Environmental determinants of landmine detection by dogs: Findings from a large-scale study in Afghanistan

This article’s purpose is to examine the strengths and weaknesses of mine-detection dogs in different environments. The experiments employed a total of 39 dogs in Afghanistan between October 2002 and July 2003. The results are discussed here

Cardiovascular disease risk factors in autistic adults: The impact of sleep quality and antipsychotic medication use

Approximately 40% of American adults are affected by cardiovascular disease (CVD) risk factors (e.g., high blood pressure, high cholesterol, diabetes, and overweight or obesity), and risk among autistic adults may be even higher. Mechanisms underlying the high prevalence of CVD risk factors in autistic people may include known correlates of CVD risk factors in other groups, including high levels of perceived stress, poor sleep quality, and antipsychotic medication use. A sample of 545 autistic adults without intellectual disability aged 18+ were recruited through the Simons Foundation Powering Autism Research, Research Match. multiple linear regression models examined the association between key independent variables (self-reported perceived stress, sleep quality, and antipsychotic medication use) and CVD risk factors, controlling for demographic variables (age, sex assigned at birth, race, low-income status, autistic traits). Overall, 73.2% of autistic adults in our sample had an overweight/obesity classification, 45.3% had high cholesterol, 39.4% had high blood pressure, and 10.3% had diabetes. Older age, male sex assigned at birth, and poorer sleep quality were associated with a higher number of CVD risk factors. Using antipsychotic medications was associated with an increased likelihood of having diabetes. Poorer sleep quality was associated with an increased likelihood of having an overweight/obesity classification. Self-reported CVD risk factors are highly prevalent among autistic adults. Both improving sleep quality and closely monitoring CVD risk factors among autistic adults who use antipsychotic medications have the potential to reduce risk for CVD

Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy

Objectives: To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population. Methods: Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy. Results: The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001). Conclusion: This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy

Prevalence and Epidemiology of Non-O157 Escherichia coli Serogroups O26, O103, O111, and O145 and Shiga Toxin Gene Carriage in Scottish Cattle, 2014-2015

International audienceCattle are reservoirs for Shiga toxin Escherichia coli (STEC), bacteria shed in animal feces. Humans are infected through consumption of contaminated food or water and by direct contact, causing serious disease and kidney failure in the most vulnerable

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

CHIASM-Net: Artificial Intelligence-Based Direct Identification of Chiasmal Abnormalities in Albinism

Purpose: Albinism is a congenital disorder affecting pigmentation levels, structure, and function of the visual system. The identification of anatomical changes typical for people with albinism (PWA), such as optic chiasm malformations, could become an important component of diagnostics. Here, we tested an application of convolutional neural networks (CNNs) for this purpose.Methods: We established and evaluated a CNN, referred to as CHIASM-Net, for the detection of chiasmal malformations from anatomic magnetic resonance (MR) images of the brain. CHIASM-Net, composed of encoding and classification modules, was developed using MR images of controls (n = 1708) and PWA (n = 32). Evaluation involved 8-fold cross validation involving accuracy, precision, recall, and F1-score metrics and was performed on a subset of controls and PWA samples excluded from the training. In addition to quantitative metrics, we used Explainable AI (XAI) methods that granted insights into factors driving the predictions of CHIASM-Net.Results: The results for the scenario indicated an accuracy of 85 ± 14%, precision of 90 ± 14% and recall of 81 ± 18%. XAI methods revealed that the predictions of CHIASM-Net are driven by optic-chiasm white matter and by the optic tracts.Conclusions: CHIASM-Net was demonstrated to use relevant regions of the optic chiasm for albinism detection from magnetic resonance imaging (MRI) brain anatomies. This indicates the strong potential of CNN-based approaches for visual pathway analysis and ultimately diagnostics

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd