Evolutionary dynamics of coexisting species.

Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2000.Ever since Maynard-Smith and Price first introduced the concept of an evolutionary stable strategy (ESS) in 1973, there has been a growing amount of work in and around this field. Many new concepts have been introduced, quite often several times over, with different acronyms by different authors. This led to other authors trying to collect and collate the various terms (for example Lessard, 1990 & Eshel, 1996) in order to promote better understanding ofthe topic. It has been noticed that dynamic selection did not always lead to the establishment of an ESS. This led to the development ofthe concept ofa continuously stable strategy (CSS), and the claim that dynamic selection leads to the establishment of an ESSif it is a CSS. It has since been proved that this is not always the case, as a CSS may not be able to displace its near neighbours in pairwise ecological competitions. The concept of a neighbourhood invader strategy (NIS) was introduced, and when used in conjunction with the concept of an ESS, produced the evolutionary stable neighbourhood invader strategy (ESNIS) which is an unbeatable strategy. This work has tried to extend what has already been done in this field by investigating the dynamics of coexisting species, concentrating on systems whose dynamics are governed by Lotka-Volterra competition models. It is proved that an ESNIS coalition is an optimal strategy which will displace any size and composition of incumbent populations, and which will be immune to invasions by any other mutant populations, because the ESNIS coalition, when it exists, is unique. It has also been shown that an ESNIS coalition cannot exist in an ecologically stable state with any finite number of strategies in its neighbourhood. The equilibrium population when the ESNIS coalition is the only population present is globally stable in a n-dimensional system (for finite n), where the ESNIS coalition interacts with n - 2 other strategies in its neighbourhood. The dynamical behaviour of coexisting species was examined when the incumbent species interacted with various invading species. The different behaviour ofthe incumbent population when invaded by a coalition using either an ESNIS or an NIS phenotype underlines the difference in the various strategies. Similar simulations were intended for invaders who were using an ESS phenotype, but unfortunately the ESS coalition could not be found. If the invading coalition use NIS phenotypes then the outcome is not certain. Some, but not all of the incumbents might become extinct, and the degree to which the invaders flourish is very dependent on the nature ofthe incumbents. However, if the invading species form an ESNIS coalition, one is certain of the outcome. The invaders will eliminate the incumbents, and stabilise at their equilibrium populations. This will occur regardless of the composition and number of incumbent species, as the ESNIS coalition forms a globally stable equilibrium point when it is at its equilibrium populations, with no other species present. The only unknown fact about the outcome in this case is the number ofgenerations that will pass before the system reaches the globally stable equilibrium consisting ofjust the ESNIS. For systems whose dynamics are not given by Lotka-Volterra equations, the existence ofa unique, globally stable ESNIS coalition has not been proved. Moreover, simulations of a non Lotka-Volterra system designed to determine the applicability ofthe proof were inconclusive, due to the ESS coalition not having unique population sizes. Whether or not the proof presented in this work can be extended to non Lotka-Volterra systems remains to be determined

Hepatitis C – Assessment to Treatment Trial (HepCATT) in primary care:study protocol for a cluster randomised controlled trial

BACKGROUND: Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial. METHODS/DESIGN: A total of 46 general practices in South West England will be randomised in a 1:1 ratio to receive either a complex intervention comprising: educational training on HCV for the practice; poster and leaflet display in the practice waiting rooms to raise awareness and encourage opportunistic testing; a HCV risk prediction algorithm based on information on possible risk markers in the electronic patient record run using Audit + software (BMJ Informatica). The audit will then be used to recall and offer patients a HCV test. Control practices will follow usual care. The effectiveness of the intervention will be measured by comparing number and rates of HCV testing, the number and proportion of patients testing positive, onward referral, rates of specialist assessment and treatment in control and intervention practices. Intervention costs and health service utilisation will be recorded to estimate the NHS cost per new HCV diagnosis and new HCV patient initiating treatment. Longer-term cost-effectiveness of the intervention in improving quality-adjusted life years (QALYs) will be extrapolated using a pre-existing dynamic health economic model. Patients' and health care workers' experiences and acceptability of the intervention will be explored through semi-structured qualitative interviews. DISCUSSION: This trial has the potential to make an important impact on patient care and will provide high-quality evidence to help general practitioners make important decisions on HCV testing and onward referral. If found to be effective and cost-effective the intervention is readily scalable and can be used to support the implementation of NICE recommendations on HCV case-finding. TRIAL REGISTRATION: ISRCTN61788850 . Registered on 24 April 2015; Protocol Version: 2.0, 22 May 2015

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT):cluster randomised controlled trial in primary care

Objective To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. Design Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. Setting and participants 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). Intervention Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients’ awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. Main outcome measures Primary outcome: uptake of HCV testing. Secondary outcomes: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. Results Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a “number needed to help” of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. Conclusion HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment

Qualitative approach to comparative exposure in alternatives assessment

Most alternatives assessments (AAs) published to date are largely hazard-based rankings, thereby ignoring potential differences in human and/or ecosystem exposures; as such, they may not represent a fully informed consideration of the advantages and disadvantages of possible alternatives. Building on the 2014 US National Academy of Sciences recommendations to improve AA decisions by including comparative exposure assessment into AAs, the Health and Environmental Sciences Institute\u27s (HESI) Sustainable Chemical Alternatives Technical Committee, which comprises scientists from academia, industry, government, and nonprofit organizations, developed a qualitative comparative exposure approach. Conducting such a comparison can screen for alternatives that are expected to have a higher or different routes of human or environmental exposure potential, which together with consideration of the hazard assessment, could trigger a higher tiered, more quantitative exposure assessment on the alternatives being considered, minimizing the likelihood of regrettable substitution. This article outlines an approach for including chemical ingredient- and product-related exposure information in a qualitative comparison, including ingredient and product-related parameters. A classification approach was developed for ingredient and product parameters to support comparisons between alternatives as well as a methodology to address exposure parameter relevance and data quality. The ingredient parameters include a range of physicochemical properties that can impact routes and magnitude of exposure, whereas the product parameters include aspects such as product-specific exposure pathways, use information, accessibility, and disposal. Two case studies are used to demonstrate the application of the methodology. Key learnings and future research needs are summarized. Integr Environ Assess Manag 2018;00:000-000. (c) 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC

Impact of rapid near-patient STI testing on service delivery outcomes in an integrated sexual health service in the United Kingdom:a controlled interrupted time series study

OBJECTIVES: To evaluate the impact of a new clinic-based rapid sexually transmitted infection testing, diagnosis and treatment service on healthcare delivery and resource needs in an integrated sexual health service. DESIGN: Controlled interrupted time series study. SETTING: Two integrated sexual health services (SHS) in UK: Unity Sexual Health in Bristol, UK (intervention site) and Croydon Sexual Health in London (control site). PARTICIPANTS: Electronic patient records for all 58 418 attendances during the period 1 year before and 1 year after the intervention. INTERVENTION: Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways. OUTCOME MEASURES: Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances and examinations. RESULTS: Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the intervention site, and the mean cost per episode decreased by 7.5% (95% CI 5.7% to 9.3%). CONCLUSIONS: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing had the intended impact, which bolsters the case for more widespread rollout in sexual health services