Search

Overlapped genes between Genes upregulated in Ptenpc-/-Smad4pc-/- tumors as compared to Ptenpc-/- tumors ({greater than or equal to}2 fold) and genes upregulated in GFP+ tumors cells from Ptenpc-/-Smad4pc-/- mice as compared to Tomato+ cells ({greater than or equal to}4 fold).

Supplementary Figure S1. CyTOF analysis of biological samples from Ptenpc-/-Smad4pc-/- mice (Related to Figure 2). Supplementary Figure S2. Strategy used for MDSCs Isolation (Related to Figure 3). Supplementary Figure S3. Treatment scheme for Gr-1 antibody, peptibody, and Cxcr2 inhibitor SB225002. Supplementary Figure S4. IHC staining of Ki67, CD45, Vimentin, Smooth muscle actin (SMA) and Trichrome staining of mouse prostate tissues treated with IgG control or Gr1 antibody. Supplementary Figure S5. The top 10 differentially expressed genes in Ptenpc-/-Smad4pc-/- tumors as compared to Ptenpc-/- tumors, identified by microarray analysis (n=5). Figure S6. Top 10 activated oncogenic signatures identified by GSEA analysis in Ptenpc-/- Smad4pc-/- tumors as compared to Ptenpc-/- tumors (n=5). Figure S7. Clustering of primary prostate tumors from Wallace et al into MDSC-high and MDSC-low subtypes.

The emergence of highly immune invasive and transmissible variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has decreased the effectiveness of existing vaccines. It is, therefore, critical to develop effective and safe therapeutics for SARS-CoV-2 infections, especially for the most vulnerable and immunocompromised patients. Neutralizing antibodies have been shown to be successful at preventing severe disease from early SARS-CoV-2 strains, although their efficacy has diminished with the emergence of new variants. Here, we aim to develop fully human and broadly neutralizing monoclonal (mAb) and bispecific (BsAb) antibodies against SARS-CoV-2 and its variants. Specifically, we first identified two antibodies from human transgenic mice that bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and are capable of neutralizing SARS-CoV-2 and variants of concern with high to moderate affinity. Two non-competing clones with the highest affinity and functional blocking of ACE2 binding were then selected to be engineered into two BsAbs, which were then demonstrated to have relatively improved affinity, ACE2 blocking ability, and pseudovirus inhibition against several variants, including Omicron (B.1.1.529). Our findings provide one mAb candidate and two bsAb candidates for consideration of further clinical development and suggest that the bispecific format may be more effective than mAbs for SARS-CoV-2 treatment.

For clinicians working in mental health services, 'aggression management' training is generally prioritised, and often mandated. Traditional 'aggression management' training has the potential to reinforce the perception that violence and aggression are inevitable, and thus defensive and coercive practices are needed. This paper outlines the principles and processes that underpinned the development of two training programs designed as recovery-oriented and trauma-informed alternatives to traditional 'aggression management' training. The focus of the paper is on exploring how 'aggression management' training can be aligned with best practice principles. The programs were developed in a metropolitan and rural mental health service and aimed to reduce the need for defensive and coercive practices by promoting therapeutic engagement. A key feature of both programs is an orientation towards safety rather than risk. By embedding the principles of recovery and trauma-informed care in their development and orienting training towards enhancing safety, clinicians are provided with a new way of conceptualising and responding to 'aggression'. Experiential methods in the delivery of the training, and the co-design and co-delivery with peer (consumer) educators were important in supporting attitudinal change. To promote safety, the language and content of training programs must reflect contemporary principles and approaches such as trauma-informed care and recovery. This paper illustrates that to be effective, these principles and approaches must not just be described, but modelled in the development, design, and delivery of the training.

The Broad Cancer Cell Line Factory (CCLF) aims to increase the number and representation of in vitro/ex vivo cell models for common and rare cancer types. Neuroendocrine tumor (NET) cell model derivation is one of the CCLFs focus because it lacks well-characterized, publicly available models.Two major barriers existed in deriving NET cell models, including how to collect sufficient patient tumor tissue samples for the model derivation pilot and how to systematically iterate model derivation strategies since there is no prior knowledge for NET cell model generation success. Thus, we partnered with the MD Anderson Cancer Center, the Dana-Farber Cancer Institute, and the Rare Cancer Research Foundation to collect patient tissue samples. All patient’s NET tissues were sequenced with a targeted Pan-Cancer panel to ensure high tumor content. To reduce fibroblast outgrowth, we combined an empirical rich media matrix (HYBRID technology) with a 3D spheroid culture system to initiate one sample in 16-64 conditions. The growing cultures at passage 3-5 were genomically credentialed to ensure the driver events matched with the original patient tissue. So far, we have received more than 70 NET samples. While several derived models are still under culture, we successfully generated 5 genomically verified NET tumor models, including small intestinal, pancreas, and liver subtypes. To phenotypically characterize these NET models, neuroendocrine biomarkers such as chromogranin A, synaptophysin, SSTR2, and VMAT 1/2 were also evaluated using qRT-PCR and ELISA. We observed that these NET spheroid models display long doubling times (2-4 weeks) at later passages which limits their utility for large scale perturbation experiments and model sharing capability with the research community. While we are currently working on several strategies to improve the propagation ability in these models, 1 (out of 5) model has reached passage 15 with a 3 day doubling time. Genomic studies, such as RNAseq, will be performed to address the model transcriptome changes after overcoming growth plateaus. Here we showed that it is feasible to derive NET models from patient biospecimens using our HYBRID strategy. As we expand our NET cohort, we will further refine disease-specific model generation protocols for different NET types. Our goal is to share our model generation experience and make these tumor cell models publicly available to the research community in order to accelerate cancer research. Citation Format: Adel Attari, Madison Liistro, Barbara Van Hare, Jennifer Chan, Emma Coleman, Tim Heffernan, Bianca Amador, Matthew Meyerson, Jesse Boehm, William Sellers, Yuen-Yi (Moony) Tseng. A systemic model derivation platform for generating 3D neuroendocrine tumor cell spheroids to accelerate cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 197.

Background Consumer peer workers are individuals with lived experience of mental health issues and recovery who are employed to use their lived experience to support others. The consumer peer workforce has expanded substantially in recent years. While some research has explored the workplace experiences of peer workers, no previous studies have explored job satisfaction, burnout or turnover intention for this workforce. Methods Consumer peer workers in New South Wales, Australia were invited to complete a survey designed to explore their workplace experiences. The survey included measures of job satisfaction, burnout, turnover intention, job demands and job resources, and satisfaction with supervision, professional development and opportunities for career progression. Questions also explored positive and negative aspects of positions. Analyses included exploration of the relationships between of job satisfaction, burnout, turnover intention, job demands and job resources as well as tabulation of common positive and negative aspects of positions. Results were also compared with findings from a previous study exploring workplace experiences of other mental health workers. Results A total of 67 peer workers participated in the study. Overall job satisfaction, burnout (disengagement and exhaustion) and turnover intention for peer workers was not significantly different to other mental health workers. Job satisfaction, disengagement, exhaustion and turnover intention were all significantly inter-related. Job resources of social support, job control, feedback, and rewards and recognition were associated with positive workplace experiences and the job demand of “physical environment” was most substantially associated with poorer workplace experiences. The most common positive aspect of positions was “connecting with consumers” and the most common negative aspect of positions was “attitudes of clinicians / workplace culture”. Access to supervision from a senior peer worker was associated with more positive workplace experiences. Conclusions This research demonstrates that while consumer peer workers do not appear to experience poorer job satisfaction or higher levels of burnout or turnover intention than other mental health workers, a range of challenges do exist. Efforts to further expand the peer workforce (especially senior peer worker roles) and to promote more positive attitudes and workplace cultures are likely to promote better workplace experiences for peer workers.

Background Mental health recovery is still largely clinically defined and as such can lack person centeredness. To address this, recovery oriented experiences are required which recognise the holistic and diverse needs of individuals. Aim The aim of the study was to examine the experiences of people living with a mental illness who participated in a recovery oriented program called Recovery Camp. The study aimed to examine how the program may have related and contributed to their mental health recovery. Methods A descriptive phenomenological approach guided the study. Consenting participants ( n =5) were interviewed and asked about their subjective experience of Recovery Camp . The interviews were digitally audio recorded and transcribed verbatim. Data were analysed using van Kaam's Psychophenomenological method. Findings This paper presents the perspective of consumers regarding the ways in which Recovery Camp facilitated mental health recovery. Data analysis revealed five themes (Self-determination, Participation, Extending Self, Relationships and Positive change) and a core essence of meaning (Empowerment). Conclusions Personal mental health recovery for people living with mental illness can be enhanced through recovery oriented mental health care approaches. Findings contribute to existing literature regarding therapeutic recreation and its link to mental health recovery.

Behaviors associated with resilience can be seen as tantamount to coping with stress and vulnerability. This is important for people who live with mental illness. This study aimed to determine whether key basic psychological needs influence resilience among people with a lived experience of mental illness. A total of 159 consumers with a lived experience of mental illness completed self-report surveys measuring resilience and the basic psychological needs (autonomy, competence, and relatedness) espoused in self-determination theory. A 2-step analysis was conducted, including Pearson product correlations and stepwise multiple regression. Higher levels of relatedness significantly predicted resilience. Competence and autonomy did not have a significant influence on resilience. Reconnecting or establishing social relationships within ones community is important for people living with mental illness. The link between resilience and relatedness ought to be considered in treatment plans.

Leisure, risk and safety are for most leisure practitioners across the globe, thoughts that arise in quick succession to determine the viability of a leisure intervention. However, in a risk aware world so focused on safety, is Leisure too safely structured to be truly beneficial to the individual?, Rarely are leisure seekers given the opportunity to fail and to learn from that experience. Lack of opportunity to face adversity in a supported way hinders the individual’s ability to learn and grow, and to develop personal resilience as a result. This paper will discuss Recovery Camp, a Therapeutic Recreation initiative developed in Australia which utilizes experiential leisure to facilitate resilience in individuals with a mental illness. This paper aims to discuss Leisure Boredom data obtained from volunteer consumers attending recovery camp in 2014 and its relationship to an individual’s personal resilience in the context of living in recovery from mental illness. Importantly Theraputic Recreation...

The concept of stigma and the stigmatizing behaviours of health-care professionals can have a profound influence on people with mental illness. A key construct that has been identified as influencing our behaviours is self-determination. As such, in the present study, we attempted to examine the connection and influence of motivational measures on the stigmatization of preregistration nurses. Data were collected once using three surveys that measured the motivational responses and stigmatizing behaviours of preregistration nurses after an approved mental health clinical placement. Using a path analysis, the results indicated that psychological needs significantly influenced preregistration nurses' self-determination towards work. In addition, self-determination was a significant influence on the stigmatization behaviours of preregistration nurses. The results of the present study provide initial empirical evidence that supports the importance of professional self-determination and the potential connection of quality care, as illustrated with the low stigmatizing behaviours of preregistration nurses who are more self-determined towards their work/career. Because of the significant results of the present study, it is recommended that future research is needed that uses self-determination theory as a lens to understand the application and importance within the field of nurse education.

People living with mental illness (consumers) often experience difficulty in achieving life goals, particularly those important for their recovery. An innovative approach to address consumers' goals for recovery can be found in the form of therapeutic recreation (TR) initiatives. Recovery Camp is a five-day TR program, bringing together people with a serious mental illness, undergraduate health students, and staff members. This article aims to examine the types of goals set by consumers in the context of Recovery Camp, and to what extent the self-identified goals were attained. The consumers (n = 27) were invited to set goals that they wished to achieve during the week. On the final day of Recovery Camp, each participant rated the degree to which they felt that each of their goals was achieved or not. The goals were themed using content analysis, revealing four key themes: connectedness, developing healthy habits, challenging oneself, and recovery. All goals were, to some extent, attained. The results suggest people with a mental illness are able to both set and evaluate the self-identified goals in the context of a TR initiative. A collaborative recovery approach indicates that goal planning should be undertaken in direct consultation with the consumer.

Preregistration education needs to ensure that student nurses are properly trained with the required skills and knowledge, and have the confidence to work with people who have a mental illness. With increased attention on non-traditional mental health clinical placements, further research is required to determine the effects of non-traditional mental health clinical placements on mental health clinical confidence. The aim of the present study was to investigate the impact of a non-traditional mental health clinical placement on mental health nursing clinical confidence compared to nursing students undergoing traditional clinical placements. Using the Mental Health Nursing Clinical Confidence Scale, the study investigated the relative effects of two placement programmes on the mental health clinical confidence of 79 nursing students. The two placement programmes included a non-traditional clinical placement of Recovery Camp and a comparison group that attended traditional clinical placements. Overall, the results indicated that, for both groups, mental health placement had a significant effect on improving mean mental health clinical confidence, both immediately upon conclusion of placement and at the 3-month follow up. Students who attended Recovery Camp reported a significant positive difference, compared to the comparison group, for ratings related to communicating effectively with clients with a mental illness, having a basic knowledge of antipsychotic medications and their side-effects, and providing client education regarding the effects and side-effects of medications. The findings suggest that a unique clinical placement, such as Recovery Camp, can improve and maintain facets of mental health clinical confidence for students of nursing.

Introduction There exists a need for innovative thinking to identify new clinical placement opportunities for nursing students. Recovery-based clinical placements for mental health nurse students remain unique and require investigation. Aim To examine the learning experience of Bachelor of Nursing students who undertook an innovative mental health clinical placement known as Recovery Camp . Design This study incorporated qualitative analysis of written reflections. Using Braun and Clarke's (2006) six phases of thematic analysis the corpus of student reflections were reviewed by three members of the research team independent to each other. Findings Four themes emerged. The theme of Pre-placement Expectations incorporates participant foci on pre-conceptions of Recovery Camp . The theme of Student Learning incorporates the ways in which participants recognised the experience of Recovery Camp influenced learning. Reflections themed under the title Placement Setting include discussion of the Recovery Camp as a clinical placement. The theme of Future Practice incorporates students' reflections on how they plan to practice as nurses as a result the learning experiences of Recovery Camp . Conclusions An immersive clinical placement such as Recovery Camp can influence students' perceptions of people with mental illness, have a positive impact on student learning and influence students' decisions about future practice. The learning experience of nursing students whom attend unique, recovery-orientated clinical placements can be both positive and educative.

Background Given the importance of perceived control to mental health and recovery, research is needed to determine strategies to increase perceived control for people with a mental illness. Aim Investigate the implications of a therapeutic recreation program on the perceived control of people with a mental illness. Method Participants of an intervention group ( n = 27) and comparison group ( n = 18) completed the Perceived Control Across Domains Scale at three time intervals. Subscale and total scores were analysed. Results and Discussion Significant variation occurred in the perceived control areas of substance use, personal cognition and personal empowerment. Implications A unique nurse led therapeutic recreation initiative, such as Recovery Camp, can improve and maintain facets of perceived control among people with mental illness.

Background The way people who experience mental illness are perceived by health care professionals, which often includes stigmatising attitudes, can have a significant impact on treatment outcomes and on their quality of life. Objective To determine whether stigma towards people with mental illness varied for undergraduate nursing students who attended a non-traditional clinical placement called Recovery Camp compared to students who attended a ‘typical' mental health clinical placement. Design Quasi-experimental. Participants Seventy-nine third-year nursing students were surveyed; n =40 attended Recovery Camp (intervention), n =39 (comparison group) attended a ‘typical' mental health clinical placement. Methods All students completed the Social Distance Scale (SDS) pre- and post-placement and at three-month follow-up. Data analysis consisted of a one-way repeated measures analysis of variance (ANOVA) exploring parameter estimates between group scores across three time points. Two secondary repeated measures ANOVAs were performed to demonstrate the differences in SDS scores for each group across time. Pairwise comparisons demonstrated the differences between time intervals. Results A statistically significant difference in ratings of stigma between the intervention group and the comparison group existed. Parameter estimates revealed that stigma ratings for the intervention group were significantly reduced post-placement and remained consistently low at three-month follow-up. There was no significant difference in ratings of stigma for the comparison group over time. Conclusions Students who attended Recovery Camp reported significant decreases in stigma towards people with a mental illness over time, compared to the typical placement group. Findings suggest that a therapeutic recreation based clinical placement was more successful in reducing stigma regarding mental illness in undergraduate nursing students compared to those who attended typical mental health clinical placements.

The provision of mental health care has recently focused on the concept of recovery-oriented care. Clinical placements are important for imparting recovery-oriented knowledge and skills to students. However, it has been determined that not all clinical placements are beneficial for future nursing professionals. The aim of this study was to examine what elements of professional learning were facilitated by engagement in a recovery- and recreation-based clinical placement for pre-registration nursing students called Recovery Camp. Qualitative data were collected through individual interviews and reflective journals of pre-registration nurses. Findings from this study indicate that Recovery Camp enhanced students' understanding of stigma, developed their professional knowledge and applied skills, and helped them gain insight into the role a consumer plays in his/her own recovery journey. Placements that allow pre-registration nurses the opportunity to authentically engage with people with a lived experience of mental illness may assist in the effective development of future professionals in meeting their diverse needs.

Engagement in clinical placements is mandatory for all pre-registration nursing programs. Although clinical placements can be valuable, recent literature illustrates that placements within a mental health setting can vary in their educational development. The aim of the current study was to examine the potential learning benefit of 20 pre-registration nursing students in an innovative, university-accredited mental health clinical placement called Recovery Camp. Recovery Camp is a 5-day immersive clinical placement, grounded in therapeutic recreation, which involves all participants engaging in a variety of activities focused on enhancing personal recovery. Qualitative data were collected using individual interviews, reflective journals, and researcher field notes. Analysis of data was conducted using an inductive thematic approach. Analysis of data revealed five themes: (a) Initial Anxiety/Nervousness , (b) Diffusion of Power , (c) Student Perceptions of Consumers , (d) Interaction and Communication , and (e) R esource Shift as a Result of Camp . Developing the professional learning of pre-registration nurses through immersion in effective clinical placements is paramount. Findings demonstrate that pre-registration nurses may benefit from clinical placements that provide immersive and collaborative experiences that allow for the development of relationship-oriented skills that can facilitate person-centered care. [ Journal of Psychosocial Nursing and Mental Health Services , 55 (2), 36–43.]

Nursing students across the globe are expected to undertake clinical placements. To date, there have been no studies that have examined the potential educational benefits for undergraduate nursing students engaged in a mental health clinical placement grounded in self-determination theory. The present study examined the experiences of undergraduate students engaged in a mental health clinical placement termed Recovery Camp. An ethnographic methodology within a case study approach was used. The researchers were immersed in the clinical placement, which took place at a YMCA camp facility. Participants were 20 3rd year undergraduate nursing students. To gain insight and understanding, the researchers used interviews, observations, and reflective journals. The constant-comparative method was used to analyse the data. Emergent themes identified from systematic analysis were: (a) social connection and (b) experiential learning. Recovery Camp facilitated a sense of inclusion and positive/supportive behaviour. It also enhanced student learning and understanding of symptoms of mental illness. Findings from this study support and extend findings for the use of therapeutic-recreation based work placement experiences in the clinical education of future nurses. Findings demonstrated a link between this type of placement and undergraduate student's development of deeper knowledge of symptoms and experiences associated with mental illness.

Many individuals with severe mental illness (SMI) require the support of an informal carer, such as a family member or close friend, to assist with everyday living. The difficulties and altered life circumstances experienced by individuals with SMI result in carers taking on significant responsibilities. The current study aimed to address the benefits to carers of several days relief from their caring responsibilities. Carers ( N = 9) of a cohort of individuals with SMI who attended a therapeutic recreation initiative, Recovery Camp, were surveyed in late May 2015. A custom-designed instrument using open and closed questions was administered. Data were analyzed using the constant-comparative method. Participants reported negative health effects that they directly associated with their caring responsibilities. The experience of having a break when their care recipient attended Recovery Camp was positive for all participants, highlighting the need for respite services. Further research is required to explore the specific respite needs of individuals who provide care to those with SMI to reduce the burden experienced by these vulnerable populations. [ Journal of Psychosocial Nursing and Mental Health Services , 54 (12), 33–38.]

Mental health consumers are often socially isolated and may lack the basic leisure competencies which serve as a critical building block for community (re)integration. Therapeutic recreation (TR), as a treatment modality for people with mental illness, is yet to be fully embraced in the Australian health-care setting, despite having a strong historical foundation in North America. A team of academics created a TR experience, termed Recovery Camp, which was designed to collectively engage consumers and future health professionals drawn from a range of discipline areas. The 2014 Recovery Camp was staged over a five day period and involved 28 adult consumers living with mental illness. Consumers undertook a diverse range of experiential recreation activities engineered to facilitate individual engagement and to encourage the development of positive therapeutic relationships and teamwork. The camp atmosphere was deliberately community-based and recovery-oriented, valuing the lived experience of mental illness. Using a 2 × 3 design involving a camp and comparison group, the study sought to examine the influence of a TR programme on the self-determination of individuals with a mental illness. Those who participated in the Recovery Camp reported an increase in awareness of self and perceived choice post-camp, relative to the comparison group. While this difference remained significant for awareness of self at three-month follow-up, there was no significant difference in perceived choice between the two groups at follow-up. Study findings serve to support the role of recreation within a recovery framework to positively change the health-related behaviour of mental health consumers.

TransPoC is a not-for-profit research organization that will deliver open-access, large-scale translational oncology platforms to enable greater clinical proof-of-concept success for new cancer therapies. TransPoC will comprise three platforms: 1. CPN - Cancer Cell “PoC” Network for screening compounds against 1000+ genomically-characterized cell lines; 2. MPN- Mouse “PoC” Network - a multi-site platform for mouse preclinical trials using genomically-characterized Patient-Derived Xenograft (PDX) models; 3. BioIT - analysis and integration of genomic information and pharmacological profiling data. Here we present an overview of the Mouse “PoC” Network, define a path to implementation of multi-center pre-clinical trials in mice and describe a pilot study to demonstrate the feasibility of implementing such a network. PDX models are increasingly used in pre-clinical studies as they capture and retain the histological, molecular, and genetic heterogeneity of the original tumor compared to cell line derived xenografts and are therefore a closer representation of a patient's tumor in situ. To enable transformative preclinical studies, models need to be characterized in a manner similar to tumor samples in The Cancer Genome Atlas and the International Cancer Genome Consortium, and must be assembled in sufficient quantity to capture clinically relevant major cancer (sub)types. To achieve this, TransPoC is building a global network of mouse PDX “hospitals” with genomic and metabolomic profiles characterized in a consistent manner. In addition, each mouse hospital will utilize common SOPs to generate comparable pharmacology data sets across sites that will include testing standard of care agents. BioIT will enable deep interrogation of data sets and provide pipelines for pharmacogenomics correlates of response to both standard and novel agents. To date, the network has collated over 2,000 PDX models and will enable sponsors to execute multi-center pre-clinical trials in a manner similar to those used in multi-institutional cooperative clinical trials. To demonstrate the viability of MPN, a pilot study has been initiated at 6 sites located in Canada, Italy, China and USA to evaluate the activity of MEK and RAF inhibitors against a panel of BRAF/KRAS mutant melanoma and colorectal cancer PDX models. An update on the initial tolerability, PK/PD/efficacy studies and molecular characterization of PDX models in the network will be presented. TransPoC continues to recruit new sites and characterize their PDX models for incorporation into MPN for use by TransPoC sponsors. Through this effort TransPoC enables rapid assessment of standard and novel investigational therapies to determine their therapeutic potential for translation to clinical trials with a mission to improve the chance of observing clinical proof-of-concept. Citation Format: Peter G. Smith, David Sutton, Andrea Bertotti, Livio Trusolino, Susan Airhart, Ming S. Tsao, Bradly G. Wouters, S. Gail Eckhardt, Lai Wang, Tim Heffernan, David Verbel, Andrea Gerken, Peter Fekkes, Lihua Yu, Lihua Yu, Markus Warmuth. Translational Proof-of-Concept (TransPoC), a not-for-profit research organization enabling access to large-scale translational oncology platforms: The Patient-Derived Xenograft network. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1191. doi:10.1158/1538-7445.AM2014-1191