Inference of hidden structures in complex physical systems by multi-scale clustering

We survey the application of a relatively new branch of statistical physics--"community detection"-- to data mining. In particular, we focus on the diagnosis of materials and automated image segmentation. Community detection describes the quest of partitioning a complex system involving many elements into optimally decoupled subsets or communities of such elements. We review a multiresolution variant which is used to ascertain structures at different spatial and temporal scales. Significant patterns are obtained by examining the correlations between different independent solvers. Similar to other combinatorial optimization problems in the NP complexity class, community detection exhibits several phases. Typically, illuminating orders are revealed by choosing parameters that lead to extremal information theory correlations.Comment: 25 pages, 16 Figures; a review of earlier work

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Zicam-Induced Damage to Mouse and Human Nasal Tissue

Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc), a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction

Sympatric woodland Myotis bats form tight-knit social groups with exclusive roost home ranges

Background: The structuring of wild animal populations can influence population dynamics, disease spread, and information transfer. Social network analysis potentially offers insights into these processes but is rarely, if ever, used to investigate more than one species in a community. We therefore compared the social, temporal and spatial networks of sympatric Myotis bats (M. nattereri (Natterer's bats) and M. daubentonii (Daubenton's bats)), and asked: (1) are there long-lasting social associations within species? (2) do the ranges occupied by roosting social groups overlap within or between species? (3) are M. daubentonii bachelor colonies excluded from roosting in areas used by maternity groups? Results: Using data on 490 ringed M. nattereri and 978 M. daubentonii from 379 colonies, we found that both species formed stable social groups encompassing multiple colonies. M. nattereri formed 11 mixed-sex social groups with few (4.3%) inter-group associations. Approximately half of all M. nattereri were associated with the same individuals when recaptured, with many associations being long-term (>100 days). In contrast, M. daubentonii were sexually segregated; only a quarter of pairs were associated at recapture after a few days, and inter-sex associations were not long-lasting. Social groups of M. nattereri and female M. daubentonii had small roost home ranges (mean 0.2 km2 in each case). Intra-specific overlap was low, but inter-specific overlap was high, suggesting territoriality within but not between species. M. daubentonii bachelor colonies did not appear to be excluded from roosting areas used by females. Conclusions: Our data suggest marked species- and sex-specific patterns of disease and information transmission are likely between bats of the same genus despite sharing a common habitat. The clear partitioning of the woodland amongst social groups, and their apparent reliance on small patches of habitat for roosting, means that localised woodland management may be more important to bat conservation than previously recognised

Obstacles to researching the researchers: A case study of the ethical challenges of undertaking methodological research investigating the reporting of randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>Recent cohort studies of randomised controlled trials have provided evidence of within-study selective reporting bias; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes. Bias resulting from selective reporting can impact on meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines.</p> <p>In 2006 we received funding to investigate if there was evidence of within-study selective reporting in a cohort of RCTs submitted to New Zealand Regional Ethics Committees in 1998/99. This research involved accessing ethics applications, their amendments and annual reports, and comparing these with corresponding publications. We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons.</p> <p>In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee. The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application. This initiated a seventeen month process to obtain ethical approval. This publication outlines what we planned to do, the issues we encountered, discusses the legal and ethical issues, and presents some potential solutions.</p> <p>Discussion and conclusion</p> <p>Methodological research such as this has the potential for public benefit and there is little or no harm for the participants (trialists) in undertaking it. Further, in New Zealand, there is freedom of information legislation, which in this circumstance, unambiguously provided rights of access and use of the information in the ethics applications. The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research.</p> <p>Methodological research, such as this, can be used to develop processes to improve quality in research reporting. Recognition of the potential benefit of this research in the broader research community, and those who sit on ethics committees, is perhaps needed. In addition, changes to the ethical review process which involve separation between those who review proposals to undertake methodological research using ethics applications, and those with responsibility for reviewing ethics applications for trials, should be considered. Finally, we contend that the research community could benefit from quality improvement approaches used in allied sectors.</p

Carotid Baroreflex Activation: Past, Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension

How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta-Analysis of Survey Data

The frequency with which scientists fabricate and falsify data, or commit other forms of scientific misconduct is a matter of controversy. Many surveys have asked scientists directly whether they have committed or know of a colleague who committed research misconduct, but their results appeared difficult to compare and synthesize. This is the first meta-analysis of these surveys

Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs? (III)

The scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products

More insight into the fate of biomedical meeting abstracts: a systematic review

BACKGROUND: It has been estimated that about 45% of abstracts that are accepted for presentation at biomedical meetings will subsequently be published in full. The acceptance of abstracts at meetings and their fate after initial rejection are less well understood. We set out to estimate the proportion of abstracts submitted to meetings that are eventually published as full reports, and to explore factors that are associated with meeting acceptance and successful publication. METHODS: Studies analysing acceptance of abstracts at biomedical meetings or their subsequent full publication were searched in MEDLINE, OLDMEDLINE, EMBASE, Cochrane Library, CINAHL, BIOSIS, Science Citation Index Expanded, and by hand searching of bibliographies and proceedings. We estimated rates of abstract acceptance and of subsequent full publication, and identified abstract and meeting characteristics associated with acceptance and publication, using logistic regression analysis, survival-type analysis, and meta-analysis. RESULTS: Analysed meetings were held between 1957 and 1999. Of 14945 abstracts that were submitted to 43 meetings, 46% were accepted. The rate of full publication was studied with 19123 abstracts that were presented at 234 meetings. Using survival-type analysis, we estimated that 27% were published after two, 41% after four, and 44% after six years. Of 2412 abstracts that were rejected at 24 meetings, 27% were published despite rejection. Factors associated with both abstract acceptance and subsequent publication were basic science and positive study outcome. Large meetings and those held outside the US were more likely to accept abstracts. Abstracts were more likely to be published subsequently if presented either orally, at small meetings, or at a US meeting. Abstract acceptance itself was strongly associated with full publication. CONCLUSIONS: About one third of abstracts submitted to biomedical meetings were published as full reports. Acceptance at meetings and publication were associated with specific characteristics of abstracts and meetings

Death, treatment decisions and the permanent vegetative state: evidence from families and experts

Some brain injured patients are left in a permanent vegetative state, i.e., they have irreversibly lost their capacity for consciousness but retained some autonomic physiological functions, such as breathing unaided. Having discussed the controversial nature of the permanent vegetative state as a diagnostic category, we turn to the question of the patients’ ontological status. Are the permanently vegetative alive, dead, or in some other state? We present empirical data from interviews with relatives of patients, and with experts, to support the view that the ontological state of permanently vegetative patients is unclear: such patients are neither straightforwardly alive nor simply dead. Having defended this view from counter-arguments we turn to the practical question as to how these patients ought to be treated. Some relatives and experts believe it is right for patients to be shifted from their currently unclear ontological state to that of being straightforwardly dead, but many are concerned or even horrified by the only legally sanctioned method guaranteed to achieve this, namely withdrawal of clinically assisted nutrition and hydration. A way of addressing this distress would be to allow active euthanasia for these patients. This is highly controversial; but we argue that standard objections to allowing active euthanasia for this particular class of permanently vegetative patients are weakened by these patients’ distinctive ontological status