The ability to predict the onset of labour is seen to be an important tool in a clinical setting. Magnetomyography has shown promise in the area of labour imminency prediction, but its clinical application remains limited due to high resource consumption associated with its broad number of channels. In this study, five electrode channels, which account for 3.3% of the total, are used alongside a novel signal decomposition algorithm and low complexity classifiers (logistic regression and linear-SVM) to classify between labour imminency due within 0–48hrs and >48hrs. The results suggest that the parsimonious representation comprising of five electrode channels and novel signal decomposition method alongside the candidate classifiers could allow for greater affordability and hence clinical viability of the magnetomyography-based prediction model, which carries a good degree of model interpretability.

Risk stratification of HPV positive women in routine cervical screeningHigh risk HPV primary screening is replacing organised cytology-based screening based on increased sensitivity to detect high grade intra-epithelial neoplasia and the very high negative predictive value which will allow extended screening intervals. The benefit of increased CIN detection and cancer prevention needs to balance against the disbenefits to screen positive women in over investigation not east the psychological impact. For colposcopy services, the English cervical screening programme reported a 80% increase in colposcopy referrals in the first round of screening, creating huge pressures on service capacity (Rebolj M et al BMJ 2019;364:l240). The lower positive predictive value also impacts on colposcopy performance with a different referral population wit proportionately less high grade CIN present. In this issue of BJOG, Gori M et al provide observational data from a large longitudinal study of routine primary HPV screening in an organised quality assured cervical screening programme in 3 regions of Italy. Whilst routinely collected data from real-world programmes will have limitations, they do provide an insight into disease detection and importantly impact on colposcopy provision. In a comparison of triage strategies, combined HPV genotyping for HPV16 and high-grade cytology offered an acceptable balance of risk of CIN3+ with number of colposcopies needed to detect one lesion. These results differ from the English pilot (Rebolj M et al 2019 BJC;121(6):455-463) where HPV16/18 genotyping detected only 1.2% more cases of CIN2+ with 5.9% additional colposcopies. Gori M et al did not combine HPV16/18 but they did report that HPV18 on genotyping was not as clinically useful at baseline or 12-month follow-up. Furthermore, 90% of women screened were aged over 35 years when HPV screening is more clinically effective whereas the English pilot started screening at age 25 years when HPV infection is more prevalent and less likely to be clinically significant. Longer follow-up, importantly at the next screening round, is not yet available when the relevance of non-HPV 16 types may be more apparent.The impact of the Covid 19 pandemic on health services and in particular screening, has sharpened the argument of risk stratification following primary screen positive testing both for service providers and those in the target population. Ciavattini A et al (2020 Int J Cancer 30(8):1097-1100) reported on suspension or postponement of cervical screening programmes across Europe relevant to both routine screening and onward referral to colposcopy. As services have needed to adapt to Covid infection rates and health service capacity, the ability to triage effectively and avoid unnecessary hospital visits is critical. Clinicians and women need information on their risk to inform clinical practice and provide reassurance. In the current second wave, the suspension of screening implemented in the first wave is no longer acceptable. Whilst data, such as these from Gori et al, continue to emerge from national and regional screening programmes, Covid has highlighted the need to be responsive and adaptive to allow cancer prevention to continue.

Photochemical reactions of small molecules occur upon irradiation by ultraviolet or visible light, and they are a very important and controversial chemical process in the Earth’s atmosphere because they impact our quality of life and health. Small-unsaturated carbonyl compounds play an important role in the chemistry of the polluted troposphere. The fluorinated aldehydes are very reactive under the sunlight driving to species that trigger more atmospheric reactions. This paper is focused on a theoretical study of the photochemistry of difluoro-crotonaldehyde using static and dynamic calculations by combination of Global Reaction Route mapping (GRRM) and Trajectory Surface Hopping (TSH) approach. The static analysis of the electronic and geometrical structures at the critical points allowed to rationalize the possible pathways that interconnect the stationary and crossing points in order to get a map of the unimolecular photochemical reactions which take place. The time evolution of the electronic states and the degrees of freedom enabled the identification of the requirements to follow the most probable deactivation pathways. This article reports the unimolecular deactivation pathways after the electronic excitation of the trans and cis isomers. In both cases, the excitation energies were calculated and compared with the analogous in the crotonaldehyde in order to elucidate the effect of fluorine atoms on the electronic structure and stabilities. After the initial excitations to the ππ* excited states, the main deactivation channels follow non-adiabatic pathways via S1/S0 conical intersections. Ultrafast processes leading to the early activation of the S1 govern the decay of the difluoro-crotonaldehyde. Depending on the nature of the S1 state before the crossing with the S0, the system can follow several reaction pathways. The main photochemical processes observed were the cis-trans isomerization, the Norrish type I reaction (α-cleavage), Norrish type II reaction (γ-hydrogen abstraction) and fluorine photodissociation. The time scale, the molecular deformations and the electronic states implied for the different photochemical processes, as well as how these compete with the photophysical deactivation are discussed.

Disturbances often disproportionately impact different vegetation layers in forests and other vertically-stratified ecosystems, shaping community structure and ecosystem function. However, disturbance-driven changes may be mediated by environmental conditions that affect habitat quality and species interactions. In a decade-long field experiment, we tested how kelp forest net primary productivity (NPP) responds to repeated canopy loss along a gradient in grazing and substrate suitability. We discovered that habitat quality can mediate the effects of intensified disturbance on canopy and understory NPP. Experimental annual and quarterly disturbances suppressed total macroalgal NPP, but effects were strongest in high-quality habitats that supported dense kelp canopies that were removed by disturbance. Understory macroalgae partly compensated for canopy NPP losses and this effect magnified with increasing habitat quality. Disturbance-driven increases in understory NPP were still rising after 5–10 years of disturbance, demonstrating the value of long-term experimentation for understanding ecosystem responses to changing disturbance regimes.

We report a case of natural healing of a ruptured unstable coronary plaque using serial OCT examination. Stenting procedure was deferred based on the angiographic and mainly OCT findings. A healing process of ruptured plaque without foreign body was studied using OCT at 3, 14 and 24 months after PCI.

Atrial tachycardia (AT) in the right atrium often occurs following open-heart surgery. Catheter ablation for these AT is challenging and can lead to unintended conduction block. We performed late-gadolinium enhancement magnetic resonance imaging prior to catheter ablation and predicted wavefront propagation during SR as well as the slow conduction zone

Grassland systems constitute a significant portion of the land area in the U.S., and as a result, harbor a significant amount of arthropod diversity. During this time of biodiversity loss around the world, bioinventories of ecologically important habitats serve as important indicators for the effectiveness of conservation efforts. We conducted a bioinventory of the foliar, soil, and dung arthropod communities in 10 cattle pastures located in the southeastern U.S. during the 2018 grazing season. In sum, 126,251 specimens were collected. From the foliar community, 13 arthropod orders were observed, with the greatest species richness found in Hymenoptera, Diptera, and Hemiptera. The soil-dwelling arthropod community contained 18 orders. The three orders comprising the highest species richness were Coleoptera, Diptera, and Hymenoptera. Lastly, 12 arthropod orders were collected from cattle dung, with the greatest species richness found in Coleoptera, Diptera, and Hymenoptera. Herbivores were the most abundant functional guild found in the foliar community, and predators were most abundant in the soil and dung communities. While bioinventories demand considerable time, energy, and resources to accomplish, the information from these inventories has many uses for conservation efforts, land management recommendations, and the direction of climate change science.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study sought to examine the relationship between socioeconomic status (SES) and OS in children with high-risk neuroblastoma, and to investigate whether SES-associated disparities have changed over time. Procedure: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991-2015 were identified through the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a sub-cohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variables reached near-significance (p≤0.1) in univariate and bivariate modeling with treatment era. Results: Among 1,217 children, 2-year OS improved from 53.0±3.4% in 1991-1998 to 76.9±2.9% in 2011-2015 (p<0.001). In univariate analyses, children with Medicaid (hazard ratio [HR]=1.40, 95% confidence interval [CI]=1.05-1.86, p=0.02) and those in high-poverty counties (HR=1.74, CI=1.17-2.60, p=0.007) experienced an increased hazard of death. No interactions between treatment era and SES variables were statistically significant in multivariable analyses, indicating that changes in OS over time did not differ between groups. Conclusions: Low SES is associated with inferior survival in children with high-risk neuroblastoma. Survival disparities have not widened over time, suggesting equitable access to and benefit from therapeutic advances. Interventions to narrow existing disparities are paramount.

BACKGROUND AND PURPOSE The cysteine674 (C674) thiol of Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is easily and irreversibly oxidized under atherosclerotic conditions. However, contribution of the C674 thiol redox status in the development of atherosclerosis remains unclear. Our goal was to elucidate the possible mechanism involved. EXPERIMENTAL APPROACH Heterozygous SERCA2 C674S knock-in (SKI) mice in which half of the C674 was substituted by serine674 were used to mimic removal of the reactive C674 thiol which occurs under patholog-ical conditions. The whole aorta and aortic root were isolated for histological analysis. Bone marrow derived macrophages (BMDMs) and a cardiac endothelial cell line were used for intra-cellular Ca2+, macrophage adhesion and protein expression analysis. KEY RESULTS SKI mice developed more severe atherosclerotic plaque and macrophage accumulation. Cell cul-ture studies suggest the partial substitution of SERCA2 C674 increased intracellular calcium lev-els and ER stress in both BMDMs and ECs. The release of pro-inflammatory factors and macro-phage adhesion increased in SKI BMDMs. In normal ECs, the overexpression of C674S mutant induced endothelial inflammation and promoted macrophage recruitment. Additionally, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, prevented the increased atherosclerosis observed in SKI mice, and alleviated ER stress and inflammatory responses in BMDMs and ECs exposed to 4-PBA. CONCLUSIONS AND IMPLICATIONS The substitution of SERCA2 C674 thiol accelerates the development of atherosclerosis by in-ducing ER stress and inflammation. Our findings highlight the importance of SERCA2 C674 redox status in the context of atherosclerosis, and open up a novel therapeutic strategy to combat atherosclerosis.

Background: Acute asthma exacerbations are a common cause for emergency department (ED) visits and hospitalizations in children. Since the outbreak of COVID-19 and the education system closure/ total lockdown in Israel on March 2020, we have noticed a decrease in pediatric ED visits and an increase in hospitalizations of asthma exacerbations. Objective: to examine the patterns of ED visits for asthma exacerbations during COVID-19 outbreak, in comparison to the previous year. Methods: a retrospective study comparing asthma related ED visits and hospitalizations among children aged 2-18 years at a tertiary center in southern Israel. Three time periods were selected: 2020A (pre- lockdown, 1/2/20-14/3/20), 2020B (lockdown, 15/3/20-15/5/20) and 2020 C (post- lockdown, 16/5/20-30/6/20) and compared to the three parallel time periods in 2019. Data regarding demographics, number of ED visits and clinical severity parameters were collected and analyzed. Results: 512 children visited the ED for asthma exacerbation: 273 children during 2019 and 239 children during 2020, with significantly fewer ED visits per day during the lockdown period (1.8 vs 1.43, p<0.001), compared to the parallel period in 2019. Significantly higher hospitalization rate (47.1% vs 33.7%, p=0.05) and longer length of stay (LOS) (3.15 vs 1.9 days, p= 0.03) were observed during the lockdown. Conclusion: lockdown is associated with fewer ED visits for asthma exacerbation, probably due to; reduced exposure to viral infections and environmental allergens, decreased availability of primary physicians and families’ reluctance to arrive to the ED. ED visits during lockdown were characterized by higher hospitalization rate and longer LOS.

We are reporting a case of neurofibromatosis type 1 in a genotype-phenotype correlation and chromosomal microarray test revealed a submicroscopic deletion on the long arm of chromosome 17, which is associated with a more severe phenotype. The presence of a more severe phenotype warrants precise monitoring of complications.

We report the case of an 81 year old lady presenting with a left pulsatile neck mass 7 years after her initial carotid endarterectomy (CEA). We were able to employ a combined hybrid trans-cervical carotid stents followed by open excision and repair for a successful outcome

Background: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). Procedure: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from 3–5 blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively). Results: By one-point sampling strategy, the most accurate predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was highly precise (r2 = 0.937; precision, 5.9%) in adolescent patients weighing > 23 kg, but the correlation was poor in infants and young children weighing ≤23 kg (r2 = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most favorable performance (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%). Conclusions: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial inter-individual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.

A document by Klaus Rose. Click on the document to view its contents.

Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

Background and Purpose: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. We now describe BW-031, a novel more potent cationic sodium channel inhibitor, test whether its application alone can inhibit the pain associated with tissue inflammation, and whether this strategy can also inhibit cough. Experimental Approach: We characterized BW-031 inhibition of sodium channels and tested BW-031 in three models of inflammatory pain: rat paw inflammation produced by Complete Freund’s Adjuvant injection or surgical incision and a mouse paw UV burn model. We also tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. Key Results: BW-031 inhibited Nav1.7 and Nav1.1 channels with ~6-fold greater potency than QX-314 when introduced inside cells and entered capsaicin-activated TRPV1 expressing sensory neurons. BW-031 inhibited inflammatory pain in all three models, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was also effective in reducing cough counts by 78-90% when applied intratracheally under isoflurane anesthesia or by aerosol inhalation in awake guinea pigs with airway inflammation produced by ovalbumin sensitization. Conclusion and Implications: BW-031 a novel cationic sodium channel inhibitor can be applied locally as a single agent to inhibit inflammatory pain and also effectively inhibits cough in a guinea pig model of nociceptor-activated cough, suggesting a new clinical approach to treating cough.

The Intermediate Disturbance Hypothesis is widely considered to be wrong but is rarely tested against alternative hypotheses. It predicts that soil disturbances and herbivory have identical impacts on species richness via identical mechanisms (reduction in biomass and in competition). An alternative hypothesis is that the specific traits of disturbance agents (small mammals) and plants differentially affects richness or abundance of different plant groups. We tested these hypotheses on a degu (Octodon degus) colony in central Chile. We ask whether native and non-native forbs respond differently to degu bioturbation on runways vs. herbivory on grazing lawns. We ask whether this can explain the increase in non-native plants on degu colonies. We found that biopedturbation did not explain the locations of non-native plants. We did not find direct evidence of grazing increasing non-native herbs either, but a grazing effect appears to be mediated by grass, which is the dominant cover. Further, we provide supplementary evidence to support our interpretation that a key mechanism of non-native spread is the formation of dry soil conditions on grazing lawns. Thus ecosystem engineering (alteration of soil qualities) may be an outcome of disturbances, which each interact with specific plant traits, to create the observed pattern of non-native spread in the colony. Based on these results we propose to extend Jentsch & White’s (2019) concept of combined pulse/ disturbance events to the long-term process duality of ecosystem engineering/ disturbance.