Kinetics of Steady-state Differentiation and Mapping of Intrathymic-signaling Environments by Stem Cell Transplantation in Nonirradiated Mice

Upon thymus entry, thymic-homing progenitors undergo distinct phases of differentiation as they migrate through the cortex to the capsule, suggesting that the signals that induce these differentiation steps may be stratified in corresponding cortical regions. To better define these regions, we transplanted purified stem cells into nonirradiated congenic recipients and followed their differentiation with respect to both tissue location and time. The earliest progenitors (DN1) remained confined to a very narrow region of the cortex for about the first 10 d of intrathymic residence; this region virtually overlaps the sites of thymic entry, suggesting that DN1 cells move very little during this lengthy period of proliferation and lineage commitment. Movement out of this region into the deeper cortex is asynchronous, and corresponds to the appearance of DN2 cells. Differentiation to the DN3 stage correlates with movement across the midpoint of the cortex, indicating that stromal signals that induce functions such as TCR gene rearrangement reside mainly in the outer half of the cortex. The minimum time to reach the capsule, and thus transit to the DP stage, is ∼13 d, with the average time a few days longer. These findings reveal for the first time the kinetics of steady-state progenitor differentiation in the thymus, as well as defining the boundaries of cortical regions that support different phases of the differentiation process. We also show that the first lineage-positive progeny of transplanted stem cells to appear in the thymus are dendritic cells in the medulla, suggesting that each new wave of new T cell production is preceded by a wave of regulatory cells that home to the medulla and ensure efficient tolerance and selection

Loss of testosterone impairs anti-tumor neutrophil function.

In men, the incidence of melanoma rises rapidly after age 50, and nearly two thirds of melanoma deaths are male. The immune system is known to play a key role in controlling the growth and spread of malignancies, but whether age- and sex-dependent changes in immune cell function account for this effect remains unknown. Here, we show that in castrated male mice, neutrophil maturation and function are impaired, leading to elevated metastatic burden in two models of melanoma. Replacement of testosterone effectively normalized the tumor burden in castrated male mice. Further, the aberrant neutrophil phenotype was also observed in prostate cancer patients receiving androgen deprivation therapy, highlighting the evolutionary conservation and clinical relevance of the phenotype. Taken together, these results provide a better understanding of the role of androgen signaling in neutrophil function and the impact of this biology on immune control of malignancies

Establishing confidence in the output of qualitative research synthesis: the ConQual approach

BACKGROUND: The importance of findings derived from syntheses of qualitative research has been increasingly acknowledged. Findings that arise from qualitative syntheses inform questions of practice and policy in their own right and are commonly used to complement findings from quantitative research syntheses. The GRADE approach has been widely adopted by international organisations to rate the quality and confidence of the findings of quantitative systematic reviews. To date, there has been no widely accepted corresponding approach to assist health care professionals and policy makers in establishing confidence in the synthesised findings of qualitative systematic reviews. METHODS: A methodological group was formed develop a process to assess the confidence in synthesised qualitative research findings and develop a Summary of Findings tables for meta-aggregative qualitative systematic reviews. RESULTS: Dependability and credibility are two elements considered by the methodological group to influence the confidence of qualitative synthesised findings. A set of critical appraisal questions are proposed to establish dependability, whilst credibility can be ranked according to the goodness of fit between the author's interpretation and the original data. By following the processes outlined in this article, an overall ranking can be assigned to rate the confidence of synthesised qualitative findings, a system we have labelled ConQual. CONCLUSIONS: The development and use of the ConQual approach will assist users of qualitative systematic reviews to establish confidence in the evidence produced in these types of reviews and can serve as a practical tool to assist in decision making.Zachary Munn, Kylie Porritt, Craig Lockwood, Edoardo Aromataris and Alan Pearso

Midwives\u27 use of best available evidence in practice: An integrative review

Aims and objectives: To synthesise international research that relates to midwives\u27 use of best available evidence in practice settings and identify key issues relating to the translation of latest evidence into everyday maternity care. Background: Midwifery is a research‐informed profession. However, a gap persists in the translation of best available evidence into practice settings, compromising gold standard maternity care and delaying the translation of new knowledge into everyday practice. Design: A five‐step integrative review approach, based on a series of articles published by the Joanna Briggs Institute (JBI) for conducting systematic reviews, was used to facilitate development of a search strategy, selection criteria and quality appraisal process, and the extraction and synthesis of data to inform an integrative review. Methods: The databases CINAHL, MEDLINE, Web of Science, Implementation Science Journal and Scopus were searched for relevant articles. The screening and quality appraisal process complied with the PRISMA 2009 checklist. Narrative analysis was used to develop sub‐categories and dimensions from the data, which were then synthesised to form two major categories that together answer the review question. Results: The six articles reviewed report on midwives\u27 use of best available evidence in Australia, the UK and Asia. Two major categories emerged that confirm that although midwifery values evidence‐based practice (EBP), evidence‐informed maternity care is not always employed in clinical settings. Additionally, closure of the evidence‐to‐practice gap in maternity care requires a multidimensional approach. Conclusion: Collaborative partnerships between midwives and researchers are necessary to initiate strategies that support midwives\u27 efforts to facilitate the timely movement of best available evidence into practice. Relevance to clinical practice: Understanding midwives\u27 use of best available evidence in practice will direct future efforts towards the development of mechanisms that facilitate the timely uptake of latest evidence by all maternity care providers working in clinical settings

The exposed Mule Creek vent deposits record the structure of a volcanic conduit during a hybrid explosive–effusive eruption

Silicic volcanic eruptions commonly begin with the explosive ejection of pyroclastic material, before transitioning to gentler effusion-dominated activity. Well-exposed dissected silicic systems are scarce and poorly studied, hindering the advances in our understanding of the explosive–effusive transition needed to improve interpretations of volcanic unrest and hazard forecasting. The Mule Creek vent (New Mexico, USA) is a dissected silicic conduit that records the processes controlling conduit formation and evolution, and the role tuffisites (fractures filled with variably welded pyroclasts) play in conduit dynamics. Here, we use decimeter-scale photo-mapping of lithostratigraphic units and thin section analysis to differentiate and interpret three dominant emplacement styles during vent evolution. First, there was repeated deposition and erosion of pyroclastic material at the conduit walls, recorded by erosive surfaces in pyroclastic breccia and agglomerates at the conduit margins. Second, sub-vertical domains of dense melt-dominated magma were emplaced and preserved as glass-dominated vitrophyre and brecciated vitrophyre, with the textural hallmarks of assembly from welding of pyroclasts. Finally, the sub-horizontal fracturing of previously deposited lithologies produced laterally cross-cutting tuffisites. The vent deposits track the widening and then narrowing of the conduit through time and reflect progressive insulation and generally higher temperatures towards the conduit center as pyroclasts accumulate. Welding of pyroclastic fill and the formation of dense vitrophyres towards the conduit center lowers deposit porosity and effective wall permeability. This drives localized gas pressure increases and results in gas-driven fracturing, generating tuffisites, which act as transient outgassing pathways. The structure of the Mule Creek vent records an explosive–effusive transition, constraining the processes controlling conduit evolution and aiding our interpretation of volcanic unrest

Development and testing of a Cognitive Behavioural Therapy resource for children's dental anxiety

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for dental anxiety; however, access to therapy is limited. The current study aimed to develop a self-help CBT resource for reducing dental anxiety in children, and to assess the feasibility of conducting a trial to evaluate the treatment efficacy and cost-effectiveness of such an intervention. A mixed methods design was employed. Within phase 1, a qualitative “person-based” approach informed the development of the self-help CBT resource. This also employed guidelines for the development and evaluation of complex interventions. Within phase 2, children, aged between 9 and 16 y, who had elevated self-reported dental anxiety and were attending a community dental service or dental hospital, were invited to use the CBT resource. Children completed questionnaires, which assessed their dental anxiety and health-related quality of life (HRQoL) prior to and following their use of the resource. Recruitment and completion rates were recorded. Acceptability of the CBT resource was explored using interviews and focus groups with children, parents/carers and dental professionals. For this analysis, the authors adhered to the Mixed Methods Appraisal Tool criteria. There were 24 families and 25 dental professionals participating in the development and qualitative evaluation of the CBT resource for children with dental anxiety. A total of 56 children agreed to trial the CBT resource (66% response rate) and 48 of these children completed the study (86% completion rate). There was a significant reduction in dental anxiety (mean score difference = 7.7, t = 7.9, df = 45, P < 0.001, Cohen’s d ES = 1.2) and an increase in HRQoL following the use of the CBT resource (mean score difference = -0.03, t = 2.14, df = 46, P < 0.05, Cohen’s d ES = 0.3). The self-help approach had high levels of acceptability to stakeholders. These findings provide preliminary evidence for the effectiveness and acceptability of the resource in reducing dental anxiety in children and support the further evaluation of this approach in a randomized control trial

Children’s experiences following a CBT intervention to reduce dental anxiety: one year on

Objective: To investigate children’s ongoing experiences of dental care and use of strategies to manage their dental anxiety following cognitive behavioural therapy (CBT). Design: A child self-completed postal questionnaire. Settings: Hospital, community and general dental practice. Subjects: Questionnaires were sent to 44 children, aged 10-17 years who had been referred to specialist services due to their dental anxiety. Intervention: Children had all previously received a guided CBT self-help intervention to reduce their dental anxiety and, on completion of treatment, had been discharged to their referring dentist. Questionnaires were sent out 12-18 months later to ascertain dental attendance patterns and application of any strategies learnt from the previous CBT intervention. Results: 22 responses (50%) were received from 16 girls and 6 boys. 82% had subsequently accessed follow up care with a general dental practitioner and over half of these had undergone a dental procedure, other than a check-up. 91% reported feeling less worried about dental visits, than previously, and described a change in cognition, behaviours, and feelings that allowed them to manage their anxiety better. Conclusions: CBT has positive immediate and longitudinal effects in reducing children’s dental anxiety. The challenge of adopting this evidence-based approach within primary care settings remains

Service evaluation of a nurse-led dental anxiety management service for adult patients

Objective: Evaluate patients’ and professionals’ experiences of a Nurse-led Dental Anxiety Management Service (NDAMS). Design: Service evaluation. Setting: The NDAMS operates as part of Sheffield Salaried Primary Dental Care Service. Subjects and methods: Questionnaire survey of anxious patients and qualitative interviews with patients and professionals Interventions: Dental nurses delivered low-level psychological interventions as part of an Integrated Care Pathway (ICP) for dental anxiety. Main outcome Measures: Dental anxiety and oral health-related quality of life (OHRQoL) questionnaires were completed by patients prior to and following NDAM. Results: A total of 187 patients were assessed as suitable for NDAM (mean age= 33.7, 77% female) and 33 had completed it at the time of the service evaluation. Of those patients who had completed the intervention significant improvements in dental anxiety and OHRQoL were reported. Professionals highlighted the importance of integrated working, adequate support and training and assessing the suitability of patients for NDAM. Conclusion: ICPs that combine pharmacological and psychological management approaches can help meet the needs of dentally anxious patients, however, early identification of patients most likely to benefit from psychological intervention should be a priority

Antecedents and outcomes of consumer environmentally friendly attitudes and behaviour

With the intensification of problems relating to the environment, a growing number of consumers are becoming more ecologically conscious in their preferences and purchases of goods. This paper presents the results of a study conducted among 500 Cypriot consumers, focusing on the factors that shape consumer environmental attitudes and behaviour, as well as on the resulting outcomes. The findings confirmed that both the inward and outward environmental attitudes of a consumer are positively influenced by his/her degree of collectivism, long-term orientation, political involvement, deontology, and law obedience, but have no connection with liberalism. The adoption of an inward environmental attitude was also found to be conducive to green purchasing behaviour that ultimately leads to high product satisfaction. On the other hand, an outward environmental attitude facilitates the adoption of a general environmental behaviour, which is responsible for greater satisfaction with life. The findings of the study have important implications for shaping effective company offerings to consumers in target markets, as well as formulating appropriate policies at the governmental level to enhance environmental sensitivity among citizens