Trapping and aerogelation of nanoparticles in negative gravity hydrocarbon flames

We report the experimental realization of continuous carbon aerogel production using a flame aerosol reactor by operating it in negative gravity (−g; up-side-down configuration). Buoyancy opposes the fuel and air flow forces in −g, which eliminates convectional outflow of nanoparticles from the flame and traps them in a distinctive non-tipping, flicker-free, cylindrical flame body, where they grow to millimeter-size aerogel particles and gravitationally fall out. Computational fluid dynamics simulations show that a closed-loop recirculation zone is set up in −g flames, which reduces the time to gel for nanoparticles by ≈10[superscript 6] s, compared to positive gravity (upward rising) flames. Our results open up new possibilities of one-step gas-phase synthesis of a wide variety of aerogels on an industrial scale

Experimental investigation of mid-infrared laser action from DY3+ doped fluorozirconate fiber

Efficient continuous-wave laser operation at 2.982 μm is achieved with a Dy3:fluoride fiber pumped using an inhouse-built 1.1 μm ytterbium (III) fiber laser. The laser output power reached is 554 mW, with a maximum slope efficiency of 18% with respect to the launched pump power. Additionally, the measured spontaneous luminescence within the visible wavelength range, under 1.1 μm pumping, is presented and attributed to excited state absorption (ESA). The influence of the ESA on the laser performance is discussed. The results confirm that high output powers from Dy: fluoride fiber laser pumped at 1.1 μm are possible

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.Knut and Alice Wallenberg Foundation Swedish Research Council Houston Methodist Hospital Fondren Foundatio

Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes

For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. IMPORTANCE The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.Peer reviewe

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Three-Dimensional Stochastic Estimation of Porosity Distribution: Benefits of Using Ground-Penetrating Radar Velocity Tomograms in Simulated-Annealing-Based or Bayesian Sequential Simulation Approaches

Estimation of the three-dimensional (3-D) distribution of hydrologic properties and related uncertainty is a key for improved predictions of hydrologic processes in the subsurface. However it is difficult to gain high-quality and high-density hydrologic information from the subsurface. In this regard a promising strategy is to use high-resolution geophysical data (that are relatively sensitive to variations of a hydrologic parameter of interest) to supplement direct hydrologic information from measurements in wells (e.g., logs, vertical profiles) and then generate stochastic simulations of the distribution of the hydrologic property conditioned on the hydrologic and geophysical data. In this study we develop and apply this strategy for a 3-D field experiment in the heterogeneous aquifer at the Boise Hydrogeophysical Research Site and we evaluate how much benefit the geophysical data provide. We run high-resolution 3-D conditional simulations of porosity with both simulated-annealing-based and Bayesian sequential approaches using information from multiple intersecting crosshole gound-penetrating radar (GPR) velocity tomograms and neutron porosity logs. The benefit of using GPR data is assessed by investigating their ability, when included in conditional simulation, to predict porosity log data withheld from the simulation. Results show that the use of crosshole GPR data can significantly improve the estimation of porosity spatial distribution and reduce associated uncertainty compared to using only well log measurements for the estimation. The amount of benefit depends primarily on the strength of the petrophysical relation between the GPR and porosity data, the variability of this relation throughout the investigated site, and lateral structural continuity at the site

Erratum to: The study of cardiovascular risk in adolescents – ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents

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‘They care rudely!’: resourcing and relational health system factors that influence retention in care for people living with HIV in Zambia.

Introduction: Despite access to free antiretroviral therapy (ART), many HIV-positive Zambians disengage from HIV care. We sought to understand how Zambian health system ‘hardware’ (tangible components) and ‘software’ (work practices and behaviour) influenced decisions to disengage from care among ‘lost-to-follow-up’ patients traced by a larger study on their current health status. Methods: We purposively selected 12 facilities, from 4 provinces. Indepth interviews were conducted with 69 patients across four categories: engaged in HIV care, disengaged from care, transferred to another facility and next of kin if deceased. We also conducted 24 focus group discussions with 158 lay and professional healthcare workers (HCWs). These data were triangulated against two consecutive days of observation conducted in each facility. We conducted iterative multilevel analysis using inductive and deductive reasoning. Results: Health system ‘hardware’ factors influencing patients’ disengagement included inadequate infrastructure to protect privacy; distance to health facilities which costs patients time and money; and chronic understaffing which increased wait times. Health system ‘software’ factors related to HCWs’ work practices and clinical decisions, including delayed opening times, file mismanagement, drug rationing and inflexibility in visit schedules, increased wait times, number of clinic visits, and frustrated access to care. While patients considered HCWs as ‘mentors’ and trusted sources of information, many also described them as rude, tardy, careless with details and confidentiality, and favouring relatives. Nonetheless, unlike previously reported, many patients preferred ART over alternative treatment (eg, traditional medicine) for its perceived efficacy, cost-free availability and accompanying clinical monitoring. Conclusion: Findings demonstrate the dynamic effect of health system ‘hardware’ and ‘software’ factors on decisions to disengage. Our findings suggest a need for improved: physical resourcing and structuring of HIV services, preservice and inservice HCWs and management training and mentorship programmes to encourage HCWs to provide ‘patient-centered’ care and exercise ‘flexibility’ to meet patients’ varying needs and circumstances

Rethinking retention: mapping interactions between multiple factors that influence long-term engagement in HIV care

Background: Failure to keep people living with HIV engaged in life-long care and treatment has serious implications for individual and population-level health. Nested within a four-province study of HIV care and treatment outcomes, we explored the dynamic role of social and service-related factors influencing retention in HIV care in Zambia. Methods: From a stratified random sample of 31 facilities, eight clinics were selected, one urban and one rural from each province. Across these sites we conducted a total of 69 in-depth interviews, including with patients (including pregnant women) engaged in-care (n = 28), disengaged from care (n = 15), engaged facility transferee (n = 12), and friends/family of deceased patients (n = 14). At the same sites we conducted 24 focus group discussions with a total of 192 lay and professional healthcare workers (HCWs). Two-day observations in each of the eight facilities helped triangulate data on operational context, provider relations and patient-provider interactions. We ordered and analysed data using an adapted version of Ewart's Social Action Theory. Results: Three overarching findings emerged. First, the experience of living with HIV and engaging in HIV care in Zambia is a social, not individual experience, influenced by social and gendered norms and life goals including financial stability, raising family and living stigma-free. Second, patients and their networks act collectively to negotiate and navigate HIV care. Anticipated responses from social network influenced patients' willingness to engage in care, while emotional and material support from those networks influenced individuals' capacity to remain in HIV care. Lastly, health system factors were most influential where they facilitated or undermined peoples' collective approach to health service use. Participants living with HIV reported facilitation of both their initial and continued engagement in care where services involved social networks, such as during couples testing and community outreach. Conversely, service features that were poorly aligned with respondents' social reality (e.g. workplace obligations) hindered long-term engagement. Conclusions: This study moves beyond listing barriers or socio-ecological groupings, to explain how social and health systems interact to produce HIV care outcomes. Our findings challenge the implicit assumption of individual agency underpinning many retention studies to highlight the social nature of illness and healthcare utilization for HIV in Zambia. This understanding of collective action for accessing and remaining in HIV care should underpin future efforts to revise and reform HIV and potentially other chronic service models and systems