Megacities and climate change: a brief overview

Cities have developed into the hotspots of human economic activity. From the appearance of the first cities in the Neolithic to 21st century metropolis their impact on the environment has always been apparent. With more people living in cities than in rural environments now it becomes crucial to understand these environmental impacts. With the immergence of megacities in the 20th century and their continued growth in both, population and economic power, the environmental impact has reached the global scale. In this paper we examine megacity impacts on atmospheric composition and climate. We present basic concepts, discuss various definitions of footprints, summarize research on megacity impacts and assess the impact of megacity emissions on air quality and on the climate at the regional to global scale. The intention and ambition of this paper is to give a comprehensive but brief overview of the science with regard to megacities and the environment

Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1 mice compared to wild-type littermates, with this effect becoming more pronounced with disease progression. The reduced FA values were therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were preserved. Significant decreases in water diffusion parallel to the white matter fibers or axial diffusivity were observed in the SOD1 mice, which can be attributed to the axonal degeneration observed by electron microscopy. At the same time, radial diffusivity perpendicular to the spinal column increased in the SOD1 mice, reflecting reduced myelination. These results demonstrate the usefulness of MRI in tracking disease progression in live animals and will aid in the assessment of treatment efficacy. This method could also potentially be adapted to aid the diagnosis and assessment of ALS progression in humans. © 2010 Elsevier Inc. All rights reserved

Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain

Cytoplasmic inclusions containing TDP-43 are a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 is an RNA binding protein involved in gene regulation through control of RNA transcription, splicing and transport. However, the function of TDP-43 in the nervous system is largely unknown and its role in the pathogenesis of ALS is unclear. The aim of this study was to identify genes in the central nervous system that are regulated by TDP-43. RNA-immunoprecipitation with anti-TDP-43 antibody, followed by microarray analysis (RIP-chip), was used to isolate and identify RNA bound to TDP-43 protein from mouse brain. This analysis produced a list of 1839 potential TDP-43 gene targets, many of which overlap with previous studies and whose functions include RNA processing and synaptic function. Immunohistochemistry demonstrated that the TDP-43 protein could be found at the presynaptic membrane of axon terminals in the neuromuscular junction in mice. In conclusion, the finding that TDP-43 binds to RNA that codes for genes related to synaptic function, together with the localization of TDP-43 protein at axon terminals, suggests a role for TDP-43 in the transport of synaptic mRNAs into distal processes

Celebrity advocacy and public engagement: the divergent uses of celebrity

This article sounds a cautionary note about the instrumental use of celebrity advocacy to (re)engage audiences in public life. It begins by setting out the steps necessary to achieve public recognition of a social problem requiring a response. It then presents empirical evidence which suggests that those most interested in celebrity, while also paying attention to the main stories of the day, are also least likely to participate in any form of politics. However, this does not rule out the possibility of forging a link between celebrity and public engagement, raising questions about what would potentially sustain such an articulation. After discussing the broader cultural context of celebrity advocacy in which perceived authenticity functions valorised form of symbolic capital, the article outlines a phenomenological approach to understanding the uses audiences make of celebrity advocacy, using the example of a Ewan McGregor UNICEF appeal for illustration. It concludes that while media encounters with celebrities can underpin a viewer’s sense of self, this is as likely to lead to the rationalisation of inaction as a positive response to a charity appeal

The Climate-system Historical Forecast Project: providing open access to seasonal forecast ensembles from centers around the globe

Fil: Tompkins, Adrian M.. The Abdus Salam; ItaliaFil: Ortiz de Zarate, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Saurral, Ramiro Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Vera, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Centre National de la Recherche Scientifique; FranciaFil: Saulo, Andrea Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Secretaria de Planeamiento. Servicio Meteorológico Nacional; ArgentinaFil: Merryfield, William J.. Canadian Centre for Climate Modelling and Analysis; CanadáFil: Sigmond, Michael. Canadian Centre for Climate Modelling and Analysis; CanadáFil: Lee, Woo Sung. Canadian Centre for Climate Modelling and Analysis; CanadáFil: Baehr, Johanna. Universitat Hamburg; AlemaniaFil: Braun, Alain. Météo-France; FranciaFil: Amy Butler. National Ocean And Atmospheric Administration; Estados UnidosFil: Déqué, Michel. Météo-France; FranciaFil: Doblas Reyes, Francisco J.. Institució Catalana de Recerca i Estudis Avancats; España. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; EspañaFil: Gordon, Margaret. Met Office; Reino UnidoFil: Scaife, Adam A.. University of Exeter; Reino UnidoFil: Yukiko Imada. Japan Meteorological Agency. Meteorological Research Institute. Climate Research Department; JapónFil: Masayoshi Ishii. Japan Meteorological Agency. Meteorological Research Institute. Climate Research Department; JapónFil: Tomoaki Ose. Japan Meteorological Agency. Meteorological Research Institute. Climate Research Department; JapónFil: Kirtman, Ben. University of Miami; Estados UnidosFil: Kumar, Arun. National Ocean And Atmospheric Administration; Estados UnidosFil: Müller, Wolfgang A.. Max-Planck-Institut für Meteorologie; AlemaniaFil: Pirani, Anna. Université Paris-Saclay; FranciaFil: Stockdale, Tim. European Centre for Medium-Range Weather; Reino UnidoFil: Rixen, Michel. World Meteorological Organization. World Climate Research Programme; SuizaFil: Yasuda, Tamaki. Japan Meteorological Agency. Climate Prediction Division; Japó

Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review.

INTRODUCTION: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. PRESENTATION OF CASE: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. DISCUSSION: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. CONCLUSION: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations in ARID1A, FBXW7, PIGR, ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

Aims Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. Methods 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. Results Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. Conclusions In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation

BAERLIN2014 - stationary measurements and source apportionment at an urban background station in Berlin, Germany

The Berlin Air quality and Ecosystem Research: Local and long-range Impact of anthropogenic and Natural hydrocarbons (BAERLIN2014) campaign was conducted during the 3 summer months (June–August) of 2014. During this measurement campaign, both stationary and mobile measurements were undertaken to address complementary aims. This paper provides an overview of the stationary measurements and results that were focused on characterization of gaseous and particulate pollution, including source attribution, in the Berlin–Potsdam area, and quantification of the role of natural sources in determining levels of ozone and related gaseous pollutants. Results show that biogenic contributions to ozone and particulate matter are substantial. One indicator for ozone formation, the OH reactivity, showed a 31% (0.82±0.44s−1) and 75% (3.7±0.90s−1) contribution from biogenic non-methane volatile organic compounds (NMVOCs) for urban background (2.6±0.68s−1) and urban park (4.9±1.0s−1) location, respectively, emphasizing the importance of such locations as sources of biogenic NMVOCs in urban areas. A comparison to NMVOC measurements made in Berlin approximately 20 years earlier generally show lower levels today for anthropogenic NMVOCs. A substantial contribution of secondary organic and inorganic aerosol to PM10 concentrations was quantified. In addition to secondary aerosols, source apportionment analysis of the organic carbon fraction identified the contribution of biogenic (plant-based) particulate matter, as well as primary contributions from vehicles, with a larger contribution from diesel compared to gasoline vehicles, as well as a relatively small contribution from wood burning, linked to measured levoglucosan