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OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics. To overcome these barriers, we introduce a cross correlation method to more accurately recover blood flow information using InGaAs/InP SPADs. METHODS: Two InGaAs/InP SPAD detectors were used for during in vitro and in vivo DCS measurements. Cross correlation of the photon streams from each detector was performed to calculate the correlation function. Detector operating parameters were varied to determine parameters which maximized measurement SNR. State-space modeling was performed to determine the detector characteristics at each operating point. RESULTS: Evaluation of detector characteristics was performed across the range of operating conditions. Modeling the effects of the detector noise on the correlation function provided a method to correct the distortion of the correlation curve, yielding accurate recovery of flow information as confirmed by a reference detector. CONCLUSION: Through a combination of cross-correlation of the signals from two detectors, model-based characterization of detector response, and optimization of detector operating parameters, the method allows for the accurate estimation of the true blood flow index. Significance: This work presents a method by which DCS can be performed at longer NIR wavelengths with existing detector technology, taking advantage of the increased SNR.

A population-level study is essential for understanding treatment effects, epidemiologic phenomena, and health care best practices. Evaluating large populations and associated data requires an analytic framework, which is commonly used by statisticians, epidemiologists, and data scientists. This document will serve to provide an overview of these commonly employed methods in allergy and immunology research. We will draw upon recent examples from the allergy-immunology literature to contextualize discrete principles of relevance to population-level analysis that include statistical features of a study population, elements of statistical inference, regression analysis, and an overview of machine learning practices. Our intent is to guide the reader through a practical description of this important quantitative discipline and facilitate greater understanding about data and result display in the medical literature.

After initial reports of anaphylaxis to the messenger RNA (mRNA) COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC) put forth guidance stating that patients with a history of anaphylaxis to vaccine components like polyethylene glycol (PEG) should not receive the mRNA COVID-19 vaccines.1 To address this clinical challenge and decrease vaccine hesitancy, we published an approach to guide COVID-19 vaccination in high-risk allergy individuals.2-4 While the etiology of anaphylaxis to mRNA COVID-19 vaccines remains unclear, PEG continues to be an important focus.5,6 Paclitaxel contains polyoxyl-35 castor oil --a PEG derivative and structurally similar to the excipient in Pfizer-BioNTech and Moderna COVID-19 vaccines-- and docetaxel contains polysorbate 80 --the excipient in Janssen COVID-19 vaccine. Given this, we sought to assess the utility of pre-vaccine excipient skin testing (ST), risk stratification and COVID-19 vaccine tolerability in oncology patients with a history of paclitaxel or docetaxel hypersensitivity reaction (HSR).

Objectives The aim of this study was to evaluate clinical characteristics, mechanisms of failure, and outcomes of transcatheter aortic valve replacement (TAVR) explantation. Background Surgical explantation following TAVR may be required for structural valve degeneration, paravalvular leak, infection, or other reasons. However, in-depth data on indications and outcomes are lacking. Methods Data from a multicenter, international registry (EXPLANT-TAVR) of patients who underwent TAVR explantation were reviewed retrospectively. Explantations performed during the same admission as initial TAVR were excluded. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 6.7 months (interquartile range [IQR]: 1.0-18.8 months) after TAVR explantation and was 97.7% complete at 30 days and 86.1% complete at 1 year. Results From November 2009 to September 2020, 269 patients across 42 centers with a mean age of 72.7 ± 10.4 years underwent TAVR explantation. About one quarter (25.9%) were deemed low surgical risk at index TAVR, and median Society of Thoracic Surgeons risk at TAVR explantation was 5.6% (IQR: 3.2%-9.6%). The median time to explantation was 11.5 months (IQR: 4.0-32.4 months). Balloon-expandable and self-expanding or mechanically expandable valves accounted for 50.9% and 49.1%, respectively. Indications for explantation included endocarditis (43.1%), structural valve degeneration (20.1%), paravalvular leak (18.2%), and prosthesis-patient mismatch (10.8%). Redo TAVR was not feasible because of unfavorable anatomy in 26.8% of patients. Urgent or emergency cases were performed in 53.1% of patients, aortic root replacement in 13.4%, and 54.6% had concomitant cardiac procedures. Overall survival at last follow-up was 76.1%. In-hospital, 30-day, and 1-year mortality rates were 11.9%, 13.1%, and 28.5%, respectively, and stroke rates were 5.9%, 8.6%, and 18.7%, respectively. Conclusions The EXPLANT-TAVR registry reveals that surgical risks associated with TAVR explantation are not negligible and should be taken into consideration in the lifetime management of aortic stenosis.

Background and Objective: Allergic reactions, including anaphylaxis, are rising among children. Little is known about health care utilization among infants and toddlers. Our objective was to characterize health care utilization and charges for acute allergic reactions (AAR). Methods: We conducted a retrospective cohort study of trends in emergency department (ED) visits and revisits, hospitalizations and rehospitalizations, and charges among infants and toddlers (ages < 3 years), with an index ED visit or hospitalization for AAR (including anaphylaxis). We used data from population-based multipayer data: State Emergency Department Databases and State Inpatient Databases from New York and Nebraska. Multivariable logistic regression was used to identify factors associated with ED revisits and rehospitalizations. Results: Between 2006 and 2015, infant and toddler ED visits for AAR increased from 27.8 per 10,000 population to 35.2 (Ptrend < 0.001), whereas hospitalizations for AAR remained stable (Ptrend = 0.11). In the one year after an index AAR visit, 5.1% of these patients had at least one AAR ED revisit and 5.9% had at least one AAR rehospitalization. Factors most strongly associated with AAR ED revisits included an index visit hospitalization and receipt of epinephrine. Total charges for AAR ED visits (2009‐2015) and hospitalizations (2011‐2015) were more than $29 million and $11 million, respectively. Total charges increased more than fourfold for both AAR ED revisits for AAR rehospitalizations during the study period. Conclusion: Infants and toddlers who presented with an AAR were at risk for ED revisits and rehospitalizations for AAR within the following year. The charges associated with these revisits were substantial and seemed to be increasing.

Supplemental Digital Content is available in the text., Background: Cardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes. This study aimed to determine the prevalence and clinical implications of COVID-19 cardiac involvement in young competitive athletes. Methods: In this prospective, multicenter, observational cohort study with data from 42 colleges and universities, we assessed the prevalence, clinical characteristics, and outcomes of COVID-19 cardiac involvement among collegiate athletes in the United States. Data were collected from September 1, 2020, to December 31, 2020. The primary outcome was the prevalence of definite, probable, or possible COVID-19 cardiac involvement based on imaging definitions adapted from the Updated Lake Louise Imaging Criteria. Secondary outcomes included the diagnostic yield of cardiac testing, predictors for cardiac involvement, and adverse cardiovascular events or hospitalizations. Results: Among 19 378 athletes tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 3018 (mean age, 20 years [SD, 1 year]; 32% female) tested positive and underwent cardiac evaluation. A total of 2820 athletes underwent at least 1 element of cardiac triad testing (12-lead ECG, troponin, transthoracic echocardiography) followed by cardiac magnetic resonance imaging (CMR) if clinically indicated. In contrast, primary screening CMR was performed in 198 athletes. Abnormal findings suggestive of SARS-CoV-2 cardiac involvement were detected by ECG (21 of 2999 [0.7%]), cardiac troponin (24 of 2719 [0.9%]), and transthoracic echocardiography (24 of 2556 [0.9%]). Definite, probable, or possible SARS-CoV-2 cardiac involvement was identified in 21 of 3018 (0.7%) athletes, including 15 of 2820 (0.5%) who underwent clinically indicated CMR (n=119) and 6 of 198 (3.0%) who underwent primary screening CMR. Accordingly, the diagnostic yield of CMR for SARS-CoV-2 cardiac involvement was 4.2 times higher for a clinically indicated CMR (15 of 119 [12.6%]) versus a primary screening CMR (6 of 198 [3.0%]). After adjustment for race and sex, predictors of SARS-CoV-2 cardiac involvement included cardiopulmonary symptoms (odds ratio, 3.1 [95% CI, 1.2, 7.7]) or at least 1 abnormal triad test result (odds ratio, 37.4 [95% CI, 13.3, 105.3]). Five (0.2%) athletes required hospitalization for noncardiac complications of COVID-19. During clinical surveillance (median follow-up, 113 days [interquartile range=90 146]), there was 1 (0.03%) adverse cardiac event, likely unrelated to SARS-CoV-2 infection. Conclusions: SARS-CoV-2 infection among young competitive athletes is associated with a low prevalence of cardiac involvement and a low risk of clinical events in short-term follow-up.

Acoustic time-of-flight (AToF) imaging has been demonstrated as a low-cost, rapid, non-destructive, operando tool to characterize processes in the flow channels and liquid-gas diffusion layer (LGDL) of polymer electrolyte membrane water electrolysers (PEMWEs). An array of 64 piezoelectric sensors was used, with all sensors emitting input pulses and detecting the acoustic wave reflected by the sample (pulse-echo mode). The shape and intensity of this reflected waveform depends on the ratio of reflection and transmission at phase interfaces and is strongly affected by resonant scattering of acoustic waves by gas bubbles. This AToF imaging technique was deployed to produce reflection intensity maps of the anode flow-field and LGDL; by measuring the AToF response for current densities ranging from 0.00 A cm−2 to 2.00 A cm−2, a close correlation was found between the acoustic attenuation in the flow-field and the production and removal of oxygen gas through the flow channels. Furthermore, a close link between the AToF response and water thickness in the LGDL was demonstrated, as supported by literature data. The application of the AToF technique has been established as a novel way of investigating PEMWE operation and as an alternative to more complex imaging techniques such as neutron imaging.

Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

Early nutritional intervention through enteral feeding can reduce treatment alterations and complications in patients with Oropharyngeal Cancer (OPC) undergoing Chemoradiation Treatment (CRT).

ObjectiveIn 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence.MethodsA needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation.ResultsEleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations.ConclusionThe 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

Flatt, AA, Esco, MR, Allen, JR, Robinson, JB, Bragg, A, Keith, CM, Fedewa, MV, and Earley, RL. Cardiac-autonomic responses to in-season training among Division-1 college football players. J Strength Cond Res 34(6): 1649-1656, 2020-Despite having to endure a rigorous in-season training schedule, research evaluating daily physiological recovery status markers among American football players is limited. The purpose of this study was to determine whether recovery of cardiac-autonomic activity to resting values occurs between consecutive-day, in-season training sessions among college football players. Subjects (n = 29) were divided into groups based on position: receivers and defensive backs (SKILL, n = 10); running backs, linebackers, and tight-ends (MID-SKILL, n = 11) and linemen (LINEMEN, n = 8). Resting heart rate (RHR) and the natural logarithm of the root mean square of successive differences multiplied by 20 (LnRMSSD) were acquired at rest in the seated position before Tuesday and Wednesday training sessions and repeated over 3 weeks during the first month of the competitive season. A position × time interaction was observed for LnRMSSD (p = 0.04), but not for the RHR (p = 0.33). No differences in LnRMSSD between days was observed for SKILL (Tuesday = 82.8 ± 9.3, Wednesday = 81.9 ± 8.7, p > 0.05). Small reductions in LnRMSSD were observed for MID-SKILL (Tuesday = 79.2 ± 9.4, Wednesday = 76.2 ± 9.5, p ≤ 0.05) and LINEMEN (Tuesday = 79.4 ± 10.5, Wednesday = 74.5 ± 11.5, p ≤ 0.05). The individually averaged changes in LnRMSSD from Tuesday to Wednesday were related to PlayerLoad (r = 0.46, p = 0.02) and body mass (r = -0.39, p = 0.04). Cardiac-parasympathetic activity did not return to resting values for LINEMEN or MID-SKILL before the next training session. Larger reductions in LnRMSSD tended to occur in players with greater body mass despite having performed lower workloads, although some individual variability was observed. These findings may have implications for how coaches and support staff address training and recovery interventions for players demonstrating inadequate cardiovascular recovery between sessions.

Childhood asthma develops in 30–40% of children with severe bronchiolitis but accurate prediction remains challenging. In a severe bronchiolitis cohort, we applied the Asthma Predictive Index (API), the modified Asthma Predictive Index (mAPI), and the Pediatric Asthma Risk Score (PARS) to predict asthma at age 5 years. We applied the API, mAPI, and PARS to the 17-center cohort of infants hospitalized with severe bronchiolitis during 2011–2014 (35th Multicenter Airway Research Collaboration, MARC-35). We used data from the first 3 years of life including parent interviews, chart review, and specific IgE testing to predict asthma at age 5 years, defined as parent report of clinician-diagnosed asthma. Among 875/921 (95%) children with outcome data, parent-reported asthma was 294/875 (34%). In MARC-35, a positive index/score for stringent and loose API, mAPI, and PARS were 24, 68, 6, and 55%, respectively. The prediction tools' AUCs (95%CI) ranged from 0.57 (95%CI 0.54–0.59) to 0.68 (95%CI 0.65–0.71). The positive likelihood ratios were lower in MARC-35 compared to the published results from the original cohorts. In this high-risk population of infants hospitalized with severe bronchiolitis, API, mAPI, and PARS had sub-optimal performance (AUC 0.8) asthma prediction tools are desired in infants hospitalized with severe bronchiolitis.

With the rapid adoption of machine learning techniques for large-scale applications in science and engineering comes the convergence of two grand challenges in visualization. First, the utilization of black box models (e.g., deep neural networks) calls for advanced techniques in exploring and interpreting model behaviors. Second, the rapid growth in computing has produced enormous datasets that require techniques that can handle millions or more samples. Although some solutions to these interpretability challenges have been proposed, they typically do not scale beyond thousands of samples, nor do they provide the high-level intuition scientists are looking for. Here, we present the first scalable solution to explore and analyze high-dimensional functions often encountered in the scientific data analysis pipeline. By combining a new streaming neighborhood graph construction, the corresponding topology computation, and a novel data aggregation scheme, namely topology aware datacubes , we enable interactive exploration of both the topological and the geometric aspect of high-dimensional data. Following two use cases from high-energy-density (HED) physics and computational biology, we demonstrate how these capabilities have led to crucial new insights in both applications.

The exome sequences of approximately 8,000 children with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) and 5,000 controls were analyzed, finding that individuals with ASD and individuals with ADHD had a similar burden of rare protein-truncating variants in evolutionarily constrained genes, both significantly higher than controls. This motivated a combined analysis across ASD and ADHD, identifying microtubule-associated protein 1A (MAP1A) as a new exome-wide significant gene conferring risk for childhood psychiatric disorders. Using samples from the Danish Neonatal Screening Biobank, children with ASD and children with ADHD were found to have similar, significantly increased rates of rare protein-truncating variants in evolutionarily constrained genes.

The IMPEDE Embolization Plug is a catheter-delivered vascular occlusion device that utilizes a porous shape memory polymer foam as a scaffold for thrombus formation and distal coils to anchor the device within the vessel. In this study, we investigated the biological response of porcine arteries to the IMPEDE device by assessing the extent of healing and overall effectiveness in occluding the vessel at 30, 60, and 90 days. Compared to control devices (Amplatzer Vascular Plug and Nester Embolization Coils), the host response to IMPEDE showed increased cellular infiltration (accommodated by the foam scaffold), which led to advanced healing of the initial thrombus to mature collagenous connective tissue (confirmed by transmission electron microscopy (TEM)). Over time, the host response to the IMPEDE device included degradation of the foam by multinucleated giant cells, which promoted fibrin and polymer degradation and advanced the healing response. Device effectiveness, in terms of vessel occlusion, was evaluated histologically by assessing the degree of recanalization. Although instances of recanalization were often observed at all time points for both control and test articles, the mature connective tissue within the foam scaffold of the IMPEDE devices improved percent vessel occlusion; when recanalization was observed in IMPEDE-treated vessels, channels were exclusively peri-device rather than intradevice, as often observed in the controls, and the vessels mostly remained >75% occluded. Although total vessel occlusion provides the optimal ischemic effect, in cardiovascular pathology, there is a progressive ischemic effect on the downstream vasculature as a vessel narrows. As such, we expect a sustained ischemic therapeutic effect to be observed in vessels greater than 75% occluded. Overall, the current study suggests the IMPEDE device presents advantages over controls by promoting an enhanced degree of healing within the foam scaffold, which decreases the likelihood of intradevice recanalization and ultimately may lead to a sustained ischemic therapeutic effect.

Though physical education instructional time varies across Canada, an idealised standard of 150 minutes per week has been identified, followed, and aspired to by many. For example, Canada’s...

Genetics provides two major opportunities for understanding human disease—as a transformative line of etiological inquiry and as a biomarker for heritable diseases. In psychiatry, biomarkers are very much needed for both research and treatment, given the heterogenous populations identified by current phenomenologically based diagnostic systems. To date, however, useful and valid biomarkers have been scant owing to the inaccessibility and complexity of human brain tissue and consequent lack of insight into disease mechanisms. Genetic biomarkers are therefore especially promising for psychiatric disorders. Genome-wide association studies of common diseases have matured over the last decade, generating the knowledge base for increasingly informative individual-level genetic risk prediction. In this review, we discuss fundamental concepts involved in computing genetic risk with current methods, strengths and weaknesses of various approaches, assessments of utility, and applications to various psychiatric disorders and related traits. Although genetic risk prediction has become increasingly straightforward to apply and common in published studies, there are important pitfalls to avoid. At present, the clinical utility of genetic risk prediction is still low; however, there is significant promise for future clinical applications as the ancestral diversity and sample sizes of genome-wide association studies increase. We discuss emerging data and methods aimed at improving the value of genetic risk prediction for disentangling disease mechanisms and stratifying subjects for epidemiological and clinical studies. For all applications, it is absolutely critical that polygenic risk prediction is applied with appropriate methodology and control for confounding to avoid repeating some mistakes of the candidate gene era.

This paper provides an account of a recent research study that investigated an international field experience—labelled as a service-learning internship—for in-service teachers. Relying upon what we know to be the advantages and benefits of similar international field experiences for pre-service teachers to frame our investigation, we explored the impact upon in-service teachers, particularly as they relate to both professional and personal growth. Analysis of questionnaire responses revealed several prominent themes. Stories and accounts of professional growth were related to: 1) creating an engaging and safe learning environment, 2) (over)planning for the unexpected, and 3) teaching with (and in front of) others. Stories and accounts of personal growth were related to: 1) letting go of control, 2) facing fears and confronting anxieties outside of one’s comfort zone, and 3) recognizing privilege and the excess of possessions. Results from this study might be of interest to those who similarly share an interest in international field experiences, service-learning, in-service teacher education, and international or global education.

Pathologic evaluation is crucial to the study of medical devices and integral to the Food and Drug Administration and other regulatory entities’ assessment of device safety and efficacy. While pathologic analysis is tailored to the type of device, it generally involves at a minimum gross and microscopic evaluation of the medical device and associated tissues. Due to the complex nature of some implanted devices and specific questions posed by sponsors, pathologic evaluation inherently presents many challenges in accurately assessing medical device safety and efficacy. This laboratory’s experience in numerous collaborative projects involving veterinary pathologists, biomedical engineers, physicians, and other scientists has led to a set of interrelated assessments to determine pathologic end points as a means to address these challenges and achieve study outcomes. Thorough device evaluation is often accomplished by utilizing traditional paraffin histology, plastic embedding and microground sections, and advanced imaging modalities. Combining these advanced techniques provides an integrative, comprehensive approach to medical device pathology and enhances medical device safety and efficacy assessment.

Lameness in cattle is a welfare concern and is associated with important economic losses in beef cattle operations. Infection of the distal interphalangeal joint (DIJ) results in severe lameness and if left untreated carries a poor prognosis. Diagnosis of DIJ infection is challenging in the field. The aim of this study was to determine factors associated with septic arthritis of the DIJ in beef cattle. Thirty-nine beef cattle with a complaint of single-foot lameness were used in this study. History and lameness examination data were recorded and analyzed. Radiographic changes and cytology of synovial fluid of the affected DIJ were used to define the presence (cases) or absence (controls) of DIJ infection. Asymmetric swelling at the coronary band of the affected foot and a lameness score of ≥4/5 significantly increased the odds (odds ratio [OR]=63.2 and OR=120, respectively) of diagnosis of septic arthritis of the DIJ in beef cattle with a single-foot lameness compared to cattle with no asymmetry of the coronary band or lameness scores

There is increasing evidence that early introduction of allergenic foods may decrease the risk of developing IgE-mediated food allergy. Patterns of food introduction before the 2015 publication of the Learning Early about Peanut Allergy (LEAP) trial are not well-studied, but are important as a baseline for evaluating subsequent changes in infant feeding practices and potentially food allergy. We performed a retrospective longitudinal study using data from a multicenter cohort of infants hospitalized with bronchiolitis between 2011–2014. The primary outcomes were IgE-mediated egg or peanut allergy by age 3 years. Of 770 participants included in the analysis, 635 (82%) introduced egg, and 221 (27%) introduced peanut by age 12 months per parent report. Four participants had likely egg allergy, and eight participants had likely peanut allergy by age 3 years. Regular infant egg consumption was associated with less egg allergy. The association was suggestive for infant peanut consumption with zero peanut allergy cases. Overall, our results suggest that early introduction of peanut was uncommon before 2015. Although limited by the small number of allergy cases, our results suggest that early introduction of egg and peanut are associated with a decreased risk of developing food allergy, and support recent changes in practice guidelines.

This cohort study examines cutaneous reactions in hospital employees who received messenger RNA COVID-19 vaccination.

The importance of extensive genetic testing of autism spectrum disorder (ASD) cases has been demonstrated repeatedly in research settings but such testing in clinical settings remains sporadic. Determining which individuals should be prioritized for expensive tests remains a challenge. Several guidelines have been released relating to clinical genetic evaluations and testing in the context of ASD and these guidelines may be informed by the results of genetic testing in large research cohorts. The current study summarizes findings from over 2,000 individuals with ASD who received genetic testing, including microarray and exome testing, through the Simons Simplex Consortium. A returnable genetic result is identified in 10% of cases, however, this yield increases based on four readily accessible phenotypes: female sex and the presence of intellectual disability, seizures or delayed walking. Combinations of these factors increase return rate further, with some combinations yielding a return rate over 50%. In conclusion, these four phenotypes provide a simple approach to prioritize genetic testing in a clinical setting and inform future clinical guidelines. Providing a systematic approach to decisions about who to test removes barriers for, and therefore decrease disparities in, reimbursable genetic testing for individuals diagnosed with ASD.

Background The Centers for Disease Control and Prevention state that a severe or immediate allergic reaction to the first dose of an mRNA COVID-19 vaccine is a contraindication for the second dose. Objective To assess outcomes associated with excipient skin testing after a reported allergic reaction to the first dose of mRNA COVID-19 vaccine. Methods We identified a consecutive sample of patients with reported allergic reactions after the first dose of mRNA COVID-19 vaccine who underwent allergy assessment with skin testing to polyethylene glycol (PEG) and, when appropriate, polysorbate 80. Skin testing results in conjunction with clinical phenotyping of the first-dose mRNA COVID-19 vaccine reaction guided second-dose vaccination recommendation. Second-dose mRNA COVID-19 vaccine reactions were assessed. Results Eighty patients with reported first-dose mRNA COVID-19 vaccine allergic reactions (n = 65; 81% immediate onset) underwent excipient skin testing. Of those, 14 (18%) had positive skin tests to PEG (n = 5) and/or polysorbate 80 (n = 12). Skin testing result did not affect tolerance of the second dose in patients with immediate or delayed reactions. Of the 70 patients who received the second mRNA COVID-19 vaccine dose (88%), 62 had either no reaction or a mild reaction managed with antihistamines (89%), but 2 patients required epinephrine treatment. Three patients with positive PEG-3350 intradermal (methylprednisolone) testing tolerated second-dose mRNA COVID-19 vaccination. Refresh Tears caused nonspecific skin irritation. Conclusions Most individuals with a reported allergic reaction to the first dose of mRNA COVID-19 vaccines, regardless of skin test result, received the second dose safely. More data are needed on the value of skin prick testing to PEG (MiraLAX) in evaluating patients with mRNA COVID-19 vaccine anaphylaxis. Refresh Tears should not be used for skin testing.

The U.S. Food and Drug Administration (FDA) has recently issued an Emergency Use Authorization (EUA) for 2 highly effective coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. This has brought hope to millions of Americans in the midst of an ongoing global pandemic. The FDA EUA guidance for both vaccines is to not administer the vaccine to individuals with a known history of a severe allergic reaction (eg, anaphylaxis) to any component of the COVID-19 vaccine. The Centers for Disease Control and Prevention (CDC) additionally advises individuals with a history of an immediate allergic reaction to a vaccine or injectable or any history of anaphylaxis be observed for 30 minutes after COVID-19 vaccination. All other individuals should be observed for 15 minutes after COVID-19 vaccination. Staff at vaccine clinics must be able to identify and manage anaphylaxis. Post–FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. To provide reassurance and support during widespread global vaccination, allergists must offer clear guidance to individuals based on the best information available, but also in accordance with the broader recommendations of regulatory agencies. This review summarizes vaccine allergy epidemiology and proposes drug and vaccine allergy expert opinion informed risk stratification for Allergy specialist use in conjunction with guidance of public health and regulatory authorities. The risk stratification schema guide care for (1) individuals with different allergy histories to safely receive their first mRNA COVID-19 vaccine and (2) individuals who develop a reaction to their first dose of mRNA COVID-19 vaccine.

BACKGROUND: The US older adult population (≥65 years) is increasing and may be at increased risk for severe anaphylaxis. Little is known about the healthcare utilization for acute allergic reactions (AAR), including anaphylaxis, among older adults. OBJECTIVES: To characterize trends in emergency department (ED) visits and hospitalizations for AAR and anaphylaxis among US older adults from 2006–2014, and to examine factors associated with severe anaphylaxis. METHODS: We performed cross-sectional analyses of trends in ED visits and hospitalizations among older adults using data from the Nationwide Emergency Department Sample and the National (Nationwide) Inpatient Sample in 2006–2014. We used International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes to identify visits for AAR, including anaphylaxis. Multivariable logistic regression modeling was used to identify factors associated with severe anaphylaxis (cardiac arrest, intubation and death). RESULTS: In 2006–2014, older adults experienced approximately 1,019,967 AAR-related ED visits; 173,844 AAR-related hospitalizations; 93,795 anaphylaxis-related ED visits; and 72,677 anaphylaxis-related hospitalizations. While AAR-related ED visit and hospitalization rates remained stable (P-trends=0.28 and 0.16, respectively), anaphylaxis-related ED visit and hospitalization rates significantly increased over time (37 visits per 100,000 population in 2006 to 51 in 2014, P-trend

Recently, we developed a time-domain diffuse correlation spectroscopy (TD-DCS) method for neurovascular sensing with higher brain sensitivity. In this paper, laser pulse shaping was designed and demonstrated for TD-DCS at 1064 nm. A quantum superconducting nanowire single-photon detector (SNSPD) with high photon detection efficiency (PDE) and low jitter collects the back-scattered light from the brain. The presented approach is the first step towards scaling up a full fiber optic cap with 96 source channels and 192 custom-made single-photon detectors which will cover most of an adult head.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. Recent advances in the field have seen the introduction of iDWS/iDCS, which have allowed for the use of conventional photodetectors to replace the single photon counting detectors required to measure the traditional, homodyne DCS signal. Here we detail a high framerate, highly parallel iDCS system at 1064 nm which allows for improved signal to noise ratio at extended source detector separations.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. DCS cerebral blood flow measurements in clinical applications have shown promise, but measurements contain contamination of the signal from changes in superficial blood flow. Recent studies have shown that moving to wavelengths beyond the water absorption peak at 970 nm when making DCS measurements improves SNR and reduced influence of superficial flow. Here, we present a DCS system operating at 1064 nm utilizing two InGaAs SPADs to calculate the cross correlation to address detector non-idealities.

Delayed Local Reactions to mRNA-1273 Vaccine Delayed cutaneous reactions developed in 12 patients days after initial injection-related symptoms resolved. The reactions, some as severe as grade 3, r...

Low cardiac output syndrome complicates recovery after cardiac surgery. We examined the incidence and risk factors for low cardiac output syndrome and its association with postoperative mortality, morbidity, resource use, and cost.This cross-sectional retrospective observational study examined patients having cardiac surgery captured in the Premier Healthcare Database. Low cardiac output syndrome was defined as the requirement for postoperative mechanical circulatory support and/or hemodynamic instability requiring prolonged inotropic support. Incidence, risk factors, and association of low cardiac output syndrome with postoperative outcomes, including mortality, hospital and intensive care unit length of stay, hospital readmission, and cost at 30 days, 90 days, and 6 months, were examined.Among 59,810 patients from 164 hospitals having cardiac surgery between July 1, 2012, and June 30, 2014, low cardiac output syndrome developed in 6067 (10.1%) patients. Patients presenting in cardiogenic shock or systolic (± diastolic) heart failure were at greatest risk. Risk-adjusted in-hospital mortality was 12-fold greater with low cardiac output syndrome (odds ratio, 12.0; 95% confidence interval, 10.6-13.5). Risk-adjusted hospital costs (2019$; median [Q1, Q3]) were $64,041 [21,439] in patients who developed low cardiac output syndrome versus $48,086 [16,098] without; P .001. Increased costs were driven by longer risk-adjusted hospital stay (10.1 [4.5] vs 8.5 [3.8] days); P .001, intensive care unit (5.5 [2.5] vs 3.3 [1.5] days; P .001) stay, and all-cause 30-day adjusted hospital readmission rates (mean [SD] 16.6 [8.2]% vs 13.9 [7.2]%; P .001).Cardiac surgical patients who develop postoperative low cardiac output syndrome suffer greater mortality and have greater resource use, health care costs, and all-cause readmission, which informs perioperative decision making, and impacts hospital performance metrics and federal priority to reduce health care costs.

The electrode drying process is a crucial step in the manufacture of lithium-ion batteries and can significantly affect the performance of an electrode once stacked in a cell. However, there is a need to develop more informative in-situ metrologies to better understand the dynamics of the drying process. Here, ultrasound acoustic based technique has been developed as an in-situ tool to study the electrode drying process using NMC622-based cathodes and graphite-based anodes. The drying dynamic evolution for cathodes dried at 40 and 60 °C, and anodes dried at 60 °C were investigated, with the attenuation of the reflective acoustic signals used to indicate the evolution physical properties of the electrode coating film. The drying-induced acoustic signal shifts were discussed critically and correlated to the reported three-stage drying mechanism, which offering a new mode to investigate the dynamic drying process. Ultrasound acoustic based measurement has been successfully shown to be a novel in-situ metrology to acquire dynamic drying profiles. The findings would potentially fulfil the research gaps between acquiring dynamic data continuously for drying mechanism study and existing research metrology. It shows the great potential to be further developed and understand the drying process to achieve a more controllable electrode manufacturing process.

Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes.

Purpose: The purpose of this study was to establish the clinical practice of physiotherapists who treat people with knee osteoarthritis (OA) in Canada and examine their knowledge, awareness, use of, and attitudes toward clinical practice guidelines (CPGs). Method: We conducted a cross-sectional survey of physiotherapists who are licensed to practise in Canada and who treat people with knee OA. Results: A total of 388 physiotherapists completed our survey. Approximately two-thirds of them (271) were aware of CPGs. Out of all CPG recommendations, most respondents provided leg strengthening exercises (380) and education (364). More than 80% believed that CPGs improved patient care and enhanced decision making and were confident in their ability to interpret CPGs. More physiotherapists (204) identified barriers to the use of CPGs than facilitators of their use (117). Physiotherapists who were employed in private practice were substantially more likely to use interventions such as acupuncture (odds ratio [OR] 5.98; 95% CI: 2.92, 12.23; p < 0.01) and joint mobilization and manipulation (OR 6.58; 95% CI: 3.45, 12.55; p < 0.01) than were physiotherapists employed in hospital settings. Conclusions: Two-thirds of respondents were aware of CPGs. Physiotherapists provided education and leg strengthening exercises more often than aerobic exercise and weight management advice. Physiotherapists employed in private practice were more likely to use adjunct interventions.

The implications of climate change for biological invasions are multifaceted and vary along the invasion process. Changes in vectors and pathways are likely to manifest in changes in transport routes and destinations, together with altered transit times and traffic volume. Ultimately, changes in the nature of why, how, and where biota are transported and introduced will pose biosecurity challenges. These challenges will require increased human and institutional capacity, as well as proactive responses such as improved early detection, adaptation of present protocols and innovative legal instruments. Invasion success and spread are expected to be moderated by the physiological response of alien and native biota to environmental changes and the ensuing changes in biotic interactions. These in turn will likely affect management actions aimed at eradicating, containing, and mitigating invasions, necessitating an adaptive approach to management that is sensitive to potentially unanticipated outcomes.

ObjectiveThe evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019.MethodsA matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥ 18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to 5 non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020.ResultsAmong 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death.ConclusionsIn this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.

In recent years, many Canadian universities have added a Fall Pause to their academic calendars. However, those who have been making these decisions have been doing so without having access to any resources that provide an overview of existing Fall Pause practices or models across the nation. Additionally, there exists a paucity of literature that provides a sound rationale for the introduction of a Fall Pause. This paucity of literature makes research-informed decision making about the introduction of a Fall Pause an especially difficult task. Given these observations, we have undertaken the task of writing this article with two goals in mind: (a) to provide an overview of the current Canadian university landscape with respect to the Fall Pause; and (b) to provide a scoping review of the related emerging literature related to the Fall Pause. With this information made available, it is our hope that university faculty and administrators will be better positioned to make informed decisions about the possible introduction or continued inclusion of a Fall Pause in their own universities’ schedules. They, and we, might also then be able to have a better (informed) sense of the research-based outcomes for those who have already introduced and/or experienced a Fall Pause. Depuis quelques années, de nombreuses universités canadiennes ont ajouté un congé d’automne à leurs calendriers universitaires. Toutefois, celles qui ont pris cette décision l’ont fait sans avoir accès aux ressources qui fournissent un aperçu des pratiques relatives au congé d’automne ou aux modèles d’un bout à l’autre du pays. De plus, il n’existe que très peu d’études qui fournissent un justificatif solide pour l’introduction d’un congé d’automne. Cette quasi absence de publications fait en sorte que la décision basée sur la recherche d’introduire un congé d’automne devient une tâche particulièrement difficile. À la lumière de ces observations, nous avons entrepris la tâche de rédiger cet article avec deux objectifs en tête : (a) fournir une vue d’ensemble du paysage actuel des universités canadiennes en ce qui se rapporte au congé d’automne, et (b) fournir un examen de la portée des publications émergentes connexes qui se rapportent au congé d’automne. Avec ces renseignements devenus disponibles, nous espérons que les professeurs et les professeures, ainsi que les administrateurs et les administratrices d’universités, seront mieux préparés à prendre des décisions éclairées sur l’introduction possible ou la continuation d’inclure un congé d’automne dans leurs calendriers universitaires. Ils pourront, et nous aussi, être également en mesure de mieux comprendre les résultats basés sur la recherche pour ceux et celles qui ont déjà introduit et/ou fait l’expérience d’un congé d’automne.

Significance: The use of diffuse correlation spectroscopy (DCS) has shown efficacy in research studies as a technique capable of noninvasively monitoring blood flow in tissue with applications in neuromonitoring, exercise science, and breast cancer management. The ability of DCS to resolve blood flow in these tissues is related to the optical sensitivity and signal-to-noise ratio (SNR) of the measurements, which in some cases, particularly adult cerebral blood flow measurements, is inadequate in a significant portion of the population. Improvements to DCS sensitivity and SNR could allow for greater clinical translation of this technique. Aim: Interferometric diffuse correlation spectroscopy (iDCS) was characterized and compared to traditional homodyne DCS to determine possible benefits of utilizing heterodyne detection. Approach: An iDCS system was constructed by modifying a homodyne DCS system with fused fiber couplers to create a Mach–Zehnder interferometer. Comparisons between homodyne and heterodyne detection were performed using an intralipid phantom characterized at two extended source–detector separations (2.4, 3.6 cm), different photon count rates, and a range of reference arm power levels. Characterization of the iDCS signal mixing was compared to theory. Precision of the estimation of the diffusion coefficient and SNR of the autocorrelation curve were compared between different measurement conditions that mimicked what would be seen in vivo. Results: The mixture of signals present in the heterodyne autocorrelation function was found to agree with the derived theory and resulted in accurate measurement of the diffusion coefficient of the phantom. Improvement of the SNR of the autocorrelation curve up to ∼2× and up to 80% reduction in the variability of the diffusion coefficient fit were observed for all measurement cases as a function of increased reference arm power. Conclusions: iDCS has the potential to improve characterization of blood flow in tissue at extended source–detector separations, enhancing depth sensitivity and SNR.

BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction. The overall prevalence of anaphylaxis appears to be rising in children, but temporal trends among infants and toddlers are not well studied. OBJECTIVE: To characterize the trends in U.S. emergency department (ED) visits and hospitalizations among infants and toddlers with anaphylaxis from 2006–2015. METHODS: We conducted a study of temporal trends in anaphylaxis among children (age

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8–22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10−7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.