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Ecosystem engineers often affect structural complexity of habitats. There are multiple methods of quantifying complexity, variously measuring topography, surface area, volume, fractal dimension, or rugosity. We compared eight methods, four employing the 3D modelling program ‘Blender’ to estimate total surface area, top surface area, their ratio, and interstitial volume; and four empirically measuring interstitial volume, fractals and two indices of rugosity. We compared these using seven metrics: 1) correlations among comparable measures; 2) consistency; 3) accuracy; 4) precision; 5) discrimination among configurations of objects; 6) discernment of complexities among zones on rocky shores; and 7) practicality. Of the eight methods, the virtual volumetric method, Blender interstitial volume, performed the best. Direct measurements of three-dimensional space related more closely to patterns in biodiversity than did measurements of two-dimensional space or indirect measures of complexity like fractals. Blender interstitial volume is thus the recommended means of measuring structural complexity of benthic environments.

In this paper, we consider the following discrete nonlinear problem which is subject to a periodic nonlinear forcing term: A u = λ u + p ( u ) + h , \begin{equation*} A u = \lambda u +p(u) + h, \end{equation*} where A A is an n × n n\times n matrix with real components, p : R n → R n p: \mathbb {R}^n\to \mathbb {R}^n is a periodic forcing term, and ⟨ h , ϕ ¯ ⟩ = 0 \langle h,\overline {\phi } \rangle =0 , where ϕ ¯ \overline {\phi } is an eigenvector of A T , A^T, the transpose of A A , corresponding to a simple real eigenvalue λ \lambda . Conditions on these terms will be provided such that this problem will have infinitely many distinct solutions. The results here are motivated by some recent results for discrete systems and by results obtained for analogous boundary value problems for semilinear elliptic problems at resonance.

The purpose of this study was to design and evaluate an instructional approach that combined strategy instruction with principles of dialogic pedagogy to improve the story writing of studen...

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...

The behavioral repertoire and environmental feature needs for thermoregulatory comfort have not been reported in the literature for large captive exotics. An observational study was done to investigate the behavioral repertoire of tigers via continuous observation, while focusing on thermoregulatory behavior, in order to examine behavioral and thermoregulatory needs of these animals, and inform microclimatic landscape design for thermal comfort. Nine Bengal tigers (n = 6 females, n = 3 males) were observed in June 2012, and behavior data were recorded every minute, while thermal images of each individual, wind speed, ambient temperature, and relative humidity were recorded every 15 min. Descriptive statistics were used to analyze the data due to the observatory nature of the study. All tigers spent on average over 45% of the time lying down, less than 19% of the time in direct sunlight and over 20% of their time in the shade. Males did more panting (25.6%) than females (15.1%). There was more individual variation in water and cave usage, compared with shade use and lying behaviors, which could be related to social pressures or basic individual preferences. In summary, shade is a very valuable thermoregulatory resource for tigers. Adding more shade structures to increase thermal comfort and increase activity in these cats (around 10% on average active behaviors) by adding to the space available in the shaded areas.

We present and analyze a three-dimensional (3D) volume of nanoscale helium bubbles in a tritium-exposed palladium alloy that we have reconstructed by transmission electron tomography. Helium nanobubbles commonly form within metals during exposure to radiation and radioactive substances. The radioactive decay of tritium stored in metal tritides often results in a high density of these nanoscale helium bubbles. A persistent question about the mechanisms of bubble nucleation and growth has been the role of lattice defects and impurities. To address this matter, we have determined the 3D positions of helium nanobubbles in a palladium–nickel alloy exposed to tritium for 3.8 years. We introduce methods to determine the 3D shapes, volumes, and spatial positions of helium bubbles as small as 1 nm within solids. We find that the size and spacing of observed nanobubbles are not correlated. Our results suggest that previous models, which hypothesize initial, rapid homogeneous nucleation of nanobubbles followed by di...

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.

Plasmons, the collective oscillations of mobile electrons in metallic nanostructures, interact strongly with light and produce vivid colors, thus offering a new route to develop color printing technologies with improved durability and material simplicity compared with conventional pigments. Over the last decades, researchers in plasmonics have been devoted to manipulating the characteristics of metallic nanostructures to achieve unique and controlled optical effects. However, before plasmonic nanostructures became a science, they were an art. The invention of the daguerreotype was publicly announced in 1839 and is recognized as the earliest photographic technology that successfully captured an image from a camera, with resolution and clarity that remain impressive even by today’s standards. Here, using a unique combination of daguerreotype artistry and expertise, experimental nanoscale surface analysis, and electromagnetic simulations, we perform a comprehensive analysis of the plasmonic properties of these early photographs, which can be recognized as an example of plasmonic color printing. Despite the large variability in size, morphology, and material composition of the nanostructures on the surface of a daguerreotype, we are able to identify and characterize the general mechanisms that give rise to the optical response of daguerreotypes. Therefore, our results provide valuable knowledge to develop preservation protocols and color printing technologies inspired by past ones.

Polymer electrolyte membrane water electrolysers (PEMWE) are a key technology for producing clean (‘green’) hydrogen for decarbonisation of the transport sector and grid stabilisation utilising increasing levels of renewable energy. In this work, acoustic emission analysis is used as a non-destructive, operando diagnostic tool to provide information about the relative number and size of gas bubbles generated locally within a PEMWE, providing effective characterisation of the local flow conditions. An optically transparent single-channel PEMWE is used to investigate the relationship between the acoustic signals obtained and the two-phase flow conditions inside the cell. The number of acoustic hits, their frequency, and average peak amplitude is reported for several flow rates and current densities. Using high-speed imaging, the average bubble number and size in the flow cannels is compared to the acoustic signal. Results show good correlation between the number of acoustic ‘hits’ and the number of bubbles passing through the flow channel. The size of bubbles is also shown to affect the average frequency of the hits. Consequently, the transition between bubbly and slug flow regime can be identified by acoustic emission analysis, paving the way for a simple, low-cost, non-destructive means of mapping flow inside commercial-scale PEMWEs.

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.

Despite expanding knowledge regarding the role of astroglia in regulating neuronal function, little is known about regional or functional subgroups of brain astroglia and how they may interact with neurons. We use an astroglia-specific promoter fragment in transgenic mice to identify an anatomically defined subset of adult gray matter astroglia. Using transcriptomic and histological analyses, we generate a combinatorial profile for the in vivo identification and characterization of this astroglia subpopulation. These astroglia are enriched in mouse cortical layer V; express distinct molecular markers, including Norrin and leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6), with corresponding layer-specific neuronal ligands; are found in the human cortex; and modulate neuronal activity. Astrocytic Norrin appears to regulate dendrites and spines; its loss, as occurring in Norrie disease, contributes to cortical dendritic spine loss. These studies provide evidence that human and rodent astroglia subtypes are regionally and functionally distinct, can regulate local neuronal dendrite and synaptic spine development, and contribute to disease.

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.

This article is drawn from a larger qualitative case study that examined the leadership context and leadership approaches of five Mi’kmaw women school principals in Mi’kmaw Kina’matnewey (MK), an A...

This paper describes results from a study that arose to explore, alongside Aboriginal teacher candidates, emerging physical education (PE) practical theory utilizing reflective journaling practices. Practical theory can be described as an individual’s personal and dynamic set of values, knowledge, and experience that guides, in part, teaching choices and behaviours. In the thematic analysis of teacher candidates’ reflective journals, care was taken to honour and confirm the voices of nine Aboriginal teacher candidates. Four key themes were identified: marginality (foreign activities and stereotypical expectations), cultural preservation through PE, Elder involvement in PE, and looking to the future. The results may serve to inform those with an interest in reflective practices in physical education teacher education (PETE) and/or Aboriginal teacher education., Le présent document décrit les résultats d’une étude qui visait à explorer, en collaboration avec des étudiants autochtones en enseignement, la théorie pratique émergente de l’éducation physique (EP) à l’aide de pratiques de tenue d’un journal réflexif. La théorie pratique peut être décrite comme l’ensemble personnel et dynamique de valeurs, de connaissances et d’expériences d’une personne qui guide, en partie, les choix et les comportements pédagogiques. Dans l’analyse thématique des journaux de réflexion des étudiantes et étudiants en enseignement, on a pris soin d’honorer et de confirmer les voix de neuf étudiantes et étudiants autochtones. Quatre thèmes clés ont été identifiés : la marginalité (activités étrangères et attentes stéréotypées), la préservation de la culture par l’éducation physique, l’engagement des aînés dans l’éducation physique et le regard vers l’avenir. Les résultats peuvent servir à informer les personnes qui s’intéressent aux pratiques de réflexion dans la formation à l’éducation physique et à la formation à l’enseignement de l’éducation physique (FEEP) ou à la formation à l’enseignement des Autochtones.

The brain has specific properties that make it uniquely dependent upon transporters. This is the 3rd edition of a biennial special issue that originates from a scientific meeting devoted to studies of transporters and their relationship to brain function and to neurodevelopmental, neurologic, and psychiatric disorders. The field continues to rapidly evolve with advances in studies of structure that inform mechanism, with genetic analyses in humans revealing surprising aspects of biology, and with integrated cellular to whole animal analyses of the role of transporters in their control of physiology and pathophysiology. This special issue includes a sampling of review articles that address timely questions of the field followed by several primary research articles.

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

Species introduced through human-related activities beyond their native range, termed alien species, have various impacts worldwide. The IUCN Environmental Impact Classification for Alien Taxa (EICAT) is a global standard to assess negative impacts of alien species on native biodiversity. Alien species can also positively affect biodiversity (for instance, through food and habitat provisioning or dispersal facilitation) but there is currently no standardized and evidence-based system to classify positive impacts. We fill this gap by proposing EICAT+, which uses 5 semiquantitative scenarios to categorize the magnitude of positive impacts, and describes underlying mechanisms. EICAT+ can be applied to all alien taxa at different spatial and organizational scales. The application of EICAT+ expands our understanding of the consequences of biological invasions and can inform conservation decisions.

Unknown SNP-to-gene regulatory architecture complicates efforts to link noncoding GWAS associations with genes implicated by sequencing or functional studies. eQTLs are used to link SNPs to genes, but expression in bulk tissue explains a small fraction of disease heritability. A simple but successful approach has been to link SNPs with nearby genes, but the fraction of heritability mediated by these genes is unclear, and gene-proximal (vs. gene-mediated) heritability enrichments are attenuated accordingly. We propose the Abstract Mediation Model (AMM) to estimate (1) the fraction of heritability mediated by the closest or kth-closest gene to each SNP and (2) the mediated heritability enrichment of a gene set (e.g. genes with rare-variant associations). AMM jointly estimates these quantities by matching the decay in SNP enrichment with distance from genes in the gene set. Across 47 complex traits and diseases, we estimate that the closest gene to each SNP mediates 27% (SE: 6%) of heritability, and that a substantial fraction is mediated by genes outside the ten closest. Mendelian disease genes are strongly enriched for common-variant heritability; for example, just 21 dyslipidemia genes mediate 25% of LDL heritability (211x enrichment, P = 0.01). Among brain-related traits, genes involved in neurodevelopmental disorders are only about 4x enriched, but gene expression patterns are highly informative, with detectable differences in per-gene heritability even among weakly brain-expressed genes.

The aim of this study was to determine clinical and echocardiographic characteristics, mechanisms of failure, and outcomes of mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER).Although100,000 mitral TEER procedures have been performed worldwide, longitudinal data on MV surgery after TEER are lacking.Data from the multicenter, international CUTTING-EDGE registry were retrospectively analyzed. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 9.0 months (interquartile range [IQR]: 1.2-25.7 months) after MV surgery, and follow-up was 96.1% complete at 30 days and 81.1% complete at 1 year.From July 2009 to July 2020, 332 patients across 34 centers underwent MV surgery after TEER. The mean age was 73.8 ± 10.1 years, median Society of Thoracic Surgeons risk for MV repair at initial TEER was 4.0 (IQR: 2.3-7.3), and primary/mixed and secondary mitral regurgitation were present in 59.0% and 38.5%, respectively. The median interval from TEER to surgery was 3.5 months (IQR: 0.5-11.9 months), with overall median Society of Thoracic Surgeons risk of 4.8% for MV replacement (IQR: 2.8%-8.4%). The primary indication for surgery was recurrent mitral regurgitation (33.5%), and MV replacement and concomitant tricuspid surgery were performed in 92.5% and 42.2% of patients, respectively. The 30-day and 1-year mortality rates were 16.6% and 31.3%, respectively. On Kaplan-Meier analysis, the actuarial estimates of mortality were 24.1% at 1 year and 31.7% at 3 years after MV surgery.In this first report of the CUTTING-EDGE registry, the mortality and morbidity risks of MV surgery after TEER were not negligible, and only 10% of patients underwent MV repair. These registry data provide valuable insights for further research to improve these outcomes.

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.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental disorders with a considerable overlap in their genetic etiology. We dissected their shared and distinct genetic architecture by cross-disorder analyses of large data sets, including samples with information on comorbid diagnoses. We identified seven loci shared by the disorders and the first five genome-wide significant loci differentiating the disorders. All five differentiating loci showed opposite allelic directions in the two disorders separately as well as significant associations with variation in other traits e.g. educational attainment, items of neuroticism and regional brain volume. Integration with brain transcriptome data identified and prioritized several significantly associated genes. Genetic correlation of the shared liability across ASD-ADHD was strong for other psychiatric phenotypes while the ASD-ADHD differentiating liability correlated most strongly with cognitive traits. Polygenic score analyses revealed that individuals diagnosed with both ASD and ADHD are double-burdened with genetic risk for both disorders and show distinctive patterns of genetic association with other traits when compared to the ASD-only and ADHD-only subgroups. The results provide novel insights into the biological foundation for developing just one or both of the disorders and for driving the psychopathology discriminatively towards either ADHD or ASD.

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). A family of five Na(+)-dependent transporters maintain low levels of extracellular glutamate and shape excitatory signaling. Shortly after the research group of the person being honored in this special issue (Dr. Baruch Kanner) cloned one of these transporters, his group and several others showed that their activity can be acutely (within minutes to hours) regulated. Since this time, several different signals and post-translational modifications have been implicated in the regulation of these transporters. In this review, we will provide a brief introduction to the distribution and function of this family of glutamate transporters. This will be followed by a discussion of the signals that rapidly control the activity and/or localization of these transporters, including protein kinase C, ubiquitination, glutamate transporter substrates, nitrosylation, and palmitoylation. We also include the results of our attempts to define the role of palmitoylation in the regulation of GLT-1 in crude synaptosomes. In some cases, the mechanisms have been fairly well-defined, but in others, the mechanisms are not understood. In several cases, contradictory phenomena have been observed by more than one group; we describe these studies with the goal of identifying the opportunities for advancing the field. Abnormal glutamatergic signaling has been implicated in a wide variety of psychiatric and neurologic disorders. Although recent studies have begun to link regulation of glutamate transporters to the pathogenesis of these disorders, it will be difficult to determine how regulation influences signaling or pathophysiology of glutamate without a better understanding of the mechanisms involved.

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 genetic etiology of autism spectrum disorder (ASD) is multifactorial with contributions from rare variants, polygenic risk, and sex. How combinations of factors determine risk for ASD is unclear. In 11,313 ASD families (N = 37,375 subjects), we investigated the effects rare and polygenic risk individually and in combination. We show that genetic liability for ASD differs by sex, with females having a greater polygenic load, and males having a lower liability threshold as evident by a negative correlation of rare and polygenic risk. Multiple genetic factors were associated with differing sets of behavioral traits with effects that differed by sex. Furthermore, the correlation of parental age with genetic risk for ASD was attributable tode novomutations and sex-biased effects of inherited risk in parents. Our results demonstrate that a phenotypic spectrum of ASD is attributable to the relative loadings and gene-by-sex effects of rare and common variation.

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.

DNA double-strand breaks (DSBs) are among the deleterious lesions that are both endogenous and exogenous in origin and are repaired by nonhomologous end joining or homologous recombination. However, the molecular mechanisms responsible for maintaining genome stability remain incompletely understood. Here, we investigate the role of two E3 ligases, Dma1 and Dma2 (homologs of human RNF8), in the maintenance of genome stability in budding yeast. Using yeast spotting assays, chromatin immunoprecipitation and plasmid and chromosomal repair assays, we establish that Dma1 and Dma2 act in a redundant and a catalysis-dependent manner in the maintenance of genome stability, as well as localize to transcribed regions of the genome and increase in abundance upon phleomycin treatment. In addition, Dma1 and Dma2 are required for the normal kinetics of histone H4 acetylation under DNA damage conditions, genetically interact with RAD9 and SAE2, and are in a complex with Rad53 and histones. Taken together, our results demonstrate the requirement of Dma1 and Dma2 in regulating DNA repair pathway choice, preferentially affecting homologous recombination over nonhomologous end joining, and open up the possibility of using these candidates in manipulating the repair pathways toward precision genome editing.

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...

Background Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation. Methods Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation. Results Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing. Conclusions Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.

The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how combinations of genetic factors determine risk is unclear. In a large family sample, we show that genetic loads of rare and polygenic risk are inversely correlated in cases and greater in females than in males, consistent with a liability threshold that differs by sex. De novo mutations (DNMs), rare inherited variants and polygenic scores were associated with various dimensions of symptom severity in children and parents. Parental age effects on risk for ASD in offspring were attributable to a combination of genetic mechanisms, including DNMs that accumulate in the paternal germline and inherited risk that influences behavior in parents. Genes implicated by rare variants were enriched in excitatory and inhibitory neurons compared with genes implicated by common variants. Our results suggest that a phenotypic spectrum of ASD is attributable to a spectrum of genetic factors that impact different neurodevelopmental processes.

Active and passive transporters constitute a gene family of approximately 2000 members. These proteins are required for import and export across the blood brain barrier, clearance of neurotransmitters, inter-cellular solute transfer, and transport across the membranes of subcellular organelles. Neurologic, neurodevelopmental, and psychiatric diseases have been linked to alterations in function and/or mutations in every one of these types of transporters, and many of the transporters are targeted by therapeutics. This is the 4th biennial special edition of Neurochemistry International that originates from a scientific meeting devoted to studies of transporters and their relationship to brain function and to neurodevelopmental, neurologic, and psychiatric disorders. This meeting provides the only international forum for the presentation and discussion of cutting-edge research on brain transporters covering fundamental aspects of transporter structure, function, and trafficking. Scientists describe the novel approaches being used to link this information to physiology/circuit function and behavior. The meeting also addresses translational topics surrounding mouse models of brain transporter disorders, novel human brain disorders arising from transporter mutations, and innovative therapeutic approaches centered on modification of transporter function. This special issue includes a sampling of review articles that address timely questions of the field and several primary research articles.

BackgroundGout is the most common inflammatory arthritis and occurs frequently in patients with renal disease often leading to a significant burden on quality of life and functional status.1,2 Despite the established connection of renal disease with gout, little has been reported on the prevalence, patient characteristics, and associations of gout with other outcomes in the US hemodialysis (HD) and peritoneal dialysis (PD) population.ObjectivesThis project used a large end-stage renal disease (ESRD) focused-database, Dialysis Outcomes and Practice Patterns Study (DOPPS), to examine gout in dialysis-dependent patients.MethodsGout patients were identified by active prescription (Rx) of (1) colchicine, (2) febuxostat, or (3) allopurinol; or by (4) prior diagnosis of gout from US cohorts of 70,297 HD (DOPPS, 2012-2020) patients and 5117 PD (Peritoneal DOPPS, 2014-2020) patients. Outcomes of HD and PD patients with and without a history of gout were compared with propensity score matching. Outcomes included erythropoietin resistance index (ERI = ESA dose/(hemoglobin*weight), cardiovascular death, all-cause mortality/hospitalization, and baseline patient-reported outcomes (PROs).ResultsGout prevalence was 13% in HD and 21% in PD and was highest among incident dialysis patients. Of the gout patients identified, the most-commonly used gout-related medications were allopurinol (9-12%), followed by colchicine (2-3%), and then febuxostat (1%, Figure 1). Both HD and PD patients with gout (vs. no gout) were older and more likely male. Gout HD and PD patients had higher BMI and higher prevalence of cardiovascular comorbidities than HD and PD patients without gout. After propensity score matching, mean ERI was 4% higher for gout vs. non-gout patients, while there was minimal evidence of association with clinical outcomes (mortality and hospitalization) or PROs.Figure 1.Gout prevalence by dialysis duration in patients undergoing HD and PD. Criteria for gout included gout diagnosis and use of a urate-lowering therapy.HD, hemodialysis; PD, peritoneal dialysis; mo, months; Rx, prescription; yrs, years. Some patients were included in multiple gout categories.ConclusionGout was common in US HD and PD patients, with a large proportion of these patients treated with drugs indicated for hyperuricemia (allopurinol and febuxostat) and gout flares (colchicine). The true prevalence of gout was likely higher than observed when considering potential under-ascertainment of gout diagnosis history in nephrology/dialysis-focused clinical settings.3 This report provides a snapshot of gout in the US dialysis population and offers opportunities to expand on research to improve awareness and care for patients with gout and ESRD.References[1]Singh JA, Strand V. Ann Rheum Dis. 2008;67:1310–6.[2]Singh JA, Cleveland JD. BMC Neph 2019;20:93.[3]Roughley M, et al. Arthritis Res Ther. 2018;20(1):243.Disclosure of InterestsAngelo Karaboyas Grant/research support from: Horizon Therapeutics, Junhui Zhao Grant/research support from: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brad Marder Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Barry Gorlitsky Consultant of: AstraZenica, Davita, Horizon Therapeutics, Jensen Pharmaceuticals, KidneyAide LLC, vinicius domingues Consultant of: Abbvie, Aurinia Pharma, Exagen, Eli Lilly, Roberto Pecoits-Filho Grant/research support from: Horizon Therapeutics, Bruce Robinson Grant/research support from: Horizon Therapeutics