Heterogeneity in the intrinsic quality and nutritional condition of individuals affects reproductive success and consequently fitness. Understanding differences in energy allocation towards survival and reproduction within and among years might help explain variability in individual fitness. Black brant (Branta bernicla nigricans) are long-lived, migratory, specialist herbivores. Long migratory pathways and short summer breeding seasons constrain the time and energy available for reproduction, thus magnifying life-history trade-offs. These constraints, combined with long lifespans and trade-offs between current and future reproductive value, provide a model system to examine the role of individual heterogeneity in driving life-history strategies and individual heterogeneity in fitness. We used hierarchical Bayesian models to examine reproductive trade-offs, modeling the relationships between within-year measures of reproductive energy allocation and among-year demographic rates of individual females breeding on the Yukon-Kuskokwim Delta, Alaska using capture-recapture and reproductive data from 1988 to 2014. We provide evidence for relationships between breeding probability and clutch size (posterior mean of β = 0.45, 95% CRI = 0.33 – 0.57, SD = 0.06), breeding probability and nest initiation date (posterior mean of β = -0.12, 95% CRI = -0.2 ¬– -0.04, SD = 0.04), and an interaction between clutch size and initiation date (posterior mean of β = -0.12, 95% CRI = -0.2 – -0.04, SD = 0.04). Average lifetime clutch size also had a weak positive relationship with survival probability (posterior mean of β = 0.03, 95% CRI = -0.01 – 0.7, SD = 0.02). Our results support the use of demographic buffering strategies for black brant; reductions in reproductive energy allocation preserve high adult survival rates during years with poor environmental conditions, maximizing future reproductive value. We also indirectly show links among environmental conditions during growth, fitness, and energy allocation, highlighting the effects of early growth conditions on individual heterogeneity, and subsequently, reproductive investment.

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T-helper (Th) and T-regulatory (Treg) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2-weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were sacrificed. Mice (n=6) were sacrificed at specified time-points for various analysis (blood leucocyte, cytokine production, and immunohistochemistry). Tumour volume was measured once every seven days. Gene expression studies were carried out on tumour-specific T-lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p<0.05), CD8+ (p<0.05) T-cells and natural killer cells (p<0.05) but suppressed Treg cells (p<0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon-gamma (IFN) and lower transforming growth factor-beta (TGF-) levels were noted in the T3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-122R), interleukin-24 (IL-24) and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the T3 fed animals. Gene expression studies showed the downregulation of seven prominent genes in splenic CD4+ T-cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T-cell dependent cell-mediated immune responses and suppressed Treg cells in the tumour microenvironment in a syngeneic mouse model of BC.

Total arch repair (TAR) has become a mainstay of the surgical management of complex pathologies of the ascending aorta and aortic arch, in particular acute Type A aortic dissections (ATAAD). TAR with devices such as the frozen elephant trunk (FET) have been shown to dramatically improve clinical outcomes in such cases. However, TAR with FET remains an immensely challenging procedure, and the risk of debilitating postoperative complications remains high. Spinal cord ischaemia (SCI) and stroke are two particularly tragic adverse outcomes of TAR with FET; it is unsurprising therefore that much research has been done to determine both the underlying cause thereof, and strategies to mitigate this risk. Mousavizadeh and colleagues produced a fascinating systematic review and meta-analysis investigating the relationship between the duration of hypothermic circulatory arrest (HCA) and the risk of developing complications including SCI and stroke. Their data seem to suggest HCA duration is a key factor in causing SCI and stroke following TAR with FET for ATAAD. However, other factors such as stent sizing and landing zone also contribute. Further prospective research into this relationship is recommended to fully elucidate what truly is to blame for these postoperative neurological complications.

Left ventricular free wall rupture (LVFWR) is a most rare but often lethal mechanical complication of acute myocardial infarction (AMI). The mortality rate for LVFWR is described from 75% to 90% and it is the cause for 20% of in-hospital deaths after AMI. Death results essentially from the limited time available for emergent intervention after onset of symptoms. Emergency surgery is indicated and normally the rupture site is easily identified, but it may not be apparent macroscopically, corresponding to transmyocardial or subepicardial dissection with an external rupture far from the infarction site, or already thrombosed and contained. Repair of the ventricular wall is usually achieved either by suturing the edges of the tear or closing it with patches of artificial material or biological tissues, usually using some kind of biological glue. However, several cases of successful conservative management have been described. In this Editorial, I comment on the metanalysis conducted by Matteucci et al, published in this issue of the Journal, including 11 non-randomized studies and enrolling a total of 363 patients, which brings a great deal of new knowledge that can help not only in the prevention but also in the management of this dreadful complication of AMI.

Introduction: Conduction system pacing (CSP) has emerged as an ideal physiologic pacing strategy for patients with permanent pacing indications. We sought to evaluate the safety and feasibility of CSP in a consecutive series of unselected patients with congenital heart disease (CHD). Methods: Consecutive patients with CHD in which CSP was attempted were included. Safety and feasibility, implant tools and electrical parameters at implant and at follow-up were evaluated. Results: A total of 20 patients were included (10 with a previous device). Ten patients had complex forms of CHD, 9 moderate defects and 1 a simple defect. His bundle pacing (HBP) or left bundle branch area pacing (LBBAP) were achieved in all patients (10 HBP, 5 LBBP and 5 left ventricular septal pacing). Procedure times and fluoroscopy times were prolongued (126±82 min and 27±30 min, respectively). CSP lead implant times widely varied ranging from 4 to 115 minutes, (mean 31±28 min) and the use of multiple delivery sheaths was frequent (50%). The QRS width was reduced from 144±32 ms at baseline to 116±16 ms with CSP. Implant electrical parameters included: CSP pacing threshold 0.85±0.61V; R wave amplitude 9.8±9.2mV and pacing impedance 735±253 Ohms, and remained stable at a median follow-up of 478 days (IQR 225-567). Systemic ventricle systolic function and NYHA class (1.50±0.51 vs 1.10±0.31; p=0.008) significantly improved at follow-up. Lead revision was required in one patient at day-4. Conclusions: Permanent CSP is safe and feasible in patients with CHD although implant technique is complex.

The recent development of ecological studies has been fueled by the introduction of massive information based on chromosome-scale genome sequences, even for species for which genetic linkage is not accessible. This was enabled mainly by the application of Hi-C, a method for genome-wide chromosome conformation capture that was originally developed for investigating the long-range interaction of chromatins. Performing genomic scaffolding using Hi-C data is highly resource-demanding and employs elaborate laboratory steps for sample preparation. It starts with building a primary genome sequence assembly as an input, which is followed by computation for genome scaffolding using Hi-C data, requiring careful validation. This article presents technical considerations for obtaining optimal Hi-C scaffolding results and provides a test case of its application to a reptile species, the Madagascar ground gecko (Paroedura picta). Among the metrics that are frequently used for evaluating scaffolding results, we investigate the validity of the completeness assessment of chromosome-scale genome assemblies using single-copy reference orthologs, and report problems of the widely used program pipeline BUSCO.

Objective To estimate the pregnancy rates and outcomes for women with cystic fibrosis (wwCF) in the UK compared to the general population and to explore the impact of the introduction of disease modifying treatments on pregnancy rates. Design A population-based cross-sectional study. Setting Electronic records of UK CF Registry Data (~99% of all CF), and conceptions data for England and Wales (E&W). Population All women aged 15-44 years who were pregnant between 2003-2017. Methods We calculated 3-yearly crude and age-specific pregnancy rates per 1,000 women years (wys), pregnancy rates for wwCF with a G551D mutation before and after Ivacaftor was introduced in 2012 and compared live birth rates. Main outcome measures Crude rates, age specific fertility, and maternal morbidity. Results The overall pregnancy rate was 23.5 (95% CI 21.9-25.3) per 1,000 wys, ~3.4fold difference to E&W women (77.7). This pattern was evident in the age specific rates, except for those aged 40-44 years where the difference in rates was much less (wwCF 8.2 per 1,000 wys vs. 13.3 in E&W). LB rate differences mirrored pregnancy rates (wwCF 17.4 per 1000 wys vs. 61.4 E&W women). Following the introduction of Ivacaftor, pregnancy rates in wwCF with G551D increased from 29.5 to 56.9 per 1000wys (2012-2014 to 2015-2017). Conclusions Pregnancy rates in wwCF are about a third of the rates in the general population but on the rise following the introduction of Ivacaftor. There is no indication that there is a reduced chance of a live birth in wwCF who become pregnant.

AIM: Influenza infection poses a severe threat to pregnant mothers, and antiviral treatment is recommended. However, the safety of neuraminidase-inhibitor antiviral medications during pregnancy has not been well described. METHODS: A systematic review and meta-analysis were performed to evaluate the adverse neonatal outcomes associated with exposure to neuraminidase inhibitors during pregnancy. The PubMed, Embase, and Cochrane Library databases were searched to identify potential studies for inclusion. RESULTS: Nine cohort studies that estimated adverse neonatal outcomes associated with exposure to neuraminidase-inhibitor medication during pregnancy were included. Exposure to a neuraminidase inhibitor during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.72–1.12, P = 0.341), low Apgar score (OR 0.96, 95% CI 0.77–1.2, P = 0.733), or preterm birth (OR 0.99, 95% CI 0.89–1.09, P = 0.771) compared with no exposure. However, exposure to a neuraminidase inhibitor was associated with a reduced risk of low birth weight (OR 0.79, 95% CI 0.68–0.92, P = 0.002) and giving birth to a small-for-gestational-age infant (OR 0.78, 95% CI 0.69–0.88, P < 0.001). Further analyses limited to oseltamivir exposure were consistent with the overall results. CONCLUSION: Exposure to neuraminidase-inhibitor medication during pregnancy does not appear to be associated with adverse neonatal outcomes. We recommend further studies to investigate this association, which will help clinicians determine whether to prescribe a neuraminidase inhibitor during pregnancy.

Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased operative morbidity and mortality. The recent increased use of direct oral anticoagulants and antiplatelet medications have made the above more challenging. In addition, cardiopulmonary bypass (CPB) with its associated hemodilution, fibrinolysis and platelet consumption may exacerbate the pre-existing coagulopathy and increase the risk of bleeding. Management decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. Attention is paid to exercising meticulous techniques, avoiding excessive hypothermia and treating coexisting issues such as sepsis. Ensuring a dry operative field upon entry by correcting the coagulopathy with reversal agents is offset by the concern of potentially hindering efforts to anticoagulate the patient (heparin resistance) in preparation for CPB, in addition to possibly increasing the risk of thromboembolism. Proper knowledge of the anticoagulants, their reversal agents, and the usefulness of laboratory testing are all essential. Platelet transfusion remains mainstay for antiplatelet medications. Four-factor prothrombin complex concentrate is considered in patients on oral anticoagulants if CPB needs to be instituted quickly. Specific reversal agents such as idarucizumab and andexanet alfa can be considered if significant tissue dissection is anticipated such as redo sternotomy, but are costly and may lead to heparin resistance and anticoagulant rebound.

Introduction Atrial fibrillation (AF) is frequent after any cardiac surgery, but evidence suggests it may have no significant impact on survival if sinus rhythm (SR) is effectively restored early after the onset of the arrhythmia. In contrast, management of preoperative AF is often overlooked during or after cardiac surgery despite several proposed protocols. This study sought to evaluate the impact of preoperative AF on mortality in patients undergoing isolated surgical aortic valve replacement (AVR). Methods We performed a retrospective, single-centre study involving 2,628 consecutive patients undergoing elective, primary isolated surgical AVR from 2008 to 2018. A total of 268/ 2,628 patients (10.1%) exhibited AF before surgery. The effect of preoperative AF on mortality was evaluated with univariate and multivariate analyses. Results Short-term mortality was 0.8% and was not different between preoperative AF and SR cohorts. Preoperative AF was highly predictive of long-term mortality (median follow-up of 4 years [Q1-Q3 2-7]; HR: 2.24, 95% CI: 1.79-2.79, P<0.001), and remained strongly and independently predictive after adjustment for other risk factors (HR: 1.54, 95% CI: 1.21-1.96, P<0.001) compared with preoperative SR. In propensity score-matched analysis, the adjusted mortality risk was higher in the AF cohort (OR: 1.47, 95% CI: 1.04-1.99, P=0.03) compared with the SR cohort. Conclusions Preoperative AF was independently predictive of long-term mortality in patients undergoing isolated surgical AVR. It remains to be seen whether concomitant surgery or other preoperative measures to correct AF may impact long-term survival.

Translocation of metabolites between different plant species provides important hints in understanding the fate of bioactive root exudates. In the present study, targeted and untargeted mass spectrometry-based metabolomics was applied to elucidate the transfer of bioactive compounds between rye and several crops and weed species. Our results demonstrated that benzoxinoids (BXs) synthesized by rye were taken up by roots of neighboring plant species and translocated into their shoots. Furthermore, we showed roots of the rye plant took up compounds originating from neighboring plants. Among the compounds taken up by rye roots, wogonin was detected in the rye shoot, which indicates the root-to-shoot translocation of this compound. Elucidating the transfer of bioactive compounds between plants is essential for understanding plant-plant interactions, developing natural pesticides and understanding their modes of action.

1) Food web models explain and predict the trophic interactions in a food web, and they can infer missing interactions among the organisms. The allometric diet breadth model (ADBM) is a food web model based on the foraging theory. In the ADBM the foraging parameters are allometrically scaled to body sizes of predators and prey. In Petchey et al. (2008), the parameterisation of the ADBM had two limitations: (a) the model parameters were point estimates, and (b) food web connectance was not estimated. 2) The novelty of our current approach is: (a) we consider multiple predictions from the ADBM by parameterising it with approximate Bayesian computation, to estimate parameter distributions and not point estimates. (b) Connectance emerges from the parameterisation, by measuring model fit using the true skill statistic, which takes into account prediction of both the presences and absences of links. 3) We fit the ADBM using approximate Bayesian computation to 16 observed food webs from a wide variety of ecosystems. Connectance was consistently overestimated in the new parameterisation method. In some of the food webs, considerable variation in estimated parameter distributions occurred, and resulted in considerable variation (i.e. uncertainty) in predicted food web structure. 4) We conclude that the observed food web data is likely missing some trophic links that do actually occur, and that the ADBM likely predicts some links that do not exist. The latter could be addressed by accounting in the ADBM for additional traits other than body size. Further work could also address the significance of uncertainty in parameter estimates for predicted food web responses to environmental change.

Infections and pandemics will condition us in an increasingly predominant way regarding diagnostic, medical and surgical activities in all specialist areas; and this particularly in cardiovascular one. Nevertheless in the future the need to cohabit with pandemic events and to be able to continue an elective and not only emergency cardiac surgery program represents an imperative.

1. Stable isotopes represent a unique approach to provide insights into the ecology of organisms. δ13C and δ15N have specifically be used to obtain information on the trophic ecology and food web interactions. Trophic discrimination factors (TDF, Δ13C and Δ15N) describe the isotopic fractionation occurring from diet to consumer tissue and these factors are critical for obtaining precise estimates within any application of δ13C and δ15N values. It is widely acknowledged that metabolism influences TDF, being responsible for different TDF between tissues of variable metabolic activity (e.g. liver vs. muscle tissue) or species body size (small vs. large). However, the connection between the variation of metabolism occurring within a single species during its ontogeny and TDF has rarely been considered. 2. Here, we conducted a 9-month feeding experiment to report Δ13C and Δ15N of muscle and liver tissue for several weight classes of Eurasian perch (Perca fluviatilis), a widespread teleost often studied using stable isotopes, but without established TDF for feeding on a natural diet. In addition, we assessed the relationship between the standard metabolic rate (SMR) and TDF by measuring their oxygen consumption of the individuals. 3. Our results showed a significant negative relationship of SMR with Δ13C, and a significant positive relationship of SMR with Δ15N of muscle tissue, but not with TDF of liver tissue. SMR varies inversely with size, which translated into a significantly different TDF of muscle tissue between size classes. 4. In summary, our results emphasize the role of metabolism in shaping specific TDF (i.e. Δ13C and Δ15N of muscle tissue), and especially highlight the substantial differences between individuals of different ontogenetic stages within a species. Our findings thus have direct implications for the use of stable isotope data and the applications of stable isotopes in food web studies.

Recent field experiments showed that predators influence the prey population not only by direct consumption but also by stimulating various defensive strategies. The cost of these defensive strategies can include energetic investment in defensive structures, reduced energy income, lower mating success, and emigration which ultimately reduces the reproduction of prey. To explore the effect of these defensive strategies (anti-predator behaviors), a modified Leslie-Gower predator-prey model with the cost of fear has been considered. Gestation delay is also incorporated in the system for a more realistic formulation. Boundedness, equilibria and stability analysis of the temporal model are studied. By considering gestation delay as a bifurcation parameter, the existence of Hopf-bifurcation around the interior equilibrium point is discussed together with the direction, stability and period of bifurcating solutions arising through Hopf-bifurcation. The spatial extension of the proposed model incorporating density-dependent cross-diffusion is also investigated and the conditions for diffusion-driven instability are obtained. To illustrate the analytical findings, detailed numerical simulations are performed. Biologically realistic Turing patterns as hexagonal spots, spots and stripes mixture, and labyrinthine type patterns are identified. It is found that the fear level has a stabilizing impact on delay induced destabilization and both stabilizing and destabilizing effects on Turing instability.

Abstract Objectives: There are several different definitions of complete revascularization on coronary surgery across the literature. Despite the importance of this definition there is no agreement on which one has the most impact. The aim of this study was to evaluate which definition of complete surgical revascularization correlates with early and late outcomes. Methods: All consecutive patients submitted to isolated CABG from 2012 to 2016 with previous myocardial scintigraphy were evaluated. Exclusion criteria: emergent procedures and previous cardiac surgery procedures. Population of 162 patients, follow-up complete in 100% patients; median 5,5 IQR 4,4-6,9 years. Each and all of the 162 patients were classified as complying or not with the four different definitions: Numerical, Functional, Anatomical Conditional and Anatomical unconditional. Univariable and multivariable analyses were developed to detect if any definition was a predictor of perioperative and long-term outcomes. Results: Complete functional revascularization was a predictor of increased survival (HR 0.47 CI95: 0,226-0,969; p=0.041). No other definitions showed effect on follow-up mortality. Age and cardiac dysfunction increased long-term mortality. The definition of complete revascularization did not have an impact on MACCE or need for revascularization Conclusions: An uniformly accepted definition of complete coronary revascularization is lacking. This research raises awareness about the importance of viability guidance for CABG.

Background: Pediatric Emergency Care Applied Research Network (PECARN) is a useful Clinical Decision Support Tool (CDST) to identify traumatic brain injuries and reduce the use of head CT scans among pediatric patients. The present Meta-analysis aims to evaluate the diagnostic accuracy of the PECARN rule from 2009 to 2020 in children with a very low risk of blunt head trauma. Methods: A detailed search was conducted from the databases of Medline (via PubMed), Cinahl (via Ebsco), Scopus, Web of Sciences, from 2009 till the end of December 2020 using the keywords like decrease use of CT scan, blunt head trauma (BHT) combined with accuracy, Pediatric Emergency Care Applied Research Network (PECARN) OR Clinical Decision Support Tool (CDST). Studies showing the diagnostic accuracy of the PECARN rule in children younger than 18 years of age with minor BHT were included. Results: 13 studies were included in the present analysis. Pooled sensitivity of 0.08, (95% confidence interval of 0.074 - 0.087), pooled specificity of 0.20 ( 95% CI of 0.196 - 0.213) and diagnostic odds ratio of 0.004 (95% CI of 0.000-0.1666) was in <2 years of age. The overall sensitivity of 0.07, specificity of 0.66, and diagnostic odds ratio of 0.54 (95% CI of 0.10 -2.78) was seen in ≥2 years of age. Overall sensitivity of 0.13 (95% CI 0.12-0.14), specificity of 0.81 (95% CI 0.80-0.82) and diagnostic odds ratio of 0.79 (95% CI of 0.08 -7.71) was in 0-18 years of age. Conclusion: The present analysis indicates the PECARN decision tool as an accurate CDST in low-risk minor blunt head trauma cases in children below two years of age and can become a useful tool in reducing Head CT’s scan overuse in pediatric emergency departments.

Telomeres are protective, nucleoprotein structures at the end of chromosomes that have been associated with lifespan across taxa. However, the extent to which these associations can be attributed to absolute length versus the rate of telomere shortening prior to sampling remains unresolved. In a longitudinal study, we examined the relationship between lifespan, telomere length and the rate of telomere shortening in wild, purple-crowned fairy-wrens (Malurus coronatus coronatus). To this end, we measured telomere length using qPCR in the blood of 59 individuals sampled as nestling and 4-14 months thereafter, and in 150 individuals sampled on average three times across adulthood. We applied within-subject centering analyses to simultaneously test for associations between lifespan and average telomere length and telomere shortening. We reveal that the rate of telomere shortening in the first year of life predicted lifespan, with individuals with faster shortening rates living less long. We also report a trend for an effect of telomere length in the first year of life on lifespan, independent of telomere shortening. In contrast, in adulthood neither telomere shortening, nor telomere length predicted lifespan, despite a considerably larger data set. Our results suggest that telomere length measured very early in life (during development) and longitudinal assessments of telomere shortening during the first year of life constitute more useful biomarkers of total life expectancy than either telomere length measured after development, or telomere shortening later in adulthood.