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Gyrodactylus salaris (Monogenea, Platyhelminthes) is a notifiable freshwater pathogen responsible for causing catastrophic damage to wild Atlantic salmon stocks, most notably in Norway. In some strains of Baltic salmon (e.g., from the river Neva) however, the impact is greatly reduced due to some form of innate resistance that regulates parasite numbers, resulting in fewer host mortalities. Gyrodactylus salaris is known from 17 European states; its status in a further 35 states remains unknown; the UK, the Republic of Ireland and certain watersheds in Finland are free of the parasite. Thus, the parasite poses a serious threat if it emerges in Atlantic salmon rearing regions throughout Europe. At present, infections are generally controlled via extreme measures such as the treatment of entire river catchments with the biocide rotenone, in order to remove all hosts, before restocking with the original genetic stock. The use of rotenone in this way in EU countries is unlikely as it would be in contravention of the Water Framework Directive. Not only are such treatments economically and environmentally costly, they also eradicate the potential for any host/parasite evolutionary process to occur. Based on previous studies, UK salmon stocks have been shown to be highly susceptible to infection, analogous to Norwegian stocks. The present study investigates the impact of a G. salaris outbreak within a naïve salmon population in order to determine long-term consequences of infection and the likelihood of coexistence. Simulation of the salmon/ G. salaris system was carried out via a deterministic mathematical modelling approach to examine the dynamics of host-pathogen interactions. Results indicated that in order for highly susceptible Atlantic strains to evolve a resistance, both a moderate-strong deceleratingly costly trade-off on birth rate and a lower overall cost of the immune response are required. The present study provides insights into the potential long term impact of G. salaris if introduced into G. salaris-free territories and suggests that in the absence of external controls salmon populations are likely to recover to high densities nearing 90% of that observed pre-infection. [ABSTRACT FROM AUTHOR]

Abstract: Traditionally, to determine the possible evolutionary behaviour of an ecological system using adaptive dynamics, it is necessary to calculate the fitness and its derivatives at a singular point. We investigate the claim that the possible evolutionary behaviour can be predicted directly from the population dynamics, without the need for calculation, by applying three criteria — one based on the form of the density dependent rates and two on the role played by the evolving parameters. Taking a general continuous time model, with broad ecological range, we show that the claim is true. Initially, we assume that individuals enter in class 1 and move through population classes sequentially; later we relax these assumptions and find that the criteria still apply. However, when we consider models where the evolving parameters appear non-linearly in the dynamics, we find some aspects of the criteria fail; useful but weaker results on possible evolutionary behaviour now apply. [Copyright &y& Elsevier]

Abstract: Trade-off shapes are crucial to evolutionary outcomes. However, due to different ecological feedbacks their implications may depend not only on the trade-off being considered but also the ecological scenario. Here, we apply a novel geometric technique, trade-off and invasion plots (TIPs), to examine in detail how the shape of trade-off relationships affect evolutionary outcomes under a range of classic ecological scenarios including Lotka–Volterra type and host–parasite interactions. We choose models of increasing complexity in order to gain an insight into the features of ecological systems that determine the evolutionary outcomes. In particular we focus on when evolutionary attractors, repellors and branching points occur and how this depends on whether the costs are accelerating (benefits become ‘increasingly’ costly), decelerating (benefits become ‘decreasingly’ costly) or constant. In all cases strongly accelerating costs lead to attractors while strongly decelerating ones lead to repellors, but with weaker relationships, this no longer holds. For some systems weakly accelerating costs may lead to repellors and decelerating costs may lead to attractors. In many scenarios it is weakly decelerating costs that lead to branching points, but weakly accelerating and linear costs may also lead to disruptive selection in particular ecological scenarios. Using our models we suggest a classification of ecological interactions, based on three distinct criteria, that can produce one of four fundamental TIPs which allow for different evolutionary behaviour. This provides a baseline theory which may inform the prediction of evolutionary outcomes in similar yet unexplored ecological scenarios. In addition we discuss the implications of our results to a number of specific life-history trade-offs in the classic ecological scenarios represented by our models. [Copyright &y& Elsevier]

Abstract: The purpose of this paper is to take an entirely geometrical path to determine the evolutionary properties of ecological systems subject to trade-offs. In particular we classify evolutionary singularities in a geometrical fashion. To achieve this, we study trade-off and invasion plots (TIPs) which show graphically the outcome of evolution from the relationship between three curves. The first invasion boundary (curve) has one strain as resident and the other strain as putative invader and the second has the roles of the strains reversed. The parameter values for one strain are used as the origin with those of the second strain varying. The third curve represents the trade-off. All three curves pass through the origin or tip of the TIP. We show that at this point the invasion boundaries are tangential. At a singular TIP, in which the origin is an evolutionary singularity, the invasion boundaries and trade-off curve are all tangential. The curvature of the trade-off curve determines the region in which it enters the singular TIP. Each of these regions has particular evolutionary properties (EUS, CS, SPR and MI). Thus we determine by direct geometric argument conditions for each of these properties in terms of the relative curvatures of the trade-off curve and invasion boundaries. We show that these conditions are equivalent to the standard partial derivative conditions of adaptive dynamics. The significance of our results is that we can determine whether the singular strategy is an attractor, branching point, repellor, etc. simply by observing in which region the trade-off curve enters the singular TIP. In particular we find that, if and only if the TIP has a region of mutual invadability, is it possible for the singular strategy to be a branching point. We illustrate the theory with an example and point the way forward. [Copyright &y& Elsevier]

Phase angle (PhA) calculated via bioelectrical impedance vector analysis (BIVA) is a measure of body cell mass and hydration that is commonly used to detect fluid imbalance and nutritional status. Phase angle is derived from the raw impedance values resistance (R) and reactance (Xc), obtained from multi-frequency bioelectrical analysis (MF-BIA). Currently there are no studies investigating the effect of acute feeding on measures of PhA obtained by MF-BIA. PURPOSE: To determine the effect of acute feeding on PhA. METHODS: Thirty-eight young adults (Age: 21.9±3.1 yrs; Height: 174.1±8.7 cm; Weight: 72.1±9.9 kg; BMI: 23.5±1.9 kg/m²) were randomized to four conditions; high carbohydrate (CHO: 116.5 g CHO; 86% of meal), high protein (PRO: 63.5 g PRO; 58% of meal), ad libitum mixed (MX: 67 g CHO, 21 g PRO; 25 g FAT) and fasted (FAST: 8 hr fast). Meals were consumed one hour prior to MF-BIA measurement. Bioelectrical impedance was measured using a tetrapolar stand-up MF-BIA device. Subjects stood for five minutes prior to measurement on the device's scale with the soles of their feet positioned on four corresponding electrodes; subjects held the handles in both hands making contact with corresponding electrodes on the thumbs and palm of each hand as impedance was measured. Separate one-way ANOVAs were used to compare PhA of the whole body (WB), trunk (TR), right arm (RA), and right leg (RL) between feeding groups. RESULTS: There was no significant difference in PhA between feeding groups for WB (p = 0.985, mean ± SD = 6.46±0.71°), TR (p = 0.918, mean ± SD = 8.95±1.64°), RA (p = 0.903, mean ± SD = 5.82±0.79°), or RL (p = 0.988, mean ± SD = 7.03±0.57°). CONCLUSION: The lack of difference between PhA values across feeding groups suggests that acute feeding does not alter hydration-sensitive MF-BIA measures of impedance values. This could indicate that current measuring practices, which typically require participants to be fasted, may not be necessary to obtain reliable body composition values. [ABSTRACT FROM AUTHOR]

Inflammasomes are multiprotein signaling platforms of the innate immune system that detect markers of physiological stress and promote the maturation of caspase-1 and interleukin 1 beta (IL-1β), IL-18, and gasdermin D. This randomized, cross-over trial investigated the influence of 2-week mixed flavonoid (FLAV) versus placebo (PL) supplementation on inflammasome activation and IL-1β and IL-18 production after 75-km cycling in 22 cyclists (42 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr postexercise (176 ± 5.4 min, 73.4 ± 2.0 %VO2max). The supplement (678 mg FLAVs) included quercetin, green tea catechins, and bilberry anthocyanins. The pattern of change in the plasma levels of the inflammasome adaptor oligomer ASC (apoptosis-associated speck-like protein containing caspase recruitment domain) was different between the FLAV and PL trials, with the FLAV ASC levels 52% lower (Cohen's d = 1.06) than PL immediately following 75-km cycling (interaction effect, p =.012). The plasma IL-1β levels in FLAV were significantly lower than PL (23–42%; Cohen's d = 0.293–0.644) throughout 21 hr of recovery (interaction effect, p =.004). The change in plasma gasdermin D levels were lower immediately postexercise in FLAV versus PL (15% contrast, p =.023; Cohen's d = 0.450). The patterns of change in plasma IL-18 and IL-37 did not differ between the FLAV and PL trials (interaction effects, p =.388,.716, respectively). These data indicate that 2-week FLAV ingestion mitigated inflammasome activation, with a corresponding decrease in IL-1β release in cyclists after a 75-km cycling time trial. The data from this study support the strategy of ingesting high amounts of FLAV to mitigate postexercise inflammation. [ABSTRACT FROM AUTHOR]

Gyrodactylus salaris is a notifiable freshwater ectoparasite of salmonids. Its primary host is Atlantic salmon (Salmo salar), upon which infections can cause death, and have led to massive declines in salmon numbers in Norway, where the parasite is widespread. Different strains of S. salar vary in their susceptibility, with Atlantic strains (such as those found in Norway) exhibiting no resistance to the parasite, and Baltic strains demonstrating an innate resistance sufficient to regulate parasite numbers on the host causing it to either die out or persist at a low level. In this study, Leslie matrix and compartmental models were used to generate data that demonstrated the population growth of G. salaris on an individual host is dependent on the total number of offspring per parasite, its longevity and the timing of its births. The data demonstrated that the key factor determining the rate of G. salaris population growth is the time at which the parasite first gives birth, with rapid birth rate giving rise to large population size. Furthermore, it was shown that though the parasite can give birth up to four times, only two births are required for the population to persist as long as the first birth occurs before a parasite is three days old. As temperature is known to influence the timing of the parasite's first birth, greater impact may be predicted if introduced to countries with warmer climates than Norway, such as the UK and Ireland which are currently recognised to be free of G. salaris. However, the outputs from the models developed in this study suggest that temperature induced trade-offs between the total number of offspring the parasite gives birth to and the first birth timing may prevent increased population growth rates over those observed in Norway. [ABSTRACT FROM AUTHOR]

Variants of the susceptible-infected-removed (SIR) model of Kermack & McKendrick (1927) enjoy wide application in epidemiology, offering simple yet powerful inferential and predictive tools in the study of diverse infectious diseases across human, animal and plant populations. Direct transmission models (DTM) are a subset of these that treat the processes of disease transmission as comprising a series of discrete instantaneous events. Infections transmitted indirectly by persistent environmental pathogens, however, are examples where a DTM description might fail and are perhaps better described by models that comprise explicit environmental transmission routes, so-called environmental transmission models (ETM). In this paper we discuss the stochastic susceptible-exposed-infected-removed (SEIR) DTM and susceptible-exposed-infected-removed-pathogen (SEIR-P) ETM and we show that the former is the timescale separation limit of the latter, with ETM host-disease dynamics increasingly resembling those of a DTM when the pathogen's characteristic timescale is shortened, relative to that of the host population. Using graphical posterior predictive checks (GPPC), we investigate the validity of the SEIR model when fitted to simulated SEIR-P host infection and removal times. Such analyses demonstrate how, in many cases, the SEIR model is robust to departure from direct transmission. Finally, we present a case study of white spot disease (WSD) in penaeid shrimp with rates of environmental transmission and pathogen decay (SEIR-P model parameters) estimated using published results of experiments. Using SEIR and SEIR-P simulations of a hypothetical WSD outbreak management scenario, we demonstrate how relative shortening of the pathogen timescale comes about in practice. With atttempts to remove diseased shrimp from the population every 24h, we see SEIR and SEIR-P model outputs closely conincide. However, when removals are 6-hourly, the two models' mean outputs diverge, with distinct predictions of outbreak size and duration. Author summary: Mathematical models of the spread and progression of communicable disease in populations are important tools in efforts to prevent and control outbreaks. A common class of disease models assume that infection is transmitted directly from infectious to susceptible individuals when they are in close proximity—so called direct transmission models. These are used widely and have proven invaluable as simplified descriptions of a wide array of infectious diseases in diverse populations. However, many pathogens spread through indirect, environmental routes of transmission, for example via contact with contaminated water sources in the case of cholera, or inhalation of infectious airborne droplets for respiratory infections, such as Covid-19. We show that direct transmission models work well for such pathogens with short environmental lifetimes and where hosts shed pathogens into the environment at high rates. This means that we do not require information about environmental pathogen levels to understand the behaviour of outbreaks caused by these pathogens. When shedding rates are also low, e.g., with macroparasitic infections, or when variable environmental factors play a role in transmissibility, then explicit modelling of both the pathogen and environmental transmission will provide a more accurate picture than a direct transmission approximation. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the biggest threats to global health, food security, and development. Antibiotic overuse and misuse are the main drivers for the emergence of resistance. It is crucial to optimise the use of existing antibiotics in order to improve medical outcomes, decrease toxicity and reduce the emergence of resistance. We formulate the design of antibiotic dosing regimens as an optimisation problem, and use an evolutionary algorithm suited to continuous optimisation (differential evolution) to solve it. Regimens are represented as vectors of real numbers encoding daily doses, which can vary across the treatment duration. A stochastic mathematical model of bacterial infections with tuneable resistance levels is used to evaluate the effectiveness of evolved regimens. The objective is to minimise the treatment failure rate, subject to a constraint on the maximum total antibiotic used. We consider simulations with different levels of bacterial resistance, two ways of administering the drug (orally and intravenously), as well as coinfections with two strains of bacteria. Our approach produced effective dosing regimens, with an average improvement in lowering the failure rate 30%, when compared with standard fixed-daily-dose regimens with the same total amount of antibiotic. [ABSTRACT FROM AUTHOR]

Phagocytosis is defined as the ingestion of particulates over 0.5 µm in diameter and is associated with cells of the immune system such as macrophages or monocytes. Neurones are not generally recognized to be phagocytic. Using light, confocal, time-lapse and electron microscopy, we carried out a wide range of in-vitro and in-vivo experiments to examine the phagocytic capacity of different neuronal cell types. We demonstrated phagocytosis of material by neurones, including cell debris and synthetic particles up to 2.8 µm in diameter. We showed phagocytosis in different neuronal types, and demonstrated that debris can be transported from neurite extremities to cell bodies and persist within neurones. Flow cytometry analysis demonstrated the lack of certain complement receptors on neurones but the presence of others, including integrin receptors known to mediate macrophage phagocytosis, indicating that a restricted set of phagocytosis receptors may mediate this process. Neuronal phagocytosis occurs in vitro and in vivo, and we propose that this is a more widespread and significant process than previously recognized. Neuronal phagocytosis may explain certain inclusions in neurones during disease, cell-to-cell spread of disease, neuronal death during disease progression and provide a potential mechanism for therapeutic intervention through the delivery of particulate drug carriers. [ABSTRACT FROM AUTHOR]

Hormonal fluctuations that occur throughout the menstrual cycle may have a significant impact on body composition and metabolism, which could alter measurement accuracy. PURPOSE: To identify the effects of menstrual cycle phase on body composition; a secondary aim was to evaluate menstrual cycle phase on resting metabolic rate (RMR) and respiratory quotient (RQ). METHODS: Body composition was obtained from a 4-compartment (4C) model (fat mass [FM], fat-free mass [FFM], and body fat percent [%BF]) and dual-energy X-ray absorptiometry (DXA; FM, lean mass [LM], trunk FM [TFM], and trunk LM [TLM]) in 19 eumenorrheic females not using any form of birth control (Mean ± Standard Deviation [SD]: Age 21.3 ± 3.1 yrs, Height 166.9 ± 5.7 cm, Weight 65.0 ± 2.2 kg). RMR (kcal/day) and RQ (a.u.) were measured via indirect calorimetry for 25 minutes. Body composition, RMR, and RQ were measured during the early follicular (EF) and mid-follicular (MF) phases. Dependent samples t-tests were used to compare outcomes between EF and MF. RESULTS: No significant differences were found in 4C outcomes (FM, FFM, and %BF; p>0.05) between EF and MF. No significant differences were found for DXA-measured LM, TLM, or %BF (p>0.05), however, DXA FM was significantly greater during EF compared to MF (Mean Difference [MD]± Standard Error [SE]: 0.29 ± 0.09 kg; p=0.005), and DXA TFM was greater during EF (Mean ± SD: 7.9 ± 2.9 kg) compared to MF (Mean ± SD: 7.8 ± 2.5 kg; p=0.06). While RMR was not significantly different between phases (MD ± SE: 6.0 ± 43.8 kcal/day; p>0.05), RQ was significantly higher during EF (Mean ± SD: 0.76 ± 0.05 a.u.) compared to MF (Mean ± SD: 0.73 ± 0.03 a.u; p=0.029). CONCLUSIONS: Often women are excluded from research due to physiological effects of hormonal fluctuations throughout the menstrual cycle; body composition from 4C or DXA do not appear to be impacted beyond measurement error as a result of compartmental changes from the menstrual cycle during the early and mid-follicular phases. Women oxidized more fat as demonstrated by a lower RQ during MF. [ABSTRACT FROM AUTHOR]

PURPOSE: Training above ventilatory threshold (VT), and corresponding heart rate, have resulted in improvements in aerobic capacity; the ability to oxidize fatty acids is a limiting factor in endurance performance. Additionally, little is known about the contribution of body composition on maximal fat oxidation (Fatmax). The purpose of this study was to characterize Fatmax and its relationship to VT in endurance trained young adult males. A secondary purpose was to understand the impact of body composition on Fatmax. METHODS: 25 trained males (Age: 22.2±2.4 yrs; Height:177.0±4.8 cm; Weight: 75.3±6.9 kg; VO2max: 50.5±14.6 mL/kg/min) were assessed for body composition using dual-energy X-ray absorptiometry to estimate lean mass (LM), fat mass (FM), and percent body fat (%BF). All subjects performed an incremental graded exercise test to volitional exhaustion. Fatmax was determined as the exercise intensity (%VO2max) at which the highest rate of fat oxidation was observed. VT was determined automatically from the software as the point by which respiration increased to compensate for CO2 and lactate accumulation. Paired t-tests were used to determine the differences between Fatmax and VT%VO2max, FatmaxVO2 and VTVO2, and HR at Fatmax and VT. Multiple linear regression was used to analyze the influence of body composition on Fatmax. RESULTS: There were no significant differences between Fatmax and VT%VO2 (Mean Difference ± Standard Error: -0.2±0.1%; p=0.107) or FatmaxVO2 and VTVO2 (-3.4±3.1 L/min; p=0.288). FatmaxHR was significantly lower than VTHR (-11.7±3.1 bpm; p=0.001). LM, FM, %BF did not significantly influence Fatmax (F=0.888, R²=0.13, p=0.464). CONCLUSIONS: The similar intensity observed between VT and Fatmax suggests training above VT could be a useful strategy for maximizing fat oxidation during exercise, thereby supporting glycogen sparing in addition to enhanced training volume and exercise adaptations. Body composition does not appear to be an important factor for Fatmax in young males. [ABSTRACT FROM AUTHOR]

Strength and conditioning is an essential aspect to athlete development. The COVID-19 pandemic forced many collegiate athletes to train at home, without access to strength and conditioning facilities. PURPOSE: To examine body composition of National Collegiate Athletic Association (NCAA) Division I football players pre- and post-COVID-19 quarantine. METHODS: Body composition of 29 NCAA Division I football players (Age=21.0±10 yrs, Ht=186.7±5.6 cm, Wt=110.5 ±22.8 kg) were measured around the start of Spring season (March) and prior to pre-season training (June) following a minimum 2h fast and having refrained from recent exercise. Whole body dual-energy x-ray absorptiometry (DXA) was used to determine regional (arms, legs, trunk) and total body fat mass (FM), lean mass (LM), and fat free mass (FFM). Fat-Free Mass Index (FFMI) was calculated (FFMI= [LM+Bone Mineral Content (BMC)]/Height2); participants were stratified by FFMI (Upper: >25 lbs/m²; n=16, Lower: <25 lbs/m², n=13). Paired samples t-tests were used to evaluate the effect of pre vs. post-COVID quarantine on body composition. RESULTS: For the total sample, trunk LM (Mean Difference ± Standard Error: -0.96± 0.21 kg, p<0.001), and trunk FFM (-0.98± 0.21 kg, p<0.001) measures significantly increased from pre¬to post-COVID quarantine. Legs FM was significantly decreased (0.46±0.19 kg, p=0.023) post-COVID-19. Players with a lower FFMI showed a significant decrease in legs FM (0.47 ± 0.17 kg, p=0.016), trunk percent fat (1.15±0.42%, p=0.017), and trunk FM (0.55± 0.19 kg, p=0.016). Players in the upper FFMI showed a significant increase in total LM (-0.96±0.42 kg, p=0.038), total FFM (-0.99± 0.43 kg, p=0.036), and a decrease in arm FFM (0.49 ± 0.22 kg, p=0.045). CONCLUSIONS: The collective improvement in trunk LM and FFM, as well as decreases in leg FM, suggest the limited access to weight room equipment did not have a detrimental effect on body composition. Upper body FFM was lost only in the more muscular cohort (FFMI <25 lbs/m²). Overall, virtual programming and nutritional support likely played an important role in the improvements and maintenance of body composition outcomes during quarantine. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic resistance. Efforts have been made to reduce unnecessary drug prescriptions, but limited work is devoted to optimising dosage regimes when they are prescribed. The design of antibiotic treatments can be formulated as an optimisation problem where candidate solutions are encoded as vectors of dosages per day. The formulation naturally gives rise to competing objectives, as we want to maximise the treatment effectiveness while minimising the total drug use, the treatment duration and the concentration of antibiotic experienced by the patient. This article combines a recent mathematical model of bacterial growth including both susceptible and resistant bacteria, with a multi-objective evolutionary algorithm in order to automatically design successful antibiotic treatments. We consider alternative formulations combining relevant objectives and constraints. Our approach obtains shorter treatments, with improved success rates and smaller amounts of drug than the standard practice of administering daily fixed doses. These new treatments consistently involve a higher initial dose followed by lower tapered doses. [ABSTRACT FROM AUTHOR]