Ceritinib shows efficacy in ALK+ NSCLC patients with BM. However, the disease will inevitably progress over time due to acquired resistance. We now report a case with BM from advanced lung adenocarcinoma with ALK mutations who exhibited a surprising and long-term response to treatment of ceritinib combined with bevacizumab.

Increase of allergic conditions has occurred at the same pace with the Great Accleration, which stands for the rapid growth rate of human activities upon Earth from 1950s. Changes of environment and lifestyle along with escalating urbanization, are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors and biologic medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: risk factors increase the risk while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fastly urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.

Odontogenic cysts are derived from odontogenic epithelium.Which may develop before or after the formation of tooth. Most of these are developmental in origin. While dentigerous cysts are common odontogenic cysts that are related to the crown of the impacted tooth and known to arise from reduced enamel epithelium.Dentigerous cyst is a type of developmental odontogenic cyst and has a rate between 20 %-24% in allthe jaw cyst.Dentigerous cyst arising from primary dentition is very rare.A 5 year-old boy with swelling and pain in the jaw that were evaluated clinically,radiographically and histopathologically it was diagnosed as dentigerous cyst arising from a denticle.

The risk of the novel coronavirus disease 2019 (COVID-19) to pediatric oncology patients is unknown. Here, we report eight pediatric oncology patients receiving active cancer therapy that tested positive for COVID-19. Three developed severe cardiorespiratory symptoms (as defined by evidence of heart failure by echocardiogram and/or intubation secondary to respiratory failure), including one death as a result of COVID-19 infection. We identified prior anthracycline exposure and pre-COVID cardiac function as significantly associated with the development of severe cardiorespiratory complications. These data merit future and further investigation of risk factors for severe complications related to COVID-19 infections in pediatric oncology patients.

NDI is rarely considered versus diabetes mellitus in the situation of polyuria. It is well known that hypokalaemia and hypercalcemia induce NDI through decreased activity of arginine vasopressin and downregulation of Aquaporin-2 water channels in the collecting ducts. However, not much is known whether hypomagnesemia can directly induce NDI.

Coronary artery aneurysms are an uncommon disease whose incidence ranges from 0.3% to 5.3%. The right coronary artery is affected in 40-70% of cases. Percutaneous coronary angioplasty is among causative factors, in particular with stent implantation. We present a case of large post-angioplasty aneurysm of the right coronary artery requiring surgical correction.

Pregnant, or potentially pregnant women have historically been excluded from clinical trials of new medications. However, it is increasingly recognised that it is imperative to generate evidence from the population in whom the drugs are likely to be used in order to inform safe, evidence-based shared clinical decision making. Reluctance by researchers and regulators to perform such studies often relates to concerns about risk, particularly to the fetus. However, this must be offset against the risk of untreated disease or using a drug in pregnancy where safety, efficacy and dosing information are not known. This review summarises the historical perspective, the ethical and legal frameworks which inform the conduct of such research, then highlights examples of innovative practice which have enabled high quality, ethical research to proceed to inform the evidence-based use of medication in pregnancy.

1. The COVID-19 pandemic has highlighted the importance of efficient sampling strategies and statistical methods for monitoring infection prevalence, both in humans and reservoir hosts. Pooled testing can be an efficient tool for learning pathogen prevalence in a population. Typically pooled testing requires a second phase follow up procedure to identify infected individuals, but when the goal is solely to learn prevalence in a population, such as a reservoir host, there are more efficient methods for allocating the second phase samples. 2. To estimate pathogen prevalence in a population, this manuscript presents an approach for data integration with two-phased testing of pooled samples that allows more efficient estimation of prevalence with less samples than traditional methods. The first phase uses pooled samples to estimate the population prevalence and inform efficient strategies for the second phase. To combine information from both phases, we introduce a Bayesian data integration procedure that combines pooled samples with individual samples for joint inferences about the population prevalence. 3. Data integration procedures result in more efficient estimation of prevalence than traditional procedures that only use individual samples or a single phase of pooled sampling. 4. The manuscript presents guidance on implementing the first phase and second phase sampling plans using data integration. Such methods can be used to assess the risk of pathogen spillover from reservoir hosts to humans, or to track pathogens such as SARS-CoV-2 in populations.

U.S Landforms and the Underground Railroad. Suggested Time: 180 Minutes 

How much troponin leak is too much before CABG?Clancy W. Mullan, MD and Arnar Geirsson, MDDivision of Cardiac SurgeryDepartment of SurgeryYale School of Medicine330 Cedar Street, BB204New Haven, CT 06511Acute myocardial infarction (MI) is a well-recognized risk factor for worse outcomes after coronary artery bypass grafting (CABG), and the proportion of patients undergoing CABG after MI appears to be increasing over time(1). With nearly a third of patients undergoing CABG having presented with MI, the question has been asked repeatedly of whether the degree of troponin leak correlates to post-operative outcomes, with conflicting results through the years(2, 3). In this edition of theJournal of Cardiac Surgery , Dr. Hess and colleagues present a compelling argument against the use of the degree of troponinemia in predicting major outcomes of surgical revascularization after non-ST elevation MI (NSTEMI). Principally, the authors demonstrate that neither troponin I leak above median nor increasing troponinemia independently predict mortality or major adverse cardiac or cerebrovascular events (MACCE). Secondarily, they find that multivariable adjustment obviates the association of peak troponin level with prolonged ventilation, prolonged intensive care unit stay, and prolonged hospital stay.With these data, the reader must ask: does there exist a residual argument for delaying surgical revascularization? A key observation in the present study is that nearly the entire cohort underwent urgent, rather than emergent or elective, revascularization. In the context of this relatively large cohort, this suggests a degree of stability to the “average” NSTEMI patient. Furthermore, given that the time from peak troponin to revascularization did not differ between the low- and high-risk cohorts and that time from peak troponin to surgery was not associated with post-operative mortality or MACCE, the data reported argue that patients can afford to wait for optimization prior to proceeding to surgery, certainly a controversial topic with a notable lack of society-level guidance that the authors appropriately address in their discussion. While the 2014 American Heart Association/American College of Cardiology guidelines for management of patients with NSTEMI provides some guidance on timing of surgical revascularization in relation to P2Y12 antiplatelet agent administration, no recommendations are provided on when to proceed with CABG otherwise. The authors findings seemingly fit directly on the middle of the debate’s metaphorical fence; however, interpretation of this is challenging given a lack of information such as time from presentation to peak troponin level, from presentation to coronary catheterization, or from catheterization to surgery.What should, then, dictate when to take a patient with NSTEMI to the operating room? There is no straightforward answer to this question, but, generally, these patients should proceed to surgery soon enough to prevent progression from a non-transmural to a transmural injury but late enough to avoids the bleeding risk of potent P2Y12 inhibitor loads (4, 5). While emergent revascularization is likely not warranted in the absence of arrythmias or evidence of continued ischemia, urgent revascularization within 24 hours should be encouraged barring prohibitive bleeding risk from an antiplatelet agent load. Interestingly, the authors did not find intra-aortic balloon pump (IABP) placement to be associated with post-operative mortality hazard, suggesting that IABPs were not especially targeted to unstable patients in their population. However, pre-operative inotrope requirement was associated with increased post-operative mortality, supporting an argument that NSTEMI patients, like their STEMI counterparts, with cardiogenic shock represent a particularly vulnerable population that should be revascularized with greater urgency. Where coronary anatomy demands surgical revascularization and cardiac surgical resources are not available, medical optimization followed by prompt referral to a surgical center is key.The tenacity with which the authors undertook the principal analyses of the manuscript should be commended. Hess et al. present a thorough and convincing argument that a patient’s risk from NSTEMI is likely fixed and dictated by the overall clinical picture rather than dependent on the degree of troponinemia and that the peak troponin level should not dictate clinical decisions.References1. Alkhouli M, Alqahtani F, Kalra A et al. Trends in characteristics and outcomes of hospital inpatients undergoing coronary revascularization in the united states, 2003-2016. JAMA Network Open 2020;3(2):e1921326-e1921326.2. Beller JP, Hawkins RB, Mehaffey JH et al. Does preoperative troponin level impact outcomes after coronary artery bypass grafting? The Annals of thoracic surgery 2018;106(1):46-51.3. Thielmann M, Massoudy P, Neuhäuser M et al. Prognostic value of preoperative cardiac troponin i in patients undergoing emergency coronary artery bypass surgery with non-st-elevation or st-elevation acute coronary syndromes. Circulation 2006;114(1 Suppl):I448-453.4. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 aha/acc guideline for the management of patients with non-st-elevation acute coronary syndromes: A report of the american college of cardiology/american heart association task force on practice guidelines. Circulation 2014;130(25):e344-426.5. Hillis LD, Smith PK, Anderson JL et al. 2011 accf/aha guideline for coronary artery bypass graft surgery. Journal of the American College of Cardiology 2011;58(24):e123-e210.

A document by Ian Sinha. Click on the document to view its contents.

Present study was conducted to analyze the role of silvipastoral systems to improve soil properties for restoration of degraded sodic soils. Ten years old tree species of Acacia nilotica, Casuarina equisetifolia and Eucalyptus tereticornis planted in a highly sodic soil (pH 10.6, EC 1.43 dSm-1 and ESP 89) were used for understory plantation of grass species like Chloris gayana, Panicum maximum and Pennisetum purpureum. Maximum growth and yield of understory grasses was recorded from treatment T4. Among the grass species, the highest nutritive value (N, P, K) was recorded in P. purpureum however, highest neutral detergent fiber and acid detergent fiber in treatment T4 and T11 respectively. The N.P, K and Na+ uptake in treatment T4 and T10 was significantly higher over rest of the treatments. A significant improvement in soils physical properties was recorded under treatment T7 and T4 which was attributed to reduced sodicity, addition of leaf litter, and increase in microbial activities due to tree and grass roots, better plant growth, and fine root decay. However, improvement in soil chemical properties was recorded under treatment T4 which may be attributed to more release of CO2 by grass roots and solublization of CaCO3.The highest MBC and MBP was recorded in treatment T7 however, highest MBN and dehydrogenase activities were recorded under treatment T4.On the basis of improvement in soil physico-chemical and biological properties in the tree+grass systems, A.nilotica+C.gayana silvipastoral system could be highly ameliorative and biomass producing system for restoration of degraded sodic soils of Indo-Gangetic plains.

The vibronic absorption spectrum of Toluidine blue O (TBO) dye in an aqueous solution was calculated using the time-dependent density functional theory (TD-DFT). The calculations were performed using all hybrid functionals supported by Gaussian16 software and 6-31++G(d,p) basis set with IEFPCM and SMD solvent models. The IEFPCM gave underestimated values of λmax in comparison with the experiment, what is a manifestation of the TD-DFT “cyanine failure”. However, the SMD made it possible to obtain good agreement between calculated and experimental spectra. The best fit was achieved using the X3LYP functional. The dipole moments and atomic charges of the ground and excited states of the TBO molecule were calculated. Photoexcitation leads to an increase in the dipole moment of the dye molecule. An insignificant photoinduced electron transfer was found in the central ring of the chromophore of the TBO molecule. Vibronic transitions play a significant role in the absorption spectrum of the dye.

A Bluetooth based, short memory, social media mobile network app.

Many organisms can reproduce both asexually and sexually. For cyclical parthenogens, periods of asexual reproduction are punctuated by bouts of sexual reproduction, and the shift from asexual to sexual reproduction has large impacts on fitness and population dynamics. We studied populations of Daphnia dentifera to determine the amount of investment in sexual reproduction as well as the factors associated with variation in investment in sex. To do so, we tracked host density, infections by nine different parasites, and sexual reproduction in 15 lake populations of D. dentifera for three years. Sexual reproduction was seasonal, with male and ephippial female production beginning as early as late September and generally increasing through November. However, there was substantial variation in the prevalence of sexual individuals across populations, with some populations remaining entirely asexual throughout the study period and others shifting almost entirely to sexual females and males. We found strong relationships between density, prevalence of infection, parasite species richness, and sexual reproduction in these populations. However, strong collinearity between density, parasitism, and sexual reproduction means that further work will be required to disentangle the causal mechanisms underlying these relationships.

Plant-plant interactions can vary depending on the severity of the environment. Positive interactions, such as facilitation, are important in early life stages while negative interactions, such as competition, predominate in later stages. Through succession, plant-plant interactions often change from facilitative to competitive. In northern temperate rainforests, gap dynamics result in tree falls that facilitate tree regeneration (nurse logs) as well as bryophyte succession. While the importance of nurse logs for tree seedlings is known, how the interactions of bryophyte communities and tree seedlings vary through succession of the log remains unclear. We examined the relationships of tree seedlings, bryophyte community composition, bryophyte depth, and percent canopy cover in 166 plots on nurse logs and the forest floor in the Hoh rainforest in Washington, USA. Tree seedling density was highest on young logs with early-colonizing bryophyte species (e.g., Rhizomnium glabrescens), and lowest on decayed logs with Hylocomium splendens, a long-lived moss that reaches depths >20 cm. As a result, bryophyte depth increased with nurse log decay and was negatively associated with tree seedling density. Tree seedling density was 4.6x higher on nurse logs than on the forest floor, which was likely due to competitive exclusion by H. splendens. Nurse logs had 17 species of bryophytes while the forest floor had six, indicating that nurse logs contribute to maintaining bryophyte diversity. Nurse logs are essential for forest dynamics as they enable both tree seedlings and smaller bryophyte species to avoid competition with the dominant forest floor bryophyte, H. splendens. Given that H. splendens has a global distribution and is often dominant in forested systems across the northern hemisphere, it is likely a widespread driver of plant community structure. Our findings indicate that plant-plant interactions shift with succession on nurse logs from facilitative to competitive and, thus, influence forest community structure and dynamics.

A regional grassland with Bermudagrass in Yangzhou City of China was adopted as the study location. Based on the analysis of the different rainfall events and soil water content data in the same periods, the response characteristics of infiltration to rainfall were revealed in a certain degree. The surface resistance parameters (rs) are calibrated according to the soil water content at the depths of a range for 0-30 cm and of the root layer (0-10 cm). Penman-Monteith (P-M) equation was adopted to estimated the hourly evapotranspiration (ET) over the Bermudagrass lawn of the soil layers for the depths of 0-30 cm (ET30) and 0-10 cm (ET10), respectively. Applicability of HYDRUS-1D model for simulating soil water content at different depths was validated. The results indicated that the infiltration depth generally varies with the rainfall event grade, and on the whole, the infiltration depth increases with the improvement of amount of rainfall; the response time for the soil water content in root layer is much shorter with the less soil water content in the topsoil (0-5.5 cm); the increase rate of soil water content raised with increasing of rainfall intensity in the state of unsaturation; ET10 accounts for about 78% of ET30, which demonstrates the water consumed by ET is mainly provided by the soil water in the root layer. the rationality of the results of different rainfall events and infiltration depth achieved by the analysis of the observed data were verified via numerical simulation using Hydrus-1D.

Background: A series of repeated questionnaire surveys among 8- and 9-year-old schoolchildren in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment during the last decade. Methods: Two further identical cross-sectional surveys were conducted in 2013 (N=2554) and 2018 (N=2648). Physician-diagnosed wheeze and asthma were analysed separately and in relation to their occurrence (recent-onset: solely within the last two years; non-current: prior to the last two years; persistent: both before and within the last two years). In addition, in 2018, spirometry was performed in participants reporting relevant symptoms and in a random sample of healthy controls. Results: The prevalence of current wheeze/asthma declined from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018. The persistent and non-current wheeze/asthma groups (both including children with symptoms at preschool age) followed this overall trend, while the prevalence of recent-onset wheeze/asthma remained unchanged. Persistent and non-current wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. Children with recent-onset wheeze/asthma and a considerable fraction of those with persistent symptoms had lower lung function. Conclusions: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. Our analysis suggests that the reversing trend is most likely attributed to changing asthma perceptions among physicians and/or parents, especially in the case of preschool children with troublesome respiratory symptoms.

Carbon allocation to non-structural carbohydrates (NSC) is essential for plant metabolism playing an important role in tree responses to drought. It is still unclear if and how interspecific hydraulic trait variation modulates NSC concentration dynamics in different plant organs, particularly in tropical tree species. We investigated whether drought-resistance strategies (inferred from hydraulic traits) explain seasonal and interannual NSC dynamics in leaves, branches, trunks, and roots in seasonal eastern Amazon tree species in Brazil. We measured NSC concentration in eight abundant species during three years, including the end of the wet and dry seasons of the typical regular years (2013-2014) and the extreme drought induced by El Niño–Southern Oscillation in 2015 (ENSO). Organs have an important contribution to explain the starch (ST), soluble sugar (SS), and NSC variance among trees. We showed seasonal and year-to-year homeostasis in ST and SS concentrations in a majority of organs during 2013 and 2014, but SS increased in all organs during the extreme ENSO drought, while the ST concentration did not. The increase in SS concentration was more evident in woody organs from species with intermediate and tolerant drought strategies. The drought-tolerant species maintain higher root starch concentrations and mobilize more SS during extreme drought.

The promotion of responsible and sustainable trade in biological resources is widely proposed as one solution to mitigate currently high levels of global biodiversity loss. Various molecular identification methods have been proposed as appropriate tools for monitoring global supply chains of commercialized animals and plants. We demonstrate the efficacy of target capture genomic barcoding in identifying and establishing the geographic origin of samples traded as Anacyclus pyrethrum, a medicinal plant assessed as globally vulnerable in the IUCN Red List. Samples collected from national and international supply chains were identified through target capture sequencing of 443 low-copy nuclear makers and compared to results derived from genome skimming of plastome, standard plastid barcoding regions and ITS. Both target capture and genome skimming provided approximately 3.4 million reads per sample, but target capture largely outperformed standard plant DNA barcodes and entire plastid genome sequences. Despite the difficulty of distinguishing among closely related species and infraspecific taxa of Anacyclus using conventional taxonomic methods, we succeeded in identifying 89 of 110 analysed samples to subspecies level without ambiguity through target capture. Furthermore, we were able to discern the geographical origin of Anacyclus samples collected in Moroccan, Indian and Sri Lankan markets, differentiating between plant materials originally harvested from diverse populations in Algeria and Morocco. With a recent drop in the cost of analysing samples, target capture offers the potential to routinely identify commercialized plant species and determine their geographic origin. It promises to play an important role in monitoring and regulation of plant species in trade, supporting biodiversity conservation efforts, and in ensuring that plant products are unadulterated, contributing to consumer protection.

A 63 year-old female with multiple atherosclerotic risk factors presented with newly diagnosed heart failure. Clinical presentation and initial work-up studies (e.g. laboratory findings, ECG, and echocardiography) were indeterminate for ischemic or non-ischemic etiology. As she developed contrast-induced nephropathy, coronary angiography was deferred and cardiac MRI was performed instead. Cardiac MRI elegantly demonstrated non-ischemic cardiomyopathy that was subsequently confirmed by invasive coronary angiography. This case emphasizes the important role of cardiac MRI in establishing the etiology of cardiomyopathy, ultimately altering the clinical management of the patient with newly diagnosed heart failure.

Background: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. Methods: All patients testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. Results: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4·15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1·12 [95% CI 0·86, 1·45], p=0·40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0·52 (0·28, 0·91), p=0·026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. Conclusions: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.

Introduction: The randomized controlled VOLCANO trial demonstrated comparable 1-year rhythm outcomes between patients with and without ablation targeting low-voltage areas (LVAs) in addition to pulmonary vein isolation among paroxysmal atrial fibrillation (AF) patients with LVAs. To compare long-term AF/atrial tachycardia (AT) recurrence rates and types of recurrent-atrial-tachyarrhythmia between treatment cohorts during a > 2-year follow-up period. Methods: An extended-follow-up study of 402 patients enrolled in the VOLCANO trial with paroxysmal AF, divided into 4 groups based on the results of voltage mapping: Group A, no LVA (n=336); group B, LVA ablation (n=30); group C, LVA presence without ablation (n=32); and group D, incomplete voltage map (n=4). Results: At 25 (23, 31) months after the initial ablation, AF/AT recurrence rates were 19% in group A, 57% in group B, 59% in group C, and 100% in group D. Recurrence rates were higher in patients with LVAs than those without (group A vs. B+C, p<0.0001), and were comparable between those with and without LVA ablation (group B vs. C, p=0.83). Among patients who underwent repeat ablation, ATs were more frequently observed in patients with LVAs (Group B+C, 50% vs. A, 14%, p<0.0001). In addition, LVA ablation increased the incidence of AT development (group B, 71% vs. C, 32%, p<0.0001), especially biatrial tachycardia (20% vs. 0%, p=0.01). Conclusion: Patients with LVAs demonstrated poor long-term rhythm outcomes irrespective of LVA ablation. ATs were frequently observed in patients with LVAs, and LVA ablation might exacerbate iatrogenic ATs.

A document by Emma Magavern. Click on the document to view its contents.