Total Body Photography and Sequential Digital Dermoscopy Imaging for Melanoma Surveillance in Patients Starting Natalizumab for Multiple Sclerosis

Introduction: Natalizumab is an integrin receptor antagonist that has been approved by the Food and Drug Administration to treat multiple sclerosis and Crohn’s disease. The drug has been linked to an increased risk of melanoma. This brief report highlights an innovative clinical approach for monitoring the skin of patients prescribed natalizumab. Methods: We include 2 cases from our skin oncology clinic and a literature review on the incidence of melanoma in patients prescribed natalizumab between 2004 and 2019. Results: In addition to our 2 cases, we found 193 reports of patients with melanoma who were prescribed natalizumab. We propose an innovative and proactive approach using total body photography and sequential digital dermoscopy imaging before starting and while treating patients with natalizumab. Discussion: Given the mechanism of action of natalizumab, many of the melanomas diagnosed likely arose from preexisting melanocytic nevi. Using total body photography before starting this high-risk medication and then sequential digital dermoscopy imaging will increase a dermatologist’s ability to recognize new and preexisting skin lesions that have evolved since the patient began taking natalizumab. Conclusions: Using the latest non-invasive technology to detect skin cancer supports systematic and objective monitoring of changing melanocytic growths in patients prescribed natalizumab, resulting in earlier detection of melanoma and greater cure rates

Tropical grassy biomes: linking ecology, human use and conservation

Tropical grassy biomes (TGBs) are changing rapidly the world over through a coalescence of high rates of land-use change, global change and altered disturbance regimes that maintain the ecosystem structure and function of these biomes. Our theme issue brings together the latest research examining the characterization, complex ecology, drivers of change, and human use and ecosystem services of TGBs. Recent advances in ecology and evolution have facilitated a new perspective on these biomes. However, there continues to be controversies over their classification and state dynamics that demonstrate critical data and knowledge gaps in our quantitative understanding of these geographically dispersed regions. We highlight an urgent need to improve ecological understanding in order to effectively predict the sensitivity and resilience of TGBs under future scenarios of global change. With human reliance on TGBs increasing and their propensity for change, ecological and evolutionary understanding of these biomes is central to the dual goals of sustaining their ecological integrity and the diverse services these landscapes provide to millions of people. This article is part of the themed issue ‘Tropical grassy biomes: linking ecology, human use and conservation’

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Evidence and morality in harm-reduction debates: can we use value-neutral arguments to achieve value-driven goals?

It is common to argue that politicians make selective use of evidence to tacitly reinforce their moral positions, but all stakeholders combine facts and values to produce and use research for policy. The drug policy debate has largely been framed in terms of an opposition between evidence and politics. Focusing on harm reduction provides useful ground to discuss a further opposition proposed by evidence advocates, that between evidence and morality. Can evidence sway individuals from their existing moral positions, so as to “neutralise” morality? And if not, then should evidence advocates change the way in which they frame their arguments? To address these questions, analysis of N=27 interviews with stakeholders involved in drug policy and harm reduction research, advocacy, lobbying, implementation and decision-making in England, UK and New South Wales, Australia, was conducted. Participants’ accounts suggest that although evidence can help focus discussions away from values and principles, exposure to evidence does not necessarily change deeply held views. Whether stakeholders decide to go with the evidence or not seems contingent on whether they embrace a view of evidence as secular faith; a view that is shaped by experience, politics, training, and role. And yet, morality, values, and emotions underpin all stakeholders’ views, motivating their commitment to drug policy and harm reduction. Evidence advocates might thus benefit from morally and emotionally engaging audiences. This paper aims to develop better tools for analysing the role of morality in decision-making, starting with moral foundations theory. Using tools from disciplines such as moral psychology is relevant to the study of the politics of evidence-based policymaking

Propagation of the Madden–Julian Oscillation and scale interaction with the diurnal cycle in a high-resolution GCM

The Madden–Julian Oscillation (MJO) is the chief source of tropical intra-seasonal variability, but is simulated poorly by most state-of-the-art GCMs. Common errors include a lack of eastward propagation at the correct frequency and zonal extent, and too small a ratio of eastward- to westward-propagating variability. Here it is shown that HiGEM, a high-resolution GCM, simulates a very realistic MJO with approximately the correct spatial and temporal scale. Many MJO studies in GCMs are limited to diagnostics which average over a latitude band around the equator, allowing an analysis of the MJO’s structure in time and longitude only. In this study a wider range of diagnostics is applied. It is argued that such an approach is necessary for a comprehensive analysis of a model’s MJO. The standard analysis of Wheeler and Hendon (Mon Wea Rev 132(8):1917–1932, 2004; WH04) is applied to produce composites, which show a realistic spatial structure in the MJO envelopes but for the timing of the peak precipitation in the inter-tropical convergence zone, which bifurcates the MJO signal. Further diagnostics are developed to analyse the MJO’s episodic nature and the “MJO inertia” (the tendency to remain in the same WH04 phase from one day to the next). HiGEM favours phases 2, 3, 6 and 7; has too much MJO inertia; and dies out too frequently in phase 3. Recent research has shown that a key feature of the MJO is its interaction with the diurnal cycle over the Maritime Continent. This interaction is present in HiGEM but is unrealistically weak

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

High prevalence of respiratory symptoms among workers in the development section of a manually operated coal mine in a developing country: A cross sectional study

BACKGROUND: Few studies of miners have been carried out in African countries; most are from South Africa, where the working conditions are assumed to be better than in the rest of Africa. Several studies have focused on respiratory disorders among miners, but development workers responsible for creating underground road ways have not been studied explicitly. This is the first study assessing the associations between exposure to dust and quartz and respiratory symptoms among coal mine workers in a manually operated coal mine in Tanzania, focusing on development workers, as they have the highest exposure to coal dust. METHODS: A cross-sectional study was carried out among 250 production workers from a coal mine. Interviews were performed using modified standardized questionnaires to elicit information on occupational history, demographics, smoking habits and acute and chronic respiratory symptoms. The relationships between current dust exposure as well as cumulative respirable dust and quartz and symptoms were studied by group comparisons as well as logistic regression. RESULTS: Workers from the development group had the highest dust exposure, with arithmetic mean of 10.3 mg/m(3 )for current respirable dust and 1.268 mg/m(3 )for quartz. Analogous exposure results for mine workers were 0.66 mg/m(3 )and 0.03 mg/m(3), respectively; and for other development workers were 0.88 mg/m(3 )and 0.10 mg/m(3), respectively. The workers from the development section had significantly higher prevalence of the acute symptoms of dry cough (45.7%), breathlessness (34.8%) and blocked nose (23.9%). In addition, development workers had significantly more chronic symptoms of breathlessness (17.0%) than the mine workers (6.4%) and the other production workers (2.4%). The highest decile of cumulative exposure to respirable dust was significantly associated with cough (OR = 2.91, 95% CI 1.06, 7.97) as were cumulative exposure to quartz and cough (OR = 2.87, CI 1.05, 7.88), compared with the reference consisting of the group of workers with the lowest quartile of the respective cumulative exposure. CONCLUSION: The development workers in a coal mine had more acute and chronic respiratory symptoms than the mine and the other production workers. In addition, there was an association between high cumulative coal dust and respiratory symptoms

Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+) Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis.Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+) T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+) but not AhR (-/-) mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment.These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation