How does scientific publishing work?

So we talk a lot about the studies we do, and we’ve had a lot of summaries on here of the published papers detailing the results of the research studies.  What might be a bit of a mystery though is how the process between those two points works…  So here’s an overview.

Once we’ve gone through all the hard slog of acquiring research data and analysing the results, we write up a report, that we generally call a manuscript.  This is normally something around 3,000 words long, and contains:

– An introduction to the area of study, why we decided to do the research, and what we expected to find (our hypothesis).

– The ‘methods’ section, which is a detailed description of what we did and how (what equipment we used, how long we measured things for, where we identified participants from, in what order our measurements were made, etc.).

– Results:  this is where we put all the numbers, in the form of tables and graphs and some explanatory text.

– The discussion, which is where we talk about what we think the results mean.  It might be that we found what we expected (i.e. supported our hypothesis), or that we got completely different results to what we hypothesised.  Either way, we discuss aspects of the study that we think were particularly strong, highlight any weaknesses, and then refer to our results within the context of other research in the same (and related) fields.  This section often contains suggestions of what future studies could do to build on the results we’re presenting.

So once we’ve written the manuscript and all authors are happy with it (everyone who has contributed significantly to the research is listed as an author, with the first person in the list being the person who did the majority of the work, and the last person being the senior academic responsible for overseeing the project), we decide on a journal to send it to.  This decision is based on the type of research study we’ve done (there are some journals more suited to studies with a pure physiology focus, and some better for more clinically-orientated work) and how significant we think the work is.  A larger study, or one with more exciting findings (perhaps that would really change the way people think about that area of study), would be sent to a more prestigious journal.

Once the journal receives the manuscript via their online submission system, it is evaluated by a member of the journal’s editorial team.  They judge whether the manuscript is the sort of thing they’re looking for, and at that point either reject it straight away (disappointing) or decide to send it out to review.  If the latter, the manuscript will be sent to usually two or three expert researchers who work in the same field to ask them to give their opinion.  These reviewers will write a report of the manuscript and suggest how suitable they think the manuscript is for publication in the journal.  The editors of the journal will take into account the opinions of all the reviewers (and these opinions won’t always agree…) and make their decision.   They will send us an email informing us of the outcome, which will be one of three things:  that the manuscript has been rejected, that it will be reconsidered after some changes are made, or that it is accepted as it stands (a relatively unusual outcome, but one that we would celebrate with some vigour!).

If the manuscript is rejected, we will look carefully at the reviewers’ comments and make any appropriate changes to the manuscript before choosing a new journal to send it to (and the process starts again).

If changes are requested, these could be relatively simple (such as adding in some more details about the participants, including some different graphs to represent the data more clearly, or referring to some other research within the discussion section), or could be complex (for example requiring some major data reanalysis or lengthy explanations of why a certain approach was chosen).  We would work on these changes and send back a revised manuscript with a detailed letter describing what changes we have (or sometimes haven’t) made and why.  These documents then are sent back to the reviewers and they write another report.  Based on this, the editors decide whether we’ve done a good enough job for the manuscript to be accepted.  Sometimes the changes and corrections process is repeated once (or more), but generally the manuscript will be accepted in response to the first or second set of changes.

Once the manuscript has been accepted by a journal (whether that’s the first, second or fifth journal to which it was sent), the journal’s editorial assistants prepare the written document in their own specific format and send ‘proofs’ to the authors to approve (making sure that everything looks correct, there are no spelling errors, and that the layout for the journal hasn’t led any data to be presented in a misleading manner).  The paper (no longer just a manuscript) is then first published online, and a few months later appears in print (though actually very few people read journals in paper form any longer).  And importantly, we add it to our CVs!

Summary of Arietta’s thesis – Ma’ayan Dee, Neta Fibeesh & Abi Mincer

Systematic review and meta-analysis of health status questionnaires in bronchiectasis

A recent study regarding Bronchiectasis questionnaires was used to understand the quality of life of patients with a chronic lung disease called Bronchiectasis. These results were used to understand the connections between HRQOL (Health Related Quality of Life) and clinical measures, which are other tools we use to assess a disease. The aims of the study were to identify all the evidence and select the appropriate studies that can later be assessed in an unbiased and balanced way. The importance of collecting this data in this way is that it provides useful insights about the quality of life of patients from a personal point of view and helps the researchers understand the effectiveness of their clinical tools.

The searching and selection process using electronic databases were used to choose appropriate studies, for instance patients with cystic fibrosis (a genetic condition) were not chosen. The studies which were chosen were analysed to check for certain criteria that made sure their results were reliable. Then, a meta-analysis (a combination of various data assessments) was used to test how strong the connections between HRQOL and the clinical measures actually were. Out of the initial 1,918 studies first identified, 43 studies were used in the reviews and 38 ended up being chosen as suitable for the meta-analysis.

Results showed that there was a strong relationship between the HRQOL and subjective outcome measures such as fatigue (tiredness) in comparison to objective measures such as ability to exercise and how severe the Bronchiectasis was revealed to be on a CT scan.

 

Development and validation of the Bronchiectasis Health Questionnaire (BHQ): a new patient-reported outcome measure

There is an insufficient amount of questionnaires in relation to assessing the health status of someone with bronchiectasis. The questionnaires themselves are easy to understand and they give an idea of the patient’s perspective. A study was conducted to develop and confirm the value of the BHQ (Bronchiectasis Health Questionnaire). The BHQ is a new tool to measure the health status for patients with bronchiectasis. Questionnaires are needed for individual conditions due to the fact that every disease has its own causes and symptoms. This means that in order to help patients with different diseases questionnaires have to be adapted in order that the questions lead to suitable answers which can thus help those asking the questions to find answers that will lead to help for those taking part.

Patients who took part in the study were recruited from two outpatients clinics. The BHQ was developed by the introduction of item generation as well as item reduction. As well as this, the BHQ was developed by repeated testing and validation.

Two hundred and six patients took part in the study and completed a questionnaire with 65 questions. Fifty five of the questions were removed from the initial questionnaire to make the tool easy to use and more valid. The final version of the BHQ consisted of 10 items with a score between 0-100 with 100 being the best health status.

The BHQ generates a total score and general consensus. It can be used in clinical and research settings in order to assess the effect of bronchiectasis from the perspective of the patient who has the disease.

 

The objective assessment of cough frequency in bronchiectasis

Bronchiectasis is the abnormal widening of the bronchi or their branches, which causes a risk of infection. Cough is a common symptom of this condition and recent advances in technology in the monitoring of cough sound have enabled the assessment of cough frequency to be used to better understand various diseases. This study was aimed at quantifying cough frequency and by doing so investigating how the cough frequency affects the health status of individuals.

54 Bronchiectasis patients were assessed along with 35 healthy people (controls). The researchers measured their health status, cough severity, lung function and 24-hour cough. 24-hour cough was measured using a small portable audio recording device.

Data revealed that the cough frequency was high for patients suffering from Bronchiectasis meaning they coughed a significant amount more that healthy people. Additionally, patients with Bronchiectasis had impaired health status. Various factors associated with the objective cough frequency included sputum production (coughing up phlegm), the frequency of antibiotics for respiratory infections and older age. However, there was no good association between cough frequency and a common lung function test (spirometry).

 

Summary

Overall the studies revealed that questionnaires were a successful technique to provide results regarding the quality of life of those suffering from Bronchiectasis. This shows that a patient’s own perspective is very valuable in medical research and not only their physical condition!

This summarises the PhD research undertaken by Arietta Spinou, under the supervision of Surinder S Birring & Rachel Garrod. The summary was produced by Neta Fibeesh, Abi Mincer & Ma’ayan Dee, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Our students’ summer contributions to the lab

It’s time for a well overdue thank you to all of our student volunteers for their contributions to the lab over the summer.  This year, instead of offering standard work experience to two or three students, as we have done in the past, we decided to ask our Student Panel members for help with a number of tasks that would be beneficial to both them and us.  An experimental approach but it worked even better than we had hoped!  So, many thanks to:

Lottricia Millett, Lily Groom, Morgan Walker, Reef Ronel, David Launer, Casril Liebert and Ashleigh Francis for writing summaries of published research papers from the lab.  All of these summaries (which were of a very high quality!) are published here on the blog as well as being displayed in the patient waiting area of the department.  A number of them have also been sent out to the patients and healthy volunteers who took part in those studies to inform them of the findings of the research to which they contributed.  Feeding back results of studies to participants is really important, and it’s great to be able to send these summaries out to people. 14222263_1788954434721939_5703414665885109122_n We also hope that the students will be able to use these summaries to demonstrate their skills when attending for university interviews and suchlike.

Kiki14088424_1787637261520323_4645596235687183587_n Riad-Forbes and Banke Faboyede for revamping the display board in our patient waiting area.  The display has photos of the researchers in the department and information about the different types of research everyone does, plus links to this blog and our Facebook & Twitter accounts.  We see a lot of people reading the information while they’re waiting so the eye-catching display is definitely doing its job!

14021567_1784513418499374_5875016027988625499_n14054994_1784058621878187_1578551485653647537_n

13906611_1778805805736802_1603152345208128348_nMiki Friend, Asha Omar, 14045962_1784058648544851_3183321450250707211_nKiki Riad-Forbes, Banke Faboyede and Muska Yarzi for putting together a database of all of Alan and Vicky’s previous research participants and sending a huge mailshot to them all with the summaries of the studies for which they volunteered.  This wasn’t the most interesting of jobs, involving lots of typing, printing, sorting piles of paper, and stuffing envelopes but was a task that probably just wouldn’t have happened otherwise.  After some delays with a new postal system at King’s we’ve just sent out 216 A4 envelopes, with a few more to go out in due course.

Neta Fibeesh, Abi Mincer and Ma’ayan Dee, for writing a summary of Arietta Spinou’s PhD thesis studies, which again will be sent out to her patient participants to inform them of the outcome of the research.  The nature of Arietta’s research is a bit different to the types of studies that most people are familiar with, so Neta, Abi and Ma’ayan did very well to summarise these studies in a way that’s accessible to people with no scientific background.

Ibtissam Adem and Deeqa Mohamed, for producing a great video of the SkinSuit study being undertaken at the KCL London Bridge campus with PhD student Phil Carvil and MSc student Alex Sehgal under Ged’s supervision.  Not only did they film it in 13892088_1778805789070137_4994973215050727729_ngreat detail, they took a lot of time to ensure they understood all of the complex science of both the suit (designed to mimic the some of the effects of gravity when astronauts are in space) and the measurements being made.  The video will be a great resource for a lot of people.

So we think that’s a pretty decent summer of work!  It has been wonderful to partner with our Student Panel members and we have been very impressed with the quality of the work they’ve all produced.  We’re already looking forward to what achievements next summer will bring!

Research summary – Morgan Walker

Airways Obstruction and Pulmonary Capillary Blood Volume in Children With Sickle Cell Disease

Catherine Wedderburn, David Rees, Susan Height, Moira Dick, Gerrard F. Rafferty, Alan Lunt, Anne Greenough

Published in the journal Pediatric Pulmonology, published online July 10th 2013

Children with Sickle Cell Disease (SCD) often face many obstacles due to the changes the condition causes in the body’s red blood cells. SCD results in anaemia, which is when there is less haemoglobin in the blood to help carry oxygen around the body. As a result, the heart has to pump much harder in order to ensure that the tissues of the body receive enough oxygen. This increased work by the heart also raises the amount of blood in the lungs, in order to allow sufficient oxygen is absorbed from the air. Children with SCD also frequently experience ‘airway obstruction’, which is the narrowing of the airways that makes it then harder to breathe. Airway narrowing can be caused by asthma, where muscles in the airways constrict, or by other causes.

This research was used to investigate whether the increased blood volume in lungs is associated with the ‘obstruction’ of the airways. The researchers tested this through testing the difference in the airways before and 30 minutes after using a medication called a bronchodilator (the blue asthma ‘reliever’ inhaler) which relaxes the airway muscles, widening the airways.   The study used measurements called spirometry, which tests the amount and speed of air that can be moved in and out of the lungs, and Impulse Oscillometry (IOS), which uses sound waves in order to assess the resistance of the airways (airway narrowing).

If the bronchodilator had a substantial effect, the researchers would be able to say that the airway obstruction was due to an asthma-type condition, as the inhaler would have relaxed the muscles and allowed air to move more easily through the airways. What the results showed, however, was that there was little change in the measurements of lung function after the inhaler was given. The researchers can therefore use this evidence to support the hypothesis that the airway obstruction in SCD may be due to increased blood volume in the lungs.

Therefore, this study suggests that treatment of non-asthma related airway obstruction in SCD patients could perhaps move away from bronchodilators and towards more effective treatments for the anaemia aspect of SCD such as blood transfusions. A great deal of further work is needed but this is a valuable insight into the a potential process underlying breathing problems in SCD.

This summary was produced by Morgan Walker, Year 13 student from Harris City Academy Crystal Palace, as part of our departmental educational outreach programme.

Research summary – Reef Ronel

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial

Matthew Maddocks, Claire M. Nolan, William D-C. Man, Michael I. Polkey, Nicholas Hart, Wei Gao, Gerrard F. Rafferty, John Moxham, Irene J. Higginson

Published in the journal Lancet Respiratory Medicine, published online December 14th 2015

Patients with severe COPD often have weak legs as breathlessness can limit their ability to be active. Normally, to combat this and other symptoms of COPD, exercise classes called Pulmonary Rehabilitation (PR) are carried out. However, more severely affected patients may struggle to do PR.

An alternative therapy was introduced, neuromuscular electrical stimulation (NMES), to COPD patients with more severe symptoms. NMES is when electricity is used to create muscle contractions, in this case in the thigh muscles. While NMES has been used to strengthen muscles in previous research, this trial is the first to explore the impact on daily activities and the first to investigate the longer-term impact of the treatment.

52 participants with very severe COPD took part in this trial over two years. Participants received 30 minutes of NMES to both sets of thigh muscles daily for 6 weeks; 27 were placebo (‘sham’ stimulation) and 25 received active NMES. The aim: to assess the effectiveness of NMES, as a therapy to be conducted unsupervised at home, and at aiding daily activities. The main measure of effectiveness in this trial was a test of how far participants could walk in 6 minutes.

The results of the walk tests strongly support the use of NMES for severe COPD patients, with the patients who received the active NMES being able to walk substantially further. During interviews active NMES participants expressed a greater ease in everyday tasks (such as climbing the stairs) and stated that they could carry out physical activities for longer. No participants reported any negative views. Unfortunately, the improvement provided by NMES quickly waned after the treatment had stopped. Therefore, all existing evidence suggests that NMES should not be considered a replacement for PR. NMES can be used as an extension to PR, and could be used when patients are unable to take part in PR programmes. In addition, the short duration of effect suggests that longer programmes need to be investigated. Nonetheless, this trial has shown that NMES is a practical home-based therapy, suited to patients with more severe symptoms and has gives suggestions for future research.

This summary was produced by Reef Ronel, Year 12 student from JFS School, as part of our departmental educational outreach programme.

Chris starts his study

Chris Harris, one of our neonatal research colleagues, has recently started measuring patients for his major study comparing the effects of two types of ventilation for babies born prematurely.  The United Kingdom Oscillation Study started in 1998 and recruited over 300 babies who were born 12-17 weeks early and needed help with their breathing from a ventilator.  All of the babies were given one of two types of breathing support – normal ventilation, where air is pushed into the lungs at a rate and depth about the same as they would do on their own, or ‘high-frequency oscillation ventilation’ or HFOV, where the lungs are inflated and then small amounts of air vibrated, or oscillated, in and out of the lungs at a very fast rate.  The idea of the HFOV is that it doesn’t involve the same amount of stretch to the lungs as normal ventilation, possibly preventing some of the damage that can occur to premature babies’ delicate lungs during the crucial weeks after birth while so much lung growth and development is taking place.  Chris is also doing some cellular biology as part of his PhD, stretching lung cells in the lab and seeing what inflammatory chemicals are released.  This will help give a more complete picture of why HFOV may (or may not) be beneficial.

The UKOS participants were last studied at 11-14 years of age; the results then showed that HFOV seemed to have protected the lungs somewhat, particularly the smaller airways further down in the lungs.  These airways are particularly prone to damage as they are still forming during the stage at which these babies were born, and the HFOV perhaps allowed those parts of the lung to continue developing more normally, as they would have done were the babies still in the womb.

The current stage of the research will make detailed lung function measurements again in as many of the participants who are able to come back for more testing, and again compare the children who received HFOV to those who received normal ventilator support.  The UKOS “babies” are now young adults, aged 16-18, and so have probably grown a huge amount since their last tests; this growth will have affected their lung function so that’s why it’s important to see how they’re getting on now.  Chris has had four patients participate so far and all has gone well thanks to their brilliant efforts, so we’re looking forward to seeing the data come in!

 

Research summary – David Launer

Pulmonary function, CT and echocardiographic abnormalities in sickle cell disease

Alan Lunt, Sujal Desai, Athol Wells, David Hansell, Sitali Mushemi, Narbeh Melikian, Ajay Shah, Swee Lay Thein, Anne Greenough

Published in the journal Thorax, August 2014

Sickle Cell Disease (SCD) is amongst the most prevalent genetic diseases worldwide. Only being inherited if both of one’s parents carry a ‘faulty’ gene in their DNA, SCD affects the Haemoglobin molecules that carry oxygen in the blood, distorting the shape of the red blood cells into so-called crescent shaped ‘sickles’.

It has been shown previously that the majority of adults with SCD have changes in their lungs that can be found on a CT scanner, a high powered X-ray scanner that can create a detailed 3D image of the lungs, including airways and blood vessels.

This study showed that findings like particularly large blood vessels in the lung were linked to reduced lung function. This study aimed to show a link between these changes in the lung and the resulting changes in heart function that one can view on an ‘echocardiogram’ in the same group of patients. An ‘echocardiogram’ is a scanner used to observe the way in which the heart functions, from ultrasound waves ‘bouncing’ off the heart. It can view the structure of the heart and vessels, as well as blood flow. In SCD the heart has to pump more blood through the lungs in order to deliver enough oxygen to the tissues.

Adults with SCD were assessed using CT, echocardiography, and other lung function tests such as lung capacity, between the years 2009-2013. This same group of adults had previously been shown to have lung changes on CT scans between 2003-2005.

Whilst there was a large variety in the lung function of the 28 patients with altered lung features, it was demonstrated that lung structure changes seen on CT scans was related to the patients’ decline in lung function, and changes in the function of the heart displayed on echocardiogram tests. Importantly, the results of the study suggest that some of the changes found in the blood vessels between the heart and lungs may be able to explain the differences in the lungs found on CT scan and the decline in lung function. The results of this study help us to understand the complex relationships between heart, lung and blood vessel function in SCD.

This summary was produced by David Launer, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Ashleigh Francis

Airway and alveolar nitric oxide production, lung function and pulmonary blood flow in sickle cell disease
Alan Lunt, Na’eem Ahmed, Gerrard F. Rafferty, Moira Dick, David Rees, Sue Height, Swee Lay Thein, Anne Greenough
Published in the journal Pediatric Research, March 2016

Patients with Sickle Cell Disease (SCD) are often assumed to have asthma because they have ‘airflow obstruction’, which is when airways become narrowed and air is not able to move out of the lungs as quickly or easily as in healthy lungs.
Inflammation in the airways is one of the main features of asthma. Nitric Oxide (NO) is a substance that is produced by the airways when they are inflamed, so therefore can be used to measure the severity of asthma in a patient and find out how inflamed their airways are.
As well as being produced in the airways, NO is also produced in blood vessels, and helps to widen blood vessels.
People with SCD are anaemic, meaning they have less haemoglobin (a protein in the body that carries oxygen) so their cells cannot carry as much oxygen. In order to compensate for this, the heart beats faster and with more power to make sure enough oxygen is picked up from the lungs and delivered to the body.
This study looked at measurements of NO from the airways (representative of asthma) and the alveoli (representative of blood vessel widening), and compared it to lung function tests (to look at airway narrowing) and measures of pulmonary blood flow (how fast blood was circulating around the lungs).
The results showed that the airway NO was not raised, but that there was still airway narrowing occurring.  There was a relationship between how fast blood was circulating through the lungs and NO from the alveoli. This might suggest that previous findings of high NO and airway narrowing resulted in a false assumption that SCD patients’ airway narrowing was down to asthma. This study suggests that the changes in heart and blood vessel function in SCD may have an effect on the airways.
This study was relevant in terms of contributing to medical research because it shows the airway narrowing in SCD patients may not always be down to asthma, so it therefore allows us to target other root causes of the problem.

This summary was produced by Ashleigh Francis, Year 13 student from Harris City Academy Crystal Palace, as part of our departmental educational outreach programme.

Research paper summary – Casril Liebert

Ankle dorsiflexor muscle size, composition and force with ageing and chronic obstructive pulmonary disease

Matthew Maddocks, Matthew Jones, Thomas Snell, Bronwen Connolly, Susanne de Wolf-Linder, John Moxham, Gerrard F. Rafferty

Published in the journal Experimental Physiology, June 2014

Chronic obstructive pulmonary disease (COPD) is the name for a group of lung diseases that cause breathing problems. COPD patients often find it hard to do exercise because their muscles may be slightly weaker compared to a healthy person. The ankle dorsiflexor muscle, at the front of the shin, is used for balance and walking. This research looked at how the ankle dorsiflexor muscles were different between 20 young healthy people, 18 healthy elderly people and 17 people with COPD. This allows us to see how COPD affects the normal ageing process of the muscle.

Firstly, we took scans of the muscle to see what it is made of. We also measured the size of the muscle. The scans showed that the COPD patients had a lot of non-useful tissue in the muscle that doesn’t help the muscle work normally. The strength of the muscle was also measured. This was done by passing electricity into the nerve to the side of the knee that supplies the dorsiflexor muscle. This caused the nerves to react and tense the muscle.

The results showed that patients with severe COPD have ankle weakness. This means that their muscles are not as strong as a healthy person and it is harder to do certain tasks that require strength. The scans also revealed that a greater muscle size was associated with a greater muscle strength, and also that tissue in the muscle without a function is a major cause of muscle weakness. The muscle composition scan discovered that fat and fluid in the muscle was often found in COPD patients. This tissue that isn’t useful creates problems which affect exercise performance and postural control, causing impaired balance and walking abnormalities. The discoveries within this study have allowed us to better understand why muscle strength in COPD patients decreases much more than seen with normal ageing.

This summary was produced by Casril Liebert, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research paper summary – David Launer

Longitudinal Assessment of Lung Function in Children With Sickle Cell Disease
Alan Lunt, Emily McGhee, Karl Sylvester, Gerrard F. Rafferty, Moira Dick, David Rees, Sue Height, Swee Lay Thein, Anne Greenough

Published in the journal Pediatric Pulmonology, December 2015

Sickle Cell Disease (SCD) is amongst the most prevalent genetic conditions worldwide. Only being inherited if both one’s parents carry a ‘faulty’ gene in their DNA, SCD affects the Haemoglobin molecules that carry Oxygen in the blood, changing the shape of the red blood cells into so-called crescent shaped ‘sickles’. Despite its commonness, with over 300,000 babies being born with SCD worldwide every year, a clear and consistent picture of how SCD affects the lungs of children with SCD had not yet been researched. This study aimed to research the lung function of children affected by the disorder over time, observing how this changed in early and later childhood, and how this was affected by episodes of ACS (Acute Chest Syndrome) in early childhood, when the sickle-shaped red blood cells can block blood vessels and lead to various different injuries.

Two groups of children were tested. The first, who were slightly younger on average, were
measured twice for their lung function over an average of 2 years, while the second group were measured twice over approximately 10 years. A number of methods were used to test each person’s lung function, including ‘spirometry’ in which the quantity of air one can force out the lungs is measured, among other values like lung capacity. These measurements were then compared to a ‘control’ group of healthy children without SCD at a similar age, to give a normal level of lung function to compare against the SCD patients’.

In both groups of children with SCD, a reduction in lung function over time was seen when compared to the groups of children without SCD. However, the lung function of those in the first, younger, group decreased at a faster rate.

The results suggest that the fastest period of deterioration in lung function takes place in early childhood. Indeed, having an episode of ACS in young childhood was the only factor found that increased the likelihood of worse overall lung function later on. This could explain the faster decline of the younger group, as ACS is more common in younger children. This would seem to conclude that a focus should be placed on preventing ACS in young children as a strategy to improve the general lung function later on of those with SCD.

This summary was produced by David Launer, Year 12 student from JFS School Harrow, as part of our departmental educational outreach programme.