Background: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA. Methods: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient. Results: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients. Conclusions: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA.

Biochar or pyrogenic carbon, obtained from thermo-chemical conversion of biomass in an anaerobic or oxygen limited environment has been in use in agriculture since long back to Neolithic era. Its unique soil ameliorating properties, render it suitable for environmental remediation as well as sustainable crop production. It improves soil physicochemical properties and plant nutrient availability, facilitates biodiversity, and reduces emission of greenhouse gases, thereby subsiding global warming. Application of biochar reduces soil erosion, improves soil hydrological properties, and soil microbial dynamics. It has synergistic effects on plant growth, disease-pest resistance, and crop yield per unit area and time. Due to its soil ameliorative effects, and soil and water conserving ability, it can very well be used in organic farming, pemaculture, dryland farming, conservation agriculture, and land remediation. Cheaper production cost, simple and easy pyrolytic technologies, easy availability of feedstock and bio-wastes in many developing countries and its long-term effects in soil not only build up soil carbon pool but also help support small and marginal farmers in resource-rich but economically deprived countries for sustainable agriculture and environment. In this review, efforts have been made to elucidate various methods of biochar synthesis, its characteristics and effects on soil properties, and plant growth and development, its role in sustainable agriculture and remediation of the environment.

Comparisons of genomes from recently diverged butterfly populations along a suture zone in central Texas have revealed high levels of divergence on the Z chromosome relative to autosomes, as measured by fixation index, $F_{st}$. The pattern of divergence appears to result from accumulation of incompatible alleles, obstructing introgression on the Z chromosome in hybrids. However, it is unknown whether this mechanism is sufficient to explain the data. Here, we simulate the effects of hybrid incompatibility on interbreeding butterfly populations using a model in which populations accumulate cross–incompatible alleles in allopatry prior to contact. We compute statistics for introgression and population divergence during contact between model butterfly populations and compare them to statistics obtained for 15 pairs of butterfly species interbreeding along the Texas suture zone. For populations that have evolved sufficiently in allopatry, the model exhibits high levels of divergence on the Z chromosome relative to autosomes in populations interbreeding on time scales comparable to periods of interglacial contact between butterfly populations in central Texas.Levels of divergence on the Z chromosome increase when interacting groups of genes are closely linked, consistent with interacting clusters of functionally related genes in butterfly genomes. Results for various periods in allopatry are in qualitative agreement with the pattern of data for butterflies, supporting a picture of speciation in which populations are subjected to cycles of divergence in glacial isolation, and partial fusion during interglacial contact.

Predicting which ecological factors constrain species distributions is a fundamental question in ecology and critical to forecasting geographic responses to global change. Darwin hypothesized that abiotic factors generally impose species’ high-latitude and high-elevation (typically cool) range limits, whereas biotic interactions more often impose species’ low-latitude/low-elevation (typically warm) limits, but empirical support has been mixed. Here, we clarify three predictions arising from Darwin’s hypothesis, and show that previously mixed support is partially due to researchers testing different predictions. Using a comprehensive literature review (886 range limits), we find that biotic interactions, including competition, predation, and parasitism, influenced species’ warm limits more often than species’ cool limits. At cool limits, abiotic factors were consistently more important than biotic interactions, but temperature contributed strongly to cool and warm limits. Our results suggest that most range limits will be sensitive to climate warming, but warm limit responses will depend strongly on biotic interactions.

In the wake of the 2020 COVID-19 epidemic, much work has been performed on the development of mathematical models for the simulation of the epidemic, and of disease models generally. Most works follow the susceptible-infected-removed (SIR) compartmental framework, modeling the epidemic with a system of ordinary differential equations. Alternative formulations using a partial differential equation (PDE) to incorporate both spatial and temporal resolution have also been introduced, with their numerical results showing potentially powerful descriptive and predictive capacity. In the present work, we introduce a new variation to such models by using delay differential equations (DDEs). The dynamics of many infectious diseases, including COVID-19, exhibit delays due to incubation periods and related phenomena. Accordingly, DDE models allow for a natural representation of the problem dynamics, in addition to offering advantages in terms of computational time and modeling, as they eliminate the need for additional, difficult-to-estimate, compartments (such as exposed individuals) to incorporate time delays. In the present work, we introduce a DDE epidemic model in both an ordinary- and partial differential equation framework. We present a series of mathematical results assessing the stability of the formulation. We then perform several numerical experiments, validating both the mathematical results and establishing model’s ability to reproduce measured data on realistic problems.

Methods The study included 59 patients with normal fetal heart structure, blood flow, and heart rhythm (fetal abnormality-negative group) and 50 patients with abnormal fetal heart structure, blood flow, and/or heart rhythm (fetal abnormality-positive group). aCMQ was performed in both groups to obtain left and right ventricular endocardial global longitudinal strain (GLSendo), mid-myocardial global longitudinal strain (GLSmid), and epicardial global longitudinal strain (GLSepi). Parameters between the two groups were compared and correlation analyses performed. A deformation analysis was performed by two trained observers, and reproducibility was assessed. Results The fetal left ventricular and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively) decreased in a gradient from the endocardium to the epicardium. LV-GLS and RV-GLS of all myocardial layers were lower in the fetal abnormality-positive than -negative group (all P<0.05). Correlation analysis showed that neither LV-GLS nor RV-GLS was significantly correlated with gestational age in the fetal abnormality-negative group (all P>0.05), whereas left ventricular GLSendo, GLSmid, and GLSepi were negatively correlated with gestational age in the fetal abnormality-positive group (r=−0.39 to −0.44, all P<0.05). Repeatability testing showed that the inter-observer and intra-observer intraclass correlation coefficients for LV-GLS and RV-GLS in each myocardial layer were >0.75 (all P<0.001). Conclusions As a new speckle tracking echocardiography tool, aCMQ has feasibility and repeatability in evaluating myocardial deformation of the fetal ventricle. This technique might provide helpful information on ventricular myocardial deformation in fetal hearts with abnormal structure or rhythm for clinical guidance in pregnancy.

Since the start of the novel coronavirus SARS-Cov-2 pandemic, a disease that has become one of the world’s greatest global health challenges, the role of the immune system has been at the forefront of scientific studies. The pathophysiology of COVID-19 is complex, which is evident by those at higher risk for poor outcome. Multiple systems contribute to thrombosis and inflammation seen in COVID-19 patients, including neutrophil dysfunction, platelet activation, endothelial cell activation. Understanding how the immune system functions in different patient cohorts (particularly given recent emerging events with the Oxford/AstraZeneca vaccine) is vital to understanding the pathophysiology of this devastating disease and for subsequent development of novel therapeutic targets and expedite possible drug repurposing strategies that could benefit society on a global scale.

Pyroptosis, is a specialized form of inflammatory cell death which aids the defensive response against invading pathogens. Its tight regulation is lost during infection by the severe acute respiratory coronavirus 2 (SARS-CoV-2) and thus uncontrolled pyroptosis disrupts the immune system and the integrity of organs defining the critical conditions in patients with high viral load. Molecular pathways engaged downstream to the formation and stabilization of the inflammasome -required to execute the process- have been uncovered and drugs are available for their regulation. On the contrary, pharmacological inferring of the upstream events -which are critical to sense and interpret the initial damage by the pathogen- is far from being elucidated. This limits our capacity to identify early markers and targets to ameliorate SARS-CoV-2 linked pyroptosis. Here we aim to raise attention on mitochondria and pathways leading to its dysfunction with the goal to inform early steps of inflammasome and devise tools to interpret and counteract diseases by the SARS-CoV-2.

Autoimmune diseases including systemic sclerosis (SSc) increase risk of developing TB. Pericostal tuberculosis (TB) is a rare presentation of skeletal TB. This case report describes pericostal TB in a SSc patient, and emphasizes significance of suspecting pulmonary and extra-pulmonary TB when patients with autoimmune disease follow atypical clinical courses.

Uncertain fractional-order differential equations driven by Liu process are of significance to depict the heredity and memory features of uncertain dynamical systems. This paper primarily investigates the reliability analysis of the uncertain fractional-order dynamic system with a state constraint. On the basis of the first-hitting time (FHT), a novel uncertain fractional-order dynamic system considering a state constraint is proposed. Secondly, in view of the relation between the initial state and the required standard, such uncertain fractional-order dynamic systems are subdivided into four types. The concept of reliability of proposed uncertain system with a state constraint is presented innovatively. Corresponding reliability indexes are ulteriorly formulated via FHT theorems. Lastly, the uncertain fractional-order dynamic system with a state constraint is applied to different physical and financial dynamical models. The analytic expression of the reliability index is derived to demonstrate the reasonableness of our model. Meanwhile, expected time response and American barrier option prices are calculated by using the predictor-corrector scheme. A sensitivity analysis is also illustrated with respect to various conditions.

The increasing salinization of coastal areas of Bangladesh reduces options for rice intensification but offers a suitable environment for shrimp and salt farming. Under these contested land use settings, adaptation decisions to address salinity require an understanding of the salinity perspectives of all farmer types. Primary data was collected from randomly selected rice, shrimp and salt farmers in two coastal sub-districts through semi-structured interviews at household level. Also, key informant interviews (KIIs) were conducted with personnel from research and extension organisations from different levels (e.g. national and local). Salinity perceptions among the various types of farmer differed. While the majority of rice farmers (87%) perceived increased salinity, just over half of the salt and shrimp farmers perceived that salinity has decreased over the past 20 years. Most rice farmers (62%) perceived anthropogenic factors as the main cause of increased salinity, while the majority of shrimp and salt farmers focused more on natural factors. Rice farmers perceived under saline conditions a yield loss (42%), followed by less income (30%). In contrast, shrimp farmers (70%) and salt farmers (55%) perceived production gains when high salinity prevailed. Rice farmers’ adaptation preferences to cope with salinity is development of salinity-tolerant rice varieties that have greater tolerance at the reproductive stages, while shrimp and salt farmers’ preferences are engineering-based solutions. Thus, research and extension services on integrated coastal resources management need to consider all livelihood perspectives, as this approach could accelerate the pace of achieving the SDGs (i.e.. SDG-1, SDG-2 and SGD-3).

Aims: Amidst the Campos the Altitude (Highland Grasslands) in the Brazilian Atlantic Forest, woody communities grow either clustered in tree islands or interspersed within the herbaceous matrix. The functional ecology, diversity and biotic processes shaping these communities are largely unstudied. We characterised the functional assembly and diversity of these tropical montane woody communities and investigated how those communities fit within the Grime’s CSR (C – competitor, S – stress-tolerant, R – ruderal) scheme, what trade-offs they exhibit and how traits and functional diversity vary in response to bamboo invasion. Methods: We sampled five leaf traits and wood density along transects covering the woody communities both inside tree islands and outside (i.e. woody plants in the grasslands community) to characterise the functional ecology of the community. We used Kruskal-Wallis test, t-test and variation partitioning to determine effects of inside vs outside the tree island and bamboo invasion on traits, woody species diversity and functional diversity. Results: We found a general SC/S strategy with drought-related functional trade-offs. Woody plants in tree islands had more acquisitive traits, whereas woody plants within the grasslands had more conservative traits. Trait variation was mostly taxonomically driven, and species composition varied between inside and outside tree islands. Leaf thickness, wood density and foliar water uptake were unrelated to CSR-strategies, suggesting independent trait dimensions and multiple drought-coping strategies within the predominant S-strategy. Bamboo-invaded islands showed lower Simpson diversity, lower functional dispersion, lower foliar water uptake and greater leaf thickness than non-invaded tree islands. Conclusions: The observed functional assembly in response to bamboo and facilitation have implications for future forest expansion and response of the communities to climate change. Further studies on eco-physiological and establishment traits and the mechanisms behind biotic interactions are needed to better understand the response of these communities to future environmental changes.

Abstract Aim: The invasion process is a complex, context-dependent phenomenon; nevertheless, it can be described using the PAB framework. This framework encompasses the joint effect of propagule pressure (P), abiotic characteristics of the environment (A), and biotic characteristics of both the invader and recipient vegetation (B). We analyzed the effectiveness of proxies of PAB factors to explain the spatial pattern of Solidago canadensis and S. gigantea invasion using invasive species distribution models. Location: Carpathian Mountains and their foreground, Central Europe. Methods: The data on species presence or absence were from an atlas of neophyte distribution based on a 2 × 2 km grid, covering approximately 31,200 km2 (7752 grid cells). Proxies of PAB factors, along with data on historical distribution of invaders were used as explanatory variables in Boosted Regression Trees models to explain the distribution of invasive Solidago. The areas with potentially lower sampling effort were excluded from analysis based on a target species approach. Results: Proxies of the PAB factors helped to explain the distribution of both S. canadensis and S. gigantea. Distributions of both species were limited climatically because a mountain climate is not conducive to their growth; however, the S. canadensis distribution pattern was correlated with proxies of human pressure, whereas S. gigantea distribution was connected with environmental characteristics. The varied responses of species with regard to distance from their historical distribution sites indicated differences in their invasion drivers. Main conclusions: Proxies of PAB are helpful in the choice of explanatory variables as well as the ecological interpretation of species distribution models. The results underline that human activity can cause variation in the invasion of ecologically similar species.

1. Plant-soil feedback (PSF) has gained attention as a mechanism promoting plant growth and coexistence. However, because most PSF research has measured monoculture growth in greenhouse conditions, field-based PSF experiments remain an important frontier for PSF research. 2. Using a four-year, factorial field experiment in Jena, Germany, we measured the growth of nine grassland species on soils conditioned by each of the target species (i.e., PSF). Plant community models were parameterized with or without these PSF effects, and model predictions were compared to plant biomass production in new and existing diversity-productivity experiments. 3. Plants created soils that changed subsequent plant biomass by 36%. However, because they were both positive and negative, the net PSF effect was 14% less growth on ‘home’ than ‘away’ soils. At the species level, seven of nine species realized non-neutral PSFs, but the two dominant species grew only 2% less on home than away soils. At the species*soil type level, 31 of 72 PSFs differed from zero. 4. In current and pre-existing diversity-productivity experiments, nine-species plant communities produced 37 to 29% more biomass than monocultures due primarily to selection effects. Null and PSF models predicted 29 to 28% more biomass for polycultures than monocultures, again due primarily to selection effects. 5. Synthesis: In field conditions, PSFs were large enough to be expected to cause roughly 14% overyielding due to complementarity, however, in plant communities overyielding was caused by selections effects, not complementarity effects. Further, large positive and large negative PSFs were associated with subdominant species, suggesting there may be selective pressure for plants to create neutral PSF. Broadly, results highlighted the importance of testing PSF effects in communities because there are several ways in which PSFs may be more or less important to plant growth in communities than suggested from simple PSF values.

Previous studies have demonstrated changes in plant growth and reproduction in response to nutrient availability, but how investigations of such responses to multiple levels of nutrient enrichment remains unclear. In this study, we manipulated nitrogen (N) and phosphorus (P) availability to examine seed production responses to three levels each of N and P addition in a factorial experiment: no N addition (0 g N m-2 yr-1), low N addition (10 g N m-2 yr-1), high N addition (40 g N m-2 yr-1), and no P addition (0 g P m-2 yr-1), low P addition (5 g P m-2 yr-1), high P addition (10 g P m-2 yr-1). Low N addition enhanced seed production by 814%, 1371%, and 1321% under ambient, low, and high P addition levels, respectively. High N addition increased seed production by 2136%, 3560%, and 3550% under ambient, low, and high P addition levels, respectively. However, P addition did not affect seed production in the absence of N addition, but it did enhance it under N addition. Furthermore, N addition enhanced seed production mainly by increasing the tiller number and inflorescence abundance per plant, whereas P addition stimulated it by decreasing the plant density yet stimulating height of plants and their seed number per inflorescence. Our results indicate seed production is limited not by P but rather by N in the temperate steppe, whereas seed production will be increased by P addition when N availability is improved. These findings enable a better understanding of plant reproduction dynamics of steppe ecosystems under intensified nutrient enrichment and can inform their improved management in the future.

Long Term Disruption of Cytokine Signalling Networks are Evident Following SARS-CoV-2 InfectionSinead Ahearn-Ford1, Nonhlanhla Lunjani1, Brian McSharry1,2, John MacSharry1,2,3, Liam Fanning1,3, Gerard Murphy4, Cormac Everard4, Aoife Barry4, Aimee McGreal4, Sultan Mohamed al Lawati4, Susan Lapthorne4, Colin Sherlock4, Anna McKeogh4, Arthur Jackson4, Eamonn Faller4, Mary Horgan3,4, Corinna Sadlier4, Liam O’Mahony1,2,3*1APC Microbiome Ireland, University College Cork, Cork, Ireland2School of Microbiology, University College Cork, Cork, Ireland3Department of Medicine, University College Cork, Cork, Ireland4 Department of Infectious Diseases, Cork University Hospital, Cork, Ireland*Corresponding author – [email protected] the Editor,The current pandemic caused by the SARS-CoV-2 virus has so far infected more than 130 million people worldwide, resulting in approximately 3 million deaths. While the current clinical and public health priorities are designed to limit severe acute and fatal episodes of the disease, and to quickly roll out vaccines to the general population, it has become apparent that there may also be significant detrimental long-term effects following SARS-CoV-2 infection that impact daily functioning and quality of life1. The mechanisms underpinning the post-acute sequelae of SARS-CoV-2 infection’s long-lasting symptoms can include direct effects of the infection (e.g. endothelial damage, lung fibrosis) or indirect effects associated with changes in the microbiome or abnormalities in inflammatory and immune signalling pathways stimulated by the infection2,3.In order to examine the potential long-term immune changes that occur following elimination of the primary infection, we examined the levels of 52 cytokines and growth factors (using MSD multiplex kits) in the serum of patients that attended follow-up post-COVID infection clinics at Cork University Hospital, Cork, Ireland (The Clinical Research Ethics Committee of the Cork Teaching Hospitals approved this study and all patients provided informed consent). All patients had been hospitalised for PCR-proven SARS-CoV-2 infection (median in-patient stay of 5.5 days, range 1 day to 24 days) during the first wave of the pandemic in Ireland (March-May 2020). 38 serum samples were obtained from 24 patients (median age 53.5 years, 11 female) at 3-9 months following hospital discharge. Clinical severity ranged from mild to critical during hospitalisation and the most common symptoms at follow-up clinics were fatigue and/or dyspnoea (supplementary Table S1). Sera obtained prior to the pandemic from 29 healthy volunteers (median age 43.2 years, 14 female) were analysed in parallel.Of the 52 analytes measured, 19 were significantly elevated in post-COVID patient sera compared to healthy controls (supplementary Table S2). These 19 mediators are illustrated as dot plots in Figure 1 and Figure 2. One group of mediators, c-reactive protein (CRP), serum amyloid A (SAA), Interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-8, IL-15, IL-16, monocyte chemotactic protein (MCP)-1 and MCP-4, can be broadly categorised as being associated with ongoing inflammatory responses (Figure 1a)4. These mediators remained as elevated in samples taken 6-9 months following hospital discharge as those levels observed 3-6 months following discharge (p<0.05 versus controls, ANOVA). A second group of mediators, vascular endothelial growth factor (VEGF-A), soluble tyrosine-protein kinase receptor Tie-2 (Tie-2), soluble intercellular adhesion molecule (ICAM-1) and basic fibroblast growth factor (bFGF), can be generally associated with endothelial dysfunction, remodelling and angiogenesis (Figure 1b)5. The remaining elevated mediators are associated with patterns of lymphocyte polarisation. Elevated IL-4, macrophage-derived chemokine (MDC) and thymic stromal lymphopoietin (TSLP) sera levels indicate activation of TH2 responses (Figure 2a), while IL-17A, macrophage inflammatory protein (MIP)-3α and IL-12/23p40 indicate ongoing TH17 activity (Figure 2b). Other indicators of TH2-associated activities are just outside statistical significance (IL-5, p=0.06; supplementary Table S2). While TH1 responses are well described to be upregulated during acute infection6, the levels of these mediators (e.g. IFN-γ, IP-10) decrease following elimination of the virus and are at control levels in our cohort of post-COVID patients (supplementary Table S2).Our data suggests that there are long term immunological consequences following SARS-CoV-2 infection, at least in those that had acute symptoms severe enough to require hospitalisation. While the relatively low number of patients included in our study at this stage does not allow us to perform subgroup analysis, it is possible that these immune mediators may associate with clinically meaningful disease variables and ultimately may be of therapeutic value, if findings are replicated in future studies. Of particular interest is the elevation in TH2-associated mediators. Could this response be a component of the mucosal repair mechanisms that occur following viral damage, or does this indicate new TH2-associated pathological immune activity that might underpin an increased risk of developing allergy or asthma? Clearly the potential immune mechanisms underpinning the emerging post-COVID clinical entities will become increasingly more important to understand as the health care systems adapt to caring for large numbers of COVID-19 survivors during the coming months and years.

Evidence-Based Medicine proposes a prescriptive model of physician decision-making in which “best evidence” is used to guide best practice. And yet, proponents of EBM acknowledge that EBM fails to offer a systematic theory of physician decision-making. In this paper, we explore how physicians from the neurology and emergency medicine communities have responded to an evolving body of evidence surrounding the acute treatment of patients with ischemic stroke. Through analysis of this case study, we argue that EBM’s vision of evidence-based medical decision-making fails to appreciate a process that we have termed epistemic evaluation. Namely, physicians are required to interpret and apply any knowledge — even what EBM would term “best evidence” — in light of their own knowledge, background and experience. This is consequential for EBM as understanding what physicians do and why they do it would appear to be essential to achieving optimal practice in accordance with best evidence.

The Asthma Predictive Index (API) predicts later asthma in preschoolers with frequent wheeze. We hypothesized that airway cytology differs between API positive(+ve)/negative(-ve) children with uncontrolled/recurrent wheezing with dominance of eosinophils in API (+ve) and neutrophils in API (-ve) groups respectively. Objective: To compare bronchoalveolar lavage (BAL) cell profiles in API (+ve)/(-ve) children with recurrent wheezing unresponsive to inhaled corticosteroids (ICS). Design: A retrospective analysis of BAL in 43 children, 3-36 months (median: 14 months) receiving ICS (31 API +ve ; 12 API -ve). BAL cell differential counts, bacterial/viral cultures, and lipid-laden macrophage percentages (LLM) were analyzed. Cell counts presented as median (range). Results: Neutrophil percentages were increased in both groups [API -ve 16% (1-76%); API +ve 42% (1-95%); P=NS]. Cell percentages were similar for lymphocytes [API-ve 12% (1-30%); API +ve 7% (1-37%)], and macrophages [API -ve 67.5% (12-97%); API +ve 41 % (2-94%)]. Eosinophil percentages were low in both groups [API -ve 1 % (1-2%); API +ve 1 % (1-11%)]. Bacterial cultures were positive in 16 (80%) API +ve and 4 (33%) API -ve patients (P=0.10). Conclusion: Cell profiles do not differ between API groups in children ≤36 months with recurrent wheezing unresponsive to ICS. Positive correlation between neutrophil percentages and positive bacterial cultures was seen independent of API. Persistent bacterial bronchitis likely plays an important role in the persistence of symptoms unresponsive to inhaled corticosteroid therapy regardless of API status with a trend to more positive cultures in API positive children.