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1.
N Engl J Med ; 391(9): 810-820, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39231343

ABSTRACT

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).


Subject(s)
Eptifibatide , Intracranial Hemorrhages , Ischemic Stroke , Peptides , Pipecolic Acids , Sulfonamides , Aged , Female , Humans , Male , Middle Aged , Arginine/administration & dosage , Arginine/adverse effects , Arginine/analogs & derivatives , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Eptifibatide/administration & dosage , Eptifibatide/adverse effects , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/epidemiology , Ischemic Stroke/mortality , Ischemic Stroke/therapy , Peptides/administration & dosage , Peptides/adverse effects , Peptides/therapeutic use , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Single-Blind Method , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Thrombolytic Therapy/adverse effects , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Thrombectomy/adverse effects , Thrombectomy/methods , Treatment Outcome , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Incidence , Adult
2.
Nat Commun ; 15(1): 6012, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039075

ABSTRACT

Gut microbiomes are widely hypothesised to influence host fitness and have been experimentally shown to affect host health and phenotypes under laboratory conditions. However, the extent to which they do so in free-living animal populations and the proximate mechanisms involved remain open questions. In this study, using long-term, individual-based life history and shallow shotgun metagenomic sequencing data (2394 fecal samples from 794 individuals collected between 2013-2019), we quantify relationships between gut microbiome variation and survival in a feral population of horses under natural food limitation (Sable Island, Canada), and test metagenome-derived predictions using short-chain fatty acid data. We report detailed evidence that variation in the gut microbiome is associated with a host fitness proxy in nature and outline hypotheses of pathogenesis and methanogenesis as key causal mechanisms which may underlie such patterns in feral horses, and perhaps, wild herbivores more generally.


Subject(s)
Feces , Gastrointestinal Microbiome , Methane , Animals , Horses/microbiology , Gastrointestinal Microbiome/genetics , Feces/microbiology , Methane/metabolism , Animals, Wild/microbiology , Metagenome , Fatty Acids, Volatile/metabolism , Metagenomics/methods , Male , Female , Canada
3.
R Soc Open Sci ; 11(3): 230740, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38571911

ABSTRACT

Social competence-defined as the ability to optimize social behaviour according to available social information-can be influenced by the social environment experienced in early life. In cooperatively breeding vertebrates, the current group size influences behavioural phenotypes, but it is not known whether the group size experienced in early life influences behavioural phenotypes generally or social competence specifically. We tested whether being reared in large versus small groups for the first two months of life affects social behaviours, and associated life-history traits, in the cooperatively breeding cichlid Neolamprologus pulcher between the ages of four and twelve months. As we predicted, fish raised in larger and more complex groups showed higher social competence later in life. This was shown in several ways: they exhibited more, and earlier, submissive behaviour in response to aggression from a dominant conspecific, and-in comparison to fish raised in small groups-they exhibited more flexibility in the expression of submissive behaviour. By contrast, there was no evidence that early social complexity, as captured by the group size, affects aggression or exploration behaviour nor did it influence the propensity to disperse or show helping behaviour. Our results emphasize the importance of early-life social complexity for the development of social competence.

4.
Ecol Evol ; 14(2): e11049, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38389999

ABSTRACT

Personality variation, defined as among-individual differences in behaviour that are repeatable across time and context, is widely reported across animal taxa. From an evolutionary perspective, characterising the amount and structure of this variation is useful since differences among individuals are the raw material for adaptive behavioural evolution. However, behavioural variation among individuals also has implications for more applied areas of evolution and ecology-from invasion biology to ecotoxicology and selective breeding in captive systems. Here, we investigate the structure of personality variation in the red cherry shrimp, Neocaridina heteropoda, a popular ornamental species that is readily kept and bred under laboratory conditions and is emerging as a decapod crustacean model across these fields, but for which basic biological, ecological and behavioural data are limited. Using two assays and a repeated measures approach, we quantify behaviours putatively indicative of shy-bold variation and test for sexual dimorphism and/or size-dependent behaviours (as predicted by some state-dependent models of personality). We find moderate-to-high behavioural repeatabilities in most traits. Although strong individual-level correlations across behaviours are consistent with a major personality axis underlying these observed traits, the multivariate structure of personality variation does not fully match a priori expectations of a shy-bold axis. This may reflect our ecological naivety with respect to what really constitutes bolder, more risk-prone, behaviour in this species. We find no evidence for sexual dimorphism and only weak support for size-dependent behaviour. Our study contributes to the growing literature describing behavioural variation in aquatic invertebrates. Furthermore, it lays a foundation for further studies harnessing the potential of this emerging model system. In particular, this existing behavioural variation could be functionally linked to life-history traits and invasive success and serve as a target of artificial selection or bioassays. It thus holds significant promise in applied research across ecotoxicology, aquaculture and invasion biology.

5.
R Soc Open Sci ; 11(1): 231732, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38234441

ABSTRACT

Diet elicits varied effects on longevity across a wide range of animal species where dietary discordance between an organisms' evolutionary and developmental dietary history is increasingly recognized to play a critical role in shaping lifespan. However, whether such changes, predominantly assessed in a single generation, lead to evolutionary shifts in lifespan remains unclear. In this study, we used an experimental evolution approach to test whether changes in an organisms' evolutionary and developmental dietary history, specifically carbohydrate content, causes lifespan evolution in Drosophila serrata. After 30 generations, we investigated the evolutionary potential of lifespan in response to four novel diets that varied systematically in their ratio of carbohydrate-protein content. We also examined developmental plasticity effects using a set of control populations that were raised on the four novel environments allowing us to assess the extent to which plastic responses of lifespan mirrored adaptive responses observed following experimental evolution. Both high- and low-carbohydrate diets elicited plastic effects on lifespan; however, the plastic responses for lifespan to developmental diets bore little resemblance to the evolved responses on evolutionary diets. Understanding the dietary conditions regulating the match/mismatch of plastic and evolved responses will be important in determining whether a particular match/mismatch combination is adaptive for lifespan. While the differences in evolutionary diet by developmental diet interactions are only beginning to be elucidated, this study lays the foundation for future investigations of carbohydrate contributions to evolved and plastic effects on health and lifespan.

6.
J Evol Biol ; 36(12): 1796-1810, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37916730

ABSTRACT

Among-individual variation in cognitive traits, widely assumed to have evolved under adaptive processes, is increasingly being demonstrated across animal taxa. As variation among individuals is required for natural selection, characterizing individual differences and their heritability is important to understand how cognitive traits evolve. Here, we use a quantitative genetic study of wild-type guppies repeatedly exposed to a 'detour task' to test for genetic variance in the cognitive trait of inhibitory control. We also test for genotype-by-environment interactions (GxE) by testing related fish under alternative experimental treatments (transparent vs. semi-transparent barrier in the detour-task). We find among-individual variation in detour task performance, consistent with differences in inhibitory control. However, analysis of GxE reveals that heritable factors only contribute to performance variation in one treatment. This suggests that the adaptive evolutionary potential of inhibitory control (and/or other latent variables contributing to task performance) may be highly sensitive to environmental conditions. The presence of GxE also implies that the plastic response of detour task performance to treatment environment is genetically variable. Our results are consistent with a scenario where variation in individual inhibitory control stems from complex interactions between heritable and plastic components.


Subject(s)
Poecilia , Animals , Poecilia/genetics , Phenotype
7.
PLoS Biol ; 21(11): e3002356, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37943730

ABSTRACT

In many cooperative societies, including our own, helpers assist with the post-natal care of breeders' young and may thereby benefit the post-natal development of offspring. Here, we present evidence of a novel mechanism by which such post-natal helping could also have beneficial effects on pre-natal development: By lightening post-natal maternal workloads, helpers may allow mothers to increase their pre-natal investment per offspring. We present the findings of a decade-long study of cooperatively breeding white-browed sparrow-weaver, Plocepasser mahali, societies. Within each social group, reproduction is monopolized by a dominant breeding pair, and non-breeding helpers assist with nestling feeding. Using a within-mother reaction norm approach to formally identify maternal plasticity, we demonstrate that when mothers have more female helpers, they decrease their own post-natal investment per offspring (feed their nestlings at lower rates) but increase their pre-natal investment per offspring (lay larger eggs, which yield heavier hatchlings). That these plastic maternal responses are predicted by female helper number, and not male helper number, implicates the availability of post-natal helping per se as the likely driver (rather than correlated effects of group size), because female helpers feed nestlings at substantially higher rates than males. We term this novel maternal strategy "maternal front-loading" and hypothesize that the expected availability of post-natal help either allows or incentivizes helped mothers to focus maternal investment on the pre-natal phase, to which helpers cannot contribute directly. The potential for post-natal helping to promote pre-natal development further complicates attempts to identify and quantify the fitness consequences of helping.


Subject(s)
Mothers , Reproduction , Male , Female , Humans , Animals , Birds
8.
Heredity (Edinb) ; 131(1): 79-85, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37244934

ABSTRACT

Several studies over recent decades have reported a lack of contemporary improvement in thoroughbred racehorse speed, despite apparent additive genetic variance and putatively strong selection. More recently, it has been shown that some phenotypic improvement is ongoing, but rates are low in general and particularly so over longer distances. Here we used pedigree-based analysis of 692,534 records from 76,960 animals to determine whether these phenotypic trends are underpinned by genetic selection responses, and to evaluate the potential for more rapid improvement. We show that thoroughbred speed in Great Britain is only weakly heritable across sprint (h2 = 0.124), middle-distance (h2 = 0.122) and long-distance races (h2 = 0.074), but that mean predicted breeding values are nonetheless increasing across cohorts born between 1995 and 2012 (and racing from 1997 to 2014). For all three race distance categories, estimated rates of genetic improvement are statistically significant and also greater than can be explained by drift. Taken together our results show genetic improvement for thoroughbred speed is ongoing but slow, likely due to a combination of long generation times and low heritabilities. Additionally, estimates of realised selection intensities raises the possibility that the contemporary selection emerging from the collective actions of horse breeders is weaker than previously assumed, particularly over long distances. We suggest that unmodelled common environment effects may have upwardly biased estimates of heritability, and thus expected selection response, previously.


Subject(s)
Horses , Animals , Horses/genetics , United Kingdom , Breeding
9.
R Soc Open Sci ; 9(10): 220691, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36249332

ABSTRACT

Effects of parental age on offspring viability have been reported in a wide range of species. However, to what extent parental age influences offspring traits beyond viability remains unclear. Moreover, previous research has primarily focused on maternal age effects. The purpose of this study was to test for paternal and maternal age effects on offspring speed in thoroughbred racehorses. We analysed over 900 000 race performances by over 100 000 horses on British racecourses between 1996 and 2019. With knowledge of the age of all 41 107 dams and 2 887 sires at offspring conception, we jointly modelled maternal and paternal age effects using a 'within-individual centring' approach. Within-parents, we identified a significant effect of maternal age on offspring speed of -0.017 yards s-1 yr-1 and a corresponding paternal age effect of -0.011 yards s-1 yr-1. Although maternal age effects were stronger (more negative), the existence and magnitude of paternal effects is particularly noteworthy, given thoroughbred sires have no involvement in parental care. Our results also suggest that the selective disappearance of both sires and dams is ongoing. These findings could potentially be used to optimize thoroughbred racehorse breeding decisions, and more generally, add to the increasing body of evidence that both maternal and paternal age affect a range of offspring characteristics.

10.
Mol Ecol ; 31(21): 5524-5537, 2022 11.
Article in English | MEDLINE | ID: mdl-36005298

ABSTRACT

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding this fish's sex-determining locus, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger "evolutionary strata". Sequences of the guppy genome show that Y is very similar to the X chromosome. Knowing which parts of the Y are completely nonrecombining, and whether there is indeed a large completely nonrecombining region, are important for understanding its evolution. Here, we describe analyses of PoolSeq data in samples from within multiple natural populations from Trinidad, yielding new results that support previous evidence for occasional recombination between the guppy Y and X. We detected recent demographic changes, notably that downstream populations have higher synonymous site diversity than upstream ones and other expected signals of bottlenecks. We detected evidence of associations between sequence variants and the sex-determining locus, rather than divergence under a complete lack of recombination. Although recombination is infrequent, it is frequent enough that associations with SNPs can suggest the region in which the sex-determining locus must be located. Diversity is elevated across a physically large region of the sex chromosome, conforming to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.


Subject(s)
Poecilia , Animals , Male , Poecilia/genetics , Linkage Disequilibrium , Recombination, Genetic/genetics , Genetic Linkage , Sex Chromosomes/genetics
11.
R Soc Open Sci ; 9(6): 220269, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35706668

ABSTRACT

There is evidence that animal personality can affect sexual selection, with studies reporting that male behavioural types are associated with success during pre- and post-copulatory sexual selection. Given these links between personality and sexual traits, and the accumulating evidence that their expression can depend on an individual's dietary status (i.e. condition), a novel prediction is that changes in a male's diet should alter both the average expression of personality and sexual traits, and their covariance. We tested these predictions using the guppy Poecilia reticulata, a species previously shown to exhibit strong condition dependence in ejaculate traits and a positive correlation between sperm production and individual variation in boldness. Contrary to expectation, we found that dietary restriction-when administered in mature adult males-did not affect the expression of either behavioural (boldness and activity) or ejaculate traits, although we did find that males subjected to dietary stress exhibited a positive association between sperm velocity and boldness that was not apparent in the unrestricted diet group. This latter finding points to possible context-dependent patterns of covariance between sexually selected traits and personalities, which may have implications for patterns of selection and evolutionary processes under fluctuating environmental conditions.

12.
Lancet Haematol ; 9(4): e250-e261, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35271808

ABSTRACT

BACKGROUND: Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS: Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS: From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION: The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation.


Subject(s)
COVID-19 , Emergency Medical Services , Shock, Hemorrhagic , Adolescent , Adult , Blood Transfusion , Humans , Male , Middle Aged , Pandemics , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/therapy , Treatment Outcome
13.
J Evol Biol ; 35(4): 657-663, 2022 04.
Article in English | MEDLINE | ID: mdl-35290690

ABSTRACT

Sex differences in lifespan remain an intriguing puzzle in evolutionary biology. While explanations range from sex differences in selection to sex differences in the expression of recessive lifespan-altering mutations (via X-linkage), little consensus has been reached. One unresolved issue is the extent to which genetic influences on lifespan dimorphism are modulated by the environment. For example, studies have shown that sex differences in lifespan can either increase or decrease depending upon the social environment. Here, we took an experimental approach, manipulating multiple axes of the social environment across inbred long- and short-lived genotypes and their reciprocal F1s in the fly Drosophila serrata. Our results reveal strong genetic effects and subtle yet significant genotype-by-environment interactions for male and female lifespan, specifically due to both population density and mating status. Further, our data do not support the idea that unconditional expression of deleterious X-linked recessive alleles in heterogametic males accounts for lower male lifespan.


Subject(s)
Drosophila , Longevity , Animals , Biological Evolution , Drosophila/genetics , Drosophila melanogaster/genetics , Female , Longevity/genetics , Male , Reproduction , Sex Characteristics
14.
Ecol Lett ; 25(5): 1139-1151, 2022 May.
Article in English | MEDLINE | ID: mdl-35235709

ABSTRACT

Life-history strategies differ with respect to investment in current versus 'future' reproduction, but when is this future? Under the novel 'temporality in reproductive investment hypothesis', we postulate variation should exist in the time frame over which reproductive costs are paid. Slow-paced individuals should pay reproductive costs over short (e.g. inter-annual) time scales to prevent reproductive costs accumulating, whereas fast-paced individuals should allow costs to accumulate (i.e. senescence). Using Fourier transforms, we quantify adjustments in clutch size with age, across four populations of blue tits (Cyanistes caeruleus). Fast populations had more prevalent and stronger long-term changes in reproductive investment, whereas slower populations had more prevalent short-term adjustments. Inter-annual environmental variation partly accounted for short-, but not long-term changes in reproductive investment. Our study reveals individuals differ in when they pay the cost of reproduction and that failure to partition this variation across different temporal scales and environments could underestimate reproductive trade-offs.


Subject(s)
Life History Traits , Passeriformes , Animals , Clutch Size , Humans , Reproduction
15.
Elife ; 112022 02 11.
Article in English | MEDLINE | ID: mdl-35144728

ABSTRACT

The vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. Natural selection should favour functional integration, leading to a prediction of genetic integration of these traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here, we demonstrate that acute stress response components in Trinidadian guppies are both heritable and integrated on the major axis of genetic covariation. This integration could either facilitate or constrain evolutionary responses to selection, depending upon the alignment of selection with this axis. Such integration also suggests artificial selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the improvement of health and welfare in captive animal populations.


Subject(s)
Behavior, Animal , Poecilia/genetics , Poecilia/physiology , Stress, Psychological/genetics , Animals , Female , Fresh Water/analysis , Hydrocortisone/analysis , Male
16.
J Intensive Care Soc ; 23(1): 11-19, 2022 Feb.
Article in English | MEDLINE | ID: mdl-37593537

ABSTRACT

Background: Control of the arterial partial pressure of carbon dioxide (PaCO2) is important in the ventilated patient. End-tidal carbon dioxide (ETCO2) levels are often used as a proxy, but are clinically limited. The difference between the PaCO2 and ETCO2 has been suggested to be 0.5-1.0 kPa. However, this has not been consistently reflected in the physiologically unstable pre-hospital patient. This study aims to elucidate the PaCO2-ETCO2 gradient for pre-hospital intubated patients. Methods: This was a retrospective, cohort study using data identified from the HEMSbase 2 database (Feb 2015-Nov 2018). Patients were included if they had documented ETCO2 and arterial PaCO2 measurements. Arterial PaCO2 data that could not be linked to within 5 minutes of ETCO2 were excluded. Bland-Altman plots were calculated to describe agreement. Results: A total of 73 patients were identified. Aetiology was arranged into three categories: 13 (17.8%) medical, 22 (30.1%) traumatic and 38 (52.1%) out-of-hospital cardiac arrest (OHCA). The median PaCO2-ETCO2 gradient was 2.0 [1.3-3.1] kPa. A PaCO2-ETCO2 gradient of 0-1 kPa was seen for only 11 (15.1%) of total patients. The Bland-Altman agreement for all aetiologies was more than the accepted gradient of 0-1 kPa with the largest bias and widest limits of agreement seen for OHCA (-3.2 [0.3 - -6.8]). Conclusion: The magnitude of the differences between the ETCO2 and PaCO2, levels of variation and inability to predict this suggest that ETCO2 is not a suitable surrogate upon which to base ventilatory settings in conditions where pH or PaCO2 require precise control.

17.
Front Vet Sci ; 9: 1046205, 2022.
Article in English | MEDLINE | ID: mdl-36590805

ABSTRACT

Chronic stress is a major source of welfare problems in many captive populations, including fishes. While we have long known that chronic stress effects arise from maladaptive expression of acute stress response pathways, predicting where and when problems will arise is difficult. Here we highlight how insights from animal personality research could be useful in this regard. Since behavior is the first line of organismal defense when challenged by a stressor, assays of shy-bold type personality variation can provide information about individual stress response that is expected to predict susceptibility to chronic stress. Moreover, recent demonstrations that among-individual differences in stress-related physiology and behaviors are underpinned by genetic factors means that selection on behavioral biomarkers could offer a route to genetic improvement of welfare outcomes in captive fish stocks. Here we review the evidence in support of this proposition, identify remaining empirical gaps in our understanding, and set out appropriate criteria to guide development of biomarkers. The article is largely prospective: fundamental research into fish personality shows how behavioral biomarkers could be used to achieve welfare gains in captive fish populations. However, translating potential to actual gains will require an interdisciplinary approach that integrates the expertise and viewpoints of researchers working across animal behavior, genetics, and welfare science.

18.
Mol Ecol ; 31(23): 6128-6140, 2022 12.
Article in English | MEDLINE | ID: mdl-33728719

ABSTRACT

Many organisms are capable of growing faster than they do. Restrained growth rate has functionally been explained by negative effects on lifespan of accelerated growth. However, the underlying mechanisms remain elusive. Telomere attrition has been proposed as a causal agent and has been mostly studied in endothermic vertebrates. We established that telomeres exist as chromosomal-ends in a model insect, the field cricket Gryllus campestris, using terminal restriction fragment and Bal 31 methods. Telomeres comprised TTAGGn repeats of 38 kb on average, more than four times longer than the telomeres of human infants. Bal 31 assays confirmed that telomeric repeats were located at the chromosome-ends. We tested whether rapid growth between day 1, day 65, day 85, and day 125 is achieved at the expense of telomere length by comparing nymphs reared at 23°C with their siblings reared at 28°C, which grew three times faster in the initial 65 days. Surprisingly, neither temperature treatment nor age affected average telomere length. Concomitantly, the broad sense heritability of telomere length was remarkably high at ~100%. Despite high heritability, the evolvability (a mean-standardized measure of genetic variance) was low relative to that of body mass. We discuss our findings in the context of telomere evolution. Some important features of vertebrate telomere biology are evident in an insect species dating back to the Triassic. The apparent lack of an effect of growth rate on telomere length is puzzling, suggesting strong telomere length maintenance during the growth phase. Whether such maintenance of telomere length is adaptive remains elusive and requires further study investigating the links with fitness in the wild.


Subject(s)
Gryllidae , Animals , Infant , Humans , Gryllidae/genetics , Temperature , Telomere Homeostasis , Longevity , Telomere/genetics
19.
Mol Ecol ; 31(5): 1337-1357, 2022 03.
Article in English | MEDLINE | ID: mdl-34170592

ABSTRACT

Parallel evolution, in which independent populations evolve along similar phenotypic trajectories, offers insights into the repeatability of adaptive evolution. Here, we revisit a classic example of parallelism, that of repeated evolution of brighter males in the Trinidadian guppy (Poecilia reticulata). In guppies, colonisation of low predation habitats is associated with emergence of 'more colourful' phenotypes since predator-induced viability selection for crypsis weakens while sexual selection by female preference for conspicuousness remains strong. Our study differs from previous investigations in three respects. First, we adopted a multivariate phenotyping approach to characterise parallelism in multitrait space. Second, we used ecologically-relevant colour traits defined by the visual systems of the two selective agents (i.e., guppy, predatory cichlid). Third, we estimated population genetic structure to test for adaptive (parallel) evolution against a model of neutral phenotypic divergence. We find strong phenotypic differentiation that is inconsistent with a neutral model but very limited support for the predicted pattern of greater conspicuousness at low predation. Effects of predation regime on each trait were in the expected direction, but weak, largely nonsignificant, and explained little among-population variation. In multitrait space, phenotypic trajectories of lineages colonising low from high predation regimes were not parallel. Our results are consistent with reduced predation risk facilitating adaptive differentiation, potentially by female choice, but suggest that this proceeds in independent directions of multitrait space across lineages. Pool-sequencing data also revealed SNPs showing greater differentiation than expected under neutrality, among which some are found in genes contributing to colour pattern variation, presenting opportunities for future genetic study.


Subject(s)
Poecilia , Animals , Biological Evolution , Color , Female , Male , Phenotype , Poecilia/genetics , Predatory Behavior
20.
Sci Adv ; 7(39): eabe8980, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34550732

ABSTRACT

Altruism is globally associated with unpredictable environments, but we do not understand why. New theory has highlighted that unpredictable environments could favor the evolution of altruism if altruistic acts reduce environmentally induced variance in the reproductive success of relatives ("altruistic bet-hedging"). Here, we show that altruism does indeed reduce environmentally induced reproductive variance in a wild cooperative bird. Our decade-long field study reveals that altruistic helping actually has no overall effect on the mean reproductive success of relatives but instead reduces their reproductive variance. This remarkable pattern arises because helpers improve reproductive performance in dry conditions but reduce it in wet conditions. Helpers thereby specifically reduce rainfall-induced reproductive variance, the very mechanism required for altruistic bet-hedging to explain the enigmatic global association between avian altruism and unpredictable rainfall.

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