Publications by authors named "Sarah McMillan"

Adolescence is a period of normative heightened sensitivity to peer influence. Individual differences in susceptibility to peers is related to individual differences in neural sensitivity, particularly in brain regions that support an increasingly greater orientation toward peers. Despite these empirically-established patterns, the more specific psychosocial and socio-cognitive factors associated with individual differences in neural sensitivity to peer influence are just beginning to gain research attention.

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DNA replication in Escherichia coli starts with loading of the replicative helicase, DnaB, onto DNA. This reaction requires the DnaC loader protein, which forms a 6:6 complex with DnaB and opens a channel in the DnaB hexamer through which single-stranded DNA is thought to pass. During replication, replisomes frequently encounter DNA damage and nucleoprotein complexes that can lead to replication fork collapse.

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Bacterial replisomes often dissociate from replication forks before chromosomal replication is complete. To avoid the lethal consequences of such situations, bacteria have evolved replication restart pathways that reload replisomes onto prematurely terminated replication forks. To understand how the primary replication restart pathway in E.

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G-quadruplexes (G4s) are highly stable, non-canonical DNA or RNA structures that can form in guanine-rich stretches of nucleic acids. G4-forming sequences have been found in all domains of life, and proteins that bind and/or resolve G4s have been discovered in both bacterial and eukaryotic organisms. G4s regulate a variety of cellular processes through inhibitory or stimulatory roles that depend upon their positions within genomes or transcripts.

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The disaccharide trehalose has long been recognized for its role as a stress solute, but in recent years some of the protective effects previously ascribed to trehalose have been suggested to arise from a function of the trehalose biosynthesis enzyme trehalose-6-phosphate (T6P) synthase that is distinct from its catalytic activity. In this study, we use the maize pathogenic fungus Fusarium verticillioides as a model to explore the relative contributions of trehalose itself and a putative secondary function of T6P synthase in protection against stress as well as to understand why, as shown in a previous study, deletion of the TPS1 gene coding for T6P synthase reduces pathogenicity against maize. We report that a TPS1-deletion mutant of F.

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Melanomas arising from the foot pad are a rare clinical entity in dogs. The biologic behaviour of foot pad malignant melanoma is not well understood, and these tumours are infrequently described. The objective of this study was to evaluate the clinical characteristics of primary canine foot pad melanoma in a larger cohort of patients.

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Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy.

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In many bacteria and eukaryotes, replication fork establishment requires the controlled loading of hexameric, ring-shaped helicases around DNA by AAA+(ATPases Associated with various cellular Activities) ATPases. How loading factors use ATP to control helicase deposition is poorly understood. Here, we dissect how specific ATPase elements of DnaC, an archetypal loader for the bacterial DnaB helicase, play distinct roles in helicase loading and the activation of DNA unwinding.

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Background: The Toronto Academic Health Sciences Network Health Professions Innovation Fellowship Program began in 2014 as a pilot initiative among 4 academic teaching hospitals in Toronto, Ontario. The purpose of the Program was to cultivate applied leadership, interprofessional collaboration, and quality improvement capacity among health professionals.

Purpose: This article reports on the evaluation findings from the initial year as well as an update on current program status and sustainability.

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Mutations in the splicing machinery have been implicated in a number of human diseases. Most notably, the U2 small nuclear ribonucleoprotein (snRNP) component SF3b1 has been found to be frequently mutated in blood cancers such as myelodysplastic syndromes (MDS). SF3b1 is a highly conserved HEAT repeat (HR)-containing protein and most of these blood cancer mutations cluster in a hot spot located in HR4-8.

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More than 100 years ago, Osler inspired educators to consider health professions education (HPE) as intricately reliant on patients. Since that time, patient involvement in HPE has taken on many different meanings. The result is a disparate body of literature that is challenging to search, making it difficult to determine how to continue to build knowledge in the field.

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The medical records of 87 dogs treated with surgery for cutaneous malignant melanoma (CMM) of the haired skin were retrospectively reviewed for overall survival time (OST), progression-free survival time (PFS), and prognostic factors. The post-surgery median PFS and median OST were 1282 days and 1363 days, respectively. The post-surgery metastatic rate was 21.

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Background: Despite international bodies calling for increased patient and family involvement, these concepts remain poorly defined within literature on critical and intensive care settings.

Objective: This scoping review investigates the extent and range of literature on patient and family involvement in critical and intensive care settings. Methodological and empirical gaps are identified, and a future agenda for research into optimizing patient and family involvement is outlined.

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Public and patient involvement (PPI) in health care may refer to many different processes, ranging from participating in decision-making about one's own care to participating in health services research, health policy development, or organizational reforms. Across these many forms of public and patient involvement, the conceptual and theoretical underpinnings remain poorly articulated. Instead, most public and patient involvement programs rely on policy initiatives as their conceptual frameworks.

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Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood.

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The rapid response system (RRS) is a patient safety initiative instituted to enable healthcare professionals to promptly access help when a patient's status deteriorates. Despite patients meeting the criteria, up to one-third of the RRS cases that should be activated are not called, constituting a "missed RRS call". Using a case study approach, 10 focus groups of senior and junior nurses and physicians across four hospitals in Australia were conducted to gain greater insight into the social, professional and cultural factors that mediate the usage of the RRS.

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This article presents emerging findings from the first year of a two-year study, which employed ethnographic methods to explore the culture of interprofessional collaboration (IPC) and family member involvement in eight North American intensive care units (ICUs). The study utilized a comparative ethnographic approach - gathering observation, interview and documentary data relating to the behaviors and attitudes of healthcare providers and family members across several sites. In total, 504 hours of ICU-based observational data were gathered over a 12-month period in four ICUs based in two US cities.

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The dynamic properties of podosomes, their ability to degrade the underlying matrix and their modulation by Toll-like receptor (TLR) signaling in dendritic cells (DCs) suggests they have an important role in migration. Integrins are thought to participate in formation and dynamics of podosomes but the multiplicity of integrins in podosomes has made this difficult to assess. We report that murine DCs that lack β2 integrins fail to form podosomes.

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Siglec-E is a sialic acid-binding Ig-like lectin expressed on murine myeloid cells. It has recently been shown to function as a negative regulator of β2-integrin-dependent neutrophil recruitment to the lung following exposure to lipopolysaccharide (LPS). Here, we demonstrate that siglec-E promoted neutrophil production of reactive oxygen species (ROS) following CD11b β2-integrin ligation with fibrinogen in a sialic acid-dependent manner, but it had no effect on ROS triggered by a variety of other stimulants.

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Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia.

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Neutrophil entry into the lung tissues is a key step in host defense to bacterial and yeast infections, but if uncontrolled can lead to severe tissue damage. Here, we demonstrate for the first time that sialic acid binding Ig-like lectin E (siglec-E) functions to selectively regulate early neutrophil recruitment into the lung. In a model of acute lung inflammation induced by aerosolized lipopolysaccharide, siglec-E-deficient mice exhibited exaggerated neutrophil recruitment that was reversed by blockade of the β2 integrin, CD11b.

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Objective: To determine the outcome in dogs undergoing urethral stent placement for management of urethral obstruction secondary to transitional cell carcinoma (TCC).

Design: Retrospective case series.

Animals: 19 dogs with histopathologically confirmed TCC.

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The immune system must be tightly regulated to prevent unwanted tissue damage caused by exaggerated immune and inflammatory reactions. Inhibitory and activating immune receptors play a crucial role in this function via phosphotyrosine-dependent signaling pathways. A significant body of evidence has accumulated suggesting that the siglec family of sialic acid binding Ig-like lectins makes an important contribution to this immunoregulation.

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OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder.

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