Leprosy and tuberculosis concomitant infection: a poorly understood, age-old relationship

Historically, archaeological evidence, post-mortem findings and retro- spective analysis of leprosy institutions’ data demonstrates a high observed incidence of concomitant infection with leprosy and tuberculosis (TB). However, reports of concomitant infection in the modern literature remain scarce, with estimates of annual new case detection rates of concomitant infection at approximately 0·02 cases per 100,000 population. Whilst the mechanism for this apparent decline in concomitant infections remains unclear, further research on this topic has remained relatively neglected. Modelling of the interaction of the two organisms has suggested that the apparent decline in observations of concomitant infection may be due to the protective effects of cross immunity, whilst more recently others have questioned whether it is a more harmful relationship, predisposing towards increased host mortality. We review recent evidence, comparing it to previously held understanding on the epidemiological relationship and our own experience of concomitant infection. From this discussion, we highlight several under-investigated areas, which may lead to improvements in the future delivery of leprosy management and services, as well as enhance understanding in other fields of infection management. These include, a) highlighting the need for greater understanding of host immunogenetics involved in concomitant infection, b) whether prolonged courses of high dose steroids pre-dispose to TB infection? and, c) whether there is a risk of rifampicin resistance developing in leprosy patients treated in the face of undiagnosed TB and other infections? Longitudinal work is still required to characterise these temporal relationships further and add to the current paucity of literature on this subject matter

Near-field emission profiling of Rainforest and Cerrado fires in Brazil during SAMBBA 2012

This discussion paper is a preprint. A revision of this manuscript was accepted for the journal Atmospheric Chemistry and Physics (ACP).We profile trace gas and particulate emissions from near-field airborne measurements of discrete smoke plumes in Brazil during the 2012 biomass burning season. The South American Biomass Burning Analysis (SAMBBA) Project conducted during September and October 2012 sampled across two distinct fire regimes prevalent in the Amazon Basin. Combined measurements from a Compact Time Of Flight Aerosol Mass Spectrometer (C-ToF-AMS) and a Single Particle Soot Photometer (SP2) are reported for the first time in a tropical biomass burning environment. Emissions from a mostly-smouldering rainforest wildfire in Rondonia state and numerous smaller flaming Cerrado fires in Tocantins state are presented. While the Cerrado fires appear to be representative of typical fire conditions in the existing literature, the rainforest wildfire likely represents a more extreme example of biomass burning with a bias towards mostly-smouldering emissions. We determined fire integrated modified combustion efficiencies, emission ratios and emission factors for trace gas and particulate components for these two fire types, alongside aerosol microphysical properties. Seven times more black carbon was emitted from the Cerrado fires per unit of fuel combustion (EFBC of 0.13 ± 0.04 g kg−1) compared to the rainforest fire (EFBC of 0.019 ± 0.006 g kg−1) and more than six times the amount of organic aerosol was emitted from the rainforest fire per unit of fuel combustion (EFOC of 5.00 ± 1.58 g kg−1) compared to the Cerrado fires (EFOC of 0.82 ± 0.26 g kg−1). Particulate phase species emitted from the fires sampled are generally lower than those reported in previous studies and in emission inventories, which is likely a combination of differences in fire combustion efficiency and fuel content, along with different measurement techniques. Previous modelling studies focussed on the biomass burning season in tropical South America have required significant scaling of emissions to reproduce in-situ and satellite aerosol concentrations over the region. Our results do not indicate that emission factors used in inventories are biased low, which could be one potential cause of the reported underestimates in modelling studies. This study supplements and updates trace gas and particulate emission factors for fire type specific biomass burning in Brazil for use in weather and climate models. The study illustrates that initial fire conditions can result in substantial differences in terms of their emitted chemical components, which can potentially perturb the Earth system.We would like to acknowledge the substantial efforts of the whole SAMBBA team before, during and after the project. Airborne data was obtained using the BAe-146-301 Atmospheric Research Aircraft (ARA) flown by Directflight Ltd and managed by the Facility for Airborne Atmospheric Measurements (FAAM), which is a joint entity of the Natural Environment Research Council (NERC) and the Met Office. Active fire data was produced by the University of Maryland and acquired from the online Fire Information for Resource Management System (FIRMS; https://earthdata.nasa.gov/data/near-real-time-data/firms/abouts; specific product: MCD14ML). E. Darbyshire was supported by NERC studentship NE/J500057/1 and NE/K500859/1. This work was supported by the NERC SAMBBA project NE/J010073/1

Near-field emission profiling of tropical forest and Cerrado fires in Brazil during SAMBBA 2012

This is the final version. Available from European Geosciences Union (EGU) / Copernicus Publications via the DOI in this record. Data availability: All raw time series data used to derive the emission ratios and factors from the FAAM research aircraft are publicly available from the Centre for Environmental Data Analysis website (http://www.ceda.ac.uk/, last access: 12 March 2018). Direct links to the flight data records are given in the reference list (Facility for Airborne Atmospheric Measurements, Natural Environment Research Council, and Met Office, 2014a, b).We profile trace gas and particulate emissions from near-field airborne measurements of discrete smoke plumes in Brazil during the 2012 biomass burning season. The South American Biomass Burning Analysis (SAMBBA) Project conducted during September and October 2012 sampled across two distinct fire regimes prevalent in the Amazon Basin. Combined measurements from a Compact Time-of-Flight Aerosol Mass Spectrometer (C-ToF-AMS) and a Single Particle Soot Photometer (SP2) are reported for the first time in a tropical biomass burning environment. Emissions from a mostly smouldering tropical forest wildfire in Rondônia state and numerous smaller flaming Cerrado fires in Tocantins state are presented. While the Cerrado fires appear to be representative of typical fire conditions in the existing literature, the tropical forest wildfire likely represents a more extreme example of biomass burning with a bias towards mostly smouldering emissions. We determined fire-integrated modified combustion efficiencies, emission ratios and emission factors for trace gas and particulate components for these two fire types, alongside aerosol microphysical properties. Seven times more black carbon was emitted from the Cerrado fires per unit of fuel combustion (EFBC of 0.13±0.04ĝ€†gĝ€†kg-1) compared to the tropical forest fire (EFBC of 0.019±0.006gĝ€†kg-1), and more than 6 times the amount of organic aerosol was emitted from the tropical forest fire per unit of fuel combustion (EFOM of 8.00±2.53gĝ€†kg-1, EFOC of 5.00±1.58gĝ€†kg-1) compared to the Cerrado fires (EFOM of 1.31±0.42gĝ€†kg-1, EFOC of 0.82±0.26gĝ€†kg-1). Particulate-phase species emitted from the fires sampled are generally lower than those reported in previous studies and in emission inventories, which is likely a combination of differences in fire combustion efficiency and fuel mixture, along with different measurement techniques. Previous modelling studies focussed on the biomass burning season in tropical South America have required significant scaling up of emissions to reproduce in situ and satellite aerosol concentrations over the region. Our results do not indicate that emission factors used in inventories are biased low, which could be one potential cause of the reported underestimates in modelling studies. This study supplements and updates trace gas and particulate emission factors for fire-type-specific biomass burning in Brazil for use in weather and climate models. The study illustrates that initial fire conditions can result in substantial differences in terms of their emitted chemical components, which can potentially perturb the Earth system.NERCMet Offic

Cost of diabetes care in out-patient clinics of Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus (DM) is a growing epidemic and the cost of treating diabetes is largely increasing. The objective of this study was to estimate the cost-of-illness of DM among attendees of out-patient clinics in Karachi, Pakistan. This is the first study conducted from a societal perspective to estimate the cost of managing diabetes in Pakistan.</p> <p>Methods</p> <p>A prevalence-based 'Cost-of-Illness' study for diabetes care was conducted in six different out-patient clinics of Karachi, Pakistan from July to September 2006. A pre-tested questionnaire was administered to collect the data from 345 randomly selected persons with diabetes.</p> <p>Results</p> <p>The annual mean direct cost for each person with diabetes was estimated to be Pakistani rupees 11,580 (US$ 197). Medicines accounted for the largest share of direct cost (46%), followed by laboratory investigations (32%). We found that increased age, the number of complications and longer duration of the disease significantly increase the burden of cost on society (p < 0.001). Comparing cost with family income it was found that the poorest segment of society is spending 18% of total family income on diabetes care.</p> <p>Conclusion</p> <p>This study concluded that substantial expenditure is incurred by people with diabetes; with the implication that resources could be saved by prevention, earlier detection and a reduction in diabetes co-morbidities and complications through improved diabetes care. Large scale and cost-effective prevention programs need to be initiated to maximise health gains and to reverse the advance of this epidemic.</p

The Eastern Origins of the Rise of the West and the “Return” of Asia

With the current interest in China (and India) proliferating within the Western Academy, this article claims that what we are witnessing today is not the rise but the “return” of China (and India). Many academics assume that the West has been the dominant civilization in the world economy in the last 500 years and that the current “rise” of China threatens to knock the West off its perch. However, this article provides an alternative take to this cherished axiom of Eurocentric world history by inverting the standard belief that the West pioneered modernity and then expanded outwards to remake the world. Thus, I argue not only that globalization preceded the rise of the West but that it was Eastern-led on the one hand and that it enabled the Western breakthrough into modernity on the other. This, in turn, rests on my claim that Chinese development stems back not to 1978 but to 960 ce as the Sung Dynasty emerged and subsequently undertook a quasi-industrial miracle. Moreover, between 1450/1492 and ca. 1830 China lay at the centre of the nascent global economy, fanning the integration process alongside other key non-Western regions such as India and West Asia/North Africa. And, while the West was the dominant player after ca. 1830 down to the turn of the third millennium, nevertheless, what we witness today is the return of China to the centre of the global economy whence it came

Comparative reliability and diagnostic performance of conventional 3T magnetic resonance imaging and 1.5T magnetic resonance arthrography for the evaluation of internal derangement of the hip

Objective; To compare the diagnostic accuracy of conventional 3T MRI against 1.5T MR arthrography (MRA) in patients with clinical femoroacetabular impingement (FAI). Methods; Sixty-eight consecutive patients with clinical FAI underwent both 1.5T MRA and 3T MRI. Imaging was prospectively analysed by two musculoskeletal radiologists, blinded to patient outcomes and scored for internal derangement including labral and cartilage abnormality. Interobserver variation was assessed by kappa analysis. Thirty-nine patients subsequently underwent hip arthroscopy and surgical results and radiology findings were analysed. Results; Both readers had higher sensitivities for detecting labral tears with 3T MRI compared to 1.5T MRA (not statistically significant p=0.07). For acetabular cartilage defect both readers had higher statistically significant sensitivities using 3T MRI compared to 1.5T MRA (p=0.02). Both readers had a slightly higher sensitivity for detecting delamination with 1.5T MRA compared to 3T MRI, but these differences were not statistically significant (p=0.66). Interobserver agreement was substantial to perfect agreement for all parameters except the identification of delamination (3T MRI showed moderate agreement and 1.5T MRA substantial agreement). Conclusion; Conventional 3T MRI may be at least equivalent to 1.5T MRA in detecting acetabular labrum and possibly superior to 1.5T MRA in detecting cartilage defects in patients with suspected FAI

The Past and Future of Evolutionary Economics : Some Reflections Based on New Bibliometric Evidence

This document is the Accepted Manuscript version of the following article: Geoffrey M. Hodgson, and Juha-Antti Lamberg, ‘The past and future of evolutionary economics: some reflections based on new bibliometric evidence’, Evolutionary and Institutional Economics Review, first online 20 June 2016. The final publication is available at Springer via doi: http://dx.doi.org/10.1007/s40844-016-0044-3 © Japan Association for Evolutionary Economics 2016The modern wave of ‘evolutionary economics’ was launched with the classic study by Richard Nelson and Sidney Winter (1982). This paper reports a broad bibliometric analysis of ‘evolutionary’ research in the disciplines of management, business, economics, and sociology over 25 years from 1986 to 2010. It confirms that Nelson and Winter (1982) is an enduring nodal reference point for this broad field. The bibliometric evidence suggests that ‘evolutionary economics’ has benefitted from the rise of business schools and other interdisciplinary institutions, which have provided a home for evolutionary terminology, but it has failed to nurture a strong unifying core narrative or theory, which in turn could provide superior answers to important questions. This bibliometric evidence also shows that no strong cluster of general theoretical research immediately around Nelson and Winter (1982) has subsequently emerged. It identifies developmental problems in a partly successful but fragmented field. Future research in ‘evolutionary economics’ needs a more integrated research community with shared conceptual narratives and common research questions, to promote conversation and synergy between diverse clusters of research.Peer reviewedFinal Accepted Versio

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p