Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach.
View Article and Find Full Text PDFAdeno-associated virus-based gene therapies have demonstrated substantial therapeutic benefit for the treatment of genetic disorders. In manufacturing processes, viral capsids are produced with and without the encapsidated gene of interest. Capsids devoid of the gene of interest, or "empty" capsids, represent a product-related impurity.
View Article and Find Full Text PDFThe objective of this study is to determine predictors of resource use among pediatric providers for common respiratory illnesses. We surveyed pediatric primary care, emergency department (ED)/urgent care (UC), and hospital medicine providers at a free-standing children's hospital system. Five clinical vignettes assessed factors affecting resource use for upper respiratory infections, bronchiolitis, and pneumonia, including provider-type, practice location, tolerance to uncertainty, and medical decision-making behaviors.
View Article and Find Full Text PDFObjective: Describe the clinical presentation, prevalence of concurrent serious bacterial infection (SBI), and outcomes among infants with omphalitis.
Methods: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants ≤90 days of age with omphalitis seen in the emergency department from January 1, 2008, to December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized.
Unlabelled: Epinephrine is the only medication that prevents morbidity and mortality in anaphylaxis. Systemic corticosteroids and H2 receptor antagonists (H2RA) may benefit select cases but are not universally indicated. This study aims to de-implement the universal use of steroids and H2RAs and emphasize epinephrine-focused care for children with anaphylaxis during acute care visits.
View Article and Find Full Text PDFBackground: Clinical practice guidelines for bronchiolitis recommend against tests and treatments that do not improve outcomes, yet most children admitted with bronchiolitis continue to receive them. An improved understanding of factors that influence care decisions across multiple stakeholders and diverse settings is needed to develop effective strategies to de-implement (or reduce) unnecessary testing and treatment.
Methods: We explored health care provider, care team, and parent perspectives on testing and treatment in bronchiolitis to develop a combined stakeholder account of care decisions.
Objectives: Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis.
Methods: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized.
Background: Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine.
View Article and Find Full Text PDFBackground: Congenital sensorineural deafness (CSD) is the most common type of deafness in Dalmatian dogs.
Objectives: To use results of CSD screening in Dalmatian dogs in the United Kingdom in genetic analysis and to determine any changes in the prevalence of CSD in this breed over time.
Animals: A total of 8955 Dalmatian puppies undergoing hearing function screening using brainstem auditory evoked response (BAER) between July 1992 and February 2019.
Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter.
View Article and Find Full Text PDFBackground: The English setter (ES) is predisposed to congenital sensorineural deafness (CSD). CSD prevalence and association with phenotype in the UK ES population are previously unreported.
Methods: The database of the authors' institution was searched for ES puppies undergoing brainstem auditory evoked response (BAER) testing for CSD screening (2000-2018).
Background: Data about congenital sensorineural deafness (CSD) in white blue-eyed cats derive mainly from research colonies, and information about client-owned cats is limited.
Objectives: To describe the prevalence of CSD in a client-owned population of white purebred kittens and colored littermates in the United Kingdom.
Animals: One hundred thirty-two solid white client-owned purebred kittens and 61 colored littermates, 6 to 21 weeks of age.
Objectives: The American Academy of Pediatrics published bronchiolitis clinical practice guidelines in 2014 recommending against the routine use of bronchodilators, chest radiographs, or respiratory viral testing in children with a clinical diagnosis of bronchiolitis. Our aim in this project was to align care with the American Academy of Pediatrics clinical practice guidelines by decreasing the overuse of these interventions.
Methods: This study included patients who were admitted to a non-ICU setting with a primary or secondary diagnosis of bronchiolitis.
Objective: Retrospective studies have shown home oxygen to be a safe alternative to hospitalization for some patients with bronchiolitis living at high altitudes. We aimed to prospectively describe adverse events, follow-up, duration of home oxygen, factors associated with failure, and caregiver preferences.
Methods: This was a prospective observational study of hypoxemic bronchiolitis patients ages 3 to 18 months who were discharged from a tertiary care pediatric emergency department on home oxygen over three winters (2011-2014).
Background: Congenital sensorineural deafness (CSD) is the most common type of deafness in dogs and it occurs in numerous canine breeds including the English bull terrier. This study estimates prevalence, heritability and genetic correlations of CSD and coat pigmentation phenotypes in the English bull terrier in England.
Results: Hearing status was assessed by brainstem auditory evoked response in 1060 English bull terrier puppies tested at 30-78 (mean 43.
The carers of all UK Kennel Club registered Italian spinoni (IS) born between January 1, 2000 and December 31, 2011 were invited to participate in the study. The carers of 47 of 63 IS diagnosed with idiopathic epilepsy (IE) returned the questionnaire, which included numerous questions on various aspects of IE including the effect of IE on the dog's carer's quality of life. Median epileptic seizure number in the three months before study end or death was five epileptic seizures, 72 per cent of dogs had cluster seizures, 94 per cent of dogs were administered one or more antiepileptic medications and 36 per cent of dogs were euthanased due to poorly controlled IE.
View Article and Find Full Text PDFBackground: Episodic muscular hypertonicity in Norwich terrier dogs was first reported in a brief communication in 1984. Since then, the condition has remained poorly characterized.
Objectives: The aims of this study were to characterize the phenomenology, clinical course, and family history of paroxysmal dyskinesia in the Norwich terrier and to estimate its prevalence in the United Kingdom.
Objectives: Prehospital pediatric airway management is difficult and controversial. Options include bag-mask ventilation (BMV), endotracheal tube (ETT), and laryngeal mask airway (LMA). Emergency Medical Services personnel report difficulty assessing adequacy of BMV during transport.
View Article and Find Full Text PDFObjective: Home O2 has been shown to reduce hospitalizations for bronchiolitis but data on outpatient management of home O2 are lacking. We aim to describe outpatient management and challenges to home O2 for bronchiolitis.
Methods: We surveyed Colorado and Utah (where home O2 use is prevalent) chapter members of the American Academy of Pediatrics regarding bronchiolitis home O2 management.
The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML).
View Article and Find Full Text PDFDrawing on an assumption of the co-construction of the material and the social, late-onset Alzheimer's disease (AD) is used as an illustrative example to assess claims for an emergent figure of the "individual genetically at risk." Current medical understanding of the genetics of AD is discussed, followed by a summary of media and AD society materials that reveal an absence of gene hype in connection with this disease. Excerpts from interviews with first-degree relatives of patients diagnosed with AD follow.
View Article and Find Full Text PDFBackground: Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color.
Hypothesis: Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene.
Objective: To estimate the heritability of atopic dermatitis in Golden and Labrador Retrievers.
Animals: 429 dogs related to 13 dogs with atopic dermatitis.
Procedure: Atopic dermatitis was defined on the basis of the type and frequency of clinical signs recorded in the clinical records, and each dog was classified with atopic dermatitis or probable atopic dermatitis or as nonatopic.