Small samples: A statistician’s nightmare

Posted on 28 Jul 2017 by Subhra Priyadarshini

What happens when a statistician is handed over a sample size of one?

Poulami Barman, a statistician at Mayo Clinic, USA faced a similar challenge while working on a prostrate cancer trial. In this guest blog piece, Poulami writes about her journey from Vellore Institute of Technology (VIT) in India to the premier US lab, how she handled the transition and the uniqueness of working on a sample size of one.

Poulami Barman

Never settle

Till high school, I was this nerd who loved both math and biology. After 12th grade, I realised I was not “nerd enough” to pursue a career in biology and decided to go the math route. I wanted the best of both worlds and chose biotechnology for a major in undergrad — it slowly became clear to me that I was wired more towards the math equations and didn’t enjoy the biology side that much. With little career advice, I thought a complete change in major was not possible, and hence got into a Masters in Bioinformatics in the US.

During the first year of grad school, all my nightmares came alive in the form of coding and the biology knowledge needed for course work. The culture shock did not make it easy and I was almost dropping out of school but stayed on when my father insisted. I got an internship at a reputed hospital — that further exposed my weak coding skills. The turning point, however, came when I got an assistantship with Dr. Yolande Tra. She recognised my skill in statistics and encouraged me to take more courses in this field.

Under Dr. Tra’s mentorship, I aced in statistical analysis class which helped me land my first full-time job as a Clinical Data Analyst at Johnson & Johnson. My excitement did not last long, as I soon realised that the job involved a lot of coding and not much statistics. I did not like the monotony of the job and decided to go back to school, but this time to get a second masters in statistics. I moved to Texas A&M University – where I enjoyed working 14-16 hours a day and realised what passion actually meant. I got a job at Mayo Clinic after Masters, and there was no looking back. I never settled for a career until I had exactly what I wanted.

Statistics in medical science

With the growing complexity of biological data and disease biology, clinicians are leaning more towards personalised care therapies. The field of oncology is no stranger to this. 4 years ago, I got involved in one such study to recruit stage IV prostate cancer patients that are castrate resistant and to find specific markers that cause drug resistance. This was to be done by sequencing their genomic data before and after Abiraterone acetate/prednisone (AA/P) treatment. The presence or absence of markers could then decide the treatment regimen for the patients.

Data was collected with trials on mice injected with tumour cells from patients. Various treatment combinations were tested on the mice models. It was like having parallel patient avatars built from mice. A similar trial was conducted at Mayo Clinic on breast cancer patients. I was lucky to be involved in both these projects at some point. This is one of the best perks of being able to work in this specific role.

The pet peeve of all statisticians is a small sample size. And I was asked to provide inferences with just one sample! The analysis needed to focus more on gene-set within patient comparisons or one-vs-many control comparisons. The ideas was to learn the association of time-to-treatment change. We found that in metastases, Wnt/β-catenin pathway activation is associated with primary AA/P resistance and increased CCP with acquired drug resistance.

It has been a unique study in many ways, and to name a few; it provided a mutational genomic landscape for metastatic prostate cancer; mice models of metastatic prostate cancer (which has never been done before); and a stepping stone to single sample (n=1) analysis. The findings from the PROstate Cancer Medically Optimized Genome Enhanced ThErapy (PROMOTE) study was recently reported in PLOS One in 2015.

Bending the rules

Being involved in interesting and challenging projects like this one, and being paid to do what I love is a dream come true. The first couple of years at Mayo, I suffered from the Imposter Syndrome. I was working closely with researchers, and highly qualified people, and only 2 masters without a doctorate seemed petty. Don’t let the misconception of requiring a doctorate to pursue a career in research deter you. As long as one has the persistence and the penchant for it, research need not be sour grapes.

From an unsure novice in the US to someone who works with the best researchers in her field, I have grown a lot. And it was not a straight line; in fact, it was the worst and the best roller coaster ride I have ever taken. Every time I see someone eating street food at 2 a m in a Bollywood movie, and every Dushera, I miss home terribly. But, I think I have made a home for myself here — a small group of friends, and if I had to call any place home, other than Kolkata, it would be my Texas family. I met my husband and now have a sweet little family here in Rochester MN.

Ageism in academic jobs in India

Posted on 20 Jul 2017 by Subhra Priyadarshini

Let’s talk career with Naturejobs

Every now and then, Indigenus brings you some interesting and relevant posts from sister blog Naturejobs, a leading online resource for scientists in academia and industry who seek guidance in developing their careers. The blog delivers a mix of expert advice and personal stories to help readers review, set and achieve their career goals.

Today we have Farah Ishtiaq, a Wellcome Trust/DBT India Alliance Intermediate Fellow at the Centre for Ecological Sciences, Indian Institute of Science, Bangalore. Her research explores the ecology and evolution of vector-borne diseases — the role of migration, host immunity, vector genetics, and climate change on malaria transmission in high-altitude Himalayan birds.

Farah shares her experience on how age and success are linked in acquiring faculty positions in India.

Farah Ishtiaq

India has recently been portrayed as a land of abundant opportunity in academia, investing seriously in research and development to attract skilled scientists. The government has introduced several attractive funding opportunities, with the aim of bringing back scientists working abroad to establish a long-term career here, and improving the overall research infrastructure. Wellcome Trust/DBT India Alliance (WT/DBT) fellowships, for example, have no age or nationality restrictions, relying on qualifications, research experience, career trajectory and the candidate’s determination to establish their own independent research.

WT/DBT India alliance was initiated to develop a large cohort of internationally competitive researchers and help in developing scientific excellence and leadership; a model recently adopted and launched by the Alliance for Accelerating Excellence in Science in Africa (AESA) as well. Since Africa shares a similar burden of healthcare with India, as well as many workplace challenges, Indian scientists are perceived as key collaborators in this mission.

There’s a problem here though: age limits on academic positions. Prospective candidates for assistant professor in India are preferred by academic institutions to be younger than 35. Although funding bodies are not hiring agencies, the age limit imposed on faculty positions by academic institutions sabotages the driving principle behind these new funding opportunities — the current system is unable to absorb enough competent, experienced scientists.

The dilemma for early-career researchers is serious; many fellows are facing this harsh reality and an uncertain future. Every research position has a maximum age limit in India; from a junior research fellow (JRF), with a cut off at 28 years old, to postdoctoral researchers where it is 35 (or 40 years for women). These limits put the Indian academic landscape in stark contrast with many other countries that also follow a tenure-track system.

A Nature special issue in 2015 explored some of the unique opportunities – and the unique problems – of working as a scientist in India

Overall, this makes India a viable option and destination only for scientists of a selected age class. And it certainly gets more complicated for women who want to pursue a career in science and raise a family, with very little allowance made for taking time out for such.

I am now in my vigorous 40s, which prevents me from being offered an entry-level faculty position. I am also a recipient of a WT/DBT India Alliance fellowship. My funding allowed me to establish an independent laboratory to study the ecology and evolution of emerging infectious diseases in wild bird populations, but despite this incredible research opportunity, I feel my career clock is ticking faster than ever. Getting funding to do science is no longer a problem, but academic policies that prevent competent scientists becoming established are preventing me from succeeding. I feel redundant — surely the quality of my science should be the focus rather than my age?

What I would have done differently

Hopefully, this should give others like me some insight on avoiding some of the mistakes I made. First, I should have found a trust-worthy mentor who could have helped me to navigate my career path.

Never put all your eggs in one basket. I should have pitched my grant idea to multiple host institutions to maximise my likelihood of finding an institution that would guarantee a more permanent position by this stage.

Do your homework in understanding the system and host academic institution. Even though I deferred my fellowship for a year as my daughter was too little to be left in a crèche, I realise I should have used that time to negotiate or better understand the policy or the institute’s vision for a research fellow like me. Many academic institutions have no guidelines on the role, involvement and career development of academic fellows.

Many academics fail to understand the role and potential of fellows like me and often consider them just as an extended postdoc — not as a long-term prospect or potential collaborator. Hence, I did not get enough of an opportunity to teach and to mentor PhD students. Having my own PhD students would have bolstered my career at this stage, and allowed me to evolve as a mentor.

Local advice & mindset

I’ve received various pieces of advice for improving my faculty application and to enhance my chances of a secure job — this was to publish my current research: i) without foreign authors; and ii) as senior or first author in more prestigious journals such as Science, Nature or PNAS. Whilst the first is possible, the second is easier said than done.

Apparently, that was the only thing my CV was missing — a clearer demonstration of my calibre and merit as an independent researcher. Interestingly, for established faculty struggling to earn tenure in India, the culture emphasises quantity of publications rather than quality.

And, whilst the second piece of advice (primarily from engineers, cell or molecular biologists) is sound, what was missing was perspective on research in the field of ecology — collecting and publishing groundbreaking ecology data in top journals can take years longer than other disciplines. The journals I have been publishing in are not familiar to some of the members of recruitment panels I’ve met with. I have even been asked if ‘Ibis’ and ‘Parasites & Vectors’ were proper journals.

Should India be a role model for developing nations?

We are struggling to keep our skilled workers, despite the spending per researcher being equivalent to a developed nation like the UK. I hope other developing countries don’t replicate the above policies, as they certainly don’t help to address some of the major longer-term developmental challenges, including a shortage of researchers. In India, with only 200,000 full time researchers (and only 14% of them women) from a population of 1.3 billion, new research institutes currently being developed end up short of skilled workers and blinkered to new research areas.

This all said, I am still very excited. I have a competitive edge and enthusiasm for research where I can play a leading role in high-quality research. Perhaps, it’s time to explore science career options elsewhere, maybe in Africa, and hope no one will question my age?

Away from home: Collaboration in a global organisation

Away from home: ‘Research not Nobel-driven’

Do you hear me?

Posted on 19 Jul 2017 by Subhra Priyadarshini

An innovative and affordable infant hearing screening device was launched in New Delhi this week. Nature India intern Kate Telma, from the Graduate Program in Science Writing at the Massachusetts Institute of Technology (MIT), attended the launch and came back educated about the significance and necessity of auditory screening for newborns.

Here’s her guest post about the device Sohum, whose name comes from Vedic philosophy – the Sanskrit meaning closely reflecting the Universe’s response to a child’s first cry.

“The most important thing is to screen babies — on time — no matter where they are born,” says Nitin Sisodia, the founder and CEO of Sohum Innovation Lab, a market-driven solutions firm that works to improve the health and incomes of people living in resource-poor settings.

Sisodia and his team of designers, engineers, & business people are now focused on spreading awareness around hearing loss, testing infants and creating an army of training audiologists to do the job. Their newborn hearing screening device Sohum measures an auditory brainstem response, considered the gold standard in auditory testing. Designed for mass screening, the test takes only 90 seconds and can be performed on an infant who is awake.

Sisodia is a 2010 School of International Biodesign (formerly Stanford India Biodesign) fellow, and was chosen to represent one of the 35 startups to visit the Silicon Valley with India’s Prime Minister Narendra Modi in 2015.

The device was developed with support from the Department of Biotechnology and mentorship from AIIMS, IIT Delhi, and Stanford University. Launched July 17 in New Delhi, it is the fourth product to come from the School of International Biodesign programme (SIB), an initiative that focuses on innovative, low-cost, ‘Made in India’ technologies and devices. Other successful products include Qora, a fecal incontinence management system that debuted in India last year.

{credit}Karthikeyan Gopinathan{/credit}

Each year, 800,000 babies are born with hearing loss — 100,000 of them in India. Roughly 90% of children with hearing impairments in the first month of life are born in low- and middle- income countries. Children in these settings are also more likely to have ear infections or meningitis, other causes for hearing loss that contribute to compromised education and employment later in life.

Ideally, hearing deficits would be detected by three months of age; by six months, the child is fitted with hearing aids or cochlear implant. Currently, hearing loss is diagnosed around age 4, and often much later. Most times, this is too late for effective intervention.

The lack of newborn screening in India has been a concern. While nearly all infants born in the US are screened, and more than 33 European countries have nation-wide screenings in place, majority of hospitals in India do not offer any hearing screening.

Sohum is easy to handle. Even semi-skilled healthcare workers can easily interpret the simple read out of “pass,” “refer,” or “redo”. Data is sent to remote audiologists for verification, and added to a central data bank. The device also functions well in noisy settings, performing with 100% sensitivity in 60 decibels — about the noise level of a busy classroom or restaurant.

The device is expected to be made available to hospitals and primary care centres across India, with plans to reach out to maternity centres and vaccination camps to screen babies born at home. Balram Bhargava, the SIB executive director had a word of advice for the Sohum team. “You will have to manufacture fast,” he said, because the need and demand are clear.

Harvesting water from dry air

Posted on 12 Jul 2017 by Subhra Priyadarshini

A team of researchers in the US made headlines some time back by developing a device that can extract potable water from ambient air¹ using only sunlight as the source of energy. K. S. Jayaraman got curious on how that could work for India. He spoke to Sameer Rao, an Indian postdoc involved in the project at the the Device Research Laboratory of Massachusetts Institute of Technology (MIT), and Omar Yaghi, who led the project at University of California, Berkeley.

Here’s Jayaraman’s guest post on the solar-powered water harvester and implications for India.

This is almost reminiscent of the famous magic trick — the “Water of India” — which India’s legendary magician P C Sorcar Jr. performed without fail in each of his stage shows. He would wave his hand in thin air, say the magic words in his characteristic style and, “by magic”, an empty jug kept on the table would constantly fill itself up. Again and again.

Now, a new research promises a potential new technology for harvesting drinking water from this hitherto neglected source – air.

Atmosphere actually contains an estimated 13,000 trillion litres of water – equivalent to nearly 10% of all fresh water present in lakes worldwide – that remains untapped. A solar-powered water harvester, which the MIT-UC Berkeley team has built, works even when relative humidity (RH) is as low as 20%, the level common in arid areas and deserts of the world.

Sameer Rao tells me their device could work well in most parts of India. Large scale use of this device can change the landscape of water utilisation in India where sunlight is abundant, Rao, a post-doctoral associate in Evelyn Wang’s lab at MIT says. The heart of the new device is a metal-organic framework (MOF) that belongs to a class of unique materials exhibiting extremely high porosity that Yaghi’s team had pioneered in the 1990s at Berkeley.

Yaghi, a chemistry professor at UC Berkeley and one of the research leads, calls this a major breakthrough in the long-standing challenge of harvesting water from the air at low humidity. “We used only ambient sunlight, with no electricity – this is a major improvement over most other air-water harvesting devices which require energy input, and therefore are economically not viable.”

MOF crystals are embedded in the copper sheet sandwiched between the solar
absorber and a condenser (in yellow).{credit}Evelyn Wang{/credit}

“They have high affinity to water molecules, to pull them out of ambient air, but do not hold on to them too tightly so that water can be concentrated and released with a slight temperature change (induced by sunlight),” Yaghi says. The adsorbed water thus released is then stored by the device in a condenser.

The adsorption-desorption experiments performed in a RH-controlled chamber in the laboratory found that the device was able to pull 2.8 liters of water from the air over a 12-hour period at RH levels as low as 20% using one kilogram of MOF. Roof top tests at MIT confirmed that the device works equally well outdoors. The scientists have found the experimental data to be in “good agreement” with a theoretical framework they had developed.

The quantity of harvested water can be scaled up by finding better MOF materials “with enhanced sorption capacity and high intra-crystalline diffusivity” that could absorb more water. The current MOF can absorb only 20 percent of its weight in water. Evelyn Wang, who led the MIT team says they “continue to improve the harvesting system to produce more water..”

“…If you are cut off somewhere in the desert, you could survive because of this device,”Wang says.

The developers hope their device, when commercialised, could help every household obtain drinking water it needs out of the air using only the power of the sun.

Rao particularly feels the social impact of this in India would be far-reaching. “It would enable greater success for government’s grass-root level programmes seeking to increase literacy and education of women and children in villages as they would get more time not having to travel long hours to fetch water from far off reservoirs for cooking and drinking.

How much would the solar water harvester cost? “We have made the significant first step by building the demonstration model combining chemistry and engineering to show how it works,” Yaghi says. “The economic aspects as well as the production of these materials and devices are the obvious next step.”

Kim, H. et al. Water harvesting from air with metal-organic frameworks powered by natural sunlight. Science. doi: 10.1126/science.aam8743 (2017)

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