Compassionate practice is expected of Registered Nurses (RNs) around the world while at the same time remaining a contested concept. Nevertheless, student nurses are expected to enact compassionate practice in order to become RNs. In order for this to happen they require professional socialisation within environments where compassion can flourish. However, there is concern that student nurse socialisation is not enabling compassion to flourish and be maintained upon professional qualification. In order to investigate this further, a Glaserian Grounded Theory study was undertaken using in-depth, digitally recorded interviews with student nurses (n=19) at a university in the north of England during 2009 and 2010. Interviews were also undertaken with their nurse teachers (n=5) and data from National Health Service (NHS) patients (n=72,000) and staff (n=290,000) surveys were used to build a contextual picture of the student experience. Within the selected findings presented, analysis of the data indicates that students aspire to the professional ideal of compassionate practice although they have concerns about how compassionate practice might fit within the RN role because of constraints on RN practice. Students feel vulnerable to dissonance between professional ideals and practice reality. They experience uncertainty about their future role and about opportunities to engage in compassionate practice. Students manage their vulnerability and uncertainty by balancing between an intention to uphold professional ideals and challenge constraints, and a realisation they might need to adapt their ideals and conform to constraints. This study demonstrates that socialisation in compassionate practice is compromised by dissonance between professional idealism and practice realism. Realignment between the reality of practice and professional ideals, and fostering student resilience, are required if students are to be successfully socialised in compassionate practice and enabled to retain this professional ideal within the demands of 21st century nursing.

OBJECTIVES This paper examines how the interaction between financial and clinical risk at two critical phases of health care reform in England has been experienced by frontline staff caring for vulnerable patients with long term conditions. METHODS The paper draws on contracting theory and two interdisciplinary and in-depth qualitative research studies undertaken in 1995 and 2007. Methods common to both studies included documentary analysis and interviews with managers and front line professionals. The 1995 study employed action-based research and included observation of community care; the 2007 study used realistic evaluation and included engagement with service user groups. RESULTS In both reform processes, financial risk was increasingly devolved to frontline practitioners and smaller organizational units such as GP commissioning groups, with payment by unit of activity, aimed at changing professionals' behaviour. This financing increased perceived clinical risk and fragmented the delivery of health and social care services requiring staff efforts to improve collaboration and integration, and created some perverse incentives and staff demoralisation. CONCLUSIONS Health services reform should only shift financial risk to frontline professionals to the extent that it can be efficiently borne. Where team work is required, contracts should reward collaborative multi-professional activity.

PURPOSE OF REVIEW: Mood regulation problems, such as severe chronic irritability or short episodes of mania-like symptoms, are common, impairing and a topic of intense recent interest to clinicians, researchers and the Diagnostic and Statistical Manual (DSM)-5 process. Here, we review the most recent findings about these two presentations and discuss the approaches to their treatment. RECENT FINDINGS: Longitudinal and genetic findings suggest that chronic irritability should be regarded as a mood problem that is distinct from bipolar disorder. A proportion of children with short (less than 4 days) episodes of mania-like symptoms seem to progress to classical (Type I or II) bipolar disorder over time in the US clinic samples. In a UK sample, such episodes were independently associated with psychosocial impairment. The evidence base for the treatment of either irritability or short-lived episodes of mania-like symptoms is still small. Clinicians should be cautious with extrapolating treatments from classical bipolar disorder to these mood regulation problems. Cognitive and behavioural therapy (CBT)-based approaches targeting general mood regulation processes may be effective for cases with severe irritability or short episodes of mania-like symptoms. SUMMARY: There is increasing research evidence for the importance of mood regulation problems in the form of either irritability or short episodes of mania-like symptoms in youth. The evidence base for their drug treatment has yet to be developed. CBT-based interventions to modify the processes of mood regulation may be a useful and well tolerated intervention for patients with these presentations.

Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated the hypothesis of a bidirectional link between adipokines and osteocalcin. Materials and Methods. In a cross-sectional study of 294 older patients with osteoporotic hip fracture, we estimated serum concentrations of leptin, adiponectin, resistin, osteocalcin, parameters of mineral metabolism, and renal function. Results. After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with resistin and positively with leptin, leptin/resistin ratio, and adiponectin/resistin ratio. In multivariate regression models, osteocalcin was an independent predictor of serum leptin, resistin, leptin/resistin, and adiponectin/resistin ratios. Conclusions. Our data support the bidirectional regulation between osteocalcin and adipokines, but contrary to the genetically modified animal models, in older subjects with osteoporotic hip fracture, serum osteocalcin is positively associated with leptin and inversely with resistin.

An inventory of topsoil soil organic carbon (SOC) content in household farms was performed in a village from a red earth region in Jiangxi Province, China in 2003. In this region, the farmland managed by each household is fragmented, consisting of several plots of land that are not necessarily adjacent to each other. A statistical analysis of SOC variation with land use and household management type, and with crop management practices was conducted. Plot size ranged from 0·007 to 0·630 ha with a mean of 0·1 ha, and SOC content ranged from 1·72 to 25·2 g/kg, varying widely with a variety of land management and agricultural practices, arising from individual household behaviours. The mean SOC content in plot size <0·1 ha was 20% lower than in plot size ⩾0·1 ha. SOC of dry crop plots was 70% lower than that in rice paddies, and SOC of plots contracted from the village was almost double that of plots leased from other householders. Moreover, a 30% increase in SOC was observed with green manure cultivation, and a 55% increase under triple cropping. The difference in SOC levels between the least and most favourable cases of household land management and agricultural practice was up to 150%. The results suggest that policies targeted at crop management alone may not deliver the expected SOC benefits if household land management is also not improved.

Purpose: This study explores what individuals with spinal cord injury (SCI) perceive to be the benefits of becoming involved in organized sport and identifies the barriers to participation. Method: Seven SCI athletes from a variety of sports were interviewed in a semi-structured format. Results: 20 benefits and 18 individual barriers were identified and categorized into sub-themes: benefits were categorized into sub-themes of "socialization,""self-worth,""physical challenge" and "emotional." Barriers were grouped into "organization,""medical,""emotional,""a lack of available information" and "views held by others." Conclusion: A variety of benefits from participating in sport were identified, including socialization, the acquisition of knowledge from others, the development of greater awareness of health and well-being issues, weight maintenance, functional development and independence. Barriers identified included financial constraints, the lack of information regarding medical complications and sporting opportunities, and the need for able-bodied support. The findings have implications for the rehabilitation of individuals with SCI.[Box: see text].

Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.

Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R(2) = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array.

The in vivo biological activities of IgG antibodies result from their bifunctional nature, in which antigen recognition by the Fab is coupled to the effector and immunomodulatory diversity found in the Fc domain. This diversity, resulting from both amino acid and glycan heterogeneity, is translated into cellular responses through Fcγ receptors (FcγRs), a structurally and functionally diverse family of cell surface receptors found throughout the immune system. Although many of the overall features of this system are maintained throughout mammalian evolution, species diversity has precluded direct analysis of human antibodies in animal species, and, thus, detailed investigations into the unique features of the human IgG antibodies and their FcγRs have been limited. We now report the development of a mouse model in which all murine FcγRs have been deleted and human FcγRs, encoded as transgenes, have been inserted into the mouse genome resulting in recapitulation of the unique profile of human FcγR expression. These human FcγRs are shown to function to mediate the immunomodulatory, inflammatory, and cytotoxic activities of human IgG antibodies and Fc engineered variants and provide a platform for the detailed mechanistic analysis of therapeutic and pathogenic IgG antibodies.

This analysis was conducted to determine whether the HCV viral kinetics (VK) model can predict viral load (VL) decreases for non-nucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after three-day monotherapy studies of patients infected with genotype 1 chronic hepatitis C virus (HCV). This analysis includes data for 8 NNPolIs and 14 PIs: VL decreases from three-day monotherapy, total plasma trough concentrations on Day 3, replicon data (EC50 and protein-shifted EC50, EC50(PS)), and for PIs, liver-to-plasma ratios (LPRs) measured in vivo in preclinical species. VK model simulations suggested that achieving additional log(10) VL decreases greater than one required 10-fold increases in Cmin. NNPolI and PI data further supported this result. The VK model was successfully used to predict VL decreases in three-day monotherapy for NNPolIs based on the EC50(PS) and the Day 3 Cmin. For PIs, however, predicting VL decreases using the same model and the EC50(PS) and Day 3 Cmin was not successful; a model including LPR values and the EC50 instead of the EC50(PS) provided a better prediction of VL decrease. These results are useful for designing phase 1 monotherapy studies for NNPolIs and PIs by clarifying factors driving VL decreases such as the Day 3 Cmin and the EC50(PS) for NNPolIs or the EC50 and LPR for PIs. This work provides a framework for understanding the PK/PD for other HCV drug classes. Availability of mechanistic data on processes driving the target concentration, such as liver uptake transporters, should help to improve the predictive power of the approach.