A system science methodology develops a new composite highly predictable index of magnetospheric activity for the community: the whole-Earth index E(1)

For community use, a new composite whole-Earth index E(1) and its matching composite solar wind driving function S(1) are derived. A system science methodology is used based on a time-dependent magnetospheric state vector and a solar wind state vector, with canonical correlation analysis (CCA) used to reduce the two state vectors to the two time-dependent scalars E(1)(t) and S(1)(t). The whole-Earth index E(1) is based on a diversity of measures via six diverse geomagnetic indices that will be readily available in the future: SML, SMU, Ap60, SYMH, ASYM, and PCC. The CCA-derived composite index has several advantages: 1) the new “canonical” geomagnetic index E(1) will provide a more powerful description of magnetospheric activity, a description of the collective behavior of the magnetosphere–ionosphere system. 2) The new index E(1) is much more accurately predictable from upstream solar wind measurements on Earth. 3) Indications are that the new canonical geomagnetic index E(1) will be accurately predictable even when as-yet-unseen extreme solar wind conditions occur. The composite solar wind driver S(1) can also be used as a universal driver function for individual geomagnetic indices or for magnetospheric particle populations. To familiarize the use of the new index E(1), its behavior is examined in different phases of the solar cycle, in different types of solar wind plasma, during high-speed stream-driven storms, during CME sheath-driven storms, and during superstorms. It is suggested that the definition of storms are the times when E(1) >1

A system science methodology develops a new composite highly predictable index of magnetospheric activity for the community: the whole-Earth index E(1)

For community use, a new composite whole-Earth index E(1) and its matching composite solar wind driving function S(1) are derived. A system science methodology is used based on a time-dependent magnetospheric state vector and a solar wind state vector, with canonical correlation analysis (CCA) used to reduce the two state vectors to the two time-dependent scalars E(1)(t) and S(1)(t). The whole-Earth index E(1) is based on a diversity of measures via six diverse geomagnetic indices that will be readily available in the future: SML, SMU, Ap60, SYMH, ASYM, and PCC. The CCA-derived composite index has several advantages: 1) the new “canonical” geomagnetic index E(1) will provide a more powerful description of magnetospheric activity, a description of the collective behavior of the magnetosphere–ionosphere system. 2) The new index E(1) is much more accurately predictable from upstream solar wind measurements on Earth. 3) Indications are that the new canonical geomagnetic index E(1) will be accurately predictable even when as-yet-unseen extreme solar wind conditions occur. The composite solar wind driver S(1) can also be used as a universal driver function for individual geomagnetic indices or for magnetospheric particle populations. To familiarize the use of the new index E(1), its behavior is examined in different phases of the solar cycle, in different types of solar wind plasma, during high-speed stream-driven storms, during CME sheath-driven storms, and during superstorms. It is suggested that the definition of storms are the times when E(1) >1

White matter microstructure associations to amyloid burden in adults with Down syndrome.

INTRODUCTION: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer's Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter. In this work, we explored the correlation of white matter microstructure with amyloid load to assess amyloid-related neurodegeneration in a cohort of adults with DS. METHODS: In this study of 96 adults with DS, the relation of white matter microstructure using diffusion tensor imaging (DTI) and amyloid plaque burden using [11C]PiB PET were examined. The amyloid load (AβL) derived from [11C]PiB was used as a global measure of amyloid burden. AβL and DTI measures were compared using tract-based spatial statistics (TBSS) and corrected for imaging site and chronological age. RESULTS: TBSS of the DTI maps showed widespread age-by-amyloid interaction with both fractional anisotropy (FA) and mean diffusivity (MD). Further, diffuse negative association of FA and positive association of MD with amyloid were observed. DISCUSSION: These findings are consistent with the white matter microstructural changes associated with AD disease progression in late onset AD in non-DS populations

White matter regions with low microstructure in young adults spatially coincide with white matter hyperintensities in older adults

Microstructural and macrostructural white matter damage occurs frequently with aging, is associated with negative health outcomes, and can be imaged non-invasively as fractional anisotropy (FA) and white matter hyperintensities (WMH), respectively. The extent to which diminished microstructure precedes or results from macrostructural white matter damage is poorly understood. This study evaluated the hypothesis that white matter areas with normatively lower microstructure in young adults are most susceptible to develop WMH in older adults. Forty-nine younger participants (age = 25.8 ± 2.8 years) underwent diffusion-weighted imaging (DWI), and 557 older participants (age = 73.9 ± 5.7 years) underwent DWI and T2-weighted magnetic resonance imaging (MRI). In older adults, WMH had a mostly periventricular distribution with higher frequency in frontal regions. We found lower FA in areas of frank WMH compared to normal-appearing white matter (NAWM) in older adults. Then, to determine if areas of normatively lower white matter microstructure spatially overlap with areas that frequently develop macrostructural damage in older age, we created a WMH frequency map in which each voxel represented the percentage of older adults with a WMH in that voxel. We found lower normative FA in young adults with regions frequently segmented as WMH in older adults. We conclude that low white matter microstructure is observed in areas of white matter macrostructural damage, but white matter microstructure is also normatively low (i.e., at ages 20–30) in regions with high WMH frequency, prior to white matter macrostructural damage

Interactive translation prediction versus conventional post-editing in practice: a study with the CasMaCat workbench

[EN] We conducted a field trial in computer-assisted professional translation to compare interactive translation prediction (ITP) against conventional post-editing (PE) of machine translation (MT) output. In contrast to the conventional PE set-up, where an MT system first produces a static translation hypothesis that is then edited by a professional (hence "post-editing"), ITP constantly updates the translation hypothesis in real time in response to user edits. Our study involved nine professional translators and four reviewers working with the web-based CasMaCat workbench. Various new interactive features aiming to assist the post-editor/translator were also tested in this trial. Our results show that even with little training, ITP can be as productive as conventional PE in terms of the total time required to produce the final translation. Moreover, translation editors working with ITP require fewer key strokes to arrive at the final version of their translation.This work was supported by the European Union’s 7th Framework Programme (FP7/2007–2013) under grant agreement No 287576 (CasMaCat ).Sanchis Trilles, G.; Alabau, V.; Buck, C.; Carl, M.; Casacuberta Nolla, F.; Garcia Martinez, MM.; Germann, U.... (2014). Interactive translation prediction versus conventional post-editing in practice: a study with the CasMaCat workbench. Machine Translation. 28(3-4):217-235. https://doi.org/10.1007/s10590-014-9157-9S217235283-4Alabau V, Leiva LA, Ortiz-Martínez D, Casacuberta F (2012) User evaluation of interactive machine translation systems. In: Proceedings of the 16th Annual Conference of the European Association for Machine Translation, pp 20–23Alabau V, Buck C, Carl M, Casacuberta F, García-Martínez M, Germann U, González-Rubio J, Hill R, Koehn P, Leiva L, Mesa-Lao B, Ortiz-Martínez D, Saint-Amand H, Sanchis-Trilles G, Tsoukala C (2014) Casmacat: A computer-assisted translation workbench. In: Proceedings of the 14th Conference of the European Chapter of the Association for Computational Linguistics, pp 25–28Alves F, Vale D (2009) Probing the unit of translation in time: aspects of the design and development of a web application for storing, annotating, and querying translation process data. Across Lang Cultures 10(2):251–273Bach N, Huang F, Al-Onaizan Y (2011) Goodness: A method for measuring machine translation confidence. In: Proceedings of the Annual Meeting of the Association for Computational Linguistics, pp 211–219Barrachina S, Bender O, Casacuberta F, Civera J, Cubel E, Khadivi S, Lagarda AL, Ney H, Tomás J, Vidal E, Vilar JM (2009) Statistical approaches to computer-assisted translation. Comput Linguist 35(1):3–28Brown PF, Della Pietra SA, Della Pietra VJ (1993) The mathematics of statistical machine translation: parameter estimation. Comput Linguist 19(2):263–311Callison-Burch C, Koehn P, Monz C, Post M, Soricut R, Specia L (2012) Findings of the 2012 workshop on statistical machine translation. In: Proceedings of the Seventh Workshop on Statistical Machine Translation, pp 10–51Carl M (2012a) The CRITT TPR-DB 1.0: A database for empirical human translation process research. In: Proceedings of the AMTA 2012 Workshop on Post-Editing Technology and Practice, pp 1–10Carl M (2012b) Translog-II: a program for recording user activity data for empirical reading and writing research. In: Proceedings of the Eighth International Conference on Language Resources and Evaluation, pp 4108–4112Carl M (2014) Produkt- und Prozesseinheiten in der CRITT Translation Process Research Database. In: Ahrens B (ed) Translationswissenschaftliches Kolloquium III: Beiträge zur Übersetzungs- und Dolmetschwissenschaft (Köln/Germersheim). Peter Lang, Frankfurt am Main, pp 247–266Carl M, Kay M (2011) Gazing and typing activities during translation : a comparative study of translation units of professional and student translators. Meta 56(4):952–975Doherty S, O’Brien S, Carl M (2010) Eye tracking as an MT evaluation technique. Mach Transl 24(1):1–13Elming J, Carl M, Balling LW (2014) Investigating user behaviour in post-editing and translation using the Casmacat workbench. In: O’Brien S, Winther Balling L, Carl M, Simard M, Specia L (eds) Post-editing of machine translation: processes and applications. Cambridge Scholar Publishing, Newcastle upon Tyne, pp 147–169Federico M, Cattelan A, Trombetti M (2012) Measuring user productivity in machine translation enhanced computer assisted translation. In: Proceedings of the Tenth Biennial Conference of the Association for Machine Translation in the AmericasFlournoy R, Duran C (2009) Machine translation and document localization at adobe: From pilot to production. In: Proceedings of MT Summit XIIGreen S, Heer J, Manning CD (2013) The efficacy of human post-editing for language translation. In: Proceedings of SIGCHI Conference on Human Factors in Computing Systems, pp 439–448Guerberof A (2009) Productivity and quality in mt post-editing. In: Proceedings of MT Summit XII-Workshop: Beyond Translation Memories: New Tools for Translators MTGuerberof A (2012) Productivity and quality in the post-editing of outputs from translation memories and machine translation. Ph.D. ThesisJust MA, Carpenter PA (1980) A theory of reading: from eye fixations to comprehension. Psychol Rev 87(4):329Koehn P (2009a) A process study of computer-aided translation. Mach Transl 23(4):241–263Koehn P (2009b) A web-based interactive computer aided translation tool. In: Proceedings of ACL-IJCNLP 2009 Software Demonstrations, pp 17–20Krings HP (2001) Repairing texts: empirical investigations of machine translation post-editing processes, vol 5. Kent State University Press, KentLacruz I, Shreve GM, Angelone E (2012) Average pause ratio as an indicator of cognitive effort in post-editing: a case study. In: Proceedings of the AMTA 2012 Workshop on Post-Editing Technology and Practice, pp 21–30Langlais P, Foster G, Lapalme G (2000) Transtype: A computer-aided translation typing system. In: Proceedings of the 2000 NAACL-ANLP Workshop on Embedded Machine Translation Systems, pp 46–51Leiva LA, Alabau V, Vidal E (2013) Error-proof, high-performance, and context-aware gestures for interactive text edition. In: Proceedings of the 2013 annual conference extended abstracts on Human factors in computing systems, pp 1227–1232Montgomery D (2004) Introduction to statistical quality control. Wiley, HobokenO’Brien S (2009) Eye tracking in translation process research: methodological challenges and solutions, Copenhagen Studies in Language, vol 38. Samfundslitteratur, Copenhagen, pp 251–266Ortiz-Martínez D, Casacuberta F (2014) The new Thot toolkit for fully automatic and interactive statistical machine translation. In: Proceedings of the 14th Annual Meeting of the European Association for Computational Linguistics: System Demonstrations, pp 45–48Plitt M, Masselot F (2010) A productivity test of statistical machine translation post-editing in a typical localisation context. Prague Bulletin Math Linguist 93(1):7–16Sanchis-Trilles G, Ortiz-Martínez D, Civera J, Casacuberta F, Vidal E, Hoang H (2008) Improving interactive machine translation via mouse actions. In: Proceedings of the Conference on Empirical Methods in Natural Language Processing, pp 485–494Simard M, Foster G (2013) Pepr: Post-edit propagation using phrase-based statistical machine translation. In: Proceedings of MT Summit XIV, pp 191–198Skadiņš R, Puriņš M, Skadiņa I, Vasiļjevs A (2011) Evaluation of SMT in localization to under-resourced inflected language. In: Proceedings of the 15th International Conference of the European Association for Machine Translation, pp 35–4

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society