What health inequalities exist in access to, outcomes from and experience of treatment for lung cancer? A scoping review.

OBJECTIVES: Lung cancer (LC) continues to be the leading cause of cancer-related deaths and while there have been significant improvements in overall survival, this gain is not equally distributed. To address health inequalities (HIs), it is vital to identify whether and where they exist. This paper reviews existing literature on what HIs impact LC care and where these manifest on the care pathway. DESIGN: A systematic scoping review based on Arksey and O'Malley's five-stage framework. DATA SOURCES: Multiple databases (EMBASE, HMIC, Medline, PsycINFO, PubMed) were used to retrieve articles. ELIGIBILITY CRITERIA: Search limits were set to retrieve articles published between January 2012 and April 2022. Papers examining LC along with domains of HI were included. Two authors screened papers and independently assessed full texts. DATA EXTRACTION AND SYNTHESIS: HIs were categorised according to: (a) HI domains: Protected Characteristics (PC); Socioeconomic and Deprivation Factors (SDF); Geographical Region (GR); Vulnerable or Socially Excluded Groups (VSG); and (b) where on the LC pathway (access to, outcomes from, experience of care) inequalities manifest. Data were extracted by two authors and collated in a spreadsheet for structured analysis and interpretation. RESULTS: 41 papers were included. The most studied domain was PC (32/41), followed by SDF (19/41), GR (18/41) and VSG (13/41). Most studies investigated differences in access (31/41) or outcomes (27/41), with few (4/41) exploring experience inequalities. Evidence showed race, rural residence and being part of a VSG impacted the access to LC diagnosis, treatment and supportive care. Additionally, rural residence, older age or male sex negatively impacted survival and mortality. The relationship between outcomes and other factors (eg, race, deprivation) showed mixed results. CONCLUSIONS: Findings offer an opportunity to reflect on the understanding of HIs in LC care and provide a platform to consider targeted efforts to improve equity of access, outcomes and experience for patients.

Supporting translation of research evidence into practice-the use of Normalisation Process Theory to assess and inform implementation within randomised controlled trials: a systematic review.

BACKGROUND: The status of randomised controlled trials (RCTs) as the 'gold standard' for evaluating efficacy in healthcare interventions is increasingly debated among the research community, due to often insufficient consideration for implementation. Normalisation Process Theory (NPT), which focuses on the work required to embed processes into practice, offers a potentially useful framework for addressing these concerns. While the theory has been deployed in numerous RCTs to date, more work is needed to consolidate understanding of if, and how, NPT may aid implementation planning and processes within RCTs. Therefore, this review seeks to understand how NPT contributes to understanding the dynamics of implementation processes within RCTs. Specifically, this review will identify and characterise NPT operationalisation, benefits and reported challenges and limitations in RCTs. METHODS: A qualitative systematic review with narrative synthesis of peer-reviewed journal articles from eight databases was conducted. Studies were eligible for inclusion if they reported sufficient detail on the use of NPT within RCTs in a healthcare domain. A pre-specified data extraction template was developed based on the research questions of this review. A narrative synthesis was performed to identify recurrent findings. RESULTS: Searches identified 48 articles reporting 42 studies eligible for inclusion. Findings suggest that NPT is primarily operationalised prospectively during the data collection stage, with limited sub-construct utilisation overall. NPT is beneficial in understanding implementation processes by aiding the identification and analysis of key factors, such as understanding intervention fidelity in real-world settings. Nearly three-quarters of studies failed to report the challenges and limitations of utilising NPT, though coding difficulties and data falling outside the NPT framework are most common. CONCLUSIONS: NPT appears to be a consistent and generalisable framework for explaining the dynamics of implementation processes within RCTs. However, operationalisation of the theory to its full extent is necessary to improve its use in practice, as it is currently deployed in varying capacities. Recommendations for future research include investigation of NPT alongside other frameworks, as well as earlier operationalisation and greater use of NPT sub-constructs. TRIAL REGISTRATION: The protocol for this systematic review was accepted for public registration on PROSPERO (registration number: CRD42022345427) on 26 July 2022.

Unpacking the 'process of sustaining'-identifying threats to sustainability and the strategies used to address them: a longitudinal multiple case study.

BACKGROUND: Although sustainability remains a recognised challenge for Quality Improvement (QI) initiatives, most available research continues to investigate sustainability at the end of implementation. As a result, the learning and continuous adjustments that shape sustainability outcomes are lost. With little understanding of the actions and processes that influence sustainability within QI initiatives, there is limited practical guidance and direction on how to enhance the sustainability of QI initiatives. This study aims to unpack the 'process of sustaining', by exploring threats to sustainability encountered throughout the implementation of QI Initiatives and identifying strategies used by QI teams to address these threats over time. METHODS: A longitudinal multiple case study design was employed to follow 4 QI initiatives over a 3-year period. A standardised sustainability tool was used quarterly to collect perceptions of sustainability threats and actions throughout implementation. Interviews (n=38), observations (32.5 h), documentary analysis, and a focus group (n=10) were conducted to enable a greater understanding of how the process of sustaining is supported in practice. Data were analysed using the Consolidated Framework for Sustainability (CFS) to conduct thematic analysis. RESULTS: Analysis identified five common threats to sustainability: workforce stability, improvement timelines, organisational priorities, capacity for improvement, and stakeholder support. Each of these threats impacted multiple sustainability constructs demonstrating the complexity of the issues encountered. In response to threats, 12 strategies to support the process of sustaining were identified under three themes: engagement (five strategies that promoted the development of relationships), integration (three strategies that supported initiatives to become embedded within local systems), and adaptation (four strategies that enhanced understanding of, and response to, emergent conditions and contextual needs). CONCLUSIONS: Sustaining improvements from QI initiatives requires continuous investment in relationships, resilience to integrate improvements in local systems, and flexibility to understand emergent conditions. Findings provide practitioners, funders, and researchers with a better understanding of, and preparation for, the threats associated with sustaining improvements from QI initiatives and offer insight into specific actions that can be taken to mitigate these risks. This learning can be used to inform future initiative design and support, to optimise the sustainability of healthcare improvements. TRIAL REGISTRATION: Not applicable.

Oral health promotion in acute hospital setting: a quality improvement programme.

Tooth extraction is the most common hospital procedure for children aged 6-10 years in England. Tooth decay is almost entirely preventable and is inequitably distributed across the population: it can cause pain, infection, school absences and undermine overall health status.An oral health programme (OHP) was delivered in a hospital setting, comprising: (1) health promotion activities; (2) targeted supervised toothbrushing (STB) and (3) staff training. Outcomes were measured using three key performance indicators (KPI1: percentage of children/families seeing promotional material; KPI2: number of children receiving STB; KPI3: number of staff trained) and relevant qualitative indicators. Data were collected between November 2019 and August 2021 using surveys and data from the online booking platform.OHP delivery was impacted by COVID-19, with interventions interrupted, reduced, eliminated or delivered differently (eg, in-person training moved online). Despite these challenges, progress against all KPIs was made. 93 posters were deployed across the hospital site, along with animated video 41% (233/565) of families recalled seeing OHP materials across the hospital site (KPI1). 737 children received STB (KPI2), averaging 35 children/month during the active project. Following STB, 96% participants stated they learnt something, and 94% committed to behaviour change. Finally, 73 staff members (KPI3) received oral health training. All people providing feedback (32/32) reported learning something new from the training session, with 84% (27/32) reporting that they would do things differently in the future.Results highlight the importance of flexibility and resilience when delivering QI projects under challenging conditions or unforeseen circumstances. While results suggest that hospital-based OHP is potentially an effective and equitable way to improve patient, family and staff knowledge of good oral health practices, future work is needed to understand if and how patients and staff put into practice the desired behaviour change and what impact this may have on oral health outcomes.

Evaluating the implementation and impact of a new model of care for integrating children and young people's acute mental healthcare in a paediatric setting: a protocol for a realist, mixed-methods approach.

INTRODUCTION: The mental health of children and young people in the UK has been declining and has continued to worsen throughout the pandemic, leading to an increase in mental health-related emergencies. In response, the Best for You programme was developed as a new service designed to integrate mental healthcare for children and young people between acute hospital and community services. The programme is comprised of four new services: a rapid assessment young people's centre with dual-trained staff, a co-located day service offering family-based care,a digital hub, designed to integrate with the fourth element of the model, namely community support and mental health services. This evaluation protocol aims to assess the development, implementation and outcomes of the Best for You programme and develops a scalable model that could be implemented in other parts of the National Health Service (NHS). METHODS AND ANALYSIS: This mixed-methods realist evaluation aims to delineate the components of the system to assess their interdependent relationships within a wider context. Data collection will include interviews, participant observations, focus groups and the collection of local quantitative healthcare data. The research will be conducted across four phases. Phase 1-captures the development of the underlying programme theory. Phase 2-a process evaluation testing the programme theory. Phase 3- an outcome and economic evaluation. Phase 4-consolidation of learning from phases 1-3 to identify barriers, facilitators and wider contextual factors that have shaped implementation drawing on the Consolidated Framework for Implementation Research. ETHICS AND DISSEMINATION: Ethical approval for the evaluation was received from the NHS local ethics committee. Embedded within the evaluation is a formative review to feedback and share learning with stakeholders to scale-up the programme. Findings from this study will be disseminated in peer-reviewed journals as well as presentations to be useful to service user organisations and networks.

Conceptualising interventions to enhance spread in complex systems: a multisite comprehensive medication review case study.

BACKGROUND: Advancing the description and conceptualisation of interventions in complex systems is necessary to support spread, evaluation, attribution and reproducibility. Improvement teams can provide unique insight into how interventions are operationalised in practice. Capturing this 'insider knowledge' has the potential to enhance intervention descriptions. OBJECTIVES: This exploratory study investigated the spread of a comprehensive medication review (CMR) intervention to (1) describe the work required from the improvement team perspective, (2) identify what stays the same and what changes between the different sites and why, and (3) critically appraise the 'hard core' and 'soft periphery' (HC/SP) construct as a way of conceptualising interventions. DESIGN: A prospective case study of a CMR initiative across five sites. Data collection included: observations, document analysis and semistructured interviews. A facilitated workshop triangulated findings and measured perceived effort invested in activities. A qualitative database was developed to conduct thematic analysis. RESULTS: Sites identified 16 intervention components. All were considered essential due to their interdependency. The function of components remained the same, but adaptations were made between and within sites. Components were categorised under four 'spheres of operation': Accessibility of evidence base; Process of enactment; Dependent processes and Dependent sociocultural issues. Participants reported most effort was invested on 'dependent sociocultural issues'. None of the existing HC/SP definitions fit well with the empirical data, with inconsistent classifications of components as HC or SP. CONCLUSIONS: This study advances the conceptualisation of interventions by explicitly considering how evidence-based practices are operationalised in complex systems. We propose a new conceptualisation of 'interventions-in-systems' which describes intervention components in relation to their: proximity to the evidence base; component interdependence; component function; component adaptation and effort.

What risks to sustainability are identified throughout care bundle implementation and how can they be addressed? A mixed methods case study.

OBJECTIVES: Despite national guidance on how to identify and treat heart failure (HF), variation in HF care persists across UK hospitals. Care bundles have been proposed as a mechanism to deliver reliable optimal care for patients; however, specific challenges to sustain care bundles in practice have been highlighted. With few studies providing insight into how to design or implement care bundles to optimise sustainability, there is little direction for practitioners seeking to ensure long-term impact of their initiatives. This study explores the sustainability risks encountered throughout the implementation of a HF care bundle (HFCB) and describes how these challenges were addressed by a multidisciplinary team (MDT) to enhance sustainability over time. DESIGN: A longitudinal mixed method case study examined the HFCB improvement initiative from September 2015 to August 2018. A standardised sustainability tool was used to collect perceptions of sustainability risks and actions throughout the initiative. Observations, key-informant interviews and documentary analysis were conducted to gain in-depth understanding of how the MDT influenced sustainability through specific actions. A qualitative database was developed using a consolidated sustainability framework to conduct thematic analysis. Sustainability outcomes were explored 1-year post funding to ascertain progress towards sustainment. RESULTS: The MDT identified six sustainability challenges for the HFCB: infrastructure limitations, coding reliability, delivery consistency, organisational fit, resource stability and demonstrating impact. The MDT undertook multiple actions to enhance sustainability, including: (1) developing a business case to address infrastructure limitations; (2) incorporating staff feedback to increase bundle usability; (3) establishing consistent training; (4) increasing reliability of baseline data; (5) embedding monitoring and communication; and (6) integrating the bundle into current practices. CONCLUSION: Through the description of challenges, actions and learning from the MDT, this study provides practical lessons for practitioners and researchers seeking to embed and sustain care bundles in practice.

Process mapping in healthcare: a systematic review.

INTRODUCTION: Process mapping (PM) supports better understanding of complex systems and adaptation of improvement interventions to their local context. However, there is little research on its use in healthcare. This study (i) proposes a conceptual framework outlining quality criteria to guide the effective implementation, evaluation and reporting of PM in healthcare; (ii) reviews published PM cases to identify context and quality of PM application, and the reported benefits of using PM in healthcare. METHODS: We developed the conceptual framework by reviewing methodological guidance on PM and empirical literature on its use in healthcare improvement interventions. We conducted a systematic review of empirical literature using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Inclusion criteria were: full text empirical study; describing the process through which PM has been applied in a healthcare setting; published in English. Databases searched are: Medline, Embase, HMIC-Health Management Information Consortium, CINAHL-Cumulative Index to Nursing and Allied Health Literature, Scopus. Two independent reviewers extracted and analysed data. Each manuscript underwent line by line coding. The conceptual framework was used to evaluate adherence of empirical studies to the identified PM quality criteria. Context in which PM is used and benefits of using PM were coded using an inductive thematic analysis approach. RESULTS: The framework outlines quality criteria for each PM phase: (i) preparation, planning and process identification, (ii) data and information gathering, (iii) process map generation, (iv) analysis, (v) taking it forward. PM is used in a variety of settings and approaches to improvement. None of the reviewed studies (N = 105) met all ten quality criteria; 7% were compliant with 8/10 or 9/10 criteria. 45% of studies reported that PM was generated through multi-professional meetings and 15% reported patient involvement. Studies highlighted the value of PM in navigating the complexity characterising healthcare improvement interventions. CONCLUSION: The full potential of PM is inhibited by variance in reporting and poor adherence to underpinning principles. Greater rigour in the application of the method is required. We encourage the use and further development of the proposed framework to support training, application and reporting of PM. TRIAL REGISTRATION: Prospero ID: CRD42017082140.

Exploring Sustainability in the Era of Differentiated HIV Service Delivery in Sub-Saharan Africa: A Systematic Review.

INTRODUCTION: The World Health Organization recommends differentiated service delivery (DSD) to support resource-limited health systems in providing patient-centered HIV care. DSD offers alternative care models to clinic-based care for people living with HIV who are stable on antiretroviral therapy (ART). Despite good patient-related outcomes, there is limited evidence of their sustainability. Our review evaluated the reporting of sustainability indicators of DSD interventions conducted in sub-Saharan Africa (SSA). METHODS: We searched PubMed and EMBASE for studies conducted between 2000 and 2019 assessing DSD interventions targeting HIV-positive individuals who are established in ART in sub-Saharan Africa. We evaluated them through a comprehensive sustainability framework of constructs categorized into 6 domains (intervention design, process, external environment, resources, organizational setting, and people involvement). We scored each construct 1, 2, or 3 for no, partial, or sufficient level of evidence, respectively. Interventions with a calculated sustainability score (overall and domain-specific) of >90% or domain-specific median score >2.7 were considered likely to be sustainable. RESULTS: Overall scores ranged from 69% to 98%. Top scoring intervention types included adherence clubs (98%) and community ART groups (95%) which comprised more than half of interventions. The highest scoring domains were design (2.9) and organizational setting (2.8). The domains of resources (2.4) and people involvement (2.3) scored lowest revealing potential areas for improvement to support DSD sustainability. CONCLUSIONS: With the right investment in stakeholder involvement and domestic funding, DSD models generally show potential for sustainability. Our results could guide informed decisions on which DSD intervention is likely to be sustainable per setting and highlight areas that could motivate further research.

Evolving quality improvement support strategies to improve Plan-Do-Study-Act cycle fidelity: a retrospective mixed-methods study.

BACKGROUND: Although widely recommended as an effective approach to quality improvement (QI), the Plan-Do-Study-Act (PDSA) cycle method can be challenging to use, and low fidelity of published accounts of the method has been reported. There is little evidence on the fidelity of PDSA cycles used by front-line teams, nor how to support and improve the method's use. Data collected from 39 front-line improvement teams provided an opportunity to retrospectively investigate PDSA cycle use and how strategies were modified to help improve this over time. METHODS: The fidelity of 421 PDSA cycles was reviewed using a predefined framework and statistical analysis examined whether fidelity changed over three annual rounds of projects. The experiences of project teams and QI support staff were investigated through document analysis and interviews. RESULTS: Although modest, statistically significant improvements in PDSA fidelity occurred; however, overall fidelity remained low. Challenges to achieving greater fidelity reflected problems with understanding the PDSA methodology, intention to use and application in practice. These problems were exacerbated by assumptions made in the original QI training and support strategies: that PDSA was easy to understand; that teams would be motivated and willing to use PDSA; and that PDSA is easy to apply. QI strategies that evolved to overcome these challenges included project selection process, redesign of training, increased hands-on support and investment in training QI support staff. CONCLUSION: This study identifies support strategies that may help improve PDSA cycle fidelity. It provides an approach to assess minimum standards of fidelity which can be replicated elsewhere. The findings suggest achieving high PDSA fidelity requires a gradual and negotiated process to explore different perspectives and encourage new ways of working.

The use of process mapping in healthcare quality improvement projects.

Introduction Process mapping provides insight into systems and processes in which improvement interventions are introduced and is seen as useful in healthcare quality improvement projects. There is little empirical evidence on the use of process mapping in healthcare practice. This study advances understanding of the benefits and success factors of process mapping within quality improvement projects. Methods Eight quality improvement projects were purposively selected from different healthcare settings within the UK's National Health Service. Data were gathered from multiple data-sources, including interviews exploring participants' experience of using process mapping in their projects and perceptions of benefits and challenges related to its use. These were analysed using inductive analysis. Results Eight key benefits related to process mapping use were reported by participants (gathering a shared understanding of the reality; identifying improvement opportunities; engaging stakeholders in the project; defining project's objectives; monitoring project progress; learning; increased empathy; simplicity of the method) and five factors related to successful process mapping exercises (simple and appropriate visual representation, information gathered from multiple stakeholders, facilitator's experience and soft skills, basic training, iterative use of process mapping throughout the project). Conclusions Findings highlight benefits and versatility of process mapping and provide practical suggestions to improve its use in practice.

Criteria for evaluating programme theory diagrams in quality improvement initiatives: a structured method for appraisal.

BACKGROUND: Despite criticisms that many quality improvement (QI) initiatives fail due to incomplete programme theory, there is no defined way to evaluate how programme theory has been articulated. The objective of this research was to develop, and assess the usability and reliability of scoring criteria to evaluate programme theory diagrams. METHODS: Criteria development was informed by published literature and QI experts. Inter-rater reliability was tested between two evaluators. About 63 programme theory diagrams (42 driver diagrams and 21 action-effect diagrams) were reviewed to establish whether the criteria could support comparative analysis of different approaches to constructing diagrams. RESULTS: Components of the scoring criteria include: assessment of overall aim, logical overview, clarity of components, cause-effect relationships, evidence and measurement. Independent reviewers had 78% inter-rater reliability. Scoring enabled direct comparison of different approaches to developing programme theory; action-effect diagrams were found to have had a statistically significant but moderate improvement in programme theory quality over driver diagrams; no significant differences were observed based on the setting in which driver diagrams were developed. CONCLUSIONS: The scoring criteria summarise the necessary components of programme theory that are thought to contribute to successful QI projects. The viability of the scoring criteria for practical application was demonstrated. Future uses include assessment of individual programme theory diagrams and comparison of different approaches (e.g. methodological, teaching or other QI support) to produce programme theory. The criteria can be used as a tool to guide the production of better programme theory diagrams, and also highlights where additional support for QI teams could be needed.

What makes a sustainability tool valuable, practical and useful in real-world healthcare practice? A mixed-methods study on the development of the Long Term Success Tool in Northwest London.

OBJECTIVES: Although improvement initiatives show benefits to patient care, they often fail to sustain. Models and frameworks exist to address this challenge, but issues with design, clarity and usability have been barriers to use in healthcare settings. This work aimed to collaborate with stakeholders to develop a sustainability tool relevant to people in healthcare settings and practical for use in improvement initiatives. DESIGN: Tool development was conducted in six stages. A scoping literature review, group discussions and a stakeholder engagement event explored literature findings and their resonance with stakeholders in healthcare settings. Interviews, small-scale trialling and piloting explored the design and tested the practicality of the tool in improvement initiatives. SETTING: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL). PARTICIPANTS: CLAHRC NWL improvement initiative teams and staff. RESULTS: The iterative design process and engagement of stakeholders informed the articulation of the sustainability factors identified from the literature and guided tool design for practical application. Key iterations of factors and tool design are discussed. From the development process, the Long Term Success Tool (LTST) has been designed. The Tool supports those implementing improvements to reflect on 12 sustainability factors to identify risks to increase chances of achieving sustainability over time. The Tool is designed to provide a platform for improvement teams to share their own views on sustainability as well as learn about the different views held within their team to prompt discussion and actions. CONCLUSION: The development of the LTST has reinforced the importance of working with stakeholders to design strategies which respond to their needs and preferences and can practically be implemented in real-world settings. Further research is required to study the use and effectiveness of the tool in practice and assess engagement with the method over time.

Identifying the challenges and facilitators of implementing a COPD care bundle.

BACKGROUND: Care bundles have been shown to improve outcomes, reduce hospital readmissions and reduce length of hospital stay; therefore increasing the speed of uptake and delivery of care bundles should be a priority in order to deliver more timely improvements and consistent high-quality care. Previous studies have detailed the difficulties of obtaining full compliance to bundle elements but few have described the underlying reasons for this. In order to improve future implementation this paper investigates the challenges encountered by clinical teams implementing a chronic obstructive pulmonary disease (COPD) care bundle and describes actions taken to overcome these challenges. METHODS: An initial retrospective documentary analysis of data from seven clinical implementation teams was undertaken to review the challenges faced by the clinical teams. Three focus groups with healthcare professionals and managers explored solutions to these challenges developed during the project. RESULTS: Documentary analysis identified 28 challenges which directly impacted implementation of the COPD care bundle within five themes; staffing, infrastructure, process, use of improvement methodology and patient and public involvement. Focus groups revealed that the five most significant challenges for all groups were: staff too busy, staff shortages, lack of staff engagement, added workload of the bundle and patient coding issues. The participants shared facilitating factors used to overcome issues including: shifting perceptions to improve engagement, further education sessions to increase staff participation and gaining buy-in from managers through payment frameworks. CONCLUSIONS: Maximising the impact of a care bundle relies on its successful and timely implementation. Teams implementing the COPD care bundle encountered challenges that were common to all teams and sites. Understanding and learning from the challenges faced by previous endeavours and identifying the facilitators to overcoming these barriers provides an opportunity to mitigate issues that waste time and resources, and ensures that training can be tailored to the anticipated challenges.

A systematic review of evidence on the links between patient experience and clinical safety and effectiveness.

OBJECTIVE: To explore evidence on the links between patient experience and clinical safety and effectiveness outcomes. DESIGN: Systematic review. SETTING: A wide range of settings within primary and secondary care including hospitals and primary care centres. PARTICIPANTS: A wide range of demographic groups and age groups. PRIMARY AND SECONDARY OUTCOME MEASURES: A broad range of patient safety and clinical effectiveness outcomes including mortality, physical symptoms, length of stay and adherence to treatment. RESULTS: This study, summarising evidence from 55 studies, indicates consistent positive associations between patient experience, patient safety and clinical effectiveness for a wide range of disease areas, settings, outcome measures and study designs. It demonstrates positive associations between patient experience and self-rated and objectively measured health outcomes; adherence to recommended clinical practice and medication; preventive care (such as health-promoting behaviour, use of screening services and immunisation); and resource use (such as hospitalisation, length of stay and primary-care visits). There is some evidence of positive associations between patient experience and measures of the technical quality of care and adverse events. Overall, it was more common to find positive associations between patient experience and patient safety and clinical effectiveness than no associations. CONCLUSIONS: The data presented display that patient experience is positively associated with clinical effectiveness and patient safety, and support the case for the inclusion of patient experience as one of the central pillars of quality in healthcare. It supports the argument that the three dimensions of quality should be looked at as a group and not in isolation. Clinicians should resist sidelining patient experience as too subjective or mood-oriented, divorced from the 'real' clinical work of measuring safety and effectiveness.

Live imaging of altered period1 expression in the suprachiasmatic nuclei of Vipr2-/- mice.

Vasoactive intestinal polypeptide and its receptor, VPAC(2), play important roles in the functioning of the brain's circadian clock in the suprachiasmatic nuclei (SCN). Mice lacking VPAC(2) receptors (Vipr2(-/-)) show altered circadian rhythms in locomotor behavior, neuronal firing rate, and clock gene expression, however, the nature of molecular oscillations in individual cells is unclear. Here, we used real-time confocal imaging of a destabilized green fluorescent protein (GFP) reporter to track the expression of the core clock gene Per1 in live SCN-containing brain slices from wild-type (WT) and Vipr2(-/-) mice. Rhythms in Per1-driven GFP were detected in WT and Vipr2(-/-) cells, though a significantly lower number and proportion of cells in Vipr2(-/-) slices expressed detectable rhythms. Further, Vipr2(-/-) cells expressed significantly lower amplitude oscillations than WT cells. Within each slice, the phases of WT cells were synchronized whereas cells in Vipr2(-/-) slices were poorly synchronized. Most GFP-expressing cells, from both genotypes, expressed neither vasopressin nor vasoactive intestinal polypeptide. Pharmacological blockade of VPAC(2) receptors in WT SCN slices partially mimicked the Vipr2(-/-) phenotype. These data demonstrate that intercellular communication via the VPAC(2) receptor is important for SCN neurons to sustain robust, synchronous oscillations in clock gene expression.

Functional significance of the uncinate processes in birds.

The functional significance of the uncinate processes to the ventilatory mechanics of birds was examined by combining analytical modeling with morphological techniques. A geometric model was derived to determine the function of the uncinate processes and relate their action to morphological differences associated with locomotor specializations. The model demonstrates that uncinates act as levers, which improve the mechanical advantage for the forward rotation of the dorsal ribs and therefore lowering of the sternum during respiration. The length of these processes is functionally important; longer uncinate processes increasing the mechanical advantage of the Mm. appendicocostales muscle during inspiration. Morphological studies of four bird species showed that the uncinate process increased the mechanical advantage by factors of 2-4. Using canonical variate analysis and analysis of variance we then examined the variation in skeletal parameters in birds with different primary modes of locomotion (non-specialists, walking and diving). Birds clustered together in distinct groups, indicating that uncinate length is more similar in birds that have the same functional constraint, i.e. specialization to a locomotor mode. Uncinate processes are short in walking birds, long in diving species and of intermediate length in non-specialist birds. These results demonstrate that differences in the breathing mechanics of birds may be linked to the morphological adaptations of the ribs and rib cage associated with different modes of locomotion.

Interaction between parental care and sibling competition: parents enhance offspring growth and exacerbate sibling competition.

Species with elaborate parental care often also show intense sibling competition over resources provided by parents, suggesting joint evolution of these two traits. Despite this, the evolution of elaborate parental care and the evolution of intense sibling competition are often studied separately. Here, we examine the interaction between parental food provisioning and sibling competition for resources through the joint manipulation of the presence or absence of parents and brood size in a species with facultative parental care: the burying beetle Nicrophorus vespilloides. The effect of the interaction between the presence or absence of parents and brood size was strong; brood size had a strong effect on growth when parents provided care, but no effect when parents were absent. As in previous studies, offspring grew faster when parents were present than when parents were absent, and offspring grew faster in smaller broods than in larger broods. Our behavioral observations showed that brood size had a negative effect on both the amount of time parents spent providing resources to individual offspring and the offspring's effectiveness of begging, confirming that the level of sibling competition increased with brood size. Furthermore, offspring in larger broods shifted more from begging toward self-feeding as they grew older compared to offspring in small broods. Our study provides novel insights into the joint evolution of parental care and sibling competition, and the evolution of offspring begging signals. We discuss the implications of our results in light of recent theoretical work on the evolution of parental care, sibling competition, and offspring begging signals.