Wednesday, 17 September 2014

Make Research Papers Free for All!

Much research that is produced is at least part funded by the taxpayer. Those papers are then published by journals who charge taxpayers to read them! There is a rising movement to make all research paid for by taxpayers available free of charge or other hindrance to taxpayers - in the UK it has been possible to access millions of academic articles free of charge since early 2014, but all are not yet open and unrestricted and access is limited to UK public libraries.

The open information source Wikipedia has been used to provide links to more free resources - mainly University repositories - that provide more links to the work of University researchers.
This has triggered the following suggestion (and a workshop) at the recent Wikimania conference:

This discussion focuses on how Wikipedia could become the entry or discovery point to all significant research for the general public, and for scholars who are working just outside of the topic of interest. For most people, even researchers from closely related areas, summaries and explanations of a piece of research can be a crucial means both to discover and to begin to get into a new piece of research. 
Currently overviews of research topics are supported through two mechanisms: reviews and “front matter” content. A review is a systematic summary of a field, written by an expert. These go out of date quickly, particularly in rapidly moving areas of research. Front matter is “News and Views” pieces, often found at the “front” of scientific journals that explain newly published research and put it in context. This often includes a discussion of explaining how the research is an important advance and its broader societal implications. 
Both of these functions could easily be provided in a more up to date and scalable manner by tapping into a global community of experts. Wikipedia articles are often the top web search result for initial queries in many research areas and these articles are a major source of traffic for scientific journals. As the first port of call for many users of research and a significant discovery route the potential for Wikipedia as a form of dynamic, expertly curated “front matter” for the whole research literature is substantial. This facilitated discussion session will focus on how this role could be enhanced, what is currently missing and what risks exist in taking this route.

So not only could Wikipedia contribute further in the publication of original research, it could also play an important role in the summarisation of whole fields of research by experts in their fields in a way that expands on current 'static' methods of the review and journal article. Wikipedia currently provides a massive encyclopedia of information on many millions of subjects, many benefiting from contributions by field experts. These online documents are edited quickly and easily by people who read them and see mistakes that can be corrected - they can then login and start typing directly into the article - a form of expert community consensus is the result.

Perhaps this same style of article writing could be used to summarise current research? A review in a static paper such as we have now goes out of date rapidly as new papers are published - indeed they are oftwn already out of date by the time they are published. A 'Wiki-review' could prevent the loss of all the effort it takes to write a review, enabling editing of just those sections that are affected by a new paper rather than rendering the whole review useless. In that way the 'Wiki-review' stays up to date and is an effective description of the state of the art of its field of research.

Of course there will be problems when two scientists fail to agree on the nuances of a particular paper in a particular field, but experience has been that compromises rise naturally out of the dispute and a form of consensus is formed.

Worth a try?

Tuesday, 16 September 2014

Damp and Mould are a Health Risk to Asthma Sufferers: A Review

There have been a series of research papers published over several years on the subject of whether damp living conditions are correlated with asthma. Some papers seem to support the claim, others do not. This most recent publication, a review from 3 labs in the UK looks at all of those papers and searches for threads of evidence running through all of them. Because this approach looks at all research taken together its conclusions are stronger than each paper looked at on its own.

Earlier papers, including the 2009 review article from the World Health Organisation have described damp as 'strongly associated' with some respiratory illnesses including exacerbation of asthma but found no strong evidence to suggest that mould itself was associated.

The findings of this new review seem to suggest more strongly that there is a link between moulds and asthma. They looked at the populations of moulds found in homes prior to the development of asthma and prior to exacerbation

Quoting from the paper:
Conclusion: Longitudinal studies assessing increased exposure
to indoor fungi before the development of asthma symptoms
suggests that Penicillium, Aspergillus, and Cladosporium species
pose a respiratory health risk in susceptible populations.
Increased exacerbation of current asthma symptoms in children
and adults were associated with increased levels of Penicillium,
Aspergillus, Cladosporium, and Alternaria species, although
further work should consider the role of fungal diversity and
increased exposure to other fungal species.
The conclusions are thus fairly strong in favour of the presence of particular moulds themselves being associated with asthma and increased asthma. This is not the same as saying that they are the cause of the asthma but this is another step in that direction. Of course it still could be that the presence of these moulds tells us that something else - the true cause - is present (e.g. the presence of mould indicates high humidity, high humidity also causes several other things to happen, one of which might cause asthma). It might also be telling us that mould spores might be a cause, as might vapours produced by moulds as both are deeply inhaled.

The authors suggest further work should identify more genus' & specific species of mould that correlate with asthma so as to get a more complete picture of what is going on in this complex scenario. Newer technologies designed to identify many hundreds of specific species based on polymerase chain reaction (PCR) are capable of doing this so they may well form the basis of future experiments. Exposure to moulds may occur more than once and this may be improtant for the development of asthma, consequently future experiments need to be designed with this in mind.

Wednesday, 10 September 2014

100% accuracy for diagnosis of Invasive Aspergillosis

A recent report on the diagnosis of invasive aspergillosis concludes that the use of a combination of two quite new PCR-based tests gives investigators the ability to detect aspergillosis with 100% accuracy. That is a pretty optimistic claim given that the best PCR-based molecular tests to date have sensitivity rates of 79% (i.e. the proportion of patients identified by the test who are known to have invasive aspergillosis) and specificity of 94% (i.e. the proportion of patients who are known not to have invasive aspergillosis that are correctly identified by the test) in blood samples - see recent diagnostics review.

The authors of the paper state that they have used two nucleic acid amplification techniques - one amplifies single standed RNA (NASBA) thus presumably largely works by amplifying expressed genes or other sequences, the other amplifies DNA sequences (qPCR) thus presumably identifies whole or fragmented fungal cells. Each will use sequences that are specific to Aspergillus.

The paper claims that use of a combination of these two tests (which separately have sensitivities of 77% and 68% respectively, specificity of 80% and 89% respectively) gives perfect specificity of 100% , meaning all those identified as not having aspergillosis were correct diagnoses.

The combination of tests also gives 100% positive predictor value (PPV) which is a measure of its accuracy i.e. the number of known positives compared with the number of positives indicated by the tests. Given that this figure refers to the proportion of a population that are identified correctly it suggests that the expected number of positives were identified. However the authors do not highlight the figure for the sensitivity of the combined tests other than mention that it was 'the most sensitive' of the combinations tested.

These figures are striking and offer much encouragement for those in need of a reliable diagnostic test for invasive aspergillosis. In this study the sample population was quite small (80 patients) and analysis was done retrospectively, which is an approach with several weaknesses.

Tuesday, 9 September 2014

Fungal Vaccine Development Supported by NIH Research Grant

New ways to treat aspergillosis and other fungal infections are urgently needed. Existing antifungal medication is very good but only seems to be able to effectively prevent 60% of deaths by invasive aspergillosis (NB NOT the form of aspergillosis referred to as semi-invasive). We need new strategies and routes of attack.

Earlier Aspergillus Website blogs have indicated that the development of a vaccine to help fight fungal infections and in particular aspergillosis would be welcome as a new method of attack available to doctors:
The work showed that it might be possible to generate a vaccine that would be able to offer protection against several fungal infections at the same time

In an earlier blog we stated:
Another approach would be to develop a pan fungal vaccine which targets most serious fungal infections. Evidence recently published (Stevens et al) suggests that a combination of glycan (cell wall component) with an immunogenic protein - based on studies from heat killed Saccharomyces (yeast), may lead to developing such a pan fungal vaccine.

This is largely the work of Prof David Stevens MD at the California Institute for Medical Research and thanks to the success of the earlier efforts his group have just received a grant to further this work:

The technology involves combining a purified fungal carbohydrate and a protein antigen into a single vaccine. In previous studies Biothera with its expertise in carbohydrate chemistry created a vaccine by conjugating beta glucan particles a major component of fungal cell walls with a nonfungal protein antigen. The new funding will extend development to conjugating beta glucan particles with a specific protein antigen shared among different fungi potentially providing the basis for a pan-fungal vaccine.

Monday, 8 September 2014

Use of Isavuconazole for Invasive Aspergillosis

The new antifungal drug isavuconazole has received approval in Europe for its as a treatment for invasive aspergillosis.

Isavuconazole (drug substance: isavuconazonium sulfate) is an investigational once-daily intravenous and oral broad-spectrum antifungal for the potential treatment of life-threatening invasive fungal infections which predominantly occur in immunocompromised patients such as cancer patients undergoing chemotherapy. It has EU and U.S. orphan drug status for the treatment of invasive aspergillosis and mucormycosis. In the U.S. isavuconazole was granted FDA fast-track status and designated a Qualified Infectious Disease Product (QIDP) for invasive aspergillosis mucormycosis and candidiasis under the U.S. GAIN Act.

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