Towards the systematic simplification of mechanistic models

Mechanistic models used for prediction should be parsimonious, as models which are over-parameterised may have poor predictive performance. Determining whether a model is parsimonious requires comparisons with alternative model formulations with differing levels of complexity. However, creating alternative formulations for large mechanistic models is often problematic, and usually time-consuming. Consequently, few are ever investigated. In this paper, we present an approach which rapidly generates reduced model formulations by replacing a model’s variables with constants. These reduced alternatives can be compared to the original model, using data based model selection criteria, to assist in the identification of potentially unnecessary model complexity, and thereby inform reformulation of the model. To illustrate the approach, we present its application to a published radiocaesium plant-uptake model, which predicts uptake on the basis of soil characteristics (e.g. pH, organic matter content, clay content). A total of 1024 reduced model formulations were generated, and ranked according to five model selection criteria: Residual Sum of Squares (RSS), AICc, BIC, MDL and ICOMP. The lowest scores for RSS and AICc occurred for the same reduced model in which pH dependent model components were replaced. The lowest scores for BIC, MDL and ICOMP occurred for a further reduced model in which model components related to the distinction between adsorption on clay and organic surfaces were replaced. Both these reduced models had a lower RSS for the parameterisation dataset than the original model. As a test of their predictive performance, the original model and the two reduced models outlined above were used to predict an independent dataset. The reduced models have lower prediction sums of squares than the original model, suggesting that the latter may be overfitted. The approach presented has the potential to inform model development by rapidly creating a class of alternative model formulations, which can be compared.

Effort-reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort

Objectives: To investigate the association between effort-reward imbalance (ERI) at work and sedentary lifestyle. Methods: Cross-sectional data from the ongoing Finnish Public Sector Study related to 30 433 women and 7718 men aged 17-64 were used (n = 35 918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as <2.00 metabolic equivalent task (MET) hours/day. Logistic regression with generalized estimating equations was used as an analysis method to include both individual and work unit level predictors in the models. Adjustments were made for age, marital status, occupational status, job contract, smoking, and heavy drinking. Results: Twenty five percent of women and 27% of men had a sedentary lifestyle. High individual level ERI was associated with a higher likelihood of sedentary lifestyle both among women (odds ratio (OR) = 1.08, 95% CI 1.01 to 1.16) and men (OR = 1.17, 95% CI 1.02 to 1.33). These associations were not explained by relevant confounders and they were also independent of work unit level job strain measured as a ratio of job demands and control. Conclusions: A mismatch between high occupational effort spent and low reward received in turn seems to be associated with an elevated risk of sedentary lifestyle, although this association is relatively weak.

Effort-reward imbalance at work and the co-occurrence of lifestyle risk factors: cross-sectional survey in a sample of 36,127 public sector employees

Background In occupational life, a mismatch between high expenditure of effort and receiving few rewards may promote the co-occurrence of lifestyle risk factors, however, there is insufficient evidence to support or refute this hypothesis. The aim of this study is to examine the extent to which the dimensions of the Effort-Reward Imbalance (ERI) model – effort, rewards and ERI – are associated with the co-occurrence of lifestyle risk factors. Methods Based on data from the Finnish Public Sector Study, cross-sectional analyses were performed for 28,894 women and 7233 men. ERI was conceptualized as a ratio of effort and rewards. To control for individual differences in response styles, such as a personal disposition to answer negatively to questionnaires, occupational and organizational -level ecological ERI scores were constructed in addition to individual-level ERI scores. Risk factors included current smoking, heavy drinking, body mass index ≥25 kg/m2, and physical inactivity. Multinomial logistic regression models were used to estimate the likelihood of having one risk factor, two risk factors, and three or four risk factors. The associations between ERI and single risk factors were explored using binary logistic regression models. Results After adjustment for age, socioeconomic position, marital status, and type of job contract, women and men with high ecological ERI were 40% more likely to have simultaneously ≥3 lifestyle risk factors (vs. 0 risk factors) compared with their counterparts with low ERI. When examined separately, both low ecological effort and low ecological rewards were also associated with an elevated prevalence of risk factor co-occurrence. The results obtained with the individual-level scores were in the same direction. The associations of ecological ERI with single risk factors were generally less marked than the associations with the co-occurrence of risk factors. Conclusion This study suggests that a high ratio of occupational efforts relative to rewards may be associated with an elevated risk of having multiple lifestyle risk factors. However, an unexpected association between low effort and a higher likelihood of risk factor co-occurrence as well as the absence of data on overcommitment (and thereby a lack of full test of the ERI model) warrant caution in regard to the extent to which the entire ERI model is supported by our evidence.

Atopic Dermatitis

A 10-year-old girl with atopic dermatitis reports itching that has recently become relentless, resulting in sleep loss. Her mother has been reluctant to treat the girl with topical corticosteroids, because she was told that they damage the skin, but she is exhausted and wants relief for her child. How should the problem be managed?

Introducing the National Library for Health Skin Conditions Specialist Library

Background: This paper introduces the new National Library for Health Skin Conditions Specialist Library http://www.library.nhs.uk/skin. Description: The aims, scope and audience of the new NLH Skin Conditions Specialist Library, and the composition and functions of its core Project Team, Editorial Team and Stakeholders Group are described. The Library's collection building strategy, resource and information types, editorial policies, quality checklist, taxonomy for content indexing, organisation and navigation, and user interface are all presented in detail. The paper also explores the expected impact and utility of the new Library, as well as some possible future directions for further development. Conclusion: The Skin Conditions Specialist Library is not just another new Web site that dermatologists might want to add to their Internet favourites then forget about it. It is intended to be a practical, "one-stop shop" dermatology information service for everyday practical use, offering high quality, up-to-date resources, and adopting robust evidence-based and knowledge management approaches.

Conflicts of interest in dermatology

Conflicts of interest exist in dermatology when professional judgement concerning a primary interest, such as research validity, may be influenced by a secondary interest, such as financial gain from a for-profit organization. Conflict of interest is a condition and not a behaviour, although there is clear evidence that gifts influence behaviour. Little has been written about conflicts of interest in dermatology. This series of papers raises awareness of the subject by exploring it in greater depth from the perspective of a dermatology researcher, an industry researcher, a dermatology journal editor, a health services researcher and a patient representative. Collectively, they illustrate the many ways in which conflicts can pervade the world of dermatology publications and patient support group activities.

Early allergen exposure and atopic eczema

Background The relationship between exposure to indoor aeroallergens in early life and subsequent eczema is unclear. We have previously failed to show any significant associations between early life exposure to house dust mite and cat fur allergens and either sensitization to these allergens or wheeze. We have also previously reported a lower prevalence of parent-reported, doctor-diagnosed eczema by age 2 years for children exposed to higher concentrations of house dust mite, but no other associations with other definitions of eczema or for exposure to cat allergen. Objectives To extend the exposure–response analysis of allergen exposure and eczema outcomes measured up to age 8 years, and to investigate the role of other genetic and environmental determinants. Methods A total of 593 children (92Æ4% of those eligible) born to all newly pregnant women attending one of three general practitioner surgeries in Ashford, Kent, were followed from birth to age 8 years. Concentrations of house dust mite and cat allergen were measured in dust samples collected from the home at 8 weeks after birth. The risk of subsequent eczema as defined by the U.K. diagnostic criteria was determined according to different levels (quintiles) of allergen exposure at birth. Results By age 8 years, 150 (25Æ3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28Æ0%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergen were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio, OR 1Æ37 for third quintile compared with first), and then to fall for the two highest quintiles (OR 0Æ66 and 0Æ71) even after controlling for confounding factors. Conclusions The lack of any clear exposure–disease relationship between allergens in early life and subsequent eczema argues against allergen exposure being a major factor causing eczema. If the lower levels of eczema at higher levels of house dust mite are confirmed, then interventions aimed at reducing house dust mite in early infancy could paradoxically increase the risk of subsequent eczema.

How to reply to referees’ comments when submitting manuscripts for publication

Background: The publication of articles in peer-reviewed scientific journals is a fairly complex and stepwise process that involves responding to referees’ comments. Little guidance is available in the biomedical literature on how to deal with such comments. Objective: The objective of this article is to provide guidance to novice writers on dealing with peer review comments in a way that maximizes the chance of subsequent acceptance. Methods: This will be a literature review and review of the author’s experience as a writer and referee. Results: Where possible, the author should consider revising and resubmitting rather than sending an article elsewhere. A structured layout for responding to referees’ comments is suggested that includes the 3 golden rules: (1) respond completely; (2) respond politely; and (3) respond with evidence. Conclusion: Responding to referees’ comments requires the writer to overcome any feelings of personal attack, and to instead concentrate on addressing referees’ concerns in a courteous, objective, and evidencebased way. (J Am Acad Dermatol 2004;51:79-83.)

How epidemiology has challenged 3 prevailing concepts about atopic dermatitis

We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple causeand- effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgEmediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a comanifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.

New treatments for atopic dermatitis

Atopic dermatitis now affects 15% to 20% of chil­ dren in developed countries, and prevalence in cities in developing countries undergoing rapid demographic changes is quickly following suit.1 Most cases of atopic dermatitis in a given community are mild, but children with moderate to severe disease can have continuous itching and associated loss of sleep. The social stigma of a visible skin disease can also be soul destroying for both patient and family. A few studies have suggested that some degree of prevention of the disease is possible,2 although these measures have not been taken up widely. In the absence of any treatment that is known to alter the clinical course of the disease, most treatment is aimed at reducing symp­ toms and signs. After a relative lull of almost 40 years, new drugs—tacrolimus and pimecrolimus—have appeared that offer different approaches to managing this miserable disease. Do they work? Are they safe? And how do they compare with existing treatments?