"Can you help me think this through?" How pediatric hospitalists learn from informal peer consultation.

Informal peer consultation (IPC), also called curbside consultation, is a common practice in medicine. Research has shown that physicians use IPC but how this learning occurs during the process has not been studied. This basic qualitative study describes how pediatric hospitalists learn during IPC, framed by Kolb's (2015) Experiential Learning Theory of Growth and Development.

Multidisciplinary Initiative to Increase Guideline-concordant Antibiotic Prescription at Discharge for Hospitalized Children with Uncomplicated Community-acquired Pneumonia.

Background: Clinical practice guidelines recommend using narrow-spectrum antibiotics to treat uncomplicated pneumonia in children. This quality improvement (QI) project aimed to evaluate if QI methods could improve guideline-concordant antibiotic prescribing at hospital discharge for children with uncomplicated pneumonia.

Methods: For this single-center QI project, we implemented QI interventions in serial plan-do-study-act cycles, focusing on the key drivers targeting general pediatric inpatient resident teams.

Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.

Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients.

Development and Implementation of a Peer Curbside Consult Service for Pediatric Hospitalists.

Objective: To describe the development and implementation of a Peer Curbside Consult Service (PCCS) for a pediatric hospital medicine (PHM) division.

Methods: We developed a pilot intervention with hospitalists at a freestanding children's hospital to provide peer consultation services for challenging clinical cases. Postconsultation surveys collected from both the requesting and consulting hospitalists provided feedback about the program.

A multicentre evaluation exploring the impact of an integrated health and social care intervention for the caregivers of ICU survivors.

Background: Caregivers and family members of Intensive Care Unit (ICU) survivors can face emotional problems following patient discharge from hospital. We aimed to evaluate the impact of a multi-centre integrated health and social care intervention, on caregiver and family member outcomes.

Methods: This study evaluated the impact of the Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme across 9 sites in Scotland.

"Sick or not sick?" A mixed methods study evaluating the rapid determination of illness severity in a pediatric emergency department.

Objectives: Experienced physicians must rapidly identify ill pediatric patients. We evaluated the ability of an illness rating score (IRS) to predict admission to a pediatric hospital and explored the underlying clinical reasoning of the gestalt assessment of illness.

Methods: We used mixed-methods to study pediatric emergency medicine physicians at an academic children's hospital emergency department (ED).

Cricopharyngeal Achalasia Presenting as Acute Dysphagia in a Pediatric Patient.

Objective: To describe a case of idiopathic cricopharyngeal achalasia (CPA) in a pediatric patient with acute onset of dysphagia managed conservatively with supportive care.

Methods: Sixteen-month-old boy presented with acute onset of gagging and coughing with feeding. His exam was notable for a well-appearing child with pooling of oral secretions and coarse breath sounds.

The mutational landscape of human somatic and germline cells.

Over the course of an individual's lifetime, normal human cells accumulate mutations. Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially.

Development, maturation, and maintenance of human prostate inferred from somatic mutations.

Clonal dynamics and mutation burden in healthy human prostate epithelium are relevant to prostate cancer. We sequenced whole genomes from 409 microdissections of normal prostate epithelium across 8 donors, using phylogenetic reconstruction with spatial mapping in a 59-year-old man's prostate to reconstruct tissue dynamics across the lifespan. Somatic mutations accumulate steadily at ∼16 mutations/year/clone, with higher rates in peripheral than peri-urethral regions.

Extensive heterogeneity in somatic mutation and selection in the human bladder.

The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted ( = 1914 microbiopsies), whole-exome ( = 655), and whole-genome ( = 88) sequencing. We found widespread positive selection in 17 genes.

Feasibility of behavioral activation group therapy in reducing depressive symptoms and improving quality of life in patients with depression: the BRAVE pilot trial.

Background: Depression impacts the lives of millions of people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has the potential for improving depressive symptoms in patients with depression. Studies evaluating the effectiveness of BA specifically in the context of group therapy programs in a hospital setting for patients with depression are limited.

The landscape of somatic mutation in normal colorectal epithelial cells.

The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer. However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals.

Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.

The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcriptional control of pancreatic islet cells has important implications for understanding the mechanisms that control their normal development, as well as the pathogenesis of metabolic diseases such as diabetes. Histones represent the main protein components of the chromatin and undergo diverse covalent modifications that are very important for gene regulation.

Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis.

Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced.

Population dynamics of normal human blood inferred from somatic mutations.

Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation.

Acceptability of the Fitbit in behavioural activation therapy for depression: a qualitative study.

Introduction: Major depressive disorder is characterised by low mood and poor motivation. Literature suggests that increased physical activity has positive effects on alleviating depression. Fitness-tracking devices may complement behavioural activation (BA) therapy to improve physical activity and mental health in patients with depression.

Suspected Pediatric Influenza Risk-Stratification Algorithm: A Clinical Decision Tool.

Background And Objectives: Influenza causes significant annual burden among children. Current guidelines recommend empiric treatment for a broadly defined group of children at high risk for influenza complications, resulting in overtreatment or costly viral testing. This study creates an algorithm for clinicians to risk stratify children with influenza-like illness (ILI) according to likelihood of influenza infection.

Behavioral activation group therapy for reducing depressive symptoms and improving quality of life: a feasibility study.

Background: Depression is associated with a loss of productivity and noticeable personal, social, and economic decline; it affects more than 350 million people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has drawn increasingly more interest as a means of treatment for major depressive disorder due to its relative cost-effectiveness and efficacy. In this study, we disseminate findings from a feasibility study evaluating barriers to implementing a group BA program for major depressive disorder.

A pragmatic pilot randomized trial to investigate the effectiveness of behavioural activation group therapy in reducing depressive symptoms and improving quality of life in patients with depression: the BRAVE pilot trial protocol.

Background: Depression is a common disorder with a lifetime prevalence of 16 %. Despite the availability of several treatment options for depression, many patients do not respond to treatment and develop chronic illness associated with several secondary comorbidities. Behavioural activation (BA) is a simple therapy that has the potential for improving symptoms of depression and quality of life in patients with depression.

Regulation of the Flt3 Gene in Haematopoietic Stem and Early Progenitor Cells.

The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential.

Modeling the voltage loss mechanisms in lithium-sulfur cells: the importance of electrolyte resistance and precipitation kinetics.

Understanding of the complex electrochemical, transport, and phase-change phenomena in Li-S cells requires experimental characterization in tandem with mechanistic modeling. However, existing Li-S models currently contradict some key features of experimental findings, particularly the evolution of cell resistance during discharge. We demonstrate that, by introducing a concentration-dependent electrolyte conductivity, the correct trends in voltage drop due to electrolyte resistance and activation overpotentials are retrieved.

The histone deacetylase inhibitor sodium valproate causes limited transcriptional change in mouse embryonic stem cells but selectively overrides Polycomb-mediated Hoxb silencing.

Background: Histone deacetylase inhibitors (HDACi) cause histone hyperacetylation and H3K4 hypermethylation in various cell types. They find clinical application as anti-epileptics and chemotherapeutic agents, but the pathways through which they operate remain unclear. Surprisingly, changes in gene expression caused by HDACi are often limited in extent and can be positive or negative.