Partitioning average competition and extreme-genotype effects in genetically diverse infections

Competition between parasite genotypes in genetically diverse infections is widespread. However, experimental evidence on how genetic diversity influences total parasite load is variable. Here we use an additive partition equation to quantify the negative effect of inter-genotypic competition on total parasite load in diverse infections. Our approach controls for extreme-genotype effects, a process that can potentially neutralise, or even reverse, the negative effect of competition on total parasite load. A single extreme-genotype can have a disproportionate effect on total parasite load if it causes the highest parasite load in its single-infection, while increasing its performance in diverse relative to single infections. We show that in theory such disproportionate effects of extreme-genotypes can lead to a higher total parasite load in diverse infections than expected, even if competition reduces individual parasite performance on average. Controlling for the extreme-genotype effect is only possible if the competition effect on total parasite load is measured appropriately as the average difference between the realised number of each parasite genotype in mixed infections and the expected number based on single infection parasite loads. We apply this approach to sticklebacks that were experimentally infected with different trematode genotypes. On average, genetically diverse infections had lower parasite loads than expected from single-infection results. For the first time we demonstrate that competition between co-infecting genotypes per se caused the parasite load reduction, while extreme-genotype effects were not significant. We thus suggest that to correctly quantify the effect of competition alone on total parasite load in genetically diverse infections, the extreme-genotype effect has to be controlled for

Questioning a South African hypertension threshold of 150 mm Hg – Authors' reply

We are grateful for the opportunity to respond to Schutte and colleagues. We agree with Schutte and colleagues that the systolic blood pressure (SBP) measurements presented in our study could contain error. However, of the potential sources of measurement error they note (whitecoat effects [+2·5 mm Hg], averaging measurements from two different waves [+3·8 mm Hg], and supine measurements [+3–10 mm Hg]), only the white-coat effects potentially applies to our study. Although we average measurements from 2 different years, we assign the resulting SBP to the last year of data. Therefore, any bias would result in SBP measurements that are conservative, rather than inflated by 3.5 mm Hg. SBP in the National Income Dynamics Survey is also measured in a sitting, not supine, position; however, Schutte and colleagues correctly identified our reporting error, and we have requested a formal correction. On balance, any measurement error is likely to be much smaller than Schutte and colleagues assert and would not change our main study conclusions

In Vitro Praziquantel Test Capable of Detecting Reduced In Vivo Efficacy in Schistosoma mansoni Human Infections

Although great reductions in human schistosomiasis have been observed after praziquantel (PZQ) mass drug administration (MDA), some individuals remain infected after multiple treatments. Many MDA programs now require monitoring for drug efficacy as a key component. No molecular tools for PZQ resistance currently exist and investigations into the dose of PZQ required to kill 50% of adult worms in vivo (ED50) present ethical, logistical, and temporal restraints. We, therefore, assessed the feasibility and accuracy of a rapid, inexpensive in vitro PZQ test in the laboratory and directly in the field in Uganda under MDA in conjunction with highly detailed infection intensity, clearance, and reinfection data. This test strongly differentiated between subsequently cleared and uncleared infections as well as differences between parasite populations pre- and post-PZQ treatments, advocating its use for on-the-spot monitoring of PZQ efficacy in natural foci. After only a few treatments, uncleared parasites were identified to be phenotypically different from drug-sensitive parasites, emphasizing the urgent need for monitoring of these repeatedly PZQ-treated populations

Systolic blood pressure and 6-year mortality in South Africa: a country-wide, population-based cohort study

Background: Improving hypertension control is an important global health priority, yet, to our knowledge, there is no direct evidence on the relationship between blood pressure and mortality in sub-Saharan Africa. We aimed to investigate the relationship between systolic blood pressure and mortality in South Africa and to assess the comparative effectiveness of different systolic blood pressure targets for clinical care and population-wide hypertension management efforts. Methods: In this country-wide, population-based cohort study, we used longitudinal data on adults aged 30 years and older from five waves (2008, 2010–11, 2012, 2014–15, and 2017) of the South African National Income Dynamics Study. We estimated the relationship between systolic blood pressure and 6-year all-cause mortality and compared the mortality reductions associated with lowering systolic blood pressure to different targets (120 mm Hg, 130 mm Hg, 140 mm Hg, 150 mm Hg). We also estimated the mean blood pressure reduction required to achieve each target, the share of the population in need of management, and the number needed to treat (NNT) to avert one death under different hypothetical population-wide scale-up scenarios. Findings: Of the 8338 age-eligible respondents in the 2010–11 survey, 4993 had all required data and were included in our study. We found a weak, non-linear relationship between systolic blood pressure and 6-year mortality, with larger incremental mortality benefits at higher systolic blood pressure values: reducing systolic blood pressure from 160 mm Hg to 150 mm Hg was associated with a relative risk of mortality of 0·95 (95% CI 0·90 to 0·99; p=0·033), reducing systolic blood pressure from 150 mm Hg to 140 mm Hg had a relative risk of 0·96 (0·91 to 1·01; p=0·12), with no evidence of incremental benefits of reducing systolic blood pressure below 140 mm Hg. At the population level, reducing systolic blood pressure to 150 mm Hg among all those with a starting systolic blood pressure of more than 150 mm Hg was associated with the lowest NNT (n=50), 3·3 deaths averted (95% CI −0·6 to 0·3) per 1000 population, blood pressure management for 16% (95% CI 15·2 to 17·3) of individuals, and a −2·7 mm Hg mean change in systolic blood pressure required to achieve the 150 mm Hg scale-up target (−3·0 to −2·5; p<0·0001). Interpretation: The relationship between systolic blood pressure and mortality is weaker in South Africa than in high-income and many low-income and middle-income countries. As such, we do not find compelling evidence in support of targets below 140 mm Hg and find that scaling up management based on a 150 mm Hg target is more efficient in terms of the NNT compared with strategies to reduce systolic blood pressure to lower values. Funding: Non

Application of targeted molecular and material property optimization to bacterial attachment-resistant (meth)acrylate polymers

Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the “hit” monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed

Evolutionary concepts in predicting and evaluating the impact of mass chemotherapy schistosomiasis control programmes on parasites and their hosts

Schistosomiasis is a parasitic disease of significant medical and veterinary importance in many regions of the world. Recent shifts in global health policy have led towards the implementation of mass chemotherapeutic control programmes at the national scale in previously ‘neglected’ countries such as those within sub-Saharan Africa. Evolutionary theory has an important role to play in the design, application and interpretation of such programmes. Whilst celebrating the rapid success achieved to date by such programmes, in terms of reduced infection prevalence, intensity and associated human morbidity, evolutionary change in response to drug selection pressure may be predicted under certain circumstances, particularly in terms of the development of potential drug resistance, evolutionary changes in parasite virulence, transmission and host use, and/or competitive interactions with co-infecting pathogens. Theoretical and empirical data gained to date serve to highlight the importance of careful monitoring and evaluation of parasites and their hosts whenever and wherever chemotherapy is applied and where parasite transmission remains

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

The roles of vicariance and isolation by distance in shaping biotic diversification across an ancient archipelago: evidence from a Seychelles caecilian amphibian

© 2020 The Authors. Published by BMC. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s12862-020-01673-wBackground Island systems offer excellent opportunities for studying the evolutionary histories of species by virtue of their restricted size and easily identifiable barriers to gene flow. However, most studies investigating evolutionary patterns and processes shaping biotic diversification have focused on more recent (emergent) rather than ancient oceanic archipelagos. Here, we focus on the granitic islands of the Seychelles, which are unusual among island systems because they have been isolated for a long time and are home to a monophyletic radiation of caecilian amphibians that has been separated from its extant sister lineage for ca. 65–62 Ma. We selected the most widespread Seychelles caecilian species, Hypogeophis rostratus, to investigate intraspecific morphological and genetic (mitochondrial and nuclear) variation across the archipelago (782 samples from nine islands) to identify patterns and test processes that shaped their evolutionary history within the Seychelles. Results Overall a signal of strong geographic structuring with distinct northern- and southern-island clusters were identified across all datasets. We suggest that these distinct groups have been isolated for ca. 1.26 Ma years without subsequent migration between them. Populations from the somewhat geographically isolated island of Frégate showed contrasting relationships to other islands based on genetic and morphological data, clustering alternatively with northern-island (genetic) and southern-island (morphological) populations. Conclusions Although variation in H. rostratus across the Seychelles is explained more by isolation-by-distance than by adaptation, the genetic-morphological incongruence for affinities of Frégate H. rostratus might be caused by local adaptation over-riding the signal from their vicariant history. Our findings highlight the need of integrative approaches to investigate fine-scale geographic structuring to uncover underlying diversity and to better understand evolutionary processes on ancient, continental islands.Funding for this research was provided by two grants from the National Science Foundation (BSR 88–17453, BSR 90–24505) [funding for fieldwork and lab work], two grants from the National Geographic Society (Grants 1977: 1633, 1743) [funding for fieldwork], three grants from the University of Michigan Office of the Vice President for Research, and a Research Partnership Award from the University of Michigan to RAN [morphology work]; a joint NHM-UCL IMPACT studentship [to fund STM’s PhD, lab work and fieldwork], Mohamed Bin Zayed Species Conservation Fund [funding for fieldwork] and Systematics Research Fund [funding for fieldwork] to STM; an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408 to LL [funding for lab work]; a NERC/BBSRC SynTax grant [funding for fieldwork and collaboration], and Darwin Initiative (grant 19–002) [funding for fieldwork, lab work and capacity building] with partners Bristol University, Islands Conservation Society, Seychelles Islands Foundation, Seychelles Ministry of Environment, Seychelles National Parks Authority, Seychelles Natural History Museum, University of Kent, Zoological Society of London to MW, DJG, JJD. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Published onlin

Exploratory Data Analysis

In the Food research and production field, system complexity is increasing and several new challenges are emerging every day. This implies a urgent necessity to extract information and obtain models capable of inferring the underlying relationships that link all the variability sources which characterize food or its production process (e.g. compositional profile, processing conditions) to very general end-properties of foodstuff, such as the healthiness, the consumer perception, the link to a territory and the effect of the production chain itself on food. This makes a \u201cdeductive\u201d, theory-driven research approach inefficient, since it is often difficult to formulate hypotheses. Explorative Multivariate Data Analysis methods, together with the most recent analytical instrumentation, offer the possibility to come back to an \u201cinductive\u201d data-driven attitude with a minimum of a priori hypotheses, instead helping in formulating new ones from the direct observation of data. The aim of this Chapter is to offer the reader an overview of the most significant tools which can be used in a preliminary, exploratory phase, ranging from the most classical descriptive statistics methods, to Multivariate Analysis methods, with particular attention to Projection methods. For all techniques, examples are given so that the main advantage of this techniques, that is a direct, graphical representation of data and their characteristics, can be immediately experienced by the reader