Background: We hypothesized that the post-operative aorto-mitral angle might relate to the occurrence of post-operative atrial arrhythmia (AA), including atrial fibrillation and atrial tachycardia, after mitral valve repair in patients with mitral regurgitation (MR). The purpose of the present study was to determine the effects of the post-operative aorto-mitral angle on new onset AA after mitral valve repair with mitral annuloplasty for treating MR. Methods: One-hundred seventy-two patients without any history of AA underwent mitral valve repair with mitral annuloplasty in our institution between 2008 and 2017. Patient information, including medical records and echocardiographic data, were retrospectively studied. Results: AA occurred in 15 (8.7%) patients during the follow-up period (median, 35.7 months; range, 0.5-132 months). The patients with AA had a longer cardiopulmonary bypass time and a smaller aorto-mitral angle at post-operative TTE than the others (119 ± 6 degrees vs. 125 ± 10 degrees, P = 0.003). There was no significant difference in the degree of post-operative residual MR or functional MS between the groups. In a multivariate Cox proportional hazards analysis, the longer cardiopulmonary bypass time and the smaller post-operative aorto-mitral angle were independent predictors of the occurrence of AA during the follow-up period (odds ratio per 10 minutes 1.11; 95% CI 1.02-1.22, P = 0.019: odds ratio 0.91; 95% CI 0.85-0.98, P = 0.012). Conclusion: A small aorto-mitral angle at post-operative TTE was a predictor of new onset AA after a mitral valve repair for treating MR.

Severe hemophilia symptoms usually start in infancy. Affected individuals require coagulation factor routinely to live a normal life. A 25-year old active-duty soldier was diagnosed with severe congenital hemophilia A after presenting with initial episode of prolonged bleeding. His case demonstrates a rare late presentation of hemophilia.

Porcine Sapovirus (SaV) was first identified by electron microscopy in the United States in 1980 and has since been reported from both asymptomatic and diarrheic pigs usually in mixed infection with other enteric pathogens. SaV as the sole etiological agent of diarrhea in naturally infected pigs has not previously been reported in the United States. Here, we used four independent lines of evidence including metagenomics analysis, real-time RT-PCR (rRT-PCR), histopathology, and in situ hybridization to confirm porcine SaV genogroup III (GIII) as the sole cause of enteritis and diarrhea in pigs. A highly sensitive and specific rRT-PCR was established to detect porcine SaV GIII. Examination of 184 fecal samples from the outbreak farm showed that pigs with clinical diarrhea had significantly lower Ct values (15.9 ± 0.59) compared to clinically unaffected pigs (35.8 ± 0.71). Further survey of 336 fecal samples from different states in the United States demonstrated that samples from pigs with clinical diarrhea had a comparable positive rate (45.3%) with those from non-clinical pigs (43.1%). However, the SaV-positive pigs with clinical diarrhea had significantly higher viral loads (Ct = 26.0 ± 0.5) than those positive but clinically healthy pigs (Ct = 33.2 ± 0.9). Phylogenetic analysis of 20 field SaVs revealed that all belonged to SaV GIII and recombination analysis indicated that intra-genogroup recombination occurred within the field isolates of SaV GIII. These results suggest that porcine SaV GIII plays an important etiologic role in swine enteritis and diarrhea and rRT-PCR is a reliable method to detect porcine SaV. Our findings provide significant insights to better understand the epidemiology and pathogenicity of porcine SaV.

With flooding being one of the numerous challenges that ecosystems face throughout the world, plants are therefore obliged to adopt plastic responses in order to cope with this environmental constraint. When flooded, the tomato hypocotyl undergoes profound changes that entail rearrangements in its physiology and metabolism. In this work, we observed that, although soil flooding markedly dampens root respiration, the submerged hypocotyl surprisingly enhances oxygen consumption in spite of hypoxic conditions. Several pieces of evidence indicate that the respiratory pathway is indeed promoted in submerged stems. Besides, underwater hypocotyls are shown to accumulate sugars. Girdling and feeding experiments revealed that leaf-derived sucrose is metabolized and channelled to maintain respiration in underwater hypocotyls. Our data suggest that high respiration is required for sucrose unloading from phloem, since inhibition of hypocotyls respiration significantly prevents sugar build-up. As substrate availability increases, respiration is fuelled even more, leading to a sustained allocation of sugars to flooded hypocotyls.

Klebsiella pneumoniae can cause community-acquired and hospital-acquired infection. It increases morbidity and mortality in high-risk patients. We present a case of invasive Klebsiella pneumoniae in poorly controlled diabetes mellitus, who ended up having a metastatic spread of Klebsiella pneumoniae involving the liver, lungs, kidneys, brain, and muscle.

We are reporting a case of breast tuberculosis (BT) that was initially misdiagnosed as a breast abscess. Fine needle aspiration cytology (FNAC) helped in diagnosing BT faster by avoiding different invasive diagnostic methods. FNAC can be used as the primary diagnostic method of choice for the diagnosis of BT.

Climate change in terms of regional warming and modifications in precipitation regimes has large impacts on streamflow in regions where both rainfall and snowmelt are important runoff generating processes like in Norway. Hydrological impacts of recent changes in climate are usually investigated by trend analyses applied on annual, seasonal, or monthly time series. However, neither of them can detect sub-seasonal changes and their underlying causes. Based on high-resolution trend analyses (i.e., applying the Mann-Kendall test on 10-day-moving-averaged daily time series), this study investigated sub-seasonal changes in daily streamflow, rainfall, and snowmelt in 61 and 51 catchments in Western vs. Eastern Norway (Vestlandet vs. Østlandet), respectively, over the period 1983-2012. The relative contribution of rainfall vs. snowmelt to daily streamflow and the changes therein have also been estimated to identify the changing relevance of these driving processes over the same period. Detected changes in daily streamflow were finally attributed to changes in the most important hydro-meteorological drivers using multiple-regression models with increasing complexity. Results reveal a coherent picture of earlier spring flow timing in both regions due to earlier snowmelt. Other streamflow trend patterns differ between both regions: Østlandet shows increased summer streamflow in catchments up to ~1100 m a.s.l. and slightly increased winter streamflow in about 50 % of the catchments, while trend patterns in Vestlandet are less coherent. The importance of rainfall for streamflow contribution has increased in both regions, and the trend attribution reveals that changes in rainfall and snowmelt can explain streamflow changes to some degree in periods and regions where they are dominant (snowmelt: spring and Østlandet; rainfall: autumn and Vestlandet). However, detected streamflow changes can be best explained by adding temperature as an additional predictor which indicates the relevance of additional driving processes for streamflow changes like increased glacier melt and evapotranspiration.

This study investigated the influence of data extension on the decomposition and prediction accuracy of runoff data series. To this end, an original data series was constructed using annual runoff data from a hydrological station in China (Tang Naihai) for the period 1956–2013, and radial basis function neural network (RBFNN) extension was applied to the original data series. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) was then applied to both data series, and their decomposition and prediction results were compared. The decomposition results indicate that the end effect significantly lowers the accuracy of low–middle frequency components. Nevertheless, the end effect could be effectively suppressed and decomposition error could be reduced by applying RBFNN extension. At the end points, the extension data series could more accurately reflect the real fluctuation characteristics of components and subsequent variation trends. Regarding component prediction, the prediction results followed the variation trend of the components themselves, with a rather large gap in the prediction results of low-frequency components between the two groups of data series. The final prediction results obtained from the reconstruction of the component prediction results suggest that the extension sequence has a clearly superior prediction accuracy than the original data series. Hence, when using the CEEMDAN method to process non-stationary hydrological data, multi-time-scale information of the data series can be obtained through reasonable extension after decomposition of the original data series. The acquired information provides evidence for the analysis and prediction of the evolution law of hydrological elements.

This talk explores roles for postdoctoral STEM researchers in the publishing industry. By sharing my experience I hope to enable a broader understanding of the different roles inside the editorial office of academic journals and the skills required for editorial positions posted by commercial and society publishers.

A document by Smaranika Panda. Click on the document to view its contents.

Background: Arterial puncture, for obtaining an analysis of blood gas, is an interventional procedure often performed in emergency departments and intensive care units. Our goal in this study is to compare the traditional method and ultrasound (US) guided method in radial artery puncture for blood gas analysis in septic shock patients. Methods: This is a prospective, randomized study. Septic shock patients over 18 years of age who needed a radial artery puncture sample for blood gas analysis were included in the study. Patients with local infection or trauma at the puncture site, arteriovenous fistula, vascular graft, coagulopathy, Allen test positive and those who did not want to participate in the study were excluded. Patients were randomized into 2 groups: radial arterial puncture obtained through an US guided technique or radial arterial puncture by conventional method. The main outcomes are success at the first entry, the number of attempts and time to success after enrollment. Results: 50 eligible patients were randomized into two groups. The success rate of the first puncture in the ultrasound group and the palpation group was 80% and 42%, respectively. The number of attempts and time to success significantly increased in conventional group. Conclusion: The US-guided method has been found to be more successful in terms of success at the first entry, number of attempts, time to success compared to the conventional method.

Background: Rural communities who consume unpasteurized and traditional fermented milk products on a regular basis, have a low prevalence of allergic diseases. Lactic acid producing bacteria present within these products, is postulated to have an allergy protective role against atopy. Objective: To characterize and compare the bacterial microbiota of fresh unpasteurised cow’s milk and to explore the effect of milk fermentation (commercially and traditionally fermented) on the bovine milk microbiota. Methods: Raw, unpasteurized cow’s milk was collected from urban and rural farms. Another sample, collected from a rural farm, was left to ferment naturally. Three different brands of commercially fermented milk samples were also analysed. The V3 and V4 regions of the 16S rRNA gene were amplified to assess microbiota composition. Results: Urban and rural fresh milk had the highest microbiota alpha diversity, and commercially bought fermented milk products, the least. Commercially fermented milk was consistently dominated by lactic acid producing bacteria, belonging to the phylum Firmicutes, while homemade fermented milk comprised of approximately 50% Firmicutes and 50% Proteobacteria. The relative abundance of several organisms differed between fermented and unfermented milk. Lactococcus lactis dominated all milk products, however its relative abundance was lower in fresh milk compared with fermented milk. Lactobacillus paracasei and Streptococcus infantis were abundant in traditionally fermented milk, but absent in commercially fermented products. Potential pathogens were demonstrated in fresh and home fermented milk. Conclusion: Commercially fermented milk can be promoted as a safe and possible allergy protective complementary feed from 1 year of age.

Etoposide is an antineoplastic agent widely used for treatment of many pediatric cancers and associated with infusion related adverse drug reactions (ADRs). In this brief report we describe etoposide infusion related ADRs that occurred over a 10-year period at two freestanding pediatric hospitals. Infusion reactions occurred in 1% of patients. Of the 32 patients that experienced adverse reactions, 41% were rechallenged after the reaction and all were able to tolerate at least one future dose with either pre-treatment or extending infusion duration.

In this paper, a stochastic phytoplankton-toxic phytoplankton-zooplankton system with Beddington-DeAngelis functional response, where both the white noise and regime switching are taken into account, is studied analytically and numerically. The aim of this research is to study the combined effects of the white noise, regime switching and toxin-producing phytoplankton (TPP) on the dynamics of the system. Firstly, the existence and uniqueness of global positive solution of the system is investigated. Then some sufficient conditions for the extinction, persistence in the mean and the existence of a unique ergidoc stationary distribution of the system are derived. Significantly, some numerical simulations are carried to verify our analytical results, and show that high intensity of white noise is harmful to the survival of plankton populations, but regime switching can balance the different survival states of plankton populations and decrease the risk of extinction. Additionally, it is found that an increase in the toxin liberation rate produced by TPP will increase the survival change of phytoplankton, while it will reduce the biomass of zooplankton. All these results may provide some insightful understanding on the dynamics of phytoplankton-zooplankton system in randomly disturbed aquatic environments.

Emerging data shows pregnant women with COVID-19 are at significantly higher risk of severe outcomes compared to non-pregnant women of similar age. This review discusses the invaluable insight revealed from vaccine clinical trials in women who were vaccinated and inadvertently became pregnant during the trial period. It further explores a number of clinical avenues in their management and proposes a drug development strategy in-line with clinical trials for vaccines and drug treatments for the drug development community. Little is known of the long-term effects of COVID-19 on the mother and the baby. We provide a rationale for our hypothesis that COVID-19 predisposes pregnant women to cardiovascular diseases later in life, in a similar way, to preeclampsia and may increase the risk of preeclampsia in their subsequent pregnancy. This is an ever-evolving landscape and early knowledge for healthcare providers and drug innovators is offered to ensure benefits outweigh the risks.

We present two patients with history of recurrent respiratory infections, fatigue and sweating. They were diagnosed with absence of connection between the main pulmonary artery (MPA) and right pulmonary artery (RPA) and bilateral ductus arteriosus, with the RPA originating from the ductus arteriosus. Treatment was approached with a hybrid strategy: percutaneous intraluminal angioplasty with a right intraductal stent and device closure of the left ductus arteriosus and followed by surgical reconstruction with interposition of a graft from RPA to MPA. Both patients had a favorable outcome.

At a time where delivering the best quality of care is the raison d’être of the health service, outliers can pose a serious challenge to both clinicians and policy makers. Methods of outlier detection are highly variable. The collection and assimilation of outcome variables can also be very challenging. Despite this, the publication of surgeon specific data has brought the concept of outliers into the public eye and the consequent punitive action affected upon surgeons can be deleterious to clinician psychology and patient perception. Simultaneously, positive outliers are rarely mentioned and never rewarded. Moving forward, the use of more objective outcomes, including novel biomarkers and patient-centred data, as well as innovative statistical strategies and management cultures, can positively evolve the healthcare paradigm for the future.

Background: Surgical aortic valve replacement (SAVR) carries the known risk of shedding debris into the left ventricle during valve leaflet excision and annulus debridement. Embolization of this debris may have devastating effects for the patient. While surgeons have developed methods to mitigate this risk, no data exists as to their efficacy. Herein, we present the first study that evaluates the efficacy of a technique for capturing debris during SAVR. Methods: Our group conducted a prospective case series of 20 patients who underwent SAVR using the insertion of an intraventricular surgical sponge prior to valve leaflet excision and annulus debridement to capture debris. Surgical sponges were grossly, radiographically, and histologically examined for the presence of cellular and acellular debris to determine the efficacy of this technique. Results: Of the 20 surgical sponges analyzed, 15 (75%) specimens registered positivity for cellular and/or acellular debris. 7 (35%) sponges were grossly positive, 15 (75%) were radiographically positive, and 4 (20%) were histologically positive for calcified debris on examination. Conclusions: This represents the first study that objectively evaluates a method used to capture debris in SAVR procedures. Our results demonstrate a high frequency of debris captured within intraventricular surgical sponges and confirms the efficacy of this technique. While this data is promising, numerous additional approaches exist to capture debris and a best practice standard should exist across the specialty. In addition, this study does not address the clinical outcomes associated with this technique. To these ends, additional data and multicenter collaboration is required.

Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity may act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association. The first case entailed a 14-year-old girl with hemoglobin SC (HbSC) disease who developed hepatic sequestration crisis that responded to a simple transfusion of erythrocytes. The second case was that of a 16-year-old boy with HbSC disease who experienced life-threatening intrahepatic cholestasis with multi-organ failure.

Dear Editor,CD4+ T helper 2 (Th2) cells play a key role in progression of allergic rhinitis (AR). Traditionally T-cells acquire the characteristics of Th2 cells in the presence of IL-4, a process that may be influenced by engagement of co-stimulatory factors expressed by antigen-presenting cells1. Notch is a co-stimulatory pathway for CD4+ T-cells, and the importance of Notch for generation of Th2 cells and the development of allergic rhinitis has been suggested in animal studies2,3. However, its potential role in the advancement of allergy in humans remains unknown. Our group has previously demonstrated that neutrophils and nasal epithelial cells promote allergic mucosal inflammation by interacting with T-cells. Based on these findings, we hypothesized that neutrophils and epithelial cells in allergic nasal mucosa induce Notch signaling in CD4+ T-cells, promoting allergic inflammation. The present study analyzed Notch ligand expression on primary nasal epithelial cells and neutrophils along with Notch receptor expression on CD4+ T-cells in patients with pollen-induced AR off season and compared with healthy control (HC). In the appendix of this article information regarding patient characteristics and methods is supplemented.Expression of Notch1-4 on T-cells was assessed by FACS. The fraction of CD4+ T-cells expressing Notch1,4 in mucosa was significantly higher in AR compared to HC (Fig 1B). No differences in Notch expression were detected in blood derived CD4+T-cells (Fig 1A). In animal models of allergic rhinitis, JAG1-Notch1,4 signaling has been demonstrated to polarize T-cell responses towards Th2, promoting an allergic inflammation3,4. Against the backdrop of our findings in CD4+ T-cells, it is tempting to suggest that the increase in Notch1,4 in allergic mucosa might be a sign of increased Th2 cell polarization and that Notch signaling maintain TH2 inflammation and consequently AR progression. In the present study no difference in the expression of Notch was detected on CD4+ T-cells in peripheral blood. However, this study was performed outside the pollen season, and it cannot be excluded that a similar signal can also be seen in the blood in patients with pollen induced symptoms. Further the expression of JAG1, JAG-2, DLL-1, and DLL-4 was also assessed with FACS. The fraction of epithelial cells expressing JAG-1 and DLL-1 was significantly elevated in AR compared to HC. (Fig 2A). The increased expression of JAG-1 and DLL-1 among patients with AR could be further corroborated by analyzing median fluorescence intensity (MFI) (Fig 2B,C). Although significant, the expression levels of DLL-1 on the surface of epithelial cells were notably lower than the corresponding expression levels of JAG-1. (Fig 2B,C). There are conflicting theories regarding in what way Notch signaling regulates T-cell functions. However, there are evidence for an instructive model where JAG-Notch1,2 interaction initiates Th2 cell differentiation, and DLL-Notch3 promotes T helper 1 (Th1) cell differentiation5. Our result illustrates a JAG-1>>DLL signaling gradient by epithelial cells supporting a Th2 outcome (Fig 2B,C). Further, the fraction of neutrophils expressing JAG-1 was significantly increased in AR compared to HC, in samples derived from mucosa and blood (Fig 2D,G). In addition, the expression levels of JAG-1 as measured by MFI, were significantly increased on neutrophils from AR compared to neutrophil from HC, in samples derived from mucosa and blood (Fig 2E,F and H,I).Together with our previous report of antigen-presenting epithelial cells, our data suggest that the increased expression of JAG-1 in epithelial cells in allergic mucosa induce a sustained Th2 polarization of Notch1 and Notch 4 expressing T-cells. In analogy, neutrophils have also been shown to present antigens to T-cells6. Hence, it might be that neutrophils in AR mucosa present antigen to T-cells promoting a Th2 polarization in CD4+ T-cells by increased expression of JAG-1.Wk 600Increased expression of jagged-1, Notch-1 and Notch-4 in nasal mucosa of patients with allergic rhinitisEric Hjalmarsson1, Marianne Petro1, Susanna Kumlien Georén1, Ola Winqvist2, Lars Olaf Cardell1,31. Division of ENT Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden2. ABClabs, Biomedicum, Stockholm Sweden3. Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, SwedenCorresponding author:Professor Lars Olaf CardellDivision of ENT Diseases, Department of Clinical Science Intervention and Technology, Karolinska Insitutet, Stockholm, SwedenPhone: +46 (0) 8 585 814 53E-mail: lars-olaf.cardell@ki.se

This paper describes a microstructure-based multiaxial non-proportional fatigue life prediction model with maximum shear strain and non-proportionality as damage parameters applied to A319 alloy. The materials made with different casting cooling rates and Sr modification are characterized and quantified in terms of secondary dendrite arm spacing (SDAS), size and aspect ratio of eutectic Si particles. Multiaxial non-proportional fatigue tests have been performed on six groups of A319 alloys to systematically analyze the effect of microstructure and loading path on the fatigue properties of Al-Si cast alloy. The first part of the paper is focused on microstructure quantitative characterization to determine the influence of different casting conditions, followed by stress response behavior and fatigue fracture analysis. Finally, quantitative relationship between six fatigue life parameters and microstructure characteristics is established and a new fatigue life prediction model is proposed to predict fatigue life of Al-Si alloy under multiaxial non-proportional loading condition.

Harvesting can magnify the destabilizing effects of environmental perturbations on population dynamics and, thereby, increase extinction risk. However, population-dynamic theory predicts that impacts of harvesting depend on the type and strength of density-dependent regulation. Here, we used population models for a range of life histories and an empirical reindeer case study to show that harvesting can actually buffer populations against environmental perturbations. This occurs because of density-dependent environmental stochasticity, where negative environmental impacts on vital rates are amplified at high population density due to intra-specific resource competition. Simulations from our population models show that even low levels of proportional harvesting may prevent overabundance, thereby dampening population fluctuations and reducing the risk of population collapse and quasi-extinction induced by environmental perturbations. Thus, depending on the species' life history and the strength of density-dependent environmental drivers, harvesting can improve population resistance to increased climate variability and extreme weather expected under global warming.

The Africanized honey bee (AHB) is a New World amalgamation of several subspecies of the western honey bee (Apis mellifera), a diverse taxon grouped into four major biogeographic lineages: A (African), M (western European), C (eastern European), and O (Middle Eastern). In 1956, accidental release of experimentally bred “Africanized” hybrids from a research apiary in Sao Paulo, Brazil initiated a hybrid species expansion that now extends from northern Argentina to northern California (U.S.A.). Here, we assess nuclear admixture and mitochondrial ancestry in 15 bees from each of four regions across this expansive range: the Isthmus of Panamá; Guanacaste, Costa Rica, Tapachula, Mexico; and San Diego, U.S.A to assess ancestry of AHB several decades following initial introduction and test the prediction that African ancestry decreases with increasing latitude. We find that AHB nuclear genomes from Central America and Mexico have majority African ancestry (Mexico, 79%; Costa Rica 90%; and Panamá 94%) with varying contributions from western and eastern European lineages. AHB from San Diego (CA) show markedly lower African ancestry (40%) with substantial genomic contributions from all four major honey bee lineages. The mitochondria of all bees sampled in Costa Rica and Panamá originated in Africa. The majority (11) of bees sampled in Mexico carried African mitochondria with the remainder carrying eastern European mitochondria. In the San Diego population, mitochondria from all four lineages are present. Genetic diversity measures from all New World populations are similar and exceed those of ancestral forms. The unique genetic makeup of the San Diego honey bee population makes it a rich source of genetic material for honey bee breeding.

Objectives and Background: Goal of Transvenous Lead Extraction (TLE) is complete removal of all targeted leads, without complications. Despite counter traction manoeuvres, efficacy rates are often hampered by broken right ventricle lead (RV-lead) tips. Mechanically powered lead extraction (Evolution sheath) is effective, however safety of dissection up to the lead tip is unclear. Therefore, we examined the feasibility and safety of RV-lead extraction requiring dissection up to the myocardium. Methods and results: From 2009 to 2018, all TLE in the Isala Heart Centre (Zwolle, The Netherlands) requiring the hand-powered mechanical Evolution system to extract RV-leads (n=185) were examined from a prospective registry. We assessed 2 groups: TLE with the first generation Evolution (n=43) with (A1,n=18) and without (A2,n=25) adhesions up to the myocardium and TLE with the Novel R/L type (n=142) of sheath with (B1,n=59) and without (B2,n=83) adhesions up to the myocardium. Complete success rate in Group B was significantly higher than group A (96.5 vs 76.7%, p=0.0354). When comparing the patients with adhesions up to the myocardium, total complete success is higher in the R/L group (61.1% vs 90.5%, p=0.0067). There were no deaths. Overall major complication rates were low (2/185;1.1%) and there was no statistically significant difference in major and minor complications between the two groups. Conclusion: Extraction strategy with the bidirectional Evolution R/L sheath for right ventricular leads with adhesions up to the myocardium is safe and feasible.