The role of neutral and adaptive evolutionary processes on patterns of genetic diversity across small cave-dwelling populations of Icelandic Arctic charr (Salvelinus alpinus).

Understanding the adaptability of small populations in the face of environmental change is a central problem in evolutionary biology. Solving this problem is challenging because neutral evolutionary processes that operate on historical and contemporary timescales can override the effects of selection in small populations. We assessed the effects of isolation by colonization (IBC), isolation by dispersal limitation (IBDL) as reflected by a pattern of isolation by distance (IBD), and isolation by adaptation (IBA) and the roles of genetic drift and gene flow on patterns of genetic differentiation among 19 cave-dwelling populations of Icelandic Arctic charr (Salvelinus alpinus). We detected evidence of IBC based on the genetic affinity of nearby cave populations and the genetic relationships between the cave populations and the presumed ancestral population in the lake. A pattern of IBD was evident regardless of whether high-level genetic structuring (IBC) was taken into account. Genetic signatures of bottlenecks and lower genetic diversity in smaller populations indicate the effect of drift. Estimates of gene flow and fish movement suggest that gene flow is limited to nearby populations. In contrast, we found little evidence of IBA as patterns of local ecological and phenotypic variation showed little association with genetic differentiation among populations. Thus, patterns of genetic variation in these small populations likely reflect localized gene flow and genetic drift superimposed onto a larger-scale structure that is largely a result of colonization history. Our simultaneous assessment of the effects of neutral and adaptive processes in a tractable and replicated system has yielded novel insights into the evolution of small populations on both historical and contemporary timescales and over a smaller spatial scale than is typically studied.

Fine scale diversity in the lava: genetic and phenotypic diversity in small populations of Arctic charr Salvelinus alpinus.

BACKGROUND: A major goal in evolutionary biology is to understand the processes underlying phenotypic variation in nature. Commonly, studies have focused on large interconnected populations or populations found along strong environmental gradients. However, studies on small fragmented populations can give strong insight into evolutionary processes in relation to discrete ecological factors. Evolution in small populations is believed to be dominated by stochastic processes, but recent work shows that small populations can also display adaptive phenotypic variation, through for example plasticity and rapid adaptive evolution. Such evolution takes place even though there are strong signs of historical bottlenecks and genetic drift. Here we studied 24 small populations of the freshwater fish Arctic charr (Salvelinus alpinus) found in groundwater filled lava caves. Those populations were found within a few km2-area with no apparent water connections between them. We studied the relative contribution of neutral versus non-neutral evolutionary processes in shaping phenotypic divergence, by contrasting patterns of phenotypic and neutral genetic divergence across populations in relation to environmental measurements. This allowed us to model the proportion of phenotypic variance explained by the environment, taking in to account the observed neutral genetic structure. RESULTS: These populations originated from the nearby Lake Mývatn, and showed small population sizes with low genetic diversity. Phenotypic variation was mostly correlated with neutral genetic diversity with only a small environmental effect. CONCLUSIONS: Phenotypic diversity in these cave populations appears to be largely the product of neutral processes, fitting the classical evolutionary expectations. However, the fact that neutral processes did not explain fully the phenotypic patterns suggests that further studies can increase our understanding on how neutral evolutionary processes can interact with other forces of selection at early stages of divergence. The accessibility of these populations has provided the opportunity for long-term monitoring of individual fish, allowing tracking how the environment can influence phenotypic and genetic divergence for shaping and maintaining diversity in small populations. Such studies are important, especially in freshwater, as habitat alteration is commonly breaking populations into smaller units, which may or may not be viable.

Evaluating real-world effectiveness of accelerated transcranial magnetic stimulation for treatment-resistant depression in a tertiary referral center based in Quebec, Canada.

OBJECTIVE: To assess the effectiveness of accelerated transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD) in a tertiary referral center in Quebec, Canada, focusing on a real-world clinical setting. METHODS: We reviewed the data of 247 TRD patients treated between January 2012 and May 2022 who received accelerated TMS. Participants were adults diagnosed with unipolar or bipolar depression, resistant to at least two antidepressant trials, and assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Significant symptom reduction was found in the completer sample (N = 147), with 46.3 % of patients meeting post-treatment response criteria and 36.1 % achieving remission. Baseline severity of depression, age, and the number of antidepressant trials were key predictors of treatment outcomes. Patients who did not complete treatment had generally more severe depressive and anxious symptoms and greater treatment resistance. No significant differences in response rates were observed across different TMS coils. CONCLUSION: The study demonstrated the effectiveness and tolerability of accelerated TMS for TRD in a real-world clinical setting.

Variation in egg size and offspring phenotype among and within seven Arctic charr morphs.

Maternal effects have the potential to alter early developmental processes of offspring and contribute to adaptive diversification. Egg size is a major contributor to offspring phenotype, which can influence developmental trajectories and potential resource use. However, to what extent intraspecific variation in egg size facilitates evolution of resource polymorphism is poorly understood. We studied multiple resource morphs of Icelandic Arctic charr, ranging from an anadromous morph-with a phenotype similar to the proposed ancestral phenotype-to sympatric morphs that vary in their degree of phenotypic divergence from the ancestral anadromous morph. We characterized variation in egg size and tested whether egg size influenced offspring phenotype at early life stages (i.e., timing of- and size at- hatching and first feeding [FF]). We predicted that egg size would differ among morphs and be less variable as morphs diverge away from the ancestral anadromous phenotype. We also predicted that egg size would correlate with offspring size and developmental timing. We found morphs had different egg size, developmental timing, and size at hatching and FF. Egg size increased as phenotypic proximity to the ancestral anadromous phenotype decreased, with larger eggs generally giving rise to larger offspring, especially at FF, but egg size had no effect on developmental rate. The interaction between egg size and the environment may have a profound impact on offspring fitness, where the resulting differences in early life-history traits may act to initiate and/or maintain resource morphs diversification.

Evaluation of the Post-COVID-19 Functional Status (PCFS) Scale in a cohort of patients recovering from hypoxemic SARS-CoV-2 pneumonia.

INTRODUCTION: COVID-19 sequelae are numerous and multisystemic, and how to evaluate those symptomatic patients is a timely issue. Klok et al proposed the Post-COVID-19 Functional Status (PCFS) Scale as an easy tool to evaluate limitations related to persistent symptoms. Our aim was to analyse PCFS Scale ability to detect functional limitations and its correlation with quality of life in a cohort of patients, 2-9 months after hospitalisation for COVID-19 hypoxemic pneumonia. METHODS: PCFS Scale was evaluated in 121 patients together with quality of life and dyspnoea questionnaires, pulmonary function tests and CT scans. RESULTS: We observed a high correlation with multiple questionnaires (Short Form-36, Hospital Anxiety and Depression Scale, modified Medical Research Council, end Borg Six-Minute Walk Test), making the PCFS Scale a quick and global tool to evaluate functional limitations related to various persistent symptoms following COVID-19 pneumonia. DISCUSSION: The PCFS Scale seems to be a suitable instrument to screen for patients who will require careful follow-up after COVID-19 hypoxemic pneumonia even in the absence of pulmonary sequelae.

Variation in parasite resistance of Arctic charr, Salvelinus alpinus, between and within sympatric morphs.

Genetic variation in resistance against parasite infections is a predominant feature in host-parasite systems. However, mechanisms maintaining genetic polymorphism in resistance in natural host populations are generally poorly known. We explored whether differences in natural infection pressure between resource-based morphs of Arctic charr (Salvelinus alpinus) have resulted in differentiation in resistance profiles. We experimentally exposed offspring of two morphs from Lake Þingvallavatn (Iceland), the pelagic planktivorous charr ("murta") and the large benthivorous charr ("kuðungableikja"), to their common parasite, eye fluke Diplostomum baeri, infecting the eye humor. We found that there were no differences in resistance between the morphs, but clear differences among families within each morph. Moreover, we found suggestive evidence of resistance of offspring within families being positively correlated with the parasite load of the father, but not with that of the mother. Our results suggest that the inherited basis of parasite resistance in this system is likely to be related to variation among host individuals within each morph rather than ecological factors driving divergent resistance profiles at morph level. Overall, this may have implications for evolution of resistance through processes such as sexual selection.

Multivariate analysis of morphology, behaviour, growth and developmental timing in hybrids brings new insights into the divergence of sympatric Arctic charr morphs.

BACKGROUND: Studying the development of fitness related traits in hybrids from populations diverging in sympatry is a fundamental approach to understand the processes of speciation. However, such traits are often affected by covariance structures that complicate the comprehension of these processes, especially because the interactive relationships between traits of different nature (e.g. morphology, behaviour, life-history) remain largely unknown in this context. In a common garden setup, we conducted an extensive examination of a large suit of traits putatively involved in the divergence of two morphs of Arctic charr (Salvelinus alpinus), and investigated the consequences of potential patterns of trait covariance on the phenotype of their hybrids. These traits were measured along ontogeny and involved growth, yolk sac resorption, developmental timing (hatching and the onset of exogeneous feeding), head morphology and feeding behaviour. RESULTS: Growth trajectories provided the strongest signal of phenotypic divergence between the two charr. Strikingly, the first-generation hybrids did not show intermediate nor delayed growth but were similar to the smallest morph, suggesting parental biases in the inheritance of growth patterns. However, we did not observe extensive multivariate trait differences between the two morphs and their hybrids. Growth was linked to head morphology (suggesting that morphological variations in early juveniles relate to simple allometric effects) but this was the only strong signal of covariance observed between all the measured traits. Furthermore, we did not report evidence for differences in overall phenotypic variance between morphs, nor for enhanced phenotypic variability in their hybrids. CONCLUSION: Our study shed light on the multivariate aspect of development in a context of adaptive divergence. The lack of evidence for the integration of most traits into a single covariance structure suggested that phenotypic constraints may not always favour nor impede divergence toward ecological niches differing in numerous physical and ecological variables, as observed in the respective habitats of the two charr. Likewise, the role of hybridization as a disruptive agent of trait covariance may not necessarily be significant in the evolution of populations undergoing resource polymorphism.

Re-identification of individuals from images using spot constellations: a case study in Arctic charr (Salvelinus alpinus).

The ability to re-identify individuals is fundamental to the individual-based studies that are required to estimate many important ecological and evolutionary parameters in wild populations. Traditional methods of marking individuals and tracking them through time can be invasive and imperfect, which can affect these estimates and create uncertainties for population management. Here we present a photographic re-identification method that uses spot constellations in images to match specimens through time. Photographs of Arctic charr (Salvelinus alpinus) were used as a case study. Classical computer vision techniques were compared with new deep-learning techniques for masks and spot extraction. We found that a U-Net approach trained on a small set of human-annotated photographs performed substantially better than a baseline feature engineering approach. For matching the spot constellations, two algorithms were adapted, and, depending on whether a fully or semi-automated set-up is preferred, we show how either one or a combination of these algorithms can be implemented. Within our case study, our pipeline both successfully identified unmarked individuals from photographs alone and re-identified individuals that had lost tags, resulting in an approximately 4% increase in our estimate of survival rate. Overall, our multi-step pipeline involves little human supervision and could be applied to many organisms.

Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus).

BACKGROUND: Organismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression. RESULTS: Craniofacial shape (i.e. the Meckel's cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel's cartilage in comparison to smaller offspring. CONCLUSIONS: This study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.

Predictive capacity of the modified SEGA frailty scale upon discharge from geriatric hospitalisation: a six-month prospective study.

The aim of this study was to describe the predictive role of the modified SEGA frailty scale on nursing home admission, readmission to hospital, falls and mortality. MATERIAL AND METHODS: We performed a prospective, single-centre cohort study in patients discharged from a geriatric hospital ward between July 2016 and February 2017, with follow-up of six months. Patients aged 65 and over who were returning home from hospital were included. The primary outcome measure was admission to a nursing home at six months. We used a Cox model to explore the predictive nature of the variables. RESULTS: Thirty-three patients (18.4%) with a mean age of 80.9 years (± 6.5) were classified as not very frail and 146 (81.6%) with a mean age of 86 years (± 6.5) as frail/very frail. After six months, 13.5% of the frail/very frail patients and 1.2% of the not very frail patients had entered a nursing home (p = 0.169). Frailty status was significantly associated with readmission to hospital at three months (p = 0.026) and single or multiple falls at six months (p = 0.003). CONCLUSION: The modified SEGA scale may predict the occurrence of adverse events and improve the transition to home.

[Predictive capacities at the end of hospitalisation in geriatrics of the modified SEGA frailty score: a 6-month prospective study]. / Capacités prédictives du score de fragilité de la grille SEGA modifiée en sortie d'hospitalisation de gériatrie : étude prospective à 6 mois.

The aim of this study was to describe the predictive role of the modified SEGA fragility score on nursing home admission, rehospitalization, falls and mortality. MATERIAL AND METHODS: We performed a prospective, single-center cohort study in patients leaving geriatric hospitalization between July 2016 and February 2017, with follow-up at 6 months. Patients 65 years of age and over, returning home, were included. The primary outcome measure was admission to an institution at 6 months. We realized a Cox model to explore the predictive character of the variables. RESULTS: Thirty-three patients (18.4%), mean age 80.9 years (± 6.5), were not very fragile. At 6 months, 13.5% of the fragile or very fragile patients and 1.2% of the patients who were not very fragile had entered the institution (p = 0.169). Fragility status was statistically significantly associated with rehospitalization at 3 months (p = 0.026) and single or multiple drop at 6 months) month (p = 0.003). CONCLUSION: The SEGAm grid would predict the occurrence of derogatory events and improve return home.

A way forward with eco evo devo: an extended theory of resource polymorphism with postglacial fishes as model systems.

A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well-suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism - emphasizing eco evo devo, and identify current gaps in knowledge.

Does blood lactate predict the chronic adaptive response to training: A comparison of traditional and talk test prescription methods.

The purpose of this study was to test the hypotheses (i) that interindividual variability in acute blood lactate responses during exercise at 65% of peak work rate (WRpeak; relative WRpeak protocol (REL)) will predict variability in the chronic responses to exercise training and (ii) that exercising at an intensity that causes uncomfortable speech production (negative talk test (TT) stage (NEG)) elicits high acute blood lactate responses and large adaptations to training. Twenty-eight participants completed 4 weeks of exercise training consisting of REL (n = 14) or NEG (TT, n = 14). Fifteen additional participants were assigned to a no-exercise control group (n = 15). In REL, acute blood lactate responses during the first training session significantly predicted changes in peak oxygen consumption (r = 0.69) after training. TT resulted in consistently high acute blood lactate responses. REL and TT improved (p < 0.05) peak oxygen consumption, WRpeak, and work rate at the onset of blood lactate accumulation (WROBLA). Despite nonsignificance, small to medium between-group effect sizes for changes in peak oxygen consumption, WRpeak, and WROBLA and a higher work rate, heart rate, rating of perceived exertion, and blood lactate during training at NEG support the potential superiority of TT over REL. When exercise is prescribed using a traditional method (a fixed percentage of WRpeak; REL), acute metabolic stress may partly explain the variance in the adaptations to training. In addition, TT elicited significant increases in peak oxygen consumption, WRpeak, and WROBLA, and although our small sample size limits our ability to confidently compare training adaptations between groups, our preliminary results suggest that future investigations with larger sample sizes should assess the potential superiority of TT over REL.

Gene expression in the phenotypically plastic Arctic charr (Salvelinus alpinus): A focus on growth and ossification at early stages of development.

Gene expression during development shapes the phenotypes of individuals. Although embryonic gene expression can have lasting effects on developmental trajectories, few studies consider the role of maternal effects, such as egg size, on gene expression. Using qPCR, we characterize relative expression of 14 growth and/or skeletal promoting genes across embryonic development in Arctic charr (Salvelinus alpinus). We test to what extent their relative expression is correlated with egg size and size at early life-stages within the study population. We predict smaller individuals to have higher expression of growth and skeletal promoting genes, due to less maternal resources (i.e., yolk) and prioritization of energy toward ossification. We found expression levels to vary across developmental stages and only three genes (Mmp9, Star, and Sgk1) correlated with individual size at a given developmental stage. Contrary to our hypothesis, expression of Mmp9 and Star showed a non-linear relationship with size (at post fertilization and hatching, respectively), whilst Sgk1 was higher in larger embryos at hatching. Interestingly, these genes are also associated with craniofacial divergence of Arctic charr morphs. Our results indicate that early life-stage variation in gene expression, concomitant to maternal effects, can influence developmental plasticity and potentially the evolution of resource polymorphism in fishes.

Moving beyond threshold-based dichotomous classification to improve the accuracy in classifying non-responders.

We examined maximal oxygen consumption responses following exercise training to demonstrate the limitations associated with threshold-based dichotomous classification of responders and non-responders and proposed alternative methods for classification. Specifically, we: 1) calculated individual probabilities of response, and 2) classified individuals using response confidence intervals (CI) and reference points of zero and a smallest worthwhile change of 0.5 METs. Our findings support the use of individual probabilities and individual CIs to improve the accuracy in non-response classification.

Variation in the magnitude of morphological and dietary differences between individuals among populations of small benthic Arctic charr in relation to ecological factors.

The early stages of intraspecific diversity are important for the evolution of diversification and speciation. Early stages of diversification can be seen in individual specialization, where individuals consume only a portion of the diet of the population as a whole, and how such specialization is related to phenotypic diversity within populations. Here, we study the strength of the relationship between morphological and dietary distances among individuals in eighteen populations of Icelandic small benthic charr. We furthermore studied if the strength of the relationship could be related to variation in local ecological factors these populations inhabit. In all the populations studied, there was a clear relationship between morphological and dietary distances, indicating that fish that had similar morphology were at the same time-consuming similar food items. Our findings show a systematic variation in the relationship between morphology and diet at early stages of diversification in a highly specialized small benthic charr morph. The results show the importance of fine scale comparisons within populations and furthermore the value that systematic comparisons among populations under parallel evolution can contribute toward our increased understanding of evolutionary and ecological processes.

Evaluation of different metrics as an index for the assessment of arterial stiffness.

Elevated intravascular pressure is a contributing factor to increased arterial stiffness, and is a risk factor for cardiovascular morbidity and mortality. Assessment of arterial stiffness is of importance in evaluating cardiovascular risk. Pulse wave velocity (PWV) has been broadly used in the assessment of arterial stiffness. We compared three different metrics of arterial stiffness to PWV. Hemodynamic recordings were carried out in anesthetized hypertensive and normotensive rats (n = 25; 13-14 weeks old). Four parameters were calculated (PWV, elastic modulus (Einc), stiffness index (ß), and pressure-strain modulus (Ep)) as metrics of arterial stiffness. Hypertensive in comparison to normotensive rats had significantly higher systolic and diastolic blood pressures. Metric for arterial stiffness were significantly (p < 0.002) higher in hypertensive animals: PWV (8.46 ± 2.01 vs. 6.39 ± 1.28 m/s), Ep (0.246 ± 0.019 vs. 0.137 ± 0.010 dyn/cm2 × 10-6), Einc (17.5 ± 1.8 vs. 10.1 ± 0.9 dyn/cm2 × 10-6), and ß (2.43 ± 0.11 vs. 1.98 ± 0.08) (mean±SE). Bland-Altman analysis revealed ß as the only metric aligned with PWV in hypertensive state. We find in state of reduced arterial compliance associated with high systemic pressure, ß but not Einc or Ep is an index of arterial stiffness showing agreement with PWV.

Role of ß2- and ß3-adrenoceptors in arterial stiffness in a state of hypertension.

An increase in arterial stiffness is associated with a high risk for morbidity and mortality in a state of elevated systemic pressure. The sympathetic nervous system plays an important role in the regulation of vascular tone via activation of ß-adrenoceptors. The aim of this investigation was to determine the involvement of ß-adrenoceptors in the control of arterial stiffness in a state of hypertension versus normotension. Pulse wave velocity (PWV), an index of vascular stiffness, was assessed in isoflurane-anaesthetized 13-14-week-old male spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. At baseline, PWV was significantly higher in SH (9.2±0.9m/s) compared to WKY rats (6.7±0.4m/s). The stimulation of ß2- but not ß3-adrenoceptors significantly reduced PWV in SH rats despite comparable reductions in blood pressure. Stimulation of ß2- or ß3-adrenoceptors did not reduce PWV in WKY rats. The administration of sodium nitroprusside (SNP) also significantly reduced PWV in SH but not WKY rats. Immunofluorescence revealed the expression of ß2- and ß3-adrenoceptors in endothelial cells and vascular smooth muscle cells of the abdominal aorta. There were no significant differences in the distribution of the expression of ß2- and ß3-adrenoceptors in endothelial and/or smooth muscle cells in blood vessels of SH compared to WKY rats. The evidence suggests that ß2-adrenoceptor stimulation and SNP infusion reduce PWV independently from reduction in blood pressure in a state of high systemic arterial pressure. A reduction in vascular tone of the central arteries may play a key role in decreasing PWV that is elevated due to stiffer arterial wall.