What guides back pain care? A content analysis of low back pain directives in the Australian context.

BACKGROUND: Low back pain (LBP) is a major cause of disease burden around the world. There is known clinical variation in how LBP is treated and addressed; with one cited reason the lack of availability, or use of, evidence-based guidance for clinicians, consumers, and administrators. Despite this a considerable number of policy directives such as clinical practice guidelines, models of care and clinical tools with the aim of improving quality of LBP care do exist. Here we report on the development of a repository of LBP directives developed in the Australian health system and a content analysis of those directives aimed at deepening our understanding of the guidance landscape. Specifically, we sought to determine: (1) What is the type, scale, and scope of LBP directives available? (2) Who are the key stakeholders that drive low back pain care through directives? (3) What content do they cover? (4) What are their gaps and deficiencies? METHODS: We used online web search and snowballing methods to collate a repository of LBP policy documents collectively called 'directives' including Models of Care (MOC), information sheets, clinical tools, guidelines, surveys, and reports, from the last 20 years. The texts of the directives were analysed using inductive qualitative content analysis adopting methods from descriptive policy content analysis to categorise and analyse content to determine origins, actors, and themes. RESULTS: Eighty-four directives were included in our analysis. Of those, 55 were information sheets aimed at either healthcare providers or patients, nine were clinical tools, three were reports, four were guidelines, four were MOC, two were questionnaires and five were referral forms/criteria. The three main categories of content found in the directives were 1. Low back pain features 2. Standards for clinical encounters and 3. Management of LBP, each of which gave rise to different themes and subthemes. Universities, not-for-profit organizations, government organisations, hospitals/Local Health Districts, professional organisations, consumers, and health care insurers were all involved in the production of policy directives. However, there were no clear patterns of roles, responsibilities or authority between these stakeholder groups. CONCLUSION: Directives have the potential to inform practice and to contribute to reducing evidence-policy-practice discordance. Documents in our repository demonstrate that while a range of directives exist across Australia, but the evidence base for many was not apparent. Qualitative content analysis of the directives showed that while there has been increasing attention given to models of care, this is not yet reflected in directives, which generally focus on more specific elements of LBP care at the individual patient and practitioner level. The sheer number and variety of directives, from a wide range of sources and various locations within the Australian health system suggests a fragmented policy landscape without clear authoritative sources. There is a need for clearer, easily accessible trustworthy policy directives that are regularly reviewed and that meet the needs of care providers, and information websites need to be evaluated regularly for their evidence-based nature and quality.

Protecting children from unhealthy food marketing: a comparative policy analysis in Australia, Fiji and Thailand.

Restrictions on marketing of unhealthy foods and beverages to children is a globally recommended policy measure to improve diets and health. The aim of the analysis was to identify opportunities to enable policy learning and shift beliefs of relevant actors, to engender policy progress on restrictions on marketing of unhealthy foods to children. We drew on the Advocacy Coalition Framework to thematically analyse data from qualitative policy interviews conducted Australia (n = 24), Fiji (n = 10) and Thailand (n = 20). In all three countries two clear and opposing advocacy coalitions were evident within the policy subsystem related to regulation of unhealthy food marketing, which we termed the 'strengthen regulation' and 'minimal/self regulation' coalitions. Contributors to policy stasis on this issue were identified as tensions between public health and economic objectives of government, and limited formal and informal spaces for productive dialogue. The analysis also identified opportunities for policy learning that could enable policy progress on restrictions on marketing of unhealthy foods to children as: taking an incremental approach to policy change, defining permitted (rather than restricted) foods, investing in new public health expertise related to emerging marketing approaches and scaling up of monitoring of impacts. The insights from this study are likely to be relevant to many countries seeking to strengthen regulation of marketing to children, in response to recent global recommendations.

A second riboflavin import system is present in flavinogenic Streptomyces davaonensis and supports roseoflavin biosynthesis.

The antibiotic roseoflavin is produced by Streptomyces davaonensis in the stationary phase of growth. To support biosynthesis of the secondary metabolite roseoflavin, S. davaonensis underwent several genetic adaptations with regard to metabolism of the roseoflavin precursor and primary metabolite riboflavin. In addition to 17 riboflavin biosynthesis genes at different chromosomal locations, S. davaonensis contains the riboflavin transporter gene ribM being part of the riboflavin biosynthetic operon ribE1MAB5H. Deletion of this operon generated riboflavin auxotrophic S. davaonensis strains. The finding that S. davaonensis ΔribE1MAB5H was able to grow in a culture medium containing low levels of riboflavin indicated that in addition to RibM, a second riboflavin transporter is present in this bacterium. The S. davaonensis genes ribXY (former rosXY) represented candidate genes for such a second riboflavin transport system and the results of our experiments now show that RibXY from S. davaonensis is a highly efficient riboflavin importer but not a roseoflavin importer.

Implementation Initiatives to Improve Low Back Pain Care in Australia: A Scoping Review.

OBJECTIVE: This scoping review aimed to comprehensively review strategies for implementation of low back pain (LBP) guidelines, policies, and models of care in the Australian health care system. METHODS: A literature search was conducted in MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, and Web of Science to identify studies that aimed to implement or integrate evidence-based interventions or practices to improve LBP care within Australian settings. RESULTS: Twenty-five studies met the inclusion criteria. Most studies targeted primary care settings (n = 13). Other settings included tertiary care (n = 4), community (n = 4), and pharmacies (n = 3). One study targeted both primary and tertiary care settings (n = 1). Only 40% of the included studies reported an underpinning framework, model, or theory. The implementation strategies most frequently used were evaluative and iterative strategies (n = 14, 56%) and train and educate stakeholders (n = 13, 52%), followed by engage consumers (n = 6, 24%), develop stakeholder relationships (n = 4, 16%), change in infrastructure (n = 4, 16%), and support clinicians (n = 3, 12%). The most common implementation outcomes considered were acceptability (n = 11, 44%) and adoption (n = 10, 40%), followed by appropriateness (n = 7, 28%), cost (n = 3, 12%), feasibility (n = 1, 4%), and fidelity (n = 1, 4%). Barriers included time constraints, funding, and teamwork availability. Facilitators included funding and collaboration between stakeholders. CONCLUSIONS: Implementation research targeting LBP appears to be a young field, mostly focusing on training and educating stakeholders in primary care. Outcomes on sustainability and penetration of evidence-based interventions are lacking. There is a need for implementation research guided by established frameworks that consider interrelationships between organizational and system contexts beyond the clinician-patient dyad.

Moving from silos to synergies: strengthening governance of food marketing policy in Thailand.

BACKGROUND: Governance processes play an important role in shaping the formulation and implementation of policy measures such as restrictions on marketing of ultra-processed foods. However, there is limited analysis of the factors that affect governance for nutrition, especially in low- and middle-income countries such as Thailand and the Southeast Asia region. This study aimed to examine governance factors that create opportunities and challenges for the introduction of policy to restrict food marketing in Thailand, in line with the WHO recommendations to restrict food marketing to children. METHODS: A qualitative study design was used. Interviews were conducted with 20 actors with experience and in depth knowledge of food marketing in Thailand, including government, civil society, industry and international organisations. Open questions were asked about experiences and perceptions of the governance processes related to policies for restricting food marketing in Thailand. Themes were derived from the 3-i Framework which relates to interests, ideas and institutions influencing the introduction of food marketing policy were identified and analysed using abductive methods. RESULTS: Actors viewed institutional challenges as a significant barrier to advancing effective regulation of food marketing. Three major clusters emerged from the data: interests (priorities, relationships), institutions (formal structures, informal structures, broader institutional strategies), and ideas (norms). The study has three major findings in relation to these factors, highlighting the influence of formal structures, institutional interests in food marketing issues, and ideas in promoting multisectoralism. The siloed nature of policymaking was reflected in the government failing to stimulate engagement among key actors, posing challenges for implementation of effective policy change. Contested interests led to disagreements between actors over food marketing agenda and thus competing policy priorities. Consistent with these findings, the lack of effective mechanisms to promote multisectoral coordination across diverse actors reinforced barriers to policy change. CONCLUSION: The findings highlight ongoing challenges to the government's aim to strengthen policy to restrict food marketing which, without greater coordination in governance mechanisms, will hinder effective regulation and the achievement of public health goals. This analysis suggests that the Government should prioritise the development of a holistic, multisectoral approach to improve governance for better nutrition outcomes by overcoming policy silos.

Towards reconciling population nutrition goals and investment policy in Thailand: understanding how investment policy actors defined, framed and prioritised nutrition.

BACKGROUND: Government's investment policy is an important driver of food system activities, which in turn influence consumers practices, dietary consumption patterns and nutrition-related health of populations. While governments globally have committed to developing coherent public policies to advance population nutrition, the objectives of investment policies are seen as being divorced from nutrition and health goals. This study aimed to examine investment policy in Thailand and explore how key actors variously define and frame their objectives in food investment policy, how nutrition issues are represented by the actors, and what discursive effects of the nutrition results were represented within the field of investment in Thailand. METHODS: This study conducted semi-structured interviews with 16 actors (from 23 recruited actors) from government, civil society, academia and industry. A coding framework was developed based on Bacchi's analytical framework encapsulated in the question "What's the problem represented to be?" which examines the problem and assumptions underlying a policy. Data coding was first undertaken by a lead researcher and then double-coded and cross-checked by research team. Disagreements were resolved with discussion until consensus was achieved. The interview data were analysed using thematic analysis. RESULTS: The principal "problem" represented in food investment policy in Thailand was the perceived irrelevance of nutrition to governmental commitments towards increasing productivity and economic growth. Technological innovation in food production and processing such as ultra-processed foods was perceived as a key driver of economic growth. The key assumption underlying this representation was the primacy of a "productivist" policy paradigm, via which the government focuses on industrially driven food and agriculture and expansion to increase productivity and economic growth. This entails that the nutrition needs of Thai people are silenced and remain unacknowledged in investment policy contexts, and also does not take cognisance of the term "nutrition" and its importance to economic growth. CONCLUSION: The findings show that nutrition was not perceived as a political priority for the government and other investment actors. Promoting productivity and economic growth were clearly positioned as the primary purposes of investment within the dominant discourse. Nutrition regulation, particularly of UPF, may conflict with current investment policy directions which prioritise development of modern food production and processing. The study suggests that comprehensive policy communication about nutrition and food classification is needed.

Building evidence into youth health policy: a case study of the Access 3 knowledge translation forum.

BACKGROUND: Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process. METHODS: The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017-2024. RESULTS: A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively. CONCLUSIONS: The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts.

The novel phosphatase RosC catalyzes the last unknown step of roseoflavin biosynthesis in Streptomyces davaonensis.

The bacterium Streptomyces davaonensis produces the antibiotic roseoflavin, which is a riboflavin (vitamin B2 ) analog. The key enzyme of roseoflavin biosynthesis is the 8-demethyl-8-amino-riboflavin-5'-phosphate (AFP) synthase RosB which synthesizes AFP from riboflavin-5'-phosphate. AFP is not a substrate for the last enzyme of roseoflavin biosynthesis the N, N-dimethyltransferase RosA, which generates roseoflavin from 8-demethyl-8-amino-riboflavin (AF). Consequently, the roseoflavin biosynthetic pathway depends on a phosphatase, which dephosphorylates AFP to AF. Here, we report on the identification and characterization of such an AFP phosphatase which we named RosC. The gene rosC is located immediately downstream of rosA and both genes are part of a cluster comprising 10 genes. Deletion of rosC from the chromosome of S. davaonensis led to reduced roseoflavin levels in the corresponding recombinant strain. In contrast to wild-type S. davaonensis, cell-free extracts of the rosC deletion strain did not catalyze dephosphorylation of AFP. RosC was purified from an overproducing Escherichia coli strain. RosC is the fastest enzyme of roseoflavin biosynthesis (kcat 31.3 ± 1.4 min-1 ). The apparent KM for the substrate AFP was 34.5 µM. Roseoflavin biosynthesis is now completely understood--it takes three enzymes (RosB, RosC, and RosA) to convert the flavin cofactor riboflavin-5'-phosphate into a potent antibiotic.

An analysis of the impact of newborn survival policies in Pakistan using a policy triangle framework.

INTRODUCTION: Pakistan has made slow progress towards reducing the newborn mortality burden; as a result, it has the highest burden of newborn mortality worldwide. This article presents an analysis of the current policies, plans, and strategies aimed at reducing the burden of newborn death in Pakistan for the purpose of identifying current policy gaps and contextual barriers towards proposing policy solutions for improved newborn health. METHODS: We begin with a content analysis of federal-level policies that address newborn mortality within the context of health system decentralization over the last 20 years. This is then followed by a case study analysis of policy and programme responses in a predominantly rural province of Pakistan, again within the context of broader health system decentralization. Finally, we review successful policies in comparable countries to identify feasible and effective policy choices that hold promise for implementation in Pakistan, considering the policy constraints we have identified. RESULTS: The major health policies aimed at reduction of newborn mortality, following Pakistan's endorsement of global newborn survival goals and targets, lacked time-bound targets. We found confusion around roles and responsibilities of institutions in the implementation process and accountability for the outcomes, which was exacerbated by an incomplete decentralization of healthcare policy-making and health service delivery, particularly for women around birth, and newborns. Such wide gaps in the areas of target-setting, implementation mechanism, and evaluation could be because the policy-making largely ignored international commitments and lessons of successful policy-making in comparable regional counties. CONCLUSIONS: Inclusion of clear goals and targets in newborn survival policies and plans, completion of the decentralization process of maternal and child healthcare service delivery, and policy-making and implementation by translating complex evidence and using regional but locally applicable case studies will be essential to any effective policy-making on newborn survival in Pakistan.

The roseoflavin producer Streptomyces davaonensis has a high catalytic capacity and specific genetic adaptations with regard to the biosynthesis of riboflavin.

The bacterium Streptomyces davaonensis synthesizes the antibiotic roseoflavin in the stationary phase of growth. The starting point for roseoflavin biosynthesis is riboflavin (vitamin B2 ) and four enzymes (RibCF, RosB, RosA and RosC) are necessary to convert a vitamin (riboflavin) into a potent, broad-spectrum antibiotic (roseoflavin). In S. davaonensis, seven enzymatic functions are required to synthesize the roseoflavin precursor riboflavin from the central building blocks GTP and ribulose 5-phosphate. When compared with other bacterial and in particular Streptomyces genomes the S. davaonensis genome contains an unusual high number (21) of putative riboflavin biosynthetic genes (rib genes), including a rib gene encoding an additional riboflavin synthase originating from an Archaeon. We show by complementation analyses and enzyme assays that 17 out of these 21 putative rib genes indeed encode for riboflavin biosynthetic enzymes. Biochemical analyses of selected enzymes support this finding. Transcriptome analyses show that all of the rib genes are expressed either in the exponential or in the stationary phase of growth and thus do not represent silent genes. We conclude that the Rib enzymes produced in the stationary phase represent a physiological adaptation to support roseoflavin biosynthesis.

Increasing the public health voice in global decision-making on nutrition labelling.

To respond to the global noncommunicable disease (NCD) crisis, the Codex Alimentarius Commission (Codex), a multilateral United Nations body responsible for work on food standards, is developing global guidance for front of pack (FoP) nutrition labelling. Guidance from Codex regarding FoP nutrition labelling at the global level will almost certainly influence national policy making. This shift in Codex's activities towards standards to address NCDs presents new risks for achievement of public health goals, as a result of the high level of industry involvement in this forum; there is a potential commercial conflict of interest held by manufacturers of products whose consumption could be discouraged by such guidance. In this Commentary, we examine the implications of Codex processes for developing robust global guidance on FoP nutrition labelling and identify opportunities to increase consideration of public health objectives. To date, there has been significantly higher representation of food industry compared to public health actors in Codex discussions on FoP nutrition labelling. Without a strong public health voice in Codex, the industry voice could dominate discussions on FoP nutrition labelling, such that subsequent global guidance prioritises future trade and profits over potential risks to public health. There is currently a critical window of opportunity for public health interests to be prioritised in this multisectoral international forum. The key public health priority for global guidance on FoP nutrition labelling is to ensure protection of policy space for national governments to implement strong and effective regulation, and allow scope for innovation. Public health actors can engage directly with Codex processes, at both the national and global level, and also need to raise awareness among domestic policy makers - including with Ministries of Agriculture and Industry, which often represent countries at Codex - regarding the importance and effectiveness of FoP labelling in NCD prevention. Increased engagement with Codex processes represents a tangible new opportunity to strengthen global governance for public health, and move towards improved coherence between trade policy and health protection goals.

Antibiotics resistance and toxin profiles of Bacillus cereus-group isolates from fresh vegetables from German retail markets.

BACKGROUND: This study aimed to evaluate the safety of raw vegetable products present on the German market regarding toxin-producing Bacillus cereus sensu lato (s.l.) group bacteria. RESULTS: A total of 147 B. cereus s.l. group strains isolated from cucumbers, carrots, herbs, salad leaves and ready-to-eat mixed salad leaves were analyzed. Their toxinogenic potential was assessed by multiplex PCR targeting the hemolysin BL (hbl) component D (hblD), non-hemolytic enterotoxin (nhe) component A (nheA), cytotoxin K-2 (cytK-2) and the cereulide (ces) toxin genes. In addition, a serological test was used to detect Hbl and Nhe toxins. On the basis of PCR and serological results, none of the strains were positive for the cereulide protein/genes, while 91.2, 83.0 and 37.4% were positive for the Hbl, Nhe and CytK toxins or their genes, respectively. Numerous strains produced multiple toxins. Generally, strains showed resistance against the ß-lactam antibiotics such as penicillin G and cefotaxim (100%), as well as amoxicillin/clavulanic acid combination and ampicillin (99.3%). Most strains were susceptible to ciprofloxacin (99.3%), chloramphenicol (98.6%), amikacin (98.0%), imipenem (93.9%), erythromycin (91.8%), gentamicin (88.4%), tetracycline (76.2%) and trimethoprim/sulfamethoxazole combination (52.4%). The genomes of eight selected strains were sequenced. The toxin gene profiles detected by PCR and serological test mostly agreed with those from whole-genome sequence data. CONCLUSIONS: Our study showed that B. cereus s.l. strains encoding toxin genes occur in products sold on the German market and that these may pose a health risk to the consumer if present at elevated levels. Furthermore, a small percentage of these strains harbor antibiotic resistance genes. The presence of these bacteria in fresh produce should, therefore, be monitored to guarantee their safety.

The Global Burden of Musculoskeletal Pain-Where to From Here?

To summarize the current understanding of the global burden of musculoskeletal pain-related conditions, consider the process of evidence generation and the steps to generate global pain estimates, identify key gaps in our understanding, and propose an agenda to address these gaps, we performed a narrative review. In the 2010 Global Burden of Disease Study (GBD), which broadened the scope of musculoskeletal conditions that were included over previous rounds, low back pain imposed the highest disability burden of all specific conditions assessed, and subsequent GBD reports further reinforce the size of this burden. Over the past decade, the GBD has produced compelling evidence of the leading contribution of musculoskeletal pain conditions to the global burden of disability, but this has not translated into global health policy initiatives. However, system- and service-level responses to the disease burden persist across high-, middle-, and low-income settings. There is a mismatch between the burden of musculoskeletal pain conditions and appropriate health policy response and planning internationally that can be addressed with an integrated research and policy agenda.

A population-based comparison of the post-operative outcomes of open and laparoscopic appendicectomy in children.

OBJECTIVE: To assess and compare the post-operative outcomes of open and laparoscopic appendicectomy in children. DESIGN: Record linkage analysis of administrative hospital (Admitted Patient Data Collection) and emergency department (Emergency Department Data Collection) data.Participants, setting: Children under 16 years of age who underwent an appendicectomy in a public or private hospital in New South Wales between January 2002 and December 2013. MAIN OUTCOME MEASURES: Association between type of appendicectomy and post-operative complications within 28 days of discharge, adjusted for patient characteristics and type of hospital. RESULTS: Of 23 961 children who underwent appendicectomy, 19 336 (81%) had uncomplicated appendicitis and 4625 (19%) had appendicitis complicated by abscess, perforation, or peritonitis. The proportion of laparoscopic appendicectomies increased from 11.8% in 2002 to 85.8% in 2013. In cases of uncomplicated appendicitis, laparoscopic appendicectomy was associated with more post-operative complications (mostly symptomatic re-admissions or emergency department presentations) than open appendicectomy (7.4% v 5.8%), but with a reduced risk of post-operative intestinal obstruction (adjusted odds ratio [aOR], 0.59; 95% CI, 0.36-0.97). For cases of complicated appendicitis, the risk of wound infections was lower for laparoscopic appendicectomy (aOR, 0.67; 95% CI, 0.50-0.90), but not the risks of intestinal obstruction (aOR, 0.97; 95% CI, 0.62-1.52) or intra-abdominal abscess (aOR, 1.06; 95% CI, 0.72-1.55). CONCLUSION: Post-appendicectomy outcomes were similar for most age groups and hospital types. Children with uncomplicated appendicitis have lower risk of post-operative bowel obstruction after laparoscopic appendicectomy than after open appendicectomy, but may be discharged before their post-operative symptoms have adequately resolved.

Self-assembly and biological activities of ionic liquid crystals derived from aromatic amino acids.

The self-assembly of amino acid-derived ionic liquid crystals (ILCs) into lamellar or micellar-like aggregates suggests that they might interact with biological membranes. To get some insight, guanidinium chlorides derived from the natural l-amino acids phenylalanine (Phe), tyrosine (Tyr) and 3,4-dihydroxyphenylalanine (DOPA) were synthesized and their mesomorphic properties were investigated via polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction (SAXS, WAXS). Mesophase types depended on the number of alkoxy side chains. Phe- and Tyr-based ILCs with one and two side chains, respectively, self-assembled into smectic A bilayers (SmA2), while Dopa-derived ILCs with three side chains formed columnar (Colh) mesophases. The mesophase ranges for Phe ILCs increased steadily with side chain length, for Tyr- and Dopa-based ILCs, however, size matching effects were observed. To clarify whether the mesomorphic behaviour has an impact on biological properties, cytotoxic and antibacterial activities of the ILCs were studied. Phe and Tyr ILCs exhibited much higher cytotoxicities (against the L-929 mouse fibroblast cell line) and/or antibacterial activities (against Staphylococcus aureus) than Dopa ILCs, which were mostly inactive. Furthermore, within each series, the side chain length largely influenced the biological activity. Thus, the bulk mesophase behaviour appeared to correlate with the biological properties, in particular, the interactions with membranes, as shown by measuring the intracellular Ca2+ concentration in human monocytic U937 cells after treatment with the amino acid-based ILCs.

Truncated borrelidin analogues: synthesis by sequential cross metathesis/olefination for the southern fragment and biological evaluation.

The construction of novel borrelidin analogues is reported in which the northern fragment is truncated to a simple hydroxyundecanecarboxylate and the original cyclopentanecarboxylic acid in the southern fragment is replaced with different six-membered rings. The required precursors were prepared by cross metathesis of the appropriate carbocycle-based homoallylic alcohol with crotonaldehyde followed by HWE olefination of the resulting enal with bromocyanophosphonate. The key aldehyde for intramolecular cross coupling was accessible by oxidation of the hydroxy group of the linked undecanecarboxylate unit. Grignard mediated macrocyclization finally yielded the borrelidin related products. The investigation is complemented by SAR studies and quantum-chemical calculations.

The for-profit sector in humanitarian response: integrating ethical considerations in public policy decision making.

The engagement of the for-profit private sector in health, social and humanitarian services has become a topic of keen interest. It is particularly contentious in those instances where for-profit organizations have become recipients of public funds, and where they become key decision-makers in terms of how, and to whom, services are provided. We put forward a framework for identifying and organizing the ethical questions to be considered when contracting government services to the for-profit sector, specifically in those areas that have traditionally remained in the public or not-for-profit spheres. The framework is designed to inform both academic debate and practical decision-making regarding the acceptability, feasibility and legitimacy of for-profit organizations carrying out humanitarian work. First, we outline the importance of posing ethical questions in government contracting for-profit vs. not-for-profit organizations. We then outline five key areas to be considered before then examining the extent to which ethics concerns are warranted and how they may be safeguarded.

Non-communicable diseases and implications for medical practice in Australia: a framework for analysis.

Non-communicable diseases (NCDs) have become leading causes of mortality and morbidity as part of historical epidemiological, demographic and nutritional transitions. There has been considerable historical analysis of the immediate and underlying causes of this change in the impacts of communicable diseases and NCDs, but far less historical analysis of how this transition has shaped medical practice. We lay out a framework for future historical analysis by proposing four domains of inquiry into key areas of change: changes in the concept of disease; evolution of medical technology; changes in workforce, including variation in roles and emerging areas of specialisation; and changes in health care structures including models of care, government responses and transitioning health systems. Our aim is to encourage analysis that takes into account key features in each of the four domains, thus enabling a more complete understanding of why, how and under what circumstances NCDs have had an effect on medical practice.

How can knowledge exchange portals assist in knowledge management for evidence-informed decision making in public health?

BACKGROUND: Knowledge exchange portals are emerging as web tools that can help facilitate knowledge management in public health. We conducted a review to better understand the nature of these portals and their contribution to knowledge management in public health, with the aim of informing future development of portals in this field. METHODS: A systematic literature search was conducted of the peer-reviewed and grey literature to identify articles that described the design, development or evaluation of Knowledge Exchange Portals KEPs in the public health field. The content of the articles was analysed, interpreted and synthesised in light of the objectives of the review. RESULTS: The systematic search yielded 2223 articles, of which fifteen were deemed eligible for review, including eight case studies, six evaluation studies and one commentary article. Knowledge exchange portals mainly included design features to support knowledge access and creation, but formative evaluation studies examining user needs suggested collaborative features supporting knowledge exchange would also be useful. Overall web usage statistics revealed increasing use of some of these portals over time; however difficulties remain in retaining users. There is some evidence to suggest that the use of a knowledge exchange portal in combination with tailored and targeted messaging can increase the use of evidence in policy and program decision making at the organisational level. CONCLUSIONS: Knowledge exchange portals can be a platform for providing integrated access to relevant content and resources in one location, for sharing and distributing information and for bringing people together for knowledge exchange. However more performance evaluation studies are needed to determine how they can best support evidence-informed decision making in public health.

The Phosphatase RosC from Streptomyces davaonensis is Used for Roseoflavin Biosynthesis and has Evolved to Largely Prevent Dephosphorylation of the Important Cofactor Riboflavin-5'-phosphate.

The antibiotic roseoflavin is a riboflavin (vitamin B2) analog. One step of the roseoflavin biosynthetic pathway is catalyzed by the phosphatase RosC, which dephosphorylates 8-demethyl-8-amino-riboflavin-5'-phosphate (AFP) to 8-demethyl-8-amino-riboflavin (AF). RosC also catalyzes the potentially cell-damaging dephosphorylation of the AFP analog riboflavin-5'-phosphate also called "flavin mononucleotide" (FMN), however, with a lower efficiency. We performed X-ray structural analyses and mutagenesis studies on RosC from Streptomyces davaonensis to understand binding of the flavin substrates, the distinction between AFP and FMN and the catalytic mechanism of this enzyme. This work is the first structural analysis of an AFP phosphatase. Each monomer of the RosC dimer consists of an α/ß-fold core, which is extended by three specific elongated strand-to-helix sections and a specific N-terminal helix. Altogether these segments envelope the flavin thereby forming a novel flavin-binding site. We propose that distinction between AFP and FMN is provided by substrate-induced rigidification of the four RosC specific supplementary segments mentioned above and by an interaction between the amino group at C8 of AFP and the ß-carboxylate of D166. This key amino acid is involved in binding the ring system of AFP and positioning its ribitol phosphate part. Accordingly, site-specific exchanges at D166 disturbed the active site geometry of the enzyme and drastically reduced the catalytic activity. Based on the structure of the catalytic core we constructed a whole series of RosC variants but a disturbing, FMN dephosphorylating "killer enzyme", was not generated.