Health disinformation & social media: The crucial role of information hygiene in mitigating conspiracy theory and infodemics.

Social media has been an effective vector for spreading disinformation about medicine and science. Informational hygiene can reduce the severity of falsehoods about health.

A dangerous balancing act: On matters of science, a well-meaning desire to present all views equally can be an Trojan horse for damaging falsehoods.

Journalistic impartiality is a laudable aim, but overly rigid application of unbiased reporting may do more harm than good. The issue of false balance in science reporting has severe consequences for health and the environment.

Evidence for hypoxia increasing the tempo of evolution in glioblastoma.

BACKGROUND: Tumour hypoxia is associated with metastatic disease, and while there have been many mechanisms proposed for why tumour hypoxia is associated with metastatic disease, it remains unclear whether one precise mechanism is the key reason or several in concert. Somatic evolution drives cancer progression and treatment resistance, fuelled not only by genetic and epigenetic mutation but also by selection from interactions between tumour cells, normal cells and physical micro-environment. Ecological habitats influence evolutionary dynamics, but the impact on tempo of evolution is less clear. METHODS: We explored this complex dialogue with a combined clinical-theoretical approach by simulating a proliferative hierarchy under heterogeneous oxygen availability with an agent-based model. Predictions were compared against histology samples taken from glioblastoma patients, stained to elucidate areas of necrosis and TP53 expression heterogeneity. RESULTS: Results indicate that cell division in hypoxic environments is effectively upregulated, with low-oxygen niches providing avenues for tumour cells to spread. Analysis of human data indicates that cell division is not decreased under hypoxia, consistent with our results. CONCLUSIONS: Our results suggest that hypoxia could be a crucible that effectively warps evolutionary velocity, making key mutations more likely. Thus, key tumour ecological niches such as hypoxic regions may alter the evolutionary tempo, driving mutations fuelling tumour heterogeneity.

Close Encounters of the Cell Kind: The Impact of Contact Inhibition on Tumour Growth and Cancer Models.

Cancer is a complex phenomenon, and the sheer variation in behaviour across different types renders it difficult to ascertain underlying biological mechanisms. Experimental approaches frequently yield conflicting results for myriad reasons, and mathematical modelling of cancer is a vital tool to explore what we cannot readily measure, and ultimately improve treatment and prognosis. Like experiments, models are underpinned by certain biological assumptions, variation of which can lead to divergent predictions. An outstanding and important question concerns contact inhibition of proliferation (CIP), the observation that proliferation ceases when cells are spatially confined by their neighbours. CIP is a characteristic of many healthy adult tissues, but it remains unclear to which extent it holds in solid tumours, which exhibit regions of hyper-proliferation, and apparent breakdown of CIP. What precisely occurs in tumour tissue remains an open question, which mathematical modelling can help shed light on. In this perspective piece, we explore the implications of different hypotheses and available experimental evidence to elucidate the implications of these scenarios. We also outline how erroneous conclusions about the nature of tumour growth may be arrived at by looking selectively at biological data in isolation, and how this might be circumvented.

Distinguishing Polemic From Commentary in Science: Some Guidelines Illustrated With the Case of Sage and Burgio (2017).

Exposure to nonionizing radiation used in wireless communication remains a contentious topic in the public mind-while the overwhelming scientific evidence to date suggests that microwave and radio frequencies used in modern communications are safe, public apprehension remains considerable. A recent article in Child Development has caused concern by alleging a causative connection between nonionizing radiation and a host of conditions, including autism and cancer. This commentary outlines why these claims are devoid of merit, and why they should not have been given a scientific veneer of legitimacy. The commentary also outlines some hallmarks of potentially dubious science, with the hope that authors, reviewers, and editors might be better able to avoid suspect scientific claims.

Dose Quantification in UV Phototherapy.

Ultraviolet light has long been used to alleviate a number of skin conditions, and its efficacy is well known. However, over-exposure to ultraviolet radiation has a number of detrimental effects and thus it is vital to maintain a dose to skin within the therapeutic window. To maximise treatment gain whilst circumventing potential side-effects of over-exposure requires accurate determination of irradiance and skin-dose. This is complicated by the fact that ultraviolet radiation is essentially absorbed at the skin surface, which means that changing orientation of the patient and source can modulate dose received. In addition, irregular patient shapes mean dose must be carefully calibrated. This chapter focuses on methods of determination of dose, clinical protocols for quantifying radiation dose received and mathematical models for estimating these quantities.

Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia.

Regions of hypoxia in tumours can be modelled in vitro in 2D cell cultures with a hypoxic chamber or incubator in which oxygen levels can be regulated. Although this system is useful in many respects, it disregards the additional physiological gradients of the hypoxic microenvironment, which result in reduced nutrients and more acidic pH. Another approach to hypoxia modelling is to use three-dimensional spheroid cultures. In spheroids, the physiological gradients of the hypoxic tumour microenvironment can be inexpensively modelled and explored. In addition, spheroids offer the advantage of more representative modelling of tumour therapy responses compared with 2D culture. Here, we review the use of spheroids in hypoxia tumour biology research and highlight the different methodologies for spheroid formation and how to obtain uniformity. We explore the challenge of spheroid analyses and how to determine the effect on the hypoxic versus normoxic components of spheroids. We discuss the use of high-throughput analyses in hypoxia screening of spheroids. Furthermore, we examine the use of mathematical modelling of spheroids to understand more fully the hypoxic tumour microenvironment.

Region of Attainable Redaction, an extension of Ellipse of Insignificance analysis for gauging impacts of data redaction in dichotomous outcome trials.

In biomedical science, it is a reality that many published results do not withstand deeper investigation, and there is growing concern over a replicability crisis in science. Recently, Ellipse of Insignificance (EOI) analysis was introduced as a tool to allow researchers to gauge the robustness of reported results in dichotomous outcome design trials, giving precise deterministic values for the degree of miscoding between events and non-events tolerable simultaneously in both control and experimental arms (Grimes, 2022). While this is useful for situations where potential miscoding might transpire, it does not account for situations where apparently significant findings might result from accidental or deliberate data redaction in either the control or experimental arms of an experiment, or from missing data or systematic redaction. To address these scenarios, we introduce Region of Attainable Redaction (ROAR), a tool that extends EOI analysis to account for situations of potential data redaction. This produces a bounded cubic curve rather than an ellipse, and we outline how this can be used to identify potential redaction through an approach analogous to EOI. Applications are illustrated, and source code, including a web-based implementation that performs EOI and ROAR analysis in tandem for dichotomous outcome trials is provided.

Impact of human papillomavirus age-related prevalence and vaccination levels on interpretation of cervical screening modalities: a modelling study.

OBJECTIVE: Cervical screening is a life-saving intervention, which reduces the incidence of and mortality from cervical cancer in the population. Human papillomavirus (HPV) based screening modalities hold unique promise in improving screening accuracy. HPV prevalence varies markedly by age, as does resultant cervical intraepithelial neoplasia (CIN), with higher rates recorded in younger women. With the advent of effective vaccination for HPV drastically reducing prevalence of both HPV and CIN, it is critical to model how the accuracy of different screening approaches varies with age cohort and vaccination status. This work establishes a model for the age-specific prevalence of HPV factoring in vaccine coverage and predicts how the accuracy of common screening modalities is affected by age profile and vaccine uptake. DESIGN: Modelling study of HPV infection rates by age, ascertained from European cohorts prior to the introduction of vaccination. Reductions in HPV due to vaccination were estimated from the bounds predicted from multiple modelling studies, yielding a model for age-varying HPV and CIN grades 2 and above (CIN2+) prevalence. SETTING: Performance of both conventional liquid-based cytology (LBC) screening and HPV screening with LBC reflex (HPV reflex) was estimated under different simulated age cohorts and vaccination levels. PARTICIPANTS: Simulated populations of varying age and vaccination status. RESULTS: HPV-reflex modalities consistently result in much lower incidence of false positives than LBC testing, with an accuracy that improves even as HPV and CIN2+ rates decline. CONCLUSIONS: HPV-reflex tests outperform LBC tests across all age profiles, resulting in greater test accuracy. This improvement is especially pronounced as HPV infection rates fall and suggests HPV-reflex modalities are robust to future changes in the epidemiology of HPV.

Is biomedical research self-correcting? Modelling insights on the persistence of spurious science.

The reality that volumes of published biomedical research are not reproducible is an increasingly recognized problem. Spurious results reduce trustworthiness of reported science, increasing research waste. While science should be self-correcting from a philosophical perspective, that in insolation yields no information on efforts required to nullify suspect findings or factors shaping how quickly science may be corrected. There is also a paucity of information on how perverse incentives in the publishing ecosystem favouring novel positive findings over null results shape the ability of published science to self-correct. Knowledge of factors shaping self-correction of science remain obscure, limiting our ability to mitigate harms. This modelling study introduces a simple model to capture dynamics of the publication ecosystem, exploring factors influencing research waste, trustworthiness, corrective effort and time to correction. Results from this work indicate that research waste and corrective effort are highly dependent on field-specific false positive rates and time delays to corrective results to spurious findings are propagated. The model also suggests conditions under which biomedical science is self-correcting and those under which publication of correctives alone cannot stem propagation of untrustworthy results. Finally, this work models a variety of potential mitigation strategies, including researcher- and publisher-driven interventions.

In silico analysis of overall survival with YBX1 in male and female solid tumours.

The Y-box binding protein-1 (YBX1) gene codes for a multifunctional oncoprotein that is increasingly being linked to the regulations of many aspects of cancer cell biology. Disparities in treatment outcomes between male and female cancer patients are increasingly reported. This study aimed to examine the relationship between YBX1 expression and overall survival in male and female patients with solid tumours. Overall survival and YBX1 expression data for cohorts of male and female cancer patients obtained from freely available databases were analysed with a cox proportional hazard model with covariates of biological sex and YBX1 expression. Kaplan-Meier curves and Violin plots were constructed for segregated male and female cohorts. High YBX1 expression was significantly associated with poor survival in 2 female-only and 4 mixed-sex cancer sites. In female lung cancer patients, better survival and lower YBX1 expression were identified. The clinical importance of YBX1 expression in cancer ought to be evaluated in a sex-specific manner, especially in lung cancer.

Prioritising Key Concepts for informed health choices in cancer: An evidence-based online educational programme.

Objective: The overabundance of health misinformation has undermined people's capacity to make evidence-based, informed choices about their health. Using the Informed Health Choices (IHC) Key Concepts (KCs), we are developing a two-stage education programme, Informed Health Choices-Cancer (IHC-C), to provide those impacted by cancer with the knowledge and skills necessary to think critically about the reliability of health information and claims and make well-informed choices. Stage 1 seeks to prioritise the most relevant Key Concepts. Methods: A project group and a patient and carer participation group completed a two-round prioritisation process. The process involved disseminating pre-reading materials, training sessions, and a structured judgement form to evaluate concepts for inclusion. Data from each round were analysed to reach a consensus on the concepts to include. Results: Fourteen participants were recruited and completed the first-round prioritisation. Fifteen participants undertook the second-round prioritisation. Nine Key Concepts were selected for the programme across five training sessions and two consensus meetings. Conclusion: The prioritised concepts identified represent the most pertinent aspects of cancer-related information for those impacted by the disease. By incorporating these concepts into educational materials and communication strategies, healthcare providers and organisations can potentially help cancer patients, survivors, and their loved ones to recognise and combat cancer-related misinformation more effectively. Innovation: This study introduces a participatory prioritisation process, which integrates the expertise of healthcare professionals with the insights of patients and carers, thereby enhancing the programme's relevance and applicability.

Investigations of cabin design in UV phototherapy.

PURPOSE: UVR phototherapy cabins exist in a huge variety of configurations and geometries. An accurate dose model has been developed which can be used to examine the question of cabin design to investigate factors influencing dose on a patient. METHODS: This work extends the existing dose model to entire cabins and investigates how cabin and reflector geometry influence resultant dose. RESULTS: The model predictions are in line with what is measured. It is found that the length and angle of the reflectors have a large influence on received dose. CONCLUSIONS: The influence of cabin geometry is important in estimating patient dose, and the findings of this work are applicable to future cabin designs.

Radiofrequency Radiation and Cancer: A Review.

IMPORTANCE: Concerns over radiofrequency radiation (RFR) and carcinogenesis have long existed, and the advent of 5G mobile technology has seen a deluge of claims asserting that the new standard and RFR in general may be carcinogenic. For clinicians and researchers in the field, it is critical to address patient concerns on the topic and to be familiar with the existent evidence base. OBSERVATIONS: This review considers potential biophysical mechanisms of cancer induction, elucidating mechanisms of electromagnetically induced DNA damage and placing RFR in appropriate context on the electromagnetic spectrum. The existent epidemiological evidence in humans and laboratory animals to date on the topic is also reviewed and discussed. CONCLUSIONS AND RELEVANCE: The evidence from these combined strands strongly indicates that claims of an RFR-cancer link are not supported by the current evidence base. Much of the research to date, however, has been undermined by methodological shortcomings, and there is a need for higher-quality future research endeavors. Finally, the role of fringe science and unsubstantiated claims in patient and public perception on this topic is highly relevant and must be carefully considered.

Balancing benefits and potential risks of vaccination: the precautionary principle and the law of unintended consequences.

Vaccination is a life-saving endeavour, yet risk and uncertainty are unavoidable in science and medicine. Vaccination remains contentious in the public mind, and vaccine hesitancy is a serious public health issue. This has recently been reignited in the discussion over potential side effects of COVID-19 vaccines, and the decision by several countries to suspend measures such as the AstraZeneca vaccine. In these instances, the precautionary principle has often been invoked as a rationale, yet such heuristics do not adequately weigh potential harms against real benefits. How we analyse, communicate and react to potential harms is absolutely paramount to ensure the best decisions and outcomes for societal health, and maintaining public confidence. While balancing benefits and risks is an essential undertaking, it cannot be achieved without due consideration of several other pertinent factors, especially in the context of vaccination, where misguided or exaggerated fears have in the past imperilled public health. While well meaning, over reactions to potential hazards of vaccination and other health interventions can have unintended consequences, and cause lingering damage to public trust. In this analysis, we explore the challenges of assessing risk and benefit, and the limitations of the precautionary principle in these endeavours. When risk is unclear, cautious vigilance might be a more pragmatic and useful policy than reactionary suspensions.

The Struggle against Cancer Misinformation.

Cancer misinformation has become an increasingly prevalent problem, imperiling public health and understanding. Cancer researchers and clinicians must play a significant role in combating its detrimental consequences.

The ellipse of insignificance, a refined fragility index for ascertaining robustness of results in dichotomous outcome trials.

There is increasing awareness throughout biomedical science that many results do not withstand the trials of repeat investigation. The growing abundance of medical literature has only increased the urgent need for tools to gauge the robustness and trustworthiness of published science. Dichotomous outcome designs are vital in randomized clinical trials, cohort studies, and observational data for ascertaining differences between experimental and control arms. It has however been shown with tools like the fragility index (FI) that many ostensibly impactful results fail to materialize when even small numbers of patients or subjects in either the control or experimental arms are recoded from event to non-event. Critics of this metric counter that there is no objective means to determine a meaningful FI. As currently used, FI is not multidimensional and is computationally expensive. In this work, a conceptually similar geometrical approach is introduced, the ellipse of insignificance. This method yields precise deterministic values for the degree of manipulation or miscoding that can be tolerated simultaneously in both control and experimental arms, allowing for the derivation of objective measures of experimental robustness. More than this, the tool is intimately connected with sensitivity and specificity of the event/non-event tests, and is readily combined with knowledge of test parameters to reject unsound results. The method is outlined here, with illustrative clinical examples.

Science and medicine are vital to the well-being of humankind. Yet for all the incredible advances science has made, the unfortunate reality is that a worrying fraction of biological research is not reliable. Erroneous results might arise by chance or because of scientists' mistakes or ineptitude. Very occasionally, researchers may behave unethically and fabricate or inappropriately manipulate their data. Inevitably, this can lead to untrustworthy research that misleads scientists and the public on questions integral to our health. Indeed, a recent study showed the results of several high-profile cancer papers could not be fully replicated. This problem is not unique to cancer, and studies on various other diseases have also not stood up to scrutiny from outside investigators. Finding ways to detect dubious results is therefore essential to protect the public's well-being and maintain public trust in science. Here, Grimes demonstrates a new tool called the 'Ellipse of Insignificance' for measuring the reliability of dichotomous studies which are commonly used in many branches of biomedical sciences, including clinical trials. These studies typically compare two groups: one which was subjected to a specific treatment, and a control group which was not. Statistical methods are then applied to estimate how likely it is that differences in the number of observed events between the groups are real or due to chance. The tool created by Grimes explores what would happen to seemingly strong results if some of the events in both the control and experimental arm of the study are recoded. It then assesses how much nudging is needed to change the statistical outcome of the experiment: the more interventions the result can withstand, the more robust the experiment. Grimes tested the tool and showed that a study suggesting a link between miscarriage and magnetic field exposure was likely unreliable because shifting the outcomes of less than two participants would change the result. Scientists could use the Ellipse of Insignificance tool to quickly identify misleading published results or potential research fraud. Doing this could benefit researchers and protect the public from potential harm. It may also help preserve research integrity, increase transparency, and bolster public trust in science.

Prioritising Informed Health Choices Key Concepts for those impacted by cancer: a protocol.

Background: Few areas of health have been as insidiously influenced by misinformation as cancer. Thus, interventions that can help people impacted by cancer reduce the extent to which they are victims of misinformation are necessary. The Informed Health Choices (IHC) initiative has developed Key Concepts that can be used in the development of interventions for evaluating the trustworthiness of claims about the effects of health treatments. We are developing an online education programme called Informed Health Choices-Cancer (IHC-C) based on the IHC Key Concepts. We will provide those impacted by cancer with the knowledge and skills necessary to think critically about the reliability of health information and claims and make informed choices. Methods: We will establish a steering group (SG) of 12 key stakeholders, including oncology specialists and academics. In addition, we will establish a patient and public involvement (PPI) panel of 20 people impacted by cancer. After training the members on the Key Concepts and the prioritisation process, we will conduct a two-round prioritisation process. In the first round, 12 SG members and four PPI panel members will prioritise Key Concepts for inclusion. In the second round, the remaining 16 PPI members will undertake the prioritisation based on the prioritised Key Concepts from the first round. Participants in both rounds will use a structured judgement form to rate the importance of the Key Concepts for inclusion in the online IHC-C programme. A consensus meeting will be held, where members will reach a consensus on the Key Concepts to be included and rank the order in which the prioritised Key Concepts will be addressed in the IHC-C programme. Conclusions: At the end of this process, we will identify which Key Concepts should be included and the order in which they should be addressed in the IHC-C programme.