Reducing bias and improving transparency in medical research: A critical overview of the problems, progress so far and suggested next steps

In recent years there has been increasing awareness of problems that have undermined trust in medical research. This review outlines some of the most important issues including research culture, reporting biases, and statistical and methodological issues. It examines measures that have been instituted to address these problems and explores the success and limitations of these measures. The paper concludes by proposing three achievable actions which could be implemented to deliver significantly improved transparency and mitigation of bias. These measures are as follows: (1) mandatory registration of interests by those involved in research; (2) that journals support the ‘registered reports’ publication format; and (3) that comprehensive study documentation for all publicly funded research be made available on a World Health Organization research repository. We suggest that achieving such measures requires a broad-based campaign which mobilises public opinion. We invite readers to feedback on the proposed actions and to join us in calling for their implementation

Conceptualising the right to data protection in an era of Big Data

In 2009, with the enactment of the Lisbon Treaty, the Charter of Fundamental Rights of the European Union entered into force. Under Article 8 of the Charter, for the first time, a stand-alone fundamental right to data protection was declared. The creation of this right, standing as a distinct right to the right to privacy, is undoubtedly significant, and it is unique to the European legal order, being absent from other international human rights instruments. This commentary examines the parameters of this new right to data protection, asking what are the principles underpinning the right. It argues that the right reflects some key values inherent in the European legal order, namely: privacy, transparency, autonomy and nondiscrimination. It also analyses some of the challenges in implementing this right in an era of ubiquitous veillance practices and Big Data

Why the fair innings argument is not persuasive

The fair innings argument (FIA) is frequently put forward as a justification for denying elderly patients treatment when they are in competition with younger patients and resources are scarce. In this paper I will examine some arguments that are used to support the FIA. My conclusion will be that they do not stand up to scrutiny and therefore, the FIA should not be used to justify the denial of treatment to elderly patients, or to support rationing of health care by age. There are six issues arising out of the FIA which are to be addressed. First, the implication that there is such a thing as a fair share of life. Second, whether it makes sense to talk of a fair share of resources in the context of health care and the FIA. Third, that 'fairness' is usually only mentioned with regard to the length of a person's life, and not to any other aspect of it. Fourth, if it is sensible to discuss the merits of the FIA without taking account of the 'all other things being equal' argument. Fifth, the difference between what is unfair and what is unfortunate. Finally, that it is tragic if a young person dies, but only unfortunate if an elderly person does

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection.

The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid glycoprotein, glucose, and biogenic amines were made on samples from symptomatic coronavirus disease 19 (COVID-19) patients who had tested positive for the SARS-CoV-2 virus (n = 17) and from age- and gender-matched controls (n = 25). Data were analyzed using an orthogonal-projections to latent structures (OPLS) method and used to construct an exceptionally strong (AUROC = 1) hybrid NMR-MS model that enabled detailed metabolic discrimination between the groups and their biochemical relationships. Key discriminant metabolites included markers of inflammation including elevated α-1-acid glycoprotein and an increased kynurenine/tryptophan ratio. There was also an abnormal lipoprotein, glucose, and amino acid signature consistent with diabetes and coronary artery disease (low total and HDL Apolipoprotein A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus multiple highly significant amino acid markers of liver dysfunction (including the elevated glutamine/glutamate and Fischer's ratios) that present themselves as part of a distinct SARS-CoV-2 infection pattern. A multivariate training-test set model was validated using independent samples from additional SARS-CoV-2 positive patients and controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2 positivity. The breadth of the disturbed pathways indicates a systemic signature of SARS-CoV-2 positivity that includes elements of liver dysfunction, dyslipidemia, diabetes, and coronary heart disease risk that are consistent with recent reports that COVID-19 is a systemic disease affecting multiple organs and systems. Metabolights study reference: MTBLS2014

A promoting early presentation intervention increases breast cancer awareness in older women after 2 years: a randomised controlled trial

BACKGROUND: We have developed the Promoting Early Presentation (PEP) Intervention to equip older women with the knowledge, skills, confidence and motivation to present promptly with breast symptoms, and thereby improve survival from breast cancer. The PEP Intervention consists of a 10-min interaction between a radiographer and an older woman, supported by a booklet. Our previous report showed that at 1 year, the PEP intervention increased the proportion who were breast cancer aware compared with usual care.METHODS: We randomised 867 women aged 67-70 years attending for their final routine appointment on the National Health Service Breast Screening Programme to receive the PEP Intervention, a booklet alone or usual care. The primary outcome was breast cancer awareness measured using a validated questionnaire asking about knowledge of breast cancer symptoms, knowledge that the risk of breast cancer increases with age and breast checking behaviour.RESULTS: At 2 years, the PEP Intervention increased the proportion who were breast cancer aware compared with usual care (21 vs 6%; odds ratio 8.1, 95% confidence interval 2.7-25.0).CONCLUSIONS: The uniquely large and sustained effect of the PEP Intervention on breast cancer awareness increases the likelihood that a woman will present promptly should she develop breast cancer symptoms up to many years later. British Journal of Cancer (2011) 105, 18-21. doi: 10.1038/bjc.2011.205 www.bjcancer.com Published online 7 June 2011 (C) 2011 Cancer Research U

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

Assessment of Forest Biomass and Carbon Stocks at Stand Level Using Site-Specific Primary Data to Support Forest Management

To quantify and map woody biomass (WB) and forest carbon (C) stocks, several models were developed. They differ in terms of scale of application, details related to the input data required and outputs provided. Local Authorities, such as Mountain Communities, can be supported in sustainable forest planning and management by providing specific models in which the reference unit is the same as the one reported in the Forest Management Plans (FMP), i.e. the forest stand. In the Lombardy Region (Northern Italy), a few studies were performed to assess WB and forest C stocks, and they were generally based on data coming from regional\u2014or national\u2014forest inventories and remote sensing, without taking into account data collected in the FMPs. For this study, the first version of the stand-level model \u201cWOody biomass and Carbon ASsessment\u201d (WOCAS) for WB and C stocks calculation was improved into a second version (WOCAS v2) and preliminary results about its first application to 2019 forest stands of Valle Camonica District (Lombardy Region) are presented. Since the model WOCAS uses the growing stock as the main driver for the calculation, it can be applied in any other forest area where the same input data are available

Investigation of low 5-year relative survival for breast cancer in a London cancer network

BACKGROUND: Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN). METHODS: We compared breast cancer that was diagnosed during 2001-2005 with that in the rest of London. RESULTS: North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15-1.41) reduced to 1.00 (95% CI: 0.89-1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year. CONCLUSION: Late diagnosis occurs in NELCN

Wave vision

The basic applications of radio waves are communication an