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Professor Gavin Reynolds Honorary Professor: Biomedical Research Centre, Sheffield Hallam University, UK Professor Emeritus: Queen’s University Belfast,

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Presentation on theme: "Professor Gavin Reynolds Honorary Professor: Biomedical Research Centre, Sheffield Hallam University, UK Professor Emeritus: Queen’s University Belfast,"— Presentation transcript:

1 Professor Gavin Reynolds Honorary Professor: Biomedical Research Centre, Sheffield Hallam University, UK Professor Emeritus: Queen’s University Belfast, UK Visiting Professor: SouthEast University, Nanjing; University of Malaya, Kuala Lumpur; Naresuan University, Thailand Past-President: British Association for Psychopharmacology Publishing your research

2 What you need for a great paper Understanding how biomedical research is done Select the right journal How to write a paper How to write to the editor How to respond to reviewer’s comments

3 How to read a paper What you want to know will determine how you read the paper What do you want to know? – Find a method – Check some data – Understand the background to your research Reading the abstract may tell you all you need, but: – It may not tell you why they did the research – It may not tell you the methods used and if they are valid

4 So you want a great paper! To have a great paper you need to have: Great results! – Which need to be novel, clear and meaningful. – But to get great results you need to have: A great project! – Which needs to be well designed, adequately powered. – But to have a great project, first you need: A great idea!

5 How biomedical research is done Identify the problem Understand the background Propose the hypothesis Design the study Do the work Collect the sample, make the measurements Analyse the data Write and publish the report Identify the next problem...

6 How biomedical research is done – an example The problem: Some drugs used to treat schizophrenia make people gain weight. This can cause increases in diabetes and heart disease People have different responses – some get very fat, some have no weight increase, even when they receive the same drug.

7 How biomedical research is done – an example Understanding the background: Antipsychotic drugs used to treat schizophrenia have effects on the brain. Our brain controls how much we eat. There are receptors in the brain affecting appetite that these drugs may block. Differences between people in weight gain may be due to genetic differences.

8 How biomedical research is done – an example Developing the hypothesis: There are genetic differences between people in weight changes after drug treatment for schizophrenia. These differences can be found in genes controlling eating. “Variability in the gene for the 5-HT2C receptor is associated with weight gain during antipsychotic drug treatment.”

9 How biomedical research is done – an example Design and do the study: Find patients with schizophrenia receiving drugs for the first time. Measure changes in weight over 10 weeks. Investigate genetic differences between patients in one gene important in controlling appetite.

10 How biomedical research is done – an example Analyse the results: Genetic differences between patients were related to the amount of weight gain. Patients with one genetic variant had much less weight gain. Change in BMI (kg/m 2 ) Period of drug treatment

11 How biomedical research is done – an example Write and publish the report:

12 How to select the right journal What is the “right” journal? – The right readership – specialist or general? – The highest impact factor? Included in Pubmed? – Previously published related papers? – Rapid publication? – Appropriate for style/format of report? – Sympathetic to Asian manuscripts?

13 How to write a paper Having great results is not enough. You need to: – Understand how your work relates to work from other groups – But don’t forget that others in your research group may be doing related work – understand that too! Write for the reader – What is interesting for you may not be for the reader – Decide what your main message is, and focus on that – Ask a colleague to read it through and criticise Be aware of other related papers – Always think about how your work adds to, or improves on, other research.

14 How to write a paper Read and follow the journal instructions – Look at the layout of published papers. You can use other papers as a “template” for your report – But do not “copy and paste” from other papers! Editors have software that can detect this! And referees hate it when they see their words repeated by someone else! – Be tidy! Use page break to separate sections, figures etc. – Tables and figures in separate files or at the end of text file – Always define abbreviations the first time you use them: “Brain-derived neurotrophic factor (BDNF) is… We measured BDNF…” – Format references correctly – Correct format for abstract and text headings

15 How to write a paper Introduction – Most journals prefer the introduction to be just a brief summary of the background leading up to your work – Go from the general to the particular: Start with a general statement of the context of your work: “Depression is common in patients with Parkinson’s disease, who frequently respond poorly to antidepressant drugs” – End with the particular focus of your research: “Thus we aimed to determine whether this genetic polymorphism is related to the response to depression of patients with PD” – Include a statement of your hypothesis or research question

16 How to write a paper Methods – For human samples, list inclusion and exclusion criteria, indicate “written informed consent” and ethical approval – For in vivo animal studies, always indicate ethical standards. – Experimental methods can be brief if they replicate published methods: “…following the method of Yang et al (2011)…” or “… based on the method of Yang et al (2011). In brief, this involved… ”

17 How to write a paper Results – Include all results you wish to report, but do not interpret or comment on them. – Refer to results in tables/figures, but do not repeat the data in the text. You can report it in another way (e.g. %). – Age, sex etc. of a sample are results, not for the methods section, unless predetermined in the sample collection Statistical results – Be accurate in describing the data – Not “…was decreased” but “…was significantly decreased” – Not “…was not decreased” but ”…was not significantly decreased”

18 Change in BMI (kg/m 2 ) 1. Statistically highly significant difference; “is significantly much less”. 2. No difference between the mean values – “no difference” is only correct here. 3. Difference is less, but does not reach statistical significance. Not: “not different”

19 How to write a paper Discussion – Good to start with a simple summary of the main findings, but don’t just repeat the results. – Relate your findings to your hypothesis. – Discuss your findings in relation to other work in the field, but don’t repeat the introduction. – Be aware of the limitations and discuss them, before the reviewer asks you to do that! – Draw conclusions

20 How to write a paper Common language errors – Affect and effect: affect is usually a verb; effect is usually a noun, meaning consequence or result of some action – Information, never informations – Evidence, never evidences – Research, never researches – Data is plural; singular is “data point” or “datum” (rarely used). Think about tense – present or past – “Wang et al (2007) found that cognition is impaired after methamphetamine administration…” – past perfect to describe what was done – present if the finding is generally true.

21 How to write to the editor Be brief – it is enough just to say: – “We wish to submit our paper entitled… for publication in …” Remember that the editor will read the abstract to understand the content of the paper – If you need to explain your work in the letter to the editor, then you have not written the abstract clearly!

22 How to write to the editor -II But you can emphasise important aspects if it is particularly notable: – “We believe the finding that … has important implications for future diagnostic testing and treatment” Remember that the editor is interested in increasing the impact factor for his journal – “As the results may be seen as controversial, they should attract substantial interest and citations”

23 How to respond to the reviewers You respond to the reviewers’ comments but you write to the editor. – So you can point out to the editor if the reviewer is wrong, or has missed something, or is being inflexible over a disputed point Make your response clear and brief - include each of the reviewer’s points in your response and address it: – The authors have not included the units in table 3 – We have now corrected this error – They have failed to cite the report that this polymorphism is associated with depression (Smith et al) – The reviewer has missed our mention on p12 of several reports failing to replicate the finding of Smith et al.

24 How to respond to the reviewers - II If you believe a reviewer to be biased, or incorrect, don’t be afraid to say so to the editor: – “While the reviewer appears to reject our findings on the basis of the work of Smith et al., this is a view that is not common to more recent studies we have cited (e.g. Jones et al)…” I usually finish by saying something like: – “We hope you agree that we have appropriately addressed all the reviewers’ concerns and believe the manuscript is now suitable for publication.”

25 Please ask me questions!

26 How to write a paper Gavin doesn’t like: – Treatment of animals. Treatment is for people who are unwell, not for healthy animals – who “receive drug” or “drug is administered to..” – and certainly not for cells! – Levels: “glutamate was determined...” easier than “glutamate levels were measured…” Or use “concentration”.

27 How to prepare a poster Title – Not too long – Interesting for delegates Abstract – Include abstract on poster only if required by the conference Introduction – Short and relevant – Include statement of hypothesis Methods – Methods used should test the hypothesis – Use graphic/chart if it helps to explain

28 How to prepare a poster – 2 Results – Initial summary – Charts/graphs are better than tables; tables are better than text. Ensure all graphs are clearly labelled! Conclusions/discussion – Interpret your results in relation to your hypothesis – Explain why it is important and interesting – Relate your findings to other published work References – Include only references that are important and relevant to your methods and conclusions

29 Poster layout Make the text readable from a distance – Lower case is easier and faster to read than UPPER CASE Do not use mixtures of fonts and font sizes – But less important sections (methods and references perhaps) could have a smaller font size – I use bold text to emphasis important statements e.g. the hypothesis in the introduction, and the main conclusion. Keep the text and graphics clear – Do not use distracting background colours Arrange the information clearly: – In columns – In labelled sections

30 Hao Tang 1,2, Umarat Srisawat 1, Caroline F Dalton 1, Zhi Jun Zhang 2 and Gavin P Reynolds 1 1 Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB 2 Zhongda Hospital, Southeast University, Nanjing, China, 210009 1. Reynolds et al. (2006) Am J Psychiat 163, 1826-1829 2. Carrard et al. (2011) J Affect Disord 132, 450-453 3. Wallwork et al. (2012) Schizophr Res 137, 246-250 4. Jacobsen et al. (2008) Mol Cell Neurosci 38: 349-358 Methylation of CpG13, but no other site, was found to correlate strongly with change in PANSS score (r=0.30, p=0.006) after antipsychotic drug treatment, and with negative symptom response (Fig 2 and Table). Table Correlation between % methylation at CpG13 and change in the 5 PANSS factors Symptom factorrp Positive0.0860.447 Negative0.4100.000 Disorganized/concrete0.1020.364 Excited0.1550.168 Depressed0.2060.065 r=0.410, p<0.001 Methods Conclusions Introduction Results References Association of the -1019C/G (rs6295) polymorphism of the 5-HT1A receptor gene (HTR1A) with negative symptom response to antipsychotic treatment in first episode psychosis 1 has been replicated in several populations. Epigenetic mechanisms such as DNA methylation are demonstrated to affect response to antidepressants and may well be important in antipsychotic response. Moreover, increased methylation of the HTR1A promoter has been found in bipolar disorder and schizophrenia compared to controls 2. To investigate whether HTR1A promoter methylation might also influence response to antipsychotic treatment, we determined cytosine methylation in the sequence around the -1019C/G polymorphism in a sample of Chinese subjects with a first psychotic episode. Drug-naive subjects with first-episode psychosis (45 male, 37 female; mean age 25.8 years) were assessed and monitored using the positive and negative syndrome scale (PANSS). Changes in PANSS and in 5 symptom factors 3 derived from PANSS were determined after 10 weeks' treatment with antipsychotic drugs. DNA was extracted from blood taken on admission and the percentage cytosine methylation determined at four sites (CpG9, 10, 11 and 13) close to rs6295, and at the C allele in rs6295 (CpG12), by pyrosequencing following bisulfite treatment (Fig 1). Figure 1. Methylated cytosine (CpG) sites (numbered 9-13) are shown in bold in the DNA sequence of HTR1A, with the rs6295 polymorphism in brackets and binding sites for transcription factors shown in frames. Figure 2. Correlation between % methylation at CpG13 and change in the negative factor score. CpG13 is found within a recognition site for the repressor activity of transcription factors HES1 and HES5, of which HES5 activity is also influenced by the nearby rs6295 allele 4. Thus cytosine methylation at this CpG site is another influence that, in addition to the rs6295 genotype, may disrupt transcription factor binding to affect expression of the 5-HT1A receptor. DNA methylation of the 5-HT1A receptor gene promoter is associated with negative syndrome response to antipsychotic drug treatment The relationship between CpG13 methylation and change in negative symptoms occurs separately within both CC genotype (r=0.422, n=46, p=0.004) and G carrier (r=0.421, n=35, p=0.012) groups (Fig 2). The correlation between CpG13 methylation and negative syndrome change is internally replicated, being present in two sample subgroups divided by rs6295 genotype. We have identified an epigenetic factor that, likely via its effects on the expression and control of the 5- HT1A receptor, can influence response to antipsychotic drug treatment, particularly response of negative symptoms.

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