Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

The manifold costs of being a non-native English speaker in science.

The use of English as the common language of science represents a major impediment to maximising the contribution of non-native English speakers to science. Yet few studies have quantified the consequences of language barriers on the career development of researchers who are non-native English speakers. By surveying 908 researchers in environmental sciences, this study estimates and compares the amount of effort required to conduct scientific activities in English between researchers from different countries and, thus, different linguistic and economic backgrounds. Our survey demonstrates that non-native English speakers, especially early in their careers, spend more effort than native English speakers in conducting scientific activities, from reading and writing papers and preparing presentations in English, to disseminating research in multiple languages. Language barriers can also cause them not to attend, or give oral presentations at, international conferences conducted in English. We urge scientific communities to recognise and tackle these disadvantages to release the untapped potential of non-native English speakers in science. This study also proposes potential solutions that can be implemented today by individuals, institutions, journals, funders, and conferences. Please see the Supporting information files (S2-S6 Text) for Alternative Language Abstracts and Figs 5 and 6.

Telehealth interventions for transition to self-management in adolescents with allergic conditions: A systematic review.

Telehealth is an emerging approach that uses technology to provide healthcare remotely. Recent publications have outlined the importance of supporting the transition to self-management of adolescents with allergic conditions. However, no synthesis of the evidence base on the use and impact of telehealth interventions for this purpose has been conducted to date. This review achieves these aims, in addition to exploring the language use surrounding these interventions, and their implementation. Four databases were searched systematically. References were independently screened by two reviewers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was undertaken. Eighteen articles were included, reporting on 15 telehealth interventions. A total of 86% targeted adolescents with asthma. Mobile applications were the most common telehealth modality used, followed by video-conferencing, web-based, virtual reality and artificial intelligence. Five intervention content categories were identified; educational, monitoring, behavioural, psychosocial and healthcare navigational. Peer and/or healthcare professional interaction, gamification and tailoring may increase engagement. The studies showed positive effects of the interventions or no difference from active controls, in self-management outcomes such as knowledge, health outcomes such as quality-of-life, and economic outcomes such as healthcare utilization. The most common implementation outcomes reported were acceptability, appropriateness, feasibility and fidelity.

Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Image-Guided Transbronchial Pulmonary Cryoablation with a Flexible Cryoprobe in Swine: Performance and Radiology-Pathology Correlation.

PURPOSE: To evaluate the performance of a prototype flexible transbronchial cryoprobe compared with that of percutaneous transthoracic cryoablation and to define cone-beam computed tomography (CT) imaging and pathology cryolesion features in an in vivo swine model. MATERIALS AND METHODS: Transbronchial cryoablation was performed with a prototype flexible cryoprobe (3 central and 3 peripheral lung ablations in 3 swine) and compared with transthoracic cryoablation performed with a commercially available rigid cryoprobe (2 peripheral lung ablations in 1 swine). Procedural time and cryoablation success rates for endobronchial navigation and cryoneedle deployment were measured. Intraoperative cone-beam CT imaging features of cryolesions were characterized and correlated with gross pathology and hematoxylin and eosin-stained sections of the explanted cryolesions. RESULTS: The flexible cryoprobe was successfully navigated and delivered to each target through a steerable guiding sheath (6/6). At 4 minutes after ablation, 5 of 6 transbronchial and 2 of 2 transthoracic cryolesions were visible on cone-beam CT. The volumes on cone-beam CT images were 55.5 cm3 (SE ± 8.0) for central transbronchial ablations (n = 2), 72.5 cm3 (SE ± 8.1) for peripheral transbronchial ablations (n = 3), and 79.5 cm3 (SE ±11.6) for peripheral transthoracic ablations (n = 2). Pneumothorax developed in 1 animal after transbronchial ablation and during ablation in the transthoracic cryoablation. Images of cryoablation zones on cone-beam CT correlated well with the matched gross pathology and histopathology sections of the cryolesions. CONCLUSIONS: Transbronchial cryoablation with a flexible cryoprobe, delivered through a steerable guiding sheath, is feasible. Transbronchial cryoablation zones are imageable with cone-beam CT, with gross pathology and histopathology similar to those of transthoracic cryoablation.

Exposure of protected areas in Central America to extreme weather events.

Central America and the Caribbean are regularly battered by megadroughts, heavy rainfall, heat waves, and tropical cyclones. Although 21st-century climate change is expected to increase the frequency, intensity, and duration of these extreme weather events (EWEs), their incidence in regional protected areas (PAs) remains poorly explored. We examined historical and projected EWEs across the region based on 32 metrics that describe distinct dimensions (i.e., intensity, duration, and frequency) of heat waves, cyclones, droughts, and rainfall and compared trends in PAs with trends in unprotected lands. From the early 21st century onward, exposure to EWEs increased across the region, and PAs were predicted to be more exposed to climate extremes than unprotected areas (as shown by autoregressive model coefficients at p < 0.05 significance level). This was particularly true for heat waves, which were projected to have a significantly higher average (tested by Wilcoxon tests at p < 0.01) intensity and duration, and tropical cyclones, which affected PAs more severely in carbon-intensive scenarios. PAs were also predicted to be significantly less exposed to droughts and heavy rainfall than unprotected areas (tested by Wilcoxon tests at p < 0.01). However, droughts that could threaten connectivity between PAs are increasingly common in this region. We estimated that approximately 65% of the study area will experience at least one drought episode that is more intense and longer lasting than previous droughts. Collectively, our results highlight that new conservation strategies adapted to threats associated with EWEs need to be tailored and implemented promptly. Unless urgent action is taken, significant damage may be inflicted on the unique biodiversity of the region.

Ciclones, olas de calor, sequías y lluvias intensas son eventos comunes en Centroamérica y el Caribe, cuya frecuencia, intensidad y duración se espera aumente durante el siglo XXI a causa del cambio climático. Sin embargo, en la actualidad, se desconoce cuál será la incidencia de estos eventos meteorológicos extremos (EME) dentro de las áreas protegidas. En este estudio examinamos la exposición histórica y futura a los extremos climáticos y comparamos el grado de exposición dentro y fuera de las áreas protegidas de toda la región por medio de 32 métricas que describen distintas dimensiones (intensidad, duración y frecuencia) de las olas de calor, los ciclones, las sequías y las precipitaciones. Los resultados indican que a medida que aumente el número de EME, las áreas protegidas estarán más expuestas a los extremos climáticos que las áreas no protegidas. Esto es especialmente cierto en el caso de las olas de calor, que, según las proyecciones, tendrán una intensidad y una duración medias significativamente mayores, y de los ciclones tropicales, que afectarán más gravemente a las zonas protegidas en los escenarios intensivos en carbono. Nuestros resultados también indican que las zonas protegidas estarán significativamente menos expuestas a sequías o lluvias torrenciales que las zonas no protegidas. Sin embargo, las sequías que podrían amenazar la conectividad entre áreas protegidas son cada vez más frecuentes en esta región. Se estima que aproximadamente el 65% del área de estudio experimentará al menos un episodio de sequía más intenso y duradero que las sequías anteriores. En conjunto, nuestros resultados ponen de relieve la necesidad de diseñar y aplicar con prontitud nuevas estrategias de conservación adaptadas a las amenazas asociadas a los EWE. A menos que se tomen medidas urgentes, la biodiversidad única de la región podría sufrir daños considerables.

Teaching children with food allergy to recognize anaphylaxis: The caregivers' perspectives.

BACKGROUND: Anaphylaxis is rising in prevalence among children. The current recommendations on the effective transition of anaphylaxis management to adolescents and young adults suggest preparation for the transition may be considered at 11-13 years of age in accordance with the patient's developmental stage. However, there has been limited research conducted on the perspective of caregivers regarding the transition of anaphylaxis management to their children. This study aims to determine the age caregivers feel it is appropriate to begin to teach their child to recognize anaphylaxis and use their adrenaline auto-injectors (AAI). METHODS: Caregivers of pediatric allergy patients who have been diagnosed with IgE-mediated food allergy and have an AAI prescription were contacted by phone and invited to complete a questionnaire about when they feel it is appropriate to begin to teach their child to recognize anaphylaxis and use their AAI. RESULTS: Of the 123 responses to the questionnaire received, 44.7% indicated that 9-11 years was the appropriate time for teaching their children to self-inject an AAI. History of severe anaphylaxis (94.3%), child's ability to describe reasons to inject adrenaline (87.8%), and demonstrate AAI use (82.1%) were "very important" readiness factors identified. Almost half of caregivers were "not confident" (8.94%) or "somewhat confident" (40.65%) in training their child to use AAI. Caregivers with higher household incomes more frequently identified themselves as the party responsible for training their children to use AAI (p = .04). CONCLUSION: Caregivers in this sample expressed different perspectives than the current guidelines regarding the timing to initiate the transition of anaphylaxis management to their child. Caregivers expressed suboptimal confidence in teaching their children to use AAI. Clinicians should be aware of the factors that may indicate caregivers' desire to initiate an earlier transition of anaphylaxis management to their child and ensure access to appropriate training, education and support is available.

Model Chemistry Recommendations for Scaled Harmonic Frequency Calculations: A Benchmark Study.

Despite the widespread popularity of scaled harmonic frequency calculations to predict experimental fundamental frequencies in chemistry, sparse benchmarking is available to guide users on the appropriate level of theory and basis set choices (model chemistry) or deep understanding of expected errors. An updated assessment of the best approach for scaling to minimize errors is also overdue. Here, we assess the performance of over 600 popular, contemporary, and robust model chemistries in the calculation of scaled harmonic frequencies, evaluating different scaling factor types and their implications in the scaled harmonic frequencies and model chemistry performance. We can summarize our results into three main findings: (1) Using model-chemistry-specific scaling factors optimized for three different frequency regions (low (<1,000 cm-1), mid (1,000-2,000 cm-1), and high (>2,000 cm-1)) results in substantial improvements in the agreement between the scaled harmonic and experimental frequencies compared to other choices. (2) Larger basis sets and more robust levels of theory generally lead to superior performance; however, the particular model chemistry choice matters and poor choices lead to significantly reduced accuracies. (3) Outliers are expected in routine calculations regardless of the model chemistry choice. Our benchmarking results here do not consider the intensity of vibrational transitions; however, we draw upon previous benchmarking results for dipole moments that highlight the importance of diffuse functions (i.e., augmented basis sets) in high-quality intensity predictions. In terms of specific recommendations, overall, the highest accuracy model chemistries are double-hybrid density functional approximations with a non-Pople augmented triple-ζ basis set, which can produce median frequency errors down to 7.6 cm-1 (DSD-PBEP86/def2-TZVPD), which is very close to the error in the harmonic approximation, i.e., the anharmonicity error. Double-ζ basis sets should not be used with double-hybrid functionals as there is no improvement compared to hybrid functional results (unlike for double-hybrid triple-ζ model chemistries). Note that 6-311G* and 6-311+G* basis sets perform like a double-ζ basis set for vibrational frequencies. After scaling, all studied hybrid functionals with non-Pople triple-ζ basis sets will produce median errors of less than 15 cm-1, with the best result of 9.9 cm-1 with B97-1/def2-TZVPD. Appropriate matching of double-ζ basis sets with hybrid functionals can produce high-quality results, but the precise choice of functional and basis set is more important. The B97-1, TPSS0-D3(BJ), or ωB97X-D hybrid density functionals with 6-31G*, pc-1, or pcseg-1 are recommended for fast routine calculations, all delivering median errors of 11-12 cm-1. Note that dispersion corrections are not easily available for B97-1; given its strong performance here, we recommend these be added to major programs in coming updates.

PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment.

BACKGROUND: Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer. METHODS: We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays. RESULTS: Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer. CONCLUSION: The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.

Woodchuck Hepatic Anatomy and Vascular Alterations Due to Hepatocellular Carcinoma with Angiographic Atlas of the Abdomen and Pelvis.

PURPOSE: To characterize the hepatic and abdominal angiographic anatomy of woodchucks and vascular changes associated with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-nine woodchucks (23 with viral-associated HCC, 6 without) underwent multiphasic computed tomography (CT). Fourteen woodchucks (8 with HCC) also underwent diagnostic angiography. Hepatic arterial diameters were measured on the CT scans. Woodchucks were divided into 3 groups: non-tumor-bearing, largest tumor supplied by the right hepatic artery (RHA), and largest tumor supplied by the left hepatic artery (LHA). Statistical analysis with a repeated measures model was performed to determine the effects of tumor location (right, left), vessel measured (RHA, LHA), and interaction between the 2 on vessel diameter. Lobar arteries supplying HCC were compared with those that did not. RESULTS: CT anatomy and normal and variant vascular anatomy were defined. In woodchucks with HCC, LHA and RHA supplying tumors had mean diameters of 2.0 mm ± 0.3 and 1.6 mm ± 0.3 versus 1.5 mm ± 0.3 and 1.1 mm ± 0.2 for non-tumor-supplying arteries (P = .0002 and P < .0001), respectively. Lobar arteries supplying tumors were similarly ectatic. The right lateral lobe artery had the most profound increase in the mean diameter when supplying tumors, measuring 1.7 mm ± 0.1 versus 1.0 mm ± 0.1 in the non-tumor-supplying artery (P < .0001). There were no differences in the diameters of the aorta and celiac, common, and proper hepatic arteries between tumor- and non-tumor-bearing woodchucks. An angiographic atlas of the abdominal vessels was generated. CONCLUSIONS: HCC tumoral vasculature in woodchucks was ectatic compared with normal vasculature. This phenomenon recapitulates human HCC and may facilitate investigation of transcatheter and drug delivery therapies in an HCC animal model.

VIBFREQ1295: A New Database for Vibrational Frequency Calculations.

High-throughput approaches for producing approximate vibrational spectral data for molecules of astrochemistry interest rely on harmonic frequency calculations using computational quantum chemistry. However, model chemistry recommendations (i.e., a level of theory and basis set pair) for these calculations are not yet available and, thus, thorough benchmarking against comprehensive benchmark databases is needed. Here, we present a new database for vibrational frequency calculations (VIBFREQ1295) storing 1295 experimental fundamental frequencies and CCSD(T)(F12*)/cc-pVDZ-F12 ab initio harmonic frequencies from 141 molecules. VIBFREQ1295's experimental data was complied through a comprehensive review of contemporary experimental data, while the ab initio data was computed here. The chemical space spanned by the molecules chosen is considered in-depth and is shown to have good representation of common organic functional groups and vibrational modes. Scaling factors are routinely used to approximate the effect of anharmonicity and convert computed harmonic frequencies to predicted fundamental frequencies. With our experimental and high-level ab initio data, we find that a single global uniform scaling factor of 0.9617(3) results in median differences of 15.9(5) cm-1. A far superior performance with a median difference of 7.5(5) cm-1 can be obtained, however, by using separate scaling factors (SFs) for three regions: frequencies less than 1000 cm-1 (SF = 0.987(1)), between 1000 and 2000 cm-1 (SF = 0.9727(6)), and above 2000 cm-1 (SF = 0.9564(4)). This sets a lower bound for the performance that could be reliably obtained using scaling of harmonic frequency calculations to predict experimental fundamental frequencies. VIBFREQ1295's most important purpose is to provide a robust database for benchmarking the performance of any vibrational frequency calculations. VIBFREQ1295 data could also be used to train machine-learning models for the prediction of vibrational spectra and as a reference and data starting point for more detailed spectroscopic modeling of particular molecules. The database can be found as part of the Supporting Information for this paper or in the Harvard DataVerse at https://doi.org/10.7910/DVN/VLVNU7.

Benefit of educational intervention on Autoinjector Technique for caregivers and paediatric patients with food allergies: A literature review.

BACKGROUND AND OBJECTIVE: The incidence of food allergy among children is on the rise. Children who are diagnosed with a food allergy receive long-term treatment for allergy management from allergy specialists, nurses and dieticians. This management may include the prescription of an adrenaline autoinjector (AAI) if the child is at risk of a severe allergic reaction (anaphylaxis). Therefore, it is important that parents of children with allergies are trained in the recognition of anaphylaxis and in the correct administration of an AAI. However, many parents are unable to correctly administer an AAI when assessed. The aim of this study is to review the current literature on caregiver's and paediatric patients' ability to use an AAI. METHODOLOGY: An electronic search to evaluate AAI technique in caregivers and children with food allergy was conducted. A total of 323 articles were screened in which 10 studies were reviewed. RESULTS: Seventy-eight percent of parents who had never been trained in the use of an AAI were unable to trigger it. In studies where paediatric patients' ability to use an AAI was assessed, a mean score of 7.78/9 was derived for AAI knowledge among adolescents. CONCLUSION: Caregivers and patient's ability to use an AAI was inconclusive, and further research should address the validation of an assessment tool for AAI use. A significant improvement in AAI use was found after an educational intervention. This highlights the need for improved education for allergic individuals and their caregivers, and further study should explore what are the best educational methods to meet these needs.

Risk taking and self-care behaviours amongst adolescents and young adults with food allergies.

BACKGROUND: Anaphylaxis is a systemic, life-threatening reaction and its prevalence is rising amongst adolescents and young adults (AYA) with food allergies. The likelihood of fatal anaphylaxis is disproportionately high in this population. The effective management of anaphylaxis can be done by adhering to various food allergy-related self-care behaviours, namely avoidance of allergens, carriage and use of adrenaline auto-injectors (AAI). Unfortunately, compliance of AYA to these behaviours is believed to be suboptimal and the likely reason behind their increased rates of fatal anaphylaxis. METHODOLOGY: To evaluate the adherence to food allergy-related self-care behaviours amongst adolescents and young adults with anaphylaxis an electronic search was conducted utilizing PubMed, MEDLINE, and CINAHL plus to identify relevant studies. 175 article abstracts were screened, and 26 remained which were read in full to determine which best satisfied the inclusion and exclusion criteria. Ultimately, 10 articles were selected for this review. RESULTS: The compliance to food allergy-related self-care behaviours amongst AYA founded to be suboptimal. AAI design, peer influence, and emotional attitudes of AYA were found to be the most significant factors influencing AYA compliance to self-care behaviours. CONCLUSIONS: The adherence of AYA to food allergy-related self-care behaviours is suboptimal and evidence on the factors affecting AYA compliance has been largely contradictory. AAI design, peer influence, and emotional attitudes are significant factors influencing AYA adherence. Therefore, further research directed at these factors is imperative in facilitating the design of guidelines to maximize the adherence of AYA to food allergy-related self-care behaviours.

Mass food challenges in a vacant COVID-19 stepdown facility: Exceptional opportunity provides a model for the future.

BACKGROUND: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi-elective procedures. For allergic children in Ireland, already waiting up to 4 years for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative, there were approx 900 children on the Children's Health Ireland (CHI) waiting list. In July 2020, a project was facilitated by short-term (6 weeks) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive (HSE), Ireland. The aim of this study was to achieve the rapid roll-out of an offsite OFC service, delivering high throughput of long waiting patients, while aligning with existing hospital policies and quality standards, international allergy guidelines and national social distancing standards. METHODS: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant paediatric allergists, consultant paediatricians, trainees and allergy clinical nurse specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors (BP, pulse and oxygen saturation) and bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardized food challenge protocols were created. Access to the onsite hotel chef facilitated food preparation. A risk register was established. RESULTS: After 6 weeks of planning, the remote centre became operational on 7/9/2020, with the capacity of 27 OFC/day. 474 challenges were commenced: 465 (98%) were completed and 9 (2%) were inconclusive. 135 (29%) OFCs were positive, with 25 (5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days. CONCLUSIONS: Oral food challenges remain a vital tool in the care of allergic children, with their cost saving and quality-of-life benefits negatively affected by a delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy-in-even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era.

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis.

BACKGROUND AND PURPOSE: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG. METHODS: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed. RESULTS: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up. CONCLUSIONS: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.

Modelling local patterns of child mortality risk: a Bayesian Spatio-temporal analysis.

BACKGROUND: Globally, child mortality rate has remained high over the years, but the figure can be reduced through proper implementation of spatially-targeted public health policies. Due to its alarming rate in comparison to North American standards, child mortality is particularly a health concern in Mexico. Despite this fact, there remains a dearth of studies that address its spatio-temporal identification in the country. The aims of this study are i) to model the evolution of child mortality risk at the municipality level in Greater Mexico City, (ii) to identify municipalities with high, medium, and low risk over time, and (iii) using municipality trends, to ascertain potential high-risk municipalities. METHODS: In order to control for the space-time patterns of data, the study performs a Bayesian spatio-temporal analysis. This methodology permits the modelling of the geographical variation of child mortality risk across municipalities, within the studied time span. RESULTS: The analysis shows that most of the high-risk municipalities were in the east, along with a few in the north and west areas of Greater Mexico City. In some of them, it is possible to distinguish an increasing trend in child mortality risk. The outcomes highlight municipalities currently presenting a medium risk but liable to become high risk, given their trend, after the studied period. Finally, the likelihood of child mortality risk illustrates an overall decreasing tendency throughout the 7-year studied period. CONCLUSIONS: The identification of high-risk municipalities and risk trends may provide a useful input for policymakers seeking to reduce the incidence of child mortality. The results provide evidence that supports the use of geographical targeting in policy interventions.

A Hybrid Visual-Based SLAM Architecture: Local Filter-Based SLAM with KeyFrame-Based Global Mapping.

This work presents a hybrid visual-based SLAM architecture that aims to take advantage of the strengths of each of the two main methodologies currently available for implementing visual-based SLAM systems, while at the same time minimizing some of their drawbacks. The main idea is to implement a local SLAM process using a filter-based technique, and enable the tasks of building and maintaining a consistent global map of the environment, including the loop closure problem, to use the processes implemented using optimization-based techniques. Different variants of visual-based SLAM systems can be implemented using the proposed architecture. This work also presents the implementation case of a full monocular-based SLAM system for unmanned aerial vehicles that integrates additional sensory inputs. Experiments using real data obtained from the sensors of a quadrotor are presented to validate the feasibility of the proposed approach.

The Cognitive-Emotional Design and Study of Architectural Space: A Scoping Review of Neuroarchitecture and Its Precursor Approaches.

Humans respond cognitively and emotionally to the built environment. The modern possibility of recording the neural activity of subjects during exposure to environmental situations, using neuroscientific techniques and virtual reality, provides a promising framework for future design and studies of the built environment. The discipline derived is termed "neuroarchitecture". Given neuroarchitecture's transdisciplinary nature, it progresses needs to be reviewed in a contextualised way, together with its precursor approaches. The present article presents a scoping review, which maps out the broad areas on which the new discipline is based. The limitations, controversies, benefits, impact on the professional sectors involved, and potential of neuroarchitecture and its precursors' approaches are critically addressed.

Monopolar Radiofrequency Energy Delivered by a Conductive Endovascular Basket or Guidewire Leads to Thermal Occlusion in a Swine Model.

PURPOSE: To assess the feasibility of inducing vascular occlusion by application of radiofrequency (RF) energy via conductive endovascular wires or baskets. MATERIALS AND METHODS: A retrievable nitinol basket and stainless steel guidewire with a platinum tip were evaluated as conductors for endovascular application of RF energy. Tissue-mimicking thermochromic gel phantoms that change color with heating were cast with 2-, 5-, and 7-mm-diameter lumens and filled with 37 oC saline. After ablation, the phantoms were sectioned, and the thermal footprints were evaluated. Six castrated male domestic swine underwent endovascular ablation using the basket in iliac arteries and guidewires in renal arteries. Post-procedural angiography was performed, and postmortem arterial segments were resected for histopathologic analysis. RESULTS: In the phantom, the depth of thermal change in the 5- and 7-mm lumens averaged 6.3 and 6.0 mm along the basket, respectively, and in the 2- and 5-mm lumens, the depth of thermal change averaged 1.9 and 0.5 mm along the wire, respectively. In the swine, RF energy delivery led to angiographic occlusion at 12 of 13 sites. Thermal injury and occlusion were similar at the proximal, middle, and distal basket treatment zone, whereas injury and occlusion decreased from the proximal to the distal end of the 5-cm wire treatment zone. CONCLUSIONS: Endovascular delivery of RF energy via a conductive basket in medium-sized arteries or a guidewire in small arteries led to acute angiographic and histologic occlusion. The potential to induce stasis might be useful in settings where rapid occlusion is desirable.

Endobronchial Navigation Guided by Cone-Beam CT-Based Augmented Fluoroscopy without a Bronchoscope: Feasibility Study in Phantom and Swine.

PURPOSE: To evaluate the accuracy of cone-beam computed tomography (CT)-based augmented fluoroscopy (AF) image guidance for endobronchial navigation to peripheral lung targets. METHODS: Prototypic endobronchial navigation AF software that superimposed segmented airways, targets, and pathways based on cone-beam CT onto fluoroscopy images was evaluated ex vivo in fixed swine lungs and in vivo in healthy swine (n = 4) without a bronchoscope. Ex vivo and in vivo (n = 3) phase 1 experiments used guide catheters and AF software version 1, whereas in vivo phase 2 (n = 1) experiments also used an endovascular steerable guiding sheath, upgraded AF software version 2, and lung-specific low-radiation-dose protocols. First-pass navigation success was defined as catheter delivery into a targeted airway segment solely using AF, with second-pass success defined as reaching the targeted segment by using updated AF image guidance based on confirmatory cone-beam CT. Secondary outcomes were navigation error, navigation time, radiation exposure, and preliminary safety. RESULTS: First-pass success was 100% (10/10) ex vivo and 19/24 (79%) and 11/15 (73%) for in vivo phases 1 and 2, respectively. Phase 2 second-pass success was 4/4 (100%). Navigation errors were 2.2 ± 1.2 mm ex vivo and 4.9 ± 3.2 mm and 4.0 ± 2.6 mm for in vivo phases 1 and 2, respectively. No major device-related complications were observed in the in vivo experiments. CONCLUSIONS: Endobronchial navigation is feasible and accurate with cone-beam CT-based AF image guidance. AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy.