Organizational Change in Complex Systems: Organizational and Leadership Factors in the Introduction of Open Dialogue to Mental Health Care Services.

Conventional mental health services are frequently criticized for failing to support people and communities in their care. Open Dialogue is a non-conventional humanistic approach to mental health care, which has been implemented in many different settings globally. At two Australian public health care services, implementation of the approach led to positive client outcomes and sustained organizational and clinical change. The aim of the study was to identify and explore the organizational, management, leadership and cultural factors that contributed to sustained implementation in these complex systems. We conducted nine individual semi-structured interviews of health care leaders and managers from the two sites. Transcriptions of the interviews were analyzed thematically. Leaders facilitated a gradual development of clinical and organizational legitimacy for the non-standardized Open Dialogue approach by holding the anxiety and frustration of practitioners and parts of the administration, cultivating cultural change and adaptation and by continually removing organizational obstacles.

Multi-family therapy for eating disorders: A systematic scoping review of the quantitative and qualitative findings.

OBJECTIVE: This study reviewed the quantitative and qualitative evidence-base for multi-family therapy (MFT) for eating disorders regarding change in physical and psychological symptoms, broader individual and family factors, and the experience of treatment. METHOD: A systematic scoping review was conducted. Four databases (PsycInfo, Medline, Embase, CENTRAL) and five grey literature databases were searched on 24th June 2021 for relevant peer-reviewed journal articles, book chapters, and dissertations. No beginning time-point was specified. Only papers that presented quantitative or qualitative data were included. No restrictions on age or diagnosis were imposed. Studies were first mapped by study design, participant age, and treatment setting, then narratively synthesized. RESULTS: Outcomes for 714 people who received MFT across 27 studies (one mixed-method, 17 quantitative and nine qualitative) were synthesized. MFT is associated with improvements in eating disorder symptomatology and weight gain for those who are underweight. It is also associated with improvements in other individual and family factors including comorbidities, self-esteem, quality of life, and some aspects of the experience of caregiving, although these findings are more mixed. MFT is generally experienced as both helpful and challenging due to the content addressed and intensive group process. DISCUSSION: MFT is associated with significant improvements in eating disorder symptoms across the lifespan and improvement in broader individual and family factors. The evidence base is small and studies are generally underpowered. Larger, higher-quality studies are needed, as is research investigating the unique contribution of MFT on outcomes, given it is typically an adjunctive treatment.

OBJETIVO: Este estudio revisó la evidencia cuantitativa y cualitativa para la terapia multifamiliar (MFT, por sus siglas en inglés) para los trastornos de la conducta alimentaria con respecto al cambio en los síntomas físicos y psicológicos, los factores individuales y familiares más extensos, y la experiencia del tratamiento. MÉTODO: Se realizó una revisión sistemática del alcance. Se realizaron búsquedas en cuatro bases de datos (PsycInfo, Medline, Embase, CENTRAL) y en cinco bases de datos de literatura gris el 24.06.2021 para obtener artículos relevantes de revistas revisadas por pares, capítulos de libros y disertaciones. No se especificó ningún punto de tiempo inicial. Sólo se incluyeron los artículos que presentaban datos cuantitativos o cualitativos. No se impusieron restricciones de edad o diagnóstico. Los estudios se mapearon primero por el diseño del estudio, la edad de los participantes y el entorno de tratamiento, y luego se sintetizaron narrativamente. RESULTADOS: Se sintetizaron los resultados de 714 pacientes que recibieron MFT en 27 estudios (un método mixto, 17 cuantitativos y nueve cualitativos). MFT se asocia con mejoras en la sintomatología del trastorno de la conducta alimentaria y el aumento de peso para aquellos que tienen bajo peso. También se asocia con mejoras en otros factores individuales y familiares, incluidas las comorbilidades, la autoestima, la calidad de vida y algunos aspectos de la experiencia del cuidador, aunque estos hallazgos son más mixtos. MFT generalmente se experimenta como útil y desafiante debido al contenido abordado y al proceso grupal intensivo. DISCUSIÓN: La MFT se asocia con mejoras significativas en los síntomas del trastorno de la conducta alimentaria a lo largo de la vida y una mejora en factores individuales y familiares más amplios. La base de evidencia es pequeña y los estudios generalmente tienen poco poder. Se necesitan estudios más grandes y de mayor calidad, al igual que la investigación que investiga la contribución única de la MFT en los resultados, dado que generalmente es un tratamiento complementario. PALABRAS CLAVE: terapia multifamiliar (MFT), terapia familiar de Maudsley, tratamiento basado en la familia (FBT), trastornos de la conducta alimentaria, anorexia nerviosa, bulimia nerviosa, niño, adolescente, adulto joven, adulto, cuidador.

"The Food Matches the Mood": Experiences of Eating Disorders in Bipolar Disorder.

Approximately 33% of those with bipolar disorder (BD) have a comorbid eating disorder (ED). However, the trajectory of these conditions has received little research attention. Nine participants who met criteria for BD and an ED participated in qualitative interviews exploring experiences of illness onset, the interaction of these conditions, and service provision. Almost all participants in the sample reported minimal to no screening of ED problems, despite their health professionals' frequent discussion of obesity. Findings suggested that ED features were diverse and evolved over time. Mania and depression were connected to ED features such as overeating and restricting, but this differed between and within participants. Most participants disclosed historic trauma which they considered central to their mental health concerns. This clinical group appears to be underserviced. Clinicians and researchers should routinely screen for ED features when treating and diagnosing BD to inform their physical and mental health interventions.

Clostridioides difficile para-Cresol Production Is Induced by the Precursor para-Hydroxyphenylacetate.

Clostridioides difficile is an etiological agent for antibiotic-associated diarrheal disease. C. difficile produces a phenolic compound, para-cresol, which selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. C. difficile decarboxylates para-hydroxyphenylacetate (p-HPA) to produce p-cresol by the action of the HpdBCA decarboxylase encoded by the hpdBCA operon. Here, we investigate regulation of the hpdBCA operon and directly compare three independent reporter systems; SNAP-tag, glucuronidase gusA, and alkaline phosphatase phoZ reporters to detect basal and inducible expression. We show that expression of hpdBCA is upregulated in response to elevated p-HPA. In silico analysis identified three putative promoters upstream of hpdBCA operon-P1, P2, and Pσ54; only the P1 promoter was responsible for both basal and p-HPA-inducible expression of hpdBCA We demonstrated that turnover of tyrosine, a precursor for p-HPA, is insufficient to induce expression of the hpdBCA operon above basal levels because it is inefficiently converted to p-HPA in minimal media. We show that induction of the hpdBCA operon in response to p-HPA occurs in a dose-dependent manner. We also identified an inverted palindromic repeat (AAAAAG-N13-CTTTTT) upstream of the hpdBCA start codon (ATG) that is essential for inducing transcription of the hpdBCA operon in response to p-HPA, which drives the production of p-cresol. This provides insights into the regulatory control of p-cresol production, which affords a competitive advantage for C. difficile over other intestinal bacteria, promoting dysbiosis.IMPORTANCEClostridioides difficile infection results from antibiotic-associated dysbiosis. para-Cresol, a phenolic compound produced by C. difficile, selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. Here, we demonstrate that expression of the hpdBCA operon, encoding the HpdBCA decarboxylase which converts p-HPA to p-cresol, is upregulated in response to elevated exogenous p-HPA, with induction occurring between >0.1 and ≤0.25 mg/ml. We determined a single promoter and an inverted palindromic repeat responsible for basal and p-HPA-inducible hpdBCA expression. We identified turnover of tyrosine, a p-HPA precursor, does not induce hpdBCA expression above basal level, indicating that exogenous p-HPA was required for p-cresol production. Identifying regulatory controls of p-cresol production will provide novel therapeutic targets to prevent p-cresol production, reducing C. difficile's competitive advantage.

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria.

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.

'Every single minute and hour is scrutinised': neoliberalism and Australian private mental health care.

There is little understanding of how recovery-oriented approaches fit within contemporary mental healthcare systems, which emphasise biomedical approaches to care, increased efficiency and cost-cutting. This article examines the established models of service delivery in a private, youth, mental health service and the impacts of the current system on staff. It explores whether the service is prepared or capable of adopting recovery-oriented approaches to care. Qualitative interviews were undertaken with staff and thematically analysed to understand the everyday practices on the unit. Data suggest that economic efficiencies and biomedical dominance largely shaped how health care was organised and delivered, which was perceived by staff as inflexible to change. Additionally, findings suggest that market-oriented principles associated with neoliberalism restricted the capacity of individuals to transform services in line with alternative models of care and lowered staff morale. These finding suggest that, while neoliberal ideologies and biomedical approaches remain dominant in organisations, there will be challenges to adopting alternative recovery-oriented models of care and promoting healthcare systems that understand mental health issues in broader socio-political contexts and can flexibly respond to the needs of service users.

Steps of care for adolescents with anorexia nervosa-A Delphi study.

OBJECTIVE: Anorexia nervosa (AN) commonly develops during adolescence. Existing literature offers some treatment guidelines, but clear clinical criteria for initial recommendations and steps of care are needed. The aim of the present study was to develop expert consensus for a stepped-care algorithm for treatment of adolescents with AN. METHOD: The Delphi approach was used to identify clinical parameters that guide initial treatment recommendations and recommendations for transitions between levels of care. The Delphi approach provides a useful expert consensus when empirical data are limited. Individuals with at least 10 years of experience in the field of adolescent AN and membership in one of three professional organizations were recruited. Twenty-five panelists participated in three rounds of iterative online questionnaires. RESULTS: Consensus was achieved on several features of a treatment algorithm. Hospitalization is recommended when medical instability, suicidality, or acute food refusal are present at any point in treatment. Family-based treatment (FBT) is recommended as the first-line treatment, with a few exceptions. Consensus was not reached on when to transition from a higher level of care to a lower level of care. DISCUSSION: Expert opinion was used to develop a consensus-based algorithm for care of adolescents with AN. Future research is needed to test whether these recommendations can be used to optimize outcomes for adolescents with AN.

Implementing a Statewide Safe to Sleep Hospital Initiative: Lessons Learned.

Sleep-related infant deaths continue to be a major, largely preventable cause of infant mortality, especially in Georgia. The Georgia Department of Public Health (DPH), as part of a multi-pronged safe infant sleep campaign, implemented a hospital initiative to (1) provide accurate safe infant sleep information to hospital personnel; (2) support hospitals in implementing and modeling safe sleep practices; and (3) provide guidance on addressing caregiver safe sleep concerns. A process evaluation was conducted to determine progress toward four goals set out by DPH: (1) all birthing hospitals have a safe infant sleep policy; (2) all safe infant sleep policies reference the AAP 2011 recommendations; (3) all safe infant sleep policies specify the type and/or content of patient safe sleep education; and (4) all hospitals require regular staff training on safe sleep recommendations. Data were collected via structured interviews and document review of crib audit data and safe sleep policies. All 79 birthing hospitals in the state participated in the statewide campaign. Prior to the initiative, 44.3% of hospitals had a safe sleep policy in place; currently, 87.3% have a policy in place. The majority (91.4%) of hospitals have provided safe sleep training to their staff at this time. Important lessons include: (1) Engagement is vital to success; (2) A comprehensive implementation guide is critical; (3) Piloting the program provides opportunities for refinement; (4) Ongoing support addresses barriers; and (5) Senior leadership facilitates success.

Role of Glycosyltransferases Modifying Type B Flagellin of Emerging Hypervirulent Clostridium difficile Lineages and Their Impact on Motility and Biofilm Formation.

Clostridium difficile is the principal cause of nosocomial infectious diarrhea worldwide. The pathogen modifies its flagellin with either a type A or type B O-linked glycosylation system, which has a contributory role in pathogenesis. We study the functional role of glycosyltransferases modifying type B flagellin in the 023 and 027 hypervirulent C. difficile lineages by mutagenesis of five putative glycosyltransferases and biosynthetic genes. We reveal their roles in the biosynthesis of the flagellin glycan chain and demonstrate that flagellar post-translational modification affects motility and adhesion-related bacterial properties of these strains. We show that the glycosyltransferases 1 and 2 (GT1 and GT2) are responsible for the sequential addition of a GlcNAc and two rhamnoses, respectively, and that GT3 is associated with the incorporation of a novel sulfonated peptidyl-amido sugar moiety whose structure is reported in our accompanying paper (Bouché, L., Panico, M., Hitchen, P., Binet, D., Sastre, F., Faulds-Pain, A., Valiente, E., Vinogradov, E., Aubry, A., Fulton, K., Twine, S., Logan, S. M., Wren, B. W., Dell, A., and Morris, H. R. (2016) J. Biol. Chem. 291, 25439-25449). GT2 is also responsible for methylation of the rhamnoses. Whereas type B modification is not required for flagellar assembly, some mutations that result in truncation or abolition of the glycan reduce bacterial motility and promote autoaggregation and biofilm formation. The complete lack of flagellin modification also significantly reduces adhesion of C. difficile to Caco-2 intestinal epithelial cells but does not affect activation of human TLR5. Our study advances our understanding of the genes involved in flagellar glycosylation and their biological roles in emerging hypervirulent C. difficile strains.

The assessment and treatment of unhealthy exercise in adolescents with anorexia nervosa: A Delphi study to synthesize clinical knowledge.

This study aimed to explore and synthesize expert clinical knowledge on defining and managing unhealthy exercise in adolescents with AN. The Delphi methodology was used. Clinicians (n = 25) considered experts in the treatment of AN in adolescents were recruited internationally to form the panel. The first round of the questionnaires was comprised of five open-ended questions regarding defining, assessing, and treating unhealthy exercise in adolescents with AN. Statements were derived from this data using content analysis, and included as Likert-based items in two subsequent rounds, in which panellists were required to rate their level of agreement for each item. All 25 respondents completed the three rounds of questionnaires. Consensus was achieved for 59.0% of the items included in the second and third round of questionnaires. Although consensus was not achieved, compulsive exercise was the preferred term for the panel when referring to unhealthy exercise in adolescents with AN. The panel clearly delineated features of unhealthy and healthy exercise, and endorsed a number of items considered important to assess for when evaluating exercise in this clinical population. A variety of treatment approaches and strategies reached consensus. Notably, for those who are medically stable and progressing toward recovery, the panel recommended initial exercise restriction practices and reintroducing healthy exercise behaviors, rather than exercise cessation practices. The current findings can serve as preliminary treatment guidelines. A unified approach to labeling and defining unhealthy exercise in the eating disorder literature and clinical settings is required to achieve further progress.

Cyclic diGMP regulates production of sortase substrates of Clostridium difficile and their surface exposure through ZmpI protease-mediated cleavage.

In Gram-positive pathogens, surface proteins may be covalently anchored to the bacterial peptidoglycan by sortase, a cysteine transpeptidase enzyme. In contrast to other Gram-positive bacteria, only one single sortase enzyme, SrtB, is conserved between strains of Clostridium difficile. Sortase-mediated peptidase activity has been reported in vitro, and seven potential substrates have been identified. Here, we demonstrate the functionality of sortase in C. difficile. We identify two sortase-anchored proteins, the putative adhesins CD2831 and CD3246, and determine the cell wall anchor structure of CD2831. The C-terminal PPKTG sorting motif of CD2831 is cleaved between the threonine and glycine residues, and the carboxyl group of threonine is amide-linked to the side chain amino group of diaminopimelic acid within the peptidoglycan peptide stem. We show that CD2831 protein levels are elevated in the presence of high intracellular cyclic diGMP (c-diGMP) concentrations, in agreement with the control of CD2831 expression by a c-diGMP-dependent type II riboswitch. Low c-diGMP levels induce the release of CD2831 and presumably CD3246 from the surface of cells. This regulation is mediated by proteolytic cleavage of CD2831 and CD3246 by the zinc metalloprotease ZmpI, whose expression is controlled by a type I c-diGMP riboswitch. These data reveal a novel regulatory mechanism for expression of two sortase substrates by the secondary messenger c-diGMP, on which surface anchoring is dependent.

Quality of life as a vulnerability and recovery factor in eating disorders: a community-based study.

BACKGROUND: Emerging evidence suggests that changes in quality of life (QoL) predicts later changes in eating disorder (ED) symptoms. The objective of this study was to explore individual sufferers' perspectives on the influence of QoL on the onset, maintenance, and/or remission of ED symptoms. METHOD: 19 women from the community with a history of eating disorders (n = 13 currently symptomatic; n = 6 recovered) were interviewed about their observations on the relationship between QoL and ED symptoms over time in their own lives. Interviews were audio-taped and transcribed, and then thematically analysed. RESULTS: Thematic analysis uncovered two major themes: 1. QoL as a Vulnerability Factor, and 2. QoL as a Recovery Factor. In relation to the first theme, onset of ED symptoms was discussed by women in this study as having been triggered by impairment in QoL, including a general sense of lacking control in life, stress, abusive intimate relationships, poor role modelling from family, physical impairment related to obesity, peer pressure, and weight-related teasing. On the other hand, and in relation to the second theme, subsequent improvement in QoL was nominated as central to symptom improvement and recovery. QoL improvement was described by participants differently, but included increased general satisfaction in life, emotional maturation, prioritising and improving physical health, the development of a supportive intimate relationship and social relationships, and having children. CONCLUSIONS: Impairment in QoL may act as a trigger for the onset and maintenance of ED symptoms, whereas improvement in QoL may be central to eating disorder improvement and eventual recovery. Treatment should involve consideration of a core focus on QoL improvement as a potential 'backdoor' approach to improving ED symptoms.

Using the theory of planned behaviour to measure motivation for recovery in anorexia nervosa.

Anorexia nervosa (AN) is a difficult to treat mental illness associated with low motivation for change. Despite criticisms of the transtheoretical stages of change model, both generally and in the eating disorders (EDs), this remains the only model to have been applied to the understanding of motivation to recover from AN. The aim of this pilot study was to determine whether the theory of planned behaviour (TPB) would provide a good fit for understanding and predicting motivation to recover from AN. Two studies were conducted - in the first study eight women who had recovered from chronic AN were interviewed about their experiences of recovery. The interview data were subsequently used to inform the development of a purpose-designed questionnaire to measure the components of the TPB in relation to recovery. In the second study, the resultant measure was administered to 67 females with a current diagnosis of AN, along with measures of eating disorder psychopathology, psychological symptoms, and an existing measure of motivation to recover (based on the transtheoretical model). Data from the interview study confirmed that the TPB is an appropriate model for understanding the factors that influence motivation to recover from AN. The results of the questionnaire study indicated that the pre-intention variables of the TPB accounted for large proportions of variance in the intention to recover (72%), and more specifically the intention to eat normally and gain weight (51%). Perceived behavioural control was the strongest predictor of intention to recover, while attitudes were more important in the prediction of the intention to eat normally/gain weight. The positive results suggest that the TPB is an appropriate model for understanding and predicting motivation in AN. Implications for theory and practice are discussed.

Clostridium difficile has a single sortase, SrtB, that can be inhibited by small-molecule inhibitors.

BACKGROUND: Bacterial sortases are transpeptidases that covalently anchor surface proteins to the peptidoglycan of the Gram-positive cell wall. Sortase protein anchoring is mediated by a conserved cell wall sorting signal on the anchored protein, comprising of a C-terminal recognition sequence containing an "LPXTG-like" motif, followed by a hydrophobic domain and a positively charged tail. RESULTS: We report that Clostridium difficile strain 630 encodes a single sortase (SrtB). A FRET-based assay was used to confirm that recombinant SrtB catalyzes the cleavage of fluorescently labelled peptides containing (S/P)PXTG motifs. Strain 630 encodes seven predicted cell wall proteins with the (S/P)PXTG sorting motif, four of which are conserved across all five C. difficile lineages and include potential adhesins and cell wall hydrolases. Replacement of the predicted catalytic cysteine residue at position 209 with alanine abolishes SrtB activity, as does addition of the cysteine protease inhibitor MTSET to the reaction. Mass spectrometry reveals the cleavage site to be between the threonine and glycine residues of the (S/P)PXTG peptide. Small-molecule inhibitors identified through an in silico screen inhibit SrtB enzymatic activity to a greater degree than MTSET. CONCLUSIONS: These results demonstrate for the first time that C. difficile encodes a single sortase enzyme, which cleaves motifs containing (S/P)PXTG in-vitro. The activity of the sortase can be inhibited by mutation of a cysteine residue in the predicted active site and by small-molecule inhibitors.

The recovery model and anorexia nervosa.

OBJECTIVE: Treatments in anorexia nervosa (AN) have not been wholly effective and, accordingly, practices need to be reviewed. The recovery model is an approach to treatment that has become a guiding principle for mental health policy worldwide that might provide promise for AN treatment. The model has received much attention in recent years; however, there is a dearth of literature exploring how useful this model is for AN. The aim of the current article was to consider the relevance of this model in AN. METHODS: This article provides a summary of the recovery model and reviews the literature to establish whether it is compatible with AN. The possible utility of the approach in AN is explored and suggestions are made as to how the model might be implemented in treatment. RESULTS: Qualitative studies examining the patient's perspective of AN support the recovery model. Many evidenced-based treatments currently used in AN have elements that are consistent with a recovery model approach. Treatments that are most consistent with recovery approaches have been effective for those with chronic AN. CONCLUSION: It is proposed that the model might offer a way in which to add to current practice and might have particular relevance for those with chronic AN. Future research is required to better understand how the model can best be utilised in AN.

"Doing the impossible": the process of recovery from chronic anorexia nervosa.

In this study, we aimed to explore the process of recovery over time from the perspective of those who had fully recovered from chronic anorexia nervosa (AN), using stringent recovery criteria. Eight women, assessed as fully recovered from chronic AN, told their story of the process of recovery. Data were analyzed using the qualitative method, narrative inquiry. Recovery was identified as a long and complex process that spanned four phases: from being unable or unready to change, to experiencing a tipping point where motivation increased and changed in quality, allowing the women to take action against the AN and finally allowing them to reflect and rehabilitate. Results provide a framework for understanding this complex process. Findings suggest that full recovery from chronic AN is possible and emphasize the importance of hope, motivation, self-efficacy, and support from others in the recovery process.

Power, position and social relations: Is the espoused absence of hierarchy in Open Dialogue naïve?

Open Dialogue practitioners aim to reduce social hierarchies by not privileging any one voice in social network conversations, and thus creating space for a polyphony of voices. This sits in contrast to the traditional privileging of those voices credited with more knowledge or power because of social position or professional expertise. Using qualitative interviews, the aim of this current study was to explore Open Dialogue practitioners' descriptions of challenges in implementing Open Dialogue at a women's health clinic in Australia. Findings revealed how attempts to rhetorically flatten hierarchies among practitioners created challenges and a lack of clarity regarding roles and responsibilities. As the practitioners tried to adjust to new ways of working, they reverted to taking up engrained positions and power aligned with more conventional social and professional roles for leading therapy and decision-making. The findings raise questions about equity-oriented ways of working, such as Open Dialogue, where intentions of creating a flattened hierarchy may allow power structures and their effects to be minimised or ignored, rather than actively acknowledged and addressed. Further research is needed to consider the implications that shifting power relations might have on the roles and responsibilities of practitioners in the move to equity-oriented services.

ADEVO: Proof-of-concept of adenovirus-directed EVOlution by random peptide display on the fiber knob.

Directed evolution of viral vectors involves the generation of randomized libraries followed by artificial selection of improved variants. Directed evolution only yielded limited results in adenovirus (AdV) engineering until now, mainly due to insufficient complexities of randomized libraries. Meanwhile, clinical applications of AdVs as gene therapy or oncolytic vectors are still hampered by the predetermined tropism of natural types. To overcome this challenge, we hypothesized that randomized peptide insertions on the capsid surface can be incorporated into the AdV bioengineering toolbox for retargeting. Here we developed AdV-directed EVOlution protocols based on fiber knob peptide display. Human AdV-C5-derived libraries were constructed following three distinct protocols and selected on a panel of cancer cell lines, with the goal of identifying variants able to infect and lyse these tumor cells more efficiently. All protocols enabled the construction of high complexity libraries with up to 9.6 × 105 unique variants, an approximate 100-fold improvement compared with previously published AdV libraries. After selection, the most enriched variants, which were robustly selected in various cancer cell lines, did not display enhanced infectivity but rather more efficient replication and cell lysis. Selected inserts also conferred enhanced lysis ability to oncolytic AdVs restricted to telomerase-expressing cell lines.

Evolutionary dynamics of Clostridium difficile over short and long time scales.

Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. However, the genetic basis for the emergence of C. difficile as a human pathogen is unclear. Whole genome sequencing was used to analyze genetic variation and virulence of a diverse collection of thirty C. difficile isolates, to determine both macro and microevolution of the species. Horizontal gene transfer and large-scale recombination of core genes has shaped the C. difficile genome over both short and long time scales. Phylogenetic analysis demonstrates C. difficile is a genetically diverse species, which has evolved within the last 1.1-85 million years. By contrast, the disease-causing isolates have arisen from multiple lineages, suggesting that virulence evolved independently in the highly epidemic lineages.

Complementary and Alternative Medicine (CAM): use and views among patients with solid organ and haematological malignancies in Northland, New Zealand.

AIMS: Complementary Alternative Medicine (CAM) use among patients with malignant diagnosis has been rising globally. This study assesses the prevalence of CAM among patients with solid organ or haematological malignancy at a regional outpatient cancer and blood service in Northland, New Zealand. Secondary objectives include determining: i) types of CAM used, ii) sources of information, and iii) patient perspectives on CAM. METHOD: In this single-centre cross-sectional study, patients attending treatment or follow-up appointments at the Jim Carney Cancer Treatment Centre (JCC) between 25 September to 20 October 2017 were invited to complete an anonymous self-administered questionnaire. RESULTS: Of the 306 assessable entries, 29% (n=89) respondents were using CAM, 10% had intentions to use CAM in the future, while 45% were undecided. Word-of-mouth (58%) was the most common source of CAM information, followed by internet sources (36%) and healthcare professionals (27%). Biologically based therapies were the most popular form of CAM used. Common reasons for CAM use include symptom relief (65%), perceived lower toxicity (62%), holistic (52%), natural (51%) and potential for cure (45%). Only 49% of CAM users felt comfortable discussing their CAM use with their oncologist/ haematologist. CONCLUSION: CAM use is common and has relevance across oncology treatment centres nationwide. Local research into CAM use can serve to raise awareness and to assist healthcare professional training in addressing CAM use in a specific patient population.