Saturday, November 01, 2014

Invisible co-passengers in your life

You think it's your body. You touch it, see it,  feel it and appreciate it. Looking at the anatomical pictures of  internal parts, you feel amazed about the complexity of your body. But is everything in your body yours? Count the cells. You will realise that majority of the cells, you carry, are not yours. Those are diverse microorganisms, mostly bacteria. According to a rough estimate, a person, having 40 lakh crore cells, caries 400 lakh crore microbes. In other words, we are ten percent human. Almost three percent of our weight comes from these tiny creatures. They are present on our skin, in cavities, even in internal organs like lung and gut. The womb that was once considered to be a sterile zone, also harbours microorganisms. All this microorganisms, in our body, as a whole constitute human microbiome. A hidden world within us.

It has long been known that our gut have bacteria that help us in various ways, from providing micronutrients like vitamins to chasing out bad microbes. They are commonly called commensals. Many of these bacteria are different types of lactobacillus, similar to the one that we use to make curd. In fact, consumption of curd is an way to supplement the existing microbes within your gut. Prolonged use of antibiotics destroys microbes in the gut, even the helpful ones. That's why patients are advised to consume probiotics as supplement. Probiotics are live microorganisms that are helpful for our health. 

Our microbiome is like a cocktail. It’s  difficult to identify and study individual microbes in it. Now, technologies exist to identify large number of different microorganisms in a mixture, in short time, using their genetic fingerprints. Such technologies have invigorated research in this field. There is also a philosophical shift among biologists. The time of over-emphasis on genes of an individual is over. Now biologists realise that we need to take the environment  into consideration to understand complexities of human physiology and diseases. The Microbiome is our immediate environment. The way we manipulate the nature around us, these microorganisms also manipulate us. And we need to understand their actions on us to maintain our health.

Take the problem of obesity. Its becoming an epidemic, even in our country. Your physician, friendly experts and the advertisements of fitness clinics must have now convinced you that our food habit and lifestyle are making us obese. Thats correct, to a large extent. But those microbes in your gut also play a role in this. Many microbes in our gut help in harvesting energy from food and affect metabolism. Therefore, variation in the microbial ecology of our gut can affect our body weight. Studies have shown that the microbiome of obese individuals is different from that of lean. In fact, one study has even shown that response to a weight-loss program has relation to individuals gut microbes. Animal studies have proved that by manipulating gut microbiome we may control obesity. One way to achieve that is to transplant a right cocktail of microorganisms in our gut. Even selective foods or antibiotics can be used to manipulate the microbial ecology. However, such works are still experimental and you have to wait some more time to add a cocktail of microbes in your fiber-rich weight-loss diet.  

But experiments are not limited to obesity. Transplantation of microbes is helping in fight against a dreaded infection. Clostridium difficile is a bacteria that causes severe diarrhea, particularly in patients using antibiotics. In many cases treatment with antibiotics does not help. Loss of friendly microbes in the gut aggravate this. Infusion, made out of stool from a healthy donor, given like an enema helps in reconstructing the lost microbial world in the gut and that contains this drug-resistant disease. Such stool transplantation has been experimentally used even in other diseases like irritable bowel syndrome.  Everyday, scientists are discovering connections between microbiome and other diverse diseases like asthma in children, autism, arthritis and even cardiovascular diseases. In fact many people believe that improved sanitation in the West is reducing childhood exposure to microorganisms, tweaking their microbiome and making them more susceptible to various diseases.

Our journey with microorganisms starts in the mother’s womb. The process of birth also adds, as microbes present in the vagina get transfered.  In fact, microbiome of children born by cesarean delivery differs from those born by normal way. After the birth, a child's microbiome is shaped by the microbes present in mothers milk. Subsequently, it keeps changing with our food habits, environment, use of antibiotics, interactions with people and pets. The hidden world within us is dynamic and keeps interacting with us. Just like the ecosystem outside, our technology and lifestyle also affects the microbial ecology within.  The biology of this ecosystem is little known. For long we have been self-centered and have written our own travelogues. Now we are learning to recognize and appreciate these invisible co-passengers of our life. Surely you will love them as much you love the mole on your cheek.

Thursday, October 23, 2014

Trajectories in Open Access

Scientific research is a social endeavor and throughout the world, it is funded primarily by public money. Therefore, there should be no barrier to the knowledge developed through such research and it should be accessible to everyone. The primary sources of such knowledge are the articles published in scientific journals. So, to spread knowledge, these articles should be freely available to everyone. The Open Access movement, which is  spreading through the academic world, is preaching this philosophy.

In the current model of publication, researchers submit their articles to journals and the journals publish the selected few after peer-review. In this process, the author voluntarily transfers the copyright of the article to the publisher. The publisher does not pay the author. But the reader, whether a researcher or a layman, has to subscribe the journal to read it. That's what most of our libraries spend money on. Over the years, the subscription fees have ballooned to such an extent that even libraries in the developed world are falling short of their budget.  

The Open Access movement strikes at this very issue. It promotes two models, to achieve open access to published work. In the first, any body is free to access the journal over the Web. Such journals are called open access journals. For publication in such a journal, authors have to pay a article-processing fee. The cost for editorial manpower, formatting, typesetting and server management are covered by that fee collected from the authors. Over the years, number of open access journals has increased exponentially, with many having doubtful reputation. Even then, several open access journals are well respected for consistently publishing high quality work. Though such journals are promoting open science, article processing charges are often very high and prohibitive for researchers working in developing countries.

The other model, for open access, is creation of public funded open access digital archives for scientific papers. PubMed Central, developed by  U.S. National Institutes of Health's National Library of Medicine, is one such digital archive, where publishers or the authors voluntarily submit a copy of their articles. In fact, such submission has been made mandatory for every work funded by NIH of USA. Some other funding agencies are also promoting the same model. Anyone having an access to the Web can read all the papers stored in such archives. Such archiving does not violate the copyrights of most of the publishers, as authors submit only their copy of the final peer-reviewed draft without having any editing and formatting by the publisher. ResearchGate, a social networking site for scientists, also follows a similar model for sharing scientific articles.

Very recently, DBT and DST, funding bodies for scientific research in India, has released the second draft on their open access policy. They have proposed establishment of open access digital archives, in different institutions as well centrally. Any publication coming out of a work funded by these agencies must be deposited in such archives. Like other such archives, authors will deposit only their own copy of the final peer-reviewed draft. Interestingly, the proposed policy explicitly discourages author-paying model of open access journals and has made it clear that they would not provide financial support for article-processing fees. This makes sense, as article-processing fees of many journals are exuberantly high for most Indian labs. Additionally, this will also discourage spread of predatory journals, many of which are published from India.

It will be interesting to follow how India's open access policy shapes eventually. But for the time being, let me imagine the evolution of the publishing industry in the age of open access. The open access digital archiving makes sense for every country and most of the major players in science would eventually move to this model. But that may trigger a trouble. A publisher takes care of peer-review, editing, formatting and publishing. They charge the fee to the reader or the author to cover the expenses for this process. The final published articles are usually smartly edited and eye candies to readers. The authors copy of the final draft deposited in open access archives are not adequately formatted but contains all the scientific contents. Therefore, though reading such a draft is bit cumbersome, but that does not affect the science. In fact, every scientist is well trained to read such drafts. If we get such final draft without any cost, why should we pay to read a well-formatted copy of the same, published by the journal? Obviously not. Eventually this will reduce the number of subscribers to such journals. So journals running on subscription based model will not survive in the world of open access. In fact all major publishers for science journal are offering some form of open access for their journals and testing the water. But we need publishers to manage the whole process of publishing scientific articles through peer-review. At least some one has to run the peer-review process and that also have a cost though the reviewers do not get paid. If the reader does not pay, the cost has to be covered by the author. And that brings us to author-paying model of current open access journals. Therefore, institutionalized discouragement to such journals may not be a good idea as we do not have an alternate model that will sustain in long run.

There is another model of science publishing. It involves post-publication peer review. In this, authors deposit articles that are published online without any peer-review. The readers can access those articles freely and can comment on those. In a variant of this model, the journal invites peers to review, once the paper is published online. arXiv, an open access server, publishes articles without peer-review and without any charges. However, it does not allow commenting or review by readers and in essence it is merely a repository.  Even then, this server is quite successful and authors regularly submit high quality articles, particularly in physics and allied subjects. Recently established PeerJ PrePrint archive is an attempt to replicate that for bio-medical sciences. It allows readers to review and comment in articles archived there. Most online journals also allows readers to comment on published peer-reviewed work. However, till now peer review by readers has not catch up the scientific world and very few readers express their opinion online. Even when they comment, those are not detailed like thorough peer-review. Currently, post-publication peer-review by readers doesn't seems to be a viable option. Over-reliance on reader's opinion may also bring  the vices of social media in science publishing. In essence, the current practice of organized peer-review managed by editors is still the gold standard. In the age of open access,  quality peer-review can be sustained only through the author-paying model. Therefore, rather than rejecting author-paying model, we need to develop technologies to reduce the cost of running the show and have to establish some peer-based mechanism to regulate this industry to maintain high standards.

Sunday, October 05, 2014

Why I may ditch the official Android App for Mendeley

In academics, you have to read regularly and have to read a lot. Online access to research articles made our life easy by making full-length research papers a click away. Gone are the days of photocopying and stacking articles in folders.  PDF files of research articles are easy to store, read, and annotate. But ease of access also increases number of papers that one downloads. As the number of papers in the hard disk crosses three digits, it becomes almost impossible to keep track of all those papers and keep those organized. This becomes more problematic if you have multiple interests. A document-cum-reference manager like Mendeley is essential to manage such large libraries. Mendeley is buggy, even after acquisition by Elsevier. Am habituated with its bugs. I use Mendeley to organize papers, with tags, notes and highlights. And am happy. But like many other Mendeley users, I had one long standing demand: to have Mendeley for Android.

In the age of tablets and phablets, users prefer to read papers in their handheld devices. It's very comfortable for me to lean back on a sofa and read a paper in PDF format in my tablet. Highlighting, marking and putting notes, on a PDF file, are easier when you use a touch-screen. Though Android exploded the market for tablets, Mendeley does not have an official Android App. There was lots of expectation that acquisition by Elsevier will lead to the release of one. Though there are news of its development, the App is not out yet. Video and screenshots of a working version of the App were shown in the recently held MDOD14. As per the announced timeline, we may expect the App to be available, for public use, some time in the next year. But even then, I expect that it will have one major limitation.

My network connection is not reliable and it's not always there with me. I prefer to have all the papers of my Mendeley library to be synced and stored in the SD card of my tablet. That's why I have a 32 GB card. This allows me to read these papers anytime, anywhere. Mendeley allows you to store PDF files in their own cloud. It’s free upto 2 GB and beyond that you have to pay. I believe the future Android App for Mendeley will be built around this cloud service. It may even allow one to download files in the device and keep those synced using the same Mendeley cloud. That's where is my trouble.

The size of my Mendeley library, with all PDFs, is already of ~3.5 GB. So I have to use a paid subscription to sync those using Mendeley. I already have a subscription for Dropbox, that I use to sync data files and official documents across multiple devices. Subscribing another cloud does not make sense for me. Additionally, Dropbox gives many options and flexibilities in file management. I want to stick to Dropbox. Therefore, an official Android App for Mendeley may not be suitable for users like me. I want to use the Mendeley but want to sync files using my Dropbox.

Fortunately there is a way out. Referey is an Android App that allows one to view and query a Mendeley database and open associated files stored locally in an Android device. I use the desktop version of Mendeley to create and update my library regularly. Mendeley creates a sqlite database file and keeps associated PDF files organized in a designated folder. I keep this folder and the database file synced with my Dropbox. These files can be now downloaded and auto-synced in my Android tablet using Dropsync. Bingo!! Now I can use Referey to explore my Mendeley database, search papers based on my tags, authors, keywords, journals, year of publication and read the associated PDF files, even in absence of any network connection. As I read those papers, I annotate them and once I have the network, Dropsync syncs those annotated PDF files with my Dropbox.

There are a few more unofficial Android App for Mendeley. But none have the ability to access and read files stored locally. Referey is minimalist and has a very amateurish interface. It does not have any inbuilt PDF reader and you should have one installed separately. Unfortunately, it does not allow editing of the database. That means you can not add any new tag to  a paper. Even then I am happy with it, as it allows me to work offline. And honestly, am not dying to get an official Android App for Mendeley.

Update: Recently purchased a Xiaomi Mi Pad running MIUI, based on Kikat. A tab is perfect for reading papers. Unfortunately, while trying Referey-dropbox-dropsync combination in this tab I met an obstacle. Thanks to Google for making life a bit difficult. From Kikat, Android does not allow third-party Apps to write to anywhere in external SD card. So even though I have a fat extrrnal SD card in my tab, Dropsync can not download all my reference PDF files to my SD card. Also Referey can not read the Mendeley sqlite database file from SD card. Thankfully there are way out. The sqlite file is small. So I kept it in the inbuilt storage of the tab. But I have kept the PDF files synced in the SD card, by a simple trick. The trick is here.

Tuesday, September 09, 2014

Critical reading of science is the critical need of this time

It is often said that the peer-review process of scientific articles is broken (1). The clamour is more in the field of biology and allied sciences. Retractions of some high profile (2) and not so-high profile papers (3) make a case for introspection on the whole peer review process. It is not that every other article is fraudulent or sloppy.  Even then, individuals doing review of a manuscript must take utmost care to read, analyse, and vet upon the quality, and originality of a work. That's the prerequisite of the culture of peer-reviewed scientific literature.

But we, individual scientists and readers of published articles are supposed to be post-publication critics. Careful reading and analysis of evidences and arguments of a article are essential for further development of science. In fact, peer-review of manuscript by anonymous subject-experts was not always there in scientific publishing. Several path-breaking papers, like Einstein’s paper on relativity (1905), and Watson and Crick’s paper on the structure of DNA (1953), were published without pre-publication peer-review the way we know it today (4). Such papers stood the test of time as hundreds of readers repeatedly read and critically analysed those, post-publication. Are you maintaining that tradition of critical reading? Do we carefully scrutinize published data and the inferences drawn from those? Unfortunately not always. And it seems critical reading of articles are becoming old-fashioned in our culture. The time is over when one used to wait for issues of well-established journals and browse through every page of those, in the library. Number of journals, and the number of articles published every day has increased exponentially. Online publication of journals have increased accessibility, but seer increase in publication volume has reduced our attention span for articles. Though e-mail alerts, tweets, posts in Facebook help to keep track of path-breaking articles, detailed study of a paper, in leisure, is becoming rare. Most of the time, we put a paper under microscope, only when it challenges our own ideas or results or the paper is published by our competing research group. We put efforts to teach our students experimental techniques and data analysis. However, we rarely teach them, systematically, how to read and analyze published articles. Journal clubs organized in many institutions gives opportunity to learn critical reading. However, such occasional events are not enough to systematically inculcate the culture of critical reading of science.

Lack of emphasis on critical reading is evident in different forms. Many a time, a published article is cherry picked, and referred, without thorough evaluation, just because it helps one to substantiate a claim. Such practice is common in articles related to molecules involved in diseases like cancer. Authors often refer published articles to substantiate possible involvement of a gene in various types of cancers without giving adequate thought over the quality of data and inferences in those referred papers. And that cycle goes on from one publication to another. Erroneous use of back-references happens frequently in use of statistical and mathematical tools. Often such published tools are used inappropriately without giving thought about the assumptions and premises mentioned in the original article. Even erroneous work get referred, copied and used repeatedly to make newer claims.

It seems, we have culturally accepted that  anything written in a peer-reviewed journal is khoser. Not just in literature, even in meetings, scholars often avoid putting up arguments and use back-references to justify their work. Back-references are essential as we do not want to reinvent wheel every day. But the culture of surrender to anything written in black-and white goes against the basic tenet of science.

Skepticism is at the heart of science. As Michael Shermer said, " Science begins with the null hypothesis, which assumes that the claim under investigation is not true until demonstrated otherwise" (5). This applies not just to statistical analysis of our data. This should be applied even when we read a published work. One should not accept the conclusions of a work just because it's published. Rather one should read the paper with skepticism, evaluate quality of data, analyze those and dissect the arguments provided by the authors.  The data and logic, presented there, should eventually be able to clear all the apprehensions of the reader.  Therefore, reading has to be dialectic.

Such critical reading enhances post-publication scrutiny. Traditionally, printed journals publish critics of published articles in form of letter to editor. Commenting on published work got easy with the advent of online publication. Various online forums has emerged to for post-publication scrutiny. PubMed Commons is a new addition to that. Critical review and online discussions have helped to discover several fraudulent publication. The recent controversy over STAP cells and subsequent retraction of the paper, is a hand-on example of success of post-publication critical review.

It is true that most of the papers will not get such extensive public scrutiny. Most of us are also not Internet-savvy and will not ever comment in public about a paper. However, we can focus on critical reading of papers in our field, particularly when we use those in our own research. Being individual we can take certain initiative to stop social acceptance and spread of sloppy or fraudulent papers. We can start with some basics:
a) Let us make sure that we refer to a paper in our manuscripts if and only if we have read that paper thoroughly and critically.
b) Let us avoid referring to review articles in our manuscripts and read the original research articles and refer those. This would avoid spread of any mistake or misinterpretation made by the author of the review article. At the same time the original research article would also get scrutinized once again.
c) Let introduce courses on writing and critical reading of scientific literature for  our PhD students. Such course should introduce students to topics like data analysis, logic, and methods of drawing inferences. Through out their schools and colleges, most students learn to follow text books, like blind faith. Learning to question words, written in black-and-white, is not easy for them. We need to encourage them to do so and make it a habit than exception. Let us first make them skeptics, then scientists.


1. Healey, N. The Problem with Peer Review. Laboratory News, March 22, 2013

3. IMTECH: CSIR scientist used faked data in seven papers. The Hindu, July 17, 2014

4. Baldwin, M. Is the Peer Review Process for Scientific Papers Broken? Time, April 29, 2014

Wednesday, July 30, 2014

Why iPad is unproductive for me

Ok! Here am back again with anti-iPad ranting. Last time, I wrote at length why I dislike iPad. That was just after I purchased my iPad 2. That's  long back. iPad has got updated, though the main complain on file structure still remains.
Even then, I thought to be rational and unbiased. I need a tablet for my work. Being an experimental biologist, I want to use the tablet for productivity: search and surf web, read books, read papers (pdf files) and comment on those,  take help of my reference management tool Mendeleye, read documents and edit those (MS Word, PowerPoint, Excel), look into my experimental results (all either MS Office files or images). I want all these files neatly synchronized between my office desktop and the tablet. And I should be able to work on these files offline too, as that's my status most of the time when am not in office.

With all these in mind, I was looking into different Android tablets. Am using Android for long and I meet all these productivity requirements with my Android phone (and a Micromax rudimentary tab). But I gave a second thought, to get away from the 'fixation' with Android. So comes iPad mini. It's 7.9 inch screen is good for me. It's light weight but well built. I could comfortably hold it in one hand while working. It's super smooth and battery life is much better than an Android device.

So I looked back to my iPad that has been hijacked by my daughter. And tried to check for my requirements. With last update and recent apps, iOS allows me to do almost all the way I want. But it still suffer from the the problem of file handling. In office, I use MS Windows. My files are organized in folders and subfolders with suitable names.  All the important  folders are autosynced with my Dropbox. I want all these files and folders autosynced in my tablet too. And the autosync should be two way. So, if I do some editing on a file in the tablet, I should get that updated file in my desktop too. And all these without disturbing the folder architecture that I am using in desktop. I already have this in my Android devices. With such synchronization, the Android phone in my pocket is essentially a smaller version of my office desktop. Don't bother about memory, I use a fat external SD card. Unfortunately, I can not achieve these in an iPad (mini). The Dropbox app in iPad does not allow two-way autosync of folders. You can use another app Documents to achieve autosync for Dropbox. But it can work two-way only when you open and edit the file within this app. That means if I comment on a synced PDF file, using Adobe PDF reader in iPad, that will not get autosynced in my Dropbox and my desktop. Android has no such limitations. I keep folder synced in the external SD card. Just like a desktop, I can access those files using any file explorer of my choice and open and edit using suitable app of my choice. Any modifications gets autosynced in all machines through Dropbox. That's call productivity.

Sorry iPad (mini), you are still an entertainment device and I will go for an Android tab.