Evidence based medicine as science

Evidence based medicine has claimed to be science on a number of occasions but it is not clear that this status is deserved. Within philosophy of science four main theories about the nature of science are historically recognised: inductivism, falsificationism, Kuhnian paradigms and research programmes. If evidence based medicine is science knowledge claims should be derived using a process that corresponds to one of these theories. This paper analyses whether this is the case. In the first section, different theories about the nature of science are introduced. In the second section, the claim that evidence based medicine is science is reinterpreted as the claim that knowledge claims derived from randomised controlled trails and meta-analyses are science. In the third section the knowledge claims valued within evidence based medicine are considered from the perspective of inductivism, falsificationism, Kuhnian paradigms and research programmes. In the final section possible counter arguments are considered. It is argued that the knowledge claims valued by evidence based medicine are not justified using inductivism, falsificationism, Kuhnian paradigms or research programmes. If these are the main criteria for evaluating if something is science or not, evidence based medicine does not meet these criteria

Statistical inference and the replication crisis

The replication crisis has prompted many to call for statistical reform within the psychological sciences. Here we examine issues within Frequentist statistics that may have led to the replication crisis, and we examine the alternative—Bayesian statistics—that many have suggested as a replacement. The Frequentist approach and the Bayesian approach offer radically different perspectives on evidence and inference with the Frequentist approach prioritising error control and the Bayesian approach offering a formal method for quantifying the relative strength of evidence for hypotheses. We suggest that rather than mere statistical reform, what is needed is a better understanding of the different modes of statistical inference and a better understanding of how statistical inference relates to scientific inference

Development and validation of a low dose simulator for computed tomography

To develop and validate software for facilitating observer studies on the effect of radiation exposure on the diagnostic value of computed tomography (CT). A low dose simulator was developed which adds noise to the raw CT data. For validation two phantoms were used: a cylindrical test object and an anthropomorphic phantom. Images of both were acquired at different dose levels by changing the tube current of the acquisition (500 mA to 20 mA in five steps). Additionally, low dose simulations were performed from 500 mA downwards to 20 mA in the same steps. Noise was measured within the cylindrical test object and in the anthropomorphic phantom. Finally, noise power spectra (NPS) were measured in water. The low dose simulator yielded similar image quality compared with actual low dose acquisitions. Mean difference in noise over all comparisons between actual and simulated images was 5.7 +/- 4.6% for the cylindrical test object and 3.3 +/- 2.6% for the anthropomorphic phantom. NPS measurements showed that the general shape and intensity are similar. The developed low dose simulator creates images that accurately represent the image quality of acquisitions at lower dose levels and is suitable for application in clinical studies.Radiolog

Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics

Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of `genetic robustness' while that of isogenic individuals gives a measure of `developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The condition for evolution of robustness as well as relationship between genetic and developmental robustness is derived through the variance of phenotypic fluctuations, which are measurable experimentally.Comment: 25 page

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Systematic review of pre-operative exercise in colorectal cancer patients

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality

Deployable Laboratory Response to Influenza Pandemic; PCR Assay Field Trials and Comparison with Reference Methods

Background: The influenza A/H1N1/09 pandemic spread quickly during the Southern Hemisphere winter in 2009 and reached epidemic proportions within weeks of the official WHO alert. Vulnerable population groups included indigenous Australians and remote northern population centres visited by international travellers. At the height of the Australian epidemic a large number of troops converged on a training area in northern Australia for an international exercise, raising concerns about their potential exposure to the emerging influenza threat before, during and immediately after their arrival in the area. Influenza A/H1N1/09 became the dominant seasonal variant and returned to Australia during the Southern winter the following year. Methods: A duplex nucleic acid amplification assay was developed within weeks of the first WHO influenza pandemic alert, demonstrated in northwestern Australia shortly afterwards and deployed as part of the pathology support for a field hospital during a military exercise during the initial epidemic surge in June 2009. Results: The nucleic acid amplification assay was twice as sensitive as a point of care influenza immunoassay, as specific but a little less sensitive than the reference laboratory nucleic acid amplification assay. Repetition of the field assay with blinded clinical samples obtained during the 2010 winter influenza season demonstrated a 91.7% congruence with the reference laboratory method. Conclusions: Rapid in-house development of a deployable epidemic influenza assay allowed a flexible laboratory response, effective targeting of limited disease control resources in an austere military environment, and provided the public health laboratory service with a set of verification tools for resource-limited settings. The assay method was suitable for rapid deployment in time for the 2010 Northern winter

Demonstration of the Effect of Generic Anatomical Divisions versus Clinical Protocols on Computed Tomography Dose Estimates and Risk Burden

Objective: Choosing to undertake a CT scan relies on balancing risk versus benefit, however risks associated with CT scanning have generally been limited to broad anatomical locations, which do not provided adequate information to evaluate risk against benefit. Our study aimed to determine differences in radiation dose and risk estimates associated with modern CT scanning examinations when computed for clinical protocols compared with those using anatomical area. Methods: Technical data were extracted from a tertiary hospital Picture Archiving Communication System for random samples of 20–40 CT examinations per adult clinical CT protocol. Organ and whole body radiation dose were calculated using ImPACT Monte Carlo simulation software and cancer incidence and mortality estimated using BEIR VII age and gender specific lifetime attributable risk weights. Results: Thirty four unique CT protocols were identified by our study. When grouped according to anatomic area the radiation dose varied substantially, particularly for abdominal protocols. The total estimated number of incident cancers and cancer related deaths using the mean dose of anatomical area were 86 and 69 respectively. Using more specific protocol doses the estimates rose to 214 and 138 incident cancers and cancer related deaths, at least doubling the burden estimated. Conclusions: Modern CT scanning produces a greater diversity of effective doses than much of the literature describes; where a lack of focus on actual scanning protocols has produced estimates that do not reflect the range and complexity of modern CT practice. To allow clinicians, patients and policy makers to make informed risk versus benefit decisions the individual and population level risks associated with modern CT practices are essential

Newcastle Disease Virus in Madagascar: Identification of an Original Genotype Possibly Deriving from a Died Out Ancestor of Genotype IV

In Madagascar, Newcastle disease (ND) has become enzootic after the first documented epizootics in 1946, with recurrent annual outbreaks causing mortality up to 40%. Four ND viruses recently isolated in Madagascar were genotypically and pathotypically characterised. By phylogenetic inference based on the F and HN genes, and also full-genome sequence analyses, the NDV Malagasy isolates form a cluster distant enough to constitute a new genotype hereby proposed as genotype XI. This new genotype is presumably deriving from an ancestor close to genotype IV introduced in the island probably more than 50 years ago. Our data show also that all the previously described neutralising epitopes are conserved between Malagasy and vaccine strains. However, the potential implication in vaccination failures of specific amino acid substitutions predominantly found on surface-exposed epitopes of F and HN proteins is discussed