The influence of childhood trauma on multiple unhealthy lifestyle behaviors in adulthood

Stress and Psychopatholog

Improvements in Cardiorespiratory Fitness are not Significantly Associated With Post-traumatic Stress Disorder Symptom Reduction in Intensive Treatment

Background: Physical activity has been found to have positive effects on symptoms of post-traumatic stress disorder (PTSD). However, the importance and role of cardiorespiratory fitness (CRF) in relation to PTSD treatment outcome is not yet clear. Objective: The purpose of the present study was to test the hypothesis that CRF would increase following intensive trauma-focused treatment (TFT) of PTSD augmented with physical activity, and that improved CRF would be associated with a significant decline in PTSD symptoms. Method: One hundred-eight individuals with severe PTSD (72% women; mean age = 40.44, SD = 11.55) were enrolled in an intensive TFT programme of 8 days within 2 consecutive weeks that consisted of daily prolonged exposure (PE), eye movement desensitization and reprocessing (EMDR) therapy and 6 hours of physical activity each day. CRF levels were assessed at baseline and post-treatment with a 6-Minute Walk Test (6MWT) and, in a subsample, with a submaximal ergometer test (PWC75%/kg). Severity of PTSD symptoms was measured with the PTSD Symptom Scale-Self Report (PSS-SR). Results: A significant increase in CRF from pre- to post-treatment and a significant decrease of PTSD-symptoms was found. However, CRF difference scores were not associated with treatment outcome. Conclusions: Although individuals with PTSD may show an increase in CRF following an intensive TFT programme augmented with physical activity and a decrease of PTSD-symptoms, the current findings do not support the notion that treatment outcome is related to CRF

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Internet-based prevention of posttraumatic stress symptoms in injured trauma patients: design of a randomized controlled trial.

Background: Injured trauma victims are at risk of developing Posttraumatic Stress Disorder (PTSD) and other post-trauma psychopathology. So far, interventions using cognitive behavioral techniques (CBT) have proven most efficacious in treating early PTSD in highly symptomatic individuals. No early intervention for the prevention of PTSD for all victims has yet proven effective. In the acute psychosocial care for trauma victims, there is a clear need for easily applicable, accessible, cost-efficient early interventions. Objective: To describe the design of a randomized controlled trial (RCT) evaluating the effectiveness of a brief Internet-based early intervention that incorporates CBT techniques with the aim of reducing acute psychological distress and preventing long-term PTSD symptoms in injured trauma victims. Method: In a two armed RCT, 300 injured trauma victims from two Level-1 trauma centers in Amsterdam, the Netherlands, will be assigned to an intervention or a control group. Inclusion criteria are: being 18 years of age or older, having experienced a traumatic event according to the diagnostic criteria of the DSM-IV and understanding the Dutch language. The intervention group will be given access to the intervention's website (www.traumatips.nl), and are specifically requested to login within the first month postinjury. The primary clinical study outcome is PTSD symptom severity. Secondary outcomes include symptoms of depression and anxiety, quality of life, and social support. In addition, a cost-effectiveness analysis of the intervention will be performed. Data are collected at one week post-injury, prior to first login (baseline), and at 1, 3, 6 and 12 months. Analyses will be on an intention-to-treat basis. Discussion: The results will provide more insight into the effects of preventive interventions in general, and Internet-based early interventions specifically, on acute stress reactions and PTSD, in an injured population, during the acute phase after trauma. We will discuss possible strengths and limitations

Genomic Evolution Shapes Prostate Cancer Disease Type

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression

Genomic evolution shapes prostate cancer disease type

H.R.F. was supported by a Cancer Research UK Programme Grant to Simon Tavaré (C14303/A17197), as, partially, was A.G.L. A.G.L. acknowledges the support of the University of St Andrews. A.G.L. and J.H.R.F. also acknowledge the support of the Cambridge Cancer Research Fund.The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Aalternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.Peer reviewe

Internet-based early intervention to prevent poststraumatic stress disorder in injury patients: Randomized controlled trial.

Background: Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective: To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients. Methods: Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale-Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented. Results: The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (P<.001) without significant differences in trend. PTSD at 12 months was diagnosed in 4.7% of controls and 4.4% of intervention group patients. There were no group differences on anxiety or depressive symptoms over time. Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms (n=20) (P<.001). Conclusions: Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high-risk individuals who are more likely to benefit from the intervention

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin