Suchergebnisse

© 2018 Background: It is now commonly accepted that there exists a form of drug supply, that involves the non-commercial supply of drugs to friends and acquaintances for little or no profit, which is qualitatively different from profit motivated 'drug dealing proper'. 'Social supply' as it has become known, has a strong conceptual footprint in the United Kingdom, shaped by empirical research, policy discussion and its accommodation in legal frameworks. Though scholarship has emerged in a number of contexts outside the UK, the extent to which social supply has developed as an internationally recognised concept in criminal justice contexts is still unclear. Methods: Drawing on an established international social supply research network across eleven nations, this paper provides the first assessment of social supply as an internationally relevant concept. Data derives from individual and team research stemming from Australia, Belgium, Canada, Czech Republic, Finland, Germany, Hong Kong, the Netherlands, England and Wales, and the United States, supported by expert reflection on research evidence and analysis of sentencing and media reporting in each context. In situ social supply experts addressed a common set of questions regarding the nature of social supply for their particular context including: an overview of social supply research activity, reflection on the extent that differentiation is accommodated in drug supply sentencing frameworks; evaluating the extent to which social supply is recognised in legal discourse and in sentencing practices and more broadly by e.g. criminal justice professionals in the public sphere. A thematic analysis of these scripts was undertaken and emergent themes were developed. Whilst having an absence of local research, New Zealand is also included in the analysis as there exists a genuine discursive presence of social supply in the drug control and sentencing policy contexts in that country. Results: Findings suggest that while social supply has been found to exist as a real and distinct behaviour, its acceptance and application in criminal justice systems ranges from explicit through to implicit. In the absence of dedicated guiding frameworks, strong use is made of discretion and mitigating circumstances in attempts to acknowledge supply differentiation. In some jurisdictions, there is no accommodation of social supply, and while aggravating factors can be applied to differentiate more serious offences, social suppliers remain subject to arbitrary deterrent sentencing apparatus. Conclusion: Due to the shifting sands of politics, mood, or geographical disparity, reliance on judicial discretion and the use of mitigating circumstances to implement commensurate sentences for social suppliers is no longer sufficient. Further research is required to strengthen the conceptual presence of social supply in policy and practice as a behaviour that extends beyond cannabis and is relevant to users of all drugs. Research informed guidelines and/or specific sentencing provisions for social suppliers would provide fewer possibilities for inconsistency and promote more proportionate outcomes for this fast-growing group.

16 páginas.-- 8 figuras.-- 2 tablas.-- 66 referencias.-- Material suplementario http://dx.doi.org/10.3389/fmicb.2015.01342 ; Volcanic caves are filled with colorful microbial mats on the walls and ceilings. These volcanic caves are found worldwide, and studies are finding vast bacteria diversity within these caves. One group of bacteria that can be abundant in volcanic caves, as well as other caves, is Actinobacteria. As Actinobacteria are valued for their ability to produce a variety of secondary metabolites, rare and novel Actinobacteria are being sought in underexplored environments. The abundance of novel Actinobacteria in volcanic caves makes this environment an excellent location to study these bacteria. Scanning electron microscopy (SEM) from several volcanic caves worldwide revealed diversity in the morphologies present. Spores, coccoid, and filamentous cells, many with hair-like or knobby extensions, were some of the microbial structures observed within the microbial mat samples. In addition, the SEM study pointed out that these features figure prominently in both constructive and destructive mineral processes. To further investigate this diversity, we conducted both Sanger sequencing and 454 pyrosequencing of the Actinobacteria in volcanic caves from four locations, two islands in the Azores, Portugal, and Hawai'i and New Mexico, USA. This comparison represents one of the largest sequencing efforts of Actinobacteria in volcanic caves to date. The diversity was shown to be dominated by Actinomycetales, but also included several newly described orders, such as Euzebyales, and Gaiellales. Sixty-two percent of the clones from the four locations shared less than 97% similarity to known sequences, and nearly 71% of the clones were singletons, supporting the commonly held belief that volcanic caves are an untapped resource for novel and rare Actinobacteria. The amplicon libraries depicted a wider view of the microbial diversity in Azorean volcanic caves revealing three additional orders, Rubrobacterales, Solirubrobacterales, and Coriobacteriales. Studies of microbial ecology in volcanic caves are still very limited. To rectify this deficiency, the results from our study help fill in the gaps in our knowledge of actinobacterial diversity and their potential roles in the volcanic cave ecosystems. ; The authors acknowledge the Spanish Ministry of Economy and Competitiveness (project CGL2013-41674-P) and FEDER Funds for financial support. AM acknowledges the support from the Marie Curie Intra-European Fellowship of the European Commission's 7th Framework Programme (PIEF-GA-2012-328689). CR was funded by the Regional Fund for Science and Technology and Pro-Emprego program of the Regional Government of the Azores, Portugal [M3.1.7/F/013/2011, M3.1.7/F/030/2011]. Her work was partly supported by National funds from the Foundation for Science and Technology of the Portuguese Government, [Understanding Underground Biodiversity: Studies in Azorean Lava Tubes (reference PTDC/AMB/70801/2006]. The authors would like to thank the TRU Innovation in Research Grant, TRU UREAP Fund, Western Economic Diversification Canada Fund, Kent Watson (assisted with the Helmcken Falls Cave sample collection), Derrick Horne (UBC BioImaging Facility for the SEM work). We acknowledged the Canadian Ministry of Forests, Lands, and Natural Resource Operations for Park Use Permit#102172. This work was also supported by the Cave Conservancy of the Virginias, the Graduate Research Allocation Committee at UNM Biology, UNM Biology Grove Scholarship, the Student Research Allocation Committee at UNM, the National Speleological Society, the New Mexico Space Grant Consortium, the New Mexico Alliance for Minority Participation Program, the New Mexico Geological Society, and Kenneth Ingham Consulting. We acknowledge support from the UNM Molecular Biology Facility, which is supported by NIH grant number P20GM103452. The authors also wish to thank Fernando Pereira, Ana Rita Varela, Pedro Correia, Berta Borges, and Guida Pires for help during field and lab work in the Azores. The authors gratefully acknowledge the photographic contributions of Kenneth Ingham and Pedro Cardoso and Michael Spilde (SEM images). The authors would like to thank Dr. Steven Van Wagoner (TRU) and Drs. Julian Davies and Vivian Miao (UBC) for their invaluable comments in manuscript preparation. We gratefully acknowledge the help and collecting permits granted by the staff of El Malpais National Monument and Hawai'i Volcanoes National Park (USA). ; Peer reviewed

Slaves and Slave Agency in the Ottoman Empire offers a new contribution to slavery studies relating to the Ottoman Empire. Given the fact that the classical binary of 'slavery' and 'freedom' derives from the transatlantic experience, this volume presents an alternative approach by examining the strong asymmetric relationships of dependency documented in the Ottoman Empire. A closer look at the Ottoman social order discloses manifold and ambiguous conditions involving enslavement practices, rather than a single universal pattern. The authors examine various forms of enslavement and dependency with a particular focus on agency, i. e. the room for maneuver, which the enslaved could secure for themselves, or else the available options for action in situations of extreme individual or group dependencies.

BACKGROUND: CRISPR-based diagnostics are a new class of highly sensitive and specific assays with multiple applications in infectious disease diagnosis. SHERLOCK, or Specific High-Sensitivity Enzymatic Reporter UnLOCKing, is one such CRISPR-based diagnostic that combines recombinase polymerase pre-amplification, CRISPR-RNA base-pairing, and LwCas13a activity for nucleic acid detection. METHODS: We developed SHERLOCK assays capable of detecting all Plasmodium species known to cause human malaria and species-specific detection of P. vivax and P. falciparum, the species responsible for the majority of malaria cases worldwide. We further tested these assays using a diverse panel of clinical samples from the Democratic Republic of the Congo, Uganda, and Thailand and pools of Anopheles mosquitoes from Thailand. In addition, we developed a prototype SHERLOCK assay capable of detecting the dihydropteroate synthetase (dhps) single nucleotide variant A581G associated with P. falciparum sulfadoxine resistance. FINDINGS: The suite of Plasmodium assays achieved analytical sensitivities ranging from 2*5-18*8 parasites per reaction when tested against laboratory strain genomic DNA. When compared to real-time PCR, the P. falciparum assay achieved 94% sensitivity and 94% specificity during testing of 123 clinical samples. Compared to amplicon-based deep sequencing, the dhps SHERLOCK assay achieved 73% sensitivity and 100% specificity when applied to a panel of 43 clinical samples, with false-negative calls only at lower parasite densities. INTERPRETATION: These novel SHERLOCK assays demonstrate the versatility of CRISPR-based diagnostics and their potential as a new generation of molecular tools for malaria diagnosis and surveillance. FUNDING: National Institutes of Health (T32GM007092, R21AI148579, K24AI134990, R01AI121558, UL1TR002489, P30CA016086).

A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.

ABSTRACTFragment‐based drug discovery is a well‐established method for the identification of chemical starting points for development into clinical candidates. Historically, crystallographic fragment screening was perceived to be low‐throughput and time consuming. However, thanks to advances in synchrotron capabilities and the introduction of dedicated facilities, such as the XChem platform at Diamond Light Source, there have been substantial improvements in throughput and integration between sample preparation, data collection and hit identification. Herein we share our experiences of establishing a crystallographic fragment screening facility, our learnings from operating a user programme for ten years and our perspective on applying structural enablement to rapidly progress initial fragment hits to lead‐like molecules.

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

Looking at refugee protection in Latin America, this landmark edited collection assesses what the region has achieved in recent years. It analyses Latin America's main documents in refugee protection, evaluates the particular aspects of different regimes, and reviews their emergence, development and effect, to develop understanding of refugee protection in the region. Drawing from multidisciplinary texts from both leading academics and practitioners, this comprehensive, innovative and highly topical book adopts an analytical framework to understand and improve Latin America's protection of refugees

Two leaders engaged in international co-operation must each build trust by credibly signalling that they will not exploit the other by defecting at the implementation stage. Previous research does not reveal the difficulty and cost of such international reassurance. The role that costly adjustments by markets play in international reassurance is analysed, showing that fully efficient information revelation can be achieved when market actors under intense competitive pressures undergo sufficiently costly adjustments in expectation of international co-operation. 'Nice' leaders can reveal their true preferences simply by saying they intend to co-operate, because 'mean' leaders are unwilling to mislead market actors into undergoing futile costly adjustments. However, market imperfections prevent full information revelation unless market actors prefer international co-operation to the status quo. (British Journal of Political Science / FUB)