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Author Yan, H.; Romero-Lopez, M.; Benitez, L.I.; Di, K.; Frieboes, H.B.; Hughes, C.C.W.; Bota, D.A.; Lowengrub, J.S. url  doi
openurl 
  Title 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal (up) Cancer Res  
  Volume 77 Issue 15 Pages 4171-4184  
  Keywords Brain Neoplasms/*pathology; Cell Transdifferentiation/physiology; Endothelial Cells/*pathology; Glioblastoma/*pathology; Humans; *Models, Theoretical; Neoplastic Stem Cells/*pathology  
  Abstract Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, cross-talk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Furthermore, GSC also transdifferentiate into bona fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional antiangiogenic therapies. Here we use three-dimensional mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSCs drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with antiangiogenic therapies reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSCs and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GECs maintain GSCs. Our study suggests that a combinatorial regimen targeting the vasculature, GSCs, and GECs, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. Cancer Res; 77(15); 4171-84. (c)2017 AACR.  
  Address Center for Complex Biological Systems, University of California, Irvine, California  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28536277 Approved no  
  Call Number ref @ user @ Serial 96585  
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Author Ribeiro, A.P.; Souza, E.R. de; Sousa, C.A.M. de url  doi
openurl 
  Title Injuries caused by firearms treated at Brazilian urgent and emergency healthcare services Type Journal Article
  Year 2017 Publication Ciencia & Saude Coletiva Abbreviated Journal (up) Cien Saude Colet  
  Volume 22 Issue 9 Pages 2851-2860  
  Keywords  
  Abstract This paper analyzes the medical care given at Brazilian urgent and emergency healthcare services to people injured by firearms in 2014. A cross-sectional study was carried out on care given to patients with firearms injuries in 24 capital cities of Brazilian states and in the Brazilian Federal District, included in the VIVA Survey. Simple and relative frequencies of the variables related to the patients and to the event were calculated, and a logistic model for complex samples was applied adopting care for firearms injuries patients as outcome. The results show the following percentages of care events as caused by firearms: 0.7% for the category 'other accidents (other than transport-related accidents)', 1.5% for self-inflicted injuries, 15.9% for injuries due to assault, and 65.1% of cases arising from legal intervention. The care given was predominantly to young male adults (age 20-39), of mixed race and with a low level of schooling. The most common injuries were: to arms and legs; and to multiple organs. The paper concludes by discussing the efforts to control firearms held by the public in Brazil, and how they can lead to severe and lethal outcomes in quarrels and interpersonal disputes.  
  Address Departamento de Estudos sobre Violencia e Saude Jorge Careli/Claves, Escola Nacional de Saude Publica, Fiocruz. Av. Brasil 4036/7 masculine, Manguinhos. 21040-210 Rio de Janeiro RJ Brasil. adalpeixoto@yahoo.com.br  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title Lesoes provocadas por armas de fogo atendidas em servicos de urgencia e emergencia brasileiros  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1413-8123 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28954136 Approved no  
  Call Number ref @ user @ Serial 97503  
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Author Nourallah, B.; Digpal, R.; Jena, R.; Watts, C. url  doi
openurl 
  Title Irradiating the Subventricular Zone in Glioblastoma Patients: Is there a Case for a Clinical Trial? Type Journal Article
  Year 2017 Publication Clinical Oncology (Royal College of Radiologists (Great Britain)) Abbreviated Journal (up) Clin Oncol (R Coll Radiol)  
  Volume 29 Issue 1 Pages 26-33  
  Keywords Adult; Brain Neoplasms/*radiotherapy; Glioblastoma/*radiotherapy; Humans; Lateral Ventricles/*radiation effects; Male; Neoplastic Stem Cells/radiation effects; Stem Cell Niche/radiation effects; Cancer stem cells; glioblastoma; neural stem cells; radiotherapy; subventricular zone  
  Abstract Glioblastoma is the most common and aggressive adult brain tumour. Over the last 10 years it has emerged that the subventricular zone (SVZ), the largest adult neural stem cell niche, has an important role in the disease. Converging evidence has implicated transformation of adult neural stems in gliomagenesis and the permissive stem cell niche in disease recurrence. Concurrently, clinical studies have suggested that SVZ involvement is a negative prognostic marker. It would follow that irradiating the SVZ may improve outcomes in glioblastoma by directly targeting this putative sanctuary site. To investigate this potential strategy, 11 retrospective studies and 1 prospective study examined the relationship between dose to the SVZ and survival outcomes in glioblastoma patients. This review summarises the theoretical underpinning of this strategy, provides a critical evaluation of the existing evidence and discusses the rationale for a clinical trial.  
  Address John van Geest Centre for Repair, Cambridge, UK; Department of Clinical Neurosciences, Division of Neurosurgery, Addenbrookes Hospital, Cambridge, UK. Electronic address: cw209@cam.ac.uk  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0936-6555 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27729188 Approved no  
  Call Number ref @ user @ Serial 96633  
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Author Foro Arnalot, P.; Pera, O.; Rodriguez, N.; Sanz, X.; Reig, A.; Membrive, I.; Ortiz, A.; Granados, R.; Algara, M. url  doi
openurl 
  Title Influence of incidental radiation dose in the subventricular zone on survival in patients with glioblastoma multiforme treated with surgery, radiotherapy, and temozolomide Type Journal Article
  Year 2017 Publication Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico Abbreviated Journal (up) Clin Transl Oncol  
  Volume Issue Pages  
  Keywords Glioblastoma; Radiotherapy; Subventricular zone  
  Abstract PURPOSE: To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide. METHODS AND MATERIALS: Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models. Covariates included: age, sex, surgery, tumor location, and concomitant and adjuvant temozolomide. RESULTS: Median progression-free survival and overall survival were 11.5 +/- 9.96 and 18.8 +/- 18.5 months, respectively. The p75 doses to the ipsilateral, contralateral and bilateral subventrivular zone were, respectively, 57.30, 48.8, and 52.7 Gy. Patients who received a dose >/=48.8 Gy in the contralateral subventricular zone had better progression-free survival than those who received lower doses (HR 0.46; 95% CI 0.23-0.91 P = 0.028). This association was not found for overall survival (HR 0.60; 95% CI 0.30-1.22 P = 0.16). Administration of adjuvant temozolomide was significantly associated with improved progression-free survival (HR 0.19; 95% CI 0.09-0.41 P < 0.0001) and overall survival (HR 0.11; 95% CI 0.05-0.24 P = 0.001). In the subgroup of 46 patients whose O6-methylguanine-DNA methyltransferase gene promoter status was known, the methylation had no effect on either progression-free survival (P = 0.491) or overall survival (P = 0.203). CONCLUSION: High-dose radiation in the contralateral subventricular zone was associated with a significant improvement in progression-free survival but not overall survival in patients treated for glioblastoma multiforme.  
  Address Universitat Pompeu Fabra, Barcelona, Spain  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1699-048X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28389881 Approved no  
  Call Number ref @ user @ Serial 96597  
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Author Ramke, J.; Petkovic, J.; Welch, V.; Blignault, I.; Gilbert, C.; Blanchet, K.; Christensen, R.; Zwi, A.B.; Tugwell, P. url  doi
openurl 
  Title Interventions to improve access to cataract surgical services and their impact on equity in low- and middle-income countries Type Journal Article
  Year 2017 Publication The Cochrane Database of Systematic Reviews Abbreviated Journal (up) Cochrane Database Syst Rev  
  Volume 11 Issue Pages Cd011307  
  Keywords  
  Abstract BACKGROUND: Cataract is the leading cause of blindness in low- and middle-income countries (LMICs), and the prevalence is inequitably distributed between and within countries. Interventions have been undertaken to improve cataract surgical services, however, the effectiveness of these interventions on promoting equity is not known. OBJECTIVES: To assess the effects on equity of interventions to improve access to cataract services for populations with cataract blindness (and visual impairment) in LMICs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 3), MEDLINE Ovid (1946 to 12 April 2017), Embase Ovid (1980 to 12 April 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 12 April 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 12 April 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 12 April 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 12 April 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included studies that reported on strategies to improve access to cataract services in LMICs using the following study designs: randomised and quasi-randomised controlled trials (RCTs), controlled before-and-after studies, and interrupted time series studies. Included studies were conducted in LMICs, and were targeted at disadvantaged populations, or disaggregated outcome data by 'PROGRESS-Plus' factors (Place of residence; Race/ethnicity/ culture/ language; Occupation; Gender/sex; Religion; Education; Socio-economic status; Social capital/networks. The 'Plus' component includes disability, sexual orientation and age). DATA COLLECTION AND ANALYSIS: Two authors (JR and JP) independently selected studies, extracted data and assessed them for risk of bias. Meta-analysis was not possible, so included studies were synthesised in table and text. MAIN RESULTS: From a total of 2865 studies identified in the search, two met our eligibility criteria, both of which were cluster-RCTs conducted in rural China. The way in which the trials were conducted means that the risk of bias is unclear. In both studies, villages were randomised to be either an intervention or control group. Adults identified with vision-impairing cataract, following village-based vision and eye health assessment, either received an intervention to increase uptake of cataract surgery (if their village was an intervention group), or to receive 'standard care' (if their village was a control group).One study (n = 434), randomly allocated 26 villages or townships to the intervention, which involved watching an informational video and receiving counselling about cataract and cataract surgery, while the control group were advised that they had decreased vision due to cataract and it could be treated, without being shown the video or receiving counselling. There was low-certainty evidence that providing information and counselling had no effect on uptake of referral to the hospital (OR 1.03, 95% CI 0.63 to 1.67, 1 RCT, 434 participants) and little or no effect on the uptake of surgery (OR 1.11, 95% CI 0.67 to 1.84, 1 RCT, 434 participants). We assessed the level of evidence to be of low-certainty for both outcomes, due to indirectness of evidence and imprecision of results.The other study (n = 355, 24 towns randomised) included three intervention arms: free surgery; free surgery plus reimbursement of transport costs; and free surgery plus free transport to and from the hospital. These were compared to the control group, which was reminded to use the “low-cost” ( USD 38) surgical service. There was low-certainty evidence that surgical fee waiver with/without transport provision or reimbursement increased uptake of surgery (RR 1.94, 95% CI 1.14 to 3.31, 1 RCT, 355 participants). We assessed the level of evidence to be of low-certainty due to indirectness of evidence and imprecision of results.Neither of the studies reported our primary outcome of change in prevalence of cataract blindness, or other outcomes such as cataract surgical coverage, surgical outcome, or adverse effects. Neither study disaggregated outcomes by social subgroups to enable further assessment of equity effects. We sought data from both studies and obtained data from one; the information video and counselling intervention did not have a differential effect across the PROGRESS-Plus categories with available data (place of residence, gender, education level, socioeconomic status and social capital). AUTHORS' CONCLUSIONS: Current evidence on the effect on equity of interventions to improve access to cataract services in LMICs is limited. We identified only two studies, both conducted in rural China. Assessment of equity effects will be improved if future studies disaggregate outcomes by relevant social subgroups. To assist with assessing generalisability of findings to other settings, robust data on contextual factors are also needed.  
  Address School of Population Health, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1361-6137 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29119547 Approved no  
  Call Number ref @ user @ Serial 97501  
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