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.

Should eye protection be worn during dermatological surgery: prospective observational study

Background There is a potential risk of infection with blood-borne viruses if a doctor receives a blood splash to a mucous membrane. The quantification of facial contamination with blood has never been documented in the context of dermatological surgery. Objectives (i) To identify the number of facial blood splashes that occur during skin surgery and to identify the procedures that present higher risks for the operator and assistant. (ii) To assess the provision of eye protection and attitudes to its use in dermatological surgery in the U.K. Methods (i) Prospective, observational study in the skin surgery suite of a U.K. teaching hospital assessing 100 consecutive dermatological surgery procedures, plus 100 consecutive operations in which an assistant was present. Primary outcome: number of face-mask visors with at least one blood splash. Secondary outcomes: to identify if any of the following variables influenced the occurrence of a blood splash: grade of operator, site and type of procedure, and the use of electrocautery. (ii) A postal survey of all U.K.-based members of the British Society of Dermatological Surgery (BSDS) was conducted assessing facilities available and the attitudes of U.K.-based clinicians to the use of face masks during surgery. Results (i) In 33% of all surgical procedures there was at least one facial splash to the operator (range 1–75) and in 15% of procedures the assistant received at least one splash (range 1–11). Use of monopolar electrocautery was significantly less likely to result in splashes to the mask compared with bipolar electrocautery [odds ratio (OR) 0Æ04; 95% confidence interval (CI) 0Æ01–0Æ19]. Compared with the head/neck, operations on the body were significantly more likely to result in splashes to the mask (OR 6Æ52) (95% CI 1Æ7–25Æ07). The type of procedure and the status of the operator did not have a bearing on the likelihood of receiving a splash to the mask. (ii) From the survey, 33 of 159 (20Æ8%) of BSDS members had no face masks available and 54 of 159 (34Æ0%) did not wear any facial protection while operating. The majority (53Æ5%) thought they received a splash in £ 1% of procedures. Conclusions There is a substantial risk of a splash of blood coming into contact with the face during dermatological surgery for both the operator and assistant, regardless of the procedure. The risk of receiving a blood splash to the face may be substantially underestimated by U.K.-based dermatologists. The use of protective eyewear is advisable at all times, but particularly when using bipolar electrocautery, or when operating on high-risk individuals.

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABAB synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.

Predicting long-term outcome after acute ischemic stroke: a simple index works in patients from controlled clinical trials

Background and Purpose—An early and reliable prognosis for recovery in stroke patients is important for initiation of individual treatment and for informing patients and relatives. We recently developed and validated models for predicting survival and functional independence within 3 months after acute stroke, based on age and the National Institutes of Health Stroke Scale score assessed within 6 hours after stroke. Herein we demonstrate the applicability of our models in an independent sample of patients from controlled clinical trials. Methods—The prognostic models were used to predict survival and functional recovery in 5419 patients from the Virtual International Stroke Trials Archive (VISTA). Furthermore, we tried to improve the accuracy by adapting intercepts and estimating new model parameters. Results—The original models were able to correctly classify 70.4% (survival) and 72.9% (functional recovery) of patients. Because the prediction was slightly pessimistic for patients in the controlled trials, adapting the intercept improved the accuracy to 74.8% (survival) and 74.0% (functional recovery). Novel estimation of parameters, however, yielded no relevant further improvement. Conclusions—For acute ischemic stroke patients included in controlled trials, our easy-to-apply prognostic models based on age and National Institutes of Health Stroke Scale score correctly predicted survival and functional recovery after 3 months. Furthermore, a simple adaptation helps to adjust for a different prognosis and is recommended if a large data set is available. (Stroke. 2008;39:000-000.)

Rail passenger crowding, stress, health and safety in Britain

There has long been a question as to whether crowding in rail passenger transport poses a threat to passenger health related to the experience of stress. A review of the scientific literature was conducted. Little rail-specific empirical research was identified. The more general research that does exist suggests that high-density environments are not necessarily perceived as crowded and that stress-related physiological, psychological and behavioural reactions do not necessarily follow from exposure to such environments. Several factors are identified that may moderate the impact of a high-density environment on perceptions of crowding and the subsequent experience and effects of stress. These include, inter alia, perceptions of control and predictability of events. However, if caused, the experience and effects of stress may be made worse by inadequate coach design that gives rise to discomfort. The model that emerges from these findings offers a suitable framework for the development of research questions that should help translate emerging knowledge into practical interventions, for the reduction of any adverse health outcomes associated with crowding.

Coarse-graining and renormalisation group methods for the elucidation of the kinetics of complex nucleation and growth processes

We review our work on generalisations of the Becker-Doring model of cluster-formation as applied to nucleation theory, polymer growth kinetics, and the formation of upramolecular structures in colloidal chemistry. One valuable tool in analysing mathematical models of these systems has been the coarse-graining approximation which enables macroscopic models for observable quantities to be derived from microscopic ones. This permits assumptions about the detailed molecular mechanisms to be tested, and their influence on the large-scale kinetics of surfactant self-assembly to be elucidated. We also summarise our more recent results on Becker-Doring systems, notably demonstrating that cross-inhibition and autocatalysis can destabilise a uniform solution and lead to a competitive environment in which some species flourish at the expense of others, phenomena relevant in models of the origins of life.

Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung

This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage dependent anion channel (VDAC) and cytochrome c in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early to mid gestation (i.e. 28 to 80 days gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days gestation (term ~147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogeny’s.

Order fulfillment in high variety production environments

Providing high levels of product variety and product customization is challenging for many companies. This paper presents a new classification of production and order fulfillment approaches available to manufacturing companies that offer high variety and/or product customization. Six categories of approaches are identified and described. An important emerging approach - open pipeline planning – is highlighted for high variety manufacturing environments. It allows a customer order to be fulfilled from anywhere in the system, enabling greater responsiveness in Build-to-Forecast systems. The links between the open pipeline approach, decoupling concepts and postponement strategies are discussed and the relevance of the approach to the volume automotive sector is highlighted. Results from a simulation study are presented illustrating the potential benefits when products can be reconfigured in an open pipeline system. The application of open pipeline concepts to different manufacturing domains is discussed and the operating characteristics of most relevance are highlighted. In addition to the automotive, sectors such as machinery and instrumentation, computer servers, telecommunications and electronic equipment may benefit from an open pipeline planning approach. When properly designed these systems can significantly enhance order fulfillment performance.

The Definition of Curriculum Areas in Occupational Health Psychology

Across the international educational landscape, numerous higher education institutions (HEIs) offer postgraduate programmes in occupational health psychology (OHP). These seek to empower the next generation of OHP practitioners with the knowledge and skills necessary to advance the understanding and prevention of workplace illness and injury, improve working life and promote healthy work through the application of psychological principles and practices. Among the OHP curricula operated within these programmes there exists considerable variability in the topics addressed. This is due, inter alia, to the youthfulness of the discipline and the fact that the development of educational provision has been managed at the level of the HEI where it has remained undirected by external forces such as the discipline’s representative bodies. Such variability makes it difficult to discern the key characteristics of a curriculum which is important for programme accreditation purposes, the professional development and regulation of practitioners and, ultimately, the long-term sustainability of the discipline. This chapter has as its focus the imperative for and development of consensus surrounding OHP curriculum areas. It begins by examining the factors that are currently driving curriculum developments and explores some of the barriers to such. It then reviews the limited body of previous research that has attempted to discern key OHP curriculum areas. This provides a foundation upon which to describe a study conducted by the current authors that involved the elicitation of subject matter expert opinion from an international sample of academics involved in OHP-related teaching and research on the question of which topic areas might be considered important for inclusion within an OHP curriculum. The chapter closes by drawing conclusions on steps that could be taken by the discipline’s representative bodies towards the consolidation and accreditation of a core curriculum.

MATCH: a new industry-focused approach to medical device development

MATCH (Multidisciplinary Assessment of Technology Centre for Healthcare) is a new collaboration in the UK that aims to support the healthcare sector by creating methods to assess the value of medical devices from concept through to mature product. A major aim of MATCH is to encourage the inclusion of the user throughout the product lifecycle in order to achieve devices that truly meet the requirements of their users. A review of the published literature indicates that user requirements are mainly collected during the design and evaluation stage of the product lifecycle whilst other areas, including the concept stage, have less user involvement. Complementing the literature review is an in-depth consultation with the medical device industry, which has identified a number of barriers encountered by companies when attempting to capture user requirements. These will be addressed by a number of case study projects, performed in collaboration with our industrial partners, that will examine the application and utility of different approaches to collecting and analysing data on user requirements. MATCH is focused on providing advice to device developers on how to select and apply methods that have maximum theoretical strength, practical application, cost-effectiveness and likelihood of wide sector acceptance. Feedback will be sought in order to ensure that the needs of the diverse medical device sector are met.