Sandbox university: Estimating influence of institutional action

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students' credits and student retention - something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology's potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

IMPORTANCE: Radiation-induced acute coronary events (ACEs) may occur as treatment-related late side effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remains to be determined. OBJECTIVE: The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in BC patients treated with radiotherapy (RT). DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: The study cohort consisted of 910 BC patients treated with postoperative RT after breast conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose (MHD), volume of the left ventricle receiving ≥ 5 Gy (LV-V5), mean LAD dose and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning CT-scans. Cox-regression analysis was used to analyse the effects on the cumulative incidence of ACEs. RESULTS: The median follow-up time was 9.2 years (range: 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n=163) the mean dose to the atherosclerotic plaque was the strongest predictor for ACE, even after correction for cardiovascular risk factors (HR: 1.269 (95% CI: 1.090-1.477), P=0.002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n=680) (hazard ratio (HR): 1.021 (95% CI: 1.003-1.039; P=0.023). CONCLUSION AND RELEVANCE: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in BC patients

A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs. Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens. Results For 63-year-old CTEPH patients with a 14-month diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at EUR 117 100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life-years and 2.04 QALYs. The associated cost increase was EUR 44 654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of EUR 21 900/QALY. Conclusion Our constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health economic standards, additional costs remain below the deemed acceptable limit of EUR 50 000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay

Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

PurposeA relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD.Patients and MethodsThe cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data.ResultsThe median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91).ConclusionA significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC. (C) 2017 by American Society of Clinical Oncology.</p

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Contains fulltext : 220729.pdf (publisher's version ) (Open Access)The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14(+) DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system

Antimicrobial Resistance, Virulence Factors and Genetic Diversity of Escherichia coli Isolates from Household Water Supply in Dhaka, Bangladesh

Background: Unsafe water supplies continue to raise public health concerns, especially in urban areas in low resource countries. To understand the extent of public health risk attributed to supply water in Dhaka city, Bangladesh, Escherichia coli isolated from tap water samples collected from different locations of the city were characterized for their antibiotic resistance, pathogenic properties and genetic diversity. Methodology/Principal Findings: A total of 233 E. coli isolates obtained from 175 tap water samples were analysed for susceptibility to 16 different antibiotics and for the presence of genes associated with virulence and antibiotic resistance. Nearly 36% (n = 84) of the isolates were multi-drug(≥3 classes of antibiotics) resistant (MDR) and 26% (n = 22) of these were positive for extended spectrum β-lactamase (ESBL). Of the 22 ESBL-producers, 20 were positive for blaCTX-M-15, 7 for blaOXA-1-group(all had blaOXA-47) and 2 for blaCMY-2. Quinolone resistance genes, qnrS and qnrB were detected in 6 and 2 isolates, respectively. Around 7% (n = 16) of the isolates carried virulence gene(s) characteristic of pathogenic E. coli; 11 of these contained lt and/or st and thus belonged to enterotoxigenic E. coli and 5 contained bfp and eae and thus belonged to enteropathogenic E. coli. All MDR isolates carried multiple plasmids (2 to 8) of varying sizes ranging from 1.2 to >120 MDa. Ampicillin and ceftriaxone resistance were co-transferred in conjugative plasmids of 70 to 100 MDa in size, while ampicillin, trimethoprim-sulfamethoxazole and tetracycline resistance were co-transferred in conjugative plasmids of 50 to 90 MDa. Pulsed-field gel electrophoresis analysis revealed diverse genetic fingerprints of pathogenic isolates. Significance: Multi-drug resistant E. coli are wide spread in public water supply in Dhaka city, Bangladesh. Transmission of resistant bacteria and plasmids through supply water pose serious threats to public health in urban areas

High-K volcanism in the Afyon region, western Turkey: from Si-oversaturated to Si-undersaturated volcanism

Volcanic rocks of the Afyon province (eastern part of western Anatolia) make up a multistage potassic and ultrapotassic alkaline series dated from 14 to 12 Ma. The early-stage Si-oversaturated volcanic rocks around the Afyon city and further southward are trachyandesitic volcanic activity (14.23 ± 0.09 Ma). Late-stage Si-undersaturated volcanism in the southernmost part of the Afyon volcanic province took place in three episodes inferred from their stratigraphic relationships and ages. Melilite– leucitites (11.50 ± 0.03 Ma), spotted rachyandesites, tephryphonolites and lamproites (11.91 ± 0.13 Ma) formed in the first episode; trachyandesites in the second episode and finally phonotephrites, phonolite, basaltic trachyandesites and nosean-bearing trachyandesites during the last episode. The parameter Q [normative q-(ne + lc + kls + ol)] of western Anatolia volcanism clearly decreased southward with time becoming zero in the time interval 10–15 Ma. The magmatism experienced a sudden change in the extent of Si saturation after 14 Ma, during late-stage volcanic activity of Afyon volcanic province at around 12 Ma, though there was some coexistence of Si-oversaturated and Si-undersaturated magmas during the whole life of Afyon volcanic province