Competências Básicas de Investigação Científica e de Publicação

1. CompetênciasBásicas de InvestigaçãoCientífica e de Publicação Physio lecture 1: Introduction, Hypotheses and Search Ganesha Associates

2. Publishing is an essential research skill Ganesha Associates

3. Publishing is an essential research skill determining likelihood of acceptance navigating a submission system in a second language assessing relevance to research topic comparing journals Peer Review Journal Selection Publication Success Writing Submission Preparation decision to re-submit, or try a different journal writing an outline understanding comments writing in English formatting to guidelines citation management long decision timelines Publication ethics

4. Me… • BSc Physics 1971, PhD Neuroscience 1976, post doc 1975-1979 • Visiting Professor, UFPe 1978-79 • Editor, Publisher, Director at Elsevier Science 1979 – 2005 • Pubmed systems expert, NCBI, NIH 2006-2007 • STM business analyst, Outsell Inc, 2009-2011 • Visiting Professor UFPe, 2006, 2007, 2008, 2012, 2013 Ganesha Associates

5. The scientific process involves making models of how things work • These evolving models are described in the scientific literature • Sometimes the models are wrong, often they are incomplete • Scientific progress is driven by the communication and publication of the results of new research, and the reinterpretation of older work • The tool which makes all of this possible is the hypothesis Ganesha Associates CC BY 3.0

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9. Experimental and observational types of research

10. Experimental vs. Observational studies No modification of experimental variables Useful to discover trends and associations Cannot directly be used to infer causality Compare responses different treatments Designed to avoid misleading results e.g. randomisation Can be used to infer cause and effect Ganesha Associates CC BY 3.0

11. Mainlearning points • Studentprojectsfallintothreecategories • No hypothesis, i.e. observational • Weakhypothesis • Strong hypothesis • The workwillbepublished in a • Nationaljournal • Lowimpactfactorjournal • High impactfactorjournal • Startingwithstronghypothesis improves your chances ofgettingpublished in a goodjournal Ganesha Associates CC BY 3.0

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13. What is a strong hypothesis ? • A strong hypothesis is based on a series of premises – things that are already known with some certainty • Each premise must be supported by references back to the (international) primary literature • So a strong hypothesis will be backed by references to recent papers in high quality journals Ganesha Associates CC BY 3.0

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15. Coin-tossing - an example • IwonderhowmanyheadsortailsIwillgetifItossthiscoin 100 times • No model • The frequencydistributionofheadsandtailswillbeapproximatedby a binomial distributionwithn=100 andp=0.5 • Simplemodel, basedonsymmetry • A detailedanalysisofthe dynamics revealsthattheprobabilityof a headis 0.51 • Complexmodel, basedonasymmetry, aerodynamics, etc Ganesha Associates CC BY 3.0

16. Coin-tossing – impact on CV 1. None, or possibly negative 2. R. A. Fisher and others did perform this experiment in the early days of biological statistics, before the advent of computers, as a proof that the binomial distribution tended towards a normal one at high levels of n. Interestingly they all found that the probability of a head p was usually slightly higher than 0.5, but this difference was ignored. 3. PersiDiacusis, Susan Holmes and Richard Montgomery (Stanford, 2004) publish a paper on the ‘Dynamical bias in the coin toss’ proving that the lack of total symmetry in a coin means that the probability of a head will always be slightly greater than 0.5. Ganesha Associates CC BY 3.0

17. Coin tossing - relevance • Ithinkthattherewillbeanassociation (+ or -) betweenmutations in gene xandsusceptibilitytodiseasey • No causal basis for arelationshipgiven • Ipredictthatmutations in gene xwillincreasesusceptibilitytodiseaseybecausepatientswithdiseaseyoftenhavelowlevelsof gene productx. • Built-in control, patientswith normal levelsofthe gene productshouldnothavethedisease. • Ipredictthatchemically non-neutral mutations in gene xwillincreasesusceptibilitytodiseasey in patientswithlowlevelsof gene productx. • Secondlevelofcontrol – neutral mutationsshouldbeasymptomatic Ganesha Associates CC BY 3.0

18. Coin-tossing – moral ofthestory • With a stronghypothesis, you: • Avoidfollowing leads which go nowhere – false positives, failearly • Avoidignoringunexpectedobservationsthat are of high interest – false negatives • May needto do lesswork ! • Will getpublished in betterjournals ! Ganesha Associates CC BY 3.0

19. Case study: Hummingbird territorial behaviour Ganesha Associates CC BY 3.0

20. Hummingbird territorial behaviour Most hummingbird species demonstrate strong territorial behavior If a bluffing charge attack does not work, the resident may engage the trespasser in a brief but intense physical battle So why do hummingbirds defend territories ? H0: Hummingbirds are randomly distributed in space and time. Ganesha Associates CC BY 3.0

21. Hummingbird territorial behaviour H1 If territory = F(energy), then behavior not species-dependent If territory = F(mating), then behaviorshould be species and sex dependent If… If… Ganesha Associates CC BY 3.0

22. Territorial behaviour in 1971 • Time, Energy, and Territoriality of the Anna Hummingbird (Calypteanna) Science 173 (1971) 818-821. • When territory quality decreases defenders may switch to less expensive forms of defense because the energy savings outweigh the loss of resources • Augmented territorial defense during the breeding season is made possible by increased feeding efficiency due to the availability at this time of very nectar-rich flowers. • Individuals with large territories are more successful reproductively. Ganesha Associates CC BY 3.0

23. Hummingbird territoriality since • Digestive physiology is a determinant of foraging bout frequency in hummingbirds. Nature. 1986 Mar 6-12;320(6057):62-3. • Mitochondrial respiration in hummingbird flight muscles. ProcNatlAcadSci U S A. 1991 Jun 1;88(11):4870-3. • Cloning and analysis of the gene encoding hummingbird proinsulin. Gen Comp Endocrinol. 1993 Jul;91(1):25-30. • Flight and size constraints: hovering performance of large hummingbirds under maximal loading. J Exp Biol. 1997 Nov;200(Pt 21):2757-63. Ganesha Associates CC BY 3.0

24. Hummingbird territoriality since • Hovering performance of hummingbirds in hyperoxic gas mixtures. J Exp Biol. 2001 Jun;204(Pt 11):2021-7. • Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds. Nutr J. 2005 Dec 13;4:36. • Neural specialization for hovering in hummingbirds: hypertrophy of the pretectal nucleus Lentiformismesencephali. J Comp Neurol. 2007 Jan 10;500(2):211-21. • Three-dimensional kinematics of hummingbird flight. J Exp Biol. 2007 Jul;210(Pt 13):2368-82. Ganesha Associates CC BY 3.0

25. Hypothesis lecture learning points • Good hypotheses build directly onto previous work • So they need to become technically more sophisticated over time moving from the general to the particular • A given problem can be associated with a number of very different hypotheses – your experiments should include tests to exclude these alternative explanations Ganesha Associates CC BY 3.0

26. Hypothesis lecture learning points • Hypotheses can be weak (observational) or strong (mechanism-based) • For example, a hypothesis which predicts that a tossed coin will end up ‘heads’ 50% of the time is much weaker than one that can predict the exact sequence of ‘heads’ and ‘tails’ • So hypothesis ‘quality’ is important Ganesha Associates CC BY 3.0

27. Types of scientific output • Abstracts • Primary journal articles • peer-reviewed interpretations of original research • Reviews • Book chapters, monographs • Conference proceedings • Lectures, seminars • Sequences, data sets • Patents, other forms of intellectual property • Blogs, tweets… Ganesha Associates

28. Some sources of scientific content • Google • PubMed/Medline (NLM) • Scopus (Elsevier) • Web of Science (Thomson Reuters) • Google Scholar • PubMed Central, PubMed Central Europe • SciELO, Biblioteca Virtual emSaude • Science Direct, Ovid, SpringerLink, Wiley Online Library, BiomedCentral, Public Library of Science, SWETSwise… • CAPES Portal de Periódicos Ganesha Associates

29. Each source is different • Free • Google, Google Scholar, Pubmed Central • Subscription • Scopus, ScienceDirect • Abstracts and citations only • PubMed, Web of Science • Full text, single publisher • SpringerLink • Full text, many publishers • Pubmed Central, SwetsWise Online Content

30. Classify sources of content Abstract only Full text Free access Subscription

31. You can get access if… • The journal is subscribed to by CAPES • You have a personal subscription • The journal is of the ‘Open Access’ type • Note: some journals only make their content ‘Open Access’ after 6 or longer months. Some journals contain a mixture of OA and non-OA articles. See http://europepmc.org/journalList for more info. • Journals in the ‘red’ categories are available anywhere. • Most journals subscribed to by CAPES will be available from more than one source. • CAPES journals are only available from computers within the University network unless you have remote access privileges. Ganesha Associates

32. So which sources should I use ? • No single source contains all of the articles relevant to your research • Google has the broadest coverage, but not all of the documents you find will be peer-reviewed articles • Scopus, WoS and PubMed give you the best balance between quality and quantity, and, in theory, should link to all the content subscribed to by CAPES, plus OA content. Ganesha Associates

33. Indexing • The purpose of an index is to optimize speed and performance in finding relevant documents for a search query. • Without an index, the search engine would have to scan every document in the corpus, which would require considerable time and computing power. • For example, while an index of 10,000 documents can be queried within milliseconds, a sequential scan of every word in 10,000 large documents could take hours. • A common type of index used for document search is the “inverted index” Ganesha Associates

34. Search: how the result list is ranked • Date of publication • Relevance • Frequency with which search terms occur in the document • Proximity of search terms • Google’s PageRank algorithm uses "link popularity”- a document is ranked higher if there are more links to it Ganesha Associates

35. So… • Using the same search terms will produce different results in different databases because: • Content different • Preparation of search terms will be different, e.g. only Pubmed uses MeSH terms • Indexing process, implementation of stemming, removal of stop words will be different • Ranking algorithms will be different

36. The question behind the query • Search engines think in terms of words, but users think in terms of sentences! • How do you spell Bousfield? • What do we know about BRCA1? • Given these symptoms, what is the most likely diagnosis? • What are the side effects of aspirin? • Has this chemical structure been synthesized before? • “Cancer causes X” vs. “Y causes cancer”

37. What real queries look like - Google • pharmacogenomics and disorders • bacteria growth casein media effect • waal pseudomonas • TRPM2 PCR mouse • Chitinases in carnivorous plants • glycerophosphoinositol 4-phosphate • Dai N, Gubler C, Hengstler P, Meyenberger C, Bauerfeind P. Improved capsule endoscopy after bowel preparation. GastrointestEndosc 2005;61(1) 28-31. Ganesha Associates

38. What real queries look like - PubMed • ATR1 HAL2 • Fuzzy[ALL] AND Hanage[AU] AND 2005[DP] • arndt and rhabdomyosarcoma • "Vorster HH"[Author] • (rotavirus infections[majr] OR rotavirus[majr]) AND english[la] AND humans[mh] NOT (editorial[pt] OR letter[pt]) Ganesha Associates

39. Search terms - summary • Make sure you understand the search term syntax used by your preferred site, i.e. AND, +, “ ”, etc • Search engines ‘see’ only certain words, not sentences • Do not use ‘stop’ words, i.e. a, the, of, before unless they are part of “a text string search” • Try to think of different ways to search for the same subject • Look beyond the first page of search results Ganesha Associates

40. BLAST results AbstractPlus AbstractPlus AbstractPlus Full Text Full Text Full Text NCBI full_report Search results Search results GOOGLE search GOOGLE search A search session may involve many information types.. Ganesha Associates

41. ? Scielo CAPES Portal Web of Science Scopus PubMed Google National Literature OA: BMC Or PLoS Science Direct Springer Link HighWire Other Databases, e.g. NCBI ...and sources Ganesha Associates

42. Quick tour