Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase

Human 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme for repairing 8-oxoguanine (8-oxoG), a mutagenic guanine base lesion produced by reactive oxygen species (ROS). A frequently occurring OGG1 polymorphism in human populations results in the substitution of serine 326 for cysteine (S326C). The 326 C/C genotype is linked to numerous cancers, although the mechanism of carcinogenesis associated with the variant is unclear. We performed detailed enzymatic studies of polymorphic OGG1 and found functional defects in the enzyme. S326C OGG1 excised 8-oxoG from duplex DNA and cleaved abasic sites at rates 2- to 6-fold lower than the wild-type enzyme, depending upon the base opposite the lesion. Binding experiments showed that the polymorphic OGG1 binds DNA damage with significantly less affinity than the wild-type enzyme. Remarkably, gel shift, chemical cross-linking and gel filtration experiments showed that S326C both exists in solution and binds damaged DNA as a dimer. S326C OGG1 enzyme expressed in human cells was also found to have reduced activity and a dimeric conformation. The glycosylase activity of S326C OGG1 was not significantly stimulated by the presence of AP-endonuclease. The altered substrate specificity, lack of stimulation by AP-endonuclease 1 (APE1) and anomalous DNA binding conformation of S326C OGG1 may contribute to its linkage to cancer incidence

Rotating superfluids in anharmonic traps: From vortex lattices to giant vortices

We study a superfluid in a rotating anharmonic trap and explicate a rigorous proof of a transition from a vortex lattice to a giant vortex state as the rotation is increased beyond a limiting speed determined by the interaction strength. The transition is characterized by the disappearance of the vortices from the annulus where the bulk of the superfluid is concentrated due to centrifugal forces while a macroscopic phase circulation remains. The analysis is carried out within two-dimensional Gross-Pitaevskii theory at large coupling constant and reveals significant differences between 'soft' anharmonic traps (like a quartic plus quadratic trapping potential) and traps with a fixed boundary: In the latter case the transition takes place in a parameter regime where the size of vortices is very small relative to the width of the annulus whereas in 'soft' traps the vortex lattice persists until the width of the annulus becomes comparable to the vortex cores. Moreover, the density profile in the annulus where the bulk is concentrated is, in the 'soft' case, approximately gaussian with long tails and not of the Thomas-Fermi type like in a trap with a fixed boundary.Comment: Published version. Typos corrected, references adde

Synthesising conceptual frameworks for patient and public involvement in research - A critical appraisal of a meta-narrative review

© 2018 The Author(s). Background: A number of conceptual frameworks for patient and public involvement (PPI) in research have been published in recent years. Although some are based on empirical research and/or existing theory, in many cases the basis of the conceptual frameworks is not evident. In 2015 a systematic review was published by a collaborative review group reporting a meta-narrative approach to synthesise a conceptual framework for PPI in research (hereafter 'the synthesis'). As the first such synthesis it is important to critically scrutinise this meta-narrative review. The 'RAMESES publication standards for meta-narrative reviews' provide a framework for critically appraising published meta-narrative reviews such as this synthesis, although we recognise that these were published concurrently. Thus the primary objective of this research was to appraise this synthesis of conceptual frameworks for PPI in research in order to inform future conceptualisation. Methods: Four researchers critically appraised the synthesis using the RAMESES publication standards as a framework for assessment. Data were extracted independently using a data extraction form closely based on the RAMESES publication standards. Each item from the standards was assessed on a four point scale (0 = unmet, 1 = minimally met, 2 = partly met, 3 = fully met). The four critical appraisals were then compared and any differences resolved through discussion. Results: A good degree of inter-rater reliability was found. A consensus assessment of the synthesis as a meta-narrative review of PPI conceptual frameworks was achieved with an average of '1' (minimally met) across all 20 items. Two key items ('evidence of adherence to guiding principles of meta-narrative review' and 'analysis and synthesis processes') were both wholly unmet. Therefore the paper did not meet our minimum requirements for a meta-narrative review. We found the RAMESES publication standards were a useful tool for carrying out a critical appraisal although some minor improvements are suggested. Conclusions: Although the aims of the authors' synthesis were commendable, and the conceptual framework presented was coherent and attractive, the paper did not demonstrate a transparent and replicable meta-narrative review approach. There is a continuing need for a more rigorous synthesis of conceptual frameworks for PPI

Engaging rural communities health policy

Aims & Rationale: The Alma-Ata Declaration espouses participation as a right for all citizens and important in the provision of primary health care. Australian health policy discourse encourages citizen engagement, but the extent to which this actually occurs remains unclear. Citizen engagement potentially offers considerable benefits for rural communities – a population with known health disadvantages. Drawing on results of a research project exploring the health policy implications for rural maternity care, this paper aims to (a) discuss the extent of community participation found in four rural north Queensland towns; and (b)consider how policy discourse around citizen engagement may be applied to rural health policies. Methods: Case studies of four rural north Queensland towns were completed. Observational, interview and documentary data were collected and qualitatively analysed via an inductive thematic technique. Findings: The case studies provided little indication of formal mechanisms through which community members could provide input to local health service delivery. Two communities demonstrated rapid mobilisation to rally and apply political pressure when their health services were threatened, but a distinction must be made between community action and true engagement processes. While mindful of the benefits, interviewees at all sites were particularly concerned about the barriers to successful community engagement, including: (i) overcoming community scepticism; (ii) concerns about representativeness; and (iii) community capacity. Benefits to the community: For rural communities, citizen engagement may have particular advantages in enhancing the appropriateness and responsiveness of local health services. Recommendations are made for improving rural communities' input to health policies which affect them

Health policy: understanding outcomes for rural maternity care

Aims and rationale: Despite government commitments to improve rural residents' access to health services, 42% of rural maternity units throughout Queensland have closed over the last 10 years. Such closures raise concerns about equity of access and quality of maternity care for rural communities. There is little literature available which discusses the impact of health policies on rural residents' experiences of accessing maternity care, or the experiences of the health professionals who provide these services. The aims of this study are twofold: (a) critically review government health policies relevant to rural maternity care; and (b) investigate the correlation between health policy discourse and the lived experiences of rural communities in providing and accessing maternity services. Approaches: Relevant Commonwealth and Queensland health policies were identified and critically reviewed. A case study approach was then used to explore the lived experiences of both providers (midwives, GP proceduralists, hospital administrators) and users (community members) of maternity care in four rural, north Queensland towns. Data comprised documentary evidence, interviews with service providers and focus groups with community members. Findings: The reduction of rural maternity services was found to have profound, multifaceted effects on local communities. Lived experiences and policy-related outcomes are discussed within four topic areas: workforce; community engagement; quality and safety of care. Benefits to the community: Understanding policy outcomes for rural maternity units should inform the development of future health policies. Recommendations are aimed at enhancing maternity care provision and access in rural communities

Health policy: outcomes for rural residents’ access to maternity care

Regular health care during pregnancy, birthing and the postnatal period is recommended for improving maternal and neonatal outcomes and accessing such care has become a common expectation for Australian families. Studies have highlighted the relative safety of birthing in rural hospitals even though these units are typically associated with low volumes of deliveries. Yet, in Queensland, the location and number of public maternity units shows a clear trend towards centralisation of services. During 1995- 2005, 43% of Queensland public maternity units closed, with the remaining units predominantly located in coastal and more populated locations. The closure of rural maternity units is not restricted to Queensland: the National Rural Health Alliance estimated 130 rural maternity units had closed across Australia throughout the decade 1996-20065. Growing numbers of closed rural maternity units raises considerable questions regarding the care accessed by rural residents. This paper presents findings from research conducted in north Queensland which examined the impact of health policy on an issue that is of central importance to rural communities—access to birthing services. A multi-dimensional understanding of access to maternity services was adopted in this study, a view which goes beyond measuring access only in terms of geographic distance. Gulliford et al have provided a constructive discussion of the multifaceted nature of access, particularly the differentiation between ‘having access’ and ‘gaining access’ to health care. Having access implies that a person has the opportunity to use a health service if they need or want it. This type of access is often measured in terms of doctors or hospital beds per capita and is dependent on the provision, and geographical allocation of resources, as well as the actual configuration of the network of health services. The authors draw attention to Mooney’s proposition that equal costs in using a service (eg costs of care, costs of travel, lost work) indicates equal access to services. On the other hand, gaining access to health care can be complicated by a variety of barriers including those of a personal nature (eg patients recognising their need to access health care); financial (that is, costs to be borne by the potential patient) or organisational (eg waiting lists)