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Addressing respect, gender equity and gender-based violence in schools has a long history. Renewed government efforts to address gender-based violence in schools through a whole school approach hav...

Issue addressed Our Watch led a complex 12-month evaluation of a whole school approach to Respectful Relationships Education (RRE) implemented in 19 schools. RRE is an emerging field aimed at preventing gender-based violence. This paper will illustrate how from an implementation science perspective, the evaluation was a critical element in the change process at both a school and policy level. Methods Using several conceptual approaches from systems science, the evaluation sought to examine how the multiple systems layers - student, teacher, school, community and government - interacted and influenced each other. A distinguishing feature of the evaluation included 'feedback loops'; that is, evaluation data was provided to participants as it became available. Evaluation tools included a combination of standardised surveys (with pre- and post-intervention data provided to schools via individualised reports), reflection tools, regular reflection interviews and summative focus groups. Results Data was shared during implementation with project staff, department staff and schools to support continuous improvement at these multiple systems levels. In complex settings, implementation can vary according to context; and the impact of evaluation processes, tools and findings differed across the schools. Interviews and focus groups conducted at the end of the project illustrated which of these methods were instrumental in motivating change and engaging stakeholders at both a school and departmental level and why. Conclusion The evaluation methods were a critical component of the pilot's approach, helping to shape implementation through data feedback loops and reflective practice for ongoing, responsive and continuous improvement. Future health promotion research on complex interventions needs to examine how the evaluation itself is influencing implementation. So what? The pilot has demonstrated that the evaluation, including feedback loops to inform project activity, were an asset to implementation. This has implications for other health promotion activities, where evaluation tools could be utilised to enhance, rather than simply measure, an intervention. The findings are relevant to a range of health promotion research activities because they demonstrate the importance of meta-evaluation techniques that seek to understand how the evaluation itself was influencing implementation and outcomes.

Summary Many small scale efficacious programs and interventions need to be ‘scaled-up’ in order to reach a larger population. Although it has been argued that interventions deemed suitable for upscaling need to have demonstrated effectiveness, be able to be implemented cost-effectively and be accepted by intended recipients, these factors alone are insufficient in explaining which programs are adopted more broadly. Upscaling research often identifies political will as a key factor in explaining whether programs are supported and up-scaled, but this research lacks any depth into how political will is formed and has not applied policy theories to understanding the upscaling process. This article uses a political science lens to examine the key factors in the upscaling process of a Respectful Relationships in Schools Program. Focus groups and interviews were conducted with project staff, managers and community organizations involved in the program. The results reveal how a key focusing event related to a highly profiled personal tragedy propelled family violence into the national spotlight. At the same time, the organization leading the respectful relationships program leveraged their networks to position the program within the education department which enabled the government to quickly respond to the issue. The study highlights that political will is not a stand-alone factor as depicted by up-scaling models, but rather is the end point of a complex process that involves many elements including the establishment of networks and aligned programs that can capitalize when opportunities arise.

ISSUE ADDRESSED Implementation fidelity relates to the degree of adherence to implementation protocols and content and helps to guide replication of evidence-based programs. In settings-based research, notions of fidelity have been applied more often to delivery of education content rather than whole of setting change. The aims of this paper were firstly, to analyse how contextual factors influenced implementation of a whole school program on respectful relationships education, and secondly given the findings, discuss whether a more flexible approach to implementation fidelity may have yielded increased school engagement. METHODS The project was conducted in 19 secondary schools in Victoria in 2015. This paper reports on focus groups and interviews which were conducted with 81 school staff and 28 staff from the lead agency, community agency partners, and departmental staff to understand the contextual factors influencing implementation. RESULTS The program followed a traditional implementation fidelity approach of considering core elements and some minor scope for adaption which engaged some regions and schools but not others. CONCLUSION An alternative notion of implementation fidelity, "fidelity to function," may have permitted increased flexibility to tailor the intervention components to suit different school and community contexts and potentially, increasing both the reach and impact of the program. SO WHAT?: Understanding how to apply notions of fidelity to guide whole of setting change are important considerations if programs are to be replicated to have wider reach and greater impact and effectiveness.

Issue addressed Our Watch led a complex 12-month evaluation of a whole school approach to Respectful Relationships Education (RRE) implemented in 19 schools. RRE is an emerging field aimed at preventing gender-based violence. This paper will illustrate how from an implementation science perspective, the evaluation was a critical element in the change process at both a school and policy level. Methods Using several conceptual approaches from systems science, the evaluation sought to examine how the multiple systems layers - student, teacher, school, community and government - interacted and influenced each other. A distinguishing feature of the evaluation included 'feedback loops'; that is, evaluation data was provided to participants as it became available. Evaluation tools included a combination of standardised surveys (with pre- and post-intervention data provided to schools via individualised reports), reflection tools, regular reflection interviews and summative focus groups. Results Data was shared during implementation with project staff, department staff and schools to support continuous improvement at these multiple systems levels. In complex settings, implementation can vary according to context; and the impact of evaluation processes, tools and findings differed across the schools. Interviews and focus groups conducted at the end of the project illustrated which of these methods were instrumental in motivating change and engaging stakeholders at both a school and departmental level and why. Conclusion The evaluation methods were a critical component of the pilot's approach, helping to shape implementation through data feedback loops and reflective practice for ongoing, responsive and continuous improvement. Future health promotion research on complex interventions needs to examine how the evaluation itself is influencing implementation. So what? The pilot has demonstrated that the evaluation, including feedback loops to inform project activity, were an asset to implementation. This has implications for other health promotion activities, where evaluation tools could be utilised to enhance, rather than simply measure, an intervention. The findings are relevant to a range of health promotion research activities because they demonstrate the importance of meta-evaluation techniques that seek to understand how the evaluation itself was influencing implementation and outcomes.

Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues. The availability of inhalation devices and unmet medical need in lung disease has focused efforts in this tissue. We report the development of a novel cell sorting method for quantitative, cell type-specific analysis of siRNA, and locked nucleic acid (LNA) ASO uptake and efficacy after intratracheal (i.t.) administration in mice. Through fluorescent dye labeling, we compare the utility of this approach to whole animal and whole tissue analysis, and examine the extent of tissue distribution. We detail rapid systemic access and renal clearance for both therapeutic classes and lack of efficacy at the protein level in lung macrophages, epithelia, or other cell types. We nevertheless observe efficient redirection of i.t. administered phosphorothioate (PS) LNA ASO to the liver and kidney leading to targeted gene knockdown. These data suggest delivery remains a key obstacle to topically administered, naked oligonucleotide efficacy in the lung and introduce inhalation as a potentially viable alternative to injection for antisense administration to the liver and kidneys.

Objective In completing this review, we aim to educate readers about the physiological importance of the hormone prolactin (PRL) in the treatment of patients with anorexia nervosa (AN). Method A comprehensive review of PRL was undertaken using existing published literature with specific focus on domains pertinent to the treatment of AN. Results Prolactin influences multiple biological processes throughout the body. Disruption in its regulation can impact women's health issues such as menstruation and bone health, which are pertinent to AN treatment. The use of antipsychotics with high D2 receptor affinity for the augmented treatment of AN increases the potential risk of PRL-mediated adverse effects. Discussion Although not intrinsic to underlying disease underpinnings, PRL has the capacity to affect and influence multiple outcome variables in treatment of patients with AN. Improved understanding, better screening and the completion of further prospective research are necessary to help facilitate and incorporate ongoing knowledge translation. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each chain that antagonises the action of the eosinophil-specific cytokine, interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides derived from AF18748 and demonstrated that the first five amino acids of the peptide do not contribute to receptor binding activity. The shortened peptide blocked IL-5-dependent adhesion of eosinophils with an IC50of 350 pM, and had no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-α or fMet-Leu-Phe. The peptides were rapidly broken down in mouse plasma through cleavage of a single chain of the dimer. However, this breakdown did not correlate with loss of biological activity, indicating that the asymmetric peptide fragment retains full receptor binding capacity. The activity of AF18748 disappeared rapidly from the blood following intravenous injection into mice. Coupling of polyethylene glycol to the N-terminus of AF18748 resulted in a moderate loss in biological potency (IC5030 nM), but the resulting conjugate persisted in the circulation for more than 8 h after injection. Despite its high potency at the human IL-5 receptor, AF18748 was unable to antagonise the activity of IL-5 on murine B13 cells, or on canine eosinophils, indicating that the peptide is highly specific for the human IL-5 receptor.

In completing this review, we aim to educate readers about the physiological importance of the hormone prolactin (PRL) in the treatment of patients with anorexia nervosa (AN).A comprehensive review of PRL was undertaken using existing published literature with specific focus on domains pertinent to the treatment of AN.Prolactin influences multiple biological processes throughout the body. Disruption in its regulation can impact women's health issues such as menstruation and bone health, which are pertinent to AN treatment. The use of antipsychotics with high D2 receptor affinity for the augmented treatment of AN increases the potential risk of PRL-mediated adverse effects.Although not intrinsic to underlying disease underpinnings, PRL has the capacity to affect and influence multiple outcome variables in treatment of patients with AN. Improved understanding, better screening and the completion of further prospective research are necessary to help facilitate and incorporate ongoing knowledge translation.

Pulmonary rehabilitation helps improve quality of life for people with COPD, writes.

A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.

The Aurora kinases have been the subject of considerable interest as targets for the development of new anticancer agents. While evidence suggests inhibition of Aurora B kinase gives rise to the more pronounced antiproliferative phenotype, the most clinically advanced agents reported to date typically inhibit both Aurora A and B. We have discovered a series of pyrazoloquinazolines, some of which show greater than 1000-fold selectivity for Aurora B over Aurora A kinase activity, in recombinant enzyme assays. These compounds have been designed for parenteral administration and achieve high levels of solubility by virtue of their ability to be delivered as readily activated phosphate derivatives. The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous pharmacokinetic properties and safety pharmacology profiles. The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials.