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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 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.

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

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.

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.

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.

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.

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.

International audience; Embodied approach postulates that knowledge and conceptual representations are grounded in action and perception. In order to investigate the involvement of sensorimotor information in conceptual and cognitive processing, researchers have collected various norms in young adults. For instance, the perceptual strength (PS) assesses perceptual experience (i.e. visual, auditory, haptic, gustatory, olfactory) associated with a concept and the body-object-interaction (BOI) assesses the ease with which a human body can interact with the referent of a word. The importance of both BOI and PS in the multimodal composition of word meaning is today well recognized. However, given the sensorimotor development of the individual from childhood to later life, it is likely that different age periods are associated with different perceptual experience and capacity to interact with objects. The purpose of this research is to investigate exploratory the effect of age on PS and BOI by comparing the evaluation of 270 French language words by young adults and healthy older people. The results showed that older adults presented similar or even higher PS for some modalities (e.g. gustatory and olfactory) and in particular for certain categories of words, while the BOI decreases. In addition to the importance of adjusting the verbal stimuli used in aging studies when dealing with multimodal representations, our results will lead us to discuss the evolution of sensorimotor representations with age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother–child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = − 0.20, p

Background Breastfeeding has many established health benefits for women and children. We examined the association between maternal education, newborn feeding in hospital, and long-term breastfeeding duration. Methods We studied 3195 Canadian mother-infant dyads in the CHILD pregnancy cohort. Newborn feeding was documented from hospital records. Caregivers reported sociodemographic factors and infant feeding at 3, 6, 12, 18, and 24 months. Results Overall, 97% of newborns initiated breastfeeding and 74% were exclusively breastfed in hospital. Exclusively breastfed newborns were ultimately breastfed longer compared with those who received formula supplementation during their hospital stay (median 11.0 vs 7.0 months, P

The clustered protocadherins (Pcdhs) comprise 58 cadherin-related proteins encoded by three tandemly arrayed gene clusters,Pcdh-α,Pcdh-β, andPcdh-γ (Pcdha,Pcdhb, andPcdhg, respectively). Pcdh isoforms from different clusters are combinatorially expressed in neurons. They form multimers that interact homophilically and mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, axonal tiling, and dendritic self-avoidance. Most studies have analyzed clusters individually. Here, we assessed functional interactions betweenPcdhaandPcdhgclusters. To circumvent neonatal lethality associated with deletion ofPcdhgs, we used Crispr-Cas9 genome editing in mice to combine a constitutivePcdhamutant allele with a conditionalPcdhgallele. We analyzed roles of Pcdhas and Pcdhgs in the retina and cerebellum from mice (both sexes) lacking one or both clusters. In retina, Pcdhgs are essential for survival of inner retinal neurons and dendritic self-avoidance of starburst amacrine cells, whereas Pcdhas are dispensable for both processes. Deletion of bothPcdhaandPcdhgclusters led to far more dramatic defects in survival and self-avoidance thanPcdhgdeletion alone. Comparisons of an allelic series of mutants support the conclusion that Pcdhas and Pcdhgs function together in a dose-dependent and cell-type-specific manner to provide a critical threshold of Pcdh activity. In the cerebellum, Pcdhas and Pcdhgs also cooperate to mediate self-avoidance of Purkinje cell dendrites, with modest but significant defects in either single mutant and dramatic defects in the double mutant. Together, our results demonstrate complex patterns of redundancy between Pcdh clusters and the importance of Pcdh cluster diversity in postnatal CNS development.SIGNIFICANCE STATEMENTThe formation of neural circuits requires diversification and combinatorial actions of cell surface proteins. Prominent among them are the clustered protocadherins (Pcdhs), a family of ∼60 neuronal recognition molecules. Pcdhs are encoded by three closely linked gene clusters calledPcdh-α,Pcdh-β, andPcdh-γ. The Pcdhs mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, and spatial patterning of axons and dendrites. Most studies to date have been limited to single clusters. Here, we used genome editing to assess interactions betweenPcdh-α andPcdh-γ gene clusters. We examined two regions of the CNS, the retina and cerebellum and show that the 14 α-Pcdhs and 22 γ-Pcdhs act synergistically to mediate neuronal survival and dendrite patterning.

BACKGROUND: A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM). AIM: To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA(1c)), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM. METHODS: This analysis was a retrospective cohort study. Criteria for inclusion were persons with unmanaged type 2 DM defined as HbA(1c) values ≥8% at time of enrolment, ≥18 years old, and enrolment in a pharmacist-managed clinic for ≥12 months. Pre- and post-intervention differences in HbA(1c), SBP and DBP values were assessed using repeated measures analysis of variance (ANOVA). The risk of diabetes-related hospitalisations was estimated during the 12 months prior and during the 12 months post-intervention, and the relative risk (RR) was calculated. RESULTS: Mean HbA(1c) values at 3, 6 and 12 months post-intervention were lower than baseline values (p < 0.05). There was no significant difference in mean HbA(1c) values at 6 or 12 months compared to 3 months post intervention. Mean SBP values at 3, 6 and 12 months were lower than baseline (p < 0.05). Likewise, mean DBP values at 6 and 12 months were lower than baseline (p < 0.05). The estimated RR of diabetes-related hospitalisations was 0.40 (95% CI: 0.20–0.83; p = 0.013). CONCLUSION: Enrolment in a pharmacist-managed diabetes program was associated with a significant reduction in HbA1c, SBP and DBP and reduction in risk of diabetes-related hospitalisations in an underserved cohort of patients with diabetes over a 12-month period.

Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval)= 1.8–124.7; quartile 2: OR=1.0, ns; quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development.

The St. Lawrence Seaway Management Corporation and the Saint Lawrence Seaway Development Corporation (U.S.), together with the Canadian Hydrographic Service and industry, have developed a dynamic Under Keel Clearance information sys tem for use in the Seaway called the Draught Information System. This has been standardized through a public process and was used in 2015 by over 20% of vessels with an increase in safe ty and a potential for an increase in load carrying capacity under suitable con di tions. This system integrates highresolution bathymetry, water level infor mation, AIS and other factors such as ship dynamics to display real-time information.

BACKGROUND Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. METHODS Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. RESULTS The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. CONCLUSIONS Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.

The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence many aspects of a neuron's function, including the number and identity of presynaptic inputs and how inputs are integrated to determine firing properties. Here, we review the mechanisms that regulate the construction of cell type–specific dendrite patterns during development. We focus on four aspects of dendrite patterning that are particularly important in determining the function of the mature neuron: (a) dendrite shape, including branching pattern and geometry of the arbor; (b) dendritic arbor size; (c) targeting of dendrites to particular locations; and (d) subdivision of dendrites into compartments with unique electrical properties or synaptic inputs.

Radiotherapy and chemotherapy are standard treatment of head and neck cancer alone or associated to surgical treatment. Early (during treatment or the following weeks) and late side effects contribute to malnutrition in this population at risk. In this context, nutritional support adapted by dietary monitoring and enteral nutrition (nasogastric tube or gastrostomy) are often necessary. The early identification of the patients with high malnutrition risk and requiring enteral nutrition is necessary to improve the tolerance and efficacy of treatment.

Resume L’irradiation encephalique localisee en conditions stereotaxiques du lit operatoire apres exerese d’une metastase constitue une alternative a l’irradiation adjuvante panencephalique. Cependant, l’irradiation cerebrale hypofractionnee est associee a un risque de radionecrose. Nous presentons ici quatre cas cliniques de radionecrose histologiquement prouvee. La presentation neuroradiologique pose le probleme d’un diagnostic differentiel avec une recidive locale. L’aspect d’imagerie par resonance magnetique (IRM) typique d’une radionecrose est une image en « poivron coupe ». Cependant, cet aspect evocateur peut etre etaye par la realisation d’une imagerie complementaire comprenant une IRM de perfusion et une tomographie par emissions de positons (TEP). Les facteurs predictifs dosimetriques de la survenue d’une radionecrose apres irradiation hypofractionnee en conditions stereotaxiques sont encore mal connus et necessitent des etudes prospectives sur de plus grosses cohortes.

Spatial patterns of neuronal connectivity are critical for neural circuit function and information processing. For many neuron types, the development of stereotyped dendritic and axonal territories involves reiterative contacts between neurites and successive re-calibration of branch outgrowth and directionality. Here I review emerging roles for members of the atypical cadherins (Fmi/Celsrs) and the clustered Protocadherins (Pcdhs) in neurite patterning. These cell-surface molecules have shared functions: they engage in homophilic recognition and mediate dynamic and contact-dependent interactions to establish reproducible and space-filling arborization patterns. As shown in genetic and molecular studies, the atypical cadherins and clustered Pcdhs serve in multiple contexts and signal diverse actions such as neurite repulsion or selective adhesion. In some cell types, they regulate the non-overlapping arrangement of branches achieved through homotypic interactions, such as in self-avoidance or tiling. In others, they promote dendritic complexity through cell-cell interactions. With critical roles in both the fine-scale arrangement of axonal and dendritic branching and the large-scale organization of axon tracts and neuronal networks, the atypical cadherins and clustered Pcdhs are key regulators of neural circuit assembly and function.

The purpose was to assess three treatments planning techniques including one in intensity-modulated radiation therapy (IMRT) for cerebral irradiation of pregnant woman, in order to limit the dose delivered to the foetus. The treatment provided was 60 Gy to the planning target volume. Estimated foetal dose was measured using an anthropomorphic phantom, on the upper and middle part of the uterus. The first plan consisted in four beams in conformational technique delivered from a Varian accelerator with a 120 leaves collimator, the second one used non-coplanar fields and the third one assessed IMRT. With the conformational technique, the dose at the upper part of the uterus was 8.3 mGy and 6.3 mGy at the middle part. The dose delivered to the foetus was higher with the non-coplanar fields. In IMRT, the dose at the upper part of the uterus was 23.8 mGy and 14.3 mGy at the middle part. The three plans used 6 MV X-rays. Because of the use of leaves and non-coplanar fields, IMRT does not seem to be the optimal technique for the treatment of pregnant woman. However, the dose delivered to the foetus remains low and below the dose of 100 mGy recommended by the International Commission of Radiological Protection. It seems possible to consider the use of this technique for a better sparing of organs at risk for the mother.

Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions.

Calcium oxalate urolithiasis results from the formation of aggregates of calcium salts in the urinary tract. Difficulties associated with effectively treating calcium oxalate urolithiasis and the proportional increase in the prevalence of calcium oxalate uroliths relative to other urolith types over the last 2 decades has increased the concern of clinicians about this disease. To determine factors associated with the development of calcium oxalate urolithiasis in dogs evaluated at general care veterinary hospitals in the United States, a retrospective case-control study was performed. A national electronic database of medical records of all dogs evaluated between October 1, 2007 and December 31, 2010 at 787 general care veterinary hospitals in the United States was reviewed. Dogs were selected as cases at the first-time diagnosis of a laboratory-confirmed urolith comprised of at least 70% calcium oxalate (n=452). Two sets of control dogs with no history of urolithiasis diagnosis were randomly selected after the medical records of all remaining dogs were reviewed: urinalysis examination was a requirement in the selection of one set (n=1808) but was not required in the other set (n=1808). Historical information extracted included urolith composition, dog's diet, age, sex, neuter status, breed size category, hospital location, date of diagnosis, and urinalysis results. Multivariable analysis showed that the odds of first-time diagnosis of calcium oxalate urolithiasis were significantly (P0.05) greater for dogs7 years, males (OR: 7.77, 95% CI: 4.93-12.26), neutered (OR: 2.58, 1.44-4.63), toy- vs. medium-sized breeds (OR: 3.15, 1.90-5.22), small- vs. medium-sized breeds (OR: 3.05, 1.83-5.08), large- vs. medium-sized breeds (OR: 0.05, 0.01-0.19), and those with a diagnosis of cystitis within the previous year (OR: 6.49, 4.14-10.16). Urinary factors significantly associated with first-time diagnosis of calcium oxalate urolithiasis were acidic vs. basic pH (OR: 1.94, 1.22-3.10), presence of RBCs (OR: 6.20, 3.91-9.83) or WBCs (OR: 1.62, 1.03-2.54), and protein concentration30 mg/dL (OR: 1.55, 1.04-2.30). Patient demographics and urinalysis results are important factors that can support risk assessment and early identification of canine oxalate urolithiasis. Therefore, periodic urolith screening and monitoring of urine parameters should be encouraged for dogs at risk of developing these uroliths.

SummaryDendrites from the same neuron usually develop nonoverlapping patterns by self-avoidance, a process requiring contact-dependent recognition and repulsion. Recent studies have implicated homophilic interactions of cell surface molecules, including Dscams and Pcdhgs, in self-recognition, but repulsive molecular mechanisms remain obscure. Here, we report a role for the secreted molecule Slit2 and its receptor Robo2 in self-avoidance of cerebellar Purkinje cells (PCs). Both molecules are highly expressed by PCs, and their deletion leads to excessive dendrite self-crossing without affecting arbor size and shape. This cell-autonomous function is supported by the boundary-establishing activity of Slit in culture and the phenotype rescue by membrane-associated Slit2 activities. Furthermore, genetic studies show that they act independently from Pcdhg-mediated recognition. Finally, PC-specific deletion of Robo2 is associated with motor behavior alterations. Thus, our study uncovers a local repulsive mechanism required for self-avoidance and demonstrates the molecular complexity at the cell surface in dendritic patterning.

Background Allergic disease is the most frequent chronic health issue in children and has been linked to early-life gut microbiome dysbiosis. Many lines of evidence suggest that microbially derived short-chain fatty acids, and particularly butyrate, can promote immune tolerance. Objective We sought to determine whether bacterial butyrate production in the gut during early infancy is protective against the development of atopic disease in children. Methods We used shotgun metagenomic analysis to determine whether dysbiosis in butyrate fermentation could be identified in human infants, before their developing allergic disease. Results We found that the microbiome of infants who went on to develop allergic sensitization later in childhood lacked genes encoding key enzymes for carbohydrate breakdown and butyrate production. Conclusions Our findings support the importance of microbial carbohydrate metabolism during early infancy in protecting against the development of allergies.

Objective—To identify factors associated with development of struvite urolithiasis in dogs evaluated at general care veterinary hospitals in the United States. Design—Retrospective case-control study. Animals—508 dogs with a first-time diagnosis of struvite urolithiasis and 7,135 control dogs. Procedures—Electronic medical records of all dogs evaluated at 787 general care veterinary hospitals in the United States between October 2007 and December 2010 were reviewed to identify dogs that developed struvite urolithiasis and 2 groups of control dogs with no history of urolithiasis. Information extracted included diet, age, sex, neuter status, breed size category, hospital location, and date of diagnosis. Urinalysis results, urolith composition, and other disease conditions were recorded if applicable. Potential risk factors were assessed with univariable and multivariable regression analysis. Results—Toy- or small-sized breeds had significantly greater odds of struvite urolithiasis, compared with medium- or large-sized breeds. Neutering significantly increased the odds of this outcome in females only; sexually intact females were more likely to develop struvite urolithiasis than were sexually intact males, but only up to 5 years of age. Urinary factors significantly associated with the outcome were basic (vs acidic) pH, presence of RBCs or WBCs, protein concentration > 30 mg/dL, and ketone concentration ≥ 5 mg/dL. Conclusions and Clinical Relevance—Evaluation of demographic characteristics and urinalysis results may be useful in the early identification of struvite urolithiasis in dogs. Periodic urinalysis in dogs is recommended because of the potential health impact of a late diagnosis of urolithiasis.

Objective—To determine whether gonadectomy or age at gonadectomy was associated with the risk that dogs would subsequently become overweight. Design—Retrospective cohort study. Animals—1,930 dogs gonadectomized between 1998 and 2001 at ≤ 6 months of age (n = 782), > 6 months to ≤ 1 year of age (861), or > 1 to ≤ 5 years of age (287) and 1,669 sexually intact dogs. Procedures—Dogs were followed-up through medical records for ≥ 10 years or until a diagnosis of overweight (defined as overweight, obese, or having a body condition score ≥ 4/5) was recorded. Information extracted included age at study entry, sex, breed, breed-size category, hospital visit frequency, and diagnosis (yes or no) of overweight or diseases that might affect body condition. Relative risk of a diagnosis of overweight was assessed among age groups of gonadectomized dogs and between gonadectomized and sexually intact dogs. Results—No difference was detected among dogs grouped according to age at gonadectomy with respect to the risk of being overweight. This risk was significantly greater in gonadectomized dogs than in sexually intact dogs, but only during the first 2 years after gonadectomy. Sexually intact male dogs were approximately 40% less likely to have this diagnosis (hazard ratio, 0.61; 95% confidence interval, 0.52 to 0.72) than were sexually intact female dogs; no difference in risk between the sexes was evident for gonadectomized dogs. Conclusions and Clinical Relevance—Gonadectomized dogs had a greater risk of being overweight than did sexually intact dogs, but this risk was not influenced by age at gonadectomy. Opportunities exist for veterinarians to provide counseling during the first years after gonadectomy to help dogs maintain a healthy weight.

Monoclonal antibodies and other biologic response modifiers have allowed for targeted drug therapy in managing various autoimmune diseases. A number of immune pathways have been exploited in the development of targeted immunomodulatory therapies, including cytokine-directed therapies such as tumor necrosis factor-alpha and interleukins, integrins, B-cells, and co-stimulation modulators. With new targeted therapies in the pipeline, more options are becoming available for treatment of autoimmune diseases. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

SummaryThe mammalian Protocadherin (Pcdh) alpha, beta, and gamma gene clusters encode a large family of cadherin-like transmembrane proteins that are differentially expressed in individual neurons. The 22 isoforms of the Pcdhg gene cluster are diversified into A-, B-, and C-types, and the C-type isoforms differ from all other clustered Pcdhs in sequence and expression. Here, we show that mice lacking the three C-type isoforms are phenotypically indistinguishable from the Pcdhg null mutants, displaying virtually identical cellular and synaptic alterations resulting from neuronal apoptosis. By contrast, mice lacking three A-type isoforms exhibit no detectable phenotypes. Remarkably, however, genetically blocking apoptosis rescues the neonatal lethality of the C-type isoform knockouts, but not that of the Pcdhg null mutants. We conclude that the role of the Pcdhg gene cluster in neuronal survival is primarily, if not specifically, mediated by its C-type isoforms, whereas a separate role essential for postnatal development, likely in neuronal wiring, requires isoform diversity.

Dendritic arborizations of many neurons are patterned by a process called self-avoidance, in which branches arising from a single neuron repel each other. By minimizing gaps and overlaps within the arborization, self-avoidance facilitates complete coverage of a neuron’s territory by its neurites. Remarkably, some neurons that display self-avoidance interact freely with other neurons of the same subtype, implying that they discriminate self from non-self. Here we demonstrate roles for the clustered protocadherins (Pcdhs) in dendritic self-avoidance and self/non-self discrimination. The Pcdh locus encodes 58 related cadherin-like transmembrane proteins, at least some of which exhibit isoform-specific homophilic adhesion in heterologous cells and are expressed stochastically and combinatorially in single neurons. Deletion of all 22 Pcdh genes in the mouse γ-subcluster (Pcdhg genes) disrupts self-avoidance of dendrites in retinal starburst amacrine cells (SACs) and cerebellar Purkinje cells. Further genetic analysis of SACs showed that Pcdhg proteins act cell-autonomously during development, and that replacement of the 22 Pcdhg proteins with a single isoform restores self-avoidance. Moreover, expression of the same single isoform in all SACs decreases interactions among dendrites of neighbouring SACs (heteroneuronal interactions). These results suggest that homophilic Pcdhg interactions between sibling neurites (isoneuronal interactions) generate a repulsive signal that leads to self-avoidance. In this model, heteroneuronal interactions are normally permitted because dendrites seldom encounter a matched set of Pcdhg proteins unless they emanate from the same soma. In many respects, our results mirror those reported for Dscam1 (Down syndrome cell adhesion molecule) in Drosophila: this complex gene encodes thousands of recognition molecules that exhibit stochastic expression and isoform-specific interactions, and mediate both self-avoidance and self/non-self discrimination. Thus, although insect Dscam and vertebrate Pcdh proteins share no sequence homology, they seem to underlie similar strategies for endowing neurons with distinct molecular identities and patterning their arborizations.

In this Letter, we report on alpha particle emission through the nuclear break-up in the reaction 40Ca on a 40Ca target at 50A MeV. It is observed that, similarly to nucleons, alpha particles can be emitted to the continuum with very specific angular distribution during the reaction. The alpha particle properties can be understood as resulting from an alpha cluster in the daughter nucleus that is perturbed by the short range nuclear attraction of the collision partner and emitted. A time-dependent theory that describe the alpha particle wave-function evolution is able to reproduce qualitatively the observed angular distribution. This mechanism offers new possibilities to study alpha particle properties in the nuclear medium., Comment: 4 pages, 3 figures

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.