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Background Errors associated with failures in filing, actioning and communicating blood test results can lead to delayed and missed diagnoses and patient harm. This study aimed to audit how blood tests in primary care are filed, actioned and communicated in primary care, to identify areas for patient safety improvements.Methods UK primary care clinicians were recruited through the Primary Care Academic CollaboraTive (PACT). PACT members audited 50 recent sets of blood tests from their practice and retrospectively extracted data on blood test result coding, actioning and communication. PACT members received a practice report, showing their own results, benchmarked against other participating practices.Results PACT members from 57 general practices across all four UK nations collected data on 2572 patients who had blood tests in April 2021. In 89.9% (n=2311) they agreed with the initial clinician’s actioning of blood tests; 10.1% disagreed, either partially (7.1%) or fully (3.0%).In 44% of patients (n=1132) an action (eg, ‘make an appointment’) was specified by the filing clinician. This action was carried out in 89.7% (n=1015/1132) of cases; in 6.8% (n=77) the action was not carried out, in 3.5% (n=40) it was unclear. In the 117 cases where the test result had not been actioned 38% (n=45) were felt to be at low risk of harm, 1.7% (n=2) were at high risk of harm, 0.85% (n=1) came to harm.Overall, in 47% (n=1210) of patients there was no evidence in the electronic health records that results had been communicated. Out of 1176 patients with one or more abnormal results there was no evidence of test communication in 30.6% (n=360). There were large variations between practices in rates of actioning and communicating tests.Conclusion This research demonstrates variation in the way blood test results are actioned and communicated, with important patient safety implications.

For the last five years, we have had the honor of serving as editors of the Journal of Public Deliberation. This issue marks the end of our editorial tenure, and we take this opportunity to both look back and think ahead. In this brief essay, we reflect on what we’ve seen during our time as editors. We begin by describing three important special issues that reflect the state of our field, then provide some details about how we have facilitated JPD’s growth over the past five years, including publication statistics and article download rates. We conclude by discussing where the journal is now and what we anticipate for its future.

This article introduces the special issue on Deliberative Democracy in an Era of Authoritarianism. The essay highlights the relationship between authoritarianism and democracy, and discusses concerns about the current rise in authoritarianism in political systems. It poses questions about how deliberative scholars and practitioners should respond to authoritarian political contexts and how deliberation should relate to more activist forms of civic engagement. Finally, it previews the articles in the special issue and urges future work in the field to take up ideas, questions, and challenges posed by these essays.

Investigators from Necker Enfants Malades Hospital, Sorbonne Paris Cite University, Raymond Poincare University, and Paris Descartes University studied motor neuron function in children with Dravet syndrome (DS).

This “Afterword” essay was written several months after the Frontiers of Democracy 2014 conference. It offers the Journal of Public Deliberation’s editors’ reflections on the conference and connections to the articles published in this special issue.

This article introduces the special “State of the Field” issue. The essay highlights some of the key tensions that our field is wrestling with at the moment, and advocates that we think carefully about the terms we use to describe our work. It previews the articles in this special issue and urges future work in the field to take up the ideas, questions, and challenges posed by these essays.

Disagreement is a fundamental part of deliberative discussion, but how group members understand their disagreement can profoundly influence their actions. These conflict frames have implications for members’ perception of both the issue and as their relationships. Drawing on Putnam’s (1990, Brummans et al., 2008) work on conflict frames, this study examines how members of an online deliberative group framed and reframed their conflicts through personal storytelling. Members drew on different models of democracy in their stories. Some managed their disagreements through reframing their conflicts and relationships as collaborative, even in response to adversarially-framed stories. This study advances research in conflict, group discussion, and deliberative discussion and offers practical suggestions for facilitators on how to recognize, interrogate, and help groups develop productive conflict frames.

This essay provides an overview of what is currently being done in the discipline of communication studies that can advance deliberative democracy, particularly in terms of student learning, and explores how those connections could be strengthened and extended. The essay is divided into three main sections. First, a brief history of the field of communication studies is provided. Next, four questions relevant to deliberative theory and practice are introduced and the teaching and research of communication scholars that provides significant responses are examined: (1) how do we improve how citizens process information and exercise judgment?, (2) how do we best deal the differences in our increasingly diverse communities?, (3) how can we better understand the processes and outcomes of deliberation?, and (4) what are the key future directions for deliberative theory and practice? Within this section, a number of the sub-fields within communication studies that connect directly or indirectly to deliberative work are introduced. The essay concludes with a review of the limitations to these connections and a “call to action” for increased public engagement.

This concluding essay reflects on how the essays included in this special issue can help address some prevailing issues in public participation scholarship. We see three themes running through the contributions to this special issue that are particularly important for public participation scholars and practitioners to consider. These issues are: citizens’ distrust of public officials, concerns about who counts as a legitimate member of the community, and challenges related to the framing the process and goals of the meeting. In this concluding essay we summarize and reflect on the insights provided by the special issue contributions. We also look ahead to assess how these contributions can inform future public participation research and practice by illuminating the importance of communication practices and public meeting formats.

This special issue of IJP2 attempts to build linkages between public participation scholarship and communication research that emphasizes close attention to naturally-occurring interaction. The essays all investigate different aspects of the communication that occurs during one public meeting: a public forum that focused on issues of economic development in Omaha, Nebraska. Through their investigation of this common case, the essays in this issue provide detailed description of some communication processes common to public meetings such as nonverbal communication, question and answer behavior, storytelling, the use of the term “community,” and the terms people use to talk about their own communication. These studies highlight how such interactive practices function in important ways to build or challenge notions of community, frame the purpose and outcome of the meeting, display power differences among participants, and clarify key community values. This collection of essays highlights how close attention to what happens during public meetings can have important implications for both the theory and practice of public participation. A full video of the meeting is available online.

This study uses discourse analysis from a Language and Social Interaction (LSI) perspective to analyze the personal stories that were told during the North Omaha Development Project (NODP) public meeting. Personal stories may not intuitively seem to be important in public meetings because they center on individual, personal experience, rather than discussing issues in public terms. However, stories help people to create and negotiate their identities, demonstrate their values, and indicate what actions ought to be taken to enact those values in meaningful ways. In the NODP public meeting, presenters and audience members told stories that demonstrated the important distinction between community members and outsiders, and offered competing notions of the community values and appropriate actions that should be taken to address neighborhood poverty. This analysis offers insights into how public participation scholars can view stories told in public meetings as well as practical implications for officials convening public meetings.

This study examines how members of deliberative groups tell and respond to personal stories during their disagreements. The study provides an in-depth qualitative analysis of some online discussions hosted by AmericaSpeaks in which New Yorkers discussed how to redevelop the site of the former World Trade Center after its destruction on September 11, 2001. Participants’ stories fell into four distinct types: adversarial argument, unitary argument, introduction, and transformation. These stories helped group members build arguments, maintain or challenge their group’s collective identity, display community values, and manage their conflicts. The findings of this study indicate that deliberative theory ought to more explicitly recognize storytelling as a legitimate form of deliberative discourse. Moreover, the study of storytelling during deliberative discussion can hold implications for group facilitators and others who wish to further deliberative ideals.

During the past fifteen years, public deliberation has become an important focus of research, theory, and public practice. This has sometimes led to a variety of narrow conceptualizations that limit deliberation to particular forms of interaction, such as small group discussion, or to divergent conceptualizations deployed in different contexts, such as for media systems versus face-to-face discussions. To address this problem, we advance a flexible yet precise definition of deliberation that has the power to organize not only deliberation theory and research but also much of the larger body of work in political communication. As defined herein, deliberation includes both analytic and social processes and provides a unifying conceptual and critical framework for studying nearly the full range of political communication topics, including informal conversation, media and public opinion, elections, government institutional behavior, jury decision making, public meetings, and civic and community life. Using our flexible conceptualization, each of these research contexts amounts to a kind of deliberative critique and empirical analysis of public life.

Abstract Background Treatment of nasal tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast‐enhanced computed tomography (DCECT) can be used to assess tumor perfusion. Objectives To assess perfusion parameters of nasal tumors (correlating with tumor type) before and during radiotherapy (RT) and find potential correlation with survival. Animals Twenty‐four client‐owned dogs with nasal tumors, including 16 epithelial tumors and 8 sarcomas. Methods Prospective cross‐sectional study. All dogs had baseline DCECT to assess fractional vascular volume (BV), blood flow (BF), and transit time (TT). Thirteen dogs had repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. Results Median BV was 17.83 mL/100 g (range, 3.63‐66.02), median BF was 122.63 mL/100 g/minute (range, 23.65‐279.99), and median TT was 8.91 seconds (range, 4.57‐14.23). Sarcomas had a significantly lower BF than adenocarcinomas (P = .002), carcinomas (P = .01), and other carcinomas (P = .001), and significantly lower BV than adenocarcinomas (P = .03) and other carcinomas (P = .004). Significant associations were found between epithelial tumors and sarcoma for change in tumor volume (P = .01), width (P = .004), and length (P = .02) in that epithelial tumors decreased in volume whereas sarcomas increased in volume. Perfusion parameters were not correlated with survival. Conclusions and Clinical Importance Nasal sarcomas have lower BV and BF than nasal carcinomas, and sarcomas have a lower size reduction than carcinomas early on during RT. Baseline results and changes in perfusion parameters may not be correlated with survival.

IntroductionTreatment of brain tumors in dogs can be associated with significant morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to assess perfusion parameters and change in size of suspected brain tumors before and during radiotherapy (RT) depending on their location and find a potential correlation with survival.MethodsSeventeen client-owned dogs with suspected brain tumors were prospectively recruited. All dogs had a baseline DCECT to assess mass size, blood volume (BV), blood flow (BF), and transit time (TT). Twelve dogs had a repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated.ResultsIntra-axial masses had lower BF (p = 0.005) and BV (p

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). The GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: Our mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

Impaired immune responses and increased susceptibility to infection characterize acute inflammatory conditions such as pancreatitis and alcoholic hepatitis and are major causes of morbidity and mortality. However, the mechanisms that drive this apparent immune paresis remain poorly understood. Monocytes mediate host responses to damage and pathogens in health and disease, and three subsets of monocytes have been defined based on CD14 and CD16 expression. We sought to determine the changes in monocyte subsets in acute pancreatitis (AP) and acute alcoholic hepatitis (AAH), together with functional consequences and mechanisms that underlie this change. Peripheral blood mononuclear cells (PBMCs) from patients with AP or AAH were compared with healthy controls. Monocyte subsets were defined by HLA-DR, CD14, and CD16 expression. Changes in surface and intracellular protein expression and phosphorylation were determined by flow cytometry. Phenotype and function were assessed following stimulation with lipopolysaccharide (LPS) or other agonists in the presence of specific inhibitors of TNFα and a disintegrin and metalloproteinase 17 (ADAM17). Patients with AP and AAH had reduced CD14++CD16+ intermediate monocytes compared to controls. Reduction of intermediate monocytes was recapitulated ex vivo by stimulating healthy control PBMCs with Toll-like receptor (TLR) agonists LPS, flagellin or polyinosilic:polycytidylic acid (poly I:C). Stimulation caused shedding of CD14 and CD16, which could be reversed using the ADAM17 inhibitor, TMI005 but not direct inhibitors of TNFα, a known ADAM17-target. Culturing PBMCs from healthy controls resulted in expansion of intermediate monocytes, which did not occur when LPS was in the culture medium. Cultured intermediate monocytes showed reduced expression of CX3CR1, CCR2, TLR4, and TLR5. We found reduced migratory responses, intracellular signaling and pro-inflammatory cytokine production, and increased expression of IL-10. Stimulation with TLR agonists results in ADAM17-mediated shedding of phenotypic markers from CD16+ monocytes, leading to apparent “loss” of intermediate monocytes. Reduction in CD14++CD16− monocytes and increased CD14++CD16+ is associated with altered responses in functional assays ex vivo. Patients with AP and AAH had reduced proportions of CD14++CD16+ monocytes and reduced phosphorylation of NFκB and IL-6 production in response to bacterial LPS. Together, these processes may contribute to the susceptibility to infection observed in AP and AAH.

Case summary An 11-year-old male neutered domestic shorthair cat presented with behavioural changes. Physical examination revealed bradycardia and a cranial abdominal mass. The cat was persistently hypoglycaemic (1.2 mmol/l; reference interval [RI] 3.5–5.5 mmol/l) with decreased fructosamine concentration suggesting chronic hypoglycaemia, and decreased insulin concentration excluding insulinoma. Alanine aminotransferase activity was markedly increased (1219.31 U/l; RI 15–60 U/l). On staging CT a large, multilobulated hepatic mass was identified, with no evidence of metastatic disease. After surgical removal serum glucose concentration and heart rate quickly returned to within the RIs. Histopathology was consistent with a solid-to-trabecular, well-differentiated, hepatocellular carcinoma. There was no recurrence of signs or mass during 8 months of follow-up, and the cat was still alive 20 months after surgery. Relevance and novel information Non-islet-cell tumour hypoglycaemia (NICTH) is a rare but life-threatening paraneoplastic syndrome. In humans, hepatocellular carcinoma is the most common epithelial tumour causing NICTH, but these are uncommon in cats, and associated paraneoplastic hypoglycaemia has not been reported. Possible mechanisms include aberrant secretion of big insulin growth factor 2; however, this could not be confirmed. NICTH should be considered in the differential diagnosis of cats with persistent hypoglycaemia.

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.

Quadruplex (G4) forming sequences in telomeric DNA and c-myc promoter regions of human DNA are associated with tumorogenesis. Ligands that can facilitate or stabilize the formation and increase the stabilization of G4 can prevent tumor cell proliferation and have been regarded as potential anti-cancer drugs. In the present study, steady state and time-resolved fluorescence measurements provide important structural and dynamical insights into the free and bound states of the therapeutically potent plant flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) in a G4 DNA matrix. The excited state intra-molecular proton transfer (ESPT) of fisetin plays an important role in observing and understanding the binding of fisetin with the G4 DNA. Differential absorption spectra, thermal melting, and circular dichroism spectroscopic studies provide evidences for the formation of G4 DNA and size exclusion chromatography (SEC) proves the binding and 1∶1 stoichiometry of fisetin in the DNA matrix. Comparative analysis of binding in the presence of EtBr proves that fisetin favors binding at the face of the G-quartet, mostly along the diagonal loop. Time resolved fluorescence anisotropy decay analysis indicates the increase in the restrictions in motion from the free to bound fisetin. We have also investigated the fingerprints of the binding of fisetin in the antiparallel quadruplex using Raman spectroscopy. Preliminary results indicate fisetin to be a prospective candidate as a G4 ligand.