Brandeis University

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

A LARGER JURISDICTION FOR PSYCHOLOGY. Introduction: Toward a Psychology of Health. What Psychology Can Learn from the Existentialists. GROWTH AND MOTIVATION. Deficiency Motivation and Growth Motivation. Defense and Growth. The Need to Know and the Fear of Knowing. GROWTH AND COGNITION. Cognition of Being in the Peak-Experiences. Peak-Experiences as Acute Identity-Experiences. Some Dangers of Being-Cognition. Resistance to Being Rubricized. CREATIVENESS. Creativity in Self-Actualizing People. VALUES. Psychological Data and Human Values. Values, Growth, and Health. Health as Transcendence of Environment. FUTURE TASKS. Some Basic Propositions of a Growth and Self-Actualization Psychology. Appendices. Bibliography. Additional Bibliography. Index.

A novel class of information-theoretic divergence measures based on the Shannon entropy is introduced. Unlike the well-known Kullback divergences, the new measures do not require the condition of absolute continuity to be satisfied by the probability distributions involved. More importantly, their close relationship with the variational distance and the probability of misclassification error are established in terms of bounds. These bounds are crucial in many applications of divergence measures. The measures are also well characterized by the properties of nonnegativity, finiteness, semiboundedness, and boundedness.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

List of notation Introduction The dynamics of nuclear spin systems Manipulation of nuclear spin Hamiltonians One-dimensional Fourier spectroscopy Multiple-quantum transitions Two-dimensional Fourier spectroscopy Two-dimensional separation of interactions Two-dimensional correlation methods based on coherence transfer Dynamic processes studied by two-dimensional exchange spectroscopy Nuclear magnetic resonance imaging References Index.

Abstract When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 ± 3 μ as, which is circular and encompasses a central depression in brightness with a flux ratio ≳10:1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 ± 0.7) × 10 9 M ⊙ . Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.

Author(s): Collaboration, The ATLAS; Aad, G; Abat, E; Abdallah, J; Abdelalim, AA; Abdesselam, A; Abdinov, O; Abi, BA; Abolins, M; Abramowicz, H; Acerbi, E; Acharya, BS; Achenbach, R; Ackers, M; Adams, DL; Adamyan, F; Addy, TN; Aderholz, M; Adorisio, C; Adragna, P; Aharrouche, M; Ahlen, SP; Ahles, F; Ahmad, A; Ahmed, H; Aielli, G; Åkesson, PF; Åkesson, TPA; Akimov, AV; Alam, SM; Albert, J; Albrand, S; Aleksa, M; Aleksandrov, IN; Aleppo, M; Alessandria, F; Alexa, C; Alexander, G; Alexopoulos, T; Alimonti, G; Aliyev, M; Allport, PP; Allwood-Spiers, SE; Aloisio, A; Alonso, J; Alves, R; Alviggi, MG; Amako, K; Amaral, P; Amaral, SP; Ambrosini, G; Ambrosio, G; Amelung, C; Ammosov, VV; Amorim, A; Amram, N; Anastopoulos, C; Anderson, B; Anderson, KJ; Anderssen, EC; Andreazza, A; Andrei, V; Andricek, L; Andrieux, M-L; Anduaga, XS; Anghinolfi, F; Antonaki, A; Antonelli, M; Antonelli, S; Apsimon, R; Arabidze, G; Aracena, I; Arai, Y; Arce, ATH; Archambault, JP; Arguin, J-F; Arik, E; Arik, M; Arms, KE; Armstrong, SR; Arnaud, M; Arnault, C; Artamonov, A; Asai, S; Ask, S

Despite the clear importance of social and environmental' influences on creative performance, a social psychology of creativity is yet to be developed. Theory and research have focused almost exclusively on a personality approach to creativity and, to a lesser extent, a cognitive-abilities approach. Following a consideration of the definition and assessment of creativity, a componential framework for conceptualizing creativity is presented here. Including domain-relevant skills, creativity-relevant skills, and task motivation as a set of necessary and sufficient components of creativity, the framework describes the way in which cognitive abilities, personality characteristics, and social factors might contribute to different stages of the creative process. The discussion emphasizes the previously neglected social factors and highlights the contributions that a social psychology of creativity can make to a comprehensive view of creative performance. A striking feature of many phenomenological accounts of creativity is the degree to which outstandingly creative individuals feel influenced by social and environmental factors. In many cases, these factors are quite ordinary, mundane events; it appears that even seemingly insignificant features of the environment can be detrimental or conducive to creativity in some individuals. For example, in a letter to a friend, Tchaikovsky (1906) described the devastating effect that

Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Preface, by Bertha G. Maslow Introduction: A. H. Maslow, by Henry Geiger Part I. HEALTH AND PATHOLOGY 1. Toward a Humanistic Biology 2 Neurosis as a Failure of Personal Growth 3. Self-Actualizing and Beyond. Part II. CREATIVENESS 4. The Creative Attitude 5. A Holistic Approach to Creativity 6. Emotional Blocks to Creativity 7. The Need for Creative People. Part III. VALUES 8. Fusions of Facts and Values 9. Notes on Being-Psychology 10. Comments from a Symposium on Human Values. Part IV. EDUCATION l. Knower and Known 2. Education and Peak Experiences 13. Goals and Implications of Humanistic Education. Part V. SOCIETY 14. Synergy in the Society and in the Individual 15. Questions for the Normative Social Psychologist 16. Synanon and Eupsychia 17. On Eupsychian Management 18. On Low Grumbles, High Grumbles and Meta-grumbles. Part VI. BEING-COGNITION 19. Notes on Innocent Cognition 20. Further Notes on Cognition. Part VII. TRANSCENDENCE AND THE PSYCHOLOGY OF BEING 21. Various Meanings of Transcendence 22. Theory Z. Part VIII. METAMOTIVATION 23. A Theory of Metamotivation: The Biological Rooting of the Value-Life. APPENDICES Appendix A: Comments on Religions, Values, and Peak-Experiences. Appendix B: Some Parallels Between Sexual and Dominance Behaviour of Infrahuman Primates. and the Fantasies of Patients in Psychotherapy. Appendix C: Adolescence and Juvenile Delinquency in Two Different Cultures. Appendix D: Criteria for Judging Needs to Be Instinctoid. Appendix E: Abraham H. Maslow: A Bibliography. Bibliography. Index.

This paper describes the database on U.S. patents that we have developed over the past decade, with the goal of making it widely accessible for research. We present main trends in U. S. patenting over the last 30 years, including a variety of original measures constructed with citation data, such as backward and forward citation lags, indices of "originality" and "generality", self-citations, etc. Many of these measures exhibit interesting differences across the six main technological categories that we have developed (comprising Computers and Communications, Drugs and Medical, Electrical and Electronics, Chemical, Mechanical and Others), differences that call for further research. To stimulate such research, the entire database-about 3 million patents and 16 million citations-is now available on the NBER website. We discuss key issues that arise in the use of patent citations data, and suggest ways of addressing them. In particular, significant changes over time in the rate of patenting and in the number of citations made, as well as the inevitable truncation of the data, make it very hard to use the raw number of citations received by different patents directly in a meaningful way. To remedy this problem we suggest two alternative approaches: the fixed-effects approach involves scaling citations by the average citation count for a group of patents to which the patent of interest belongs; the quasi-structural approach attempts to distinguish the multiple effects on citation rates via econometric estimation.

We explore the usefulness of patent citations as a measure of the "importance" of a firm's patents, as indicated by the stock market valuation of the firm's intangible stock of knowledge. Using patents and citations for 1963-1995, we estimate Tobin's q equations on the ratios of R&amp;D to assets stocks, patents to R&amp;D, and citations to patents. We find that each ratio significantly affects market value, with an extra citation per patent boosting market value by 3%. Further findings indicate that "unpredictable" citations have a stronger effect than the predictable portion, and that self-citations are more valuable than external citations.

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

This chapter contains sections titled: Historical Introduction The Chou and Fasman Predictive Method Definition of Conformational Regions Refinement of Conformational Parameters Application of Chou-Fasman Method Comparison of Predictive Methods Computerized Chou-Fasman Method Future Directions

Shulamit Reinharz here examines the wide range of experiments feminist researchers undertake. Her goal is to help explain the relationship between feminism and methodology and to challenge stereotypes that might exist about 'feminist research methods'. Reinharz concludes that there is no one feminist method, but rather a variety of perspectives or questions that feminists bring to traditional methods. She argues that this diversity of methods has been of great value to feminist scholarship. She also includes an extensive bibliography which catalogues feminist scholarship over the last two decades. There are a few edited volumes on the subject but currently no authored text.

Abstract In this paper, I will discuss four major topics relating to current research in lexical semantics: methodology, descriptive coverage, adequacy of the representation, and the computational usefulness of representations. In addressing these issues, I will discuss what I think are some of the central problems facing the lexical semantics community, and suggest ways of best approaching these issues. Then, I will provide a method for the decomposition of lexical categories and outline a theory of lexical semantics embodying a notion of cocompositionality and type coercion, as well as several levels of semantic description, where the semantic load is spread more evenly throughout the lexicon. I argue that lexical decomposition is possible if it is performed generatively. Rather than assuming a fixed set of primitives, I will assume a fixed number of generative devices that can be seen as constructing semantic expressions.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Gravitational actions which include terms quadratic in the curvature tensor are renormalizable. The necessary Slavnov identities are derived from Becchi-Rouet-Stora (BRS) transformations of the gravitational and Faddeev-Popov ghost fields. In general, non-gauge-invariant divergences do arise, but they may be absorbed by nonlinear renormalizations of the gravitational and ghost fields (and of the BRS transformations). Fortunately, these artifactual divergences may be eliminated by letting the coefficient of the harmonic gauge-fixing term tend to infinity, thus considerably simplifying the renormalization procedure. Coupling to other renormalizable fields may then be handled in a straightforward manner.

This book is an introduction to the contemporary representation theory of Artin algebras, by three very distinguished practitioners in the field. Beyond assuming some first-year graduate algebra and basic homological algebra, the presentation is entirely self-contained, so the book is a suitable introduction for any mathematician (especially graduate students) to this field. The main aim of the book is to illustrate how the theory of almost split sequences is used in the representation theory of Artin algebras. However, other foundational aspects of the subject are developed. These results give concrete illustrations of some of the more abstract concepts and theorems. The book includes complete proofs of all theorems, and numerous exercises.

Buku ini merupakan volume ke delapan dalam seri Current Studies in Linguistics. Buku ini mencoba menjawab pertanyaan-pertanyaan linguistik seperti konsep makna dan juga tentang struktur makna.