Do we consent to rules of consent and confidentiality?

Confidentiality and informed consent are important concepts enabling the sharing of sensitive data. In a paper on this topic of this issue, Williams and Pigeot ( 2017 ) discuss that these have to be balanced with openness to ensure research standards. In this opinion paper, we give some background on how the paper by Williams and Pigeot evolved, reflect on their concepts, and provide some examples of the application of these concepts in various settings relevant to biostatisticians working in health research.     

Measurement error caused by spatial misalignment in environmental epidemiology

In many environmental epidemiology studies, the locations and/or times of exposure measurements and health assessments do not match. In such settings, health effects analyses often use the predictions from an exposure model as a covariate in a regression model. Such exposure predictions contain some measurement error as the predicted values do not equal the true exposures. We provide a framework for spatial measurement error modeling, showing that smoothing induces a Berkson-type measurement error with nondiagonal error structure. From this viewpoint, we review the existing approaches to estimation in a linear regression health model, including direct use of the spatial predictions and exposure simulation, and explore some modified approaches, including Bayesian models and out-of-sample regression calibration, motivated by measurement error principles. We then extend this work to the generalized linear model framework for health outcomes. Based on analytical considerations and simulation results, we compare the performance of all these approaches under several spatial models for exposure. Our comparisons underscore several important points. First, exposure simulation can perform very poorly under certain realistic scenarios. Second, the relative performance of the different methods depends on the nature of the underlying exposure surface. Third, traditional measurement error concepts can help to explain the relative practical performance of the different methods. We apply the methods to data on the association between levels of particulate matter and birth weight in the greater Boston area.     

Barriers to application of genetically modified lactic acid bacteria

To increase the acceptability of food products containing genetically modified microorganisms it is necessary to provide in an early stage to the consumers that the product is safe and that the product provide a clear benefit to the consumer. To comply with the first requirement a systematic approach to analyze the probability that genetically modified lactic acid bacteria will transform other inhabitants of the gastro-intestinal (G/I) tract or that these lactic acid bacteria will pick up genetic information of these inhabitants has been proposed and worked out to some degree. From this analysis it is clear that reliable data are still missing to carry out complete risk assessment. However, on the basis of present knowledge, lactic acid bacteria containing conjugative plasmids should be avoided. Various studies show that consumers in developed countries will accept these products when they offer to them health or taste benefits or a better keepability. For the developing countries the biggest challenge for scientists is most likely to make indigenous fermented food products with strongly improved microbiological stability due to broad spectra bacteriocins produced by lactic acid bacteria. Moreover, these lactic acid bacteria may contribute to health.     

Evaluating interventions in health: a reconciliatory approach

Health-related Quality of Life measures have recently been attacked from two directions, both of which criticize the preference-based method of evaluating health states they typically incorporate. One attack, based on work by Daniel Kahneman and others, argues that 'experience' is a better basis for evaluation. The other, inspired by Amartya Sen, argues that 'capability' should be the guiding concept. In addition, opinion differs as to whether health evaluation measures are best derived from consultations with the general public, with patients, or with health professionals. And there is disagreement about whether these opinions should be solicited individually and aggregated, or derived instead from a process of collective deliberation. These distinctions yield a wide variety of possible approaches, with potentially differing policy implications. We consider some areas of disagreement between some of these approaches. We show that many of the perspectives seem to capture something important, such that it may be a mistake to reject any of them. Instead we suggest that some of the existing 'instruments' designed to measure HR QoLs may in fact successfully already combine these attributes, and with further refinement such instruments may be able to provide a reasonable reconciliation between the perspectives.     

Dietary intake and cancer mortality in Japan

We examined the correlation between the prefectural variation of standardized mortality ratio (SMR) for lung and colon cancer and the consumption of foods using dietary data from National Nutrition Survey in Japan from 1976 to 1995. We found partly the same results on promoting factors and preventing factors of these cancers as the previously reported large scale cohort studies. But, we also found the inconsistent results. This might be partly because of the limitation of data collection method in the National Nutrition Survey. It was thought that the method of National Nutrition Survey should be modified to monitor nutrition and health conditions to correspond the epidemiological study and to prevent chronic diseases.     

Elicitation of Expert Prior Opinion: Application to the MYPAN Trial in Childhood Polyarteritis Nodosa

Objectives

Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa).

Methods

A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.

Results

A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.

Conclusions

We suggest that the methodological template we propose could be applied to trial design for other rare diseases.     

Modeling different behaviors in disclosing risk perception

In many fields, people are requested to express their level of awareness about some risk (mainly associated with health, environment, energy, etc.) by selecting a category in an ordered scale. We propose a model for such ordinal data by taking into account that the observed response does not necessarily reflect the respondent's true opinion since the final answer can be inaccurate or completely random. The proposed model hypothesizes three behaviors in the process of answering: accurate interviewees express their risk perception exactly, uncertain ones randomly select the response according to the uniform distribution, and inaccurate interviewees make evaluation errors but with high probability they choose a rating close to the true one. Statistical inference for the proposed models is addressed without assuming that the model, to be fitted, is correctly specified. Two real case studies on the awareness of geo-hydrological risk and work-related stress risk are considered using the proposed methodology.     

A place of digital X-ray fluorography in the detection of lung diseases in the public health facilities of the Russian Federation

The paper shows the authors' opinion as to the use of digital X-ray fluorography (DXF) to detect pathology of the lung, primarily its tuberculosis and cancer from organizational-and-methodological and purely diagnostic standpoints. Based on a great body of data pooling 21,295 studies of patients, which comprised two (screening and routine clinical) groups, they authors state their views on the place and role of lung DXF in the work of public health facilities in the Russian Federation (RF). The objectivity of the authors' opinion is confirmed by the different nature of a lung abnormality detected by DXF at both the municipal and regional levels of the RF public health system and by a comparative analysis of the findings with those of film fluorography, routine X-ray study, linear tomography, X-ray computed tomography (XCT), and surgical evidence. The study has allowed the authors to express their opinion by recommending DXF as a method for primary diagnosis of lung diseases instead of film fluorography and routine X-ray study and to appreciate it in screenings. The authors' data indicate that XCT in its simplest variant rather than linear tomography should become the optimum method that specifies the diagnosis of lung diseases detected by DXT.     

Are we selecting appropriate metrics to assess human impacts on biodiversity?

Biased and subjective choices of metrics to be used in ecological studies could lead researchers to reach misleading conclusions regarding patterns of biodiversity response to human disturbances. Nevertheless, little attention has been given to the choices of variables in the majority of studies published to date. Here, we used the literature concerning land use change effects on dung beetles to assess the extent to which variables commonly employed in ecological studies correspond to those deemed to be most important by researchers of the same studies. Specifically, we examined both biodiversity (response) and environmental (explanatory) metrics from a comprehensive literature review and compared their use with their relative importance, according to a survey of the authors of the studies. Our results highlight marked disparities between researchers opinion expressed in our survey and their choice of variables in published papers. We suggest that these disparities are due to the high costs of sampling and processing some variables, logistical constraints and different perceptions of importance amongst researchers. We highlight the importance of these issues for our understanding of the biodiversity consequences of land use change, and highlight some recommendations for alleviating this issue.     

Sterolomics: State of the art,developments, limitations and challenges

Sterolomics can be thought of as the quantitative determination of the entire complement of molecules based on the cyclopentanoperhydrophenanthrene skeleton in a system. Mass spectrometry is the dominant analytical technology employed. In this article we highlight some pitfalls in analysis, data interpretation and annotation. We give our opinion on how some of these pitfalls can best be avoided. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.     

Reporting of lipidomics data should be standardized

This article highlights, to our opinion, some of the most pertinent issues related to producing high quality lipidomics data. These issues include pitfalls related to sample collection and storage, lipid extraction, the use of shotgun and LC-MS-based lipidomics approaches, and the identification, annotation and quantification of lipid species. We hope that highlighting these issues will help stimulate efforts to implement reporting standards for dissemination of lipidomics data. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.     

Conflicts of interest in e-cigarette research: A public good and public interest perspective

The tobacco industry’s involvement in the electronic cigarette research that informs public health policy is controversial. On the one hand, some are concerned that their involvement presents conflicts of interest that bias research outputs and invalidate the policies that use them. On the other hand, some have argued that the tobacco industry may support valid research and contribute to the goals of public health, for instance, if the interests of the e-cigarette industry could be part of a tobacco smoking cessation policy. We approach this debate from the ethical perspective of the public interest and the public good, considering how legitimate researchers can square their expert opinion with validating tobacco industry-funded research, given the perfidy of the tobacco industry and paucity of robust, conclusive evidence on the public health impacts of liberalizing e-cigarette use.     

Arabidopsis thaliana proliferating cell nuclear antigen has several potential sumoylation sites

Proliferating cell nuclear antigen (PCNA) is post-translationally modified in yeast and animal cells. Major studies carried out in the last decade have focused on the role of sumoylated and ubiquitinated PCNA. Using different approaches, an interaction between plant PCNA and SUMO both in vivo and in bacteria has been demonstrated for the first time. In addition, identical sumoylation patterns for both AtPCNA1 and 2 were observed in bacteria. The plant PCNA sumoylation pattern has been shown to differ significantly from that of Saccharomyces cerevisiae. This result contrasts with a common opinion based on previous structural analysis of yeast, human, and plant PCNAs, which treats PCNA as a highly conserved protein even between species. Analyses of AtPCNA post-translational modifications using different SUMO proteins (SUMO1, 2, 3, and 5) revealed similar modification patterns for each tested SUMO protein. Potential target lysine residues that might be sumoylated in vivo were identified on the basis of in bacteria AtPCNA mutational analyses. Taken together, these results clearly show that plant PCNA is post-translationally modified in bacteria and may be sumoylated in a plant cell at various sites. These data open up important new perspectives for further detailed studies on the role of PCNA sumoylation in plant cells.     

Modeling Mosquitoes and their Potential Odonate Predators Under Different Land Uses

To efficiently face the accelerated landscape transformation and its consequences in restructuring biotic communities and ecosystem services, one first question is which regional systems deserve prioritization for empirical assessments and interventive strategies. For the particular case of vector-borne disease control, we should consider generalist predators exhibiting differential responses to land-use change, as is the case of odonate insects. Thus, our aim was to infer land uses in Mexico where odonates (i.e., damselflies and dragonflies) might have some potential to predate mosquitoes of medical relevance. The study area included the hydrological basins of central Mexico. We modelled 167 species of odonates, four species of mosquitoes, and 51 land-use categories. Inferring spatial co-occurrence patterns from data mining and complex networks, we identified: (1) the ecological network of odonates and mosquitoes and (2) the land uses shared by these two groups. We inferred that 34% of odonate species co-occur with mosquitoes of medical relevance mainly in some preserved—mountain mesophyll cloud forest, high evergreen rainforest, and low tropical dry forest—but also in highly modified—human settlements, irrigation-based and pastures crop fields—land uses with strong human presence. Our findings highlight the relevance of community-regional studies for understanding the public health consequences of landscape change.

     

Predictive Assessment of Fish Health and Fish Kills in the Neuse River Estuary Using Elicited Expert Judgment

Declining fish health and the occurrence of large fish kills are some of the more publicly meaningful indicators of water quality in the impaired Neuse River Estuary, North Carolina. It is generally believed that such problems are caused by the widespread depletion of dissolved oxygen—an indirect result of anthropogenic nutrient pollution. However, the development of scientific simulation models to predict how improvements in oxygen conditions will improve the health of fish and reduce the frequency of fish kills has proven elusive. As a pragmatic solution to this problem, the expert opinion of estuarine fisheries scientists in possession of relevant data and experience was elicited. The relations between joint and conditional probabilities were exploited to translate quantities that are normally hard to assess into quantities that can be drawn more directly from the experiential knowledge of the experts. A combined model of expert opinion was constructed as an influence diagram, and Monte Carlo simulation was used to generate predictions of fish health and fish kills in the Neuse River Estuary under current and improved oxygen conditions. Full model results are expressed as probability distributions, capturing the effects of natural variability and knowledge uncertainty—both contributors to total ecological risk.     

Debate on GMOs health risks after statistical findings in regulatory tests

We summarize the major points of international debate on health risk studies for the main commercialized edible GMOs. These GMOs are soy, maize and oilseed rape designed to contain new pesticide residues since they have been modified to be herbicide-tolerant (mostly to Roundup) or to produce mutated Bt toxins. The debated alimentary chronic risks may come from unpredictable insertional mutagenesis effects, metabolic effects, or from the new pesticide residues. The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats, which are biochemically assessed. The tests are not compulsory, and are not independently conducted. The test data and the corresponding results are kept in secret by the companies. Our previous analyses of regulatory raw data at these levels, taking the representative examples of three GM maize NK 603, MON 810, and MON 863 led us to conclude that hepatorenal toxicities were possible, and that longer testing was necessary. Our study was criticized by the company developing the GMOs in question and the regulatory bodies, mainly on the divergent biological interpretations of statistically significant biochemical and physiological effects. We present the scientific reasons for the crucially different biological interpretations and also highlight the shortcomings in the experimental protocols designed by the company. The debate implies an enormous responsibility towards public health and is essential due to nonexistent traceability or epidemiological studies in the GMO-producing countries.     

The Anatomy of Developmental Predictors of Healthy Lives Study (TADPOHLS)

Numerous studies have followed people across significant portions of their lives. Secondary analyses with these studies offer opportunities to study life trajectories across diverse samples. To aid integrative efforts, we introduce The Anatomy of Developmental Predictors of Healthy Lives Study (TADPOHLS), a data base that categorizes items and constructs from 14 prospective longitudinal studies that followed participants from adolescence into adulthood. To classify items and measures, we created an extensive typology that provides a common language for categorizing study concepts. We illustrate the utility of the data base by examining adolescent perseverance and optimism as predictors of physical health outcomes across six studies. Adolescent perseverance and optimism were related to better physical health outcomes 15 to 20 years later. Overall, the data base offers a resource that contributes toward life-span studies of positive psychological and physical health.     

People's concerns about biotechnology: some problems and some solutions

Pharmaceuticals and vaccines made by genetic engineering are well accepted all over the world. In contrast, there are many people, particularly in Europe, who are worried that food, made by the same new technology, may harm their health or cause damage to the environment. This is despite the growing evidence that genetically modified crops have the potential to improve world food security and the fact that there have, as yet, been no adverse results of their use in the food chain. Because of these worries and the mechanisms of politics, agricultural biotechnology has become the target of concerns about food safety (BSE, Foot & Mouth Disease), along with globalisation and the power of multinational companies. These concerns will, hopefully, be overcome by a more open and well-informed dialogue between scientists, opinion leaders, educators and the public. If judiciously applied, genetically modified crops will help increase sustainability and the fight against hunger in the world.     

Issues Related to Chemical Analysis,Data Reporting,and Use: Implications for Human Health Risk Assessment of PCBs and PBDEs in Fish Tissue

Recent reports in the scientific literature and the media, related to elevated levels of polychlorinated biphenyls (PCBs) and polybrominated diethyl ethers (PBDEs) in farmed and wild salmon have had significant impacts on public opinion and consumer behavior, influencing the sales of farmed salmon in North America and Europe. The assessment of contaminants in fatty fish, an important source of omega-3 fatty acids, is therefore an exercise in balancing risks and benefits. Human health risk assessors and risk managers will benefit from an understanding of the level of uncertainty that is integrated into all aspects of evaluating risk in this context. Significant variability exists in the way in which analyses are conducted, how data are reported, and how they are used in risk assessments. We conducted an analytical review of PCB and PBDE data in farmed and wild salmon, and identified critical issues having implications on human health risk assessment from fish consumption. These issues include: analytical methodologies used, quantification issues, reporting of QA/QC information, tissue sampling, nature of tissue analyzed, and laboratory competence. This article reviews and outlines these issues, discusses their implications for human health risk assessment, and recommends the consistent application of analytical fish tissue data in human health risk assessment.     

Confidence intervals of effect size for paired studies

To construct a confidence interval of effect size in paired studies, we propose four approximate methods--Wald method, variance-stabilizing transformation method, and signed and modified signed log-likelihood ratio methods. We compare these methods using simulation to determine those that have good performance in terms of coverage probability. In particular, simulations show that the modified signed log-likelihood ratio method produces a confidence interval with a nearly exact coverage probability and highly accurate and symmetric error probabilities even for very small samples. We apply the methods to data from an iron deficiency anemia study.