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Author (up) Bryant, R.A.; O'Donnell, M.L.; Creamer, M.; McFarlane, A.C.; Silove, D. file  url
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  Title A multisite analysis of the fluctuating course of posttraumatic stress disorder Type Journal Article
  Year 2013 Publication JAMA Psychiatry Abbreviated Journal JAMA Psychiatry  
  Volume 70 Issue 8 Pages 839-846  
  Keywords Adolescent; Adult; Aged; Australia/epidemiology; Brain Injuries/diagnosis/epidemiology/*psychology; *Disease Progression; Female; Humans; Injury Severity Score; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Stress Disorders, Post-Traumatic/diagnosis/epidemiology/*psychology; Stress, Psychological/complications/diagnosis/epidemiology; Time Factors; Young Adult  
  Abstract IMPORTANCE: Delayed-onset posttraumatic stress disorder (PTSD) accounts for approximately 25% of PTSD cases. Current models do not adequately explain the delayed increases in PTSD symptoms after trauma exposure. OBJECTIVE: To test the roles of initial psychiatric reactions, mild traumatic brain injury (MTBI), and ongoing stressors on delayed-onset PTSD. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients were selected from recent admissions to 4 major trauma hospitals across Australia. A total of 1084 traumatically injured patients were assessed during hospital admission from April 1, 2004, through February 28, 2006, and 785 (72.4%) were followed up at 3, 12, and 24 months after injury. MAIN OUTCOME AND MEASURE: Severity of PTSD was determined at each assessment with the Clinician-Administered PTSD Scale. RESULTS: Of those who met PTSD criteria at 24 months, 44.1% reported no PTSD at 3 months and 55.9% had subsyndromal or full PTSD. In those who displayed subsyndromal or full PTSD at 3 months, PTSD severity at 24 months was predicted by prior psychiatric disorder, initial PTSD symptom severity, and type of injury. In those who displayed no PTSD at 3 months, PTSD severity at 24 months was predicted by initial PTSD symptom severity, MTBI, length of hospitalization, and the number of stressful events experienced between 3 and 24 months. CONCLUSIONS AND RELEVANCE: These data highlight the complex trajectories of PTSD symptoms over time. This study also points to the roles of ongoing stress and MTBI in delayed cases of PTSD and suggests the potential of ongoing stress to compound initial stress reactions and lead to a delayed increase in PTSD symptom severity. This study also provides initial evidence that MTBI increases the risk of delayed PTSD symptoms, particularly in those with no acute symptoms.  
  Call Number Serial 1306  
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Author (up) Ebos, J.M.L.; Kerbel, R.S. file  url
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  Title Antiangiogenic therapy: impact on invasion, disease progression, and metastasis Type Journal Article
  Year 2011 Publication Nature Reviews. Clinical Oncology Abbreviated Journal Nat Rev Clin Oncol  
  Volume 8 Issue 4 Pages 210-221  
  Keywords Angiogenesis Inhibitors/*therapeutic use; Animals; Clinical Trials as Topic; Disease Progression; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms/blood supply/*drug therapy/*pathology; Neovascularization, Pathologic/*prevention & control; Vascular Endothelial Growth Factor A/antagonists & inhibitors  
  Abstract Antiangiogenic drugs targeting the VEGF pathway have slowed metastatic disease progression in some patients, leading to progression-free survival (PFS) and overall survival benefits compared with controls. However, the results are more modest than predicted by most preclinical testing and benefits in PFS are frequently not accompanied by overall survival improvements. Questions have emerged about the basis of drug resistance and the limitations of predictive preclinical models, and also about whether the nature of disease progression following antiangiogenic therapy is different to classic cytotoxic therapies-in particular whether therapy may lead to more invasive or metastatic behavior. In addition, because of recent clinical trial failures of antiangiogenic therapy in patients with early-stage disease, and the fact that there are hundreds of trials underway in perioperative neoadjuvant and adjuvant settings, there is now greater awareness about the lack of appropriate preclinical testing that preceded these studies. Improved preclinical assessment of all stages of metastatic disease should be a priority for future antiangiogenic drug discovery and development.  
  Call Number Serial 1197  
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Author (up) Ewers, M.; Frisoni, G.B.; Teipel, S.J.; Grinberg, L.T.; Amaro, E.J.; Heinsen, H.; Thompson, P.M.; Hampel, H. file  url
doi  openurl
  Title Staging Alzheimer's disease progression with multimodality neuroimaging Type Journal Article
  Year 2011 Publication Progress in Neurobiology Abbreviated Journal Prog Neurobiol  
  Volume 95 Issue 4 Pages 535-546  
  Keywords Alzheimer Disease/complications/*diagnosis; Brain/growth & development/metabolism/pathology/*radionuclide imaging; Brain Mapping; Cognition Disorders/diagnosis/etiology/radionuclide imaging; *Disease Progression; Humans; *Positron-Emission Tomography  
  Abstract Rapid developments in medical neuroimaging have made it possible to reconstruct the trajectory of Alzheimer's disease (AD) as it spreads through the living brain. The current review focuses on the progressive signature of brain changes throughout the different stages of AD. We integrate recent findings on changes in cortical gray matter volume, white matter fiber tracts, neuropathological alterations, and brain metabolism assessed with molecular positron emission tomography (PET). Neurofibrillary tangles accumulate first in transentorhinal and cholinergic brain areas, and 4-D maps of cortical volume changes show early progressive temporo-parietal cortical thinning. Findings from diffusion tensor imaging (DTI) for assessment fiber tract integrity show cortical disconnection in corresponding brain networks. Importantly, the developmental trajectory of brain changes is not uniform and may be modulated by several factors such as onset of disease mechanisms, risk-associated and protective genes, converging comorbidity, and individual brain reserve. There is a general agreement between in vivo brain maps of cortical atrophy and amyloid pathology assessed through PET, reminiscent of post mortem histopathology studies that paved the way in the staging of AD. The association between in vivo and post mortem findings will clarify the temporal dynamics of pathophysiological alterations in the development of preclinical AD. This will be important in designing effective treatments that target specific underlying disease AD mechanisms.  
  Call Number Serial 526  
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Author (up) Galatzer-Levy, I.R.; Ankri, Y.; Freedman, S.; Israeli-Shalev, Y.; Roitman, P.; Gilad, M.; Shalev, A.Y. file  url
openurl 
  Title Early PTSD symptom trajectories: persistence, recovery, and response to treatment: results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS) Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 8 Pages e70084  
  Keywords Adolescent; Adult; Aged; Cognitive Therapy/methods; Cohort Studies; Data Interpretation, Statistical; Disease Progression; Female; Humans; Israel; Likelihood Functions; Male; Middle Aged; Models, Statistical; Psychometrics; Stress Disorders, Post-Traumatic/*diagnosis/*therapy; Symptom Assessment; Time Factors; Treatment Outcome  
  Abstract CONTEXT: Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder's pathogenesis and prophylaxis. OBJECTIVES: To describe discrete symptom trajectories and examine their relevance for preventive interventions. DESIGN: Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data. SETTING: Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity. PARTICIPANTS: Adult survivors of potentially traumatic events consecutively admitted to the hospital's emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months. APPROACH: We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8+/-5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8+/-42.4 days. CBT effectively reduced PTSD symptoms in the entire sample. MAIN OUTCOME MEASURE: Latent trajectories of PTSD symptoms; effects of CBT on these trajectories. RESULTS: THREE TRAJECTORIES WERE IDENTIFIED: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes. CONCLUSIONS: The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.  
  Call Number Serial 1307  
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Author (up) Kahrilas, P.J.; Boeckxstaens, G. file  url
openurl 
  Title The spectrum of achalasia: lessons from studies of pathophysiology and high-resolution manometry Type Journal Article
  Year 2013 Publication Gastroenterology Abbreviated Journal Gastroenterology  
  Volume 145 Issue 5 Pages 954-965  
  Keywords Algorithms; Disease Progression; Esophageal Achalasia/*classification/*physiopathology; Humans; Manometry/*methods; Muscle Contraction/physiology; Muscle Relaxation/physiology; Peristalsis/physiology; *Phenotype; Achalasia; Dysphagia; Egj; Ept; Esophageal Motility; Hsv-1; Irp; Les; Pathogenesis; Tlesr; esophageal pressure topography; esophagogastric junction; herpes simplex virus 1; integrated relaxation pressure; lower esophageal sphincter; transient lower esophageal sphincter relaxation  
  Abstract High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of achalasia. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific. Laboratory studies indicate that achalasia is an autoimmune disease in which esophageal myenteric neurons are attacked in a cell-mediated and antibody-mediated immune response against an uncertain antigen. This autoimmune response could be related to infection of genetically predisposed subjects with herpes simplex virus 1, although there is substantial heterogeneity among patients. At one end of the spectrum is complete aganglionosis in patients with end-stage or fulminant disease. At the opposite extreme is type III (spastic) achalasia, which has no demonstrated neuronal loss but only impaired inhibitory postganglionic neuron function; it is often associated with accentuated contractility and could be mediated by cytokine-induced alterations in gene expression. Distinct from these extremes is progressive plexopathy, which likely arises from achalasia with preserved peristalsis and then develops into type II achalasia and then type I achalasia. Variations in its extent and rate of progression are likely related to the intensity of the cytotoxic T-cell assault on the myenteric plexus. Moving forward, we need to integrate the knowledge we have gained into treatment paradigms that are specific for individual phenotypes of achalasia and away from the one-size-fits-all approach.  
  Call Number Serial 2091  
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Author (up) Naxerova, K.; Jain, R.K. file  url
openurl 
  Title Using tumour phylogenetics to identify the roots of metastasis in humans Type Journal Article
  Year 2015 Publication Nature Reviews. Clinical Oncology Abbreviated Journal Nat Rev Clin Oncol  
  Volume 12 Issue 5 Pages 258-272  
  Keywords Disease Progression; Epigenomics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Microsatellite Repeats; Models, Biological; Neoplasm Metastasis/genetics/*pathology; Neoplasms/genetics; Neoplastic Cells, Circulating/pathology; Phylogeny; Polymorphism, Single Nucleotide  
  Abstract In cancer, much uncertainty remains regarding the origins of metastatic disease. Models of metastatic progression offer competing views on when dissemination occurs (at an early or late stage of tumour development), whether metastases at different sites arise independently and directly from the primary tumour or give rise to each other, and whether dynamic cell exchange occurs between synchronously growing lesions. Although it is probable that many routes can lead to the establishment of systemic disease, clinical observations suggest that distinct modes of metastasis might prevail in different tumour types. Gaining a more-comprehensive understanding of the evolutionary processes that underlie metastasis is not only relevant from a basic biological perspective, but also has profound clinical implications. The 'tree of life' of metastatic cancer contains answers to many outstanding questions about the development of systemic disease, but has only been reconstructed in a limited number of patients. Here we review available data on the phylogenetic relationships between primary solid tumours and their metastases, and examine to what degree they support different models of metastatic progression. We provide a description of experimental methods for lineage tracing in human cancer, ranging from broad DNA-sequencing approaches to more-targeted techniques, and discuss their respective benefits and caveats. Finally, we propose future research questions in the area of cancer phylogenetics.  
  Call Number Serial 1928  
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Author (up) Pikarsky, E.; Porat, R.M.; Stein, I.; Abramovitch, R.; Amit, S.; Kasem, S.; Gutkovich-Pyest, E.; Urieli-Shoval, S.; Galun, E.; Ben-Neriah, Y. file  url
openurl 
  Title NF-kappaB functions as a tumour promoter in inflammation-associated cancer Type Journal Article
  Year 2004 Publication Nature Abbreviated Journal Nature  
  Volume 431 Issue 7007 Pages 461-466  
  Keywords ATP Binding Cassette Transporter, Sub-Family B/deficiency/genetics; ATP-Binding Cassette Transporters/genetics; Animals; Carcinoma, Hepatocellular/*complications/etiology/*metabolism/pathology; Chronic Disease; Disease Progression; Hepatitis/complications/etiology/metabolism/pathology; Hepatocytes/metabolism/pathology; I-kappa B Proteins/metabolism; Inflammation/*complications/*metabolism/pathology; Liver/metabolism/pathology; Mice; Mice, Knockout; NF-kappa B/*metabolism; Paracrine Communication; Tumor Necrosis Factor-alpha/metabolism  
  Abstract The causes of sporadic human cancer are seldom recognized, but it is estimated that carcinogen exposure and chronic inflammation are two important underlying conditions for tumour development, the latter accounting for approximately 20% of human cancer. Whereas the causal relationship between carcinogen exposure and cancer has been intensely investigated, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. We proposed that activation of the nuclear factor kappaB (NF-kappaB), a hallmark of inflammatory responses that is frequently detected in tumours, may constitute a missing link between inflammation and cancer. To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a prototype of inflammation-associated cancer. We monitored hepatitis and cancer progression in Mdr2-knockout mice, and here we show that the inflammatory process triggers hepatocyte NF-kappaB through upregulation of tumour-necrosis factor-alpha (TNFalpha) in adjacent endothelial and inflammatory cells. Switching off NF-kappaB in mice from birth to seven months of age, using a hepatocyte-specific inducible IkappaB-super-repressor transgene, had no effect on the course of hepatitis, nor did it affect early phases of hepatocyte transformation. By contrast, suppressing NF-kappaB inhibition through anti-TNFalpha treatment or induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma. Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases.  
  Call Number Serial 2053  
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Author (up) Shrestha, R.; Trauger-Querry, B.; Loughrin, A.; Appleby, B.S. file  url
openurl 
  Title Visual art therapy in sporadic Creutzfeldt-Jakob disease: a case study Type Journal Article
  Year 2016 Publication Neurocase Abbreviated Journal Neurocase  
  Volume 22 Issue 2 Pages 243-247  
  Keywords Adult; Art Therapy/*methods; Cerebral Cortex/diagnostic imaging/pathology; Creutzfeldt-Jakob Syndrome/diagnostic imaging/pathology/*rehabilitation; Diffusion Magnetic Resonance Imaging; Female; Fluorodeoxyglucose F18/pharmacokinetics; Humans; Photic Stimulation/*methods; Positron-Emission Tomography; Treatment Outcome; Visual Perception/physiology; Prion disease; art therapy; disease progression; patient outcome; sporadic Creutzfeldt-Jakob disease  
  Abstract This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals.  
  Call Number Serial 2087  
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