Synthesis of Cyclic α-Diones, a Class of Natural Flavor Compounds

A practical and generally applicable synthesis of the important flavor ingredients corylone (5) and its alkyl homologues 11, 13, 15, and 16 is described, based on alkylation of methyl 4-methoxyacetoacetate (6) with an α-chloro-ketone and subsequent cyclization, hydrolysis, and decarboxylation. The one-pot transformation of methyl 4-chloroacetoacetate to 17 through four consecutive steps is demonstrated. The principle has also been used to prepare the six-membered ring analogues 23 and 24

Administrative Coding in Electronic Health Care Record-Based Research of NAFLD: An Expert Panel Consensus Statement

cited By 0Background and Aims Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and Results Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.Peer reviewe

The future of International Classification of Diseases coding in steatotic liver disease:An expert panel Delphi consensus statement

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%).CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.</p

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Evaluation of Radiation Components in a Global Freshwater Model with Station-Based Observations

In many hydrological models, the amount of evapotranspired water is calculated using the potential evapotranspiration (PET) approach. The main driver of several PET approaches is net radiation, whose downward components are usually obtained from meteorological input data, whereas the upward components are calculated by the model itself. Thus, uncertainties can be large due to both the input data and model assumptions. In this study, we compare the radiation components of the WaterGAP Global Hydrology Model, driven by two meteorological input datasets and two radiation setups from ERA-Interim reanalysis. We assess the performance with respect to monthly observations provided by the Baseline Surface Radiation Network (BSRN) and the Global Energy Balance Archive (GEBA). The assessment is done for the global land area and specifically for energy/water limited regions. The results indicate that there is no optimal radiation input throughout the model variants, but standard meteorological input datasets perform better than those directly obtained by ERA-Interim reanalysis for the key variable net radiation. The low number of observations for some radiation components, as well as the scale mismatch between station observations and 0.5° × 0.5° grid cell size, limits the assessment

The emergence of patent races in lignocellulosic biofuels, 2002–2015

How does increasing economic and technological interest in biofuels shape the nature of the intellectual property rights (IPR) in the industry? Is the technological nature of biofuel patents and inventions, as well as the business itself undergoing a transformation? This article provides a patent analysis of lignocellulosic biofuels with U.S. patent publications between 2002 and 2015 in order to shed light on the broader economic and regulatory factors affecting the development of new technologies in the area. Patent applications in the technology have increased about eightfold in this period and count about 130–150 per year currently, and could soon reach 200 annual filings. Specifically, we analyse in what ways the nature of lignocellulosic biofuel technologies is changing, and our results suggest that this business is indeed being transformed by increasing research and development (R&amp;D) and IPR efforts, material in an evident patent race. We document a relatively small, but nascent technology, with some key technology areas increasing between four- and tenfold, over the last decade. Technologically leading countries are the U.S., followed by Germany, Japan, France and the U.K. We argue that intensified global and industry-wide claims for IPR reveal an ongoing patent race with multiple implications for the industry and engineering community. Most importantly, industry's technological interdependence is likely to increase as the likelihood for broad, exclusive patent regimes diminishes, making the industry more likely to explore increasingly collaborative technological solutions when carrying out R&amp;D and investing in new production facilities in the future

CCDC 237718: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures