Search

OBJECTIVE To identify more effective language strategies for helping pet owners appreciate the value and importance of preventive veterinary care and encouraging more regular visits. SAMPLE 15 pet owners representing a mix of demographic and other characteristics. PROCEDURES This qualitative study began with a communication and research audit, followed by interviews with subject matter experts, development of language stimuli (messages about the importance of veterinary care and encouraging pet owners to prioritize wellness visits), three 2-hour online focus group sessions with study participants (4 to 6/group) to test and discuss the language stimuli, and 1-hour one-on-one interviews with 5 of these participants to measure emotional responses to optimized stimuli. RESULTS Language stimuli testing showed that simply telling pet owners how veterinary care is valuable does not work. What did work was focusing on the pet owner’s relationship with their pet, tying preventive care into the animal’s overall health and happiness, and emphasizing a veterinarian’s experience versus their qualifications. Personalized recommendations were perceived as most valuable to owners. Addressing cost head-on, demonstrating understanding, empowering pet owners to ask questions, and providing payment options were identified as strategies that could help owners see they can afford routine care now. CLINICAL RELEVANCE Results suggested that by focusing on experience, relationships, and personalized care, veterinarians can address pet owners’ concerns while promoting the importance of preventive care, including regular checkups. Additional research is needed to evaluate the impact of this language on pet owner perceptions, behaviors, and outcomes in clinical settings.

Identifying optimal machine learning pipelines for computer-aided diagnosis is key for the development of robust, reproducible, and clinically relevant imaging biomarkers for endometrial carcinoma. The purpose of this study was to introduce the mathematical development of image descriptors computed from spherical harmonics (SPHARM) decompositions as well as the associated machine learning pipeline, and to evaluate their performance in predicting deep myometrial invasion (MI) and histopathological high-grade in preoperative multiparametric magnetic resonance imaging (MRI).This retrospective study included 128 women with histopathology-confirmed endometrial carcinomas who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. SPHARM descriptors of each tumor were computed on multiparametric MRI images (T2-weighted, diffusion-weighted, dynamic contrast-enhanced-MRI and apparent diffusion coefficient maps). Tensor-based logistic regression was used to classify two-dimensional SPHARM rotationally-invariant descriptors. Head-to-head comparisons with radiomics analyses were performed with DeLong tests with Bonferroni-Holm correction to compare diagnostic performances.With all MRI contrasts, SPHARM analysis resulted in area under the curve, sensitivity, specificity, and balanced accuracy values of 0.94 (95% confidence interval [CI]: 0.85, 1.00), 100% (95% CI: 100, 100), 74% (95% CI: 51, 92), 87% (95% CI: 78, 98), respectively, for predicting deep MI. For predicting high-grade tumor histology, the corresponding values for the same diagnostic metrics were 0.81 (95% CI: 0.64, 0.90), 93% (95% CI: 67, 100), 63% (95% CI: 45, 79) and 78% (95% CI: 64, 86). The corresponding values achieved via radiomics were 0.92 (95% CI: 0.82, 0.95), 82% (95% CI: 65, 93), 80% (95% CI: 51, 94), 81% (95% CI: 70, 91) for deep MI and 0.72 (95% CI: 0.58, 0.83), 93% (95% CI: 65, 100), 55% (95% CI: 41, 69), 74% (95% CI: 52, 88) for high-grade histology. The diagnostic performance of the SPHARM analysis was not significantly different (P = 0.62) from that of radiomics for predicting deep MI but was significantly higher (P = 0.044) for predicting high-grade histology.The proposed SPHARM analysis yields similar or higher diagnostic performance than radiomics in identifying deep MI and high-grade status in histology-proven endometrial carcinoma.

Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood.In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years.Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models.We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years.We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

OBJECTIVE To determine whether career choice and starting salary of new DVM graduates in the US were associated with their educational debt accrued during veterinary school. SAMPLE Up to 48,527 fourth-year students at US veterinary schools who responded to the AVMA Senior Survey in 2001 through 2021 and accepted a full-time position or advanced education opportunity. PROCEDURES To determine whether career choice was associated with educational debt, multiple linear regression was performed, controlling for graduation year, gender, age, marital status, having children, tuition level, and school location. The correlation between educational debt and starting salary was also determined. RESULTS On average, mean educational debt increased by $6,110 each successive year. A mean of 60.5% of respondents accepted positions in private practice (public practice, 3.3%; advanced education, 36.2%). Respondents choosing public practice had a mean of $24,913 less debt than those choosing advanced education, controlling for other factors. Respondents choosing public practice also had less debt than those choosing private practice, but debt did not differ significantly between private practice and advanced education. The correlation between educational debt and starting salary was significant but low (r = 0.177). CLINICAL RELEVANCE Findings suggested that the amount of debt incurred during veterinary school was associated with new veterinarians’ career paths. Notably, graduates with higher debt levels appeared to seek higher paying jobs or clinical training that might lead to higher paying jobs, leaving public practice—a field in which critical needs have been identified—underrepresented despite the availability of loan forgiveness programs and other incentives.

Background/Objective The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity. We aim to investigate whether longitudinal shifts within the bacterial community between 3 months and 1 year of life are associated with preschool BMI z-score trajectories. Methods BMI trajectories from birth to 5 years of age were identified using group-based trajectory modeling in 3059 children. Their association with familial and environmental factors were analyzed. Infant gut microbiota at 3 months and 1 year was defined by 16S RNA sequencing and changes in diversity and composition within each BMIz trajectory were analyzed. Results Four BMIz trajectories were identified: low stable, normative, high stable, and rapid growth. Infants in the rapid growth trajectory were less likely to have been breastfed, and gained less microbiota diversity in the first year of life. Relative abundance of Akkermansia increased with age in children with stable growth, but decreased in those with rapid growth, abundance of Ruminococcus and Clostridium at 1 year were elevated in children with rapid growth. Children who were breastfed at 6 months had increased levels of Sutterella, and decreased levels of Ruminococcus and Clostridium. Conclusion This study provides new insights into the relationship between the gut microbiota in infancy and patterns of growth in a cohort of preschool Canadian children. We highlight that rapid growth since birth is associated with bacteria shown in animal models to have a causative role in weight gain. Our findings support a novel avenue of research targeted on tangible interventions to reduce childhood obesity.

OBJECTIVE To characterize and compare fourth-year students of US veterinary schools graduating with and without related educational debt (ie, DVM debt) from 2001 through 2020. SAMPLE 45,756 fourth-year veterinary students who participated in the annual AVMA Senior Survey from 2001 through 2020. PROCEDURES Survey data were summarized for variables hypothesized to be associated with DVM debt. Multivariable modeling was used to investigate associations between these variables and the likelihood of graduating with DVM debt. RESULTS Mean DVM debt increased fairly steadily from $56,824 in 2001 (n = 1,587) to $157,146 in 2020 (2,859). Of 45,756 students, 6,129 (13.4%) had no DVM debt. Attending Tuskegee University and having children (both men and women) were associated with an increased likelihood of DVM debt. Attending certain other veterinary schools and more recent survey year were associated with a decreased likelihood. For 2020, the likelihood of DVM debt decreased with increasing percentage of tuition paid by family and increased with increasing percentage of tuition paid by educational loans, being a woman with children, and increasing total cost of attendance. No association was found with state cost of living index or per capita income. CLINICAL RELEVANCE Results suggested a growing rift between US veterinary students who cannot afford tuition and fees without accumulating financially concerning levels of debt and those who have the financial ability or family situation to fully fund veterinary school. Efforts should be undertaken to recruit across socioeconomic statuses and provide meaningful scholarships to students with greatest financial needs to support diversity, equity, and inclusion in veterinary medicine.

Innovations in imaging hardware have led to a revolution in our ability to visualise vascular networks in 3D at high resolution. The segmentation of microvascular networks from these 3D image volumes and interpretation of their meaning in the context of physiological and pathological processes unfortunately remains a time consuming and error-prone task. Deep learning has the potential to solve this problem, but current supervised analysis frameworks require human-annotated ground truth labels. To overcome these limitations, we present an unsupervised image-to-image translation deep learning model called thevessel segmentation generative adversarial network(VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of an imaging system in order to learn how to segment vasculature from 3D biomedical images. To demonstrate the potential of VAN-GAN, the framework was applied to the challenge of segmenting vascular networks from images acquired using mesoscopic photoacoustic imaging (PAI). With a variety ofin silico,in vitroandin vivopathophysiological data, including patient-derived breast cancer xenograft models, we show that VAN-GAN facilitates accurate and unbiased segmentation of 3D vascular networks from PAI volumes. By leveraging synthetic data to reduce the reliance on manual labelling, VAN-GAN lower the barriers to entry for high-quality blood vessel segmentation to benefit imaging studies of vascular structure and function.

Visual impairments in albinism result from decreased ipsilateral retinal projections. In this issue of Neuron, Slavi, Balasubramanian, and colleagues

Accurate quantification of left atrium (LA) scar in patients with atrial fibrillation is essential to guide successful ablation strategies. Prior to LA scar quantification, a proper LA cavity segmentation is required to ensure exact location of scar. Both tasks can be extremely time-consuming and are subject to inter-observer disagreements when done manually. We developed and validated a deep neural network to automatically segment the LA cavity and the LA scar. The global architecture uses a multi-network sequential approach in two stages which segment the LA cavity and the LA Scar. Each stage has two steps: a region of interest Neural Network and a refined segmentation network. We analysed the performances of our network according to different parameters and applied data triaging. 200+ late gadolinium enhancement magnetic resonance images were provided by the LAScarQS 2022 Challenge. Finally, we compared our performances for scar quantification to the literature and demonstrated improved performances.

Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs-at-risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a diverse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.

ImportanceDespite advances in asthma therapeutics, the burden remains highest in preschool children; therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings.ObjectiveTo develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden.Design, Setting, and ParticipantsThe cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022.ExposuresThe CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age.Main Outcomes and MeasuresWithin the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values.ResultsAmong 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years; 1324 [52.7%] male; 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94; 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73; 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70; 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82; 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87; 95% CI, 0.80-0.94).Conclusions and RelevanceIn this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.

SUMMARYThe retina is an exquisitely patterned tissue, with neuronal somata positioned at regular intervals to completely sample the visual field. Cholinergic amacrine cells are spectacular exemplars of precision, distributing in two radial layers and tangentially, forming regular mosaics. Here, we investigated how the intracellular phosphatase Pten and the cell adhesion molecule Dscam cooperate to regulate amacrine cell patterning. Using double mutants to test epistasis, we found that Pten and Dscam function in parallel pathways to regulate amacrine cell positioning. Mechanistically, Pten regulates endocytic remodeling of cell adhesion molecules (Dscam, Megf10, Fat3), which are aberrantly redistributed in Pten conditional-knock-out (cKO) amacrine cells. Furthermore, extracellular vesicles derived from multivesicular endosomes have altered proteomes in PtencKO retinas. Consequently, Wnt signaling is elevated in PtencKO retinal amacrine cells, the pharmacological disruption of which phenocopies PtencKO patterning defects. Pten thus controls endocytic trafficking of critical cell adhesion/signaling molecules to control amacrine cell spacing.HIGHLIGHTSPten and Dscam act in parallel pathways to regulate amacrine cell spacingEndocytic remodeling of cell adhesion molecules is perturbed in PtencKO retinasExtracellular vesicle content is altered in PtencKO retinasPerturbation of Wnt signaling phenocopies defects in amacrine cell positioningeTOC BLURBPatterns in nature range from stereotyped distributions of colored patches on butterfly wings to precise neuronal spacing in the nervous system. Waddington proposed that built-in constraints canalize developmental patterns. Touahri et al. identified Pten-mediated endocytic trafficking of cell adhesion/signaling molecules as a novel constraint measure controlling retinal amacrine cell patterning.

Objective To estimate the effects of practice ownership on wellbeing of US private practice veterinarians. Sample 1,217 practice owners and 1,414 associate veterinarians (ie, nonowners) who participated in the 2021 AVMA Census of Veterinarians and Practice Owners Survey. Procedures A professional quality of life instrument was used to measure compassion satisfaction (CS; a positive attribute), burnout (BO), and secondary traumatic stress (STS) in practice owners and nonowners both as scores and as score categories (low, moderate, and high CS, BO, and STS). For hypothesis tests, propensity score matching was used, with owners (n = 595) matched to nonowners (595) on several demographic and employment factors. Results Owners had significantly (P < .001) higher CS scores (mean ± SE, 34.1 ± 0.3) and lower BO scores (26.1 ± 0.3) than nonowners (32.8 ± 0.3 and 26.9 ± 0.3, respectively), but STS scores were comparable between groups (27.4 ± 0.3 and 27.5 ± 0.3; P = .55). The prevalence of low CS scores and high BO scores was significantly (P < .001) higher for nonowners versus owners (53.8% vs 42.7% and 51.6% vs 46.4%, respectively). Both owners and nonowners had a high prevalence of high STS scores (81.8% and 83.2%, respectively; P = .53). Clinical Relevance Results suggested that practice ownership confers a benefit to private practice veterinarians in terms of CS and BO, but not STS. The prevalence of poor CS, BO, and STS scores was higher than reported previously for 2016 to 2018, suggesting an impact of the COVID-19 pandemic. The high prevalence of high STS scores in both groups warrants attention and action to protect the welfare of the veterinary workforce and support optimal patient care.

OBJECTIVE To determine prevalences of low compassion satisfaction (CS), high burnout (BO), and high secondary traumatic stress (STS) scores among full-time US veterinarians and estimate effects of selected demographic, employment-related, and education-related factors on those scores. SAMPLE 5,020 full-time veterinarians who participated in the 2016, 2017, and 2018 AVMA Census of Veterinarians surveys. PROCEDURES Data were obtained from census surveys regarding demographic, employment-related, and education-related factors, and scores assigned to items from a professional quality-of-life instrument designed to measure CS and compassion fatigue (ie, BO and STS) were compared between and among various demographic and employment groups. RESULTS Overall, 35.5% of veterinarians were classified as having low CS scores, 50.2% as having high BO scores, and 58.9% as having high STS scores. Controlling for other variables, high educational debt was associated with low CS, high BO, and high STS scores. Veterinarians who spent ≥ 75% of their time working with dogs or cats had higher BO and STS scores than did those who spent < 25% of their time. Veterinarians with more experience and higher annual incomes had higher CS scores and lower BO and STS scores. Women had higher BO and STS scores than did men, but no gender differences were observed in CS scores. CONCLUSIONS AND CLINICAL RELEVANCE Several variables were identified that may put veterinarians at higher risk than others for compassion fatigue and low CS. These findings may be useful in the development of resources and targeted initiatives to support and defend veterinarian well-being.

Photoacoustic mesoscopy visualises vascular architecture and associated tissue structures at high resolution at up to 3 mm depth. The technique has shown promise in both preclinical and clinical imaging studies, with possible applications in oncology and dermatology, however, the accuracy and precision of photoacoustic mesoscopy has not been well established. Here, we present a performance evaluation of a commercial photoacoustic mesoscopy system for imaging vascular structures. Typical artefact types are first highlighted and limitations due to non-isotropic illumination and detection are evaluated with respect to rotation, angularity, and depth of the target. Then, using tailored phantoms and mouse models we demonstrate high system precision, with acceptable coefficients of variation (COV) between repeated scans (short term (1h): COV=1.2%; long term (25 days): COV=9.6%), from target repositioning (without: COV=1.2%, with: COV=4.1%), or from varyingin vivouser experience (experienced: COV=15.9%, unexperienced: COV=20.2%). While our findings support the robustness of the technique, they also underscore the general challenges of limited field-of-view photoacoustic systems in accurately imaging vessel-like structures, thereby guiding users to correctly interpret biologically-relevant information.

Rationale: There are limited tools to identify which children are at greatest risk for developing sleep-disordered breathing (SDB)-associated behavioral morbidity.Objectives: To examine association...

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Myrtha E Reyna-Vargas,1 Arpita Parmar,2 Diana L Lefebvre,3 Meghan B Azad,4– 6 Allan B Becker,4,5 Stuart E Turvey,7 Theo J Moraes,1 Wendy Lou,8 Padmaja Subbarao,1,8 Malcolm R Sears,3 Piushkumar J Mandhane,9 Indra Narang1,10 1Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada; 2Sculich School of Medicine and Dentistry, Western University, London, ON, Canada; 3Department of Medicine, McMaster University, Hamilton, ON, Canada; 4Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada; 5Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Children’s Hospital, Winnipeg, MB, Canada; 6Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; 7Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada; 8Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 9Department of Pediatrics, University of Alberta, Edmonton, AB, Canada; 10Faculty of Medicine, University of Toronto, Toronto, ON, CanadaCorrespondence: Indra Narang, The Hospital for Sick Children, 555 University Ave-Hill Wing Room #4534, Toronto, ON, M5G 1X8, Canada, Email indra.narang@sickkids.caIntroduction: Decreased sleep duration and increased screen time as early as preschool age may contribute to overweight and obesity. The effects of bedtime together with nocturnal sleep duration remain unclear with a paucity of data evaluating these associations longitudinally. We aim to evaluate the independent and joint effects of sleep duration, sleep bedtime, and screen time at 3 years of age on BMI status, particularly overweight and obesity by age 5 years.Methods: Data from 2185 participants of the CHILD Cohort Study were analyzed longitudinally using generalized estimating equations (GEE). Models included changes in overweight/obesity status from 3 to 5 years of age as outcome, and nocturnal sleep duration, bedtime, and daily screen time at 3 years of age as explanatory variables. The joint effects of nocturnal sleep time and excess screen time, late bedtime on overweight/obesity were subsequently analyzed.Results: The median nocturnal sleep time at 3 and 5 years of age was 11.0 hours/night [IQR 10.5, 11.5]. A total of 14.5% children went to bed after 9PM at 3 years and 7.2% at 5 years. Median screen time was 1.0 hr/day [IQR 1.0, 2.0] at both ages. Longitudinal analyses showed that sleeping less than 10.5 hours at age 3 years was associated with 46% greater odds of overweight/obesity by age 5 years (OR 1.46, 95% CI 1.07, 2.00). The risk was higher when coupled with late bedtime after 9pm (OR 1.60, 95% CI 1.12, 2.31). Children with both short nocturnal sleep duration and excess screen time (> 1hr/day) had twice the associated risk of overweight/obesity by age 5 years (OR 1.96, 95% CI 1.34, 2.88).Conclusion: Nocturnal sleep duration and screen time are modifiable risk factors in young children, which may have important implications for obesity prevention as early as infancy.Keywords: Nocturnal sleep, bedtime, BMI

SummaryLight touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and brainstem. We found that the clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required in somatosensory neurons for normal behavioral reactivity to a range of tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions and peripheral axonal branching through neuron-glia interactions. The Pcdhgc3 isoform mediates homophilic interactions between sensory axons and spinal cord neurons to promote synapse formation in vivo, and is sufficient to induce postsynaptic specializations in vitro. Moreover, loss of Pcdhgs and somatosensory synaptic inputs to the dorsal horn lead to fewer corticospinal synapses onto dorsal horn neurons. These findings reveal essential roles for Pcdhg isoform diversity in somatosensory neuron synapse formation, peripheral axonal branching, and step-wise assembly of central mechanosensory circuitry.

New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.

Rationale: Sleep study interpretation in children needs to be based on age-specific normal values. Although several studies have reported normal cardiorespiratory parameters during sleep in childre...

Background World Health Organization (WHO) growth standards for children aged 0 to 5 years describe growth under optimal conditions and were adopted for use in Canada in 2012. We are seeking to validate these charts in a well-characterized, longitudinal cohort of healthy, Canadian youngsters, assess tracking over time, and evaluate the prognostic implications of early growth. Methods Data from 2,795 mother–infant dyads from the CHILD birth cohort were classified by feeding modality at 6 months as exclusively breastfed, partially breastfed, or formula-fed. WHO z-scores (z) were calculated at birth, 3 months, 1 year, and 3 years. Receiver operator characteristics (ROC) assessed the predictive performance of early weight (WT), weight-for-length (WfL), or body mass index (BMI) z-scores for overweight/obesity at 3 years. Results Compared to WHO standards, Canadian children at birth had lower median WfLz (−0.73) and BMIz (−0.29), with more positive scores by 3 years (WfLz=BMIz=0.58). At both 1 and 3 years, formula feeding was associated with higher scores than breastfeeding, even after regression adjustment for covariates. Head circumference z-score was typically positive at all times and regardless of feeding modality. At 1 year, ROC area under the curve was 0.79 for WTz, WfLz, and BMIz, and BMIz>0.88 identified children with increased risk of overweight/obesity (BMIz >2) at age 3 years (20.3% versus 3.0%, P Conclusions Compared to WHO growth charts, Canadian children at 3 years show an upward shift in BMIz and WfLz, particularly when formula-fed. Infant growth parameters may identify infants with increased risk of overweight/obesity at age 3 years; early recognition may allow targeting infants at higher risk.

OBJECTIVE To determine the contributions of veterinarians and support staff to revenue and veterinarian productivity (ie, number of patients seen/full-time–equivalent veterinarian/wk) in private mixed and companion animal practices in the US and identify staff-to-veterinarian labor ratios (SVLRs) that maximized these 2 practice outputs. SAMPLE 409 owners of mixed and companion animal practices who participated in the 2020 AVMA Practice Owner Survey. PROCEDURES Data regarding owner demographics, practice characteristics, labor (defined as mean total hours worked/wk), and gross revenue in 2019 were obtained from participating practices. Multivariable ordinary least-squares regression was used to identify factors associated with revenue and productivity as well as the SVLRs at which revenue and productivity were maximized. RESULTS For each 10% increase in total veterinarian hours worked per week, revenue increased by a mean of approximately 9%. A 1-unit increase in total number of technician hours used to support 1 hour of veterinarian work was associated with a 20.5% increase in revenue but with no change in productivity. The same increase in total number of nonmedical staff hours was associated with a 17.0% increase in revenue and 14.4% increase in productivity. In terms of revenue, the optimal SVLRs for veterinary technicians and nonmedical staff were 9:1 and 8:1, respectively. In terms of productivity, the optimal SVLR for nonmedical staff was 10:1. CLINICAL RELEVANCE Findings confirmed the important role of nonveterinarian staff in revenue and veterinarian productivity in mixed animal and companion animal practices and may be useful for making evidence-based staffing decisions.

SUMMARYNeurons form cell type-specific morphologies that are shaped by molecular cues and their cellular events governing dendrite growth. One growth rule is distributing dendrites uniformly within a neuron’s territory by avoiding sibling or ‘self’ branches. In mammalian neurons, dendrite self-avoidance is regulated by the clustered Protocadherins (cPcdhs), a large family of recognition molecules. Genetic and molecular studies suggest that the cPcdhs mediate homophilic recognition and repulsion between self-dendrites but this model has not been tested through direct investigation of self-avoidance during development. Here we performed live imaging and 4D quantifications of dendrite morphogenesis to define the cPcdh-dependent mechanisms of self-avoidance. We focused on the mouse retinal starburst amacrine cell (SAC), which requires the gamma-Pcdhs (Pcdhgs) and self/non-self recognition to establish a stereotypic radial morphology while permitting dendritic interactions with neighboring SACs. Through morphogenesis, SACs extend a transient population of dynamic filopodia that fill the growing arbor and contact nearby self-dendrites. Compared to non-self-contacting filopodia, self-contacting events have longer lifetimes and a subset persists as filopodia bridges. In the absence of thePcdhgs, non-self-contacting filopodia dynamics are unaffected but self-contact-induced retractions are significantly diminished. Filopodia bridges accumulate, leading to the bundling of dendritic processes and disruption to the arbor shape. By tracking dendrite self-avoidance in real-time, our findings demonstrate that the γ-Pcdhs selectively mediate contact-induced retractions upon filopodia self-recognition. Our results also illustrate how self-avoidance shapes the stochastic and space-filling behaviors of filopodia for robust dendritic pattern formation in mammalian neurons.HIGHLIGHTSDendrite self-avoidance proceeds through interstitial filopodia and contact-induced retractions between sibling processes.Self-contacting filopodia exhibit longer lifetimes and a subset of contacts persist.Pcdhgs selectively regulate self-contact-induced retractions.Loss ofPcdhgsand filopodia self-avoidance disrupts dendritic arbor shape.

The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50-80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze.LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SFAt age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p .01), IS (mean (SD): -0.14 (0.59), p .01), and NCS (mean (SD): -0.08 (1.06), p .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87).LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Radiotherapy is recognized globally as a mainstay of treatment in most solid tumors and is essential in both curative and palliative settings. Ionizing radiation is frequently combined with surgery, either preoperatively or postoperatively, and with systemic chemotherapy. Recent advances in imaging have enabled precise targeting of solid lesions yet substantial intratumoral heterogeneity means that treatment planning and monitoring remains a clinical challenge as therapy response can take weeks to manifest on conventional imaging and early indications of progression can be misleading. Photoacoustic imaging (PAI) is an emerging modality for molecular imaging of cancer, enabling non-invasive assessment of endogenous tissue chromophores with optical contrast at unprecedented spatio-temporal resolution. Preclinical studies in mouse models have shown that PAI could be used to assess response to radiotherapy and chemoradiotherapy based on changes in the tumor vascular architecture and blood oxygen saturation, which are closely linked to tumor hypoxia. Given the strong relationship between hypoxia and radio-resistance, PAI assessment of the tumor microenvironment has the potential to be applied longitudinally during radiotherapy to detect resistance at much earlier time-points than currently achieved by size measurements and tailor treatments based on tumor oxygen availability and vascular heterogeneity. Here, we review the current state-of-the-art in PAI in the context of radiotherapy research. Based on these studies, we identify promising applications of PAI in radiation oncology and discuss the future potential and outstanding challenges in the development of translational PAI biomarkers of early response to radiotherapy.

To distinguish benign from malignant cystic renal lesions (CRL) using a contrast-enhanced CT-based radiomics model and a clinical decision algorithm.This dual-center retrospective study included patients over 18 years old with CRL between 2005 and 2018. The reference standard was histopathology or 4-year imaging follow-up. Training and testing datasets were acquired from two institutions. Quantitative 3D radiomics analyses were performed on nephrographic phase CT images. Ten-fold cross-validated LASSO regression was applied to the training dataset to identify the most discriminative features. A logistic regression model was trained to classify malignancy and tested on the independent dataset. Reported metrics included areas under the receiver operating characteristic curves (AUC) and balanced accuracy. Decision curve analysis for stratifying patients for surgery was performed in the testing dataset. A decision algorithm was built by combining consensus radiological readings of Bosniak categories and radiomics-based risks.A total of 149 CRL (139 patients; 65 years [56-72]) were included in the training dataset-35 Bosniak(B)-IIF (8.6% malignancy), 23 B-III (43.5%), and 23 B-IV (87.0%)-and 50 CRL (46 patients; 61 years [51-68]) in the testing dataset-12 B-IIF (8.3%), 10 B-III (60.0%), and 9 B-IV (100%). The machine learning model achieved high diagnostic performance in predicting malignancy in the testing dataset (AUC = 0.96; balanced accuracy = 94%). There was a net benefit across threshold probabilities in using the clinical decision algorithm over management guidelines based on Bosniak categories.CT-based radiomics modeling accurately distinguished benign from malignant CRL, outperforming the Bosniak classification. The decision algorithm best stratified lesions for surgery and active surveillance.• The radiomics model achieved excellent diagnostic performance in identifying malignant cystic renal lesions in an independent testing dataset (AUC = 0.96). • The machine learning-enhanced decision algorithm outperformed the management guidelines based on the Bosniak classification for stratifying patients to surgical ablation or active surveillance.

BACKGROUND Maternal pre-postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. OBJECTIVE We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. METHODS 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. RESULTS Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (β=-0.07, P

Background Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. Objectives The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. Methods In a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. Results Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. Conclusions This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. To characterize exposure to phthalates during infancy and early childhood. Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. The highest urinary concentration was for the metabolite MBP at all ages (GM: 15–32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5–15.1 ng/mL at 3 months and 1.9–32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

This exploratory study uses data from 413 principals to examine whether and how competency-based education has been implemented in the Northeast states and the extent to which there is variation in implementation between states with different policies. Results suggest that competency-based practices that are most similar to current practices are reported more and practices that diverge from current practices are reported less. There were statistically significant differences between states with “advanced” and nonexistent competency-based education policies on three measures. Secondary principals could use this study to understand key features of the reform and the likely barriers and challenges to implementation regardless of their state policy context.

Objectives Primary: examine associations between meeting the 24-Hour Movement Guidelines for the Early Years and behavioral and emotional problems in a large sample of 3-year-old children. Secondary: determine the proportion of children meeting the Canadian 24-Hour Movement Guidelines. Design Cross-sectional. Methods Participants were 3-year olds (n = 539) from the Edmonton site of the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Physical activity and sleep duration were accelerometer-derived while screen time was parent-reported. Meeting the overall guidelines was defined as: (1) ≥180 min/day of total physical activity, including 60 min/day of moderate- to vigorous-intensity physical activity, (2) ≤1 h/day of screen time, and (3) 10–13 h of sleep per 24-hour period. Externalizing, internalizing, and total problem scores (lower scores representing fewer problems) were calculated from the parent-reported Child Behavior Checklist (CBCL). Descriptive statistics and linear regression models were completed. Results Only 5% of children met the overall guidelines (all three recommendations), with 19.3%, 50.5%, and 83.1% meeting the physical activity, screen time, and sleep recommendations, respectively. Meeting more recommendations was associated with lower scores for total (B = −1.78, 95%CI: −3.03, −0.54), externalizing (B = −1.51, 95%CI: −2.80, −0.22) and internalizing (B = −1.35, 95%CI: −2.60, −0.01) problems. Similar findings were also observed for the specific combinations of: (1) physical activity and screen time and (2) sleep duration and screen time. Conclusions Meeting more recommendations within the 24-hour Movement Guidelines was associated with fewer behavioral and emotional problems at 3-years. Few 3-year-olds met the overall guidelines. Findings support an integrated approach for healthy growth and development.

Rationale Sleep duration is critical to growth, learning, and immune function development in infancy. Strategies to ensure that national recommendations for sleep duration in infants are met require knowledge of perinatal factors that affect infant sleep. Objectives To investigate the mechanistic pathways linking maternal education and infant sleep. Methods An observational study was conducted on 619 infants whose mothers were enrolled at the Edmonton site of the CHILD birth cohort. Infant sleep duration at three months was assessed using the Brief Infant Sleep Questionnaire. Maternal education was collected via maternal report. Prenatal and postnatal depression scores were obtained from the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Birth records and maternal report were the source of covariate measures. Mediation analysis (PROCESS v3.0) was used to examine the indirect effects of maternal education on infant sleep duration mediated through prenatal depression and birth mode. Measurements and main results At three months of age, infants slept on average 14.1 h. Lower maternal education and prenatal depression were associated with significantly shorter infant sleep duration. Emergency cesarean section birth was associated with 1-hour shorter sleep duration at three months compared to vaginal birth [without intrapartum antibiotic prophylaxis] (β: −0.99 h; 95% CI: −1.51, −0.48). Thirty percent of the effect of lower maternal education on infant total sleep duration was mediated sequentially through prenatal depression and birth mode (Total Indirect Effects: −0.12, 95% CI: −0.22, −0.03, p Conclusions Prenatal depression and birth mode sequentially mediate the effect of maternal education on infant sleep duration.

The objective of this population-based retrospective cohort study was to identify factors associated with lifespan in pet dogs evaluated at primary care veterinary hospitals. Dogs ≥3 mo of age that visited any of 787 US hospitals at least twice from January 1, 2010, through December 31, 2012, were included. Survival curves were constructed for dogs by reproductive status, breed, body size, and purebreed (versus mixed-breed) status. Multivariate Cox proportional hazard regression was performed to identify factors associated with lifespan. There were 2,370,078 dogs included in the study, of whom 179,466 (7.6%) died during the study period. Mixed-breed dogs lived significantly longer than purebred dogs, and this difference was more pronounced as body size increased. Controlling for other factors, dogs of either sex had a greater hazard of death over the study follow-up period if sexually intact rather than gonadectomized. For dogs who lived to 2 yr of age, the hazard of death decreased with increasing frequency of dental scaling. Our findings support previous reports of the impact of body size and gonadectomy on lifespan and provide new evidence in support of ultrasonic dental scaling and mixed breeding.

This study examined the influence of physical health and well-being vulnerability on participation in physical activities, and whether motor skill proficiency mediated this relationship. Kindergarten children (n = 260) completed the Test of Gross Motor Development-2 and the Children’s Assessment of Participation and Enjoyment survey. A multivariate analysis of covariance was used to compare the motor skills and participation in physical activities of children in schools classified as more or less vulnerable. We also examined whether motor skill proficiency mediated the relationship between vulnerability status and participation. Children in neighborhoods with higher vulnerability demonstrated lower motor skill proficiency and participation. Object control skill proficiency mediated the relationship between vulnerability and participation. Children from more vulnerable schools started their school career with less developed motor skills and a narrower array of recreation participation. Children in vulnerable neighborhoods need more opportunities to master object controls skills and access recreational activities. Fortunately, motor skill proficiency among children considered ‘at risk’ is amenable to improvement and intervention early in the children’s school career may have a beneficial impact on children’s physical activity at school and beyond the school environment.