Transforming the future of health together: The Learning Health Systems Consensus Action Plan.

The Learning Health Community is an emergent global multistakeholder grassroots incipient movement bonded together by a set of consensus developed at the 2012 Learning Health System (LHS) Summit. The Learning Health Community's Second LHS Summit was convened on December 8 to 9, 2016 building upon LHS efforts taking shape in order to achieve consensus on actions that, if taken, will advance LHSs and the LHS vision from what remain appealing concepts to a working reality for improving the health of individuals and populations globally. An iterative half-year collaborative revision process following the Second LHS Summit led to the development of the .

Metal worker's lung: spatial association with .

Background: Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak.

Objectives: After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone.

Patient-centered drug development and the Learning Health System.

Patient-centered drug development (PCDD) is a shift in the way that drugs are developed, systematically incorporating patient participation in all stages of medicines development. The more the research sector understands the needs and values of patients, the more effective and efficient it can be in bringing meaningful drugs and evidence to patients and providers. In this paper, we describe PCDD, provide examples of PCDD work across the phases of drug development, and discuss the challenges to making PCDD systematic.

Prevention of Tracheostomy-Related Hospital-Acquired Pressure Ulcers.

Objective To determine if standardization of perioperative tracheostomy care procedures decreased the incidence of hospital-acquired tracheostomy-related pressure ulcers. Methods All patients at least 18 years old who underwent placement of a tracheostomy tube in the operating room from July 1, 2014, through June 30, 2015, were cared for postoperatively through an institutionally adopted quality improvement protocol. This included 4 elements: (1) placement of a hydrocolloid dressing underneath the tracheostomy flange in the postoperative period, (2) removal of plate sutures within 7 days of the tracheostomy procedure, (3) placement of a polyurethane foam dressing after suture removal, and (4) neutral positioning of the head.

Creating and using real-world evidence to answer questions about clinical effectiveness.

New forms of evidence are needed to complement evidence generated from randomised controlled trials (RCTs). Real-World Evidence (RWE) is a potential new form of evidence, but remains undefined. This paper sets to fill that gap by defining RWE as the output from a rigorous research process which: (1) includes a clear a priori statement of a hypothesis to be tested or research question to be answered; (2) defines the data sources that will be used and critically appraises their strengths and weaknesses; and (3) applies appropriate methods, including advanced analytics.

Histology atlas of the developing mouse hepatobiliary system with emphasis on embryonic days 9.5-18.5.

Animal model phenotyping, in utero exposure toxicity studies, and investigation into causes of embryonic, fetal, or perinatal deaths have required pathologists to recognize and diagnose developmental disorders in spontaneous and engineered mouse models of disease. In mammals, the liver is the main site of hematopoiesis during fetal development, has endocrine and exocrine functions important for maintaining homeostasis in fetal and adult life; and performs other functions including waste detoxification, production and removal of glucose, glycogen storage, triglyceride and fatty acid processing, and serum protein production. Due to its role in many critical functions, alterations in the size, morphology, or function(s) of the liver often lead to embryonic lethality.

Gestational diabetes mellitus resulting from impaired beta-cell compensation in the absence of FoxM1, a novel downstream effector of placental lactogen.

Objective: The objectives of the study were to determine whether the cell cycle transcription factor, FoxM1, is required for glucose homeostasis and beta-cell mass expansion in maternal islets during pregnancy and whether FoxM1 is essential for placental lactogen (PL)-induced beta-cell proliferation.

Research Design And Methods: beta-Cell mass, beta-cell proliferation, and glucose homeostasis were assessed in virgin, pregnant, and postpartum mice with a pancreas-wide Foxm1 deletion (FoxM1(Deltapanc)). Wild-type islets were cultured with or without PL and examined for Foxm1 induction.

Connective tissue growth factor (CTGF) inactivation leads to defects in islet cell lineage allocation and beta-cell proliferation during embryogenesis.

The factors necessary for normal pancreatic islet morphogenesis have not been well characterized. Here we report that connective tissue growth factor (CTGF) is involved in the establishment of normal islet endocrine cell ratio and architecture. CTGF is a secreted protein known to modulate several growth factor-signaling pathways including TGF-beta, BMP, and Wnt.

pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis.

The pdx1 gene is essential for pancreatic organogenesis in humans and mice; pdx1 mutations have been identified in human diabetic patients. Specific inactivation of pdx1 in adult beta cells revealed that this gene is required for maintenance of mature beta cell function. In the following study, a Cre-lox strategy was used to remove pdx1 function specifically from embryonic beta cells beginning at late-gestation, prior to islet formation.

Maintenance of hepatic nuclear factor 6 in postnatal islets impairs terminal differentiation and function of beta-cells.

The Onecut homeodomain transcription factor hepatic nuclear factor 6 (Hnf6) is necessary for proper development of islet beta-cells. Hnf6 is initially expressed throughout the pancreatic epithelium but is downregulated in endocrine cells at late gestation and is not expressed in postnatal islets. Transgenic mice in which Hnf6 expression is maintained in postnatal islets (pdx1(PB)Hnf6) show overt diabetes and impaired glucose-stimulated insulin secretion (GSIS) at weaning.