Background: Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints which has led to variations in constraints over the years. In this study we identify these variations in dose constraints within pediatric trials both in the United States (US) and in Europe used in the past 30 years. Procedure: All pediatric trials from the Children’s Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs-at-risk (OARs), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US trials and European trials Results: One hundred and five closed trials were included—93 US trials and 12 European trials. Thirty-eight separate OARs were found with high dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, US constraints were higher for seven OARs, lower for one, and identical for five. No OARs had constraints change systematically over the last 30 years. Conclusion: Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.

The rapid adaptation of SARS-CoV-2 within the host species and the increased viral transmission triggered the evolution of different SARS-CoV-2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS-CoV-2, the ongoing surge in the number of SARS-CoV-2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS-CoV-2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor-binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N-terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4-10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co-evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS-CoV-2 variants. Further, vaccines inducing both humoral and cell-mediated immune responses might prevent the escape of SARS-CoV-2 variants from neutralizing antibodies.

Individuals diagnosed with schizophrenia spectrum disorders (SSD) exhibit a constellation of sensory and perceptual impairments, including hyporeactivity to external input. However, individuals with SSD also report subjective experiences of sensory flooding, suggesting sensory hyperexcitability. To identify the extent to which behavioral indices of hyperexcitability are related to non-psychotic symptoms of schizophrenia, we tested a non-clinical population measured for schizophrenia-like traits (schizotypy), and a behavioral measure of sensory hyperexcitability, specifically the number of illusions seen in the Pattern Glare Test. Two samples totaling 913 individuals completed an online version of the Schizotypal Personality Questionnaire – Brief Revised (SPQ-BR) and the Pattern Glare Test. Individuals with higher schizotypy traits reported more illusions in the Pattern Glare Test. Additionally, one of the three SPQ-BR factors, the disorganized factor, significantly predicted the number of illusions reported. These data illustrate the potential for research in non-clinical samples to inform clinically relevant research.

Global food demand is expected to increase in the next decades pushing agricultural expansion and deforestation. However, food production in agricultural lands is just one dimension of food security, to which forest goods and services also contribute. In this paper, we aimed to explore the relationship between forest cover and food security. We hypothesised that food security is improved by both human-made and green infrastructure combined. To test this relationship, we explore the relationships between forest cover and a multidimensional index of food security that included both socioeconomic and natural variables taken from Brazilian official databases for 1,141 municipalities of the Brazilian Caatinga (a seasonally tropical dry forest). The index was formed by 12 principal components axes (12 PCs) and we found that financial poverty (PC 1) and economic inequality (PC 2) were the main determinants of food insecurity in Caatinga. We found that lowest food security values were found in two contrasting contexts: one is represented by poor and unequal municipalities with high forest cover while the other refers to poor and less unequal municipalities but with little forest cover. Municipalities with intermediate levels of forest cover had slightly higher food security, a consistent pattern across time (2006 and 2017). Win-win scenarios where both forest cover and food security increased with time were almost as common as lose-lose situations (25% and 22% respectively). This suggests a sort of balance between forests and human-made land uses and reinforces that natural capital contributes to food security. Zero-hunger is a main issue for sustainable development goals and our results adds to the notion that both sustainable use of forests and socioeconomic improvements must coexist rather than being treated as antagonistic policies.

Background: COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity’s effect on immune responses to COVID-19 vaccines is still unknown. Methods: We performed a meta-analysis of the literature and compared immune responses to COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Results: Totally, 11 studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (SMD = -0.228, 95% CI (-0.437, -0.019), P<0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. Conclusion: The present meta-analysis suggested that obesity was significantly associated with decreased responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel this relationship to prevent COVID-19 infection and transmission.

The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma are not well understood. We investigated whether the ambient levels of fine PM with aerodynamic diameter ≤ 2.5 microns (PM 2.5) are associated with alterations in circulating monocytes in children with or without asthma. Increased exposure to ambient PM 2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or LPS. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

Early warning signals (EWSs) represent a potentially universal tool for identifying whether a system is approaching a tipping point, and have been applied in fields including ecology, epidemiology, economics, and physics. This potential universality has led to the development of a suite of computational approaches aimed at improving the reliability of these methods. Classic methods based on univariate data have a long history of use, but recent theoretical advances have expanded EWSs to multivariate datasets, particularly relevant given advancements in remote sensing. More recently, novel machine learning approaches have been developed but have not been made accessible in the R environment. Here, we present EWSmethods – an R package that provides a unified syntax and interpretation of the most popular and cutting edge EWSs methods applicable to both univariate and multivariate time series. EWSmethods provides two primary functions for univariate and multivariate systems respectively, with two forms of calculation available for each: classical rolling window time series analysis, and the more robust expanding window. It also provides an interface to the Python machine learning model EWSNet which predicts the probability of a sudden tipping point or a smooth transition, the first of its form available to R users. This note details the rationale for this open-source package and delivers an introduction to its functionality for assessing resilience. We have also provided vignettes and an external website to act as further tutorials and FAQs.

Background: Occupational Therapists are needed for meeting the health, rehabilitation, and occupational needs of the population worldwide, but there is no strategy for strengthening the occupational therapy workforce against a backdrop of an insufficient and inequitable supply worldwide. Objective: To perform a situational assessment of occupational therapy workforce development and research toward informing a global human resources strategy for strengthening the profession. Method: A multi-methods design incorporating SWOT analysis based on scoping review findings, workforce development frameworks, and expert feedback. Results: Strengths included identified workforce research trends, gaps, and findings. Weaknesses included a shortage of workforce research, lack of uniform and readily available workforce datasets, absence of workforce research programs, over-reliance on descriptive and non-experimental research, lack of research on workforce topics (e.g., diversity), and lack of labor market or economic analyses. Opportunities are the availability of guidance and tools for strengthening the health and rehabilitation workforce worldwide, and increased membership from low- and middle-income countries (LMICs) in the international professional federation. Threats include the suboptimal funding of occupational therapy workforce research, the lack of profession-specific data on cross-professional datasets and studies, suboptimal educational capacity in LMICs, lack of universal professional regulation and uniform workforce data collection in many contexts, and a perceived lower priority of this health workforce focused on health and wellbeing rather than medical outcomes. Conclusion: This SWOT analysis identifies strengths and opportunities to be seized and weaknesses and threats to be addressed by development of a strategy for the global strengthening of the occupational therapy workforce.

Background There is a need for vaccines that can induce effective systemic, respiratory mucosal and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA and cellular immunity. Methods The aim of the present study was to determine the effectiveness of a new administration method of intratracheal (IT) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AS03 (S1-AS03 vaccine). Results S1-SF-10-IT vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-IT showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AS03-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AS03-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF10-IT, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusion Based on the need for effective systemic, respiratory and cellular immunity, the S1-SF-10-IT vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.

Synovial chondromatosis is a rare benign condition characterized by chondral proliferation from synovium forming loose bodies which can occur extra-articularly and intra-articularly. Surgical removal remains the mainstay of treatment for synovial chondromatosis. Due to the risk of recurrence, every case must be followed up with an MRI.

Soil phosphorus (P) is an essential nutrient that controls wetland productivity and ecological functions. However, the effects of soil P forms on P availability during wetland degradation are relatively unknown. Soil samples from differently degraded marshes, including relatively pristine marsh (RPM), lightly degraded marsh (LDM), moderately degraded marsh (MDM), and heavily degraded marsh (HDM), were collected to investigate the changes in soil P forms and its regulation on P availability in the Zoige Plateau, China. We observed that compared with RPM, the main changes in total P concentration were a significant increase of 31.6%–44.2% in the 0–30 cm soil layers of LDM and MDM, and the available P concentration increased in LDM and MDM but decreased in HDM with a lower P activation coefficient. Marsh degradation increased the concentration and proportion of dicalcium phosphates, P occluded in iron hydroxides, and organic P but decreased those of iron oxide surfaces adsorbed P and apatite P. Soil available P was mainly related to organic P and P non-occluded in iron oxide minerals that might also be non-negligible direct source of available P. The transformation from apatite P to organic P was an important regulation mechanism of P availability in soils during marsh degradation. This study revealed the risk of P limitation in heavily degraded marsh soils and established the mechanism by which marsh degradation significantly influences soil P availability. Therefore, some measure of on improving P availability should be implement for the ecological restoration of heavily degraded marsh in the future, such as grazing exclusion and the application of organic fertiliser.

We report the case of a 33-year-old man with a self-inflicted neck wound with severe hypopharynx injury, and hemorrhagic shock, which was well-managed by a trauma surgeon trained in esophageal surgery. Training in cervical lymph node dissection for esophageal cancer could be useful for management of penetrating neck injuries.

Substance use disorder (SUD) is a chronic condition with maintained abuse of a substance leading to physiological and psychological alterations and often changes in cognitive and social behaviours. Current therapies mainly consist of psychotherapy coupled with medication; however, alarmingly high relapse rates reveal the shortcomings of the current standard of care. The signalling and expression profile, and neurological function of the serotonin 2C receptor (5-HT2C receptor) make it an ideal candidate of interest for the treatment of SUD. This is further corroborated by pre-clinical and clinical evidence of therapeutically relevant compounds acting at the 5-HT2C receptor. Notwithstanding, drug binding at closely related serotonin receptor subtypes has impeded drug development. More recently, psychedelics, which broadly act at 5-HT2 receptors, have indicated promising potential for the treatment of SUD, implicating in part, the 5-HT2C receptor. The modern psychedelic movement has rekindled therapeutic interest in the 5-HT2C receptor, resulting in an influx of new studies, especially structural analyses. This review delves into the structural, molecular and cellular mechanisms governing the 5-HT2C receptor function, in the context of SUD. This provides the basis of the preclinical and clinical evidence for their role in SUD and highlights the potential for future exploration.

Chaotic flow inside porous media accelerates the transport, mixing, and reaction of molecules and particles in widespread natural and factitious processes. Current macroscopic models based on the average pore-scale variations show obvious limitations in the prediction of many chemical processes. In this paper, we reconstruct microscopic foam structures using Micro Computed Tomography to simulate fluid flow in structured ZSM-5@SiC foam catalyst. Moreover, we propose a conceptual model based on the microscopic mean square displacement theory to characterize the effective dispersion inside an open-cell foam. This model will explain the flow characteristics of confined fluid inside the porous media from fluid elements perspective. Particularly, dispersion factor and structure factor, as key parts of this model, perfectly interpret the driving characteristics of pressure drop, velocity different, and reaction in continuous foam media flow. This work also provides a unique means of predicting reaction kinetics of confined fluid in structured foam catalyst.

Nowadays, the copper nitride (Cu 3N) is of great interest as a new solar absorber material, flexible and lightweight thin film solar cells. This material is a metastable semiconductor, non-toxic, composed of earth-abundant elements, and its band gap energy can be easily tunable in the range 1.4 to 1.8 eV. For this reason, it has been proposed for many applications in the solar energy conversion field. The main aim of this work is to evaluate the properties of the Cu 3N thin films fabricated by reactive radio-frequency (RF) magnetron sputtering at different RF power values to determine its potential as light absorber. The Cu 3N films were fabricated at room temperature (RT) from a Cu metallic target at the RF power ranged from 25 to 200 W on different substrates (silicon and glass). The pure nitrogen flux was set to 20 sccm, and the working pressures were set to 3.5 Pa and 5 Pa. The XRD results showed a transition from (100) to (111) preferred orientations when RF power increased; the AFM images revealed a granular morphology, while FTIR and Raman spectra exhibited the characteristics peaks related to Cu-N bonds, which became narrower when the RF power increased. Finally, to stablish the suitability of these films as absorber, the band gap energy was calculated from transmission spectra.

Aims: Nusinersen is administered intrathecally for treating spinal muscular atrophy (SMA). Procedural sedation is common with intrathecal treatment in children. This retrospective study presents our experience with procedural sedation during the intrathecal treatment of pediatric patients with SMA I, II, and III. Methods: Data were collected the from the anesthesia charts and electronic medical records of 14 pediatric patients with SMA types I, II, and III who underwent procedural sedation for repeated intrathecal treatments for SMA. Intravenous induction was performed, and patients were oxygenated with a face mask or nasal cannula while spontaneous breathing continued. Results: Fourteen patients were included in the study: one SMA I, eight SMA II, and five SMA III. They underwent 88 intrathecal nusinersen injections totally. In the one SMA I patient, of eight months, the procedure was performed under local anesthesia. In all other patients, the treatments were performed under procedural sedation. Different combinations of midazolam, ketamine, propofol, fentanyl, and remifentanil were used. The mean doses of the agents used were 0.03 mg/kg, 0.97 mg/kg, 2.71 mg/kg, 0.84 mcg/kg and 0.5 mcg/kg respectively. There were no intraoperative or postoperative complications. Conclusion: We found the procedural sedation to be sufficient, effective, and safe in SMA II and III pediatric patients who underwent nusinersen treatment intrathecally, provided anesthetic agents are titrated.and administered carefully.

Comment on: Effects of COVID-19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia

LEO satellite networks have risen to the forefront of study with the dynamic topology changes, varying service requirements and intermittent inter-satellite links (ISLs). Resource scheduling mechanism is the key to determining communication efficiency. However, the state-of-the-art cannot achieve high resource efficiency under both heavy and burst traffic loads, and the applicability of parameters design is insufficient under intermittent ISLs. Considering this, we propose a dynamic even distribution mechanism combined with network coding DENC. This novel mechanism obtains the service requirements and allocates resources dynamically through the even distribution algorithm to balance between network maintenance overhead and idle resources waste, and improves the success probability of transmission based on network coding to balance between retransmission and redundancy. In this paper, we establish performance analysis and resource efficiency optimization models to optimize the parameters such as maintenance frequency and coding coefficient. Besides, we construct a system-level simulation platform. Mathematical and simulation results indicate that the DENC performs better than SAHN-MAC, ICSMA, CSMA-TDMA and HTM under dynamic service requirements and intermittent ISLs, and the resource efficiency can be improved by about 130%.