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.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density. Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics. Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs. Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.

A general model for MAC generation using direct injection

This paper presents a model for generating a MAC tag by injecting the input message directly into the internal state of a nonlinear filter generator. This model generalises a similar model for unkeyed hash functions proposed by Nakano et al. We develop a matrix representation for the accumulation phase of our model and use it to analyse the security of the model against man-in-the-middle forgery attacks based on collisions in the final register contents. The results of this analysis show that some conclusions of Nakano et al regarding the security of their model are incorrect. We also use our results to comment on several recent MAC proposals which can be considered as instances of our model and specify choices of options within the model which should prevent the type of forgery discussed here. In particular, suitable initialisation of the register and active use of a secure nonlinear filter will prevent an attacker from finding a collision in the final register contents which could result in a forged MAC.

Making space for knowledge generation and place for knowledge communities : an analysis of the Australian practice

In the era of global knowledge economy, urban regions—seeking to increase their competitive edge, become destinations for talent and investment, and provide prosperity and quality of life to their inhabitants—have little chance achieving their development goals without forming effective knowledge-based urban development strategies. This paper aims to shed light on the planning and development processes of the knowledge-based urban development phenomenon with respect to the construction of knowledge community precincts aimed at making space for knowledge generation and place for knowledge communities. Following to a thorough review of the literature on knowledge-based urban development and strategic asset-based planning, the paper undertakes policy and best practice analyses to learn from the planning and development processes of internationally renowned knowledge community precincts—from Copenhagen, Eindhoven and Singapore. In the light of the analyses findings, this paper scrutinises major Australian knowledge community precinct initiatives—from Sydney, Melbourne and Brisbane—to better understand the dynamics of national practices, and benchmark them against the international best practice cases. The paper concludes with a discussion on the study findings and recommendations for successfully establishing space and place for both knowledge economy and society in Australian cities.

Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

Prenatal Vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation

In a previous study, we demonstrated that mouse adult F(1) offspring, exposed to a vitamin d deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F(2) females whose F(1) parents (males or females) were vitamin d-deprived when developing in the uterus of F(0) females. Unexpectedly, we observed that the vitamin d deficiency affecting the F(0) pregnant mice induced a precocious and more severe EAE in the F(2) generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents' dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin d status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

Influence of Rainfall and Catchment Characteristics on Urban Stormwater Quality

The accuracy and reliability of urban stormwater quality modelling outcomes are important for stormwater management decision making. The commonly adopted approach where only a limited number of factors are used to predict urban stormwater quality may not adequately represent the complexity of the quality response to a rainfall event or site-to-site differences to support efficient treatment design. This paper discusses an investigation into the influence of rainfall and catchment characteristics on urban stormwater quality in order to investigate the potential areas for errors in current stormwater quality modelling practices. It was found that the influence of rainfall characteristics on pollutant wash-off is step-wise based on specific thresholds. This means that a modelling approach where the wash-off process is predicted as a continuous function of rainfall intensity and duration is not appropriate. Additionally, other than conventional catchment characteristics, namely, land use and impervious surface fraction, other catchment characteristics such as impervious area layout, urban form and site specific characteristics have an important influence on both, pollutant build-up and wash-off processes. Finally, the use of solids as a surrogate to estimate other pollutant species was found to be inappropriate. Individually considering build-up and wash-off processes for each pollutant species should be the preferred option.

Preparing the next generation of HRM professionals : an international comparison of tertiary HRM programs

The future of the HRM profession depends to at least some extent on the quality of preparation of the next generation of HR professionals. This paper examines bachelor degree programs in HRM and the role of professional associations as influencers of curricula. Some 39% of the 599 AACSB and EQUIS-accredited institutions sampled offer undergraduate degrees in HRM. The programs vary in emphasis on HRM competencies. Unsurprisingly, all include foundation work (perhaps a third of the content) in business management. Grouping degree content by regions globally allows benchmarking of degrees against international trends, along with consideration of the increasingly significant influence on curricula by professional bodies, in preparing the next generation of HRM practitioners to manage in organisations that will require strategic thinking, specialist technical skills, and interpersonal competence.

Essential elements for recruitment and retention : Generation Y

Purpose: Generation Y (Gen Y) is the newest and largest generation entering the workforce. Gen Y may differ from previous generations in work-related characteristics which may have recruitment and retention repercussions. Currently, limited theoretically-based research exists regarding Gen Y’s work expectations and goals in relation to undergraduate students and graduates. Design/methodology/approach: This study conducted a theoretically-based investigation of the work expectations and goals of student- and working-Gen Y individuals based within a framework incorporating both expectancy-value and goal setting theories. N = 398 provided useable data via an on-line survey. Findings: Overall, some support was found for predictions with career goals loading on a separate component to daily work expectations and significant differences between student- and working- Gen Y on career goals. No significant differences were found, however, between the two groups in daily work expectations. Research limitations/implications: Future research may benefit from adopting a theoretical framework which assesses both daily work expectations and career goals when examining the factors which motivate Gen Y’s decisions to join and remain at a particular organisation. Practical implications: At a practical level, based on the findings, some examples are provided of the means by which organisations may draw upon daily work expectations and career goals of importance to Gen Y and, in doing so, influence the likelihood that a Gen Y individual will join and remain at their particular organisation. Originality/value: This research has demonstrated the utility of adopting a sound theoretical framework in furthering understanding about the motivations which influence organisations’ ability to recruit and retain Gen Y, among both student Gen Y as well as those Gen Y individuals who are already working.

Supplementary Information : Hogan, Holland, Holloway, Petit and Read : Read Classification for Next Generation Sequencing, ESANN 2013, April 2013

This item provides supplementary materials for the paper mentioned in the title, specifically a range of organisms used in the study. The full abstract for the main paper is as follows: Next Generation Sequencing (NGS) technologies have revolutionised molecular biology, allowing clinical sequencing to become a matter of routine. NGS data sets consist of short sequence reads obtained from the machine, given context and meaning through downstream assembly and annotation. For these techniques to operate successfully, the collected reads must be consistent with the assumed species or species group, and not corrupted in some way. The common bacterium Staphylococcus aureus may cause severe and life-threatening infections in humans,with some strains exhibiting antibiotic resistance. In this paper, we apply an SVM classifier to the important problem of distinguishing S. aureus sequencing projects from alternative pathogens, including closely related Staphylococci. Using a sequence k-mer representation, we achieve precision and recall above 95%, implicating features with important functional associations.

Trip generation in Australia : Practical issues

An online survey was conducted to investigate the views and experiences of Australian traffic and transport professionals about practical problems and issues in terms of trip generation and trip chaining for use in Transport Impact Assessment (TIA). Findings from this survey revealed that there is a shortage of appropriate data related to trip generation estimation for use in TIAs in Australia. Establishing a National Trip Generation Database (NTGD) with a centralised responsible organisation for collecting and publishing trip generation data based on federal and state governments’ contribution was found the most accepted solution for resolving this shortage as well as providing national standards and guidelines associated with trip generation definitions, data collection methodology, and TIA preparation process based on updated research. Finally, the study recognised the importance of the trip chaining effects on trip generation estimation and identified most prevalent land uses subject to trip chaining in terms of TIA.

Peer assisted learning, skills development and Generation Y : a case study of a first year undergraduate law unit

The majority of current first year university students belong to Generation Y. Consequently, research suggests that, in order to more effectively engage them, their particular learning preferences should be acknowledged in the organisation of their learning environments and in the support provided. These preferences are reflected in the Torts Student Peer Mentor Program, which, as part of the undergraduate law degree at the Queensland University of Technology, utilises active learning, structured sessions and teamwork to supplement student understanding of the substantive law of Torts with the development of life-long skills. This article outlines the Program, and its relevance to the learning styles and experiences of Generation Y first year law students transitioning to university, in order to investigate student perceptions of its effectiveness – both generally and, more specifically, in terms of the Program’s capacity to assist students to develop academic and work-related skills.

Decentralized detector generation in cooperative intrusion detection system

We consider Cooperative Intrusion Detection System (CIDS) which is a distributed AIS-based (Artificial Immune System) IDS where nodes collaborate over a peer-to-peer overlay network. The AIS uses the negative selection algorithm for the selection of detectors (e.g., vectors of features such as CPU utilization, memory usage and network activity). For better detection performance, selection of all possible detectors for a node is desirable but it may not be feasible due to storage and computational overheads. Limiting the number of detectors on the other hand comes with the danger of missing attacks. We present a scheme for the controlled and decentralized division of detector sets where each IDS is assigned to a region of the feature space. We investigate the trade-off between scalability and robustness of detector sets. We address the problem of self-organization in CIDS so that each node generates a distinct set of the detectors to maximize the coverage of the feature space while pairs of nodes exchange their detector sets to provide a controlled level of redundancy. Our contribution is twofold. First, we use Symmetric Balanced Incomplete Block Design, Generalized Quadrangles and Ramanujan Expander Graph based deterministic techniques from combinatorial design theory and graph theory to decide how many and which detectors are exchanged between which pair of IDS nodes. Second, we use a classical epidemic model (SIR model) to show how properties from deterministic techniques can help us to reduce the attack spread rate.