Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

Unintended Consequences of Incentive Provision for Behaviour Change and Maintenance around Childbirth

Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation

ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination

Female leadership in French voluntary associations

Drawing on a recent national survey, this paper focuses on the female representation on executive committees in French voluntary associations. To begin with, we observe that this representation is very unequal according to the different officer positions. It is especially low among presidents. Then we study the relationship between the associations' attributes and the likelihood of women being appointed as executive committee members. We notice that the probabilities that women hold president, treasurer and secretary positions are highly correlated to each other. We find that the proportion of female officers is higher in organizations whose activities pertain to social service, health and humanitarian sectors. It is lower in the oldest associations and it decreases as their geographical area of activity increases and as their budget becomes larger. The probability that associations have female presidents is higher in associations with few volunteers

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

Functional Deficits in nNOSμ-Deficient Skeletal Muscle: Myopathy in nNOS Knockout Mice

Skeletal muscle nNOSμ (neuronal nitric oxide synthase mu) localizes to the sarcolemma through interaction with the dystrophin-associated glycoprotein (DAG) complex, where it synthesizes nitric oxide (NO). Disruption of the DAG complex occurs in dystrophinopathies and sarcoglycanopathies, two genetically distinct classes of muscular dystrophy characterized by progressive loss of muscle mass, muscle weakness and increased fatigability. DAG complex instability leads to mislocalization and downregulation of nNOSμ; but this is thought to play a minor role in disease pathogenesis. This view persists without knowledge of the role of nNOS in skeletal muscle contractile function in vivo and has influenced gene therapy approaches to dystrophinopathy, the majority of which do not restore sarcolemmal nNOSμ. We address this knowledge gap by evaluating skeletal muscle function in nNOS knockout (KN1) mice using an in situ approach, in which the muscle is maintained in its normal physiological environment. nNOS-deficiency caused reductions in skeletal muscle bulk and maximum tetanic force production in male mice only. Furthermore, nNOS-deficient muscles from both male and female mice exhibited increased susceptibility to contraction-induced fatigue. These data suggest that aberrant nNOSμ signaling can negatively impact three important clinical features of dystrophinopathies and sarcoglycanopathies: maintenance of muscle bulk, force generation and fatigability. Our study suggests that restoration of sarcolemmal nNOSμ expression in dystrophic muscles may be more important than previously appreciated and that it should be a feature of any fully effective gene therapy-based intervention

PathogenMip Assay: A Multiplex Pathogen Detection Assay

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe

Understanding emotionally relevant situations in primary care dental practice: 1. Clinical situations and emotional responses

Background and aims. The stressful nature of dental practice is well established. Much less information is available on the coping strategies used by dentists and the emotions which underlie the stressful experience. Previous research has been almost exclusively questionnaire-based, limiting the range of emotions explored. This study used qualitative methods to explore the full extent of emotions and coping strategies associated with stressful events in primary dental practice. Method. Semi-structured interviews were conducted with 20 dentists in Lincoln and the surrounding area. Verbatim transcriptions were analysed using thematic analysis. Results. Participants reported a wide variety of stressful situations, consistent with the existing literature, which were associated with a diverse range of negative emotional responses including anxiety, anger and sadness. Dentists tended to have more difficulty identifying positive events and emotions. The designation of a situation as stressful or otherwise was dependent on the dentist's personal interpretation of the event. Data relating to the effects of stressors and the coping strategies used by dentists will be presented in subsequent papers. Conclusion. The situations which dentists find difficult are accompanied by a diverse set of emotions, rather than omnipresent 'stress.' This has implications for stress management programmes for those in dental practic