Background: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. Methods: Six hundred and ninety-eight healthy children (ages 0 to 18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA) based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). Results: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV were 0.99, 0.99, and 0.99 respectively. The ICC for interobserver variability for EDV, ESV, and SV were 0.98, 0.94, and 0.98 respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). Conclusions: We report pediatric Z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.
Invasive ants shape assemblages and interactions of native species, but their effect on fundamental ecological processes is poorly understood. In East Africa, Pheidole megacephala ants have invaded monodominant stands of the ant-tree Acacia drepanolobium, extirpating native ant defenders and rendering trees vulnerable to canopy damage by vertebrate herbivores. We used experiments and observations to quantify direct and interactive effects of invasive ants and large herbivores on A. drepanolobium photosynthesis over a 2-year period. Trees that had been invaded for ≥ 5 years exhibited 69% lower whole-tree photosynthesis during key growing seasons, resulting from interaction between invasive ants and vertebrate herbivores that caused leaf- and canopy-level photosynthesis declines. We also surveyed trees shortly before and after invasion, finding that recent invasion induced only minor changes in leaf physiology. Our results from individual trees likely scale up, highlighting the potential of invasive species to alter ecosystem-level carbon fixation and other biogeochemical cycles.
Article type: News and Views: Groundbreaking Discoveries in ImmunologyTitle: Uncovering the influence of diet and gut microbiota in human serum metabolomeAuthors: David Obeso1,2‡, Elisa Zubeldia-Varela1,2‡ and Alma Villaseñor11Instituto de Medicina Molecular Aplicada (IMMA), Departamento de Ciencias Médicas Básicas. Facultad de Medicina. Universidad San Pablo-CEU, CEU Universities, Madrid, España.2Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, España.‡: These Authors have equally contributedCorrespondence: Alma Villaseñor, Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, EspañaEmail address:firstname.lastname@example.orgKeywords: Metabolomics, Diet, Microbiota, Allergy, Serum, MetabolomeAbbreviations: MS, mass spectrometry; LC, liquid chromatography; short chain fatty acids (SCFA)Acknowledgement: We would like to thank Anna Głobińska for her assistance in generating the graphical figure. AV Gratefully acknowledges the Martín-Carbajo family for supporting her scientific development through the X Mario Martín Velamazán award.Author contributions: D.O., E.Z-V. and A.V contributed to the writing of the manuscript and have given approval to the manuscript. A.V. supervised the final version.
Over the past fifteen years, the number of papers focused on “eco-evo dynamics” has increased exponentially (Figure 1). This pattern suggests the rapid growth of a new, integrative discipline. We argue that this overstates the case. First, the terms “eco-evo dynamics” and “eco-evo interactions” are used too imprecisely. As a result, many studies that claim to describe eco-evo dynamics are actually describing basic ecological or evolutionary processes. Second, these terms are often used as if the study of how ecological and evolutionary processes are intertwined is novel when, in fact, it is not. The result is confusion over what the term “eco-evolution” and its derivatives describe, a loss of appreciation for the history of genuine eco-evolutionary studies, and a loss of appreciation for the novelty associated with the original rise of the term. We advocate a more precise definition of eco-evolution that is more useful in our effort to understand and characterize the diversity of ecological and evolutionary processes and that focuses attention on the subset of those processes that offer novel results.
Global influenza virus circulation declined and has been below traditional seasonal levels during the COVID-19 pandemic.1-3 We reviewed WHO influenza surveillance outputs from May 1-December 31, 2020 (epidemiologic weeks 18-53) from tropical Asian countries. For each country we report influenza surveillance specimens tested, and the percentage positive for influenza, by type and subtype. We compared current data to historical data from 2015-2019 in order to place the current season in historical context. Twelve included countries tested 17,407 surveillance specimens, with 592 (3.4%) testing positive for influenza viruses. From April 27-July 26, 2020 (epidemiologic weeks 18-30), specimens tested decreased from an average of 14,102 per year in 2015-2019 to 3,969 (71.9% decrease) and influenza positivity from 22% to <1%. During weeks 31-53, specimens tested decreased from an average of 24,782 per year in 2015-2019 to 13,438 (45.8% decrease) and influenza positivity from 18% to 4%. In six countries that maintained testing of surveillance specimens for >90% of weeks, influenza circulation was unseasonably low, or absent, during weeks 18-30, 2020. However, during weeks 31-53, the percentage of surveillance specimens testing positive for influenza approached or reached positivity rates of 2015-2019 in Bangladesh and Cambodia; and increased but remained lower than historical positivity in Lao PDR and Viet Nam. The data presented here are a reminder that the low levels of influenza circulation in the northern hemisphere in summer 2020 may not necessarily persist into the upcoming influenza season, and influenza surveillance and prevention strategies should continue as planned and not be delayed.
Research hypotheses have been a cornerstone of science since before Galileo. Many have argued that inclusion of multiple hypotheses (1) encourage discovery of mechanisms, and (2) reduce bias – both features that should increase transferability and reproducibility. However, we are entering a new era of big data and highly predictive models where some argue the hypothesis is outmoded. Indeed, using a detailed literature analysis, we found prevalence of hypotheses in eco-evo research is very low (6.7-26%) and static from 1990-2015, a pattern mirrored in an extensive literature search (N=302,558 articles). Our literature review also indicates that neither grant success or citation rates were related to the inclusion of hypotheses, which may provide disincentive for hypothesis formulation. Here we confront common justifications for avoiding hypotheses and present new arguments based on benefits to the individual. Although hypotheses are not always necessary, we expect their continued and increased use will help our fields move toward greater understanding, reproducibility, prediction, and effective conservation of nature.
Both termites and large mammalian herbivores (LMH) are savanna ecosystem engineers that have profound impacts on ecosystem structure and function. Both of these savanna engineers modulate many common and shared dietary resources such as woody and herbaceous plant biomass, yet few studies have addressed how they impact one another. In particular, it is unclear how herbivores may influence the abundance of long-lived termite mounds via changes in termite dietary resources such as woody and herbaceous biomass. While it has long been assumed that abundance and areal cover of termite mounds in the landscape remains relatively stable, most data are observational, and few experiments have tested how termite mound patterns may respond to biotic factors such as changes in large herbivore communities. Here, we use a broad tree density gradient and two landscape-scale experimental manipulations—the first a multi-guild large herbivore exclosure experiment and the second a tree removal experiment– to demonstrate that patterns in termite mound abundance and cover are unexpectedly dynamic. Termite mound abundance, but not areal cover not significantly, is positively associated with experimentally controlled presence of cattle, but not wild mesoherbivores (15-1000 kg) or megaherbivores (elephants and giraffes). Herbaceous productivity and tree density, termite dietary resources that significantly affected by different LMH treatments, are both positive predictors of termite mound abundance. Experimental reductions of tree densities are associated with lower abundances of termite mounds. These results reveal a richly interacting web of relationships among multiple savanna ecosystem engineers and suggest that termite mound abundance and areal cover is intimately tied to herbivore-driven resource availability.
Growth-differentiation factor 15 (GDF15) is an inflammatory cytokine involved in energy homeostasis. Its circulating levels are acutely increased by the type 2 diabetes medication metformin, resulting in reduced appetite and weight loss. We identified a genetic variant at the GDF15 gene to proxy a small, lifelong increase in circulating GDF15 levels, and leveraged it in colocalization and Mendelian randomization analyses to investigate the effects of chronically elevated GDF15 levels on body mass index (BMI) and type 2 diabetes liability. The results provide human genetic evidence supporting that chronically elevated GDF15 levels increase BMI. There was no genetic evidence to support bi-directional effects, or that chronically elevated GDF15 levels directly affect liability to type 2 diabetes. Our results contrast the BMI lowering effects of an acute increase in GDF15 levels observed after metformin use. These findings have direct implications for informing pharmacological strategies aimed at targeting GDF15 levels for weight loss.
Background: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. Methods: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases, and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PVR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory confirmed cases were mapped and six genomes of viruses were fully sequenced. Results: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2 positive patients, the median age was 39 years (CI95%: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A, and 20B in favour of several independent introduction of viruses. Conclusions. Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.
Background: The success of coronary artery bypass grafting surgery (CABG) is dependent on long-term graft patency, which is negatively related to early wall thickening. Avoiding high-pressure distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening. Methods: A single-centre, factorial randomised controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial-intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months. Results: 96 eligible participants were recruited. With conventional harvest, low-pressure testing tended to yield a thinner vessel wall compared to high-pressure (mean difference MD (low minus high) -0.059mm, 95%CI -0.12, +0.0039, p=0.066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD (pedicle minus conventional) -0.057mm, 95%CI -0.12, +0.0037, p=0.066, test for interaction p=0.07). Lumen diameter was similar across groups (harvest comparison p=0.81; pressure comparison p=0.24). Low pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p=0.0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p=0.0041). Conclusions: Conventional saphenous vein graft preparation with low pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events.
Bilateral antegrade selective cerebral perfusion has the undisputed advantage of being more physiological and theoretically ensuring complete perfusion of the whole brain. However, it requires longer execution times and manipulation of the epiaortic vessels. On the other hand, unilateral selective cerebral perfusion (u-ASCP) avoids the vessels manipulation, placement of catheters into the ostia of the great vessels which clutters the operative field and incurs both atherosclerotic and air embolism risk. Neverthless, an ongoing debate about which technique yields the best clinical outcomes is still open.
If it an’t broke, don’t fix itBerhane Worku MD1, Meghann M Fitzgerald21: Department of Cardiothoracic Surgery, Weill Cornell Medical College2. Department of Anesthesiology, Weill Cornell Medical CollegeAntifibrinolytics and TEGCorresponding Author:Berhane WorkuDepartment of Cardiothoracic SurgeryWeill Cornell Medical College525 East 68th Street M-404New York, NY 10065Despite evidence of associated morbidity and mortality, blood products are administered to over half of cardiac surgical patients, accounting for approximately 20% of their worldwide use1,2. These statistics attest to the ubiquitous and refractory nature of bleeding after cardiac surgery. In an attempt to curb the excessive use of blood products after cardiac surgery viscoelastic testing in the form of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) have been increasingly utilized. Rapid intraoperative assessment allows for targeted correction of coagulopathy due to residual heparinization, coagulation factor deficiency, hypofibrinogenemia, and platelet dysfunction. Hyperfibrinolysis can also be assessed, although management is rarely altered as the routine administration of lysine analog antifibrinolytics has been given a class I recommendation by the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists and has become the standard practice at most cardiac surgical centers.Cardiopulmonary bypass is known to result in transient t-PA and subsequent d-dimer level elevations (a marker of hyperfibrinolysis)3,4. The efficacy of the lysine analog antifibrinolytics, tranexamic acid andε-aminocaproic acid, have been extensively studied in this setting. D-dimer levels are significantly blunted by antifibrinolytics, and an abundance of literature demonstrates reductions in chest tube bleeding, blood product use, and reoperation for bleeding with the use of these agents4-6. A similar amount of evidence points to their safety, with no increase in thrombotic complications, including stroke, myocardial infarction, graft closure, or mortality seen5-7. A higher risk of seizures is noted with tranexamic acid, although this appears to be dose dependent and nonexistent with ε-aminocaproic acid2. If the ultimate goal is to reduce bleeding and blood product usage, it would seem that antifibrinolytics offer one way to do this safely.In the current manuscript, Sussman et. al. retrospectively analyze 78 cardiac surgical patients who had an intraoperative TEG performed with the goal of describing the distribution of fibrinolytic phenotypes in this population8. Forty five percent demonstrated physiologic fibrinolysis, 32% hypo fibrinolysis, and 23% hyperfibrinolysis (LY30 <0.8%, 0.8-3%, >3%). Forty seven percent received antifibrinolytic agents. Outcomes including “morbidity” and time with chest tube were higher in those who received antifibrinolytics. This is a perhaps the first study of its kind to describe the prevalence of hyperfibrinolysis in cardiac surgical patients as measured by point of care testing. It is also a very relevant study in an era in which the benefits of targeted therapy for coagulopathy are increasingly recognized.The current data suggests that half of patients undergoing cardiac surgery demonstrate physiologic fibrinolysis and a third demonstratehypo fibrinolysis (a theoretically pro thrombotic state)8. The worse outcomes seen in patients receiving antifibrinolytics suggests that their administration in the setting of a potentially prothrombotic state was to blame. However, several limitations merit mention. It appears that TEG is not routinely performed on all patients. The population under study may therefore reflect one undergoing more extensive surgery with more coagulopathy in whom TEG is more likely to be performed. Since the actual timing of the TEG is not detailed, the true baseline fibrinolytic phenotype of patients treated with antifibrinolytics is not clear as the TEG results may have been obtained after the initiation of antifibrinolytics. Furthermore, while surgical procedures performed weren’t delineated, patients receiving antifibrinolytics more frequently had “valve disease” and “heart failure” and underwent on-pump surgery. Patients receiving antifibrinolytic therapy were therefore sicker and likely underwent more extensive on-pump valve surgery, while patients who did not receive antifibrinolytics were most likely undergoing off-pump coronary bypass surgery. Finally, the increased “morbidity” in patients receiving antifibrinolytics appear to be bleeding related (thrombotic complications were not listed separately). Perhaps additional antifibrinolytics were needed.The authors are to be commended for recognizing a lack of complete understanding of coagulation in the cardiac surgical population and attempting to determine the benefit of targeted antifibrinolytic therapy. Any time a practice is performed indiscriminately, there is room for improvement. However, before we contemplate altering an evidence-based practice that reduces bleeding, we need to demonstrate a benefit for such a change. Not all bleeding is purely surgical or purely medical; there is overlap. Few areas of medicine highlight how much art prevails over our current scientific understanding. Too many times since the introduction of point-of-care testing, the surgeon and anesthesiologist battle over the merits of administering blood products to a clinically bleeding patient with a normal coagulation profile. Targeted correction of coagulopathy is conceptually attractive, but the reality is not as clearly defined. Reductions in bleeding seen with antifibrinolytics occur both in on-pump and off-pump surgery which should be enough proof to continue its application until better evidence and understanding emerges6. Certainly, there is more work to be done, but with regard to antifibrinolytics it seems fitting to recognize: If it ain’t broke, don’t fix it.REFERENCESAbdelmotieleb M, Agarwal S. Viscoelastic testing in cardiac surgery. Transfusion 2020;60:52-60Harvey R, Salehi A. Con: Antifibrinolytics should not be used routinely in low-risk cardiac surgery. J Cardiothorac Vasc Anesth 2016;30:248-251Gielen C, Brand A, van Heerde W, Stijnen T, Klautz R, Eikenboom J. Hemostatic alterations during coronary artery bypass grafting. Thromb Res 2016;140:140-146Slaughter T, Faghih F, Greenberg C, Leslie J, Sladen R. The effects of ε-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery. Anesth Analg 1997;85:1221-6Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper J, Marasco S, McNeil J, Bussieres JS, McGuinness S, Byrne K, Chan MTV, Landoni G, Wallace S. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 2017;376:136-48Zhang Y, Bai Y, Chen M, Zhou Y, Yu X, Zhou H, Chen G. The safety and efficiency of intravenous administration of tranexamic acid in coronary artery bypass grafting (CABG): a meta-analysis of 28 randomized controlled trials. BMC Anesthesiol 2019;19:104Kasrki J, Djaiani G, Carroll J, Iwanochko M, Seneviratne P, Liu P, Kucharczyk W, Fedorko L, David T, Cheng D. Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: A prospective randomized controlled clinical trial. J Thorac Cardiovasc Surg 2005;130:309-14Sussman MS, Urrechaga EM, Cioci AC, Iyengar RS, Herrington TJ, Ryon EL, Namias N, Galbut DL, Salerno TA, Proctor KG. Do all cardiac surgery patients benefit from antifibrinolytic therapy? J Card Surg in press
Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic “real-world” database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.
The European corn borer (ECB) Ostrinia nubilalis is a widespread pest of cereals. Mating disruption with the sex pheromone is a potentially attractive method for managing this pest. The goal of this study was to develop a biotechnological method for the production of ECB sex pheromone. Our approach was to engineer the oleaginous yeast Yarrowia lipolytica to produce (Z)-11-tetradecenol (Z11-14:OH), which can be chemically acetylated to (Z)-11-tetradecenyl acetate (Z11-14:OAc), the main pheromone component of the Z-race of O. nubilalis. Fatty acyl-CoA desaturases (FAD) and fatty acyl-CoA reductases (FAR) from nine different species of Lepidoptera were screened individually and in combinations. A titer of 29.2±1.6 mg/L Z11-14:OH was reached in small-scale cultivation with an optimal combination of a FAD (Lbo_PPTQ) from Lobesia botrana and FAR (HarFAR) from Helicoverpa armigera. When the second copies of FAD and FAR genes were introduced, the titer improved 2.1-fold. The native FAS1 gene’s overexpression led to a further 1.5-fold titer increase. When the same engineered strain was cultivated in controlled 1 L bioreactors in fed-batch mode, 188.1±13.4 mg/L of Z11-14:OH was obtained. Fatty alcohols were chemically acetylated to obtain Z11-14:OAc. Electroantennogram experiments showed that males of the Z-race of O. nubilalis were responsive to biologically-derived pheromone blend. Behavioral bioassays in a wind tunnel revealed attraction of male O. nubilalis at a level similar to that of the chemically synthesized pheromone used as a control, although full precopulatory behavior was observed less often. The study paves the way for the production of ECB pheromone by fermentation.