An international team of over forty stratigraphic experts have helped to build the most up-to-date international stratigraphic framework for the Precambrian and Phanerozoic. This successor to A ...Geologic Time Scale 1989 by W. Brian Harland et al. (CUP 0521 387655) begins with an introduction to the theory and methodology behind the construction of the new time scale. The main part of the book is devoted to the scale itself, systematically presenting the standard subdivisions at all levels using a variety of correlation markers. Extensive use is made of isotope geochronology, geomathematics and orbital tuning to produce a standard geologic scale of unprecedented detail and accuracy with a full error analysis. A wallchart summarising the whole time scale, with paleogeographic reconstructions throughout the Phanerozoic, is included in the back of the book. The time scale will be an invaluable reference source for academic and professional researchers and students.
Since the original fitting of Grimme’s DFT-D3 damping parameters, the number and quality of benchmark interaction energies has increased significantly. Here, conventional benchmark sets, which focus ...on minimum-orientation radial curves at the expense of angular diversity, are augmented by new databases such as side chain–side chain interactions (SSI), which are composed of interactions gleaned from crystal data and contain no such minima-focused bias. Moreover, some existing databases such as S22×5 are extended to shorter intermolecular separations. This improved DFT-D3 training set provides a balanced description of distances, covers the entire range of interaction types, and at 1526 data points is far larger than the original training set of 130. The results are validated against a new collection of 6773 data points and demonstrate that the effect of refitting the damping parameters ranges from no change in accuracy (LC-ωPBE-D3) to an almost 2-fold decrease in average error (PBE-D3).
Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. ...Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map.
The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast and has yet to be distilled into an executive molecular ...program. We developed a data-constrained, computational approach to reduce complexity and to derive a set of functionally validated components and interaction combinations sufficient to explain observed ES cell behavior. This minimal set, the simplest version of which comprises only 16 interactions, 12 components, and three inputs, satisfies all prior specifications for self-renewal and furthermore predicts unknown and nonintuitive responses to compound genetic perturbations with an overall accuracy of 70%. We propose that propagation of ES cell identity is not determined by a vast interactome but rather can be explained by a relatively simple process of molecular computation.
Summary Background Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this ...treatment combination provided greater survival benefit than did chlorambucil or fludarabine. Methods 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. Findings There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38% vs 15%, respectively; overall response rate 94% vs 80%, respectively; p<0·0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0·006 and 0·04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0·00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (VH ) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. Interpretation Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.
For effective catchment management and intervention in hydrological systems a process-based understanding of hydrological connectivity is required so that: i) conceptual rather than solely empirical ...understanding drives how systems are interpreted; and ii) there is an understanding of how continuous flow fields develop under different sets of environmental conditions to enable managers to know when, where and how to intervene in catchment processes successfully. In order to direct future research into process-based hydrological connectivity this paper: i) evaluates the extent to which different concepts of hydrological connectivity have emerged from different approaches to measure and predict flow in different environments; ii) discusses the extent to which these different concepts are mutually compatible; and iii) assesses further research to contribute to a unified understanding of hydrological processes. Existing research is categorised into five different approaches to investigating hydrological connectivity: i) evaluating soil–moisture patterns (soil–moisture connectivity); ii) understanding runoff patterns and processes on hillslopes (flow-process connectivity); iii) investigating topographic controls (terrain-connectivity) including the impact of road networks on hydrological connectivity and catchment runoff; iv) developing models to explore and predict hydrological connectivity; and v) developing indices of hydrological connectivity. Analysis of published research suggests a relationship between research group, approach, geographic setting and the interpretation of hydrological connectivity. For further understanding of hydrological connectivity our knowledge needs to be developed using a range of techniques and approaches, there should be common understandings between researchers approaching the concept from different perspectives, and these meanings need to be communicated effectively with those responsible for land management.
The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates ...of oral conditions for the period of 1990 to 2015. Since death as a direct result of oral diseases is rare, DALY estimates were based on years lived with disability, which are estimated only on those persons with unmet need for dental care. We used our data to assess progress toward the Federation Dental International, World Health Organization, and International Association for Dental Research’s oral health goals of reducing the level of oral diseases and minimizing their impact by 2020. Oral health has not improved in the last 25 y, and oral conditions remained a major public health challenge all over the world in 2015. Due to demographic changes, including population growth and aging, the cumulative burden of oral conditions dramatically increased between 1990 and 2015. The number of people with untreated oral conditions rose from 2.5 billion in 1990 to 3.5 billion in 2015, with a 64% increase in DALYs due to oral conditions throughout the world. Clearly, oral diseases are highly prevalent in the globe, posing a very serious public health challenge to policy makers. Greater efforts and potentially different approaches are needed if the oral health goal of reducing the level of oral diseases and minimizing their impact is to be achieved by 2020. Despite some challenges with current measurement methodologies for oral diseases, measurable specific oral health goals should be developed to advance global public health.
Psi4 is an ab initio electronic structure program providing methods such as Hartree–Fock, density functional theory, configuration interaction, and coupled-cluster theory. The 1.1 release represents ...a major update meant to automate complex tasks, such as geometry optimization using complete-basis-set extrapolation or focal-point methods. Conversion of the top-level code to a Python module means that Psi4 can now be used in complex workflows alongside other Python tools. Several new features have been added with the aid of libraries providing easy access to techniques such as density fitting, Cholesky decomposition, and Laplace denominators. The build system has been completely rewritten to simplify interoperability with independent, reusable software components for quantum chemistry. Finally, a wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natural orbitals, orbital-optimized perturbation and coupled-cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational self-consistent field, density cumulant functional theory, algebraic-diagrammatic construction excited states, improvements to the geometry optimizer, and the “X2C” approach to relativistic corrections, among many other improvements.
We analyze the complete set of in-situ meteorological data obtained from the Viking landers in the 1970s to todays Curiosity rover to review our understanding of the modern near-surface climate of ...Mars, with focus on the dust, CO2 and H2O cycles and their impact on the radiative and thermodynamic conditions near the surface. In particular, we provide values of the highest confidence possible for atmospheric opacity, atmospheric pressure, near-surface air temperature, ground temperature, near-surface wind speed and direction, and near-surface air relative humidity and water vapor content. Then, we study the diurnal, seasonal and interannual variability of these quantities over a span of more than twenty Martian years. Finally, we propose measurements to improve our understanding of the Martian dust and H2O cycles, and discuss the potential for liquid water formation under Mars present day conditions and its implications for future Mars missions.
PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small ...biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.
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