BlogForever D3.3: Development of the Digital Rights Management Policy

This report presents a set of recommended practices and approaches that a future BlogForever repository can use to develop a digital rights management policy. The report outlines core legal aspects of digital rights that might need consideration in developing policies, and what the challenges are, in particular, in relation to web archives and blog archives. These issues are discussed in the context of the digital information life cycle and steps that might be taken within the workflow of the BlogForever platform to facilitate the gathering and management of digital rights information. Further, the reports on interviews with experts in the field highlight current perspectives on rights management and provide empirical support for the recommendations that have been put forward

A full approximation scheme multilevel method for nonlinear variational inequalities

We present the full approximation scheme constraint decomposition (FASCD) multilevel method for solving variational inequalities (VIs). FASCD is a common extension of both the full approximation scheme (FAS) multigrid technique for nonlinear partial differential equations, due to A.~Brandt, and the constraint decomposition (CD) method introduced by X.-C.~Tai for VIs arising in optimization. We extend the CD idea by exploiting the telescoping nature of certain function space subset decompositions arising from multilevel mesh hierarchies. When a reduced-space (active set) Newton method is applied as a smoother, with work proportional to the number of unknowns on a given mesh level, FASCD V-cycles exhibit nearly mesh-independent convergence rates, and full multigrid cycles are optimal solvers. The example problems include differential operators which are symmetric linear, nonsymmetric linear, and nonlinear, in unilateral and bilateral VI problems.Comment: 25 pages, 9 figure

Connectivity in the Deep: Phylogeography of the Velvet Belly Lanternshark

PublishedThe velvet belly lanternshark, Etmopterus spinax, is a deep-sea bioluminescent squaloid shark, found predominantly in the northeast Atlantic and Mediterranean Sea. It has been exposed to relatively high levels of mortality associated with by-catch in some regions. Its late maturity and low fecundity potentially renders it vulnerable to over-exploitation, although little remains known about processes of connectivity between key habitats/regions. This study utilised DNA sequencing of partial regions of the mitochondrial control region and nuclear ribosomal internal transcribed spacer 2 to investigate population structure and phylogeography of this species across the northeast Atlantic and Mediterranean Basin. Despite the inclusion of samples from the range edges or remote locations, no evidence of significant population structure was detected. An important exception was identified using the control region sequence, with much greater (and statistically significant) levels of genetic differentiation between the Mediterranean and Atlantic. This suggests that the Strait of Gibraltar may represent an important bathymetric barrier, separating regions with very low levels of female dispersal. Bayesian estimation of divergence time also places the separation between the Mediterranean and Atlantic lineages within the last 100,000 years, presumably connected with perturbations during the last Glacial Period. These results demonstrate population subdivision at a much smaller geographic distance than has generally been identified in previous work on deep-sea sharks. This highlights a very significant role for shallow bathymetry in promoting genetic differentiation in deepwater taxa. It acts as an important exception to a general paradigm of marine species being connected by high levels of gene-flow, representing single stocks over large scales. It may also have significant implications for the fisheries management of this species.We would like to thank Trude Thangstad, Merete Kvalsund (Institute of Marine Research, Norway), Cecilia Pinto, Eleonora de Sabata and the scientists and crew of the RV Celtic Explorer for assistance in the collection of samples. Funding for this project was provided by the University of Salford and the University of Bristol. We are grateful to all those who helped with sample collection, including the MEDITS survey programme, the Department of Fisheries and Marine Research (DFMR) of Cyprus, the Annual Demersal and Deep Water Fish Monitoring Surveys financed by the Azores Government and the CONDOR project (supported by a grant from Iceland, Liechtenstein, Norway through the EEA Financial Mechanism (PT0040/2008)

Stereoselective Metal-Free Reduction of Chiral Imines in Batch and Flow Mode: A Convenient Strategy for the Synthesis of Chiral Active Pharmaceutical Ingredients

he convenient, metal-free reduction of imines that contain an inexpensive and removable chiral auxiliary allowed for the synthesis of the immediate precursors of chiral active pharmaceutical ingredients (APIs). This protocol was carried out under batch and flow conditions to give the correspoding prod- ucts in high yields with almost complete stereocontrol. In the presence of trichlorosilane, an inexpensive and nontoxic reduc- ing agent, and an achiral Lewis base such as N,N-dimethyl- Introduction The pharmaceutical industry is gradually progressing towards enantiopure formulations. Most newly introduced drugs are chiral, and it is expected that approximately 95 % of pharma- ceutical drugs will be chiral by 2020. [1] In this context, chiral amines are considered a class of paramount importance, be- cause they are found in a plethora of compounds such as those of pharmaceutical interest as well as those developed for agro- chemicals, fragrances, and fine chemicals. [2] The reduction of the C=N group is one of the most widely used approaches to synthesize chiral amines, and over the last ten years, successful catalytic enantioselective methods based on both metal-pro- moted [3] and organocatalyzed [4] strategies have been devel- oped. When an industrial synthesis of a chiral pharmaceutical prod- uct must be planned, however, issues such as the chemical effi- ciency and robustness of the procedure, its general applicabil- ity, and economic considerations become crucially important. For these reasons, the applications of many chiral catalytic sys- tems are often not feasible, and the use of inexpensive and readily available chiral auxiliaries becomes an attractive and economic alternative. This also holds true for the synthesis of [a] Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, 20133 Milano, Italy E-mail: [email protected] http://users2.unimi.it/Benagliagroup [b] Istituto di Scienze e Tecnologie Molecolari ISTM-CNR, Via Golgi 19, 20133 Milano, Italy [c] Department of Chemistry and Chemistry Center of Évora, University of Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal Supporting information and ORCID(s) from the author(s) for this article are available on the WWW under http://dx.doi.org/10.1002/ejoc.201601268. Eur. J. Org. Chem. 2017, 39–44 © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim39 formamide, the formal syntheses of Rivastgmine, calcimimetic NPS R-568, and a Rho kinases inhibitor were successfully accom- plished. For the first time, both the diastereoselective imine re- duction and the auxiliary removal were efficiently performed in a micro- or mesoreactor under continuous-flow conditions, which paved the way towards the development of a practical process for the syntheses of industrially relevant, biologically active, enantiopure N-alkylamine

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Measurements of integrated and differential cross sections for isolated photon pair production in pp collisions at √s=8 TeV with the ATLAS detector

A measurement of the production cross section for two isolated photons in proton-proton collisions at a center-of-mass energy of √s=8 TeV is presented. The results are based on an integrated luminosity of 20.2 fb−1 recorded by the ATLAS detector at the Large Hadron Collider. The measurement considers photons with pseudorapidities satisfying |ηγ|40GeV and EγT,2>30 GeV for the two leading photons ordered in transverse energy produced in the interaction. The background due to hadronic jets and electrons is subtracted using data-driven techniques. The fiducial cross sections are corrected for detector effects and measured differentially as a function of six kinematic observables. The measured cross section integrated within the fiducial volume is 16.8 ± 0.8  pb . The data are compared to fixed-order QCD calculations at next-to-leading-order and next-to-next-to-leading-order accuracy as well as next-to-leading-order computations including resummation of initial-state gluon radiation at next-to-next-to-leading logarithm or matched to a parton shower, with relative uncertainties varying from 5% to 20%

Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS

Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively