Species status of Neisseria gonorrhoeae: Evolutionary and epidemiological inferences from multilocus sequence typing

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2007 Bennett et al; licensee BioMed Central Ltd.Background: Various typing methods have been developed for Neisseria gonorrhoeae, but none provide the combination of discrimination, reproducibility, portability, and genetic inference that allows the analysis of all aspects of the epidemiology of this pathogen from a single data set. Multilocus sequence typing (MLST) has been used successfully to characterize the related organisms Neisseria meningitidis and Neisseria lactamica. Here, the same seven locus Neisseria scheme was used to characterize a diverse collection of N. gonorrhoeae isolates to investigate whether this method would allow differentiation among isolates, and to distinguish these three species. Results: A total of 149 gonococcal isolates were typed and submitted to the Neisseria MLST database. Although relatively few (27) polymorphisms were detected among the seven MLST loci, a total of 66 unique allele combinations (sequence types, STs), were observed, a number comparable to that seen among isolate collections of the more diverse meningococcus. Patterns of genetic variation were consistent with high levels of recombination generating this diversity. There was no evidence for geographical structuring among the isolates examined, with isolates collected in Liverpool, UK, showing levels of diversity similar to a global collection of isolates. There was, however, evidence that populations of N. meningitidis, N. gonorrhoeae and N. lactamica were distinct, with little support for frequent genetic recombination among these species, with the sequences from the gdh locus alone grouping the species into distinct clusters. Conclusion: The seven loci Neisseria MLST scheme was readily adapted to N. gonorrhoeae isolates, providing a highly discriminatory typing method. In addition, these data permitted phylogenetic and population genetic inferences to be made, including direct comparisons with N. meningitidis and N. lactamica. Examination of these data demonstrated that alleles were rarely shared among the three species. Analysis of variation at a single locus, gdh, provided a rapid means of identifying misclassified isolates and determining whether mixed cultures were present.This study is funded by the Wellcome Trust and European Unio

Sub-nanosecond signal propagation in anisotropy engineered nanomagnetic logic chains

Energy efficient nanomagnetic logic (NML) computing architectures propagate and process binary information by relying on dipolar field coupling to reorient closely-spaced nanoscale magnets. Signal propagation in nanomagnet chains of various sizes, shapes, and magnetic orientations has been previously characterized by static magnetic imaging experiments with low-speed adiabatic operation; however the mechanisms which determine the final state and their reproducibility over millions of cycles in high-speed operation (sub-ns time scale) have yet to be experimentally investigated. Monitoring NML operation at its ultimate intrinsic speed reveals features undetectable by conventional static imaging including individual nanomagnetic switching events and systematic error nucleation during signal propagation. Here, we present a new study of NML operation in a high speed regime at fast repetition rates. We perform direct imaging of digital signal propagation in permalloy nanomagnet chains with varying degrees of shape-engineered biaxial anisotropy using full-field magnetic soft x-ray transmission microscopy after applying single nanosecond magnetic field pulses. Further, we use time-resolved magnetic photo-emission electron microscopy to evaluate the sub-nanosecond dipolar coupling signal propagation dynamics in optimized chains with 100 ps time resolution as they are cycled with nanosecond field pulses at a rate of 3 MHz. An intrinsic switching time of 100 ps per magnet is observed. These experiments, and accompanying macro-spin and micromagnetic simulations, reveal the underlying physics of NML architectures repetitively operated on nanosecond timescales and identify relevant engineering parameters to optimize performance and reliability.Comment: Main article (22 pages, 4 figures), Supplementary info (11 pages, 5 sections

RecVAE: a New Variational Autoencoder for Top-N Recommendations with Implicit Feedback

Recent research has shown the advantages of using autoencoders based on deep neural networks for collaborative filtering. In particular, the recently proposed Mult-VAE model, which used the multinomial likelihood variational autoencoders, has shown excellent results for top-N recommendations. In this work, we propose the Recommender VAE (RecVAE) model that originates from our research on regularization techniques for variational autoencoders. RecVAE introduces several novel ideas to improve Mult-VAE, including a novel composite prior distribution for the latent codes, a new approach to setting the $\beta$ hyperparameter for the $\beta$-VAE framework, and a new approach to training based on alternating updates. In experimental evaluation, we show that RecVAE significantly outperforms previously proposed autoencoder-based models, including Mult-VAE and RaCT, across classical collaborative filtering datasets, and present a detailed ablation study to assess our new developments. Code and models are available at https://github.com/ilya-shenbin/RecVAE.Comment: In The Thirteenth ACM International Conference on Web Search and Data Mining (WSDM '20), February 3-7, 2020, Houston, TX, USA. ACM, New York, NY, USA, 9 page

Comparative case studies in integrated care implementation from across the globe: A quest for action

© 2019 The Author(s). Background: Integrated care is the coordination of general and behavioral health and is a highly promising and practical approach to improving healthcare delivery and patient outcomes. While there is growing interest and investment in integrated care implementation internationally, there are no formal guidelines for integrated care implementation applicable to diverse healthcare systems. Furthermore, there is a complex interplay of factors at multiple levels of influence that are necessary for successful implementation of integrated care in health systems. Methods: Guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework (Aarons et al., 2011), a multiple case study design was used to address two research objectives: 1) To highlight current integrated care implementation efforts through seven international case studies that target a range of healthcare systems, patient populations and implementation strategies and outcomes, and 2) To synthesize the shared and unique challenges and successes across studies using the EPIS framework. Results: The seven reported case studies represent integrated care implementation efforts from five countries and continents (United States, United Kingdom, Vietnam, Israel, and Nigeria), target a range of clinical populations and care settings, and span all phases of the EPIS framework. Qualitative synthesis of these case studies illuminated common outer context, inner context, bridging and innovation factors that were key drivers of implementation. Conclusions: We propose an agenda that outlines priority goals and related strategies to advance integrated care implementation research. These goals relate to: 1) the role of funding at multiple levels of implementation, 2) meaningful collaboration with stakeholders across phases of implementation and 3) clear communication to stakeholders about integrated care implementation. Trial registration: Not applicable

Developing Health Information Literacy in Disadvantaged and Dependent Circumstances: The Everyday Role of Family Nurses

This paper examines the challenges of developing health information literacy (HIL) amongst disadvantaged and dependent populations from the perspective of non-information professionals occupying everyday support roles. Our participants were a team of UK Family Nurses providing outreach support to vulnerable young mothers from areas of multiple deprivations. Our data collection methods were observation, interviews, and focus groups. Our participants all believe that they have an important role in developing HIL in clients but are unfamiliar with fundamental overarching information literacy (IL) concepts and models. Consequently, their confidence in their own ability to develop HIL skills in clients is limited. We discuss that to extend primary healthcare practices beyond HIL support to HIL education requires not only IL training, but also an appropriate pedagogical approach adaptable to semi-structured problematic situations. We raise important questions regarding approaches to developing HIL in disadvantaged population

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Formation and evolution of early-type galaxies. II. Models with quasi-cosmological initial conditions

In this study, with the aid of N-Body simulations based on quasi-cosmological initial conditions, we have followed the formation and evolution of two models of early-type galaxies, from their separation from global expansion of the Universe to their collapse to virialized structures, the formation of stars and subsequent nearly passive evolution. The cosmological background we have considered is the Standard CDM. The models have significantly different nitial total mass. Particular care has been paid to the star formation process, heating and cooling of gas, and chemical enrichment. In both models star formation is completed within the first Gyrs of evolution. The structural properties of the present-day models are in good agreement with current observations. The chemical properties, mean metallicity and metallicity gradients also agree with available observational data. Finally, conspicuous galactic winds are found to occur. The models conform to the so-called revised monolithic scheme, because mergers of substructures have occurred very early in the galaxy life. Our results agree with those obtained in other similar recent studies, thus strengthening the idea that the revised monolithic scheme is the right trail to follow in the forest of galaxy formation and evolution.Comment: 21 pages, 19 figures, 3 tables. To be published on Astronomy & Astrophysics (accepted April 12, 2006

“Sexual” Population Structure and Genetics of the Malaria Agent P. falciparum

The population genetics and structure of P. falciparum determine the rate at which malaria evolves in response to interventions such as drugs and vaccines. This has been the source of considerable recent controversy, but here we demonstrate the organism to be essentially sexual, in an area of moderately high transmission in the Lower Shire Valley, Malawi. Seven thousand mosquitoes were collected and dissected, and genetic data were obtained on 190 oocysts from 56 infected midguts. The oocysts were genotyped at three microsatellite loci and the MSP1 locus. Selfing rate was estimated as 50% and there was significant genotypic linkage disequilibrium (LD) in the pooled oocysts. A more appropriate analysis searching for genotypic LD in outcrossed oocysts and/or haplotypic LD in the selfed oocysts found no evidence for LD, indicating that the population was effectively sexual. Inbreeding estimates at MSP1 were higher than at the microsatellites, possibly indicative of immune action against MSP1, but the effect was confounded by the probable presence of null mutations. Mating appeared to occur at random in mosquitoes and evidence regarding whether malaria clones in the same host were related (presumably through simultaneous inoculation in the same mosquito bite) was ambiguous. This is the most detailed genetic analysis yet of P. falciparum sexual stages, and shows P. falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines

Testing the dark energy with gravitational lensing statistics

We study the redshift distribution of two samples of early-type gravitational lenses, extracted from a larger collection of 122 systems, to constrain the cosmological constant in the LCDM model and the parameters of a set of alternative dark energy models (XCDM, Dvali-Gabadadze-Porrati and Ricci dark energy models), under a spatially flat universe. The likelihood is maximized for $\Omega_\Lambda= 0.70 \pm 0.09$ when considering the sample excluding the SLACS systems (known to be biased towards large image-separation lenses) and no-evolution, and $\Omega_\Lambda= 0.81\pm 0.05$ when limiting to gravitational lenses with image separation larger than 2" and no-evolution. In both cases, results accounting for galaxy evolution are consistent within 1$\sigma$. The present test supports the accelerated expansion, by excluding the null-hypothesis (i.e., $\Omega_\Lambda = 0$) at more than 4$\sigma$, regardless of the chosen sample and assumptions on the galaxy evolution. A comparison between competitive world models is performed by means of the Bayesian information criterion. This shows that the simplest cosmological constant model - that has only one free parameter - is still preferred by the available data on the redshift distribution of gravitational lenses. We perform an analysis of the possible systematic effects, finding that the systematic errors due to sample incompleteness, galaxy evolution and model uncertainties approximately equal the statistical errors, with present-day data. We find that the largest sources of systemic errors are the dynamical normalization and the high-velocity cut-off factor, followed by the faint-end slope of the velocity dispersion function.Comment: 14 pages, 10 figures, accepted for publication in The Astrophysical Journal. Updated to match print versio

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe