar Platform of Almeria) station placed at the south-east of Spain. Thus, the sensitivity to the aerosol information input has been addressed by comparing the estimations using aerosol input from AERONET data with those using aerosol dataset such as MODIS or MISR (based on satellite) and MACC (based on reanalysis). Sensitivity to the clear sky model choice has been also studied by using three different models, from the simpler ESRA model (in terms of input parameters) to the most sophisticated REST2. Finally, three global to direct conversion models (Louche, DirInt and DirIndex) have been included to explore the sensitivity of the direct normal irradiance estimations. The sensitivity analysis has shown the interrelations between the different cases according to the uncertainty of the input information used. The results have been analyzed for clear and non-clear sky conditions separately and for the DNI irradiance range of 400-900Wm-2 as a case of special interest for the concentrating solar power applications. The work presented here has as novelty the analysis of the propagation of uncertainty of individual models and atmospheric datasets in the framework of a satellite-based model for solar irradiance computation and their relative weights to the final performance of the model. An underestimation of AOD by 50% causes an error in the global horizontal irradiance calculated by a clear sky model of 3-5% depending on the model used, and slightly less for an overestimation of AOD. For DNI the error ranges are 12-15% and 9-12% for 50% underestimation and overestimation of AOD respectively. © 2014 Elsevier Ltd