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AIMS AND METHOD: We aimed to co-design an intervention optimising the benefits of online arts and culture for mental health in young people for subsequent testing in a trial. Co-design followed the double diamond phases of design, discover, define, develop and deliver. RESULTS: Navigating the views of all co-designers to produce a testable resource demanded in-depth understanding, and frequent iterations in multiple modalities of the theoretical basis of the intervention, amplification of youth voice and commitment to a common goal. CLINICAL IMPLICATIONS: Co-design with a broad range of collaborators with a shared vision was valued by young co-designers and produced an effective intervention. Co-design allowed the theoretical basis to be followed and refined to create an engaging, practical and testable web experience, aiming to optimise the mental health benefits of online arts and culture for young people in a randomised controlled trial.
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Millions of households globally rely on uncultivated ecosystems for their livelihoods. However, much of the understanding about the broader contribution of uncultivated ecosystems to human wellbeing is still based on a series of small-scale studies due to limited availability of large-scale datasets. We pooled together 11 comparable datasets comprising 232 settlements and 10,971 households in ten low-and middle-income countries, representing forest, savanna and coastal ecosystems to analyse how uncultivated nature contributes to multi-dimensional wellbeing and how benefits from nature are distributed between households. The resulting dataset integrates secondary data on rural livelihoods, multidimensional human wellbeing, household demographics, resource tenure and social-ecological context, primarily drawing on nine existing household surveys and their associated contextual information together with selected variables, such as travel time to cities, population density, local area GDP and land use and land cover from existing global datasets. This integrated dataset has been archived with ReShare (UK Data Service) and will be useful for further analyses on nature-wellbeing relationships on its own or in combination with similar datasets.
Subject(s)
Ecosystem , Poverty , Sustainable Development , Humans , Family Characteristics , Rural PopulationABSTRACT
OBJECTIVES: This study aimed to understand young people's perception of the potential utility of arts and culture, focusing on online access, for supporting their mental health. DESIGN: A qualitative interview study. SETTING: Online. PARTICIPANTS: Participants were selected by purposeful sampling from an online survey of arts and culture for mental health and well-being. METHOD: Individual semi-structured interviews were conducted from 30 July 2020 to 9 September 2020. Rich interview data were analysed using reflexive thematic analysis. RESULTS: Thirteen participants aged 18-24 who were socio-demographically diverse and varied in their use of online arts and culture (OAC) and in their level of psychological distress were interviewed. Six themes, 'Characteristics of other activities', 'Online engagement', 'Human connection', 'Mechanisms of impact', 'Mental health outcomes' and 'Engagement optimisation', were identified along with subthemes. Participants identified that online engagement had some advantages over in-person engagement and benefits were greater with familiarity and regular use. Participants described that human connection was the feature of OAC most likely to benefit mental health and emphasised the importance of representation. Mechanisms included improving perspective, reflection, learning, escapism, creativity, exploration and discovery. Outcomes were described as the disruption of negative thought patterns, lifting of mood and increased feelings of calm and proactivity. CONCLUSIONS: This study demonstrates that young people have a critical level of insight and understanding regarding their mental health and ways in which it might be improved. These findings can be used to optimise the mental health benefits of OAC in an engaging and acceptable way for young people. These methodologies could be applied to other types of community resources for mental health.
Subject(s)
Emotions , Mental Health , Humans , Adolescent , Qualitative Research , AffectABSTRACT
OBJECTIVE: We aimed to compare a co-produced online intervention encompassing the diverse human stories behind art and artefacts, named Ways of Being (WoB), with a typical museum website, the Ashmolean (Ash) on negative affect (NA), positive affect (PA) and psychological distress (K10). METHODS: In this parallel group RCT, 463 YP aged 16-24 were randomly assigned, 231 to WoB and 232 to Ash. RESULTS: Over the intervention phase (an aggregate score including all post-allocation timepoints to day-five) a group difference was apparent in favour of WoB for NA (WoB-Ash n=448, NA -0.158, p=0.010) but no differences were detected for PA or K10 and differences were not detected at week six. Group differences in NA in favour of WoB were detected in specific subgroups, e.g. ethnic minorities and males. Across participants (from both groups) mean K10 and NA improved between baseline and six weeks despite increased COVID-19 restrictions. Trial recruitment was rapid, retention high and feedback positive with broad geographical, occupational and ethnic diversity. CONCLUSIONS: Online engagement with arts and culture has the potential to impact on mental health in a measurable way in YP with high unmet mental health needs.
Subject(s)
COVID-19 , Internet-Based Intervention , Male , Humans , Mental Health , MuseumsABSTRACT
BACKGROUND: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we aimed to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations. METHODS: We followed 3 patients with resectable disease and 4 patients with unresectable disease, including 4 patients with ≥ 3 serial follow-up samples, of whom 2 were rare long survivors (> 5 years). We performed whole exome sequencing of tumour gDNA and plasma ctDNA (n = 20) collected over a ~ 2-year period from diagnosis through treatment to death or final follow-up. Plasma from 3 chronic pancreatitis cases was used as a comparison for analysis of ctDNA mutations. RESULTS: We detected > 55% concordance between somatic mutations in tumour tissues and matched serial plasma. Mutations in ctDNA were detected within known PDAC driver genes (KRAS, TP53, SMAD4, CDKN2A), in addition to patient-specific variants within alternative cancer drivers (NRAS, HRAS, MTOR, ERBB2, EGFR, PBRM1), with a trend towards higher overall mutation loads in advanced disease. ctDNA alterations with potential for therapeutic actionability were identified in all 7 patients, including DNA damage response (DDR) variants co-occurring with hypermutation signatures predictive of response to platinum chemotherapy. Longitudinal tracking in 4 patients with follow-up > 2 years demonstrated that ctDNA mutant allele fractions and clonal trends were consistent with CA19-9 measurements and/or clinically reported disease burden. The estimated prevalence of 'stem clones' was highest in an unresectable patient where changes in ctDNA dynamics preceded CA19-9 levels. Longitudinal evolutionary trajectories revealed ongoing subclonal evolution following chemotherapy. CONCLUSION: These results provide proof-of-concept for the use of exome sequencing of serial plasma to characterise patient-specific ctDNA profiles, and demonstrate the sensitivity of ctDNA in monitoring disease burden in PDAC even in unresectable cases without matched tumour genotyping. They reveal the value of tracking clonal evolution in serial ctDNA to monitor treatment response, establishing the potential of applied precision medicine to guide stratified care by identifying and evaluating actionable opportunities for intervention aimed at optimising patient outcomes for an otherwise intractable disease.
Subject(s)
Carcinoma, Pancreatic Ductal , Circulating Tumor DNA , Pancreatic Neoplasms , Biomarkers, Tumor/genetics , CA-19-9 Antigen , Carcinoma, Pancreatic Ductal/pathology , Circulating Tumor DNA/genetics , Humans , Mutation , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Pancreatic NeoplasmsABSTRACT
Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post-surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri-tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter-patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri-tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri-tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Subject(s)
Breast Neoplasms , Breast/pathology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Early Detection of Cancer , Female , Humans , United KingdomABSTRACT
COVID-19 recovery is an opportunity to enhance life chances by Building Back Better, an objective promoted by the UN and deployed politically at national level. To help understand emergent and intentional opportunities to Build Back Better, we propose a research agenda drawing from geographical thinking on social contracts, assemblage theory and the politics of knowledge. This points research towards the ways in which everyday and professional knowledge cocreation constrains vision and action. Whose knowledge is legitimate, how legitimacy is ascribed and the place of science, the media and government in these processes become sites for progressive Building Back Better.
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AIMS AND METHOD: To gain a deeper understanding of the use of online culture and its potential benefits to mental health and well-being, sociodemographic characteristics and self-reported data on usage, perceived mental health benefits and health status were collected in an online cross-sectional survey during COVID-19 restrictions in the UK in June-July 2020. RESULTS: In total, 1056 people completed the survey. A high proportion of participants reported finding online culture helpful for mental health; all but one of the benefits were associated with regular use and some with age. Reported benefits were wide-ranging and interconnected. Those aged under 25 years were less likely to be regular users of online culture or to have increased their use during lockdown. CLINICAL IMPLICATIONS: There may be benefits in targeting cultural resources for mental health to vulnerable groups such as young adults.
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BACKGROUND: Despite the high prevalence of common mental disorders in adolescents and young adults, and their association with poor health and socio-economic outcomes throughout the lifespan, many young people do not seek or receive help for such disorders. There is growing interest in the community sector in supporting mental health in young people; however, there is little by way of experimental research in this area. During the COVID-19 pandemic and lockdown, we designed an online cultural experience to reduce anxiety and depression and support mental health in people aged 16-24. METHODS/DESIGN: The O-ACE POP (Online Active Community Engagement Proof of Principle) study is a UK-based online randomised controlled trial of an online cultural experience named Ways of Being, involving human centred narratives and viewpoints, compared with a typical museum website (the Ashmolean Museum). We aim to compare efficacy on affect, symptoms of epression and anxiety, flourishing and loneliness as well as investigating potential mechanisms of action. DISCUSSION: The COVID-19 pandemic has provided a unique opportunity to design an innovative approach to supporting mental health in young adults. Findings derived from this study will allow us to evaluate the efficacy of this intervention and will inform the design of studies to further refine the resource and test it further. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663594. Registered on 11 December 2020 (submitted in same form 27 November 2020). Protocol v1.0: 27 November 2020. Date recruitment began: 4 December 2020. Recruitment complete (estimate): February 2021.
Subject(s)
COVID-19 , Pandemics , Adolescent , Communicable Disease Control , Humans , Mental Health , Museums , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment OutcomeABSTRACT
BACKGROUND: Clostridioides difficile infection (CDI) is a healthcare-acquired infection (HAI) causing significant morbidity and mortality. Welsh CDI rates are high in comparison with those in England and Scotland. OBJECTIVES: This retrospective ecological study used aggregated disease surveillance data to understand the impact of total and high-risk Welsh GP antibiotic prescribing on total and stratified inpatient/non-inpatient CDI incidence. METHODS: All cases of confirmed CDI, during the financial years 2014-15 to 2017-18, were linked to aggregated rates of antibiotic prescribing in their GP surgery and classified as 'inpatient', 'non-inpatient' or 'unknown' by Public Health Wales. Multivariable negative-binomial regression models, comparing CDI incidence with antibiotic prescribing rates, were adjusted for potential confounders: location; age; social deprivation; comorbidities (estimated from prevalence of key health indicators) and proton pump inhibitor (PPI) prescription rates. RESULTS: There were 4613 confirmed CDI cases, with an incidence (95% CI) of 1.44 (1.40-1.48) per 1000 registered patients. Unadjusted analysis showed that an increased risk of total CDI incidence was associated with higher total antibiotic prescribing [relative risk (RR) (95% CI)â=â1.338 (1.170-1.529) per 1000 items per 1000 specific therapeutic group age-sex related GP prescribing units (STAR-PU)] and that high-risk antibiotic classes were positively associated with total CDI incidence. Location, age ≥65 years and diabetes were associated with increased risk of CDI. After adjusting for confounders, prescribing of clindamycin showed a positive association with total CDI incidence [RR (95% CI)â=â1.079 (1.001-1.162) log items per 1000 registered patients]. CONCLUSIONS: An increased risk of CDI is demonstrated at a primary care practice population level, reflecting their antibiotic prescribing rates, particularly clindamycin, and population demographics.
Subject(s)
Clostridioides difficile , Clostridium Infections , Cross Infection , Aged , Anti-Bacterial Agents/therapeutic use , Clostridioides , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Cross Infection/drug therapy , Cross Infection/epidemiology , Humans , Incidence , Retrospective Studies , Wales/epidemiologyABSTRACT
Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease. A total of nine previously unreported stage-specific candidate genes with prognostic significance were also found. Here, we integrate gene expression data from disparate sample types, disease stages and technical platforms into one coherent whole, to give a global view of the expression changes associated with the development and progression of PC from normal tissue through to metastatic disease. Summary and individual data are available online at the Prostate Integrative Expression Database (PIXdb), a user-friendly interface designed for clinicians and laboratory researchers to facilitate translational research.
ABSTRACT
Widespread mammographic screening programs and improved self-monitoring allow for breast cancer to be detected earlier than ever before. Breast-conserving surgery is a successful treatment for select women. However, up to 40% of women develop local recurrence after surgery despite apparently tumor-free margins. This suggests that morphologically normal breast may harbor early alterations that contribute to increased risk of cancer recurrence. We conducted a comprehensive transcriptomic and proteomic analysis to characterize 57 fresh-frozen tissues from breast cancers and matched histologically normal tissues resected proximal to (<2 cm) and distant from (5-10 cm) the primary tumor, using tissues from cosmetic reduction mammoplasties as baseline. Four distinct transcriptomic subtypes are identified within matched normal tissues: metabolic; immune; matrisome/epithelial-mesenchymal transition, and non-coding enriched. Key components of the subtypes are supported by proteomic and tissue composition analyses. We find that the metabolic subtype is associated with poor prognosis (p < 0.001, HR6.1). Examination of genes representing the metabolic signature identifies several genes able to prognosticate outcome from histologically normal tissues. A subset of these have been reported for their predictive ability in cancer but, to the best of our knowledge, these have not been reported altered in matched normal tissues. This study takes an important first step toward characterizing matched normal tissues resected at pre-defined margins from the primary tumor. Unlocking the predictive potential of unexcised tissue could prove key to driving the realization of personalized medicine for breast cancer patients, allowing for more biologically-driven analyses of tissue margins than morphology alone.
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Resource-based livelihoods are uncertain and potentially unstable due to variability over time, including seasonal variation: this instability threatens marginalised populations who may fall into poverty. However, empirical understanding of trajectories of household well-being and poverty is limited. Here, we present a new household-level model of poverty dynamics based on agents and coping strategies-the Household Economy And Poverty trajectory (HEAP) model. HEAP is based on established economic and social insights into poverty dynamics, with a demonstration of the model calibrated with a qualitative and quantitative household survey in coastal Bangladesh. Economic activity in Bangladesh is highly dependent on natural resources; poverty is widespread; and there is high variability in ecosystem services at multiple temporal scales. The results show that long-term decreases in poverty are predicated more on the stability of, and returns from, livelihoods rather than their diversification. Access to natural resources and ecosystem service benefits are positively correlated with stable income and multidimensional well-being. Households that remain in poverty are those who experience high seasonality of income and are involved in small scale enterprises. Hence, seasonal variability in income places significant limits on natural resources providing routes out of poverty. Further, projected economic trends to 2030 lead to an increase in well-being and a reduction in poverty for most simulated household types.
Subject(s)
Ecosystem , Family Characteristics , Models, Theoretical , Poverty , Bangladesh/epidemiology , Geography , Humans , Income , Seasons , Socioeconomic FactorsABSTRACT
Coeliac disease (CD) is an immune-mediated systemic disorder caused by the ingestion of gluten. In children, it may present with intestinal or extra-intestinal manifestations such as diarrhoea, weight loss, iron deficiency anaemia or faltering growth. Diagnosis is confirmed by small bowel biopsies showing histological changes consistent with enteropathy. In 2012, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition revised the CD guidelines and suggested that, in a selective group of symptomatic children, CD can be diagnosed without the need for small-bowel biopsies. Management of CD is through strict adherence to a life-long gluten-free diet (GFD). CD is of great public health significance as its prevalence in developing countries has been found to be similar to that in developed countries. Early recognition and treatment improves prognosis. Patients and families require long term support to enable effective adherence to a GFD lifestyle. This alone can be challenging, but through support of health professionals and dietitians, can improve patient outcomes. In resource-limited settings medical professionals need to be creative in formulating cheaper and locally sourced gluten free options in close cooperation with the dietitians thereby ensuring availability of gluten free food items at affordable prices. In this paper, we gave an overview of the subject followed by authors' view to emphasize the need for improved awareness in resource-limited settings.
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BACKGROUND: Celiac disease (CD) is a lifelong condition with significant morbidity and requires an accurate diagnosis. Guidelines for pediatric CD were revised by the European and British Societies of Paediatric Gastroenterology Hepatology and Nutrition in 2012 and 2013, respectively. New recommendations introduced non-biopsy pathway (NBP) of diagnosis for a selective group of symptomatic children whose anti-tissue transglutaminase (anti-tTG) antibody titer is greater than ten times upper limit of normal. A clear understanding of the guidelines amongst consultant pediatricians will ensure all children with suspected CD receive a prompt and secure diagnosis. The aim of this study was to establish the interpretation and implementation of the revised guideline for CD amongst consultant general pediatricians in Southwest England (SWE) during the study period. METHODS: Telephone/email survey was conducted amongst consultant general pediatricians (n ≈ 140) working in 12 secondary care hospitals across SWE. The survey included eight questions incorporating three main themes: understanding of diagnostic pathway particularly for non-biopsy diagnosis, awareness of laboratory tests involved, and variations in practice in relation to the revised guidelines. RESULTS: Responses were available from 101/140 (72%). One hundred respondents were aware of the revised guidelines for diagnosing CD. However, only 17 respondents stated all the criteria of the guideline required for diagnosis by NBP, with further 17 seeking immediate advice from a specialist. Forty-four listed both the criteria for HLA-DQ2/DQ8 testing applicable to pediatricians. Forty-nine out of 100 pediatricians would commence gluten-free diet only after all the results were available. Thirty-three pediatricians also considered asymptomatic children with high anti-tTG titer eligible for diagnosis of CD by NBP. CONCLUSIONS: There is a need for improved understanding of revised CD guidelines amongst consultant general pediatricians especially while using the NBP and requesting HLA-DQ2/DQ8 testing.
Subject(s)
Celiac Disease/diagnosis , Gastroenterology , Health Knowledge, Attitudes, Practice , Pediatrics , Practice Patterns, Physicians' , Autoantibodies/blood , Celiac Disease/diet therapy , Diet, Gluten-Free , England , GTP-Binding Proteins/immunology , Genetic Testing , HLA-DQ Antigens/genetics , Haplotypes , Humans , Practice Guidelines as Topic , Protein Glutamine gamma Glutamyltransferase 2 , Surveys and Questionnaires , Transglutaminases/immunologyABSTRACT
Innovations in -omics technologies have driven advances in biomedical research. However, integrating and analysing the large volumes of data generated from different high-throughput -omics technologies remain a significant challenge to basic and clinical scientists without bioinformatics skills or access to bioinformatics support. To address this demand, we have significantly updated our previous O-miner analytical suite, to incorporate several new features and data types to provide an efficient and easy-to-use Web tool for the automated analysis of data from '-omics' technologies. Created from a biologist's perspective, this tool allows for the automated analysis of large and complex transcriptomic, genomic and methylomic data sets, together with biological/clinical information, to identify significantly altered pathways and prioritize novel biomarkers/targets for biological validation. Our resource can be used to analyse both in-house data and the huge amount of publicly available information from array and sequencing platforms. Multiple data sets can be easily combined, allowing for meta-analyses. Here, we describe the analytical pipelines currently available in O-miner and present examples of use to demonstrate its utility and relevance in maximizing research output. O-miner Web server is free to use and is available at http://www.o-miner.org.
Subject(s)
Data Analysis , Genomics/statistics & numerical data , Software , Computational Biology , DNA Methylation , Databases, Genetic/statistics & numerical data , Gene Dosage , Gene Expression Profiling/statistics & numerical data , Humans , Internet , Neoplasms/genetics , Sequence Analysis, RNA/statistics & numerical data , Software Design , Whole Genome Sequencing/statistics & numerical dataABSTRACT
OBJECTIVES: Rates of Clostridioides (Clostridium) difficile infection (CDI) are higher in North Wales than elsewhere in the UK. We used WGS to investigate if this is due to increased healthcare-associated transmission from other cases. METHODS: Healthcare and community C. difficile isolates from patients across North Wales (February-July 2015) from glutamate dehydrogenase (GDH)-positive faecal samples underwent WGS. Data from patient records, hospital management systems and national antimicrobial use surveillance were used. RESULTS: Of the 499 GDH-positive samples, 338 (68%) were sequenced and 299 distinct infections/colonizations were identified, 229/299 (77%) with toxin genes. Only 39/229 (17%) toxigenic isolates were related within ≤2 SNPs to ≥1 infections/colonizations from a previously sampled patient, i.e. demonstrated evidence of possible transmission. Independent predictors of possible transmission included healthcare exposure in the last 12 weeks (P = 0.002, with rates varying by hospital), infection with MLST types ST-1 (ribotype 027) and ST-11 (predominantly ribotype 078) compared with all other toxigenic STs (P < 0.001), and cephalosporin exposure in the potential transmission recipient (P = 0.02). Adjusting for all these factors, there was no additional effect of ward workload (P = 0.54) or failure to meet cleaning targets (P = 0.25). Use of antimicrobials is higher in North Wales compared with England and the rest of Wales. CONCLUSIONS: Levels of transmission detected by WGS were comparable to previously described rates in endemic settings; other explanations, such as variations in antimicrobial use, are required to explain the high levels of CDI. Cephalosporins are a risk factor for infection with C. difficile from another infected or colonized case.
Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/epidemiology , Clostridium Infections/transmission , Whole Genome Sequencing , Clostridioides difficile/drug effects , Clostridium Infections/history , Clostridium Infections/microbiology , Feces/chemistry , Feces/microbiology , Female , Geography, Medical , History, 21st Century , Humans , Incidence , Male , Molecular Epidemiology , Public Health Surveillance , Risk Factors , Wales/epidemiologyABSTRACT
BACKGROUND: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. OBJECTIVE: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. DESIGN, SETTING, AND PARTICIPANTS: Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure was assessed using log-rank analysis and Cox regression analysis. RESULTS AND LIMITATIONS: Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p=2.65×10-5, p=4.28×10-5, and p=2.98×10-8). When these three datasets were combined the independent predictive value of DESNT membership was p=1.61×10-7 compared with p=1.00×10-5 for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. CONCLUSIONS: Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease. PATIENT SUMMARY: Prostate cancer, unlike breast cancer, does not have a robust classification framework. We propose that this failure has occurred because prostate cancer samples selected for analysis frequently have heterozygous compositions (individual samples are made up of many different parts that each have different characteristics). Applying a mathematical approach that can overcome this problem we identify a novel poor prognosis category of human prostate cancer called DESNT.
Subject(s)
Neoplasm Recurrence, Local/epidemiology , Prostatic Neoplasms/genetics , Bayes Theorem , Cell Adhesion/genetics , Cytoskeleton/genetics , Gene Expression Profiling , Humans , Ion Transport/genetics , Kallikreins/blood , Male , Neoplasm Recurrence, Local/blood , Prognosis , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/classification , Prostatic Neoplasms/surgeryABSTRACT
Sexual misconduct remains a problem on college campuses despite years of documentation and research, and program development and implementation. The purpose of this study was to conduct systematic theory-based formative audience research to understand how college women and men make meaning of sexual assault and bystander intervention. A total of 69 men and women aged 18 to 24 years participated in eight gender-specific focus group discussions. A grounded theory approach was used to identify patterns and themes across the data. Themes emerging from the data included the following: (a) female participants' experiences of sexism and misogyny, (b) the myth that rape is falsely reported, (c) complex understandings of consent and entitlement, (d) the reluctance to stop someone from having a "good time," (e) the role of alcohol as a moderating factor in sexual misconduct and bystander intervention, and (f) preference for direct and impactful messaging. This study informs researchers and practitioners about college students' perceptions of, and experiences with, bystander intervention and sexual assault. Practitioners can use this information to develop effective mixed media, campus-wide social marketing campaigns.
Subject(s)
Sex Offenses/psychology , Social Responsibility , Students/psychology , Aggression , Female , Humans , Male , Rape/psychology , Research Design , Sex Offenses/statistics & numerical data , Students/statistics & numerical data , Universities , Young AdultABSTRACT
The concept of community is often used in environmental policy to foster environmental stewardship and public participation, crucial prerequisites of effective management. However, prevailing conceptualizations of community based on residential location or resource use are limited with respect to their utility as surrogates for communities of shared environment-related interests, and because of the localist perspective they entail. Thus, addressing contemporary sustainability challenges, which tend to involve transnational social and environmental interactions, urgently requires additional approaches to conceptualizing community that are compatible with current globalization. We propose a framing for redefining community based on place attachment (i.e., the bonds people form with places) in the context of Australia's Great Barrier Reef, a World Heritage Area threatened by drivers requiring management and political action at scales beyond the local. Using data on place attachment from 5,403 respondents residing locally, nationally, and internationally, we identified four communities that each shared a type of attachment to the reef and that spanned conventional location and use communities. We suggest that as human-environment interactions change with increasing mobility (both corporeal and that mediated by communication and information technology), new types of people-place relations that transcend geographic and social boundaries and do not require ongoing direct experience to form are emerging. We propose that adopting a place attachment framing to community provides a means to capture the neglected nonmaterial bonds people form with the environment, and could be leveraged to foster transnational environmental stewardship, critical to advancing global sustainability in our increasingly connected world.