Statutory and policy-based eco-disaster risk reduction in SADC member states.

Unlabelled: Effective legislative framework is the cornerstone of managing hazards and disasters because they have become policy problems of global and local concern. This research study aims at understanding the implementation, strengths and gaps of policies related to Eco-DRR in SADC member states. In particular, attempts to critically analyse the making of DRM policies, as well as the variables underpinning these policies, given the high level of disaster losses.

Kinetic modelling of glycolytic oscillations.

Glycolytic oscillations have been studied for well over 60 years, but aspects of their function, and mechanisms of regulation and synchronisation remain unclear. Glycolysis is amenable to mechanistic mathematical modelling, as its components have been well characterised, and the system can be studied at many organisational levels: in vitro reconstituted enzymes, cell free extracts, individual cells, and cell populations. In recent years, the emergence of individual cell analysis has opened new ways of studying this intriguing system.

Colposcopy referral rates post-introduction of primary screening with human papillomavirus testing: evidence from a large British Columbia cohort study.

Background: Shifting from cytology to human papillomavirus (HPV)-based cervical cancer screening will initially increase colposcopy referrals. The anticipated impact on health systems has been raised as a concern for implementation. It is unclear if the higher rate of colposcopy referrals is sustained after initial HPV-based screens or reverts to new lower baselines due to earlier detection and treatment of precancer.

Age-Specific Trends of Invasive Cervical Cancer Incidence in British Columbia, Canada, 1971-2017.

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971-2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method.

Is distance from equilibrium a good indicator for a reaction's flux control?

By analysing a large set of models obtained from the JWS Online and Biomodels databases, we tested to what extent the disequilibrium ratio can be used as an estimator for the flux control of a reaction, a discussion point that was already raised by Kacser and Burns, and Heinrich and Rapoport in their seminal MCA manuscripts. Whereas no functional relation was observed, the disequilibrium ratio can be used as an estimator for the maximal flux control of a reaction step. We extended the original analysis of the relationship by incorporating the overall pathway disequilibrium ratio in the expression, which made it possible to make explicit expressions for flux control coefficients.

A detailed kinetic model of glycolysis in Plasmodium falciparum-infected red blood cells for antimalarial drug target identification.

Upon infection by the malaria parasite Plasmodium falciparum, the glycolytic rate of a red blood cell increases up to 100-fold, possibly contributing to lactic acidosis and hypoglycemia in patients with severe malaria. This dramatic increase in glucose uptake and metabolism was correctly predicted by a newly constructed detailed enzyme kinetic model of glucose metabolism in the trophozoite-infected red blood cell. Subsequently, we expanded the model to simulate an infected red blood cell culture, including the different asexual blood-stage forms of the malaria parasite.

Inhibitor titrations reveal low control of glyceraldehyde 3-phosphate dehydrogenase and high control of hexokinase on glycolytic flux in an aggressive triple-negative breast cancer cell line.

The glycolytic flux, and in particular lactate production, is strongly increased in cancer cells compared to normal cells, a characteristic often referred to as aerobic glycolysis or the Warburg effect. This makes the glycolytic pathway a potential drug target, in particular if the flux control distribution in the pathway has shifted due to the metabolic reprogramming in cancer cells. The flux response of a drug is dependent on both the sensitivity of the target to the drug and the flux control of the target, and both these characteristics can be exploited to obtain selectivity for cancer cells.

Community-integrated self-collected HPV-based cervix screening in a low-resource rural setting: a pragmatic, cluster-randomized trial.

Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervix screening (SCS) as well as attendance at treatment for HPV-positive participants are needed to inform policy on optimal integration of cervical cancer screening programs within existing infrastructure in low-resource settings. ASPIRE Mayuge was a pragmatic cluster-randomized trial in rural Mayuge district, Uganda, comparing the superiority of two recruitment implementation strategies for SCS: Door-to-Door versus Community Health Day. Villages were randomized (unblinded) to a strategy, and participants aged 25-49 years with no previous history of hysterectomy or treatment for cervical cancer or pre-cancer were eligible.

3D Bioelectronics with a Remodellable Matrix for Long-Term Tissue Integration and Recording.

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy.

Experiences with thermal ablation for cervical precancer treatment after self-collection HPV-based screening in the ASPIRE Mayuge randomized trial.

Cervical cancer remains a significant public health burden in low-resourced countries. Thus, the WHO prioritized cervix screening, and recently recommended thermal ablation treatment for cervical precancer. However, there is limited information on side effects during treatment and recovery, and acceptability among those treated.

Organic electronic transmembrane device for hosting and monitoring 3D cell cultures.

3D cell models have made strides in the past decades in response to failures of 2D cultures to translate targets during the drug discovery process. Here, we report on a novel multiwell plate bioelectronic platform, namely, the e-transmembrane, capable of supporting and monitoring complex 3D cell architectures. Scaffolds made of PEDOT:PSS [poly(3,4-ethylenedioxythiophene):polystyrene sulfonate] are microengineered to function as separating membranes for compartmentalized cell cultures, as well as electronic components for real-time in situ recordings of cell growth and function.

Disaster resilience framework indicators for a city's disaster resilience planning strategy.

Determining the level of a city's disaster resilience and developing a disaster resilience strategy is an important process towards understanding the current and potential future risk of cities. However, the process of determining and mapping the level of urban disaster resilience presents a challenge for the City of Tshwane, as it requires a consolidated and coordinated commitment and collaboration from various role players. This research study developed disaster resilience framework indicators for the City of Tshwane to determine its current disaster resilience and to contribute to its disaster resilience and sustainable development planning strategy.

Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results.

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial.

BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface.

Human papillomavirus-based screening at extended intervals missed fewer cervical precancers than cytology in the HPV For Cervical Cancer (HPV FOCAL) trial.

While cervix screening using cytology is recommended at 2- to 3-year intervals, given the increased sensitivity of human papillomavirus (HPV)-based screening to detect precancer, HPV-based screening is recommended every 4- to 5-years. As organized cervix screening programs transition from cytology to HPV-based screening with extended intervals, there is some concern that cancers will be missed between screens. Participants in HPV FOr CervicAL Cancer (HPV FOCAL) trial received cytology (Cytology Arm) at 24-month intervals or HPV-based screening (HPV Arm) at 48-month intervals; both arms received co-testing (cytology and HPV testing) at exit.

The Path to Eliminating Cervical Cancer in Canada: Past, Present and Future Directions.

Cervical cancer remains a common cancer affecting women in Canada. While cervical cancer incidence and mortality in Canada have declined for several decades due to the success of organized, provincial cervical cancer screening programs, further decreases will require enhancement of primary, secondary, and tertiary prevention efforts. The present commentary provides a historical overview of cervical cancer trends in Canada, presents current statistics on cervical cancer incidence, mortality and survival, and discusses future directions in relation to cervical cancer elimination.

Organic Bioelectronics for Systems.

Bioelectronics have made strides in improving clinical diagnostics and precision medicine. The potential of bioelectronics for bidirectional interfacing with biology through continuous, label-free monitoring on one side and precise control of biological activity on the other has extended their application scope to systems. The advent of microfluidics and the considerable advances in reliability and complexity of models promise to eventually significantly reduce or replace animal studies, currently the gold standard in drug discovery and toxicology testing.

Women's acceptability of and experience with primary human papillomavirus testing for cervix screening: HPV FOCAL trial cross-sectional online survey results.

Objective: To study participant's acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in future acceptability of screening.

Design: Cross-sectional online survey of clinical trial participants.

Setting: Primary care, population-based Cervix Screening Program, British Columbia, Canada.

Modelling microprosodic effects can lead to an audible improvement in articulatory synthesis.

When pitch is explicitly modelled for parametric speech synthesis, microprosodic variations of the fundamental frequency f are usually disregarded by current intonation models. While there are numerous studies dealing with the nature and the origin of microprosody, little research has been done on its audibility and its effect on the naturalness of synthetic speech. In this work, the influence of obstruent-related microprosodic variations on the perceived naturalness of articulatory speech synthesis was studied.

High-risk HPV prevalence among women undergoing cervical cancer screening: Findings a decade after HPV vaccine implementation in British Columbia, Canada.

Background: British Columbia (BC) introduced a publicly funded, school-based human papillomavirus (HPV) immunization program in 2008 with the quadrivalent vaccine. In 2010/2011, a baseline evaluation of HPV prevalence was conducted among women undergoing cervical cancer screening. After 10 years of publicly funded HPV vaccination, HPV-type prevalence was re-evaluated.

Uncovering the effects of heterogeneity and parameter sensitivity on within-host dynamics of disease: malaria as a case study.

Background: The fidelity and reliability of disease model predictions depend on accurate and precise descriptions of processes and determination of parameters. Various models exist to describe within-host dynamics during malaria infection but there is a shortage of clinical data that can be used to quantitatively validate them and establish confidence in their predictions. In addition, model parameters often contain a degree of uncertainty and show variations between individuals, potentially undermining the reliability of model predictions.

Long-term cervical precancer outcomes after a negative DNA- or RNA-based human papillomavirus test result.

Background: Cervical cancer, a preventable disease associated with the human papillomavirus, is responsible for significant morbidity and mortality globally. Primary human papillomavirus testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. Screening programs must select the most appropriate assay from several available assays for their population.

Sociodemographic characteristics of women with invasive cervical cancer in British Columbia, 2004-2013: a descriptive study.

Background: Although cancer screening has led to reductions in the incidence of invasive cervical cancer (ICC) across Canada, benefits of prevention efforts are not equitably distributed. This study investigated the sociodemographic characteristics of women with ICC in British Columbia compared with the general female population in the province.

Methods: In this descriptive study, data of individuals 18 years and older diagnosed with ICC between 2004 and 2013 were obtained from the BC Cancer Registry.