tbuckley/cabot-search huggingface dataset:
School-based programmes to reduce and prevent substance use in different age groups: What works for whom? Systematic review and meta-regression analysis
Authors: Simone A. Onrust, Roy Otten, Jeroen Lammers, Filip Smit
Journal: Clinical Psychology Review (2015)

Findings from systematic reviews and meta-analyses about the effectiveness of school-based programmes to prevent or reduce substance abuse are inconclusive. We hypothesise that in order to be effective, programmes have to be aligned with the developmental stages of the intended target group (childhood, early, middle, or late adolescence). The present study provides an overview of universal and targeted programmes, while distinguishing four age groups and examining which intervention characteristics are the effective components for the respective groups. Databases were searched for controlled studies of school-based programmes, evaluating their effectiveness on either smoking, alcohol or drug use. Multivariate meta-regression analysis was used to analyse the associations between effects and programme characteristics. Our meta-analysis evaluates 288 programmes with a total of 436,180 participants. The findings support our hypothesis that specific aspects of the school-based programmes are effective in some developmental stages, but not for other age groups. The differences in effectiveness are systematically related to psychological and cognitive needs and capacities. Our findings highlight the importance of considering a developmental perspective when designing and offering school-based prevention programmes. The various developmental stages offer different possibilities and opportunities for the reduction and prevention of substance use.
Acute Increase of Cardiac Output Reduces Central Sleep Apneas in Heart Failure Patients
Authors: Piergiuseppe Agostoni, Mauro Contini, Carlo Vignati, Alberico Del Torto, Giorgio De Vecchi Lajolo, Elisabetta Salvioni, Emanuele Spadafora, Carolina Lombardi, Gino Gerosa, Tomaso Bottio, Marco Morosin, Vincenzo Tarzia, Silvia Scuri, Gianfranco Parati, Anna Apostolo
Journal: Journal of the American College of Cardiology (2015)
All Drug-Eluting Stents Are Equal, But Some Drug-Eluting Stents Are More Equal Than Others⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Bradley H. Strauss
Journal: Journal of the American College of Cardiology (2006)
Immunomodulation: checkpoint blockade etc.: Fig. 1.
Authors: William T. Curry, Michael Lim
Journal: Neuro-Oncology (2015)

The immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Checkpoint inhibitors manipulate the co-stimulatory response between antigen-presenting cells and immune cells—or between the tumor and immune cells—to elicit an antitumor immune response that would have otherwise been suppressed. Checkpoint inhibitors have shown great promise in the clinics, and some inhibitors such as anti-CTLA-4 antibodies and anti-PD-1 antibodies have gained FDA approval for certain tumors. Here we will discuss the current state of checkpoint inhibitors, biomarker strategies, and management of associated toxicities in glioblastoma.
Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection
Authors: Adam L. Bailey, Michael Lauck, Mariel Mohns, Eric J. Peterson, Kerry Beheler, Kevin G. Brunner, Kristin Crosno, Andres Mejia, James Mutschler, Matthew Gehrke, Justin Greene, Adam J. Ericsen, Andrea Weiler, Gabrielle Lehrer-Brey, Thomas C. Friedrich, Samuel D. Sibley, Esper G. Kallas, Saverio Capuano, Jeffrey Rogers, Tony L. Goldberg, Heather A. Simmons, David H. O’Connor
Journal: Science Translational Medicine (2015)

A monkey model of human pegivirus infection provides new insights into the biology of this virus.
Target Ranges of Oxygen Saturation in Extremely Preterm Infants
Authors: Eunice Shriver, Waldemar Carlo
Journal: New England Journal of Medicine (2010)

Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes.We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant.The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events.A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)
Comparison of BEACOPP and ABVD chemotherapy in intermediate stage Hodgkin’s lymphoma: Results of the fourth interim analysis of the HD 11 trial of the GHSG
Authors: B. C. Klimm, A. Engert, C. Brillant, H. T. Eich, H. K. Mueller-Hermelink, R. Herrmann, A. Ho, W. Hiddemann, R. Greil, V. Diehl
Journal: Journal of Clinical Oncology (2005)

6507 Background: Combined modality treatment is the standard treatment for intermediate stage Hodgkin’s lymphoma (HL). Despite high complete remission (CR) rates, failure rates are remarkably higher in this group of patients. In the HD 11 multicenter trial of the GHSG the BEACOPP regimen was introduced to intermediate stages in an attempt to improve therapy outcome. Simultaneously, the possibility to reduce the IF-RT dose from 30 Gy to 20 Gy is evaluated. Methods: Between May 1998 and July 2002, 1363 patients (16–75 years old) with intermediate stage HL (CS I, IIA with risk factors or IIB with elevated ESR and/or >= 3 nodal areas) were randomised according to a 2 x 2 factorial design between: 4 ABVD + 30 Gy IF-RT (arm A), 4 ABVD + 20 Gy IF-RT (arm B), 4 BEACOPP basis + 30 Gy IF-RT (arm C), and 4 BEACOPP basis + 20 Gy IF-RT (arm D). Results: In the fourth interim analysis in August 2003, 1047 (77%) patients were evaluable for chemotherapy and 982 (72%) for radiotherapy. Patient characteristics were well balanced between the treatment arms with regard to age, gender, clinical stage, histopathology and performance status. 95.1% patients reached CR, 2.0% suffered from progression, the relapse rate was 5.9%, the mortality rate 3.2%. The most frequent haematological toxicity was leucopenia observed in 33% of patients (ABVD: 27%, BEACOPP: 40%). Infection rate was 5% (ABVD: 4%, BEACOPP:7%). Nine secondary neoplasias were observed: 2 AML, 3NHL, 4 solid tumors. After a median observation time of two years overall survival (OS) was 97.4% (95%-CI: 96–98) and freedom from treatment failure (FFTF) was 89.9% (95%-CI: 88–92). Both for FFTF and OS, there was no sequential significant difference either between ABVD and BEACOPP arms nor between 30 Gy and 20 Gy IF-RT arms. Conclusions: Thus far, no differences in treatment outcome were detected, neither between the two chemotherapy regimes nor between the different doses of radiotherapy. The low FFTF (89,9% at two years) led us to further intensification of chemotherapy by the introduction of 2 cycles of escalated BEACOPP (+ 2 ABVD) versus 4 ABVD in the subsequent HD14 trial for intermediate stage HL. No significant financial relationships to disclose.
Rectal Biopsies: Inaccuracy of Histological Grading in Carcinoma of the Rectum
Authors: F H Smedley, R W Hoile, D A Macfarlane
Journal: Journal of the Royal Society of Medicine (1984)

In a consecutive series of 70 patients with carcinoma of the rectum, 42 had operable tumours and in these the histology of the initial biopsy was compared with that of the excised specimen. In 9 of the 42 patients the histological grading of the original biopsy was different from that of the final specimen; in 3 the carcinoma was missed despite repeated preoperative biopsies; and in 5, errors were made in the diagnosis of carcinoma in polyps. In 5 of 7 cases of poorly differentiated carcinoma the initial biopsies indicated moderate differentiation: there was therefore a 70% inaccuracy in the preoperative diagnosis of poorly differentiated carcinoma of the rectum. The implications of this inaccuracy for the surgery of rectal cancer are discussed.
Rectal Cancer
Authors: Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Anne Covey, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman, Charles Fuchs, Jean L. Grem, Krystyna Kiel, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Sujata Rao, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, Constantinos Sofocleous, James Thomas, Alan P. Venook, Christopher Willett
Journal: Journal of the National Comprehensive Cancer Network (2009)

In 2009 an estimated 40,870 new cases of rectal cancer will occur in the United States (23,580 cases in men; 17,290 cases in women).During the same year, an estimated 49,920 people will die from rectal and colon cancers. 1 Although colorectal cancer is ranked as the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States, mortality from colorectal cancer has decreased during the past 30 years.This decrease may be due to earlier diagnosis through screening and better treatment modalities.The recommendations in these clinical practice guidelines are classified as category 2A except where noted, meaning that there is uniform NCCN consensus, based on lower-level evidence (including
Abstract IA11: Targeting enhancers in CNS tumors
Authors: James Bradner
Journal: Cancer Research (2015)

Abstract Master regulatory transcription factors instruct cell specification and dynamically modulate cell state via interactions with cis-regulatory elements, or enhancers, that together coordinate transcriptional programs. With an interest in understanding chromatin-dependent signal transduction to RNA polymerase in developmental and disease biology, we have undertaken to discover and optimize small molecule modulators of chromatin regulatory factors that function at enhancers. This research has produced informative chemical probes, with which we have validated hypotheses regarding BRD4 in chromatin-dependent signal transduction from MYC to promote cell growth, and the influence of EZH2 on silencing developmental programs. The mechanistic study of protoypical inhibitors of BRD4 and EZH2 led to the development of genome-wide measurements of drug localization, leading to insights into how small molecules modulate chromatin structure and function as well as fundamental insights into the organization of the regulatory landscape of the human genome. Here, mechanistic insights into the role of enhancers and enhancer factors in CNS tumors will be discussed, as well as translational opportunities for the development of epigenome-directed drugs in adult and pediatric tumors. Citation Format: James Bradner. Targeting enhancers in CNS tumors. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA11.
The effectiveness of the department of defense’s field manual 3-11 in detecting, deterring and degrading the breach of a combat base by a human-borne with bioagent (HBBA): perceptions of security personnel
Authors: George Edafese Alakpa, John W. Collins
Journal: Military Medical Research (2015)

The department of defense’s FM 3-11 is among the military’s field manuals for preparing for, reacting to and recovering from chemical, biological, radiological and nuclear attacks. Since post 9-11, U.S. military service members have been deployed in the global war on terrorism. This study attempted to determine the effectiveness of the FM 3-11 in detecting, deterring or preventing a human-borne with bioagent (HBBA) terrorist breach at an entry control point (ECP). This time-specific, cross-sectional study disseminated a validated survey tool with Cronbach’s α > 0.82 to respondents who have had antiterrorism training and combat ECP experience. The return rate was greater than 75.0 %; however, many of the respondents failed to meet the inclusion criteria. Consequently, only 26 questionnaires were included in the sample. The results revealed that while over 60.0 % of the respondents either strongly agreed or agreed that biointelligence, the deployment of biodetectors and the use of biowarning systems could be effective in preventing an ECP breach by a terrorist with a bioagent, the use of protective equipment and immunization to decontaminate service members or other TTPs would never prevent a breach. A large percentage of respondents claimed that soldiers at the ECP lacked the devices or the knowledge to detect an HBBA at an ECP, and 72.0 % suggested modifying current ECP TTPs to include education, training and equipment for security personnel at military base ECPs. If obtained from appropriate sources and communicated to the personnel at the ECP in an effective or timely manner, the possible effectiveness of certain TTPs in the FM 3-11, specifically FM 3-11.86 (intelligence), might increase.
Commentary 1 on “Airway inflammation in the elite athlete and type of sportAirway inflammation in the elite athlete and type of sport”
Authors: José Naranjo Orellana
Journal: British Journal of Sports Medicine (2008)

The prevalence of exercise-induced asthma and bronchial hyper-reactivity is very high in elite athletes, especially in those who train in a microenvironment of chlorine gases (indoor swimming pools).This paper explores …
Analysis of EGFR pathway mediators in KRAS wild-type primary tumors is not representative of their status in related metastases.
Authors: P. Cejas, M. Lopez-Gomez, C. Aguayo, R. Madero, J. De Castro, C. Belda-Iniesta, J. Barriuso, E. Burgos, M. Gonzalez-Baron, J. Feliu
Journal: Journal of Clinical Oncology (2010)

3589 Background: KRAS mutated CRC patients are nonresponsive to anti-EGFR. In contrast, the clinical benefit of KRAS wild type is uncertain and needs further studies. Our retrospective study compared the status of the most relevant EGFR pathway downstream regulators between primary tumors and related metastases of KRAS wild type patients. Methods: One hundred and seventeen pairs of primaries and metastases from patients diagnosed with CRC were tested for KRAS mutated status. Wild type KRAS pairs were further analyzed downstream for EGFR mediators and for EGFR itself. Pair concordance and impact of clinicopathological variables was analyzed. Patients were anti-EGFR therapy naive. Results: The level of concordance in the presence of KRAS mutations was 92% between the primary tumor and the related metastases. KRAS wild type pairs were analyzed for BRAF and PI3KCA mutational status and for EGFR and pAKT expression and PTEN lost in patients pairs and levels of concordances were 100%, 94%, 61%, 53% and 73% respectively. Of the 61% KRAS wild type patients, only 18% showed complete concordance between the primary tumor and the related metastases for the rest of the five markers analyzed. Thus, 82% of KRAS wild type pairs showed a different EGFR pathway status between the primary tumor and the related metastasis. Conclusions: In this most extensive study to date of tumoral pairs, results show that for 82% of the KRAS wild type patients, the analysis of the primary tumor is not representative of the related metastases, suggesting the need for rebiopsy of the metastases to adjust the anti-EGFR therapy predictive value of some EGFR mediators. No significant financial relationships to disclose.
PIK3CA Mutations Can Be Acquired during Tumor Progression in Breast Cancer.
Authors: J. Dupont, J. Dupont, A. Laenkholm, A. Laenkholm, A. Knoop, A. Knoop, M. Ewertz, M. Ewertz, C. Barrett, W. Hackl, R. Bandaru, T. Crowell, J. Rheinhardt, W. Liu, H. Gardner
Journal: Cancer Research (2009)

Abstract Background: Activation of the PI3K pathway by somatic mutations in the PI3KCA oncogene plays an important role in breast cancer. Mutations in PI3KCA have been described in approximately 30 % of breast carcinomas. Dysregulation of the PI3K pathway may have a significant impact on primary or acquired resistance towards endocrine and anti HER2 targeted therapy. The objective of this study was to assess changes in mutations in PI3KCA between the primary tumor and corresponding later metastatic lesions.Material: Formalin-fixed paraffin-embedded tumor blocks were available from 104 paired samples from primary tumors and corresponding distant metastases. In 99 patients paired PI3KCA mutation results were obtained.Methods: H&amp;E sections were generated from each formalin-fixed paraffin-embedded tumor block, and thus guided two 1mm cores were obtained for Tumour microarray (TMA) preparation and DNA extraction for mutational analysis. In samples with scant tumor tissue macrodissection was made. Mutations in exon 9 (E542K, E545K) and in exon 20 (H1047L, H1047R) in the helical and the kinase domains of the PIK3CA gene encoding the catalytic p110 subunit of PI3K were analyzed by primer extension methodology using the SNaPshot Multiplex kit from ABI.Results: The PIK3CA mutations were detected in 36 % (37/102 patients) of the primary tumors or axillary nodes, with 14 % exon 9 mutations (E542K, E545K) and 25 % exon 20 mutations (H1047R, H1047L). In metastatic lesions there were mutations in 45 % (46/103), with 13 % exon 9 mutations (E542K, E545K) and 36 % exon 20 mutations (H1047R, H1047L). There was a clear increase in Exon 20 mutations in metastases (P = 0.07) suggesting that mutations in PIK3CA can be acquired during tumor progression. Exon 20 mutations were acquired in 21 % of the patients in the metastatic setting compared with the primary tumor. There was no significant change in exon 9 mutations between primary tumor and metastatic lesion. Expression analysis of other markers of interest: HER2, PTEN, p-AKT, pS6, p-ERK, KI67, cyclin D1 are being made.Conclusion: These data suggest that PI3KCA mutations can be acquired during tumor progression, indicating an increase in the activation of the PI3K pathway. Our data show that approximately half of the tumors at relapse are addicted to the PI3K pathway. The study confirms the necessity of performing tumor marker expression analysis in the metastatic lesion when it comes to treatment decision making. Correlations between the mutations, other markers of the pathway, and clinical data will be presented at the meeting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6023.
Full Donor T Cell Chimerism Predicts Transplant Outcomes In High Risk AML But Not In Intermediate Risk AML After a T-Deplete Alemtuzumab Conditioned Transplant
Authors: Amy Gudger, Vidhya Murthy, Duncan J Murray, Ben Bailiff, Maria Mushkbar, Jonathan ray Lancashire, Phillip Nicolson, Kathy Holder, Lynda Baker, Lynn Bratby, Bhuvan Kishore, Richard Lovell, Shankaranarayana Paneesha, Nikolousis Emmanouil
Journal: Blood (2013)
Lack of effect of bevacizumab on wound healing/bleeding complications when given 28–60 days following primary cancer surgery
Authors: F. Scappaticci, L. Fehrenbacher, T. Cartwright, J. Hainsworth, W. Heim, J. Berlin, F. Kabbinavar, W. Novotny, H. Hurwitz
Journal: Journal of Clinical Oncology (2004)

3530 Background: Bevacizumab [Avastin (BV)] is a humanized monoclonal antibody directed against vascular endothelial growth factor. A recent randomized, double-blinded, Phase III trial showed that addition of Avastin to chemotherapy (bolus irinotecan, 5-FU, leucovorin -IFL) increased survival compared with IFL alone. Antiangiogenic therapy has previously shown delay in wound healing in preclinical models. Therefore, we undertook an analysis of wound healing in subjects receiving BV plus bolus IFL and BV plus 5-FU/LV versus those that received bolus IFL alone. Methods: Wound healing and bleeding complications were analyzed in subjects who underwent primary cancer surgery (i.e., colonic or rectal resection to remove tumor) within 28–60 days of starting study treatment. Sixty-day post-operative adverse events reported as abnormal healing, wound dehiscence, delayed wound healing, bowel perforation, fistula, abscess, and hemorrhage were studied. Results: A total of 150 subjects receiving BV plus bolus IFL and 37 subjects receiving BV plus 5-FU/LV underwent prior cancer surgery before initial use of BV plus chemotherapy compared with 155 subjects who received bolus IFL alone. The incidence of Grade 3 / 4 wound healing / bleeding in subjects was 1 subject (0.65 %) in the bolus IFL arm alone, 3 subjects (2.0 %) in the BV + bolus IFL arm, and no subjects (0 %) in the BV + 5-FU/LV arm. Conclusions:These results suggest that surgery in subjects within 28–60 days before the initial use of Avastin does not lead to a significantly increased incidence of wound healing / bleeding complications. These results are encouraging for the planned evaluation of Avastin in adjuvant colorectal trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Bais; Genentech; Pfizer; USON Genentech Genentech Genentech; GlaxoSmithKline; Pfizer; Roche