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Social-emotional problems can emerge as early as the first years of life and are associated with a broad range of negative outcomes throughout the lifespan. There is convincing evidence that poorer executive functions (EF) are associated with more social-emotional problems during childhood and adolescence. However, the nature, persistence, and direction of the associations between different components of EF and social-emotional problems in toddlerhood remain unclear. Using two complementary statistical approaches, the present study aimed to (a) identify the role of EF components (inhibitory control, cognitive flexibility, and working memory) in the emergence and maintenance of social-emotional problems during toddlerhood, and (b) explore potential bidirectional associations between toddlers’ EF and social-emotional problems. EF and social-emotional problems were assessed around 13, 19, and 28 months of age in a sample of 133 typically developing toddlers (51% boys) from mostly White middle-class families. At each time point, EF were measured with three behavioral tasks and social-emotional problems with a well-validated questionnaire completed by mothers. Multilevel growth models revealed a significant increase in social-emotional problems across toddlerhood and a negative association between inhibitory control and social-emotional problems that persisted across time. Controlling for stability across time, cross-lagged panel models indicated that child inhibitory control at 19 months negatively predicted child social-emotional problems at 28 months, but not the reverse. This study highlights that toddlerhood is a period of significant increase in social-emotional problems and provides evidence for the protective role of early inhibitory control skills against the development of social-emotional problems during toddlerhood.

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.5, 15, 150 and 300 pM) of a PBDE mixture from one to six days post-fertilization (dpf). Hatching rates, mortality and general morphology were assessed during the exposure period. A delay in hatching was observed at the two highest PBDEs concentrations and mortality rate increased at 6 dpf. By 4 dpf, larvae exposed to 150 pM and 300 pM PBDEs developed an upcurved phenotype. Analysis of motor behavior at 6 dpf revealed that PBDE exposure acutely reduced locomotion. To further analyze these motor deficits, we assessed the neural network density and motor neuron and neuromuscular junctions (NMJ) development by immunostaining and imaging. Acetylated α-tubulin staining revealed a significant loss of neurons in a dose-dependent manner. Synaptic vesicle protein 2 (SV2) and ⍺-bungarotoxin (⍺-BTX) staining revealed a similar pattern, with a significant loss of SV2 and nicotinic acetylcholine receptors, thus preventing the colocalization of presynaptic neurons with postsynaptic neurons. Consistent with these results, the presence of cleaved caspase-3 and acridine orange positive cells showed increased cell death in zebrafish larvae exposed to PBDEs. Our results suggest that exposure to PBDEs leads to deficits in the zebrafish neuromuscular system through neuron death, inducing morphological and motor deficiencies throughout their development. They provide valuable insight into the neurotoxic effects of PBDEs, further highlighting the relevance of the zebrafish model in toxicological studies.

Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema.

The Ross procedure is a surgical option for congenital aortic stenosis that involves replacing the diseased aortic valve with a pulmonary autograft. Little is known about outcomes in children, particularly those younger than 1 year.

Purpose: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. Methods: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden’s statistic. Results: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. Conclusion: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Meaningful interpretation of U isotope measurements relies on unraveling the impact of reduction mechanisms on the isotopic fractionation. Here, the isotope fractionation of hexavalent U [U(VI)] was investigated during its reductive mineralization by magnetite to intermediate pentavalent U [U(V)] and ultimately tetravalent U [U(IV)]. As the reaction proceeded, the remaining aqueous phase U [containing U(VI) and U(V)] systematically carried light isotopes, whereas in the bicarbonate-extracted solution [containing U(VI) and U(V)], the δ238U values varied, especially when C/C0approached 0. This variation was interpreted as reflecting the variable relative contribution of unreduced U(VI) (δ238U < 0‰) and bicarbonate-extractable U(V) (δ238U > 0‰). The solid remaining after bicarbonate extraction included unextractable U(V) and U(IV), for which the δ238U values consistently followed the same trend that started at 0.3–0.5‰ and decreased to ∼0‰. The impact of PIPES buffer on isotopic fractionation was attributed to the variable abundance of U(V) in the aqueous phase. A few extremely heavy bicarbonate-extracted δ238U values were due to mass-dependent fractionation resulting from several hypothesized mechanisms. The results suggest the preferential accumulation of the heavy isotope in the reduced species and the significant influence of U(V) on the overall isotopic fractionation, providing insight into the U isotope fractionation behavior during its abiotic reduction process.

The aim of this work consists of identifying the material behavior of Alucobond composite structures subjected to ballistic impact. The composite is made of Aluminum alloy AW5005 and LDPE (low-density polyethylene). The mechanical properties of these materials are described in term of strain rate and temperature dependencies. Quasi-static tensile and compression tests for Alucobond are performed at four different strain rates, i.e. 0.0001 0.001, 0.01, and 0.03 s-1. Moreover, in dynamic regime the used strain rate ranges in compression and perforation tests are (104s-1≤ ε˙≤ 105s-1) at temperatures ranging from room temperature 20 °C to 100 °C. Various parameters influence the behavior of the Alucobond structure under impact: the geometry and the mechanical properties of the projectile, the initial impact velocity, and the thermomechanical behavior of the target. Numerous quasi-static and dynamic original test results (traction and perforation over a wide range of strain rates at room temperature and high temperature) are presented. Numerical simulations, particularly using the finite element (FE) method with the ABAQUS explicit code, are also effective supplements for theoretical and more detailed experimental investigations, which were carried out to analyze the dynamic behavior of impacted structures.

We report the fabrication and characterization of a plasmonic metasurface comprising electrically-contacted sub-wavelength gold dipole nanoantennas, conformally coated by a thin hafnia film, an indium tin oxide layer and a backside mirror, forming metal–oxide–semiconductor (MOS) capacitors, for use as an electrically-tunable reflectarray or metasurface. By voltage biasing the nanoantennas through metallic connectors and leveraging the carrier refraction effect in the MOS capacitors, our measurements demonstrate phase control in reflection over a range of about 30°, with a constant magnitude of reflection coefficient of 0.5, and the absence of secondary lobes. Comprehensive electromagnetic and quantum carrier models of the structure are developed and are in excellent agreement with the measurements. The metasurface holds promise for use as an optical phased array.

Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population.

Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic–systemic interactions to guide future research directions.

This study aims to optimize a single preparation methodology based on solid-phase extraction (SPE) that could fit both target and non-target screening of organic biomarkers in raw wastewater, allowing the cross-comparison of results obtained from a same dataset. The efficiency of SPE sorbents used alone (HLB) or in combination in a multilayer cartridge was evaluated based on (i) the extraction recovery and matrix effect in environmental samples (surface water and wastewater) for a list of biomarkers (pharmaceuticals, licit and illicit drugs, artificial sweeteners, isoprostanes, polyphenols) and (ii) a number of detected features and their intensity in HRMS. The selected method uses a combination of three SPE sorbents mixed together (HLB, X-AW and X-CW) and seems to take full advantage of each, providing satisfactory validation parameters (recovery, instrumental limit of detection, linearity range and limit of quantification) over a large range of physico-chemical properties while ensuring promising results for non-target screening applications. Of the 65 targeted compounds, nearly all of them (47) were detected in wastewater influent samples with concentration above the limit of quantification, while at the same time over 10 000 features were recorded according to the high resolution mass spectrometry (HRMS) fingerprint, holding out the promise that a common protocol for these two analyses, with their very contrasting constraints and objectives, is possible.

High-throughput experimentation (HTE) has the potential to improve our understanding of organic chemistry by systematically interrogating reactivity across diverse chemical spaces. Notable bottlenecks include few publicly available large-scale datasets and the need for facile interpretation of these data’s hidden chemical insights. Here we report the development of a high-throughput experimentation analyser, a robust and statistically rigorous framework, which is applicable to any HTE dataset regardless of size, scope or target reaction outcome, which yields interpretable correlations between starting material(s), reagents and outcomes. We improve the HTE data landscape with the disclosure of 39,000+ previously proprietary HTE reactions that cover a breadth of chemistry, including cross-coupling reactions and chiral salt resolutions. The high-throughput experimentation analyser was validated on cross-coupling and hydrogenation datasets, showcasing the elucidation of statistically significant hidden relationships between reaction components and outcomes, as well as highlighting areas of dataset bias and the specific reaction spaces that necessitate further investigation.

IMPORTANCE: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. OBJECTIVE: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. DESIGN, SETTING, AND PARTICIPANTS: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. MAIN OUTCOMES/MEASURES: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. RESULTS: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. CONCLUSIONS AND RELEVANCE: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Stable composite objects, such as hadrons, nuclei, atoms, molecules and superconducting pairs, formed by attractive forces are ubiquitous in nature. By contrast, composite objects stabilized by means of repulsive forces were long thought to be theoretical constructions owing to their fragility in naturally occurring systems. Surprisingly, the formation of bound atom pairs by strong repulsive interactions has been demonstrated experimentally in optical lattices1. Despite this success, repulsively bound particle pairs were believed to have no analogue in condensed matter owing to strong decay channels. Here we present spectroscopic signatures of repulsively bound three-magnon states and bound magnon pairs in the Ising-like chain antiferromagnet BaCo2V2O8. In large transverse fields, below the quantum critical point, we identify repulsively bound magnon states by comparing terahertz spectroscopy measurements to theoretical results for the Heisenberg–Ising chain antiferromagnet, a paradigmatic quantum many-body model2–5. Our experimental results show that these high-energy, repulsively bound magnon states are well separated from continua, exhibit notable dynamical responses and, despite dissipation, are sufficiently long-lived to be identified. As the transport properties in spin chains can be altered by magnon bound states, we envision that such states could serve as resources for magnonics-based quantum information processing technologies6–8.

Equiatomic CoCrFeMnNi high entropy alloy (HEA) powder was processed by laser powder bed fusion (LPBF) additive manufacturing (AM). The properties of the spherical pre-alloyed CoCrFeMnNi powder were characterized and its processability using LPBF AM was systematically investigated through the volumetric energy density (VED) based on the surface roughness, defects (micro-cracks and porosity) and densification. After optimization, LPBF processing at a VED of 104 J/mm3achieved highly dense and crack-free vertical and horizontal test specimens with a porosity fraction lower than 0.01% and micro-pores having a mean size of, respectively, 25.9 μm and 13.4 μm, as determined from X-ray micro-computed tomography (μCT) inspection. Scanning electron microscope (SEM) analysis of the as-built (AB) CoCrFeMnNi processed at a VED of 104 J/mm3showed a heterogeneous solidification microstructure, consisting of columnar grains with a cellular subgrain structure, and electron backscattered diffraction (EBSD) revealed a crystallographic texture mainly along the < 100 > direction. Post treatment with hot isostatic pressing (HIP) was effective in closing the remnant micro-pores in the bulk volume of the AB CoCrFeMnNi. Also, the cellular sub-grain structure in the AB CoCrFeMnNi completely disappeared after HIP and the resulting microstructure consisted of recrystallized equiaxed grains with annealing twins. The room temperature tensile response was anisotropic for AB CoCrFeMnNi with horizontally built specimens exhibiting higher strength and fracture strains (global and local) compared to vertically built ones; HIP reduced the anisotropy in the tensile properties and led to similar tensile strength with elongation values that were ~ 50% higher than in the AB condition. The HIPed CoCrFeMnNi also displayed higher Charpy impact toughness and absorbed energy at both room and liquid nitrogen temperatures compared to the AB material. Examination of the fracture surfaces after tensile and Charpy impact testing revealed ductile features with characteristic dimpled appearance and pointed to the important role of the remnant micro-pores on failure in the AB CoCrFeMnNi. Tribological assessments pointed to the superior low-stress abrasion resistance of AB and HIPed CoCrFeMnNi compared to 316L stainless steel (SS), which was included in this study to reinforce the analysis. SEM observations revealed that scratching and micro-fracture are the dominant wear mechanisms for the CoCrFeMnNi HEA, whereas ploughing and cutting parallel to the abrasive flow direction are the dominant mechanisms for 316L SS. To the authors’ knowledge, this study is the first to evaluate and report the low-stress abrasion resistance of any high entropy alloy. To understand the corrosion behavior, polarization curves of AB and HIPed CoCrFeMnNi were measured in 3.5 wt% NaCl and 1N H2SO4solutions, and the results were compared to those of 316L SS. The findings indicate that AB and HIPed CoCrFeMnNi outperform 316L SS in a chloride-containing environment, but not in an acid-containing environment. Additionally, observations of hydrogen permeability revealed that AB CoCrFeMnNi permeates a lower volume of hydrogen atoms (by ~ 5 times) compared to 316L SS, despite its higher (by nearly 3 times) diffusion coefficient. Electrochemical hydrogen permeation data showed that the concentration of atomic hydrogen in the sub-surface of AB and HIPed CoCrFeMnNi was, respectively, about 32 and 26 times lower than in 316L SS. This study provides important material–structure–property data and indicates a promising outlook for LPBF of the CoCrFeMnNi HEA with high-performance.

The telementoring Project ECHO (Extension for Community Healthcare Outcomes) model has been shown to improve disease management in diabetes in many underserved communities. The authors aim to evaluate if ECHO could also be an effective tool for quality improvement (QI) of diabetes care in these communities.

We propose an energy transfer model with a cubic atomic population dependence to accurately model the behavior of various reported high-power erbium-doped fluoride fiber lasers operating near 2.8 microns. We first show that the previously introduced weakly interacting (WI) and strongly interacting (SI) models are not adequate for precisely modeling such high-power erbium-doped fluoride fiber lasers. We compare results obtained with the WI and SI models to the proposed model by simulating 4 different highly doped (7 mol.%) fiber lasers previously reported in the literature. Laser efficiencies and powers are reproduced with great accuracy. In addition, four other fiber laser systems based on erbium concentrations varying from 1–6 mol.% are also simulated with good accuracy using the proposed model with the exact same set of spectroscopic parameters, which confirms its validity for various erbium doping concentrations. Redshifting of laser wavelength is also taken into account by considering the full cross section spectra and computing signal powers over several wavelength channels.

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1–2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.

Prenatal diagnosis of pericardial mass, with associated large pericardial effusion, resected postnatally and diagnosed to be ectopic hepatic tissue on pathology.

Bi2WO6has been actively investigated as a viable photocatalysis substitute for TiO2. This along with progress in designing qubit hosts using W5+centers encourages the development of single crystal growths of this material using the floating zone technique. Single crystals of Bi2WO6–xwere grown using a laser diode floating zone furnace. Laue diffraction and single crystal X-ray diffraction confirm development of single crystalline domains. Williamson–Hall analysis shows annealed floating zone crystals contain less strain compared to unannealed and flux grown samples. Fitting of the heat capacity data shows two optical phonon modes modeled by Einstein oscillators, with the lower energy oscillator decreasing post annealing. The band gap is estimated as 2.6 eV using hyperspectral imaging, showing an additional absorption band present in the oxygen-deficient samples compared to those grown via flux. This additional absorption is tunable via annealing post growth. Overall, this technique demonstrates the feasibility of growing large single crystals of Bi2WO6with tunable W5+centers for potential application in photocatalysis and quantum information.

Background and Purpose The Neurology Mortality Review Committee at our institution identified variability in location of death for patients on our inpatient neurology services. Hospice may increase the number of patients dying in their preferred locations. This study aimed to characterize patients who die on inpatient neurology services and explore barriers to discharge to hospice.Methods This retrospective study was completed at a single, quaternary care medical center that is a Level I Trauma Center and Comprehensive Stroke Center. Patients discharged by an inpatient neurology service between 6/2019-1/2021 were identified and electronic medical record review was performed on patients who died in the hospital and who were discharged to hospice.Results 69 inpatient deaths and 74 discharges to hospice occurred during the study period. Of the 69 deaths, 54 occurred following withdrawal of life sustaining treatment (WLST), of which 14 had a referral to hospice placed. There were 88 “hospice-referred” patients and 40 “hospice-eligible” patients. Hospice-referred patients were less likely to require the intensive care unit than hospice-eligible patients. Hospice-referred patients had their code status changed to Do Not Intubate earlier and were more likely to have advanced directives available.Conclusion Our data highlight opportunities for further research to improve discharge to hospice including interhospital transfers, advanced directives, earlier goals of care discussions, palliative care consultations, and increased hospice bed availability. Importantly, it highlights the limitations of using in-hospital mortality as a quality indicator in this patient population.

The sui generisdatabase right is an intellectual property right created in the European Union to stimulate investment in the curation of databases. Since its inception, communities engaged in research and development efforts have questioned its potential to incentivise database production, and posit that it stifles productive downstream uses of existing datasets. European courts have restricted the right’s ambit through a restrictive interpretation of the circumstances in which it applies, which we argue, enables downstream use of biological databases. Nonetheless, residual ambiguities about potential infringement of the right exist. The prospect of unintentional infringement can frustrate downstream innovation. These ambiguities are compounded because the criteria that determine whether or not the right applies are reliant on information that is not available to the prospective downstream users of public datasets. Repealing the sui generisdatabase right is recommended. Legislatures are advised to refrain from the implementation of broad novel intellectual property rights in the future, without first adopting safeguards that mitigate the potential for such rights to frustrate the reuse of available intangibles to the detriment of pro-social innovation.

Since it inhabits young leaves and buds of strawberry (Fragaria× ananassaDuchesne) crowns, cyclamen mite (Phytonemus pallidusBanks) is a difficult pest to control with biological or chemical means once it is present in a field. Controlled atmosphere temperature treatment (CATT) is a successful technique that has been commercially used in the Netherlands for nearly 2 decades to disinfect strawberry nursery stock, including elimination of cyclamen mite. During CATT, plants are treated at 35 °C, 50% CO2, and 10% O2under high relative humidity for 48 h. The objective of this study was to test CATT against P. pallidusin North America at a scale that can be easily used on-farms by strawberry growers. Two greenhouse experiments were conducted where infested trayplants were treated with CATT or the acaricide abamectin, and P. pallidusnumber were compared to control plants. Plants were destructively sampled after 4 weeks, and CATT reduced mobile forms of P. pallidusby 99.9% in both experiments. Abamectin used in the first experiment had an efficacy of 95.5%. Our findings suggest that CATT is effective at nearly eliminating P. pallidusfrom strawberry planting material, and its application could reduce risks of field infestations and the need for multiple acaricide applications. While our results are encouraging, additional research is needed to assess the effects of CATT on strawberry plant survival, growth, and fruit production.

The article focuses on the power of grassroots advocacy in the field of school psychology and it emphasizes the efforts of the Minnesota Collective for Educational Equity (MnCEE) in advocating for policy changes related to the identification of specific learning disabilities (SLDs) and equity-centered multi-tiered systems of support (MTSS). It highlights the value of collaborative partnerships in accomplishing real change through advocacy and the role of school psychologists as advocates.

Human genetic syndromes are often challenging to diagnose clinically. Facial phenotype is a key diagnostic indicator for hundreds of genetic syndromes and computer-assisted facial phenotyping is a promising approach to assist diagnosis. Most previous approaches to automated face-based syndrome diagnosis have analyzed different datasets of either 2D images or surface mesh-based 3D facial representations, making direct comparisons of performance challenging. In this work, we developed a set of subject-matched 2D and 3D facial representations, which we then analyzed with the aim of comparing the performance of 2D and 3D image-based approaches to computer-assisted syndrome diagnosis. This work represents the most comprehensive subject-matched analyses to date on this topic. In our analyses of 1907 subject faces representing 43 different genetic syndromes, 3D surface-based syndrome classification models significantly outperformed 2D image-based models trained and evaluated on the same subject faces. These results suggest that the clinical adoption of 3D facial scanning technology and continued collection of syndromic 3D facial scan data may substantially improve face-based syndrome diagnosis.

Lung ultrasound (LUS) is an important imaging modality used by emergency physicians to assess pulmonary congestion at the patient bedside. B-line artifacts in LUS videos are key findings associated with pulmonary congestion. Not only can the interpretation of LUS be challenging for novice operators, but visual quantification of B-lines remains subject to observer variability. In this work, we investigate the strengths and weaknesses of multiple deep learning approaches for automated B-line detection and localization in LUS videos. We curate and publish, BEDLUS, a new ultrasound dataset comprising 1,419 videos from 113 patients with a total of 15,755 expert-annotated B-lines. Based on this dataset, we present a benchmark of established deep learning methods applied to the task of B-line detection. To pave the way for interpretable quantification of B-lines, we propose a novel “single-point” approach to B-line localization using only the point of origin. Our results show that (a) the area under the receiver operating characteristic curve ranges from 0.864 to 0.955 for the benchmarked detection methods, (b) within this range, the best performance is achieved by models that leverage multiple successive frames as input, and (c) the proposed single-point approach for B-line localization reaches an F$_{1}$-score of 0.65, performing on par with the inter-observer agreement. The dataset and developed methods can facilitate further biomedical research on automated interpretation of lung ultrasound with the potential to expand the clinical utility.

In 2015 staff in Harvard University’s Widener Library discovered an unidentified white powder in a few early twentieth-century books in Persian and Urdu languages that had been acquired four years previously from a rare book dealer in Pakistan. The powder was positively identified as the insecticides Dichlorodiphenyltrichloroethane(DDT), Coumaphos, and several derivatives. Later it became evident that these volumes were part of a large collection and that potentially thousands of volumes were contaminated. Various exposure assessments were followed by cleaning and reassessment which revealed that risks to persons were infinitely small. However, a bioassay revealed that the pesticide residues were still biologically active. The transparency of communication and demonstrated collaboration between Safety, Facilities, and Library personnel generated trust among staff that their health and safety were paramount. This trust was key to subsequent incidents of contaminated collections and our response to the COVID-19 pandemic.

IMPORTANCE: Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs. OBJECTIVE: To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF. DESIGN, SETTING, AND PARTICIPANTS: This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat. INTERVENTIONS: Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA. MAIN OUTCOMES AND MEASURES: The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables. RESULTS: Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02150902

Limited studies are available on how decisions and perceptions on SARS-CoV-2 vaccination have changed since the start of vaccination availability. We performed a qualitative study to identify factors critical to SARS-CoV-2 vaccination decision making and how perspectives evolved among African American/Black, Native American, and Hispanic communities disproportionately affected by COVID-19 and social and economic disadvantage. We conducted 16 virtual meetings, with 232 participants in wave 1 meetings (December 2020) and with 206 returning participants in wave 2 meetings (January and February 2021). Wave 1 vaccine concerns in all communities included information needs, vaccine safety, and speed of vaccine development. Lack of trust in government and the pharmaceutical industry was influential, particularly among African American/Black and Native American participants. Participants showed more willingness to get vaccinated at wave 2 than at wave 1, indicating that many of their information needs had been addressed. Hesitancy remained greater among African American/Black and Native American participants than among Hispanic participants. Participants in all groups indicated that conversations tailored to their community and with those most trustworthy to them would be helpful. To overcome vaccine hesitancy, we propose a model of fully considered SARS-CoV-2 vaccine decision making, whereby public health departments supply information, align with community values and recognize lived experiences, offer support for decision making, and make vaccination easy and convenient.

Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer. Herein, we present the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1 starting from hits identified via virtual screening. Key components of this discovery effort were structure-based drug design aided by analyses of normalized B-factors and optimization of lipophilic efficiency.

The selection of a climate-appropriate asphalt binder is essential in ensuring the longevity of pavement surfaces. As the selection methodology depends on the pavement's temperature, several models predict pavement temperatures based on recorded ambient air temperatures and other related factors. A commonality between the most predominant pavement temperature models is the geographical limitations to their application. As a result, widely used models such as LTPP and SHRP do not return accurate values for more Northern temperatures, as observed in Canada. Thus, a new pavement temperature model has been developed for use across Canadian pavements. The resulting model returned satisfactory accuracy upon validation and represented a good alternative for Canadian pavement designers. Additionally, a software tool title CABS has been developed to select asphalt binders based on the predicted pavement temperatures to implement the model.

This article reports a slow-light fiber-Bragg-grating (FBG) pressure sensor that functions both as a microphone and a hydrophone and pushes the limit of acoustic pressure resolution of conventional FBG sensors operated without external diaphragms. The sensor utilizes a narrow slow-light resonance to enhance its optical response (greater transmission change per wavelength shift), a soft polymeric coating to enhance its acoustic response (greater wavelength shift per pressure), and an ultranarrow linewidth laser to reduce its laser frequency noise (which often dominates in such sensors). The coated fiber microphone exhibits an average resolution of $\sim 210 ~\mu $ Pa/ $\surd $ Hz (100 Hz–10 kHz), which is ~6 times better than the previous record. When used as a hydrophone, the resolution is $\sim 880 ~\mu $ Pa/ $\surd $ Hz (1–100 kHz), which is better than the previous record for a passive FBG hydrophone by a factor of ~23 over the same acoustic frequency range. The wavelength shift per unit pressure is larger for the coated FBG than for the bare FBG by a measured factor of ~16 in air and ~3.7 in water. This last value differs markedly from a published ~300-fold enhancement using a conventional FBG hydrophone coated with the same polymer. It is shown that most of this discrepancy is due to a referencing error in the publication that reported this improvement. With further improvement, slow-light FBGs could be utilized for high-resolution applications, such as in the deep sea and seismic research.

The coming-into-force of the EU General Data Protection Regulation (GDPR) is a watershed moment in the legal recognition of enforceable rights to informational self-determination. The rapid evolution of legal requirements applicable to data use, however, has the potential to outstrip the capabilities of networks of biomedical data users to respond to the shifting norms. It can also delegitimate established institutional bodies that are responsible for assessing and authorising the downstream use of data, including research ethics committees and institutional data custodians. These burdens are especially pronounced for clinical and research networks that are of transnational scale, because the legal compliance burden for outbound international data transfers from the EEA is especially high. Legislatures, courts, and regulators in the EU should therefore implement the following three legal changes. First, the responsibilities of particular actors in a data sharing network should be delimited through the contractual allocation of responsibilities between collaborators. Second, the use of data through secure data processing environments should not trigger the international transfer provisions of the GDPR. Third, the use of federated data analysis methodologies that do not provide analysis nodes or downstream users access to identifiable personal data as part of the outputs of those analyses should not be considered circumstances of joint controllership, nor lead to the users of non-identifiable data to be considered controllers or processors. These small clarifications of, or modifications to, the GDPR would facilitate the exchange of biomedical data amongst clinicians and researchers.

Background and Objectives:Patients undergoing maintenance hemodialysis have an attenuated immune response to vaccination. The aim of our study was to determine the predictive factors for humoral response to vaccination with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) in patients on maintenance hemodialysis. Design, Setting, Participants, and Measurements:In this retrospective, single-center study, we included patients on maintenance hemodialysis already vaccinated with two doses of the BNT162b2 vaccine (Pfizer-BioNTech) and with a post-vaccination serological follow-up. Results:252 patients were included for study with a mean age of 71.9 (±14.4) years. Twelve patients (4.7%) were under immunosuppressive therapy (calcineurin inhibitors: n= 4; chemotherapy for myeloma: n= 3; last infusion of rituximab over the previous 4 years: n= 2; abatacept: n= 2; adalimumab n= 1). Three of these patients were under immunosuppressive therapy for nonrenal solid organ transplantation. Multivariate analysis identified immunosuppressive therapy (OR 4.73 [1.38–16.17], p= 0.013) and lower baseline albumin levels (OR 1.23 [1.09–1.38], p< 0.001) as independent predictive factors of nonresponse to vaccination. Older age (β = −0.59 ± 0.21, p= 0.006) and immunosuppressive therapy (β = 40.33 ± 13.33, p= 0.003) were significantly associated with lower humoral response to vaccination. Conclusions:Approximately 90% of patients under maintenance hemodialysis developed specific antibodies to the BNT162b2 mRNA vaccine. Immunosuppressive therapy, malnutrition, and older age were associated with a higher risk of nonseroconversion or lower humoral response to mRNA-based vaccination against SARS-CoV-2. We strongly recommend serological monitoring after vaccination to determine booster timing, especially for patients with malnutrition or on immunosuppressive therapy.

La qualité de vie et le bien-être psychologique des patients traités pour un cancer de la thyroïde sont essentiels compte tenu de leur survie très prolongée. Le traitement fait appel à une chirurgie souvent complétée par une thérapie par iode radioactif (RAI). Cette étude vise à examiner les effets potentiels de la thérapie par RAI sur la qualité de vie liée à la santé (Qdv), les symptômes d’anxiété et de dépression, et l’état nutritionnel six mois après traitement.

The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings.

Pain in adolescence can lead to the development of serious mental health issues, including suicidality. This risk may be strengthened among youth exposed to more adverse childhood experiences (ACEs; abuse, neglect, household challenges). This longitudinal study examined the role of ACEs in the relationship between pain and later suicidality onset and severity among a cohort of adolescents at risk for developing mental health problems. Participants were 139 healthy youth (Mage= 13.74 years, standard deviation = 1.56, 64% female) between the ages of 11 to 17 years, recruited based on parental history of depression or anxiety. Youth completed validated measures of internalizing symptoms, ACEs, and pain characteristics at baseline and follow-up diagnostic interviews 9 and/or 18 months later to assess for onset and severity of suicidality. After controlling for demographics, baseline internalizing symptoms, and ACEs, worse pain interference and increased ACEs at baseline predicted increased suicidality severity at follow-up. Moderation analyses revealed that there was a significant interaction between ACEs and pain interference and pain intensity. Increased pain interference (b = 7.65, P < .0001) or intensity (b = 6.96, P = .0003) was only associated with increased suicidality severity at follow-up in youth with high levels of ACEs. This study demonstrates that ACEs strengthen the relationship between pain and later suicidality severity among youth at risk of developing mental health problems. Findings underscore the critical need to adopt a trauma-informed lens to pediatric pain prevention and treatment (eg, screening for ACEs) and for the pain to be on the child's mental health agenda.

The bacterial cell-division protein FtsZ has been a promising antibiotic target for over a decade now, but there is still a need for more work in this area. So far there are no FtsZ targeting drugs commercially available. We have analyzed a wide variety of prospective drugs and their interactions with multiple FtsZ species using both free and directed docking simulations. Our goal is to present a standardized computational screening method for potential drug compounds targeting FtsZ. Our work is an example of a way to compare many proposed drugs and FtsZ species combinations relatively quickly. A common method for comparison can yield new results that individual studies and varying methods might not show, as we demonstrate here. To our knowledge this is one of the first, if not the first, computational docking study on the new E. coli FtsZ structures obtained in 2020.

Les réactions cutanées chez l’enfant, dans un contexte de prise médicamenteuse, sont un motif très fréquent de consultation. L’hypothèse d’une toxidermie est donc souvent soulevée. Cependant, une éruption en contexte fébrile chez l’enfant est dans la majorité des cas une infection, en particulier une infection virale. Les toxidermies sont un défi diagnostique afin d’arrêter, sans délai, les médicaments imputables pour ne pas mettre en danger les enfants. À l’inverse, il est fondamental de ne pas surdiagnostiquer les allergies médicamenteuses car cela est préjudiciable pour les prises en charge thérapeutiques ultérieures. Devant toute éruption, la réalisation d’une frise médicamenteuse est indispensable pour le raisonnement allergologique, ainsi qu’une bonne connaissance sémiologique des différentes toxidermies et de leurs diagnostics différentiels.

Investigating how solid matter behaves at enormous pressures, such as those found in the deep interiors of giant planets, is a great experimental challenge. Over the past decade, computational predictions have revealed that compression to terapascal pressures may bring about counter-intuitive changes in the structure and bonding of solids as quantum mechanical forces grow in influence1–6. Although this behaviour has been observed at modest pressures in the highly compressible light alkali metals7,8, it has not been established whether it is commonplace among high-pressure solids more broadly. We used shaped laser pulses at the National Ignition Facility to compress elemental Mg up to 1.3 TPa, which is approximately four times the pressure at the Earth’s core. By directly probing the crystal structure using nanosecond-duration X-ray diffraction, we found that Mg changes its crystal structure several times with non-close-packed phases emerging at the highest pressures. Our results demonstrate that phase transformations of extremely condensed matter, previously only accessible through theoretical calculations, can now be experimentally explored.

AbstractThis article explores how the logic underlying modal practices tends to modulate the population’s responsiveness to improvements in global transport supply. Based on a quantitative survey conducted in 2018–2019 among the working population of the cantons of Bern, Geneva and Vaud, it presents the construction of eight types, each of which corresponds to a specific combination of action logic and allows segmentation of travel behaviour. The exploration of the links between this typology and three metropolitan areas shows that the weight of the types within the active population is associated with the quality of the transport offered, especially at the workplace, and that the use of the different means of transport for commuting within the types stays consistent with the opinions of the respondents, as confirmed by an ordinal regression. All the results presented in this article show that a modal shift objective in daily mobility requires a strategy that is segmented by these types.

This review aimed to synthesize existing information on Muslim parent perceptions and attitudes toward their child(ren) with autism based on their religious beliefs. Eleven peer-reviewed articles were included. Several religious beliefs guided parental perceptions and were subsequently categorized as either positive or mixed attitudes toward their children with autism, which rendered common themes. The results allow for an exploratory examination of cross-cultural similarities and differences as well as common coping approaches engaged in by Muslim parents. Practical implications include enhancing diversity research, practitioner cultural competence, cultural sensitivity, responsive practice, and efficacious practice within the bounds of social justice.