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Under a Creative Commons license.-- Review.-- et al. ; Targeted therapies and the consequent adoption of >personalized> oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity >broad-spectrum> therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered. ; Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIHAR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Amancio Carnero was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.); ; Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant AI076535; ; Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza "would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant"; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program 'Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 'Biomimetic Radical Chemistry'; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365); ; Lorne J. Hofseth was supported by NIH grants (1R01CA151304, 1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, Ollie och Elof Ericssons Stiftelse, Linkopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S. Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee. ; This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant R01 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and AI110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States' Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5I01-BX001517-02; Valter D. Longo acknowledges support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221); ; Ander Matheu is funded by Carlos III Health Institute (AM: CP10/00539), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 "IDEAL"); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell'IRPEF–Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K. Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement n°278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007–2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Québec Santé (FR: 22624), and the Terry Fox Research Institute (FR: 1030); ; Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013–14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro Sanchez-Garcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XWH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U. Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011); ; Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013. ; Peer Reviewed

Inhaltsangabe: Introduction: The question of how and if children acquire language has long been of perennial interest: is language innate or not? If it is, what then is the proto-language? The first phylogenetic 'study' was conducted as early as the 7th century BC: pharaoh Psammetich I. undertook to determine what the proto-language is by giving two infants to a foster father who was not allowed to talk to them. After two years of no linguistic input they could only speak one word – 'bek' – which was assumed to be the Phrygian word for bread (bekos). In the 16th century Akbar the Great initiated the first ontogenetic study. By having two infants raised by a mute woman he proved that children do not learn to speak if they do not hear anyone speak. Since then ample questions concerning first language acquisition have been faced and replied to in detail and at great length. Yet, there are still some left unanswered or even unasked. One of the topics that have not been of great interest so far is the acquisition of interjections not only in first language but also in foreign language learning. In fact, interjections play an important role in communicative as well as non-communicative contexts, and their actual linguistic value and role were underestimated and misjudged for quite a long time: Interjections are among the most little studied of language phenomena; as one looks for references to them in the works of linguists, one is struck by the fact that they are very rarely mentioned, and where they are mentioned, it is usually only briefly and cursorily. Only recently have linguists delved into the subject of interjections and discovered that this particular linguistic phenomenon provides in fact ample opportunity for study and research. Moreover, with the interest in interjections the problem arose to determine what actually defines an interjection. As we shall see, opinions on this point differ considerably and attempts at agreeing upon the definition of interjections have been unsuccessful so far. Yet, there are some general tendencies which will form the basis for how the term interjection is used in this paper, and discussion of this point will be postponed until part II. Now, this M.A. thesis aims at gaining an insight into the acquisition of interjections in early childhood. This field has been neglected so far but merits in fact extensive and thorough inspection. This paper consists of three main parts, with the first two parts forming the basis for my study in part III.: in the first part I will provide a brief overview on child language acquisition, focussing particularly on phonological development. The second part consists of a theoretical disquisition on interjections to illustrate what characteristics they have and what peculiarities they show. In the third and final part I will come to my study on the acquisition of interjections in early childhood.Inhaltsverzeichnis:Table of Contents: 0.Introduction1 I.Part I. - Child Language Acquisition3 I.1Preliminary Remarks3 I.1.1Why Do We Learn to Speak at All?3 I.1.2Anatomic Implications4 I.2Basic Principles5 I.2.1The Neonate5 I.2.2First Vocalisations5 I.2.3The Babbling Period6 I.2.4Prosodics7 I.2.5Early Word Comprehension and Production8 I.3Phonology9 I.4Grammatical Acquisition13 I.5Semantics14 I.6Summary: Child Language Acquisition14 II.Part II. - Interjections17 II.1What Is an Interjection? Approaches and Introduction17 II.2Brief Overview: History of the Study of Interjections18 II.3Primary and Secondary Interjections20 II.4Features of Interjections21 II.4.1Why Are There Similarities across Different Languages?21 II.4.1.1The Pooh-pooh Theory22 II.4.1.2Physiological Determinants23 II.4.1.3Formal Constraints24 II.4.2An Attempt at Classifying Interjections25 II.4.2.1Tesnière's Classification of Interjections26 II.4.2.2Jacob and Wilhelm Grimm's Classification of Interjections28 II.4.2.3Ameka's Classification of Interjections29 II.4.3Parameters of Interjectionality31 II.4.3.1Functional and Pragmatic Features32 II.4.3.1.1Emotivity and Expressiveness32 II.4.3.1.2Non-referentiality33 II.4.3.1.3The Role of Interjections in Speech Acts33 II.4.3.1.4Monologicity36 II.4.3.2Formal Features38 II.4.3.2.1Prosodic and Suprasegmental Characteristics40 II.4.3.2.2Phonotactics and Syllable Structure41 II.4.3.2.3Phonology42 II.4.3.3Orthography43 II.4.3.4Morphology44 II.4.3.5Lexical Structures44 II.4.3.6Syntax45 II.4.3.7Semiotic Structures47 II.4.3.8Semantic Properties48 II.4.3.9Summary: Features of Primary and Secondary Interjections54 II.4.3.10The Linguisticality of Interjections55 II.5Interjections in the English Language55 II.5.1Interjections of Disgust56 II.5.2Interjections Containing an Element of Surprise57 II.5.2.1Oh!57 II.5.2.2Wow!58 II.5.2.3Whoops! and Oops!58 II.5.3Interjections of Pain58 II.5.4Other Interjections58 II.6The Acquisition of Interjections60 III.Part III. - Study: The Acquisition of Interjections in Early Childhood62 III.1Introductory Remarks62 III.1.1Definition of Interjections62 III.1.2Previous Studies66 III.1.3Purpose of Present Study66 III.2Criteria for Selection and Detailed Description of the Interjections for Analysis67 III.2.1Interjections of Pain68 III.2.1.1Function68 III.2.1.2Usage68 III.2.1.3Degree of Linguisticality70 III.2.1.4Origin70 III.2.1.5Form70 III.2.1.6Affiliation to Words and Phrases71 III.2.2Interjections of Disgust71 III.2.2.1Function71 III.2.2.2Usage72 III.2.2.2.1Ugh!72 III.2.2.2.2Yuck!73 III.2.2.2.3Phew!74 III.2.2.3Degree of Linguisticality75 III.2.2.4Origin75 III.2.2.5Form76 III.2.2.6Affiliation to Words and Phrases76 III.2.3"Spill Cries"78 III.2.3.1Function78 III.2.3.2Usage78 III.2.3.3Degree of Linguisticality79 III.2.3.4Origin79 III.2.3.5Form80 III.2.3.6Affiliation to Words and Phrases80 III.2.4Preliminary Thoughts and Hypotheses about the Outcome of My Study81 III.2.4.1Interjections of Pain81 III.2.4.2Interjections of Disgust81 III.2.4.3'Spill Cries'82 III.3Database and Method82 III.3.1Source and Format of Data82 III.3.2Characteristics of Data82 III.3.3Method83 III.4Results84 III.4.1Interjections of Pain84 III.4.1.1Ow!84 III.4.1.2Ouch!93 III.4.2Interjections of Disgust94 III.4.2.1Ugh!94 III.4.2.2Yuck!96 III.4.2.3Phew!97 III.4.3'Spill Cries'97 III.4.3.1Whoops! and Its Variants97 III.4.3.2Whoopsadaisy! and Its Variants102 III.5Discussion103 III.5.1Order of Acquisition103 III.5.2Uses and Their Developmental Change105 III.5.3Comparison of Study Results: Asano - Stange105 III.6For Further Study108 III.7Conclusion110 References Appendix App. 1 IPA symbols used to transcribe the speech sounds in this thesis App. 2 Reasons for the production of Ow! - interjectional usage only App. 3 Deutsche Zusammenfassung der ArbeitTextprobe:Text Sample: Chapter II.4.1.1, The Pooh-pooh Theory: Wundt claimed that primary interjections represent the transition from the imitation of animal sounds to language, i.e. from natural animal sounds to inarticulate exclamatory sounds to articulate emotional sounds. According to Wundt, language evolved in such a way that the articulate emotional sounds used to express moderate emotions were replaced step by step by language, and were henceforth used with intense emotions only Similarly, the interjectional theory – also nicknamed pooh-pooh theory – claims that 'language is derived from instinctive ejaculations called forth by pain or other intense sensations or feelings'. This theory was also put forward by the abbé Regnier, quoted in Beauzée: 'l'interjection … est peut-être la première voix articulée dont les hommes se sont servis'. Hence, interjections may open up the way for an ontogenetic and phylogenetic approach to the development of language. Sapir, however, negates the possibility of interjections being instinctive: he claims that '(interjections) are only superficially of an instinctive nature' and that their phonetic shape is conventional – using this as evidence that 'all of language is conventional, and no part of it instinctive'. Jespersen's also objects to the Pooh-pooh theory but he bases his assumption on a different argument: he maintains that 'the usual interjections are abrupt expressions for sudden sensations and emotions; they are therefore isolated in relation to the speech material used in the rest of the language'. Thus, his argument is that since interjections are not part of language proper, they cannot be a precursor of language. At any rate, it has been suggested that interjections represent some kind of protolanguage, which could explain the similarities between interjections across different languages. We should keep in mind, however, that although interjections are universal to all languages, they are not the same in all languages: it follows that interjections must be (at least to a certain extent) language-specific – they might show formal and/or functional similarities in some cases, though. Physiological Determinants: So let us assume that interjections are not some sort of protolanguage – how then can we account for the cross-linguistic similarities? Although de Brosses claims that interjections are not learnt but are natural expressions of a man's emotions, he also puts their universality down to physiological causes: 'toutes (interjections) tiennent immédiatement à la fabrique générale de la machine organique et au sentiment de la nature humaine, qui est partout le même dans les grands et premiers mouvements corporels'. In The Expression of Emotions in Man and Animals, Darwin also gives an explanation for interjections based on purely physiological reasons: As the sensation of disgust primarily arises in connection with the act of eating or tasting something, it is natural that its expression should consist chiefly in movements around the mouth. … With respect to the face, moderate disgust is exhibited in various ways: by the mouth being widely opened, as if to let an offensive morsel drop out; by spitting; by blowing out of the protruded lips; or by a sound as of clearing the throat. Such guttural sounds are written ach or ugh; and their utterance is sometimes accompanied by a shudder… Extreme disgust is expressed by movements round the mouth identical with those preparatory to the act of vomiting. … As the sense of smell is so intimately connected with that of taste, it is not surprising that an excessively bad odour should excite retching or vomiting in some persons, quite as readily as the thought of bad food does; and that, as a further consequence, a moderately offensive odour should cause the various expressive movements of disgust. Note that gestures, facial expressions and body language are biologically determined, hence universal. This fact might account for the resemblance between interjections of different languages, for there is a close link between gestures and the like and interjections. Taking the above extract into consideration, I can assuredly claim that the sounds produced in these circumstances can indeed resemble the English interjections of disgust, namely Phew! and Ugh!. Later on in the same work Darwin notes the following on the expression of surprise: '… whenever astonishment, surprise or amazement is felt …, our mouths are generally opened; yet the lips are often a little protruded… As a strong expiration naturally follows the deep inspiration which accompanies the first sense of startled surprise, and as the lips are often protruded, the various sounds which are then commonly uttered can apparently be accounted for … One of the commonest sounds is a deep Oh; and this would naturally follow … from the mouth being moderately opened and the lips protruded'. Oh! is the most common interjection in the English language, and it is also frequently used in many other (if not all?) languages, e.g. in the Romance languages, in German, Welsh, Russian, etc. For further comments on Oh! see chapter II.5.2.1 below. So basically, some of the primary interjections can indeed be explained by physiological attributes. These are by definition not language-specific because they are biological, hence universal. This phenomenon elucidates why interjections might have been misconceived as some sort of protolanguage. Formal Constraints: A third explanation for the similarities between interjections across different languages refers to formal constraints. To clarify this point I need to go a bit farther back. Even though interjections might not elicit a response from the hearer, they do serve nonetheless a communicative purpose: they do mean something, and this meaning is expressed orally. Now, the usage of interjections and especially which interjection is used depends on the context or circumstances and the mental process in the speaker. Different interjections have different functions which concern the hearer. Thus, interjections are an important communicative means for the processing of the common communicative system of speaker and listener. The communicative function of the interjections requires an extremely economic form: the phonetic units of interjections are of minimal complexity due to the shortness and the simple forms. Besides, their prosodic features facilitate their identification in the ongoing discourse. The argument that interjections are similar because of formal constraints is as follows: Aufgrund der formalen Erfordernisse, die durch die funktionalen Zwecke des Gesamtbereichs der Interjektion bedingt sind, bieten sich bei der Sprachbildung nicht beliebig viele Arten von Mitteln an, die diesem Zweck optimal genügen. Die Verwendung kleinster Einheiten und deren Kombinatorik ist optimal geeignet, den funktional geforderten Ökonomiebedürfnissen Rechnung zu tragen. So ist es nicht erstaunlich, dass Sprachen unterschiedlichsten Typs und ohne Rücksicht auf die Bildungsformen zu diesem Mittel der Interjektionsbildung gegriffen haben. Somit ergibt sich eine Erklärungsweise für die Übereinstimmung von Interjektionen in den verschiedenen Sprachen, die nicht auf deren 'Vorsprachlichkeit' zurückzugreifen braucht. So in principle their universality is traced back to formal constraints due to economic reasons. Tesnière observes with regard to the semantic complexity of interjections: 'certaines interjections arrivent même à exprimer des états d'âme et d'esprit si nuancés et si complexes, qu'elles en disent à elles seules plus qu'une phrase entière, et qu'il faut de longues périphrases pour en analyser et en définir le contenu sémantique'. This is another criterion for the economic aspect of interjections: they express in a clear and brief manner what is going on in the speaker's mind, and the listener can understand easily and without delay what is being expressed. All the above mentioned efforts to account for the quasi-universality of (some primary) interjections make sense to a certain extent, and I presume the truth lies somewhere in a blend between all of them. Nevertheless, I need to stress that, for the most part, interjections differ considerably cross-linguistically and are often among 'the most characteristic peculiarities of individual cultures'.

Urbanization has led to increased wheat imports by non-traditional, wheat producing countries. Globally, Southeast Asia has had the most rapid increase in wheat consumption. Over the past decade, Thailand, Indonesia, the Philippines, Laos, and Vietnam have attempted to assess the feasibility of initiating domestic wheat production to substitute or supplement their imports of wheat. All of these countries have areas suitable for wheat production, but no production experience, indigenous consumption, or marketing structures for wheat to provide a base for expansion. Despite the appeal of developing domestic wheat production, it must be considered essentially an experimental venture. Thus while it has been possible to gain the enthusiasm of technical people, it may not necessarily rate high on the list of government priorities. The main difficulties of developing wheat in Thailand have surprisingly not been technical issues, such as poor plant development, pests, and diseases. Instead, the unfamiliarity of the crop amongst scientists, extension workers, and farmers has been the key constraint. Functionally this has resulted in a number of problems in unexpected areas; • Identifying the areas where wheat would have a comparative advantage over other crops was not clear for some time. As a result, early extension efforts were scattered and shifted from area to area. • The recommended technology for planting wheat was too intensive and liable to misinterpretation by farmers, which led to repeated crop failures in the early years of the program. Easily adopted technologies that allowed reliable crop establishment by farmers took some time to evolve. • Local grain merchants had no knowledge of wheat and were not prepared to purchase small volumes from isolated groups of farmers. This created a lack of confidence in the crop among farmers and extension workers. These issues were recognized as being significant once the production program was in the progress and they had to be dealt with as they were encountered. The program in Thailand is notable in that it has not been structured as a pilot project with a specific pilot area for production; special fund allocations; or any program to buy back the crop from farmers. Instead, the program has been implemented within existing planning, budgeting, and operating procedures of the various government institutions involved. This has had inherent difficulties, but has also led to some innovative initiatives. In the long run, these have given the program greater strength and sustainability: • The difficulty of marketing small quantities of the crop was initially addressed by attempting to promote local use of the crop. • The Department of Agricultural Extension (DOAE) has begun to develop a market structure for wheat ased on local independent grain merchants. This should expand dynamically with a minimal input of government funds. • A wide range of institutions has been involved in the program, which gave the program access to inspiration and initiatives from different directions.This has helped maintain momentum to a greater degree than if only one institution were involved. • Finally, the problem of developing appropriate production technologies for a diverse production environment, was solved through a process of cross-fertilization between researchers on-farm trials, and farmers' informal trials. This interaction between research and extension evolved through a "participatory extension" approach that engaged farmers in the process of fine tuning the technologies to their particular situation. Most of the major crops that have been introduced to Thailand since World War II (i.e., maize, cassava, soybean, and tobacco) have been export-driven, with the private sector playing an active role in supplying farmers with inputs, production technologies, and a waiting market. Wheat, on the other hand, is competing with efficiently produced imports, with all stages of the program for developing production; technology development, seed supply, and marketing, being led by the govemment sector. This offers a unique opportunity to draw useful lessons. At this point, the technical viability of wheat production has been established. Dynamic expansion of the crop has yet to occur and will depend on the program's successful transition from being government-sponsored to the private sector. Final establishment of the crop will also depend on factors outside of the program's control, such as world prices for wheat. This Report focuses on the processes and dynamics of wheat's introduction and its expansion, the underlying constraints and imperatives, and the roles and interactions of the various cooperating institutions. The three chapters covering these topics are briefly summarized below. Chapter I. Promoting "Local Use" of Wheat as a Strategy for Developing Crop Production Extension efforts to introduce wheat to small farmers in northern Thailand began in the early 1980s. The program was immediately faced with the problem of disposing of the small output being generated by scattered groups of farmers. To escape this problem, local use of the wheat was promoted as a substitute for selling it. This was intended to allow farmers time to begin to obtain reasonable yields so that it would be economic for them to produce and permit production volume to increase sufficiently so that local grain merchants could purchase and ship the harvest to the flour mills in Bangkok. Local use was promoted on two levels: direct consumption within farm families to supplement their staple diet of rice, and sale of locally milled whole-wheat flour to food vendors. Whole-wheat flour was selected due to the simple grinding process involved and the feasibility of blending it with commercial white flour. The program developed several ways of preparing food that allowed wheat to be included in the food habits of local Thai farmers and the ethnic hilltribe people. These dishes were readily accepted on the basis of taste, but the long preparation and/or cooking time prohibited their ready adoption into the farm family diet. However, there are some indications that ethnic hilltribe people could fit the more basic preparations into their diets and daily routines. The was a consistent interest among farmers' housewives to use wheat for various types of snacks. A number of small bakeries started using methods of milling and baking, based on locally available technologies and materials. In the end, the main obstacle to widespread replication of such enterprises was not poor market acceptance or the lack of appropriate technologies, but the lack of middlemen who would maintain a stock of wheat in the village. Without material readily available, there was little opportunity for potential entrepreneurs to begin trial operations. Overall, the local use effort was not successful in its main objective of generating home consumption in the place of selling the crop. However, there were indications that local use of wheat could develop in certain situations once production became more commonplace. While unsuccessful in this primary goal, the effort di help to popularize the new crop among women farmers. The interest and cooperation that the program engendered was significant. Therefore, when trying to stimulate interest in a new crop, the local use concept should not be rejected out of hand. Chapter II. Developing Production: Initiatives and Constraints The current program to establish wheat production is the latest attempt to do so over the past 50 years. The Department of Agricultural Extension (DOAE) initiated the program with a series of multilocation trials, beginning in the 1983/84 cool season. A wdespread wheat promotion campaign began four years later (1987/88 cool season). As a key element of the campaign, the DOAE has provided free seed and fertilizer. Where substantial production areas developed, mobile threshers were made available free of charge. Production has been promoted in ,both rainfed and irrigated environments. A rough estimate of the area in these two production domains is 110,000 and 55,000 ha, respectively. Extension efforts have alternately targeted rainfed and irrigated environments as the expectation of success in the two domains changed. By 1990/91 season, "production centers" of wheat had been established in six of Thailand's eight provinces. The production area in 1995/96 had reached a modest 742 ha and 720 ha for rainfed and irrigated areas, respectively, with a total of about 1500 ha. Early extension efforts were plagued by consistent crop failure due to farmers' unfamiliarity with the crop. In irrigated areas, farmers consistently over-irrigated, over-seeded, or left seed uncovered. Rainfed areas had similar problems of over-seeding and poor seed-cover. In rainfed production the seeding date has to coincide with the last storms of the wet season. As the pattern of these late storms changes from year to year, this has necessarily prolonged the learning curve for rainfed farmers. Thus the yields for rainfed production have been slower to rise. Such a set of management errors is typical for any extension program introducing a new crop. But in the case of wheat, the technology extended to farmers played a major role in their onsistent crop failures. It was not until more appropriate technologies were developed that extension began to achieved any success he severity of these management errors has been reduced (but not eliminated) so that the average yields for the 1996 harvest were approximately 1 t/ha and 0.64 t/ha for irrigated and rainfed areas, respectively. This is still below the calculated "break-even" point of 1.2 and 0.82 t/ha for irrigated and rainfed areas, respectively. However, farmers with a number of years experience growing the crop are achieving double these yields. Marketing has been a major issue for wheat. The DOAE made a concerted effort to develop a market structure based on independent local grain merchants. They acted at two levels. In Bangkok, guaranteed prices of 7.4 Bt/kg (0.30 US$/kg) at the mill door and procedures for handling the crop were established with mill representatives. At the local level, extension workers selected local grain merchants and introduced them to farmers. The two groups held yearly marketing meetings before crop harvest. The system has some rough spots, but the network of local grain merchants purchasing the crop is increasing each season. This structure should expand dynamically as production expands without continued coordination by government institutions. This attempt to engage the private sector, should it prove effective, will have been achieved with minimal government expenditure. The crop is at its "watershed" in Thailand. There are expanding centers of production in both rainfed and irrigated areas, appropriate technologies are available, and marketing links with flour mills in Bangkok have been established. However, dynamic expansion is yet to occur. Government support of free seed has reached the limit of its usefulness now and is beginning to inhibit dynamic expansion. Average yields are still depressed by the typical management errors noted in the early years of extension, and by market links, which are not yet responsive. All of these problems can be managed. However, the overall constraint is the lack of any real drive from the mills as the end users. The government sector has succeeded in establishing the basis for wheat production in northern Thailand. Its job is more or less done. At some point the private sector will need to become a driving force. When the program began in early 1980s, wheat prices were low, but they have risen substantially since, so that domestic wheat should now be cheaper than imported wheat. Chapter III. Developing Appropriate Technologies in a Diverse Production Environment The initial research effort was confined to experiment stations where scientists themselves had to become familiar with the crop's characteristics. The original recommended technology was time-and labor-intensive, and was open to misinterpretation by traditional rice farmers. It is unlikely that any extension program based on this technology would have been successful. Most of the more appropriate technologies that are now being adopted were identified through fairly informal on-farm trials. The research program has changed considerably over the last 12 years. Research is now strictly oriented towards production problems and has a strong on-farm component. In addition, scientists are beginning to examine the focus ofthe research program in the context of the diversity of the production environments. Since the beginning of widespread promotion of the crop to farmers in the 1987/88 season, there have been dramatic shifts in the preferred technology used. Perhaps as few as 10% of the farmers are still using the originally recommended technology. Broadcasting instead of row seeding, minimum tillage instead of soil preparation, and the use of mulch to alter the micro-climate of the crop are some of the changes that promise to increase yields and/or reduce inputs. There have been several stages in the evolution of appropriate production technologies, and the specific technology preferred at a particular site varies according to local conditions. Farmers themselves have played an active role in adapting and innovating appropriate technologies. This is perhaps to be expected with a new crop. An extension approach in which farmers are presented with a number of alternative technologies appears to be effective in engaging them to evaluate and adapt the technologies. Because there is a definite contributing role for the farmers with this extension approach, it is called "participatory." This participatory approach could offer a way around the impasse that farming systems research (FSR) faces; in diverse production environments where any technology developed will be necessarily site specific, the need for repeated trials for each environment places a load on institutionalized FSR that it will never be able to meet. Participatory extension prompts the farmers to fine-tune the technologies themselves and should allow FSR to focus on issues that are beyond farmers' resources to deal with. Tviability of institutional adoption of participatory extension was investigated through an action research program funded by Canada's International Development Research Center (IORC) within the existing Thai Wheat Program.

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples. ; 3C. Three-City Study. The work was made possible by the participation of the control subjects, the patients, and their families. We thank Dr. Anne Boland (CNG) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille and the Centre National de Génotypage. The 3C Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM "Cohortes et collections de données biologiques" programme. Lille Génopôle received an unconditional grant from Eisai. AGES. Age, Gene/Environment Susceptibility-Reykjavik Study. This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC. Atherosclerosis Risk in Communities study. The ARIC study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This work as well as YL and AK were supported by the German Research Foundation (KO 3598/2-1, KO 3598/3-1 and CRC1140 A05 to AK). ASPS. Austrian Stroke Prevention Study. The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. We thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA-bank. BMES. Blue Mountains Eye Study. The BMES has been supported by the Australian RADGAC grant (1992- 94) and Australian National Health & Medical Research Council, Canberra Australia (Grant Nos: 974159, 211069, 991407, 457349). The GWAS studies of Blue Mountains Eye Study population are supported by the Australian National Health & Medical Research Council (Grant Nos: 512423, 475604, 529912) and the Wellcome Trust, UK (2008). EGH and JJW are funded by the Australian National Health & Medical Research Council Fellowship Schemes. CILENTO. Italian Network on Genetic Isolates – Cilento. We thank the populations of Cilento for their participation in the study. The study was supported by the Italian Ministry of Universities and CNR 36 (PON03PE_00060_7, Interomics Flagship Project), the Assessorato Ricerca Regione Campania, the Fondazione con il SUD (2011-PDR-13), and the Istituto Banco di Napoli - Fondazione to MC. COLAUS. The CoLaus authors thank Yolande Barreau, Mathieu Firmann, Vladimir Mayor, Anne-Lise Bastian, Binasa Ramic, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne Ecoffey and Sylvie Mermoud for data collection. The CoLaus study received financial contributions from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, the Swiss National Science Foundation (33CSCO- 122661, 3200BO-111361/2, 3100AO-116323/1, 310000-112552). The computations for CoLaus imputation were performed in part at the Vital-IT center for high performance computing of the Swiss Institute of Bioinformatics. We thank Vincent Mooser for his contribution to the CoLaus study. EGCUT. Estonian Genome Center University of Tartu. EGCUT received financing from FP7 grants (278913, 306031, 313010) and targeted financing from Estonian Government (SF0180142s08). EGCUT studies were covered from Infra-structure grant no. 3.2.0304.11-0312 funded mostly by the European Regional Development Fund, Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG). We acknowledge EGCUT technical personnel, especially Mr V. Soo and S. Smit. Data analyses were carried out in part in the High Performance Computing Center of the University of Tartu. FamHS. Family Heart Study. The FHS work was supported in part by NIH grants 5R01HL08770003, 5R01HL08821502 (Michael A. Province) from the NHLBI and 5R01DK07568102, 5R01DK06833603 from the NIDDK (I.B.B.). The authors thank the staff and participants of the FamHS for their important contributions. FHS. Framingham Heart Study. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. GENDIAN. GENetics of DIAbetic Nephropathy study. The support of the physicians, the patients, and the staff of the Diabetes Zentrum Mergentheim (Head: Prof. Dr. Thomas Haak), the diabetes outpatient clinic Dr Nusser - Dr Kreisel, the dialysis centers KfH Amberg, KfH Bayreuth, KfH Deggendorf, KfH Donauwörth, KfH Freising, KfH Freyung, KfH Fürth, KfH Hof, KfH Ingolstadt, KfH Kelheim, KfH München Elsenheimerstraße, KfH München-Schwabing, KfH Neumarkt, KfH Neusäß, KfH Oberschleißheim, KfH Passau, KfH Plauen, KfH Regensburg Günzstraße, KfH Regensburg Caritas-Krankenhaus, KfH Straubing, KfH Sulzbach-Rosenberg, KfH Weiden, Dialysezentrum Augsburg Dr. Kirschner, Dialysezentrum Bad Alexandersbad, KfH Bamberg, Dialysezentrum Emmering, Dialysezentrum Klinikum Landshut, Dialysezentrum Landshut, Dialysezentrum Pfarrkirchen, Dialysezentrum Schwandorf, Dr. Angela Götz, the medical doctoral student Johanna Christ and the Study Nurse Ingrid Lugauer. The expert technical assistance of Claudia Strohmeier is acknowledged. Phenotyping was funded by the Dr. Robert PflegerStiftung (Dr Carsten A. Böger), the MSD Stipend Diabetes (Dr Carsten A. Böger) and the University Hospital of Regensburg (intramural grant ReForM A to Dr. A. Götz, ReForM C to Dr. Carsten Böger). Genome-wide genotyping was funded by the KfH Stiftung Präventivmedizin e.V. (Dr. Carsten A. Böger, Dr. Jens Brüning), the Else Kröner-Fresenius-Stiftung (2012_A147 to Dr Carsten A. Böger and Dr Iris M. Heid) and the University Hospital Regensburg (Dr Carsten A. Böger). Data analysis was funded by the Else 37 Kröner-Fresenius Stiftung (Dr. Iris M. Heid and Dr. Carsten A. Böger: 2012_A147; Dr. Carsten A. Böger and Dr. Bernhard K. Krämer: P48/08//A11/08). GENDIAN Study Group: Mathias Gorski, Iris M. Heid, Bernhard K. Krämer, Myriam Rheinberger, Michael Broll, Alexander Lammert, Jens Brüning, Matthias Olden, Klaus Stark, Claudia Strohmeier, Simone Neumeier, Sarah Hufnagel, Petra Jackermeier, Emilia Ruff, Johanna Christ, Peter Nürnberg, Thomas Haak, Carsten A. Böger. HABC. Health Aging and Body Composition Study. The HABC study was funded by the National Institutes of Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. HCS. Hunter Community Study. The University of Newcastle provided $300,000 from its Strategic Initiatives Fund, and $600,000 from the Gladys M Brawn Senior Research Fellowship scheme; Vincent Fairfax Family Foundation, a private philanthropic trust, provided $195,000; The Hunter Medical Research Institute provided media support during the initial recruitment of participants; and Dr Anne Crotty, Prof. Rodney Scott and Associate Prof. Levi provided financial support towards freezing costs for the long-term storage of participant blood samples. The authors would like to thank the men and women participating in the HCS as well as all the staff, investigators and collaborators who have supported or been involved in the project to date. A special thank you should go to Alison Koschel and Debbie Quain who were instrumental in setting up the pilot study and initial phase of the project. HPFS. Health Professionals Follow-Up Study. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental & Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). We thank the staff and participants of the NHS and HPFS for their dedication and commitment. INGI-CARLANTINO. Italian Network on Genetic Isolates – Carlantino. We thank Anna Morgan and Angela D'Eustacchio for technical support. We are grateful to the municipal administrators for their collaboration on the project and for logistic support. We thank all participants to this study. INGI-FVG. Italian Network on Genetic Isolates – Friuli Venezia-Giulia. We thank Anna Morgan and Angela D'Eustacchio for technical support. We are grateful to the municipal administrators for their collaboration on the project and for logistic support. We thank all participants to this study. 38 INGI-VAL BORBERA. Italian Network on Genetic Isolates – Val Borbera. We thank the inhabitants of the Val Borbera who made this study possible, the local administrations and the ASL-Novi Ligure (Al) for support. We also thank Clara Camaschella for data collection supervision and organization of the clinical data collection, Fiammetta Vigano` for technical help and Corrado Masciullo for building the analysis platform. The research was supported by funds from Compagnia di San Paolo, Torino, Italy; Fondazione Cariplo, Italy and Ministry of Health, Ricerca Finalizzata 2008 and 2011/2012, CCM 2010, PRIN 2009 and Telethon, Italy to DT. IPM. Mount Sinai BioMe Biobank Program. The Mount Sinai BioMe Biobank Program is supported by The Andrea and Charles Bronfman Philanthropies. KORA-F3 and F4. The genetic epidemiological work was funded by the NIH subcontract from the Children's Hospital, Boston, US, (H.E.W., I.M.H, prime grant 1 R01 DK075787-01A1), the German National Genome Research Net NGFN2 and NGFNplus (H.E.W. 01GS0823; WK project A3, number 01GS0834), the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ, and by the Else KrönerFresenius-Stiftung (P48/08//A11/08; C.A.B., B.K.K; 2012_A147 to CAB and IMH.). The Genetic Epidemiology at the University of Regensburg received financial contributions from the BMBF (01ER1206 and 01ER1507). The kidney parameter measurements in F3 were funded by the Else Kröner-FreseniusStiftung (C.A.B., B.K.K.) and the Regensburg University Medical Center, Germany; in F4 by the University of Ulm, Germany (W.K.). Genome wide genotyping costs in F3 and F4 were in part funded by the Else Kröner-Fresenius-Stiftung (C.A.B., B.K.K.). De novo genotyping in F3 and F4 were funded by the Else Kröner-Fresenius-Stiftung (C.A.B., B.K.K.). The KORA research platform and the MONICA Augsburg studies were initiated and financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, by the German Federal Ministry of Education and Research and by the State of Bavaria. Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum München. The LINUX platform for computation were funded by the University of Regensburg for the Department of Epidemiology and Preventive Medicine at the Regensburg University Medical Center. LIFELINES. The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. Lifelines group authors: Behrooz Z Alizadeh1 , H Marike Boezen1 , Lude Franke2 , Pim van der Harst3 , Gerjan Navis4 , Marianne Rots5 , Harold Snieder1 , Morris Swertz2 , Bruce HR Wolffenbuttel6 and Cisca Wijmenga2 1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands 2. Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands 3. Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands 4. Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands 5. Department of Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands 6. Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands MESA. Multi-Ethnic Study of Atherosclerosis. University of Washington (N01-HC-95159),Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University 39 (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC- 95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL- 071205) MICROS. Microisolates in South Tyrol study. We owe a debt of gratitude to all participants. We thank the primary care practitioners R. Stocker, S. Waldner, T. Pizzecco, J. Plangger, U. Marcadent and the personnel of the Hospital of Silandro (Department of Laboratory Medicine) for their participation and collaboration in the research project. In South Tyrol, the study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). NESDA. The Netherlands Study of Depression and Anxiety. The infrastructure for the NESDA study is funded through the Geestkracht programme of the Dutch Scientific Organization (ZON-MW, grant number 10-000-1002) and matching funds from participating universities and mental health care organizations. Genotyping in NESDA was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health. NHS. Nurses' Health Study. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental & Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). The NHS renal function and albuminuria work was supported by DK66574. Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). We thank the staff and participants of the NHS and HPFS for their dedication and commitment. NSPHS. The Northern Swedish Population Health Study. The NSPHS was supported by grants from the Swedish Natural Sciences Research Council, the European Union through the EUROSPAN project (contract no. LSHG-CT-2006-018947), the Foundation for Strategic Research (SSF) and the Linneaus Centre for Bioinformatics (LCB). We are also grateful for the contribution of samples from the Medical Biobank in Umeå and for the contribution of the district nurse Svea Hennix in the Karesuando study. RS-I. The Rotterdam Study. The GWA study was funded by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Dr Michael 40 Moorhouse, Marijn Verkerk, and Sander Bervoets for their help in creating the GWAS database. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the participants and staff from the Rotterdam Study, the participating general practitioners and the pharmacists. We would like to thank Dr. Tobias A. Knoch, Luc V. de Zeeuw, Anis Abuseiris, and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and # 01 IG 07015 G, for access to their grid resources. Abbas Dehghan is supported by NWO grant (vici, 918-76-619). SAPALDIA. Swiss Study on Air Pollution and Lung Diseases in Adults. The SAPALDIA Team: Study directorate: T Rochat (p), NM Probst Hensch (e/g), N Künzli (e/exp), C Schindler (s), JM Gaspoz (c) Scientific team: JC Barthélémy (c), W Berger (g), R Bettschart (p), A Bircher (a), O Brändli (p), C Brombach (n), M Brutsche (p), L Burdet (p), M Frey (p), U Frey (pd), MW Gerbase (p), D Gold (e/c/p), E de Groot (c), W Karrer (p), R Keller (p), B Martin (pa), D Miedinger (o), U Neu (exp), L Nicod (p), M Pons (p), F Roche (c), T Rothe (p), E Russi (p), P Schmid-Grendelmeyer (a), A Schmidt-Trucksäss (pa), A Turk (p), J Schwartz (e), D. Stolz (p), P Straehl (exp), JM Tschopp (p), A von Eckardstein (cc), E Zemp Stutz (e). Scientific team at coordinating centers: M Adam (e/g), C Autenrieth (pa), PO Bridevaux (p), D Carballo (c), E Corradi (exp), I Curjuric (e), J Dratva (e), A Di Pasquale (s), E Dupuis Lozeron (s), E Fischer (e), M Germond (s), L Grize (s), D Keidel (s), S Kriemler (pa), A Kumar (g), M Imboden (g), N Maire (s), A Mehta (e), H Phuleria (exp), E Schaffner (s), GA Thun (g) A Ineichen (exp), M Ragettli (e), M Ritter (exp), T Schikowski (e), M Tarantino (s), M Tsai (exp) (a) allergology, (c) cardiology, (cc) clinical chemistry, (e) epidemiology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (n) nutrition, (o) occupational health, (p) pneumology, (pa) physical activity, (pd) pediatrics, (s) statistics. Funding: The Swiss National Science Foundation (grants no 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO- 104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton's Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA. The study could not have been done without the help of the study participants, technical and administrative support and the medical teams and field workers at the local study sites. Local fieldworkers : Aarau: S Brun, G Giger, M Sperisen, M Stahel, Basel: C Bürli, C Dahler, N Oertli, I Harreh, F Karrer, G Novicic, N Wyttenbacher, Davos: A Saner, P Senn, R Winzeler, Geneva: F Bonfils, B Blicharz, C Landolt, J Rochat, Lugano: S Boccia, E Gehrig, MT Mandia, G Solari, B Viscardi, Montana: AP Bieri, C Darioly, M Maire, Payerne: F Ding, P Danieli A Vonnez, Wald: D Bodmer, E Hochstrasser, R Kunz, C Meier, J Rakic, U Schafroth, A Walder. Administrative staff: C Gabriel, R Gutknecht. SHIP and SHIP-TREND. The Study of Health in Pomerania. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network 41 'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus program of the InterSystems GmbH. The SHIP authors are grateful to Mario Stanke for the opportunity to use his Server Cluster for the SNP imputation as well as to Holger Prokisch and Thomas Meitinger (Helmholtz Zentrum München) for the genotyping of the SHIP-TREND cohort. TRAILS. TRacking Adolescents' Individual Lives. Trails is a collaborative project involving various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. TRAILS has been financially supported by grants from the Netherlands Organization for Scientific Research NWO (Medical Research Council program grant GB-MW 940-38-011; ZonMW Brainpower grant 100-001-004; ZonMw Risk Behavior and Dependence grants 60- 60600-98-018 and 60-60600-97-118; ZonMw Culture and Health grant 261-98-710; Social Sciences Council medium-sized investment grants GB-MaGW 480-01-006 and GB-MaGW 480-07-001; Social Sciences Council project grants GB-MaGW 457-03-018, GB-MaGW 452-04-314, and GB-MaGW 452-06- 004; NWO large-sized investment grant 175.010.2003.005; NWO Longitudinal Survey and Panel Funding 481-08-013); the Sophia Foundation for Medical Research (projects 301 and 393), the Dutch Ministry of Justice (WODC), the European Science Foundation (EuroSTRESS project FP-006), and the participating universities. We are grateful to all adolescents, their parents and teachers who participated in this research and to everyone who worked on this project and made it possible. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation. WGHS. Women's Genome Health Study. The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen. YFS. Young Finns Study. The YFS has been financially supported by the Academy of Finland: grants 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi), the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (grant 9M048 and 9N035 for TeLeht), Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Tampere Tuberculosis Foundation and Emil Aaltonen Foundation (T.L). The technical assistance in the statistical analyses by Ville Aalto and Irina Lisinen is acknowledged. ; Peer Reviewed

It is widely recognized that broadband is of fundamental importance to the social and economic development of a nation. The focus of the paper is on infrastructure-related actions; measures to stimulate demand for broadband are, therefore, only marginally addressed. This paper aims to provide a platform for debate with the Russian counterparts in the sector, and to discuss the measures needed to develop broadband in support of actions aimed at economic growth. This paper examines the broadband market in Russia and preconditions for its sustainable development. It begins by presenting arguments demonstrating the importance of broadband to the overall economic development of Russia, including from the perspective of diversification of the economy and new job creation. The paper benchmarks Russia s broadband performance with Organization of Economic Cooperation and Development (OECD) comparators, as well as with other nations leading the way in broadband diffusion. The paper takes stock of the existing broadband market structure in Russia and its main players as they stand today, including the regulatory and legal environment of the market for both fixed and mobile broadband. Finally, the paper provides a set of recommendations that addresses the issue of sustainability in Russian broadband delivery, and how it can continue its acceleration in the years to come.

Productivity in the agricultural sector is inherently dependent on weather, such as variations in rainfall and temperature. As a result, weather risk events can cause losses in yield and production that translate into economic losses for producers, as well as other sector stakeholders that depend on income from agricultural trade, transport, processing, or export. This document is a guide for development practitioners and strategically presents a variety of mapping techniques for agricultural risk management and illustrates the application of these techniques for informing public and private sector development strategies. The introduction places weather risk mapping within the broader context of agricultural risk, explaining how mapping can enable risk identification, assessment and management activities, and each chapter elaborates on one or more of the technical components. A basic definition of agro-meteorology is provided, along with a discussion of different mapping techniques. The guide presents the available remote (satellite) databases of agro-meteorological variables that can be used for the purpose of weather risk mapping, assessing the advantages and drawbacks of each database and their suitability for different purposes. The document reviews current risk mapping analyses based on historical weather observations, which are typically used for risk identification and assessment, including climatologies, hazard and risk maps, climate regionalizations and agro-ecological zones (AEZ). The document also reviews forward-looking mapping techniques, known as diagnostic and forecasting analyses, specific examples of which are drawn from the United States, the European Union, and Australia. Finally, the guide provides instruction on how and why to conduct agro-ecological zoning, a technique that can be used to assess land-use types, land resources, land suitability, and climatic and agro-climatic regionalizations, as well as to inform land use recommendations. The concluding chapter demonstrates a step-by-step application of agro-ecological zoning in a case study of Mozambique.

In mid-2014, the Government of Ukraine (GoU) requested technical assistance and financial support from the inter¬national community to assess and plan priority recovery and peacebuilding efforts in the conflict-affected regions of eastern Ukraine. Following these requests, and within the framework of the 2008 Joint Declaration on Post-Crisis Assessments and Recovery Planning, the EU, UN, and WBG agreed to support the government in undertaking a Recovery and Peacebuilding Assessment (RPA). This assessment follows the Post-Conflict Needs Assessment (PCNA) methodology. In view of the continuing conflict in eastern Ukraine, it was decided to undertake an initial rapid assess¬ment as a first phase of activity, which would provide an analytical and programmatic baseline for recovery efforts to inform urgent interventions and provide a basis for scaling up recovery plan¬ning and responses as the situation and needs evolve on the ground. This report summarizes the findings and recommendations of the first phase of the RPA, which was undertaken in the period November 2014 to February 2015. In light of the dynamic and fluid nature of the situation in eastern Ukraine, these findings should be considered as a snapshot in time. In particular, the assessment of infrastructure damage is limited to the damage that occurred on or before November 2014. Furthermore, the number of registered internally displaced persons (IDPs), utilized as a reference to estimate the needs of this affected population, corresponds to the official government estimates as of February 2015.

This new flagship report for the eTransform Africa Project, produced by the World Bank and the African Development Bank, with the support of the African Union, identifies best practice in the use of Information and communication technologies (ICTs) in key sectors of the African economy. Under the theme transformation-ready, the growing contribution of ICTs to agriculture, climate change adaptation, education, financial services, government services, and health is explored. In addition, the report highlights the role of ICTs in enhancing African regional trade and integration as well as the need to build a competitive ICT industry to boost innovation, job creation, and the export potential of African companies.

In 2012, the Mexican Presidency of the G20 introduced inclusive green growth as a cross-cutting priority on the G20 development agenda. The second meeting of the G20 Development Working Group (DWG), hosted by the Government of the Republic of Korea, took place in Seoul the 19th and 20th of March 2012. As agreed during the first DWG meeting, this second meeting focused on the priorities for their presidency in the first half of 2012: infrastructure, food security and inclusive green growth (IGG). At its Seoul meeting, the DWG also agreed that IGG co-facilitators and relevant international organizations (IOs) should work together in 2012 to develop a nonprescriptive good practices guide/toolkit on enabling national policy frameworks for inclusive green growth to support countries who voluntarily wish to design and implement affordable and inclusive green growth policies, with the aim of achieving sustainable development and poverty alleviation. The toolkit is organized as follows. First, the necessity of applying the different tools in the context of a broad inclusive green growth strategy is stressed, and a harmonized framework combining approaches and tools identified by all four IOs is set forth. Second, the document offers an overview of key tools that can be mobilized to implement an inclusive green growth strategy. Quick technical descriptions of these tools are offered along with suggested sources for further details. Finally, capacity building and knowledge sharing initiatives are presented, with the Green Growth Knowledge Platform (GGKP) highlighted as a powerful collaborative tool to advance policies for inclusive green economies.

Global agriculture will face multiple challenges over the coming decades. It must produce more food to feed an increasingly affluent and growing world population that will demand a more diverse diet, contribute to overall development and poverty alleviation in many developing countries, confront increased competition for alternative uses of finite land and water resources, adapt to climate change, and contribute to preserving biodiversity and restoring fragile ecosystems. Climate change will bring higher average temperatures, changes in rainfall patterns, and more frequent extreme events, multiplying the threats to sustainable food security. Addressing these challenges requires co-ordinated responses from the public and private sectors and civil society that will need to be adapted to the specific circumstances of different types of farmers in countries at all levels of development. The recommendations provided are broadly of two types: specific actions that can contribute in some way to improving productivity growth or sustainable resource use (whether building on existing initiatives or suggesting new activities) and more general proposals that may not be actionable as presented but that serve to highlight areas for priority attention. This report also invites G20 countries to engage in a medium, to long-term, analysis-based peer review of policies fostering sustainable productivity growth, which would identify specific constraints and opportunities, beginning with their own food and agriculture sectors. In addition to possible benefits to participating countries, a peer review process could contribute to the identification of best policies and best policy packages to achieve the widely held aim of sustainably improving productivity of the global food and agriculture system. While such an initiative is proposed to and for G20 countries, it could have much wider application to interested countries.

In the wake of the revolution, Tunisian society is currently undergoing a significant transformation. In late 2011, the country's first representative government in more than three decades was formed, as the Constituent Assembly was seated. Hundreds of legitimate candidates ran in an election that was free, fair, and enjoyed nearly 90 percent participation by eligible voters. 'Tunisia: from revolutions to institutions,' published one year after the exile of Ben Ali, seeks to describe the factors driving this transformation, examining how specific elements of society have changed, or not changed, in the post-revolutionary period. Information and communication technologies (ICTs), which played a central role in the lead-up to the revolution as well as the revolution itself, have continued to influence rapid changes in the past year. This report charts the application of these technologies by citizens, civil society, entrepreneurs, and government stakeholders. It also identifies openings to capitalize on technology's ability to improve governance, expand economic opportunity, and encourage social cohesion.

Monitoring and evaluation (M&E) is an extremely complex, multidisciplinary and skill intensive endeavor. Government-wide M&E is even more so because it requires detailed knowledge across and within sectors, as well as of interactions among planning, budgeting, and implementation functions in the public sector. The situation is complicated even further when the machinery of government is decentralized, with powers and functions distributed across three spheres of government. This paper outlines the process of implementing a government-wide monitoring and evaluation (GWM&E) system in South Africa. The first section sketches the context that created the impetus for establishing such a system. This context is clearly shaping the evolution of the system and influencing its longer-term sustainability. The second section outlines the various stages of conceptualizing and implementing the GWM&E system, which is currently very much a 'work in progress.' The third section reviews international experiences for lessons learned, which may also be germane to the South African context, noting similarities and differences in approach. Some of the critical implementation factors relate to the role of political leadership and championing of M&E, incentives for promoting usage of M&E findings, dealing with information and data constraints, capacity building, "ownership" of the M&E system by line ministries and other agencies, and managing the challenges of change. The fourth section examines a range of challenges and difficulties encountered in South Africa. The final section reflects on lessons distilled from the South African experience to date.

This report is the product of a comprehensive study on Benin. It highlights the country s geographical and economic situation and concentrates in particular on environmental conditions and the challenges facing Benin. This report covers the financing of priority environmental activities, as well as allocations to programs designed to improve the environment and living conditions of the population. The environmental analysis of Benin seeks to help the Government integrate the environment into policy formulation by analyzing cross-cutting aspects and the challenges of implementing sound environmental management, and creating a platform for strengthening the country s capacities in order to facilitate sustainable natural resource and environmental management. To this end, a number of measures have been recommended, among them the establishment of effective policies and institutions based on sound governance and improved effectiveness, and the mobilization of financing for environmental protection and natural resource management. The study includes the analysis of a case study on three cities: Porto-Novo, Cotonou, and Parakou, and examines the impact of environmental problems and environmental management challenges on these cities.

Biologically diverse ecosystems in countries served by the World Bank provide an array of valuable economic services. While the benefits of conserving ecosystems frequently outweigh the costs, conversion of these ecosystems to other uses occurs anyway, because many ecosystem benefits are of a public good nature, without markets that would reflect their real value. The objective of this paper was defined at a Concept review meeting held on December 2009 and is to increase the understanding on how biodiversity is incorporated in a development agency such as the World Bank Group (WBG) and how the WBG can enhance its role in biodiversity and ecosystems protection and management as a key ingredient to reach development sustainability. In order to define a reasonable strategy to prepare this paper, two approaches were used: the first was to carry out background and analytical studies, and the second was to consult with a wide range of stakeholders including Bank staff, Non-Governmental Organizations (NGOs), and indigenous groups. Biodiversity provides many instrumental benefits, from food and fuel to recreation. But even where biodiversity is not immediately instrumental, it represents global public goods that must be protected, if only for their potential value in the future. The Global Environment Facility (GEF) has been the mainstay of grants implemented by the Bank ($1.4 billion) for biodiversity conservation and management, but the Bank has itself committed $2 billion in loans and has leveraged $2.9 billion in co-financing.

This report seeks to inform the development of a framework for addressing governance reform in fragile and conflict affected environments through are view of international experiences. The report analyzes the experience both of countries that sustained a transition to peace and those that fell back into conflict. Pertinent lessons will be drawn selectively from a range of fragile and conflict affected countries, including Haiti, Cambodia, Bosnia and Herzegovina, Mozambique, Liberia, Timor-Leste, Afghanistan, Rwanda, Indonesia, Sierra Leone, and Angola. No specific typologies have been adopted or formed in order to assess these lessons, because typologies can be limiting and experiences can be better assessed based on the specificity of each country's context. The first section of the report sets out broadly accepted definitions of key terms such as governance, state building, and fragility. The second section reviews experiences with diverse governance dimensions and explores the objectives, opportunities, and constraints associated with each.