Archive for August 2014
Valorisation of food residues: waste to wealth using green chemical technologies
Corresponding author: Emerson L Schultz emerson.schultz@embrapa.br
Embrapa Agroenergy, Parque Estação Biológica, PqEB s/n – Av.W3 Norte (final), Brasília, 70770-901, DF, Brazil
Chemical and Biological Technologies in Agriculture 2014, 1:7 doi:10.1186/s40538-014-0007-z
Abstract
According to estimates from the International Energy Agency, global energy consumption will increase by at least one third, between 2010 and 2035. The additional power required will be provided not only by fossil sources but also by renewables. While the world energy matrix is supplied only by 13.2% from renewable sources, Brazil has different scenery with renewables accounting for 42.4% of the energy matrix. This work aimed to evaluate the potential use of oleaginous in biorefineries considering the produced quantity, prices, and costs of raw materials and products. Considering the availability of these raw materials, the results showed significant opportunities that can be exploited in Brazil, within the biorefinery concept. Soybean oil is the main raw material for biodiesel production in Brazil, although there are many other vegetable oils with potential for this purpose. Related to the production costs, the soybean biodiesel has higher costs than diesel. Then, this biofuel is only produced due to Brazilian regulatory rules and public subsidies. In order to become this production favorable in the market environment, it is essential to aggregate value to all byproducts and residues generated along the biodiesel production chain. Glycerin is a byproduct of biodiesel that could be used, in a glycerol biorefinery concept, as raw material for the production of value-added products through chemical, biochemical, or thermochemical routes.
Keywords: Biorefinery; Oleaginous; Soybean; Biodiesel; Glycerin; Biofuels; Chemicals; Energy; Prices and costs
The electronic version of this article is the complete one and can be found online at: http://www.chembioagro.com/content/1/1/7
image source: Texas A&M And University of Arkansas Work Cooperatively To Improve Soybean Crops
Embrapa Agroenergy, Parque Estação Biológica, PqEB s/n – Av.W3 Norte (final), Brasília, 70770-901, DF, Brazil
Chemical and Biological Technologies in Agriculture 2014, 1:7 doi:10.1186/s40538-014-0007-z
Abstract
According to estimates from the International Energy Agency, global energy consumption will increase by at least one third, between 2010 and 2035. The additional power required will be provided not only by fossil sources but also by renewables. While the world energy matrix is supplied only by 13.2% from renewable sources, Brazil has different scenery with renewables accounting for 42.4% of the energy matrix. This work aimed to evaluate the potential use of oleaginous in biorefineries considering the produced quantity, prices, and costs of raw materials and products. Considering the availability of these raw materials, the results showed significant opportunities that can be exploited in Brazil, within the biorefinery concept. Soybean oil is the main raw material for biodiesel production in Brazil, although there are many other vegetable oils with potential for this purpose. Related to the production costs, the soybean biodiesel has higher costs than diesel. Then, this biofuel is only produced due to Brazilian regulatory rules and public subsidies. In order to become this production favorable in the market environment, it is essential to aggregate value to all byproducts and residues generated along the biodiesel production chain. Glycerin is a byproduct of biodiesel that could be used, in a glycerol biorefinery concept, as raw material for the production of value-added products through chemical, biochemical, or thermochemical routes.
Keywords: Biorefinery; Oleaginous; Soybean; Biodiesel; Glycerin; Biofuels; Chemicals; Energy; Prices and costs
The electronic version of this article is the complete one and can be found online at: http://www.chembioagro.com/content/1/1/7
image source: Texas A&M And University of Arkansas Work Cooperatively To Improve Soybean Crops
The Kardashian index: a measure of discrepant social media profile for scientists
Correspondence: Neil Hall neil.hall@liverpool.ac.uk
Centre for Genomic Research, University of Liverpool, Liverpool L69 7ZB, UK
Genome Biology 2014, 15:424 doi:10.1186/s13059-014-0424-0
Abstract
In the era of social media there are now many different ways that a scientist can build their public profile; the publication of high-quality scientific papers being just one. While social media is a valuable tool for outreach and the sharing of ideas, there is a danger that this form of communication is gaining too high a value and that we are losing sight of key metrics of scientific value, such as citation indices. To help quantify this, I propose the ‘Kardashian Index’, a measure of discrepancy between a scientist’s social media profile and publication record based on the direct comparison of numbers of citations and Twitter followers.
The electronic version of this article is the complete one and can be found online at: http://genomebiology.com/2014/15/7/424
image source: http://oncirculation.com/2013/08/14/social-media-and-science/
Centre for Genomic Research, University of Liverpool, Liverpool L69 7ZB, UK
Genome Biology 2014, 15:424 doi:10.1186/s13059-014-0424-0
Abstract
In the era of social media there are now many different ways that a scientist can build their public profile; the publication of high-quality scientific papers being just one. While social media is a valuable tool for outreach and the sharing of ideas, there is a danger that this form of communication is gaining too high a value and that we are losing sight of key metrics of scientific value, such as citation indices. To help quantify this, I propose the ‘Kardashian Index’, a measure of discrepancy between a scientist’s social media profile and publication record based on the direct comparison of numbers of citations and Twitter followers.
The electronic version of this article is the complete one and can be found online at: http://genomebiology.com/2014/15/7/424
image source: http://oncirculation.com/2013/08/14/social-media-and-science/
Creativity from Hong Kong arrives KickStarter - Umbrella Here - Light up your umbrella for sharing
Forget bringing an umbrella is not uncommon in Hong Kong. In Singapore, all taxi will be occupied and you will be trapped together with hopeless. I believe this will be the same case in your city. Let's take a look how this Hong Kong's innovation helps solving this problem.
Umbrella Here - Light up your umbrella for sharing
"Umbrella Here is a light that can be attached on an umbrella. It is controlled by a mobile app that tells people that this umbrella is available for sharing. Just like the light you would see on a taxi. When the light is on, it represents that strangers are welcome to come in and share your umbrella."
I hope this really help.
Learn more about this invention: http://www.umbrellahere.com/#design
Tag :
kickstarter,
startups,
Methane hydrate from the ocean
There is an article from NBC this morning "Climate Bomb? Methane Vents Bubble on Seafloor off east Coast: Study". It reports the possible methane leakage at the Altantic Ocean along the U.S. East Coast. The phase "Climate BOMB" caught my eyes. Definitely, on the bright side, scientists and engineers have been trying to catch this "BUBBLES" for our daily energy consumption.
Here is another article suggested about methane hydrates from BBC:
Methane hydrate: Dirty fuel or energy saviour?
Here are brief summaries about methane hydrates:
Climate change impacts on methane hydrates [worldoceanreview.com]
Methane Hydrates and Contemporary Climate Change [Nature.com]
Towards Safer, More Comfortable Living through Shimizu's Sustained, Long-Term Research Efforts [www.shimz.co.jp]
More about Methane Hydrate on Youtube:
Methane hydrate the clean fuel of the future?
Japan successfully extracts gas from offshore methane hydrate
Did Methane Cause Mass Extinction? HD
image source: www.oilfreefun.com/2013/02/methane-hydrate-releases-geoengineering.html, www.nature.com/scitable/knowledge/library/methane-hydrates-and-contemporary-climate-change-24314790
A stamp collection celebrating the International Year of Crystallography 2014
Interesting stamp collection about international year of crystallography
Portugal
Switzerland
Slovak
Belgium
Israel
India
Moldavia
Liechtenstein
Austria
UK
Image source: PDB, http://www.iycr2014.org/
Crystallography? maybe a photo competition helps to explain crystallography in your daily life
Do you know what is crystallography? Do you the year 2014 is the International Year of Crystallography 2014?
If you don't know what is crystallography, the follow articles are suggested:
Crystallography: Atomic secrets, NATURE
More on Youtube:
Celebrating Crystallography - An animated adventure
Understanding Crystallography - Part 1: From Proteins to Crystals
Understanding Crystallography - Part 2: From Crystals to Diamond
There are a lot of activities around to the world this year to celebrate the International Year of Crystallography 2014. A photo contest - Crystallography in Everyday Life - was completed successfully and the first prize was announced: Gingerbread Men and Ice Crystals won the Agilent Prize:
Want to see more:
image source: http://www.iycr2014.org/participate/photo-competition
A brain-inspired computer & a IBM chip with NO clock
See how IBM redefine information processing with a cognitive chip - TrueNorth.
"Unlike the prevailing von Neumann architecture—but like the brain—TrueNorth has a parallel, distributed, modular, scalable, fault-tolerant, flexible architecture that integrates computation, communication, and memory and has no clock."
features at a glance:
"The architecture can solve a wide class of problems from vision, audition, and multi-sensory fusion, and has the potential to revolutionize the computer industry by integrating brain-like capability into devices where computation is constrained by power and speed" - Dharmendra Modha, IBM Fellow
see more:
Introducing a Brain-inspired Computer
Brain Power
Cognitive computing
IBM Research Creates New Foundation to Program SyNAPSE Chips
image source: http://www.research.ibm.com/articles/brain-chip.shtml
"Unlike the prevailing von Neumann architecture—but like the brain—TrueNorth has a parallel, distributed, modular, scalable, fault-tolerant, flexible architecture that integrates computation, communication, and memory and has no clock."
features at a glance:
- One million individually programmable neurons--sixteen times more than the current largest neuromorphic chip
- 256 million individually programmable synapses on chip which is a new paradigm
- 5.4B transistors. By device count, largest IBM chip ever fabricated, second largest (CMOS) chip in the world
- 4,096 parallel and distributed cores, interconnected in an on-chip mesh network
- Over 400 million bits of local on-chip memory (~100 Kb per core) to store synapses and neuron parameters
"The architecture can solve a wide class of problems from vision, audition, and multi-sensory fusion, and has the potential to revolutionize the computer industry by integrating brain-like capability into devices where computation is constrained by power and speed" - Dharmendra Modha, IBM Fellow
see more:
Introducing a Brain-inspired Computer
Brain Power
Cognitive computing
IBM Research Creates New Foundation to Program SyNAPSE Chips
image source: http://www.research.ibm.com/articles/brain-chip.shtml
Article Collection: Spotlight on Breast Cancer
Guest edited by Debu Tripathy tripathy@med.usc.edu
University of Southern California, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, NTT-3429, Los Angeles 90033, CA, USA
This article collection in BMC Medicine aims to highlight the latest progress in breast cancer risk profiling, detection and treatment, as well as the long-term issues faced by those surviving breast cancer. We are seeking submissions of research articles covering all areas of breast cancer medicine, including clinical studies of new therapies, molecular genomics and translational advances. If you have any research you would like us to consider for inclusion in this article collection, please email bmcmedicineeditorial@biomedcentral.com.
"Breast cancer is the most common cancer type in women worldwide, with around 1.5 million new cases diagnosed every year. Despite the high incidence, advances in detection and treatment in recent years mean that more women than ever are surviving breast cancer, with an 89% 5-year survival rate in Western countries. Although men can also be affected, male breast cancer is very rare, accounting for less than 1% of all cancer in men.
Advances in molecular subtyping of breast cancer and the development of targeted therapies have greatly impacted breast cancer survival rates, and many clinical trials are now underway to determine the best therapeutic strategy for those with different types of breast cancer, as well as in the pre- and post-surgical setting. Although breast cancer risk increases greatly with age, around 7% of all cases occur in women under 40, and there are unique issues facing younger women with breast cancer, such as long-term treatment effects and the impact on fertility. As people are living longer with breast cancer, clinicians are increasingly recognizing the impact of disease prognosis and treatment on quality of life, with ongoing efforts aimed at defining the optimal treatment strategy for individual patients."
Forum
Next generation sequencing and tumor mutation profiling: are we ready for routine use in the oncology clinic?
Debu Tripathy, Kathleen Harnden, Kimberly Blackwell, Mark Robson
BMC Medicine 2014, 12:140 (12 August 2014)
Minireview
Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials
Pernelle Lavaud, Fabrice Andre
BMC Medicine 2014, 12:132 (12 August 2014)
Question and Answer
Advances in treating HER2-positive breast cancer: an interview with Sunil Verma
Sunil Verma
BMC Medicine 2014, 12:129 (12 August 2014)
Opinion
Do statins increase and Mediterranean diet decrease the risk of breast cancer?
Michel de Lorgeril, Patricia Salen
BMC Medicine 2014, 12:94 (5 June 2014)
Commentary
Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors
Michel de Lorgeril, Patricia Salen
BMC Medicine 2014, 12:54 (27 March 2014)
Minireview
Molecular determinants of context-dependent progesterone receptor action in breast cancer
Christy R Hagan, Carol A Lange
BMC Medicine 2014, 12:32 (20 February 2014)
Commentary
Understanding breast cancer stem cell heterogeneity: time to move on to a new research paradigm
Ferdinando Mannello
BMC Medicine 2013, 11:169 (23 July 2013)
Minireview
Genetic heterogeneity in breast cancer: the road to personalized medicine?
Richard D Baird, Carlos Caldas
BMC Medicine 2013, 11:151 (21 June 2013)
Question and Answer
Video Q&A: molecular profiling of breast cancer
Carlos Caldas
BMC Medicine 2013, 11:150 (21 June 2013)
Original Page: Spotlight on breast cancer
Image source: Breast Cancer Revelation: Other Hormone Receptors Could be Targeted for Novel Therapies
University of Southern California, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, NTT-3429, Los Angeles 90033, CA, USA
This article collection in BMC Medicine aims to highlight the latest progress in breast cancer risk profiling, detection and treatment, as well as the long-term issues faced by those surviving breast cancer. We are seeking submissions of research articles covering all areas of breast cancer medicine, including clinical studies of new therapies, molecular genomics and translational advances. If you have any research you would like us to consider for inclusion in this article collection, please email bmcmedicineeditorial@biomedcentral.com.
"Breast cancer is the most common cancer type in women worldwide, with around 1.5 million new cases diagnosed every year. Despite the high incidence, advances in detection and treatment in recent years mean that more women than ever are surviving breast cancer, with an 89% 5-year survival rate in Western countries. Although men can also be affected, male breast cancer is very rare, accounting for less than 1% of all cancer in men.
Advances in molecular subtyping of breast cancer and the development of targeted therapies have greatly impacted breast cancer survival rates, and many clinical trials are now underway to determine the best therapeutic strategy for those with different types of breast cancer, as well as in the pre- and post-surgical setting. Although breast cancer risk increases greatly with age, around 7% of all cases occur in women under 40, and there are unique issues facing younger women with breast cancer, such as long-term treatment effects and the impact on fertility. As people are living longer with breast cancer, clinicians are increasingly recognizing the impact of disease prognosis and treatment on quality of life, with ongoing efforts aimed at defining the optimal treatment strategy for individual patients."
Forum
Next generation sequencing and tumor mutation profiling: are we ready for routine use in the oncology clinic?
Debu Tripathy, Kathleen Harnden, Kimberly Blackwell, Mark Robson
BMC Medicine 2014, 12:140 (12 August 2014)
Minireview
Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials
Pernelle Lavaud, Fabrice Andre
BMC Medicine 2014, 12:132 (12 August 2014)
Question and Answer
Advances in treating HER2-positive breast cancer: an interview with Sunil Verma
Sunil Verma
BMC Medicine 2014, 12:129 (12 August 2014)
Opinion
Do statins increase and Mediterranean diet decrease the risk of breast cancer?
Michel de Lorgeril, Patricia Salen
BMC Medicine 2014, 12:94 (5 June 2014)
Commentary
Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors
Michel de Lorgeril, Patricia Salen
BMC Medicine 2014, 12:54 (27 March 2014)
Minireview
Molecular determinants of context-dependent progesterone receptor action in breast cancer
Christy R Hagan, Carol A Lange
BMC Medicine 2014, 12:32 (20 February 2014)
Commentary
Understanding breast cancer stem cell heterogeneity: time to move on to a new research paradigm
Ferdinando Mannello
BMC Medicine 2013, 11:169 (23 July 2013)
Minireview
Genetic heterogeneity in breast cancer: the road to personalized medicine?
Richard D Baird, Carlos Caldas
BMC Medicine 2013, 11:151 (21 June 2013)
Question and Answer
Video Q&A: molecular profiling of breast cancer
Carlos Caldas
BMC Medicine 2013, 11:150 (21 June 2013)
Image source: Breast Cancer Revelation: Other Hormone Receptors Could be Targeted for Novel Therapies
Move a Paralyzed Fingers and Hand
It is amazing to see how the advancement in neuroengineering is now being implemented into medical surgery. This time, a tiny chip bring the signal from a user's brain to his paralyzed arm, bypass the damaged spinal code, and control the movement of his fingers:
"Ian Burkhart, a 23-year-old quadriplegic from Dublin, Ohio, is the first patient to use Neurobridge, an electronic neural bypass for spinal cord injuries that reconnects the brain directly to muscles, allowing voluntary and functional control of a paralyzed limb."
for details:
For the first time, a paralyzed man can move his fingers and hand with his own thoughts…
Watch Youtube:
image source: www.battelle.org, medicalcenter.osu.edu
"Ian Burkhart, a 23-year-old quadriplegic from Dublin, Ohio, is the first patient to use Neurobridge, an electronic neural bypass for spinal cord injuries that reconnects the brain directly to muscles, allowing voluntary and functional control of a paralyzed limb."
for details:
For the first time, a paralyzed man can move his fingers and hand with his own thoughts…
Watch Youtube:
Fields Medalist Announced in Seoul ICM 2014. Congratulation to all winners
There are four winners for Fields Medal in 2014. They are:
CNRS, France & IMPA, Brazil
for his profound contributions to dynamical systems theory have changed the face of the field, using the powerful idea of renormalization as a unifying principle.
- Renormalization [Encyclopedia of Mathematics]
========================================================================
Princeton University, USA
for developing powerful new methods in the geometry of numbers and applied them to count rings of small rank and to bound the average rank of elliptic curves.
- Geometry of numbers [Encyclopedia of Mathematics]
========================================================================
University of Warwick, UK
for his outstanding contributions to the theory of stochastic partial differential equations, and in particular created a theory of regularity structures for such equations.
========================================================================
Stanford University, USA
for her outstanding contributions to the dynamics and geometry of Riemann surfaces and their moduli spaces.
- Riemann surfaces [Encyclopedia of Mathematics]
Check ICM2014 for more descriptions about their researches.
image source: www.icm2014.org
Google[x] Developed Contact Lens Measure Blood Glucouse
Google and Novartis are now working together to develop Google[x] smart contact lens into wearable blood glucose sensors, helping thousands patients suffering from diabetes.
How it works?
"We’re now testing a smart contact lens that’s built to measure glucose levels in tears using a tiny wireless chip and miniaturized glucose sensor that are embedded between two layers of soft contact lens material. We’re testing prototypes that can generate a reading once per second. We’re also investigating the potential for this to serve as an early warning for the wearer, so we’re exploring integrating tiny LED lights that could light up to indicate that glucose levels have crossed above or below certain thresholds."
Does it mean your eye will change color?
Btw, what is the chemistry inside the lens that allows continuous blood glucose level monitoring?
Related News:
image source: http://www.dailymail.co.uk/sciencetech/article-2693326/Googles-smart-contact-lenses-coming-eye-near-soon-Lenses-diabetics-farsighted-set-production.html
How it works?
"We’re now testing a smart contact lens that’s built to measure glucose levels in tears using a tiny wireless chip and miniaturized glucose sensor that are embedded between two layers of soft contact lens material. We’re testing prototypes that can generate a reading once per second. We’re also investigating the potential for this to serve as an early warning for the wearer, so we’re exploring integrating tiny LED lights that could light up to indicate that glucose levels have crossed above or below certain thresholds."
Does it mean your eye will change color?
Btw, what is the chemistry inside the lens that allows continuous blood glucose level monitoring?
Related News:
- Google unveils 'smart contact lens' to measure glucose levels
- Google Smart Contact Lens Focuses On Healthcare Billions
- Google's smart contact lens is coming to an eye near you: Lenses for diabetics and the farsighted to go into production
image source: http://www.dailymail.co.uk/sciencetech/article-2693326/Googles-smart-contact-lenses-coming-eye-near-soon-Lenses-diabetics-farsighted-set-production.html
MIT $100K
It is always excited to see how MIT cultivate entrepreneurship among the MIT students and researchers. This time is MIT $100K. Congratulation to all winners.
"One competition – three contests – from September to May. MIT $100K Entrepreneurship Competition brings together students and researchers in the MIT community and outside to act on their talent, ideas and energy to launch tomorrow’s leading firms. The competition is run as a series of distinct contests – Pitch, Accelerate, and Launch. Each contest focuses on developing specific founding skills and for each contest MIT $100K brings together a network of resources – top venture capitalists, entrepreneurs, media exposure, mentors, educational guidance, networking. Finally over $350K in cash and prizes are awarded to help participants through the new venture construction process."
For more information: www.mit100k.org
image source: mit100k.org
"One competition – three contests – from September to May. MIT $100K Entrepreneurship Competition brings together students and researchers in the MIT community and outside to act on their talent, ideas and energy to launch tomorrow’s leading firms. The competition is run as a series of distinct contests – Pitch, Accelerate, and Launch. Each contest focuses on developing specific founding skills and for each contest MIT $100K brings together a network of resources – top venture capitalists, entrepreneurs, media exposure, mentors, educational guidance, networking. Finally over $350K in cash and prizes are awarded to help participants through the new venture construction process."
For more information: www.mit100k.org
image source: mit100k.org
Ebola 2014
Learn more about Ebola.
Ebola virus disease, WHO
The Ebola virus, Visual Science *****
2014 Ebola Outbreak in West Africa, CDC, US
Ebola virus disease, WHO
- Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness in humans.
- EVD outbreaks have a case fatality rate of up to 90%.
- EVD outbreaks occur primarily in remote villages in Central and West Africa, near tropical rainforests.
- The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
- Fruit bats of the Pteropodidae family are considered to be the natural host of the Ebola virus.
- Severely ill patients require intensive supportive care. No licensed specific treatment or vaccine is available for use in people or animals
The Ebola virus, Visual Science *****
2014 Ebola Outbreak in West Africa, CDC, US
Tag :
general,
Five questions that need answering when considering the design of clinical trials
Corresponding author: Hugh Davies hughdavies@nhs.net
Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Faculty of Medicine, Ludwig-Maximilians University, Munich, Germany
Trials 2014, 15:286 doi:10.1186/1745-6215-15-286
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The electronic version of this article is the complete one and can be found online at: http://www.trialsjournal.com/content/15/1/286
image source: http://www.discoveriesmagazine.org/features/clinical-trials-101-feature/clinical-trials-101.jpg
Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Faculty of Medicine, Ludwig-Maximilians University, Munich, Germany
Trials 2014, 15:286 doi:10.1186/1745-6215-15-286
----------------------------------------------------------------------------
Main text
The HRA Guidance
This HRA guidance poses five questions [4]:
1) Is there a clear research question?
2) Will the proposed study design answer the research question?
3) Are the assumptions used in the sample size calculation appropriate?
4) How will safety and efficacy be monitored during the trial?
5) How will the trial be registered and subsequently published?
Document structure
The HRA guidance is separated into four layers, providing increasing detail, as required. Layer I sets out in tabular form the questions and considerations that researchers, sponsors, peer reviewers and RECs should ask. By clicking over a question or specific words or phrases in the table in Layer I the reader can navigate to a more detailed discussion of the topic in Layer II. From Layer II the reader can navigate to more comprehensive explanations of individual components of the sample size in Layer III. Finally, Layer IV provides explanatory notes on some underlying statistical principles.
The five questions
The HRA guidance is built on the following core concepts: that sound planning is critical to the outcome of an interventional clinical trial and its ethical acceptability (bad science is bad ethics); all trials must be registered; and the results should be published [5,6]. A researcher should identify the primary research question to be answered; explain why it is important to patients and health-care practitioners; show that the study design is appropriate to answer the question posed, in particular that the sample size is likely to be adequate to meet the pre-specified aims of the study; and describe the plan to disseminate the results of the study.
Is there a clear research question?
The definition of the research question is key to research design. All research must have a primary question, clearly stated in advance, and founded on a systematic review of what is already known[5,7-9]. Researchers who plan studies without reviewing what has been done, risk performing research for which the answer is already known or exposing participants to ineffective or an inferior treatment [8-10].
The planning of a clinical trial depends on the primary question, and researchers should clearly and simply explain in the study protocol what the trial is aiming to show, why it is worth asking and, through consultation with public and patient groups, why this is worthwhile to patients. The primary question should be consistently stated throughout the study protocol. Population, intervention, comparator and outcome (PICO) is one useful way of formulating a research question[11].
Will the proposed design answer the research question?
The research protocol should explain how the proposed study methodology is appropriate for the question posed, demonstrate that the design is likely to answer the research question, and why it is the best approach. The design should be underpinned by a systematic review of the existing evidence, which should be reported in the protocol [8,9]. Absence of a systematic review raises the question: what is the design based on?
Unfortunately, our and other research has found that study protocols often lack important information on study design, which hinders external review [2,3,7,12]. The HRA guidance therefore encourages researchers to explain:
• how the proposed research method is appropriate for the question posed
• the reasoning behind the choice of any treatment difference sought, as well as the other parameters used in the determination of the sample size
• how the relevant successes and failures of previous studies have been taken into account in the design of the planned trial
• the reason for the choice of comparators
• the randomisation and blinding methods
• the suitability of the statistical tests
• how the sample to be studied is representative and thus, generalisable to the wider group of patients
Are the assumptions used in the sample size calculation appropriate?
Researchers should provide all the information needed to allow an independent reviewer to both reproduce the target sample size and understand the rationale for the assumptions used in the calculation. The HRA guidance provides a checklist of the information that should be reported in the study protocol for the sample size determination. Each item is linked to more detailed explanations. Specific guidance is given on reporting sample sizes based on confidence intervals, group sequential, factorial, cluster and time-to-event studies.
The sample size determination checklist requests that researchers:
• Explain what the study is aiming to show
• Describe the design of the study
• State clearly the primary outcome measure
• State the test procedure on which the sample size is based
• State the allocation ratio
• State and justify the difference sought, if the study is aiming to show superiority
• State and justify the acceptance margin, if the study is aiming to demonstrate
• non-inferiority or equivalence
• Report all parameters used in the sample size calculation
• Explain the rationale for the parameters used in the sample size calculation
• Describe any procedures to re-estimate the sample size during the study
• Report the Type I error
• Report the Type II error
• Describe any adjustments for multiple testing (multiplicity), if the study has multiple endpoints, interim analyses, or multiple arms
• State the number of patients or events required for the analysis
• Explain the allowance (if any) for dropouts
• State the total number of patients to be enrolled
Particular emphasis is placed on the need to provide a reasoned explanation of why the treatment difference and other design assumptions are plausible for the planned study, taking into account all existing data. The importance of the difference sought, i.e. why it is worthwhile to patients, should also be explained. The justification could include reference to consultations with the public and patient groups, existing literature or published studies in which the minimum clinically important difference has been empirically determined.
Researchers should be rigorous in the determination of design assumptions [1-3]. Sample size re-estimation should be considered if there is a high degree of uncertainty [13]. Manipulating the sample size calculation, sometimes called the sample size ‘game’ or ‘samba’, to produce the desired statistical power by inappropriately overestimating the treatment effect (known as ‘optimism bias’ – the unwarranted belief in the efficacy of new therapies) or underestimating the variability leads to ‘underbuilt’ studies with insufficient power and inconclusive results [14,15]. Such studies are not ethical and waste valuable resources [16-18].
Sample size determinations must be realistic [19]. If the sample size required to detect the treatment difference of interest is unfeasible, then this should be explained in the research protocol. A well-designed and implemented trial, even one with lower power (and precision), will still yield unbiased results, which can be combined with similar unbiased trials in a meta-analysis[14].
How will safety and efficacy be monitored during the trial?
All studies should be monitored for protocol compliance, adverse effects, patient recruitment, etc. If treatment is of long duration then accumulating efficacy data should be monitored for overwhelming evidence of efficacy or harm. No study should continue to recruit patients once the main comparisons have revealed clear-cut differences [5].
The repeated significance testing of accumulating data does have statistical implications [5]. Thus, the research protocol should describe how multiple testing has been accounted for in the sample size determination [2,3,7]. If there is a great deal of uncertainty surrounding the design assumptions then researchers are asked to consider re-estimating the sample size during the course of the study.
How will the trial be registered and subsequently published?
For clinical trials, HRA has now established that a favourable REC opinion is contingent upon trial registration in publicly accessible databases, unless acceptable reasons are provided for not doing so. The REC also needs to be assured that results will be placed in the public domain. Researchers are expected to:
• publish their results in full and in a reasonable timescale, even when they do not match expectations
• follow reporting guidelines for clinical trials (e.g., CONSORT [20])
• discuss their findings in the context of an updated systematic review of relevant research
• provide their results to others doing systematic reviews of similar topics
The electronic version of this article is the complete one and can be found online at: http://www.trialsjournal.com/content/15/1/286
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