Objective: To quantify the association between prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants and ADHD in offspring, with quantification of exposure misclassification bias. Design: Norwegian Mother, Father and Child Cohort Study (MoBa), linked to national health registries. Setting: Norway. Population: 6395 children born to women who self-reported depression/anxiety in pregnancy and were either medicated with SSRI/SNRI in pregnancy (n=818) or non-medicated (n=5228), or did not report depression/anxiety but used antidepressants six months prior to pregnancy (discontinuers, n=349). Main outcome measure: Diagnosis of ADHD or redeemed prescription for ADHD medication in children, and mother-reported symptoms of ADHD at child age five years. Results: When the hazard was averaged over the duration of the study’s follow-up, there was no difference in ADHD risk between ever in-utero SSRI/SNRI-exposed children and comparators (weighted Hazard Ratio (wHR): 1.07, 95% Confidence Interval (CI): 0.76-1.51, vs. non-medicated; wHR: 1.53, 95% CI: 0.77-3.07, vs. discontinuers). Underestimation of effects due to exposure misclassification was modest. At early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with non-medicated, and so were ADHD symptoms (weighted β: -0.23, 95% CI: -0.39, -0.08); this risk became elevated at child age 7-9 years (wHR: 1.93, 95% CI: 1.22-3.05). Maternal depression/anxiety prior to pregnancy was independently associated with child ADHD. Conclusion: Prenatal SSRI/SNRI exposure is unlikely to considerably increase the risk of child ADHD beyond that posed by the underlying psychiatric illness. The elevated risk at child age 7-9 years needs to be further elucidated.

In ectothermic predator-prey relationships, the capacity for prey to successfully evade predation will depend upon physiological and behavioural responses that relate to both players’ thermal biology. On the Izu Islands of Japan, we investigated how a prey lizard species has responded physiologically and thermally to the presence of a snake predator over evolutionary time in addition to recent climatic warming. Foraging lizard body temperatures have increased by 1.0°C from 1981 to 2019 while lizard body temperatures were 3.4°C warmer on islands where the snake predator is present relative to snake-free islands. We also found that warmer prey body temperatures result in faster running speeds of the prey at temperatures suboptimal for the snake predator. The results show that lizard body temperatures have increased with warming but not to the same extent as that exerted by predation pressure. However, further warming could irrevocably alter this and other ectothermic predator-prey relationships.

Forecasts of forest responses to climate variability are governed by climate exposure and ecosystem sensitivity, but ecosystem model projections and process representations are under-constrained by data at multidecadal and longer timescales. Here, we assess ecosystem sensitivity to centennial-scale hydroclimate variability, by comparing dendroclimatic and pollen-inferred reconstructions of drought, forest composition and biomass for the last millennium with five ecosystem model simulations. In both observations and models, spatial patterns in ecosystem responses to hydroclimate variability are strongly governed by ecosystem sensitivity rather than climate exposure. Ecosystem sensitivity was highest in simpler models and higher than observations, suggesting that interactions among biodiversity, demography, and ecophysiology processes dampen the sensitivity of forest composition and biomass to climate variability and change. By integrating ecosystem models with observations from timescales extending beyond the instrumental record, we can better understand and forecast the mechanisms regulating forest sensitivity to climate variability in a complex and changing world.

1. Species are not genetically homogeneous, as the genetic structure among populations is related to the degree of isolation amongst them, such as isolation-by-distance, isolation-by-barrier and isolation-by-environment. 2. To decipher the isolation processes that drive population structuring in Jenynsia lineata we analyzed 221 sequences of the mitochondrial cytochrome c oxidase I gene (COI), which came from 19 localities. Jenynsia lineata is a small viviparous fish that inhabits a wide range of habitats in South America. Then, we examined the influence of the three most common types of isolation to explain the genetic variation found in this species. 3. Our results revealed a marked structuration, with three groups: i) La Plata/Desaguadero Rivers (sampling sites across Argentina, Uruguay, and Southern Brazil), ii) Central Argentina, and iii) Northern Argentina. A distance-based redundancy analysis including the explanatory variables geographical distances, altitude, latitude, basin, was able to explain up to 65% of the genetic structure. A variance partitioning analysis showed that the two most important variables underlying the structuration in J. lineata were altitude (isolation-by-environment) and type of basin (isolation-by-barrier). 4. Our results show that in this species, the processes of population diversification are complex and are not limited to a single mechanism. Population-structuring may lead to population reproductive isolation and ultimately to speciation. 5. This study demonstrated that the process of diversification of populations is complex and is not limited to a single mechanism. The processes that play a prominent role in this study could explain the high rate of diversity that characterizes freshwater fish species. And these processes in turn are the basis for possible speciation events.

The paper deals with the problem of ultra-light and light aircraft structural health monitoring. The phenomenological basis and engineering decisions for methods to monitor accumulated fatigue damage and to register overstress of aircraft principal structural elements have been shown. The proposed fatigue indicator is lightweight and autonomous; the output information of the indicator reflects the inhering feature of the fatigue damage – appearance and growth of surface extrusions and intrusions. The overstress indicator simplicity and correctness of the information is provided by “fuse” principle of the design.

Aims: Catheter ablation (CA) for atrial fibrillation (AF) has a considerable risk of procedural complications. Major vascular complications (MVCs) appear to be the most frequent. This study investigated gender differences in MVCs in patients undergoing CA for AF. Methods: A total of 4734 CAs for AF (65% paroxysmal, 26% repeated procedures) were performed at our center between January 2006 and August 2018. Patients (71% males) aged 60 ± 10 years and had body mass index of 29 ± 4 kg/m2. Radiofrequency point-by-point ablation was employed in 96.3% procedures with the use of 3D navigation systems and facilitated by intracardiac echocardiography. Pulmonary vein isolation was mandatory; cavotricuspid isthmus and left atrial substrate ablation were performed in 22% and 38% procedures, respectively. MVCs were defined as those that resulted in permanent injury, required intervention, or prolonged hospitalization. Their rates and risk factors were compared between genders. Results: A total of 112 (2.4%) MVCs were detected: 54/1512 (3.5%) in females and 58/3222 (1.8%) in males (P < 0.0001). On multivariate analysis, lower body height was the only risk factor for MVCs in females (P = 0.0005). On the contrary, advanced age was associated with MVCs in males (P = 0.006). Conclusion: Females have a higher risk of MVCs following CA for AF compared to males. This difference is driven by lower body size in females. Low body height in females and advanced age in males are independent predictors of MVCs. US-guided venipuncture lowered the MVC rate in males.

Aneurysms of a single aortic sinus are not uncommon and it may also involve dilation of the ascending aorta as well. The dilated aortic sinus usually alters the geometry of the aortic root and patients will present more often with an aortic insufficiency. Both ruptured and non-ruptured sinus of valsalva aneurysm (SOVA) can be complicated by aortic regurgitation, occurring in up to 30% to 50% of patients [1]. Unruptured SOVA are asymptomatic, but can present as dyspnea, palpitations, angina or arrhythmia. The treatment options for unruptured SOVA include aortic root reconstruction or replacement, aortic valve repair or replacement, Bentall procedure or patch repair of the SOVA.Aortic valve resuspension is a widely practised in repair for acute Type A aortic dissection. This procedure was first described by Walter G Wolfe from the Duke University, Durham. In his original series, 24 of the 30 patients with acute aortic dissection had resuspension of the aortic valve. Further “a woven Dacron® graft was then sutured beginning at the junction of the left and right coronary cusps. The graft was fashioned and sutured above the left coronary orifice around and down to the commissure of the left and non-coronary cusps. The graft suture line was then extended along the non-coronary cusp and then around the right coronary artery completing the suture line ”[2]. Three years later, in his updated case series he added, “the proplapsing portion of the aortic valve (usually the non-coronary cusp) was resuspended with pledgeted sutures in order to restore competency of the valve ”. It worth noting that he described a surgical procedure wherein, the aortic valve was resuspensed and supracoronray aorta was replaced.In the recently published article [4], the authors have successfully performed a “Wolfe Procedure” in a 78 year old female and followed up the patient for 2 years. Though authors have conscientiously extricated the option of root repair or replacement, it still raises a few concerns about the procedure which they have performed. The authors mention of a “predominant expansion of the non-coronary sinus and thinning of the wall at the level of FC 22 mm and SV 76, 7x62 mm, ST-zone 38 mm”. Though not sure of the abbreviations, Figure 1 shows an enlarged non-coronary aortic sinus. Dilated aortic sinus / annulus will distort the aortic root leading to aortic insufficiency. It is surprising that the authors have not mentioned about the status of the aortic valve and is highly inconceivable that the patient will not be having any aortic valve insufficieny for such a large aneurysm. The status of Aortic root aneurysm was detected in preoperative echocardiogram, while the status of the aortic valve was noted intraoperatively - “aortic valve leaflets did not close due to the expansion of the non-coronary sinus” . Though they have not mentioned about the aortic valve while presenting the case report, but when opening the discussion, they mention that the, “case report describes the treatment of an aortic root aneurysm by the replacement of the aortic valve together with the placement of an interposition graft with proximal scallop to recreate the non-coronary sinus (i.e., Wolfe procedure)” . It is not clear whether the authors have replaced the aortic valve in their patient or they describe in general. In either of the situations, the procedure describe by Wolfe does not mandate replacement of aortic valve; it is rather a resuspension of the valve.They have argued that the Euroscore II of 19.39% is high in regards to “patient’s age, female sex, the center’s estimated surgical volume, and the present comorbidities ”. It has to be noted that ‘Center’s surgical volume’ is not a variable in Euroscore II. It should be further emphasised, that the authors have not any mentioned any comorbidities of the patients including the left ventricular function while presenting the case. Earlier studies have reported the overestimation of surgical risk in septuagenarians and octogenarians by Euroscore II [5,6,7]. It is a well-known fact that the coronary artery of elderly patients has to be evaluated before any open heart surgery; more so when have symptoms of angina. Though the authors mention that the elderly lady had coronary heart disease with class III angina pectoris, there is no description of the native coronary arteries in the manuscript. Atrial fibrillation or arrythimas are well known presentation symptom for patients with SOVA. This may be due to compression of the coronary arteries or any chamber(s) of the heart. A preoperative CT aortagram could have added value in this regard which the authors have not provided. It is mentioned that there is “dilation of the ascending, arch, and descending aorta” preoperatively. After the procedure the size of the aortic arch is 28 mm. It is so intriguing to know the mechanism of decrease in aortic arch size postoperatively after the so called “Wolfe Procedure”. As an aortic surgeon it is curious to note the ‘plunger-top’ of a syringe buried inside the vascular graft in Figure 3. Not sure why and how it was buried, but it would be of great value, if the authors could describe the technique of using the same in detail in a separate manuscript.

Wide complex tachycardia with changing QRS-axis on loop recorderShort title: QRS-axis changes on loop recorder

Editorial: Long-term respiratory complications of OA-TOF: The need for better data and a more specialised multidisciplinary approach

The inverse problems of determining the energy-temperature relation α(t) and the heat conduction relation k(t) functions in the one-dimensional integro– differential heat equation are investigated. The direct problem is the initial-boundary problem for this equation. The integral terms have the time convolution form of unknown kernels and direct problem solution. As additional information for solving inverse problems, the solution of the direct problem for x = x₀ is given. At the beginning an auxiliary problem, which is equivalent to the original problem is introduced. Then the auxiliary problem is reduced to an equivalent closed system of Volterra-type integral equations with respect to unknown functions. Applying the method of contraction mappings to this system in the continuous class of functions with weighted norms, we prove the main result of the article, which is a global existence and uniqueness theorem of inverse problem solutions.

Abstract Background: Evidence showed that the sensation of nasal breathing is related to variations in nasal mucosa temperature produced by airflow. An appropriate nasal airflow is necessary for changing mucosal temperature. Therefore, the correlation between objective measurements of nasal airflow and patient-reported evaluation of nasal breathing should be dependent on the level of nasal airflow. Objectives: To find if the correlation between patient-reported assessment of nasal breathing and objective measurement of nasal airflow is dependent on the severity of symptoms of nasal obstruction or on the level of nasal airflow. Methods: The airway of 79 patients was evaluated using NOSE score and peak nasal inspiratory flow (PNIF). Three subgroups were created based on NOSE and three subgroups were created based on PNIF level to find if correlation was dependent on nasal symptoms or airflow. Results: The mean value of PNIF for the 79 patients was 92.6 l/min (SD 28.1 l/min). The mean NOSE score was 48.4 (SD 24.4). The correlation between PNIF and NOSE was statistically significant (p=0.03), but with a weak association between the two variables (r=-0.248). Evaluation of correlation based on symptoms demonstrated a weak or very weak association in each subgroup (r=-0.250, r=-0.007, r=-0.104). Evaluation of correlation based on nasal airflow demonstrated a very weak association for the subgroups with middle-level and high PNIF values (r=-0.190, r=-0.014), but a moderate association for the subgroup with low PNIF values (r=-0.404). Conclusions: This study demonstrated a weak correlation between NOSE scores and PNIF values in patients non-selected according to symptoms of nasal obstruction or to airflow. It demonstrated that patients with symptoms of nasal obstruction have different levels of nasal airflow and that low nasal airflow prevents the sensation of good nasal breathing. Therefore, patients with symptoms of nasal obstruction may require improving nasal airflow to improve nasal breathing sensation.

Invasive pathogens can be a threat when they affect human health, food production or ecosystem services, by displacing resident species, and we need to understand the cause of their establishment. We studied the patterns and causes of the establishment of the pathogen Dickeya solani that recently invaded potato agrosystems in Europe by assessing its invasion dynamics and its competitive ability against the closely-related resident D. dianthicola species. Epidemiological records over one decade in France revealed the establishment of D. solani and the maintenance of the resident D. dianthicola in potato fields exhibiting blackleg symptoms. Using experimentations, we showed that D. dianthicola caused a higher symptom incidence on aerial parts of potato plants than D. solani, while D. solani was more aggressive on tubers (i.e. with more severe symptoms). In co-infection assays, D. dianthicola outcompeted D. solani in aerial parts, while the two species co-existed in tubers. A comparison of 76 D. solani genomes (56 of which having been sequenced here) revealed balanced frequencies of two previously uncharacterized alleles, VfmBPro and VfmBSer, at the vfmB virulence gene. Experimental inoculations showed that the VfmBSer population was more aggressive on tubers while the VfmBPro population outcompeted the VfmBSer population in stem lesions, suggesting an important role of the vfmB virulence gene in the ecology of the pathogens. This study thus brings novel insights allowing a better understanding of the pattern and causes of the D.solani invasion into potato production agrosystems, and the reasons why the endemic D.dianthicola nevertheless persisted.

Wind erosion is the main form of soil erosion in arid and semi-arid areas. It leads to soil loss and land degradation, which aggravates ecosystem vulnerability and threatens regional sustainable development. The assessment of wind erosion and the study of its driving factors can reduce soil wind erosion and provide decision-making assistance to solve environmental problems. Southern Africa is affected by severe soil erosion, which has brought a series of development problems, such as food crises and poverty. This study used meteorological and remote sensing data, and the revised wind erosion equation model to explore the temporal and spatial dynamics of soil erosion in southern Africa from 1991 to 2015. The impact of climate dynamics on soil wind erosion was also analyzed. The results showed that wind erosion fluctuated during the study period, and it first showed a downward trend and then stabilized at a relatively low level after 2010. Soil wind erosion across 66.65% of the study area significantly decreased (p < 0.05) and near-surface wind speed was the most important factor. The change in wind speed had a positive impact on soil wind erosion across 68.18% of the area. Temperature and precipitation were significantly related to soil wind erosion over 18.96% and 24.63% of the area, respectively. Both can also indirectly affect soil wind erosion through their effects on vegetation cover. This study will help decision-makers to evaluate areas that are at high-risk from soil erosion in southern Africa and enable them to effectively protect fragile ecosystems.

Von Willebrand disease (VWD), the most prevalent congenital bleeding disorder, arises from a deficiency in von Willebrand factor (VWF), which has crucial roles in hemostasis. The present study investigated functional consequences and underlying pathomolecular mechanisms of several VWF propeptide (VWFpp) variants detected in our cohort of VWD patients for the first time. Transient expression experiments in HEK293T cells demonstrated that four out of the six investigated variants (p.Gly55Glu, p.Val86Glu, p.Trp191Arg, and p.Cys608Trp) severely impaired secretion. Their co-transfections with the wt partly corrected VWF secretion, displaying loss of large/intermediate multimers. Immunostaining of the transfected HEK293 cells illustrated the retention of the VWF variants in the endoplasmic reticulum (ER). Docking of the COP I and COP II cargo recruitment proteins, ADP-ribosylation factor 1 and Sec24, onto the N-terminal VWF model (D1D2D´D3) revealed that these variants occur at VWFpp putative interfaces, which can hinder VWF loading at the ER exit quality control. Furthermore, quantitative and automated morphometric exploration of the 3-dimensional immunofluorescence images showed changes in the number/size of the VWF storage organelles, Weibel-Palade body (WPB)-like vesicles. The result of this study highlighted the significance of the VWFpp variants on anterograde ER-Golgi trafficking of VWF as well as the biogenesis of WPB-like vesicles.

Tissue damage associated with trauma might release a sufficient autoantigen substrate to break immune tolerance. In a previous study, we showed that the leukopenia observed following severe inflammation is related to adenosine A1-receptor (A1R) desensitization and A2AR upregulation. We hypothesized that, under destructive pathological conditions this mechanism is beneficial in reducing prevalence of autoimmunity. In this study, we aim to evaluate the protective role of A1R and A2AR in prevention of autoimmune diseases. We used two murine models of autoimmune diseases: type 1 diabetes (T1D) induced by low-dose streptozotocin and pristane-induced lupus (PIL) and on neutrophils we studied NETosis regulation by adenosine. In both the T1D and PIL models, A1R-KO mice were predisposed to the development of autoimmunity. In the PIL model, in WT mice, parallel to the decline of A1R mRNA levels, lymphocytes number dropped (-85%) 6h after pristane injection. WT mice remained without any sign of disease at 36 weeks. In contrast, following pristane 43% of A1R-KO mice suffered from lupus-like disease. Compared to A1R-KO, in WT mice at 10 days A2AR mRNA levels were significantly higher. Similar to PIL, in T1D model the presence of A1R and A2AR was protective. In addition, we found that A1R increases and A2AR suppresses NETosis. We suggest that adenosine-dependent immune suppression and reduction in neutrophil extracellular traps (NETs) limits the reactive T-cells and development of anti-double strand DNA (dsDNA) antibodies that promote autoimmunity.

Population size is a central parameter for conservation, however monitoring abundance is often problematic for threatened marine species. Despite substantial investment in research, many marine species remain data-poor resulting in uncertain population forecasts and restricting the evaluation of past and present conservation actions. Such is the case for the white shark (Carcharodon carcharias), a highly mobile apex predator for whom population monitoring is a conservation priority following substantial declines recorded through the 20th century. Here, we estimate the effective number of breeders that successfully contribute offspring in one reproductive cycle (Nb) providing a snapshot of recent reproductive effort in an east-Australian New Zealand population of white shark. Nb was estimated over four consecutive age cohorts (2010, 2011, 2012, 2013) using two genetic estimators (linkage-disequilibrium; LD and sibship assignment; SA) based on genetic data derived from two types of genetic markers (single-nucleotide-polymorphisms; SNPs and microsatellite loci). While estimates of Nb using different marker types produced comparable estimates, microsatellite loci were the least precise. The LD and SA estimates of Nb within cohorts using SNPs were comparable, for example the 2013 age-cohort Nb(SA) was 289 (95%CI 200-461) and Nb(LD) was 208.5 (95%CI 116.4-712.7). We show that over the time period studied Nb was stable and ranged between 206.1(±45.9) and 252.0(±46.7) per year using a combined estimate of Nb(SA+LD) from SNP loci, and a simulation approach showed that in this population effective population size (Ne) per generation can be expected to be larger than Nb per reproductive cycle. This study demonstrates how breeding population size can be monitored over time to provide insight into the effectiveness of recovery and conservation measures for the white shark, where the methods described here may be applicable to other data-poor species of conservation concern.

This paper is devoted to the study of a nonlinear pseudoparabolic equation in an annular with Robin-Dirichlet conditions. At first, by applying the standard Faedo-Galerkin method, we prove existence and uniqueness results. Next, using concavity method, we prove blow-up results for solutions when the initial energy is nonnegative or negative, then we also establish the lifespan for the equation via finding the upper bound and the lower bound for the blow-up times. Finally, we give a sufficient condition for the global existence and decay of weak solutions.

Objectives: To explore the safety and efficacy of total thoracoscopic repair of ventricular septal defects (VSD). We compared clinical outcomes of VSD via a total thoracoscopic approach with those of mini-sternotomy. Methods: We retrospectively reviewed clinical data from patients with VSD from 2012 to January 2019. According to the surgical pattern, they were divided into two groups: the total thoracoscopic surgery group (36 patients, 27 females, aged 29.08 ± 9.52 years), and a mini-sternotomy group (31 patients, 12 females, aged 28.39 ± 8.67 years). Results: There were no deaths in either group. In the thoracoscopic group, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were significantly longer than those of the mini-sternotomy group (CPB time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001; ACC time: 111.78 ± 23.16 min vs 77.58 ± 37.90 min, respectively, p < 0.001). Tracheal intubation time (6.42 ± 3.85 hours vs 28.55 ± 123.18 hours, p = 0.325), intensive care unit (ICU) stay time (20.47 ± 9.52 hours vs 49.65 ± 163.72 hours, p = 0.330), postoperative hospital stay time (5.11 ± 2.48 days vs 5.90 ± 6.27 days, p = 0.488) and chest drainage (139.86 ± 111.71 ml vs 196.13 ± 147.34 ml, p = 0.081) tended to be lower in the thoracoscopy group, although there was no significant difference. No residual shunt or tricuspid regurgitation was found at follow-up. Conclusions: Total thoracoscopic repair is safe and effective in patients with VSD, with or without tricuspid regurgitation.