Feasibility and limitations of using commercial databases to evaluate residential mobility in registry-based research on childhood cancer.

BACKGROUND: Researchers have used commercial databases containing residential addresses to reduce exposure misclassification in case-control studies. Our objective is to evaluate the potential systematic bias regarding case status when reconstructing residential locations from commercial databases. METHODS: Our study population of 3640 Colorado-born children includes 520 children diagnosed with acute lymphocytic leukemia between 2002 and 2019. We aligned addresses and date ranges obtained from LexisNexis with registry dates to determine three dichotomous outcomes: Found in LexisNexis, conception date found in LexisNexis, and reference date/diagnosis date found in LexisNexis. We applied logistic regression to determine whether outcomes differed by case status. RESULTS: Mothers of cases were 39% more likely to be found in LexisNexis than mothers of controls (OR = 1.39, 95% CI: 0.97, 2). Of the mothers found in LexisNexis, a conception address was 33% more likely (OR= 1.33, 95% CI: 1.06, 1.66) and a reference/diagnosis address was 60% more likely (OR= 1.60, 95% CI: 1.21, 2.12) to be found for mothers of cases than mothers of controls. CONCLUSION: This study indicates that use of commercial databases to reconstruct residential locations may systematically bias results in case-control studies of childhood cancers.

Evaluating the sensitivity of mortality attributable to pollution to modeling Choices: A case study for Colorado.

We evaluated the sensitivity of estimated PM2.5 and NO2 health impacts to varying key input parameters and assumptions including: 1) the spatial scale at which impacts are estimated, 2) using either a single concentration-response function (CRF) or using racial/ethnic group specific CRFs from the same epidemiologic study, 3) assigning exposure to residents based on home, instead of home and work locations for the state of Colorado. We found that the spatial scale of the analysis influences the magnitude of NO2, but not PM2.5, attributable deaths. Using county-level predictions instead of 1 km2 predictions of NO2 resulted in a lower estimate of mortality attributable to NO2 by âˆ¼ 50 % for all of Colorado for each year between 2000 and 2020. Using an all-population CRF instead of racial/ethnic group specific CRFs results in a 130 % higher estimate of annual mortality attributable for the white population and a 40 % and 80 % lower estimate of mortality attributable to PM2.5 for Black and Hispanic residents, respectively. Using racial/ethnic group specific CRFs did not result in a different estimation of NO2 attributable mortality for white residents, but led to âˆ¼ 50 % lower estimates of mortality for Black residents, and 290 % lower estimate for Hispanic residents. Using NO2 based on home instead of home and workplace locations results in a smaller estimate of annual mortality attributable to NO2 for all of Colorado by 2 % each year and 0.3 % for PM2.5. Our results should be interpreted as an exercise to make methodological recommendations for future health impact assessments of pollution.

Health Symptoms and Proximity to Active Multi-Well Unconventional Oil and Gas Development Sites in the City and County of Broomfield, Colorado.

City and County of Broomfield (CCOB) residents reported over 500 health concerns between January 2020 and December 2021. Our objective was to determine if CCOB residents living within 1 mile of multi-well unconventional oil and gas development (UOGD) sites reported more frequent health symptoms than residents living > 2 miles away. We invited 3993 randomly selected households to participate in a health survey. We applied linear regression to test associations between distance to UOGD and summed Likert scores for health symptom categories. After covariate adjustment, respondents living within 1 mile of one of CCOB's UOGD sites tended to report higher frequencies of upper respiratory, lower respiratory, gastrointestinal and acute symptoms than respondents living more than 2 miles from the sites, with the largest differences for upper respiratory and acute symptoms. For upper respiratory and acute symptoms, scores differed by 0.81 (95% CI: 0.06, 2.58) and 0.75 (95% CI: 0.004, 1.99), respectively. Scores for adults most concerned about air pollution, noise and odors trended higher within 1 mile for all symptom categories, while scores among adults least concerned trended lower. Scores trended higher for lower respiratory, gastrointestinal and acute symptoms in children living within 2 miles of UOGD, after covariate adjustment. We did not observe any difference in the frequency of symptoms reported in unadjusted results. Additional study is necessary to understand relationships between proximity to UOGD and health symptoms.

Understanding Emerging Environmental Health Concerns and Environmental Public Health-Tracking Priorities Among State and Local Professionals in Colorado.

CONTEXT: Colorado is experiencing dramatic changes related to population growth, climate change, and expanded industrial activity. Local and state public health professionals are trying to address a growing array of unique public health issues with stagnant or limited resources. OBJECTIVES: To understand, through perspectives from local and state public health professionals, the alignment of contemporary environmental and community health issues with state and local capacity and state environmental public health-tracking priorities. DESIGN: During 2014-2015, we conducted semistructured interviews which informed the development of a statewide survey of Colorado's professionals from public health, emergency management, forestry, and transportation. SETTING: This work took place in Colorado. PARTICIPANTS: Fifteen professionals from public (n = 9), academic (n = 4), and private (n = 2) sectors were interviewed. Forty-seven professionals, representing 34 counties and 40 public agencies, completed the 25-minute online survey. MAIN OUTCOME MEASURES: Environmental and community health concerns; contributing factors to environmental concerns; strengths and limitations of capacity to respond to issues; and frequency of community engagement activities. RESULTS: Top environmental health concerns were indoor air pollution (eg, radon), outdoor air pollution, and waste management. Transportation, extreme weather (eg, wildfires), and oil and gas development were most frequently reported as major contributing factors to concerns. Obesity, physical inactivity, and mental illness were the top community health concerns. To remain prepared for emerging challenges, professionals cited a need for more spatiotemporal-refined data related to their top concerns in the environmental public health-tracking database, and support from local, state, and federal agencies, in addition to personnel and funding. To address concerns, participants reported frequently working with government officials, advisory committees, and media outlets. CONCLUSIONS: This project illuminates opportunities to strengthen connections between the state's environmental public health-tracking priorities and local-level capacity related to professionals' top concerns. It also suggests reinforcing and broadening partnerships to improve data infrastructure and inform environmental public health priorities.

Value improvement at the point of care: engaging and empowering front-line teams with a new quality improvement methodology.

BACKGROUND: Healthcare organisations require systems to consistently meet the needs of their patients while providing excellent quality of care. The value improvement (VI) approach was developed by the Institute for healthcare improvement and successfully piloted at Raigmore Hospital, Scotland. It showed positive results in improving outcomes and reducing costs. Our multidisciplinary team from a tertiary care cardiac hospital in Doha, Qatar wanted to see if we could improve value in a clinically and geographically distinct context. We sought to understand the effectiveness of this approach as an integrative management philosophy that aims for continuous improvement in the quality of services by increasing efficiency and reducing waste. METHODS: This study evaluates the outcomes achieved from applying the VI methodology. The method is rooted in a framework that emphasises standardisation, continuous process improvement and rightsizing capacity to demand. The main tools include a data box score, a visual management board and weekly communication huddles. RESULTS: As a result of the VI methodology, our team achieved improvements across performance, staff capacity and cost domains. Compared with the 4-8 weeks baseline data collection period, these improvements included an increase in discharges before 13:00 hour by 61%, a reduction in the number of blood samples per patient per day by 20%, an increase in nursing time spent in direct patient care by 18%, and an increase in staff satisfaction to 40%. CONCLUSIONS: We found that the VI approach offered a systematic method for continuously improving the quality of care by focusing attention each week on safety, efficiency and patient experience. The team improved numerous processes and outcomes resulting in a positive impact on patients and families and increased the engagement of staff in continuous improvement. In this way, we improved our capacity to undertake and complete quality projects.

Associations Between Socioeconomic Context and Congenital Heart Disease Related Outcomes in Adolescents and Adults.

Little is known about the relation between socioeconomic factors and health outcomes in adults and adolescents with congenital heart defects (CHD). Population-level data from the Colorado CHD surveillance system from 2011 to 2013 was used to examine the association between area deprivation and outcomes including hospitalizations, emergency department visits, cardiac procedures, all-cause and cardiac-related mortality, and major adverse cardiac events. Socioeconomic context was measured by the Area Deprivation Index at census tract level. Missing race/ethnicity was imputed using the Bayesian Improved Surname Geocoding algorithm. Generalized linear models were utilized to examine health disparities across deprivation quintiles after adjusting for insurance type, race/ethnicity, age, gender, urbanicity, and CHD severity in 5,748 patients. Cases residing in the most deprived quintile had 51% higher odds of inpatient admission, 74% higher odds of emergency department visit, 41% higher odds of cardiac surgeries, and 45% higher odds of major adverse cardiac events compared with cases in the least deprived quintile. Further, rates of hospitalizations, emergency department admissions, and cardiac surgeries were elevated in the most deprived compared with the least deprived quintile. Mortality was not significantly different across quintiles. In conclusion, findings suggest significant health equity issues for adolescent and adults with CHD based on area-based deprivation.

Population-level surveillance of congenital heart defects among adolescents and adults in Colorado: Implications of record linkage.

BACKGROUND: The objective was to describe the design of a population-level electronic health record (EHR) and insurance claims-based surveillance system of adolescents and adults with congenital heart defects (CHDs) in Colorado and to evaluate the bias introduced by duplicate cases across data sources. METHODS: The Colorado CHD Surveillance System ascertained individuals aged 11-64 years with a CHD based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic coding between 2011 and 2013 from a diverse network of health care systems and an All Payer Claims Database (APCD). A probability-based identity reconciliation algorithm identified duplicate cases. Logistic regression was conducted to investigate bias introduced by duplicate cases on the relationship between CHD severity (severe compared to moderate/mild) and adverse outcomes including all-cause mortality, inpatient hospitalization, and major adverse cardiac events (myocardial infarction, congestive heart failure, or cerebrovascular event). Sensitivity analyses were conducted to investigate bias introduced by the sole use or exclusion of APCD data. RESULTS: A total of 12,293 unique cases were identified, of which 3,476 had a within or between data source duplicate. Duplicate cases were more likely to be in the youngest age group and have private health insurance, a severe heart defect, a CHD comorbidity, and higher health care utilization. We found that failure to resolve duplicate cases between data sources would inflate the relationship between CHD severity and both morbidity and mortality outcomes by ~15%. Sensitivity analyses indicate that scenarios in which APCD was excluded from case finding or relied upon as the sole source of case finding would also result in an overestimation of the relationship between a CHD severity and major adverse outcomes. DISCUSSION: Aggregated EHR- and claims-based surveillance systems of adolescents and adults with CHD that fail to account for duplicate records will introduce considerable bias into research findings. CONCLUSION: Population-level surveillance systems for rare chronic conditions, such as congenital heart disease, based on aggregation of EHR and claims data require sophisticated identity reconciliation methods to prevent bias introduced by duplicate cases.

Air Monitoring Stations Far Removed from Drilling Activities do not Represent Residential Exposures to Marcellus Shale Air Pollutants. Response to the Paper by Hess et al. on Proximity-Based Unconventional Natural Gas Exposure Metrics.

In their study "Assessing Agreement in Exposure Classification between Proximity-Based Metrics and Air Monitoring Data in Epidemiology Studies of Unconventional Resource Development" [...].

Factors Influencing the Implementation of a Hospitalwide Intervention to Promote Professionalism and Build a Safety Culture: A Qualitative Study.

BACKGROUND: There is widespread recognition that creating a safety culture supports high-quality health care. However, the complex factors affecting cultural change interventions are not well understood. This study examines factors influencing the implementation of an intervention to promote professionalism and build a safety culture at an Australian hospital. METHODS: The study was completed midway into the three-year intervention and involved collecting qualitative data from two sources. First, face-to-face interviews were conducted pre- and mid-intervention with a purposely selected sample. Second, a survey with three open-ended questions was completed one year into the intervention by clinical and patient support staff. Data from interviews and survey questions were analyzed using a combination of inductive and deductive approaches. RESULTS: A total of 25 participants completed preintervention interviews, and 24 took part mid-intervention. Of the 2,047 staff who completed the survey (61% response rate), 59.1% of respondents answered at least one open-ended question. Multiple interrelated factors were identified as enhancing intervention implementation. These include sustaining a favorable implementation climate, leaders consistently demonstrating behaviors that support a safety culture, increasing compatibility of working conditions with intervention aims, building confidence in systems to address unprofessional behaviors, and responding to evolving needs. CONCLUSION: Strengthening safety culture remains an enduring challenge, but this study yields valuable insights into factors influencing implementation of a multifaceted behavior change intervention. The findings provide a basis for practical strategies that health care leaders seeking cultural improvements can employ to enhance the delivery of similar interventions and address potential impediments to success.

Congenital heart defects and intensity of oil and gas well site activities in early pregnancy.

BACKGROUND: Preliminary studies suggest that offspring to mothers living near oil and natural gas (O&G) well sites are at higher risk of congenital heart defects (CHDs). OBJECTIVES: Our objective was to address the limitations of previous studies in a new and more robust evaluation of the relationship between maternal proximity to O&G well site activities and births with CHDs. METHODS: We employed a nested case-control study of 3324 infants born in Colorado between 2005 and 2011. 187, 179, 132, and 38 singleton births with an aortic artery and valve (AAVD), pulmonary artery and valve (PAVD), conotruncal (CTD), or tricuspid valve (TVD) defect, respectively, were frequency matched 1:5 to controls on sex, maternal smoking, and race and ethnicity yielding 2860 controls. We estimated monthly intensities of O&G activity at maternal residences from three months prior to conception through the second gestational month with our intensity adjusted inverse distance weighted model. We used logistic regression models adjusted for O&G facilities other than wells, intensity of air pollution sources not associated with O&G activities, maternal age and socioeconomic status index, and infant sex and parity, to evaluate associations between CHDs and O&G activity intensity groups (low, medium, and high). RESULTS: Overall, CHDs were 1.4 (1.0, 2.0) and 1.7 (1.1, 2.6) times more likely than controls in the medium and high intensity groups, respectively, compared to the low intensity group. PAVDs were 1.7 (0.93, 3.0) and 2.5 (1.1, 5.3) times more likely in the medium and high intensity groups for mothers with an address found in the second gestational month. In rural areas, AAVDs, CTDs, and TVDs were 1.8 (0.97, 3.3) and 2.6 (1.1, 6.1); 2.1 (0.96, 4.5) and 4.0 (1.4, 12); and 3.4 (0.95, 12) and 4.6 (0.81, 26) times more likely than controls in the medium and high intensity groups. CONCLUSIONS: This study provides further evidence of a positive association between maternal proximity to O&G well site activities and several types of CHDs, particularly in rural areas.

Environmental Justice in Unconventional Oil and Natural Gas Drilling and Production: A Critical Review and Research Agenda.

The drilling phase of oil and natural gas development is a growing area of environmental justice (EJ) research, particularly in the United States. Its emergence complements the longstanding EJ scholarship on later phases of the oil and gas commodity chain, such as pipeline transport, refining, and consumption. The growing scholarly attention to the EJ implications of drilling has been prompted by the surge in development of unconventional oil and gas resources in recent decades. More specifically, the oil and gas industry's adoption of horizontal drilling and hydraulic fracturing (a.k.a., "fracking" or "fracing") as methods for extracting oil and gas from a wider range of geologic formations has simultaneously heightened oil and gas production, brought extractive activities closer to more people, intensified them, and made well pad siting more flexible. Here, we provide a critical review of the novel EJ research questions that are being prompted by these on-the-ground changes in extractive techniques and patterns, propose an interdisciplinary conceptual framework for guiding EJ inquiry in this context, discuss key methodological considerations, and propose a research agenda to motivate future inquiry.

Community Noise and Air Pollution Exposure During the Development of a Multi-Well Oil and Gas Pad.

Unconventional oil and gas development (UOGD) in the United States is increasingly being conducted on multiwell pads (MWPs) and in residential areas. We measured air pollution, noise, and truck traffic during four distinct phases of UOGD: drilling, hydraulic fracturing, flowback, and production. We monitored particulate matter (PM2.5), black carbon (BC), A-weighted (dBA), and C-weighted (dBC) noise using real-time instruments on 1 and 5 min time scales, and truck traffic for 4-7 days per phase at a large 22-well pad sited in a residential area of Weld County, Colorado. Hydraulic fracturing, which requires frequent truck trips to move supplies and diesel engines to power the process, had the highest median air pollution levels of PM2.5 and BC and experienced the greatest number of heavy trucks per hour compared to other phases. Median air pollution was lowest during drilling at this MWP, possibly because an electric drill rig was used. The equivalent continuous noise level ( Leq) exceeded guidelines of 50 dBA and 65 dBC for A-weighted and C-weighted noise, respectively, during all development phases. Our data show that these multiple stressors are present around the clock at these sites, and this work provides baseline measurements on likely human exposure levels near similarly sized MWPs.

CHD4 regulates the DNA damage response and RAD51 expression in glioblastoma.

Glioblastoma (GBM) is a lethal brain tumour. Despite therapy with surgery, radiation, and alkylating chemotherapy, most people have recurrence within 6 months and die within 2 years. A major reason for recurrence is resistance to DNA damage. Here, we demonstrate that CHD4, an ATPase and member of the nucleosome remodelling and deactetylase (NuRD) complex, drives a component of this resistance. CHD4 is overexpressed in GBM specimens and cell lines. Based on The Cancer Genome Atlas and Rembrandt datasets, CHD4 expression is associated with poor prognosis in patients. While it has been known in other cancers that CHD4 goes to sites of DNA damage, we found CHD4 also regulates expression of RAD51, an essential component of the homologous recombination machinery, which repairs DNA damage. Correspondingly, CHD4 suppression results in defective DNA damage response in GBM cells. These findings demonstrate a mechanism by which CHD4 promotes GBM cell survival after DNA damaging treatments. Additionally, we found that CHD4 suppression, even in the absence of extrinsic treatment, cumulatively increases DNA damage. Lastly, we found that CHD4 is dispensable for normal human astrocyte survival. Since standard GBM treatments like radiation and temozolomide chemotherapy create DNA damage, these findings suggest an important resistance mechanism that has therapeutic implications.

Effect of an opioid management program for Colorado workers' compensation providers on adherence to treatment guidelines for chronic pain.

OBJECTIVE: The aim of this study was to examine adherence of state guidelines for Colorado workers' compensation physicians/providers treating individuals as injured workers with chronic pain after initiation of an opioid management program and provider incentives. METHODS: A retrospective cohort of chronic, non-cancer pain claims was constructed from the Colorado's workers' compensation database. Adherence to treatment guidelines and opioid prescribing practices were evaluated during implementation of a new billing code to incentivize adherence. RESULTS: Overall, less than 33% of claims showed evidence of opioid management. Comprehensive opioid management was observed in only 4.4% of claims. In 2010, after implementing the new billing code, the ratio of long acting opioids to short acting opioids decreased from 0.2 to 0.13; returning to 0.2 in one year. Similarly, morphine equivalent doses declined for a short period. CONCLUSIONS: Incentivizing physicians to adhere to chronic pain management guidelines only temporarily improves prescribing practices.

Relationships between indicators of cardiovascular disease and intensity of oil and natural gas activity in Northeastern Colorado.

BACKGROUND: Oil and natural gas (O&G) extraction emits pollutants that are associated with cardiovascular disease, the leading cause of mortality in the United States. OBJECTIVE: We evaluated associations between intensity of O&G activity and cardiovascular disease indicators. METHODS: Between October 2015 and May 2016, we conducted a cross-sectional study of 97 adults living in Northeastern Colorado. For each participant, we collected 1-3 measurements of augmentation index, systolic and diastolic blood pressure (SBP and DBP), and plasma concentrations of interleukin (IL)- 1ß, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). We modelled the intensity of O&G activity by weighting O&G well counts within 16 km of a participant's home by intensity and distance. We used linear models accounting for repeated measures within person to evaluate associations. RESULTS: Adjusted mean augmentation index differed by 6.0% (95% CI: 0.6, 11.4%) and 5.1% (95%CI: -0.1, 10.4%) between high and medium, respectively, and low exposure tertiles. The greatest mean IL-1ß, and α-TNF plasma concentrations were observed for participants in the highest exposure tertile. IL-6 and IL-8 results were consistent with a null result. For participants not taking prescription medications, the adjusted mean SBP differed by 6 and 1 mm Hg (95% CIs: 0.1, 13 mm Hg and -6, 8 mm Hg) between the high and medium, respectively, and low exposure tertiles. DBP results were similar. For participants taking prescription medications, SBP and DBP results were consistent with a null result. CONCLUSIONS: Despite limitations, our results support associations between O&G activity and augmentation index, SBP, DBP, IL-1ß, and TNF-α. Our study was not able to elucidate possible mechanisms or environmental stressors, such as air pollution and noise.

Measuring environmental noise from airports, oil and gas operations, and traffic with smartphone applications: laboratory and field trials.

Environmental noise from sources such as traffic, airports, and oil and gas (O&G) operations is associated with nuisance and health concerns. Smartphones with external microphones have been recommended for environmental noise monitoring and may be useful tools for citizen science, but are not validated against reference methods. We evaluated laboratory performance of three smartphone/application (app) configurations recommended for environmental noise measurement. Two smartphone/app configurations were also compared to a reference sampler, a type 1 sound level meter (SLM) at ten outdoor sites with traffic, airport, and O&G noise. To evaluate performance, we compared the mean squared error, variance, bias, and Krippendorff's Alpha by smartphone/app combination and testing location for both audible (A-weighted) and low-frequency (C-weighted) noise. We observed that laboratory measurements were in strong agreement with a reference sampler. The field A-weighted noise level results had strong agreement with the SLM at several outdoor sites, but our C-weighted noise results ranged from moderate to substantial agreement. For our tested configurations, we find that smartphones with external microphones are reliable proxies for measuring A- and C-weighted noise in a laboratory setting. Outdoor performance depends on noise source type, weighting, and precision and accuracy needs of the investigation.

Truck and Multivehicle Truck Accidents with Injuries Near Colorado Oil and Gas Operations.

Unconventional and conventional oil and gas (O&G) operations raise public health concerns, such as the potential impacts from trucking activity in communities that host these operations. In this work, we used two approaches to evaluate accidents in relation to O&G activities in the State of Colorado. First, we calculated the rate of truck accidents by computing the ratio of accident count and county population. When comparing counties with increased O&G operations to counties with less activity, we found that counties with more activity have greater rates of truck traffic accidents per capita (Rate Ratio = 1.07, p < 0.05, 95% CI: 1.01⁻1.13). Second, we laid a grid over the eleven counties of interest and counted, for each cell, the number of truck accidents, the number of multivehicle accidents with injuries, the number of homes, and the number of O&G wells. We then applied hurdle count models, using the accident counts as the outcomes and the number of homes and number of wells as independent variables. We found that both independent variables are significant predictors of truck accidents and multivehicle truck accidents. These accidents are of concern since they can have an impact on the people who live near O&G operations.

Phosphorylation of Drosophila Brahma on CDK-phosphorylation sites is important for cell cycle regulation and differentiation.

The SWI/SNF ATP-dependent chromatin-remodeling complex is an important evolutionarily conserved regulator of cell cycle progression. It associates with the Retinoblastoma (pRb)/HDAC/E2F/DP transcription complex to modulate cell cycle-dependent gene expression. The key catalytic component of the SWI/SNF complex in mammals is the ATPase subunit, Brahma (BRM) or BRG1. BRG1 was previously shown to be phosphorylated by the G1-S phase cell cycle regulatory kinase Cyclin E/CDK2 in vitro, which was associated with the bypass of G1 arrest conferred by BRG1 expression. However, it is unknown whether direct Cyclin E/CDK2-mediated phosphorylation of BRM/BRG1 is important for G1-S phase cell cycle progression and proliferation in vivo. Herein, we demonstrate for the first time the importance of CDK-mediated phosphorylation of Brm in cell proliferation and differentiation in vivo using the Drosophila melanogaster model organism. Expression of a CDK-site phospho-mimic mutant of Brm, brm-ASP (all the potential CDK sites are mutated from Ser/Thr to Asp), which acts genetically as a brm loss-of-function allele, dominantly accelerates progression into the S phase, and bypasses a Retinoblastoma-induced developmental G1 phase arrest in the wing epithelium. Conversely, expression of a CDK-site phospho-blocking mutation of Brm, brm-ALA, acts genetically as a brm gain-of-function mutation, and in a Brm complex compromised background reduces S phase cells. Expression of the brm phospho-mutants also affected differentiation and Decapentaplegic (BMP/TGFß) signaling in the wing epithelium. Altogether our results show that CDK-mediated phosphorylation of Brm is important in G1-S phase regulation and differentiation in vivo. ABBREVIATIONS: A-P: Anterior-Posterior; BAF: BRG1-associated factor; BMP: Bone Morphogenetic Protein; Brg1: Brahma-Related Gene 1; Brm: Brahma; BSA: Bovine Serum Albumin; CDK: Cyclin dependent kinase dpp: decapentaplegic; EdU: 5-Ethynyl 2'-DeoxyUridine; EGFR: Epidermal Growth Factor Receptor; en: engrailed; GFP: Green Fluorescent Protein; GST: Glutathione-S-Transferase; HDAC: Histone DeACetylase; JNK: c-Jun N-terminal Kinase; Mad: Mothers Against Dpp; MAPK: Mitogen Activated Protein Kinase; MB:: Myelin Basic Protein; nub: nubbin; pH3: phosphorylated Histone H3; PBS: Phosphate Buffered Saline; PBT: PBS Triton; PFA: ParaFormAldehydep; Rb: Retinoblastoma protein; PCV: Posterior Cross-Vein; Snr1: Snf5-Related 1; SWI/SNF: SWitch/Sucrose Non-Fermentable; TGFß: Transforming Growth Factor ß; TUNEL: TdT-mediated dUTP Nick End Labelling; Wg: Wingless; ZNC: Zone of Non-Proliferating Cells.