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Due to technological advancements, robotics is findings its way into the classroom. However, workload for teachers is high, and teachers sometimes lack the knowledge to implement robotics education. A key factor of robotics education is peer learning, and having students (near-)peers teach them robotics could diminish workload. Therefore, this study implemented near-peer teaching in robotics education. 4 K10-11 secondary school students were teachers to 83 K5-6 primary school students. The intervention included 4 3-hour robotics lessons in Dutch schools. Primary school students completed a pre- and post-intervention questionnaire on their STEM-attitudes and near-peer teaching experience, and a report on their learning outcomes. Interaction with near-peer teachers was observed. After the lessons, a paired-samples t-test showed that students had a more positive attitude towards engineering and technology. Students also reported a positive near-peer teaching experience. Conventional content analysis showed that students experienced a gain in programming and robotics skill after the lessons, and increased conceptual understanding of robotics. The role the near peer teachers most frequently fulfilled was formative assessor. Near-peer teachers could successfully fulfil a role as an engaging information provider. This study shows that near-peer teachers can effectively teach robotics, diminishing workload for teachers. Furthermore, near-peer robotics lessons could lead to increased STEM-attitudes.

Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.

BackgroundAdjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration).Methods and findingsBetween June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses.ConclusionsAlthough MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen.Trial registrationHVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

Intense development of Offshore Wind Farms (OWFs) has occurred in the North Sea with several more farms planned for the near future. These OWFs pose a threat to marine megafauna stressing the need to mitigate the impact of human activities. To help mitigate impacts, the Before After Gradient (BAG) design was proposed. We explored the use of the BAG method on megafauna sightings recorded at different distances from OWFs in the southern North Sea. We predicted intra-annual variability in species distribution, then correlated species distribution with the presence of operational OWFs and investigated the potential impact the operation of prospective OWFs may have on species distribution. Four patterns of intra-annual variability were predicted: species most abundant in spring, in winter, in both spring and winter, or all year round. We recommend that future OWF constructions be planned in summer and early fall to minimise impact on cetaceans and that offshore areas off northern France and Belgium be avoided to minimise impact on seabirds. Our prospective analysis predicted a decreased density for most species with the operation of prospective OWFs. Prospective approaches, using e.g. a BAG design, are paramount to inform species conservation as they can forecast the likely responses of megafauna to anthropogenic disturbances.

The distribution of wild animals and their monitoring over large areas raises many logistical and technical difficulties that hinder the collection of observation data. The use of Geographic Information Systems (GIS) has increased significantly in recent years. QGIS, an open-source GIS software dedicated to the processing of geospatial data, enables the development of dedicated plugins for specific workflows. The open-source PelaSIG plugin has been developed in Python for QGIS 3 to facilitate and standardise the different steps before and after distance sampling surveys. It brings together a set of tools for survey preparation, automatic data checking, visualisation and presentation of survey effort and sightings to provide an adapted workflow. This plugin is currently designed to process dedicated aerial datasets collected with the SAMMOA software during marine megafauna surveys (i.e., marine mammals, seabirds, elasmobranchs, sea turtles, etc.). Here, we first describe the different tools already available, and then, we present an application with the dataset from the aerial survey of the ACCOBAMS Survey Initiative (ASI) conducted in 2018 over the Mediterranean Sea and using a multi-target protocol.

Summary: Bacillus velezensis isolates are among the most promising plant-associated beneficial bacteria used as biocontrol agents. However, various aspects of the chemical communication between the plant and these beneficials, determining root colonization ability, remain poorly described. Here we investigated the molecular basis of such interkingdom interaction occurring upon contact between Bacillus velezensis and its host via the sensing of pectin backbone homogalacturonan (HG). We showed that B. velezensis stimulates key developmental traits via a dynamic process involving two conserved pectinolytic enzymes. This response integrates transcriptional changes leading to the switch from planktonic to sessile cells, a strong increase in biofilm formation, and an accelerated sporulation dynamics while conserving the potential to efficiently produce specialized secondary metabolites. As a whole, we anticipate that this response of Bacillus to cell wall–derived host cues contributes to its establishment and persistence in the competitive rhizosphere niche and ipso facto to its activity as biocontrol agent.

Abstract Introduction Over the last 5 years, the analysis of respiratory patterns presents a growing usage in clinical and research purposes, but there is still currently a lack of easy‐to‐use and affordable devices to perform such kind of evaluation. Objectives The aim of this study is to validate a new specifically developed method, based on Kinect sensor, to assess respiratory patterns against spirometry under various conditions. Methods One hundred and one participants took parts in one of the three validations studies. Twenty‐five chronic respiratory disease patients (14 with chronic obstructive pulmonary disease (COPD) [65 ± 10 years old, FEV1 = 37 (15% predicted value), VC = 62 (20% predicted value)], and 11 with lung fibrosis (LF) [64 ± 14 years old, FEV1 = 55 (19% predicted value), VC = 62 (20% predicted value)]) and 76 healthy controls (HC) were recruited. The correlations between the signal of the Kinect (depth and respiratory rate) and the spirometer (tidal volume and respiratory rate) were computed in part 1. We then included 66 HC to test the ability of the system to detect modifications of respiratory patterns induced by various conditions known to modify respiratory pattern (cognitive load, inspiratory load and combination) in parts 2 and 3. Results There is a strong correlation between the depth recorded by the Kinect and the tidal volume recorded by the spirometer: r = 0.973 for COPD patients, r = 0.989 for LF patients and r = 0.984 for HC. The Kinect is able to detect changes in breathing patterns induced by different respiratory disturbance conditions, gender and oral task. Conclusions Measurements performed with the Kinect sensors are highly correlated with the spirometer in HC and patients with COPD and LF. Kinect is also able to assess respiratory patterns under various loads and disturbances. This method is affordable, easy to use, fully automated and could be used in the current clinical context. Respiratory patterns are important to assess in daily clinics. However, there is currently no affordable and easy‐to‐use tool to evaluate these parameters in clinics. We validated a new system to assess respiratory patterns using the Kinect sensor in patients with chronic respiratory diseases.

Abstract Species Distribution Models are commonly used with surface dynamic environmental variables as proxies for prey distribution to characterise marine top predator habitats. For oceanic species that spend lot of time at depth, surface variables might not be relevant to predict deep-dwelling prey distributions. We hypothesised that descriptors of deep-water layers would better predict the deep-diving cetacean distributions than surface variables. We combined static variables and dynamic variables integrated over different depth classes of the water column into Generalised Additive Models to predict the distribution of sperm whales Physeter macrocephalus and beaked whales Ziphiidae in the Bay of Biscay, eastern North Atlantic. We identified which variables best predicted their distribution. Although the highest densities of both taxa were predicted near the continental slope and canyons, the most important variables for beaked whales appeared to be static variables and surface to subsurface dynamic variables, while for sperm whales only surface and deep-water variables were selected. This could suggest differences in foraging strategies and in the prey targeted between the two taxa. Increasing the use of variables describing the deep-water layers would provide a better understanding of the oceanic species distribution and better assist in the planning of human activities in these habitats.

Due to technological advancements, robotics is findings its way into the classroom. However, workload for teachers is high, and teachers sometimes lack the knowledge to implement robotics education. A key factor of robotics education is peer learning, and having students (near-)peers teach them robotics could diminish workload. Therefore, this study implemented near-peer teaching in robotics education. 4 K10-11 secondary school students were teachers to 83 K5-6 primary school students. The intervention included 4 3-hour robotics lessons in Dutch schools. Primary school students completed a pre- and post-intervention questionnaire on their STEM-attitudes and near-peer teaching experience, and a report on their learning outcomes. Interaction with near-peer teachers was observed. After the lessons, a paired-samples t-test showed that students had a more positive attitude towards engineering and technology. Students also reported a positive near-peer teaching experience. Conventional content analysis showed that students experienced a gain in programming and robotics skill after the lessons, and increased conceptual understanding of robotics. The role the near peer teachers most frequently fulfilled was formative assessor. Near-peer teachers could successfully fulfil a role as an engaging information provider. This study shows that near-peer teachers can effectively teach robotics, diminishing workload for teachers. Furthermore, near-peer robotics lessons could lead to increased STEM-attitudes.

Abstract Background Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome. Methods We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months. Discussion We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO. Trial registration ClinicalTrials.gov NCT04536272 . Registered on 2 September 2020. Netherlands Trial Register NL7969

Machine learning models have proven to be reliable methods in classification tasks. However, little research has been conducted on the classification of dwelling characteristics based on smart meter and weather data before. Gaining insights into dwelling characteristics, which comprise of the type of heating system used, the number of inhabitants, and the number of solar panels installed, can be helpful in creating or improving the policies to create new dwellings at nearly zero-energy standard. This paper compares different supervised machine learning algorithms, namely Logistic Regression, Support Vector Machine, K-Nearest Neighbor, and Long-short term memory, and methods used to correctly implement these algorithms. These methods include data pre-processing, model validation, and evaluation. Smart meter data, which was used to train several machine learning algorithms, was provided by Groene Mient. The models that were generated by the algorithms were compared on their performance. The results showed that the Long-short term memory performed the best with 96% accuracy. Cross Validation was used to validate the models, where 80% of the data was used for training purposes and 20% was used for testing purposes. Evaluation metrics were used to produce classification reports, which indicates that the Long-short term memory outperforms the compared models on the evaluation metrics for this specific problem.

Objective: This study aimed to determine the frequency of spastic equinovarus foot (SEF) treatments. Materials and Methods: the medical files of 622 patients treated for SEF were reviewed. Results: SEF resulted from stroke in 66%. The most frequent pattern was equinovarus in 56%, knee recurvatum in 55%, and claw toes in 41%. Patients benefited from surgical treatment in 59%, including neurotomy in 22%, tendon surgery in 12%, and a combined surgery in 25%. Conclusion: Surgery was performed in 59% of the cases. The type of treatment was influenced by the preoperative diagnostic nerve block assessment.

In this study the electron density of an atmospheric plasma generated between a pin electrode and a water surface is measured by determining the Stark broadening of H α and H β emission lines. Comparable values for the electron density are achieved using the H α and H β broadening obtained in separate measurements. During the temporally evolving system, increasing electron densities are measured of 0.5 − 3 ⋅ 10 15 cm−3 during the plasma treatment of 5–10 min. The effect of the water temperature on plasma-water interaction is investigated by heating the water to ≈ 70 ∘ C prior to the measurements. This resulted in higher gas temperatures during the discharge up to 2500 K and 4000 K for positively and negatively pulsed discharge, respectively. Furthermore, an earlier increase of electron density and conductivity of the water is measured for the preheated experiments. The humidity of the gas is likely to be an important parameter causing the observed results. [ABSTRACT FROM AUTHOR]

Plants, being sessile organisms, constantly need to respond to environmental stresses, often leading to the accumulation of reactive oxygen species (ROS). While ROS can be harmful, they also act as second messengers guiding plant growth and stress responses. Because chloroplasts are sensitive to environmental changes and are both a source and a target of ROS during stress conditions, they are important in conveying environmental changes to the nucleus, where acclimation responses are coordinated to maintain organellar and overall cellular homeostasis. ANAC102 has previously been established as a regulator of β-cyclocitral-mediated chloroplast-to-nucleus signaling, protecting plants against photooxidative stress. However, debates persist about where ANAC102 is located—in chloroplasts or in the nucleus. Our study, utilizing the genomic ANAC102 sequence driven by its native promoter, establishes ANAC102 primarily as a nuclear protein, lacking a complete N-terminal chloroplast-targeting peptide. Moreover, our research reveals the sensitivity of plants overexpressing ANAC102 to severe superoxide-induced chloroplast oxidative stress. Transcriptome analysis unraveled a dual role of ANAC102 in negatively and positively regulating genome-wide transcriptional responses to chloroplast oxidative stress. Through the integration of published data and our own study, we constructed a comprehensive transcriptional network, which suggests that ANAC102 exerts direct and indirect control over transcriptional responses through downstream transcription factor networks, providing deeper insights into the ANAC102-mediated regulatory landscape during oxidative stress. [ABSTRACT FROM AUTHOR]

Simple Summary: This nationwide cohort study evaluated the incidence and severity of immune-related adverse events (irAEs) in melanoma patients receiving adjuvant versus advanced anti-PD-1 therapy. A total of 1465 advanced melanoma patients and 908 adjuvant-treated patients were included. Patients in the adjuvant group were younger, had superior ECOG performance status, and had fewer comorbidities compared to those in the advanced group. No significant difference was observed in the incidence of grade III-IV irAEs between the two groups. However, higher ECOG status (>1) and the presence of any comorbidities were independently associated with an increased risk of irAE development across both treatment settings. Although adjuvant therapy was not linked to a heightened risk of severe irAEs compared to advanced therapy, it was more frequently discontinued due to toxicity in the adjuvant group. These findings provide critical insights for informing patient consultations regarding adjuvant anti-PD-1 treatment. Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment. [ABSTRACT FROM AUTHOR]

Abstract Aim Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. Methods and results The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R) will collect data from ACHD evaluated or listed for heart or heart‐combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989–2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All‐cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. Conclusion The ARTORIA‐R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Computational thinking is a popular student skill on a steep rise today. Nevertheless, the assessment of this skill is a matter of contention. This pilot study examines whether computational and logical thinking are related. Therefore, we investigated the effect of a robotics course concerning logical thinking and computational thinking on 14-year-old Dutch students. Thirty-five students were pre-tested to assess their logical thinking and post-tested for their logical thinking and their computational thinking. The intervention group (N = 11) followed a robotics course between the pre- and post-test. This study's results show a significant positive correlation between computational and logical thinking. This study, with small sample size, does not show the effect of the robotics course on either logical or computational thinking.

Although the first dissection of the human ovary dates back to the 17th century, its characterization is still limited. Here, the authors have unraveled a unique biophysical and topological phenotype of reproductive-age tissue, bridging biophysics and female fertility and providing a blueprint for the artificial ovary.

Out-of-field patient doses in proton therapy are dominated by neutrons. Currently, they are not taken into account by treatment planning systems. There is an increasing need to include out-of-field doses in the dose calculation, especially when treating children, pregnant patients, and patients with implants. In response to this demand, this work presents the first steps towards a tool for the prediction of out-of-field neutron doses in pencil beam scanning proton therapy facilities. As a first step, a general Monte Carlo radiation transport model for simulation of out-of-field neutron doses was set up and successfully verified by comparison of simulated and measured ambient neutron dose equivalent and neutron fluence energy spectra around a solid water phantom irradiated with a variation of different treatment plan parameters. Simulations with the verified model enabled a detailed study of the variation of the neutron ambient dose equivalent with field size, range, modulation width, use of a range shifter, and position inside the treatment room. For future work, it is planned to use this verified model to simulate out-of-field neutron doses inside the phantom and to verify the simulation results by comparison with previous in-phantom measurement campaigns. Eventually, these verified simulations will be used to build a library and a corresponding tool to allow assessment of out-of-field neutron doses at pencil beam scanning proton therapy facilities.

Artificial Neural Networks (ANNs) have achieved unequaled performance for numerous problems in many areas of Science, Business, Public Policy, and more. While experts are familiar with performance-oriented software and underlying theory, ANNs are difficult to comprehend for non-experts because it requires skills in programming, background in mathematics and knowledge of terminology and concepts. In this work, we release EpyNN, an educational Python resource meant for a public willing to understand key concepts and practical implementation of scalable ANN architectures from concise, homogeneous and idiomatic source code. EpyNN contains an educational Application Programming Interface (API), educational workflows from data preparation to ANN training and a documentation website setting side-by-side code, mathematics, graphical representation and text to facilitate learning and provide teaching material. Overall, EpyNN provides basics in Python for individuals who wish to learn, teach or develop from scratch.

PurposeThis study aims to characterize the neutron radiation field inside a scanning proton therapy treatment room including the impact of different pediatric patient sizes.Materials and MethodsWorking Group 9 of the European Radiation Dosimetry Group (EURADOS) has performed a comprehensive measurement campaign to measure neutron ambient dose equivalent, H*(10), at eight different positions around 1-, 5-, and 10-year-old pediatric anthropomorphic phantoms irradiated with a simulated brain tumor treatment. Several active detector systems were used.ResultsThe neutron dose mapping within the gantry room showed that H*(10) values significantly decreased with distance and angular deviation with respect to the beam axis. A maximum value of about 19.5 µSv/Gy was measured along the beam axis at 1 m from the isocenter for a 10-year-old pediatric phantom at 270° gantry angle. A minimum value of 0.1 µSv/Gy was measured at a distance of 2.25 m perpendicular to the beam axis for a 1-year-old pediatric phantom at 140° gantry angle.The H*(10) dependence on the size of the pediatric patient was observed. At 270° gantry position, the measured neutron H*(10) values for the 10-year-old pediatric phantom were up to 20% higher than those measured for the 5-year-old and up to 410% higher than for the 1-year-old phantom, respectively.ConclusionsUsing active neutron detectors, secondary neutron mapping was performed to characterize the neutron field generated during proton therapy of pediatric patients. It is shown that the neutron ambient dose equivalent H*(10) significantly decreases with distance and angle with respect to the beam axis. It is reported that the total neutron exposure of a person staying at a position perpendicular to the beam axis at a distance greater than 2 m from the isocenter remains well below the dose limit of 1 mSv per year for the general public (recommended by the International Commission on Radiological Protection) during the entire treatment course with a target dose of up to 60 Gy. This comprehensive analysis is key for general neutron shielding issues, for example, the safe operation of anesthetic equipment. However, it also enables the evaluation of whether it is safe for parents to remain near their children during treatment to bring them comfort. Currently, radiation protection protocols prohibit the occupancy of the treatment room during beam delivery.

Transplantation of heart following donation after circulatory death (DCD) was recently introduced into clinical practice. Ex vivo reperfusion following DCD and retrieval is deemed necessary in order to evaluate the recovery of cardiac viability after the period of warm ischemia. We tested the effect of four different temperatures (4 °C—18 °C—25 °C—35 °C) on cardiac metabolism during 3-h ex vivo reperfusion in a porcine model of DCD heart. We observed a steep fall in high-energy phosphate (ATP) concentrations in the myocardial tissue at the end of the warm ischemic time and only limited regeneration during reperfusion. Lactate concentration in the perfusate increased rapidly during the first hour of reperfusion and slowly decreased afterward. However, the temperature of the solution does not seem to have an effect on either ATP or lactate concentration. Furthermore, all cardiac allografts showed a significant weight increase due to cardiac edema, regardless of the temperature.

Combining forest growth models with remotely sensed data is possible under a generalized hierarchical model-based (GHMB) inferential framework. This implies the existence of two submodels: the growth model itself (⁠|$\mathcal{M}_{1}$|⁠) and a second submodel that links the growth predictions to some remotely sensed variables (⁠|$\mathcal{M}_{2}$|⁠). Analytical GHMB estimators are available to fit submodel |$\mathcal{M}_{2}$| and account for the uncertainty stemming from submodel |$\mathcal{M}_{1}$|⁠ , i.e. the growth model. However, when the growth model is individual based, it is usually too complex to be differentiated with respect to its parameters. As a result, the analytical GHMB estimators cannot be used. In this study, we developed a bootstrap approach for the GHMB inferential framework in order to combine individual-based forest growth models with remotely sensed data. Through simulation studies, we showed that the bootstrap estimators were nearly unbiased when both submodels were linear. The estimator of the parameter estimates remained nearly unbiased when submodel |$\mathcal{M}_{1}$| became complex, i.e. non-differentiable, and submodel |$\mathcal{M}_{2}$| was nonlinear with heterogeneous variances and correlated error terms. The variance estimator showed some biases but these were relatively small. We further demonstrated through a real-world case study that the predictions of a complex individual-based model could be linked to a Landsat-8 near-infrared spectral band in the boreal forest zone of Quebec, Canada. [ABSTRACT FROM AUTHOR]

Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments. Unfortunately, no method exists in clinics for the computation of the out-of-field dose distributions in proton therapy. To help overcome this limitation, a computational tool has been developed based on the Monte Carlo code TOPAS. The purpose of this work is to evaluate the accuracy of this tool in comparison to experimental data obtained from an anthropomorphic phantom irradiation. An anthropomorphic phantom of a 5-year-old child (ATOM, CIRS) was irradiated for a brain tumor treatment in an IBA Proteus Plus facility using a pencil beam dedicated nozzle. The treatment consisted of three pencil beam scanning fields employing a lucite range shifter. Proton energies ranged from 100 to 165 MeV. A median dose of 50.4 Gy(RBE) with 1.8 Gy(RBE) per fraction was prescribed to the initial planning target volume (PTV), which was located in the cerebellum. Thermoluminescent detectors (TLDs), namely, Li-7-enriched LiF : Mg, Ti (MTS-7) type, were used to detect gamma radiation, which is produced by nuclear reactions, and secondary as well as recoil protons created out-of-field by secondary neutrons. Li-6-enriched LiF : Mg,Cu,P (MCP-6) was combined with Li-7-enriched MCP-7 to measure thermal neutrons. TLDs were calibrated in Co-60 and reported on absorbed dose in water per target dose (μGy/Gy) as well as thermal neutron dose equivalent per target dose (μSv/Gy). Additionally, bubble detectors for personal neutron dosimetry (BD-PND) were used for measuring neutrons (>50 keV), which were calibrated in a Cf-252 neutron beam to report on neutron dose equivalent dose data. The Monte Carlo code TOPAS (version 3.6) was run using a phase-space file containing 1010 histories reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1) on all voxels scoring more than 50% of the maximum dose. The primary beam was modeled following a Fermi–Eyges description of the spot envelope fitted to measurements. For the Monte Carlo simulation, the chemical composition of the tissues represented in ATOM was employed. The dose was tallied as dose-to-water, and data were normalized to the target dose (physical dose) to report on absorbed doses per target dose (mSv/Gy) or neutron dose equivalent per target dose (μSv/Gy), while also an estimate of the total organ dose was provided for a target dose of 50.4 Gy(RBE). Out-of-field doses showed absorbed doses that were 5 to 6 orders of magnitude lower than the target dose. The discrepancy between TLD data and the corresponding scored values in the Monte Carlo calculations involving proton and gamma contributions was on average 18%. The comparison between the neutron equivalent doses between the Monte Carlo simulation and the measured neutron doses was on average 8%. Organ dose calculations revealed the highest dose for the thyroid, which was 120 mSv, while other organ doses ranged from 18 mSv in the lungs to 0.6 mSv in the testes. The proposed computational method for routine calculation of the out-of-the-field dose in proton therapy produces results that are compatible with the experimental data and allow to calculate out-of-field organ doses during proton therapy.

Abstract Background Since its discovery in 2007, the importance of the human gut bacterium Prevotella copri (P. copri) has been widely recognized with its links to diet and health status and potential as next generation probiotic. Therefore, precise, convenient and cost-effective diagnostic tools for the detection and quantification of P. copri from clinical and environmental samples are needed. Results In this study, a Sybr Green qPCR protocol for P. copri detection and quantification was developed and tested on P. copri-spiked murine faeces samples targeting both the 16S rRNA gene and P. copri genome specific genes. The use of one 16S rRNA primer pair and 2 genome specific primer pairs resulted in at least 10x higher specificity and sensitivity than the primer-only PCR currently cited in the literature, reaching a sensitivity of 103 CFU/mL. Furthermore, we showed that the new 16S rRNA primer set provided the best balance of detection of a wide range of P. copri strains, while avoiding off-target detection of other Prevotella genus species. The quantification of P. copri in human stool samples using the new 16S rRNA primers also correlated well with 16S rRNA high throughput MiSeq sequencing data (r 2 = 0.6604, p = 0.0074). The two genome specific primer pairs on the other hand uniquely detect the DSM18205 reference strain, allowing differential detection of indigenous and experimentally administered P. copri populations. Finally, it was shown that SYBR green qPCR mixes have an influence on sensitivity and specificity, with Biorad SsoAdvanced Universal SYBR Green Supermix performing the best under our test conditions of six commercially available SYBR green master mixes. Conclusions This improved qPCR-based method will allow accurate P. copri identification and quantification. Moreover, this methodology can also be applied to identify other bacterial species in complex samples.

Abstract Over the past 35 years, ~1700 articles have characterized protein O-GlcNAcylation. Found in almost all living organisms, this post-translational modification of serine and threonine residues is highly conserved and key to biological processes. With half of the primary research articles using human models, the O-GlcNAcome recently reached a milestone of 5000 human proteins identified. Herein, we provide an extensive inventory of human O-GlcNAcylated proteins, their O-GlcNAc sites, identification methods, and corresponding references ( www.oglcnac.mcw.edu ). In the absence of a comprehensive online resource for O-GlcNAcylated proteins, this list serves as the only database of O-GlcNAcylated proteins. Based on the thorough analysis of the amino acid sequence surrounding 7002 O-GlcNAc sites, we progress toward a more robust semi-consensus sequence for O-GlcNAcylation. Moreover, we offer a comprehensive meta-analysis of human O-GlcNAcylated proteins for protein domains, cellular and tissue distribution, and pathways in health and diseases, reinforcing that O-GlcNAcylation is a master regulator of cell signaling, equal to the widely studied phosphorylation.

Non-nutritive sweeteners (NNS) are popular sugar replacements used in foods, beverages, and medications. Although NNS are considered safe by regulatory organizations, their effects on physiological processes such as detoxification are incompletely understood. Previous studies revealed that the NNS sucralose (Sucr) altered P-glycoprotein (PGP) expression in rat colon. We also demonstrated that early-life exposure to NNS Sucr and acesulfame potassium (AceK) compromises mouse liver detoxification. Building upon these initial discoveries, we investigated the impact of AceK and Sucr on the PGP transporter in human cells to assess whether NNS influence its key role in cellular detoxification and drug metabolism. We showed that AceK and Sucr acted as PGP inhibitors, competing for the natural substrate-binding pocket of PGP. Most importantly, this was observed after exposure to concentrations of NNS within expected levels from common foods and beverage consumption. This may suggest risks for NNS consumers, either when taking medications that require PGP as the primary detoxification transporter or during exposure to toxic compounds.

Because of its hands-on and integrative approach to STEM, educational robotics has become increasingly popular in recent years. Yet, a gender gap still exists in attitudes towards STEM studies and careers, especially among middle and high school students, potentially resulting in a lack of women in the STEM workforce. This study explores the effect of a robotics curriculum on Dutch 7th- and 8th-grade students’ attitude towards STEM subjects and careers, as assessed by the S-STEM survey. The results revealed no difference between the pre-test and post-test in attitudes toward STEM for both boys and girls. However, boys scored significantly higher than girls on attitude towards technology, engineering and future STEM studies on the post-test. A post hoc analysis revealed a significant difference between boys and girls on their attitude towards engineering and technology during the pre-test. These results demonstrate the difference between boys and girls in their attitudes towards STEM subjects and careers within the context of robotics education. Considering the lack of research on educational robotics among young teenagers, this field needs to be further studied to assess its effect on gender differences within attitudes towards STEM.

Background and Aims Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. Methods A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. Results During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P =.001] and age >50 years (HR 1.7, P =.016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P <.001) was a predictor of VAs. Conclusions ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation. [ABSTRACT FROM AUTHOR]