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Group 3 innate lymphoid cells (ILC3) are potent effector cells with critical roles in enforcing immunity, barrier integrity and tissue homeostasis along the gastrointestinal tract. ILC3 are considered to be primarily tissue-resident cells, seeding the gastrointestinal tract during embryonic stages. However, the mechanisms through which ILC3 are maintained within these tissues are poorly understood. Here, we report that ILC3 are minimally replenished from bone marrow precursors in healthy adult mice, persist in the tissue for extended periods of time in the gut, and display a quiescent phenotype. Strikingly, despite robustly producing cytokines, LTi-like ILC3 remain non-proliferative during enteric bacterial infection. Survival of LTi-like ILC3 was found to be dependent upon the balance of the metabolic activity required to drive effector function and anti-apoptotic programs. Notably, the pro-survival protein Bcl-2 was required for the survival of LTi-like ILC3 but was rendered partially dispensable if mitochondrial respiration was inhibited. Together we demonstrate LTi-like ILC3 are a quiescent-like population that persists independently of haematopoietic replenishment to survive within the tissue microenvironment.

The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in xerostomia, or chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant cell type in the salivary glands and are attractive therapeutic targets due to their unrivalled capacity to drive tissue repair and regeneration. Yet, the nature and role of macrophages in salivary gland homeostasis and whether or not they contribute to tissue repair/regeneration following injury is not well understood. Here, we have used single cell RNA-seq, multi-parameter flow cytometry and fluorescence microscopy to map the heterogeneity of the salivary gland macrophage compartment throughout development and following radiation-induced injury. We show that there are highly dynamic changes in the composition of the salivary gland macrophage compartment with age, in part due to changes in the ontogeny of these cells, determined using a suite of complementary fate mapping systems. A combination of mutant mice and antibody blockade demonstrates that salivary gland macrophages are dependent on CSF1, but not IL-34 or GM-CSF, for their development and maintenance. Finally, using an in vivo model of radiation-induced salivary gland injury combined with a novel Mafb-specific depletion system, we demonstrate an essential role for macrophages. Without macrophages the clearance of cells with DNA damage, and effective tissue repair following such injury, is severely comprised. Our data, therefore, indicate a strong case for exploring the therapeutic potential of manipulating macrophages in order to promote tissue repair and thus minimise salivary gland dysfunction after radiotherapy.

Parallelism, the evolution of similar traits in populations diversifying in similar conditions, provides strong evidence of adaptation by natural selection. Many studies of parallelism focus on comparisons of different ecotypes or contrasting environments, defined a priori, which could upwardly bias the apparent prevalence of parallelism. Here, we estimated genomic parallelism associated with components of environmental and phenotypic variation at an intercontinental scale across four freshwater adaptive radiations (Alaska, British Columbia, Iceland and Scotland) of the three-spined stickleback (Gasterosteus aculeatus). We combined large-scale biological sampling and phenotyping with restriction site associated DNA sequencing (RAD-Seq) data from 73 freshwater lake populations and four marine ones (1,380 fish) to associate genome-wide allele frequencies with continuous distributions of environmental and phenotypic variation. Our three main findings demonstrate that (1) quantitative variation in phenotypes and environments can predict genomic parallelism; (2) genomic parallelism at the early stages of adaptive radiations, even at large geographic scales, is founded on standing variation; and (3) similar environments are a better predictor of genome-wide parallelism than similar phenotypes. Overall, this study validates the importance and predictive power of major phenotypic and environmental factors likely to influence the emergence of common patterns of genomic divergence, providing a clearer picture than analyses of dichotomous phenotypes and environments.

Macrophages are central elements of all organs, where they have a multitude of physiological and pathological functions. The first macrophages are produced during fetal development, and most adult organs retain populations of fetal-derived macrophages that self-maintain without major input of hematopoietic stem cell-derived monocytes. Their developmental origins make macrophages highly susceptible to environmental perturbations experienced in early life, in particular the fetal period. It is now well recognized that such adverse developmental conditions contribute to a wide range of diseases later in life. This chapter explores the notion that macrophages are key targets of environmental adversities during development, and mediators of their long-term impact on health and disease. We first briefly summarize our current understanding of macrophage ontogeny and their biology in tissues and consider potential mechanisms by which environmental stressors may mediate fetal programming. We then review evidence for programming of macrophages by adversities ranging from maternal immune activation and diet to environmental pollutants and toxins, which have disease relevance for different organ systems. Throughout this chapter, we contemplate appropriate experimental strategies to study macrophage programming. We conclude by discussing how our current knowledge of macrophage programming could be conceptualized, and finally highlight open questions in the field and approaches to address them.

Introduction The benefits of cardiac rehabilitation (CR) in patients with ischaemic cardiomyopathy are well-known. However, inflammatory states have been associated to an increased risk of cardiovascular events. Purpose Evaluate the impact of CR in the serum levels of inflammatory biomarkers and identify potential predictors of that effect. Methods We retrospectively studied consecutive patients with ischaemic cardiomyopathy who completed a CR programme between 2011 and 2017. Patients underwent a supervised exercise training protocol, twice a week during a period of 8 to 12 weeks. Functional capacity was evaluated by metabolic equivalents assessed prior the beginning and 3 months after the programme with a symptom limited exercise treadmill test. Patients without levels of serum C-reactive protein at beginning and at the end of CR programme were excluded. Median variation of serum C-reactive protein was assessed and two groups were defined: one with levels above that and one with levels below. Results Of 250 patients (60.3±11.1 years, 84% male), 67% were admitted after an acute myocardial infarction. Left ventricular ejection fraction ≤40% before CR was present in 32% of individuals. Median levels of serum C-reactive protein before CR were 8.8 (3.1–21.7) mg/L and median variation after CRP was a decrease of 5.1 (0.9–17.7) mg/L (p5.1mg/L of serum C-reactive protein had lower prevalence of hypertension (18% versus 30%, p=0.02), higher prevalence of obesity (16% versus 7%, p=0.03), lower levels of HDL cholesterol (38.3 [11.1] versus 43.2 [12.6], p5.1mg/L had also higher reduction of NT-proBNP after CR comparing to baseline (491.1 [142.7–948.5] versus 162.0 [30.9–295.2], p Conclusions Serum levels of inflammatory biomarkers decreased after CR in patients with ischaemic cardiomyopathy. Normotension, obesity, lower HDL and higher levels of natriuretic peptides are associated to a better response. Funding Acknowledgement Type of funding sources: None.

The purpose of this work is to determine the values of electrical parameters of synchronous and induction machines to validate electrical interactions between an induction generator and a synchronous generator. The generators are connected in two ways: (i) isolated from the common bus and (ii) parallel to the common bus in steady state, subject to nonlinear load. They are old and refurbished machines; thus, the parametric regression methodology is used to determine the electrical parameter values. After the computational model validation, analyses are performed by various system configurations to confirm the repowering and to analyze the system harmonic current flow. The results obtained comparing the computer simulation and experimental tests prove that the validated model represents the real system. With an experimentally validated computational model, it is possible to verify the occurrence of system repowering and the increased value of harmonic distortions in the induction generator terminals, acting as a preferential path for harmonic currents.

Funding Acknowledgements Type of funding sources: None. Background Syncope is a common reason for emergency department attendance. This entity may be associated with significant morbidity and mortality and its differential diagnosis is not straightforward. Arrhythmic causes include tachycardia and bradycardia; the later may require pacemaker implantation. Many hospitals lack a dedicated syncope unit to approach these patients. So, patients’ triage may fall into medical or surgical (trauma) areas. Purpose To describe the population of patients that required permanent pacemaker implantation in the year of 2019, particularly those who had a previous visit to the emergency department with syncope or presyncope. Methods Single-center descriptive analysis of patients that implanted a permanent pacemaker in 2019 (inclusion criteria). Additional information was collected in patients with emergency department visits in the 365 days that preceded the device implantation. Results In 2019, a total of 398 patients were admitted for pacemaker implantation in 2019, 55% male (n = 218), 45% female (n = 180), with mean age of 79 years. Regarding indications for pacing, 41% (n= 156) had complete atrioventricular (AV) block, 26% (n = 105) had a second degree AV block, 16% (n = 64) had sinus node dysfunction, 13.5% (n = 53) had atrial fibrillation with slow ventricular conduction, and 3.5% (n = 14) had other indications. Twenty-two percent (n = 88) of patients had a previous visit to the emergency department (other than the ones that triggered the pacemaker implantation) with complaints of syncope (60%) or presyncope (40%). Of these, 73% (n = 64) were referred to a medical area and 27% (n = 24) were referred to a surgical area; 40 patients presented with traumatic lesions (68% cranioencephalic trauma and 32% other traumas). Of the 88 patients, only 67% (n = 59) performed an ECG and only 23% (n = 20) were referred for observation by a cardiologist in the emergency department. Comparing medical and surgical triage, we observe that patients referred to the surgical area were less likely to perform an ECG and to be observed by a cardiologist (with statistical significance). Conclusions Our work describes a common problem in hospitals without dedicated syncope evaluation units. As all the patients ended up implanting a pacemaker, it is interesting to observe that 22%of these had a "warning" visit to the emergency and 33% of the last did not get and ECG. Also, trauma-oriented approaches result in a lower likelihood of performing a complete evaluation of the cause of the syncopal event. This analysis highlights the need for a comprehensive and multidisciplinary approach of patients presenting with syncope and presyncope to promote early identification and treatment of arrhythmic causes, reducing patient morbidity and healthcare costs.

Funding Acknowledgements Type of funding sources: None. INTRODUCTION Symptoms like syncope and palpitations are frequent and represent a diagnostic challenge. The implantable loop recorder (LR) is an important diagnostic tool, in selected cases. AIM To describe the main implantation indications of LR and to evaluate the diagnostic findings and therapeutic interventions. METHODS A retrospective study of patients (pts) that underwent LR implantation in our hospital from 2014 to 2019. For each pt the indication for implantation, baseline characteristics, previous study, recorded tracing and interventions were evaluated. RESULTS A total of 52 pts were included, 56% women, with a mean age of 60 years old. The implantation indications were recurrent syncope/ presyncope in 47 pts (90%) and palpitations in 5 pts (10%). All pts had a baseline echocardiogram and electrocardiogram, with 90% in sinus rhythm. QRS complex and atrial-ventricular conduction was normal in 50% of the pts. Previous to LR implantation, 46 pts (89%) had performed Holter, 19 (37%) carotid sinus massage, 14 (27%) Tilt table test, 29 (56%) stress test, 11(21%) ambulatory blood pressure monitoring and 9 (17%) electrophysiological study. During the monitoring period, 27 pts (52%) had recurrence of the symptoms. In this subgroup, we observed that 67% had a rhythmic cause capable of justified the symptoms, with a median of 5 months since implantation until diagnosis. In addition, the LR was useful in ruling out a rhythmic cause for symptoms in 33% of the cases. In the 47 pts with syncope/presyncope: 6(13%) had sinus node dysfunction, 4 (9%) had atrioventricular conduction disturbance, 1(2%) had atrial fibrillation (AF) and 3 (6%) had ventricular dysrhythmias. In the 5 pts with palpitations: 1(20%) had AF ad 3 (60%) had paroxysmal supraventricular tachycardia. LR results led to cardiac device implantation in 13 pts (pacemaker-9, implantable cardioverter desfibrillator-4). In addition, 2 pts are waiting for electrophysiological study and eventual ablation and 3 pts initiated antiarrhythmic therapy, and those with new diagnosis of AF also initiated oral anticoagulants. CONCLUSION In this study, the implantation of LR was useful to clarify the cause of the symptomology in 52% of the pts. In 35% of pts with symptom-rhythm correlation it ensured timely introduction of therapeutic approach with a positive impact on life quality.

Background: Chronic tubulointerstitial fibrosis is a common final pathway leading to end stage kidney disease in cats and has no effective treatment. The use of cell-based molecules to treat kidney fibrosis may be a promising approach. The objectives were to test the effects of intra-renal chemokine CXCL12 injection in a pre-clinical cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis and then, within a clinical pilot study, test the safety/feasibility of CXCL12 injection in cats that might have early chronic kidney disease (CKD).Methods:Pre-clinical: Thirty cats received intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls (n = 6/group). Kidney collagen content was quantified 4 months post-treatment using Masson's Trichrome and Picrosirius Red (PSR) stained tissues. In a separate study (n = 2) exploring short-term effects of CXCL12, 200 ng CXCL12 was injected into I/R kidneys and then harvested either 30 min (n = 1) or 1 month (n = 1) post-injection. Kidney concentrations of CXCL12, matrix metalloproteinase 1 (MMP-1), and lysyl oxidase-like enzyme 2 (LOXL-2) were quantified via ELISA. Clinical Pilot: 14 client-owned cats with potential early kidney disease received a single-treatment, bilateral intra-renal injection of 200 ng CXCL12 (n = 7), or received no injection (n = 7). Blood/urine samples were collected monthly for 9 months to assess renal function and CKD staging.Results:Pre-clinical: I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal (ps < 0.05 vs. untreated). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal (p < 0.001 vs. untreated). Early changes in kidney MMP-1, associated with collagen breakdown, and subsequent decreases in LOXL-2, associated with collagen cross-linking, in response to CXCL12 treatment may contribute to these findings. Clinical Pilot: Bilateral intra-renal injection of CXCL12 using ultrasound guidance in cats with CKD was feasible and safe in a general practice clinical setting with no obvious side effects noted during the 9-month follow-up period.Conclusions: Intra-renal injection of CXCL12 may prove to be an effective treatment for kidney fibrosis in cats with CKD. Additional mechanistic and clinical evaluations are needed.

The temporal behavior of TeO2-ZnO pellets of different Nd concentrations is studied. A shortening of the decay time is observed, indicating random laser behavior for this new laser material.

Stability metrics are used to quantify a system’s ability to maintain equilibrium under disturbances. We did not identify the proposition of a stability metric using sensitivity analysis within the literature. This work proposes a system stability metric and its application to an electrical repowering system. The methodology for applying the proposed metric comprises: (i) system parameters sensitivity analysis and spider diagram construction, (ii) determining the array containing the line segments inclination angles of each spider diagram curve, and (iii) stability calculation using the array mean and maximum inclination value of a line segment. After simulating the model built for the electrical repowering system and applying the methodology, we obtain results regarding the sensitivity indices and stability values of system inputs relative to their outputs, considering the original system and with reduced parameters. Using the stability study, it was possible to determine different stability categories for the system parameters, which indicates the need for different analysis levels.

An experiment to measure the speed of gravitational signals in short distances has been developed with the intention to study its behavior when a medium different from air is allocated between the emitter and the detection and check if the speed of the interaction changes. The experiment is composed of three sapphire bars that vibrates, and as they vibrate its creates a tidal gravitational wave signal that interacts with another sapphire bar, this bar is monitored by a very pure microwave signal and its amplitude and phase are measured and the gravity speed is calculated, all system is cooled to a temperature of 4.2 K to increase sensitivity and kept in high vacuum. The sapphire bar needs to be suspended to avoid seismic noise and other interference. This work models the sapphire bar with the suspension, a wire that suspends the bar by its center and has its performance calculated in a finite element modelling. The final result shows that the mechanical behavior of the sapphire bar is not affected by the suspension.

The resonant-mass gravitational wave detector SCHENBERG is a spherical detector that operates with a central frequency close to 3200 Hz and a bandwidth around 200 Hz. It has a spherical mass that works as an antenna whose weight is 1150 kg and is connected to the outer environment by a suspension system designed to attenuate local noise due to seism as well as other sources; the sphere is suspended by its center of mass. When a gravitational wave passes by the detector, the antenna is expected to vibrate. This motion should be monitored by six parametric microwave transducers whose output signals will be digitally analyzed. In order to determine the detector performance better, it is necessary to obtain the vibration frequencies of the sphere with a better precision. To achieve such a goal the sphere with the holes to mount the transducers and the central hole from which the sphere is suspended is simulated in a finite element method program when the gravity is applied to the sphere and the deformation is kept. After that the vibration normal modes of the sphere are calculated and they are compared to the experimental results.

Interferometric gravitational wave detectors (IGWD) are a very complex detector, the need to lock the detector in a dark fringe condition besides the vibrations that affect the mirrors, creates the necessity of using active suspension systems. These active systems make the system reach the desired sensitivity but make the calibration of such detectors much more difficult. To solve this problem a calibrator is proposed, a resonant mass gravitational wave detector could be used to detect the same signal in a narrower band and use the measured amplitude to calibrate the IGWD, as resonant mass gravitational wave detectors are easily calibrated. This work aims to obtain the expected sensitivity of such a calibrator by using lumped modelling in such mechanical detectors. The calibrator is modelled as a spring mass system and the sensitivity curve is presented calculated in by a matlab program. The curve shows that using state of art parameters for the detector the final sensitivity is close to the quantum limit and can be used to calibrate the IGWDs.

Interferometric gravitational wave detectors (IGWD) are a very complex detector, the need to lock the detector in a dark fringe condition besides the vibrations that affect the mirrors, creates the necessity of using active suspension systems. These active systems make the system reach the desired sensitivity but make the calibration of such detectors much more difficult. To solve this problem a calibrator is proposed, a resonant mass gravitational wave detector could be used to detect the same signal in a narrower band and use the measured amplitude to calibrate the IGWD, as resonant mass gravitational wave detectors are easily calibrated. This work aims to design the mechanical antenna of such a calibrator. The main difficulty is to design the calibrator is the frequencies required to make the detection. These massive detectors usually were made in frequencies close to 1 kHz and the frequency range to operate for better sensitivity is around 100 Hz. The antenna is modelled in finite elements method and a design of such an antenna is presented.

This article proposes a comparison between mathematical modeling and experimental results of the electric interactions of a synchronous and an induction generator. The electric system is composed by a synchronous generator operating in parallel with the induction generator, both through a common bus, connected to nonlinear loads. Measurements are made at several points for different system configurations presenting the repowering effect. The analysis of the harmonic flow and the sensitivity of the system parameters are performed. To make predictions in the system, a validated computational model with experimental data is proposed. The results obtained comparing the mathematical modeling and experimental tests show the increase of the active power by the induction generator, as well as the circulation of harmonic currents in the common bus. The results obtained through the computational model present predictions of load unbalance and increase in the system harmonic distortions. The sensitivity analysis confirms the induction generator influences on the system harmonic flow.

Tissue engineering and regenerative medicine have important implications for women with acquired or congenital disorders of reproductive organs. The field of reproductive medicine has expanded significantly over the past decades making impressive strides in assisted reproductive technologies, hormonal therapy, and organ transplantation techniques. Restoration and maintenance of normal organ function requires the development of biological substitutes or enhancements that can provide structural support as well as a favorable microenvironment for cells and tissues to grow and restore physiological activities. Tissue engineering technologies hold significant potential for developing therapeutic strategies for female infertility and associated reproductive issues. Here, we summarize major achievements in engineering tissues for each organ of the female reproductive system.

Aims: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62,. 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease. © 2020 European Society of Cardiology

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P 75 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF ≤45%. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

Aims: We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal. Methods and results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently. associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. © 2020 European Society of Cardiology

Parallelism, the evolution of similar traits in populations diversifying in similar conditions, provides good evidence of adaptation by natural selection. Many studies of parallelism have focused on comparisons of strongly different ecotypes or sharply contrasting environments, defined a priori, which could upwardly bias the apparent prevalence of parallelism. Here, we estimated genomic parallelism associated with individual components of environmental and phenotypic variation at an intercontinental scale across four adaptive radiations of the three-spined stickleback (Gasterosteus aculeatus), by associating genome-wide allele frequencies with continuous distributions of environmental and phenotypic variation. We found that genomic parallelism was well predicted by parallelism of phenotype-environment associations, suggesting that a quantitative characterization of phenotypes and environments can provide a good prediction of expected genomic parallelism. Further, we examined the explanatory power of genetic, phenotypic, and environmental similarity in predicting parallelism. We found that parallelism tended to be greater for geographically proximate, genetically similar radiations, highlighting the significant contingency of standing variation in the early stages of adaptive radiations, before new mutations accumulate. However, we also demonstrate that distance within multivariate environmental space predicts parallelism, after correction for genetic distance. This study thus demonstrates the relative influences of environment, phenotype and genetic contingency on repeatable signatures of adaptation in the genome.

Bioengineered uterine tissue could provide a treatment option for women with uterine factor infertility. In large animal models, reconstruction of the uterus has been demonstrated only with xenogeneic tissue grafts. Here we use biodegradable polymer scaffolds seeded with autologous cells to restore uterine structure and function in rabbits. Rabbits underwent a subtotal uterine excision and were reconstructed with autologous cell-seeded constructs, with nonseeded scaffolds or by suturing. At 6 months postimplantation, only the cell-seeded engineered uteri developed native tissue-like structures, including organized luminal/glandular epithelium, stroma, vascularized mucosa and two-layered myometrium. Only rabbits with cell-seeded constructs had normal pregnancies (four in ten) in the reconstructed segment of the uterus and supported fetal development to term and live birth. With further development, this approach may provide a regenerative medicine solution to uterine factor infertility. The rabbit uterus is reconstructed using synthetic scaffolds seeded with cells.

There has been a large focus on the genetics of traits involved in adaptation, but knowledge of the environmental variables leading to adaptive changes is surprisingly poor. Combined use of environmental data with morphological and genomic data should allow us to understand the extent to which patterns of phenotypic and genetic diversity within a species can be explained by the structure of the environment. Here, we analyse the variation of populations of three‐spined stickleback from 27 freshwater lakes on North Uist, Scotland, that vary greatly in their environment, to understand how environmental and genetic constraints contribute to phenotypic divergence. We collected 35 individuals per population and 30 abiotic and biotic environmental parameters to characterize variation across lakes and analyse phenotype–environment associations. Additionally, we used RAD sequencing to estimate the genetic relationships among a subset of these populations. We found a large amount of phenotypic variation among populations, most prominently in armour and spine traits. Despite large variation in the abiotic environment, namely in ion composition, depth and dissolved organic Carbon, more phenotypic variation was explained by the biotic variables (presence of predators and density of predator and competitors), than by associated abiotic variables. Genetic structure among populations was partly geographic, with closer populations being more similar. Altogether, our results suggest that differences in body shape among stickleback populations are the result of both canalized genetic and plastic responses to environmental factors, which shape fish morphology in a predictable direction regardless of their genetic starting point.

Laser Interferometers Gravitational Wave detectors have more than 100 active attenuator systems, the normal methods for calibration seems to not work properly. This work aims to model a calibrator for this detector in the form of a resonant-mass Nb gravitational detector thar has the same sensitivity of LIGO detector bur operating in a narrow band. This detector will detect the same gravitational wave and use this signal to calibrate LIGO. A simulation in a lumped model is made and it shows that the calibration is achievable.

In order to investigate the behavior of gravitational signals while travelling through a medium an experiment was designed, aimed at measuring the speed of these signals over short distances. The experiment contains 2 sapphire devices that behave as a detector, which are suspended in vacuum and cooled down to 4.2 K. The amplitude of the detecting device is measured by an ultralow, phase-noise microwave signal that uses resonance in the whispering gallery modes. Since sapphire has a quite high mechanical Q, the detection band is expected to be small, thus reducing the detection sensitivity. A new shape for the detecting device is presented in this work, yielding a detection band of several hundred Hertz. With the aid of a Finite Element Program the normal mode frequencies of the detector are determined.