An analysis of the subtypes of dengue fever infections in Barbados 2003–2007 by reverse transcriptase polymerase chain reaction

<p>Abstract</p> <p>Background</p> <p>To perform a retrospective analysis of patients with IgM antibodies to dengue fever infection to determine the serotypes present by molecular techniques. A representative sample (~20%/per year) of patients diagnosed with dengue fever infection were selected based on the detection of IgM antibodies in the acute phase serum sample. RNA was extracted from each sample and reverse transcribed. Following this, the amplicons were electrophoresed and serotyped based on band sizes.</p> <p>Results</p> <p>This study consisted of 71 males and 101 females ranging in age from 0 – 50+ yrs giving a total of 172 persons with an average of 34.4 patients per year. Onset averaged 6.9 days ranging from 0–90 days. Common symptoms were as follows: fever (69%), headache (52%), arthralgia (36%), ocular pain (32%), emesis (15%) and lumbar pain (15%). All patients investigated with the exception of one, were infected with DENV-3.</p> <p>Conclusion</p> <p>DENV-3 is currently circulating on the island and not DENV-1 or DENV-2 as in previous years. This has implications for the enhancement of clinical, laboratory and environmental surveillance systems.</p

A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome

DNA topoisomerases are required to resolve DNA topological stress. Despite this essential role, abortive topoisomerase activity generates aberrant protein-linked DNA breaks, jeopardising genome stability. Here, to understand the genomic distribution and mechanisms underpinning topoisomerase-induced DNA breaks, we map Top2 DNA cleavage with strand-specific nucleotide resolution across the S. cerevisiae and human genomes—and use the meiotic Spo11 protein to validate the broad applicability of this method to explore the role of diverse topoisomerase family members. Our data characterises Mre11-dependent repair in yeast and defines two strikingly different fractions of Top2 activity in humans: tightly localised CTCF-proximal, and broadly distributed transcription-proximal, the latter correlated with gene length and expression. Moreover, single nucleotide accuracy reveals the influence primary DNA sequence has upon Top2 cleavage—distinguishing sites likely to form canonical DNA double-strand breaks (DSBs) from those predisposed to form strand-biased DNA single-strand breaks (SSBs) induced by etoposide (VP16) in vivo

BlinkML: Efficient Maximum Likelihood Estimation with Probabilistic Guarantees

The rising volume of datasets has made training machine learning (ML) models a major computational cost in the enterprise. Given the iterative nature of model and parameter tuning, many analysts use a small sample of their entire data during their initial stage of analysis to make quick decisions (e.g., what features or hyperparameters to use) and use the entire dataset only in later stages (i.e., when they have converged to a specific model). This sampling, however, is performed in an ad-hoc fashion. Most practitioners cannot precisely capture the effect of sampling on the quality of their model, and eventually on their decision-making process during the tuning phase. Moreover, without systematic support for sampling operators, many optimizations and reuse opportunities are lost. In this paper, we introduce BlinkML, a system for fast, quality-guaranteed ML training. BlinkML allows users to make error-computation tradeoffs: instead of training a model on their full data (i.e., full model), BlinkML can quickly train an approximate model with quality guarantees using a sample. The quality guarantees ensure that, with high probability, the approximate model makes the same predictions as the full model. BlinkML currently supports any ML model that relies on maximum likelihood estimation (MLE), which includes Generalized Linear Models (e.g., linear regression, logistic regression, max entropy classifier, Poisson regression) as well as PPCA (Probabilistic Principal Component Analysis). Our experiments show that BlinkML can speed up the training of large-scale ML tasks by 6.26x-629x while guaranteeing the same predictions, with 95% probability, as the full model.Comment: 22 pages, SIGMOD 201

Real-Time Feedback of Air Quality in Children’s Bedrooms Reduces Exposure to Secondhand Smoke

Introduction:Secondhand smoke (SHS) exposure creates health risks for nonsmokers and is especially detrimental to children. This study evaluated whether immediate feedback in response to poor indoor air quality in children’s bedrooms can reduce the potential for SHS exposure, as measured by adherence to a World Health Organization (WHO) indoor air standard.Methods:Homes that contained children and an adult who regularly smoked inside (n=298) had an air particle monitor installed in the child’s bedroom. These devices measured the concentration of particulate matter (PM2.5) for approximately three months and, for half of the participants, immediately provided aversive feedback in response to elevated PM2.5. Hierarchical linear models were fit to the data to assess whether the intervention increased the probability that: 1) a given day was below the WHO guideline for daily exposure, and 2) a household established and maintained a smoke-free home (SFH), operationalized as achieving 30 consecutive days below the WHO guideline. The intervention’s impact was calculated as groupby- time effects.Results:The likelihood that a child’s bedroom met the WHO indoor air quality standard on a given day increased such that the baseline versus post-baseline odds ratio (OR) of maintaining indoor PM2.5 levels below the WHO guideline was 2.38 times larger for participants who received the intervention. Similarly, the baseline versus post-baseline OR associated with achieving an SFH was 3.49 times larger for participants in the intervention group.Conclusions:The real-time intervention successfully drove clinically meaningful changes in smoking behavior that mitigated indoor PM2.5 levels in children’s bedrooms and thereby reduced SHS exposure. These results demonstrate the effectiveness of targeting sensitive microenvironments by giving caregivers actionable information about children’s SHS risks. Future extensions should examine additional microenvironments and focus on identifying the potential for SHS exposure before it occurs

Electrical Polarization of Titanium Surfacesfor the Enhancement of Osteoblast Differentiation

Electrical stimulation has been used clinically to promote bone regeneration in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports suggesting its beneficial effects on bone formation. However, the use of electrical stimulation of titanium (Ti) implants to enhance osseointegration is less understood, in part because of the few in vitro models that attempt to represent the in vivo environment. In this article, the design of a new in vitro system that allows direct electrical stimulation of osteoblasts through their Ti substrates without the flow of exogenous currents through the media is presented, and the effect of applied electrical polarization on osteoblast differentiation and local factor production was evaluated. A custom-made polycarbonate tissue culture plate was designed to allow electrical connections directly underneath Ti disks placed inside the wells, which were supplied with electrical polarization ranging from 100 to 500 mV to stimulate MG63 osteoblasts. Our results show that electrical polarization applied directly through Ti substrates on which the cells are growing in the absence of applied electrical currents may increase osteoblast differentiation and local factor production in a voltage-dependent manner. Bioelectromagnetics © 2013 Wiley Periodicals, IncElectrical stimulation has been used clinically to promote bone regeneration in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports suggesting its beneficial effects on bone formation. However, the use of electrical stimulation of titanium (Ti) implants to enhance osseointegration is less understood, in part because of the few in vitro models that attempt to represent the in vivo environment. In this article, the design of a new in vitro system that allows direct electrical stimulation of osteoblasts through their Ti substrates without the flow of exogenous currents through the media is presented, and the effect of applied electrical polarization on osteoblast differentiation and local factor production was evaluated. A custom-made polycarbonate tissue culture plate was designed to allow electrical connections directly underneath Ti disks placed inside the wells, which were supplied with electrical polarization ranging from 100 to 500 mV to stimulate MG63 osteoblasts. Our results show that electrical polarization applied directly through Ti substrates on which the cells are growing in the absence of applied electrical currents may increase osteoblast differentiation and local factor production in a voltage-dependent manner. Bioelectromagnetics © 2013 Wiley Periodicals, In

Differential responses of osteoblast lineage cells to nanotopographically-modified, microroughened titaniumealuminumevanadium alloy surfaces

Surface structural modifications at the micrometer and nanometer scales have driven improved success rates of dental and orthopaedic implants by mimicking the hierarchical structure of bone. However, how initial osteoblast-lineage cells populating an implant surface respond to different hierarchical surface topographical cues remains to be elucidated, with bone marrow mesenchymal stem cells (MSCs) or immature osteoblasts as possible initial colonizers. Here we show that in the absence of any exogenous soluble factors, osteoblastic maturation of primary human osteoblasts (HOBs) but not osteoblastic differentiation of MSCs is strongly influenced by nanostructures superimposed onto a microrough Ti6Al4V (TiAlV) alloy. The sensitivity of osteoblasts to both surface microroughness and nanostructures led to a synergistic effect on maturation and local factor production. Osteoblastic differentiation of MSCs was sensitive to TiAlV surface microroughness with respect to production of differentiation markers, but no further enhancement was found when cultured on micro/nanostructured surfaces. Superposition of nanostructures to microroughened surfaces affected final MSC numbers and enhanced production of vascular endothelial growth factor (VEGF) but the magnitude of the response was lower than for HOB cultures. Our results suggest that the differentiation state of osteoblast-lineage cells determines the recognition of surface nanostructures and subsequent cell response, which has implications for clinical evaluation of new implant surface nanomodifications.Surface structural modifications at the micrometer and nanometer scales have driven improved success rates of dental and orthopaedic implants by mimicking the hierarchical structure of bone. However, how initial osteoblast-lineage cells populating an implant surface respond to different hierarchical surface topographical cues remains to be elucidated, with bone marrow mesenchymal stem cells (MSCs) or immature osteoblasts as possible initial colonizers. Here we show that in the absence of any exogenous soluble factors, osteoblastic maturation of primary human osteoblasts (HOBs) but not osteoblastic differentiation of MSCs is strongly influenced by nanostructures superimposed onto a microrough Ti6Al4V (TiAlV) alloy. The sensitivity of osteoblasts to both surface microroughness and nanostructures led to a synergistic effect on maturation and local factor production. Osteoblastic differentiation of MSCs was sensitive to TiAlV surface microroughness with respect to production of differentiation markers, but no further enhancement was found when cultured on micro/nanostructured surfaces. Superposition of nanostructures to microroughened surfaces affected final MSC numbers and enhanced production of vascular endothelial growth factor (VEGF) but the magnitude of the response was lower than for HOB cultures. Our results suggest that the differentiation state of osteoblast-lineage cells determines the recognition of surface nanostructures and subsequent cell response, which has implications for clinical evaluation of new implant surface nanomodifications

Role of a2b1 integrins in mediating cell shape on microtextured titanium surfaces

Surface microroughness plays an important role in determining osteoblast behavior on titanium. Previous studies have shown that osteoblast differentiation on microtextured titanium substrates is dependent on alpha-2 beta-1 (a2b1) integrin signaling. This study used focused ion beam milling and scanning electron microscopy, combined with three-dimensional image reconstruction, to investigate early interactions of individual cells with their substrate and the role of integrin a2b1 in determining cell shape. MG63 osteoblast-like cells on sand blasted/acid etched (SLA) Ti surfaces after 3 days of culturing indicated decreased cell number, increased cell differentiation, and increased expression of mRNA levels for a1, a2, aV, and b1 integrin subunits compared to cells on smooth Ti (PT) surfaces. a2 or b1 silenced cells exhibited increased cell number and decreased differentiation on SLA compared to wild-type cells. Wild-type cells on SLA possessed an elongated morphology with reduced cell area, increased cell thickness, and more apparent contact points. Cells on PT exhibited greater spreading and were relatively flat. Silenced cells possessed a morphology and phenotype similar to wild-type cells grown on PT. These observations indicate that surface microroughness affects cell response via a2b1 integrin signaling, resulting in a cell shape that promotes osteoblastic differentiation. VC 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 564–573, 2015.Surface microroughness plays an important role in determining osteoblast behavior on titanium. Previous studies have shown that osteoblast differentiation on microtextured titanium substrates is dependent on alpha-2 beta-1 (a2b1) integrin signaling. This study used focused ion beam milling and scanning electron microscopy, combined with three-dimensional image reconstruction, to investigate early interactions of individual cells with their substrate and the role of integrin a2b1 in determining cell shape. MG63 osteoblast-like cells on sand blasted/acid etched (SLA) Ti surfaces after 3 days of culturing indicated decreased cell number, increased cell differentiation, and increased expression of mRNA levels for a1, a2, aV, and b1 integrin subunits compared to cells on smooth Ti (PT) surfaces. a2 or b1 silenced cells exhibited increased cell number and decreased differentiation on SLA compared to wild-type cells. Wild-type cells on SLA possessed an elongated morphology with reduced cell area, increased cell thickness, and more apparent contact points. Cells on PT exhibited greater spreading and were relatively flat. Silenced cells possessed a morphology and phenotype similar to wild-type cells grown on PT. These observations indicate that surface microroughness affects cell response via a2b1 integrin signaling, resulting in a cell shape that promotes osteoblastic differentiation. VC 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 564–573, 2015

Rough titanium alloys regulate osteoblast production of angiogenic factors

Multiple biomaterials are clinically available to spine surgeons for performing interbody fusion. Poly-ether-ether-ketone (PEEK) is used frequently for lumbar spine interbody fusion, but alternative materials are also used, including titanium (Ti) alloys. Previously, we showed that osteoblasts exhibit a more differentiated phenotype when grown on machined or grit-blasted titanium aluminum vanadium (Ti6Al4V) alloys with micron-scale roughened surfaces than when grown on smoother Ti6Al4V surfaces or on tissue culture polystyrene (TCPS). We hypothesized that osteoblasts cultured on rough Ti alloy substrates would present a more mature osteoblast phenotype than cells cultured on PEEK, suggesting that textured Ti6Al4V implants may provide a more osteogenic surface for interbody fusion devices. PURPOSE: The aim of the present study was to compare osteoblast response to smooth Ti6Al4V (sTiAlV) and roughened Ti6Al4V (rTiAlV) with their response to PEEK with respect to differentiation and production of factors associated with osteogenesis. STUDY DESIGN: This in vitro study compared the phenotype of human MG63 osteoblast-like cells cultured on PEEK, sTiAlV, or rTiAlV surfaces and their production of bone morphogenetic proteins (BMPs). METHODS: Surface properties of PEEK, sTiAlV, and rTiAlV discs were determined. Human MG63 cells were grown on TCPS and the discs. Confluent cultures were harvested, and cell number, alkaline phosphatase–specific activity, and osteocalcin were measured as indicators of osteoblast maturation. Expression of messenger RNA (mRNA) for BMP2 and BMP4 was measuredMultiple biomaterials are clinically available to spine surgeons for performing interbody fusion. Poly-ether-ether-ketone (PEEK) is used frequently for lumbar spine interbody fusion, but alternative materials are also used, including titanium (Ti) alloys. Previously, we showed that osteoblasts exhibit a more differentiated phenotype when grown on machined or grit-blasted titanium aluminum vanadium (Ti6Al4V) alloys with micron-scale roughened surfaces than when grown on smoother Ti6Al4V surfaces or on tissue culture polystyrene (TCPS). We hypothesized that osteoblasts cultured on rough Ti alloy substrates would present a more mature osteoblast phenotype than cells cultured on PEEK, suggesting that textured Ti6Al4V implants may provide a more osteogenic surface for interbody fusion devices. PURPOSE: The aim of the present study was to compare osteoblast response to smooth Ti6Al4V (sTiAlV) and roughened Ti6Al4V (rTiAlV) with their response to PEEK with respect to differentiation and production of factors associated with osteogenesis. STUDY DESIGN: This in vitro study compared the phenotype of human MG63 osteoblast-like cells cultured on PEEK, sTiAlV, or rTiAlV surfaces and their production of bone morphogenetic proteins (BMPs). METHODS: Surface properties of PEEK, sTiAlV, and rTiAlV discs were determined. Human MG63 cells were grown on TCPS and the discs. Confluent cultures were harvested, and cell number, alkaline phosphatase–specific activity, and osteocalcin were measured as indicators of osteoblast maturation. Expression of messenger RNA (mRNA) for BMP2 and BMP4 was measure

Novel Technologies for Assessing Dietary Intake: Evaluating the Usability of a Mobile Telephone Food Record Among Adults and Adolescents

The development of a mobile telephone food record has the potential to ameliorate much of the burden associated with current methods of dietary assessment. When using the mobile telephone food record, respondents capture an image of their foods and beverages before and after eating. Methods of image analysis and volume estimation allow for automatic identification and volume estimation of foods. To obtain a suitable image, all foods and beverages and a fiducial marker must be included in the image