Unexpected diversity and complexity of the Guerrero Negro hypersaline microbial mat

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 72 (2006): 3685-3695, doi:10.1128/AEM.72.5.3685-3695.2006.We applied nucleic acids-based molecular methods, combined with estimates of biomass (ATP), pigments and microelectrode measurements of chemical gradients, to map microbial diversity vertically on the mm-scale in a hypersaline microbial mat from Guerrero Negro, Baja California Sur, Mexico. To identify the constituents of the mat, small-subunit ribosomal RNA genes were amplified by PCR from community genomic DNA extracted from layers, cloned and sequenced. Bacteria dominated the mat and displayed unexpected and unprecedented diversity. The majority (1336) of 1586 bacterial 16S rRNA sequences generated were unique, representing 752 species (≥97% rRNA sequence identity) in 42 of the main bacterial phyla, including 15 novel candidate phyla. The diversity of the mat samples differentiated according to the chemical milieu defined by concentrations of O2 and H2S. Chloroflexi formed the majority of the biomass by percentage of bulk rRNA and of clones in rRNA gene libraries. This result contradicts the general belief that Cyanobacteria dominate these communities. Although Cyanobacteria constituted a large fraction of the biomass in the upper few mm (>80% of total rRNA and photosynthetic pigments), Chloroflexi sequences were conspicuous throughout the mat. Filamentous Chloroflexi were identified by fluorescent in-situ hybridization within the polysaccharide sheaths of the prominent cyanobacterium Microcoleus chthonoplastes in addition to free-living in the mat. The biological complexity of the mat far exceeds that observed in other polysaccharide-rich microbial ecosystems, such as human and mouse distal guts, and suggests that positive feedbacks exist between chemical complexity and biological diversity.R. Ley was supported in part by an NRC- NASA Astrobiology Institutes Post Doctoral Associateship, J. Spear by an Agouron Institute postdoctoral fellowship. This work was supported by the NASA Cooperative Agreement with the University of Colorado Center for Astrobiology to N. R. Pace

Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling

Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer

Integration of a nationally procured electronic health record system into user work practices

BACKGROUND: Evidence suggests that many small- and medium-scale Electronic Health Record (EHR) implementations encounter problems, these often stemming from users' difficulties in accommodating the new technology into their work practices. There is the possibility that these challenges may be exacerbated in the context of the larger-scale, more standardised, implementation strategies now being pursued as part of major national modernisation initiatives. We sought to understand how England's centrally procured and delivered EHR software was integrated within the work practices of users in selected secondary and specialist care settings. METHODS: We conducted a qualitative longitudinal case study-based investigation drawing on sociotechnical theory in three purposefully selected sites implementing early functionality of a nationally procured EHR system. The complete dataset comprised semi-structured interview data from a total of 66 different participants, 38.5 hours of non-participant observation of use of the software in context, accompanying researcher field notes, and hospital documents (including project initiation and lessons learnt reports). Transcribed data were analysed thematically using a combination of deductive and inductive approaches, and drawing on NVivo8 software to facilitate coding. RESULTS: The nationally led "top-down" implementation and the associated focus on interoperability limited the opportunity to customise software to local needs. Lack of system usability led users to employ a range of workarounds unanticipated by management to compensate for the perceived shortcomings of the system. These had a number of knock-on effects relating to the nature of collaborative work, patterns of communication, the timeliness and availability of records (including paper) and the ability for hospital management to monitor organisational performance. CONCLUSIONS: This work has highlighted the importance of addressing potentially adverse unintended consequences of workarounds associated with the introduction of EHRs. This can be achieved with customisation, which is inevitably somewhat restricted in the context of attempts to implement national solutions. The tensions and potential trade-offs between achieving large-scale interoperability and local requirements is likely to be the subject of continuous debate in England and beyond with no easy answers in sight

Preventing Violence in Seven Countries: Global Convergence in Policies

Do governments take the measures that are supported by the best scientific evidence available? We present a brief review of the situation in: Australia, Canada, Germany, the Netherlands, Spain, the United Kingdom, and the United States. Our findings show surprisingly similar developments across countries. While all seven countries are moving towards evidence-based decision making regarding policies and programs to prevent violence, there remain a number of difficulties before this end can be achieved. For example, there continue to be few randomized controlled trials or rigorous quasi-experimental studies on aggression and violence. Results from experimental research are essential to both policy makers and researchers to determine the effectiveness of programs as well as increase our knowledge of the problem. Additionally, all noted that media attention for violence is high in their country, often leading to management by crisis with the result that policies are not based on evidence, but instead seek to appease public outrage. And perhaps because of attendant organizational problems (i.e., in many countries violence prevention was not under the guise of one particular agency or ministry), most have not developed a coordinated policy focusing on the prevention of violence and physical aggression. It is hypothesized that leaders in democratic countries, who must run for election every 4 to 6 years, may feel a need to focus on short-term planning rather than long-term preventive policies since the costs, but not the benefits for the latter would be incurred while they still served in office. We also noted a general absence of expertise beyond those within scientific circles. The need for these ideas to be more widely accepted will be an essential ingredient to real and sustaining change. This means that there must be better communication and increased understanding between researchers and policy makers. Toward those ends, the recent establishment of the Campbell Collaboration, formed to provide international systematic reviews of program effectiveness, will make these results more available and accessible to politicians, administrators and those charged with making key policy decision

Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

ICAR: endoscopic skull‐base surgery

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Towards an appreciation of ethics in social enterprise business models

How can a critical analysis of entrepreneurial intention inform an appreciation of ethics in social enterprise business models? In answering this question, we consider the ethical commitments that inform entrepreneurial action (inputs) and the hybrid organisations that emerge out of these commitments and actions (outputs). Ethical theory can be a useful way to re-orient the field of social enterprise so that it is more critical of bureaucratic (charitable) and market-driven (business) enterprises connected to neo-liberal doctrine. Social enterprise hybrid business models are therefore reframed as outcomes of both ethical and entrepreneurial intentions. We challenge the dominant conceptualisation of social enterprise as a hybrid blend of mission and market (purpose-versus-resource) by reframing hybridity in terms of the moral choice of economic system (redistribution, reciprocity and market) and social value orientation (personal, mutual or public benefit). We deconstruct the political foundations of charitable trading activities (CTAs), co-operative and mutual enterprises (CMEs) and socially responsible businesses (SRBs) by examining the rationalities (formal, social and substantive) and ethical commitments (utilitarian, communitarian, pragmatic) that underpin them. Whilst conceptual modelling of social enterprise is not new, this paper contributes to knowledge by developing a theory of social enterprise ethics based on the moral/political choices that are made by entrepreneurs (knowingly and unknowingly) when choosing between systems of economic exchange and social value orientation, then expressing it through a legal form