Pharmacokinetics and safety profile of artesunate-amodiaquine co-administered with antiretroviral therapy in malaria uninfected HIV-positive Malawian adults.

There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus infected (HIV+) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared area under the concentration time curve from 0 to 28 days (AUC0-28 days) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy naive HIV+ adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria uninfected adults (n=6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort (n=25/arm) received the full regimen. In step 1, there were no safety signals and significant differences in desethylamodiaquine AUC0-28 days among participants in the ritonavir-boosted lopinavir, nevirapine and antiretroviral therapy-naive arms. In step 2, compared with the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC0-28 days, (geometric mean [95% CI]; 23,822 [17,458-32506] vs 48,617 [40,787-57,950] ng.hr/mL, p < 0.001). No significant differences in AUC0-28 days were observed between nevirapine and antiretroviral therapy-naïve arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy naïve (0.0% [0/25]) arm (risk difference 20% [95% CI:4.3-35.7] p=0.018). Ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure which may compromise artesunate-amodiaquine’s efficacy. Co-administration of nevirapine and artesunate amodiaquine may be associated with hepatoxicity

Factors that sustain indigenous youth mentoring programs : a qualitative systematic review

Background Indigenous youth worldwide continue to experience disproportional rates of poorer mental health and well-being compared to non-Indigenous youth. Mentoring has been known to establish favorable outcomes in many areas of health but is still in its early phases of research within Indigenous contexts. This paper explores the barriers and facilitators of Indigenous youth mentoring programs to improve mental health outcomes and provides evidence for governments’ response to the United Nations Declaration on the Rights of Indigenous Peoples. Methods A systematic search for published studies was conducted on PubMed, Embase, Scopus, CINAHL, and grey literature through Trove, OpenGrey, Indigenous HealthInfoNet, and Informit Indigenous Collection. All papers included in the search were peer-reviewed and published from 2007 to 2021. The Joanna Briggs Institute approaches to critical appraisal, data extraction, data synthesis, and confidence of findings were used. Results A total of eight papers describing six mentoring programs were included in this review; six papers were from Canada, and two originated from Australia. Studies included mentor perspectives (n=4) (incorporating views of parents, carers, Aboriginal assistant teachers, Indigenous program facilitators, young adult health leaders, and community Elders), mentee perspectives (n=1), and both mentor and mentee perspectives (n=3). Programs were conducted nationally (n=3) or within specific local Indigenous communities (n=3) with varying mentor styles and program focus. Five synthesized findings were identified from the data extraction process, each consisting of four categories. These synthesized findings were: establishing cultural relevancy, facilitating environments, building relationships, facilitating community engagement, and leadership responsibilities, which were discussed in the context of extant mentoring theoretical frameworks. Conclusion Mentoring is an appropriate strategy for improving general well-being. However, more research is needed to explore program sustainability and maintaining outcomes in the long term

Genomic analysis of serogroup Y Neisseria meningitidis isolates reveals extensive similarities between carriage and disease-associated organisms

Background. Neisseria meningitidis is a frequent colonizer of the human nasopharynx with asymptomatic carriage providing the reservoir for invasive, disease-causing strains. Serogroup Y (MenY) strains are a major cause of meningococcal disease. High resolution genetic analyses of carriage and disease isolates can establish epidemiological relationships and identify potential virulence factors. Methods. Whole genome sequence data were obtained from UK MenY carriage isolates from 1997-2010 (n=99). Sequences were compared to those from MenY invasive isolates from 2010 and 2011 (n=73) using a gene-by-gene approach. Results. Comparisons across 1,605 core genes resolved 91% of isolates into one of eight clusters containing closely related disease and carriage isolates. Six clusters contained carried meningococci isolated in 1997-2001 suggesting temporal stability. One cluster of isolates, predominately sharing the designation Y: P1.5-1,10-1: F4-1: ST-1655 (cc23), was resolved into a sub-cluster with 86% carriage isolates and a second with 90% invasive isolates. These subclusters were defined by specific allelic differences in five core genes encoding glycerate kinase (glxK), valine-pyruvate transaminase (avtA), superoxide dismutase (sodB) and two hypothetical proteins. Conclusions. High resolution genetic analyses detected long-term temporal stability and temporally-overlapping carriage and disease populations for MenY clones but also evidence of a disease-associated clone

Changes in serogroup and genotype prevalence among carried meningococci in the United Kingdom during vaccine implementation.

BACKGROUND: Herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. A large multicenter study investigated the effect of meningococcal serogroup C conjugate vaccine introduction on the meningococcal population. METHODS: Carried meningococci in individuals aged 15-19 years attending education establishments were investigated before and for 2 years after vaccine introduction. Isolates were characterized by multilocus sequence typing, serogroup, and capsular region genotype and changes in phenotypes and genotypes assessed. RESULTS: A total of 8462 meningococci were isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup 29E. Clonal complexes were associated with particular serogroups and their relative proportions fluctuated, with 12 statistically significant changes (6 up, 6 down). The reduction of ST-11 complex serogroup C meningococci was probably due to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254 meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex meningococci (from 6.7% to 10.6%) were less clear. CONCLUSIONS: Natural fluctuations in carried meningococcal genotypes and phenotypes a can be affected by the use of conjugate vaccines, and not all of these changes are anticipatable in advance of vaccine introduction

EpiCollect: Linking Smartphones to Web Applications for Epidemiology, Ecology and Community Data Collection

Epidemiologists and ecologists often collect data in the field and, on returning to their laboratory, enter their data into a database for further analysis. The recent introduction of mobile phones that utilise the open source Android operating system, and which include (among other features) both GPS and Google Maps, provide new opportunities for developing mobile phone applications, which in conjunction with web applications, allow two-way communication between field workers and their project databases.Here we describe a generic framework, consisting of mobile phone software, EpiCollect, and a web application located within www.spatialepidemiology.net. Data collected by multiple field workers can be submitted by phone, together with GPS data, to a common web database and can be displayed and analysed, along with previously collected data, using Google Maps (or Google Earth). Similarly, data from the web database can be requested and displayed on the mobile phone, again using Google Maps. Data filtering options allow the display of data submitted by the individual field workers or, for example, those data within certain values of a measured variable or a time period.Data collection frameworks utilising mobile phones with data submission to and from central databases are widely applicable and can give a field worker similar display and analysis tools on their mobile phone that they would have if viewing the data in their laboratory via the web. We demonstrate their utility for epidemiological data collection and display, and briefly discuss their application in ecological and community data collection. Furthermore, such frameworks offer great potential for recruiting 'citizen scientists' to contribute data easily to central databases through their mobile phone

Making Birmingham a Flood Resilient City: Challenges and Opportunities

The city of Birmingham has experienced a number of significant flooding events in the past two decades. The impacts of these flood events include physical damage to critical infrastructure, as well as significant losses caused by business interruption and general disruption to communities. Human losses and impacts can be life changing. This study identifies the current challenges and opportunities of managing flood risk in the city of Birmingham, drawing on a desk-based account of current flood risk management (FRM) practice and diagnostic evidence. This interrogation adopts the use of a ‘flood resilience circle model’ to consider ways to address the challenges in a methodological manner aligned to an integrated approach to flood risk management. Solutions aligned to the key FRM stages of prevention, preparation, response and recovery are provided. The findings will be of interest to policy makers and decision makers on how to address current weaknesses in FRM practices towards the prospect of a sustainable approach that improves the resilience of the city and delivers multiple benefits. Recommendations made include the adoption of a blue-green systems approach, the development of a new communication strategy aligned to motivating behaviour change, and improved flood forecasting especially for surface water flooding

Knowledge formalization in experience feedback processes : an ontology-based approach

Because of the current trend of integration and interoperability of industrial systems, their size and complexity continue to grow making it more difficult to analyze, to understand and to solve the problems that happen in their organizations. Continuous improvement methodologies are powerful tools in order to understand and to solve problems, to control the effects of changes and finally to capitalize knowledge about changes and improvements. These tools involve suitably represent knowledge relating to the concerned system. Consequently, knowledge management (KM) is an increasingly important source of competitive advantage for organizations. Particularly, the capitalization and sharing of knowledge resulting from experience feedback are elements which play an essential role in the continuous improvement of industrial activities. In this paper, the contribution deals with semantic interoperability and relates to the structuring and the formalization of an experience feedback (EF) process aiming at transforming information or understanding gained by experience into explicit knowledge. The reuse of such knowledge has proved to have significant impact on achieving themissions of companies. However, the means of describing the knowledge objects of an experience generally remain informal. Based on an experience feedback process model and conceptual graphs, this paper takes domain ontology as a framework for the clarification of explicit knowledge and know-how, the aim of which is to get lessons learned descriptions that are significant, correct and applicable

Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci.

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.The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity

ARTEMIS: A complete mission architecture to bridge the gap between humanity and near-Earth asteroids

Asteroid retrieval missions have recently attracted increasing interest from the community and could provide opportunities for scienti c exploration, resource utilisation and even the development of planetary defence strategies. This paper was developed as a result of a 6-month MSc group project, realised by a total of 14 students at Cran eld University pursuing the Astronautics & Space Engineering degree. An overall system design is proposed for a technology demonstrator mission to move a near-Earth asteroid into an easily-accessible location where it could be further explored by future missions. The target nal orbit is a southern halo orbit around the Lagrange point (L2) on the Sun-Earth system. ARTEMIS (Asteroid Retrieval Technology Mission) abides by ESAs constraints for a Large (L) mission call: realised in only one launch with Ariane 64, an operational duration of less than 15 years and a cost at completion of at most e1100M. The proposed mission combines the design of optimal trajectories, employs advanced solar electric propulsion and introduces a be tting level of spacecraft autonomy. The target is the 2006 RH120 asteroid, with an approximate diameter of 6.5 m and mass of roughly 350 tons. To re ne existing data, the ARROW CubeSat mission (Asteroid Reconnaissance to Research Object Worthiness) is to be launched a year prior to the main mission to probe the asteroid via a y-by. ARROW will provide valuable information, such as the asteroids spin rate, rotational axis and better mass estimate, increasing the overall chance of mission success. The main mission will then capture and secure the asteroid using a mechanism of arm-like booms with xenon- lled VectranTM bags. To allow for proper adaptability to the objects shape and mass distribution, as well as preserve the asteroid unaltered, the mechanism is fully contained in fabric that encapsulates the asteroid. The paper concludes that such a mission is conditionally feasible, and summarises the design process resulting in the nal overall mission baseline design. It also examines the practicality of the suggested design for future missions such as space debris removal or its ability to retrieve celestial bodies with variable mass and shape. Proper adaptation of the design could allow for retrieval of similar size or smaller objects. The future implementation of this mission may further the understanding of the origin of the solar system and act as a catalyst to a new celestial body exploitation industry

Genomic analysis of urogenital and rectal Neisseria meningitidis isolates reveals encapsulated hyperinvasive meningococci and coincident multidrug-resistant gonococci.

OBJECTIVE: Invasive meningococcal disease (IMD) outbreaks in men who have sex with men (MSM) have been associated with meningococcal colonisation of the urethra and rectum, but little is known about this colonisation or co-colonisation with the closely related gonococcus. Whole genome sequencing (WGS) was employed to explore these phenomena. METHODS: Meningococci isolated from the urogenital tract and rectum (n=23) and coincident gonococci (n=14) were analysed by WGS along with contemporary meningococci from IMD (n=11). All isolates were obtained from hospital admissions in Brighton, UK, 2011-2013. Assembled WGS were deposited in the PubMLST/neisseria database (http://pubmlst.org/neisseria) and compared at genomic loci common to gonococci or meningococci. RESULTS: As expected, most meningococci from IMD were encapsulated and belonged to hyperinvasive lineages. So too were meningococci found in the urogenital tract and rectum, contrasting to those asymptomatically carried in the nasopharynx where such meningococci are rare. Five hyperinvasive meningococcal lineages and four distinct gonococcal genotypes were recovered, including multiresistant ST-1901 (NG MAST-1407) gonococci. CONCLUSIONS: These data were consistent with a predisposition for potentially virulent encapsulated hyperinvasive meningococci to colonise the urethra and rectum, which suggests their involvement in MSM IMD outbreaks. The coincidence of multiresistant gonococci raises wider public health concerns