Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits

Background Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Methods Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Results Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence's of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6 %, 12.8 %, 4.6 % and 8.3 % respectively. Conclusions Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa : a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

International students using online information resources to learn : complex experience and learning needs

This paper reports the findings of a qualitative study which investigated 25 international students’ use of online information resources for study purposes at two Australian universities. Using an expanded critical incident approach, the study viewed international students through an information literacy lens, as information-using learners. The findings are presented in two complementary parts: as a word picture that describes their whole experience of using online information resources to learn; and as a tabulated set of critical findings that summarises their associated information literacy learning needs. The word picture shows international students’ resource use as a complex interplay of eight inter-related elements: students; information-learning environment; interactions (with online resources); strengths-challenges; learning-help; affective responses; reflective responses; cultural-linguistic dimensions. In using online resources, the international students experience an array of strengths and challenges, and an apparent information literacy imbalance between their more developed information skills and less developed critical information use. The critical findings about information literacy needs provide a framework for developing an inclusive informed learning approach that responds to international students’ complex information using experiences and needs. While the study is situated in Australia, the findings are of potential interest to educators, information professionals and researchers worldwide who seek to support learning in culturally diverse higher education contexts.

Review of refugee mental health interventions following resettlement : best practice and recommendations

There are increasing numbers of refugees worldwide, with approximately 16 million refugees in 2007 and over 2.5 million refugees resettled in the United States since the start of its humanitarian program. Psychologists and other health professionals who deliver mental health services for individuals from refugee backgrounds need to have confidence that the therapeutic interventions they employ are appropriate and effective for the clients with whom they work. The current review briefly surveys refugee research, examines empirical evaluations of therapeutic interventions in resettlement contexts, and provides recommendations for best practices and future directions in resettlement countries. The resettlement interventions found to be most effective typically target culturally homogeneous client samples and demonstrate moderate to large outcome effects on aspects of traumatic stress and anxiety reduction. Further evaluations of the array of psychotherapeutic, psychosocial, pharmacological, and other therapeutic approaches, including psychoeducational and community-based interventions that facilitate personal and community growth and change, are encouraged. There is a need for increased awareness, training and funding to implement longitudinal interventions that work collaboratively with clients from refugee backgrounds through the stages of resettlement.

Using scenarios to explore the social aspects of design led innovations

Emerging technologies have redefined the way people go about everyday life. An increasing array of online and on-the-go solutions supporting remote work, entertainment on demand, information sharing, social communication, telehealth and beyond, are now available at the touch of a screen. This paper discusses concept of scenarios as a design tool that can be successfully employed by organisations as an innovative design led approach to: (i) understand people’s everyday practices in current social contexts in order to identify opportunities and emerging markets, and (ii) reveal stakeholder relationships existing in the provision of services within current everyday practices. To illustrate this approach, two case studies will be presented: the first focusing on a real industry project exploring opportunities for the development of future health care services, the second focusing on people’s access to services as part of a transport journey experience. This paper aims to demonstrate the use of scenarios as part of a design led innovation approach to understand the social aspects and their complexities of new designs in an increasing everyday technological driven context.

Signal transduction mechanisms underlying growth hormone receptor action

Our understanding of the mechanisms of action of GH and its receptor, the GHR, has advanced significantly in the last decade and has provided some important surprises. It is now clear that the GH-GHR axis activates a number of inter-related signalling pathways, not all of which are dependent on the intracellular tyrosine kinase, JAK2 as originally postulated. JAK2-independent pathways, mediated via the Src family kinases, together with a number of negative regulators of GH signalling and emerging cross-talk mechanisms with other growth factor receptors, provide a complex array of mechanisms that are capable of fine-tuning responses to GH in a cell context dependent manner. Additionally, it is also now clear that GH and the GHR can translocate to the nucleus of target cells and initiate, as yet not well defined, nuclear responses. Continued emphasis on elucidation of these complex mechanisms is critical to provide further insights into the diverse physiological and pathophysiological effects of GH.

Reduced Il17a expression distinguishes a Ly6cloMHCIIhi macrophage population promoting wound healing

Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6cloMHCIIhi “noninflammatory” subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88−/− models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A−/− mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10−8). More than 70 prostate cancer susceptibility loci, explaining ~30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.

An evolutionary computation approach to three-dimensional path planning for unmanned aerial vehicles with tactical and kinematic constraints

This paper presents a novel evolutionary computation approach to three-dimensional path planning for unmanned aerial vehicles (UAVs) with tactical and kinematic constraints. A genetic algorithm (GA) is modified and extended for path planning. Two GAs are seeded at the initial and final positions with a common objective to minimise their distance apart under given UAV constraints. This is accomplished by the synchronous optimisation of subsequent control vectors. The proposed evolutionary computation approach is called synchronous genetic algorithm (SGA). The sequence of control vectors generated by the SGA constitutes to a near-optimal path plan. The resulting path plan exhibits no discontinuity when transitioning from curve to straight trajectories. Experiments and results show that the paths generated by the SGA are within 2% of the optimal solution. Such a path planner when implemented on a hardware accelerator, such as field programmable gate array chips, can be used in the UAV as on-board replanner, as well as in ground station systems for assisting in high precision planning and modelling of mission scenarios.

Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Learning landscapes 2.0 : warning - assembly required

Twenty first century learners operate in organic, immersive environments. A pedagogy of student-centred learning is not a recipe for rooms. A contemporary learning environment is like a landscape that grows, morphs, and responds to the pressures of the context and micro-culture. There is no single adaptable solution, nor a suite of off-the-shelf answers; propositions must be customisable and infinitely variable. They must be indeterminate and changeable; based on the creation of learning places, not restrictive or constraining spaces. A sustainable solution will be un-fixed, responsive to the life cycle of the components and materials, able to be manipulated by the users; it will create and construct its own history. Learning occurs as formal education with situational knowledge structures, but also as informal learning, active learning, blended learning social learning, incidental learning, and unintended learning. These are not spatial concepts but socio-cultural patterns of discovery. Individual learning requirements must run free and need to be accommodated as the learner sees fit. The spatial solution must accommodate and enable a full array of learning situations. It is a system not an object. Three major components: 1. The determinate landscape: in-situ concrete 'plate' that is permanent. It predates the other components of the system and remains as a remnant/imprint/fossil after the other components of the system have been relocated. It is a functional learning landscape in its own right; enabling a variety of experiences and activities. 2. The indeterminate landscape: a kit of pre-fabricated 2-D panels assembled in a unique manner at each site to suit the client and context. Manufactured to the principles of design-for-disassembly. A symbiotic barnacle like system that attaches itself to the existing infrastructure through the determinate landscape which acts as a fast growth rhizome. A carapace of protective panels, infinitely variable to create enclosed, semi-enclosed, and open learning places. 3. The stations: pre-fabricated packages of highly-serviced space connected through the determinate landscape. Four main types of stations; wet-room learning centres, dry-room learning centres, ablutions, and low-impact building services. Entirely customised at the factory and delivered to site. The stations can be retro-fitted to suit a new context during relocation. Principles of design for disassembly: material principles • use recycled and recyclable materials • minimise the number of types of materials • no toxic materials • use lightweight materials • avoid secondary finishes • provide identification of material types component principles • minimise/standardise the number of types of components • use mechanical not chemical connections • design for use of common tools and equipment • provide easy access to all components • make component size to suite means of handling • provide built in means of handling • design to realistic tolerances • use a minimum number of connectors and a minimum number of types system principles • design for durability and repeated use • use prefabrication and mass production • provide spare components on site • sustain all assembly and material information

Calculation of engine parameters using reconfigurable hardware

The feasibility of real-time calculation of parameters for an internal combustion engine via reconfigurable hardware implementation is investigated as an alternative to software computation. A detailed in-hardware field programmable gate array (FPGA)-based design is developed and evaluated using input crank angle and in-cylinder pressure data from fully instrumented diesel engines in the QUT Biofuel Engine Research Facility (BERF). Results indicate the feasibility of employing a hardware-based implementation for real-time processing for speeds comparable to the data sampling rate currently used in the facility, with acceptably low level of discrepancies between hardware and software-based calculation of key engine parameters.

A Material Reverie

excerpt: from soil and stone is a work consisting of fifty drawings on paper organised in a grid. Each drawing is small, only 19 by 14 centimetres, and set out in portrait format. They each reference, either explicitly or abstractly, natural phenomena. These include plant forms, pollens, seeds, pods, and leaf shapes and each is painted with a dizzying and liquid array of techniques and technical finesse. Colour is used sparingly but tellingly, and all are generously and wetly composed, with each seeming to flow into the necessary rightness of composition. Within the overall work the feel is sometimes of the archive, a personal kind where pressed flowers are stumbled upon within a book. At other times they seem to image the stellar as one confronts the immensity of some planet suspended in the void. Again, as a recurring theme in Reynolds’ oeuvre, the notion of the taxonomy is sounded. The drawings are laid out to display difference and reveal through contrast essence. It is a mapping that illuminates a generous plentitude.

Surviving an avalanche of data

Open the sports or business section of your daily newspaper, and you are immediately bombarded with an array of graphs, tables, diagrams, and statistical reports that require interpretation. Across all walks of life, the need to understand statistics is fundamental. Given that our youngsters’ future world will be increasingly data laden, scaffolding their statistical understanding and reasoning is imperative, from the early grades on. The National Council of Teachers of Mathematics (NCTM) continues to emphasize the importance of early statistical learning; data analysis and probability was the Council’s professional development “Focus of the Year” for 2007–2008. We need such a focus, especially given the results of the statistics items from the 2003 NAEP. As Shaughnessy (2007) noted, students’ performance was weak on more complex items involving interpretation or application of items of information in graphs and tables. Furthermore, little or no gains were made between the 2000 NAEP and the 2003 NAEP studies. One approach I have taken to promote young children’s statistical reasoning is through data modeling. Having implemented in grades 3 –9 a number of model-eliciting activities involving working with data (e.g., English 2010), I observed how competently children could create their own mathematical ideas and representations—before being instructed how to do so. I thus wished to introduce data-modeling activities to younger children, confi dent that they would likewise generate their own mathematics. I recently implemented data-modeling activities in a cohort of three first-grade classrooms of six year- olds. I report on some of the children’s responses and discuss the components of data modeling the children engaged in.

The Citizen’s Round Table process : canvassing public opinion on energy technologies to mitigate climate change

This study draws on communication accommodation theory, social identity theory and cognitive dissonance theory to drive a ‘Citizen’s Round Table’ process that engages community audiences on energy technologies and strategies that potentially mitigate climate change. The study examines the effectiveness of the process in determining the strategies that engage people in discussion. The process is designed to canvas participants’ perspectives and potential reactions to the array of renewable and non-renewable energy sources, in particular, underground storage of CO2. Ninety-five people (12 groups) participated in the process. Questionnaires were administered three times to identify changes in attitudes over time, and analysis of video, audio-transcripts and observer notes enabled an evaluation of level of engagement and communication among participants. The key findings of this study indicate that the public can be meaningfully engaged in discussion on the politically sensitive issue of CO2 capture and storage (CCS) and other low emission technologies. The round table process was critical to participants’ engagement and led to attitude change towards some methods of energy production. This study identifies a process that can be used successfully to explore community attitudes on politically-sensitive topics and encourages an examination of attitudes and potential attitude change.