The ENCOMPASS framework:a practical guide for the evaluation of public health programmes in complex adaptive systems

BackgroundSystems thinking embraces the complexity of public health problems, including childhood overweight and obesity. It aids in understanding how factors are interrelated, and it can be targeted to produce favourable changes in a system. There is a growing call for systems approaches in public health research, yet limited practical guidance is available on how to evaluate public health programmes within complex adaptive systems. The aim of this paper is to present an evaluation framework that supports researchers in designing systems evaluations in a comprehensive and practical way.MethodsWe searched the literature for existing public health systems evaluation studies. Key characteristics on how to conduct a systems evaluation were extracted and compared across studies. Next, we overlaid the identified characteristics to the context of the Lifestyle Innovations Based on Youth Knowledge and Experience (LIKE) programme evaluation and analyzed which characteristics were essential to carry out the LIKE evaluation. This resulted in the Evaluation of Programmes in Complex Adaptive Systems (ENCOMPASS) framework.ResultsThe ENCOMPASS framework includes five iterative stages: (1) adopting a system dynamics perspective on the overall evaluation design; (2) defining the system boundaries; (3) understanding the pre-existing system to inform system changes; (4) monitoring dynamic programme output at different system levels; and (5) measuring programme outcome and impact in terms of system changes.ConclusionsThe value of ENCOMPASS lies in the integration of key characteristics from existing systems evaluation studies, as well as in its practical, applied focus. It can be employed in evaluating public health programmes in complex adaptive systems. Furthermore, ENCOMPASS provides guidance for the entire evaluation process, all the way from understanding the system to developing actions to change it and to measuring system changes. By the nature of systems thinking, the ENCOMPASS framework will likely evolve further over time, as the field expands with more completed studies

On the Life History of Wireworms of the Genus Agriotes, Esch., with Some notes on that of Athous Haemorrhoidalis, F. Part II

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GASPS observations of Herbig Ae/Be stars with PACS/Herschel. The atomic and molecular content of their protoplanetary discs

We observed a sample of 20 representative Herbig Ae/Be stars and five A-type debris discs with PACS onboard of Herschel. The observations were done in spectroscopic mode, and cover far-IR lines of [OI], [CII], CO, CH+, H2O and OH. We have a [OI]63 micron detection rate of 100% for the Herbig Ae/Be and 0% for the debris discs. [OI]145 micron is only detected in 25%, CO J=18-17 in 45% (and less for higher J transitions) of the Herbig Ae/Be stars and for [CII] 157 micron, we often found spatially variable background contamination. We show the first detection of water in a Herbig Ae disc, HD 163296, which has a settled disc. Hydroxyl is detected as well in this disc. CH+, first seen in HD 100546, is now detected for the second time in a Herbig Ae star, HD 97048. We report fluxes for each line and use the observations as line diagnostics of the gas properties. Furthermore, we look for correlations between the strength of the emission lines and stellar or disc parameters, such as stellar luminosity, UV and X-ray flux, accretion rate, PAH band strength, and flaring. We find that the stellar UV flux is the dominant excitation mechanism of [OI]63 micron, with the highest line fluxes found in those objects with a large amount of flaring and greatest PAH strength. Neither the amount of accretion nor the X-ray luminosity has an influence on the line strength. We find correlations between the line flux of [OI]63 micron and [OI]145 micron, CO J = 18-17 and [OI]6300 \AA, and between the continuum flux at 63 micron and at 1.3 mm, while we find weak correlations between the line flux of [OI]63 micron and the PAH luminosity, the line flux of CO J = 3-2, the continuum flux at 63 micron, the stellar effective temperature and the Brgamma luminosity. (Abbreviated version)Comment: 20 pages, 29 figures, accepted by Astronomy and Astrophysic

Simultaneous multi-slice accelerated 4D-MRI for radiotherapy guidance

4D-MRI is becoming increasingly important for daily guidance of thoracic and abdominal radiotherapy. This study exploits the simultaneous multi-slice (SMS) technique to accelerate the acquisition of a balanced turbo field echo (bTFE) and a turbo spin echo (TSE) coronal 4D-MRI sequence performed on 1.5 T MRI scanners. SMS single-shot bTFE and TSE sequences were developed to acquire a stack of 52 coronal 2D images over 30 dynamics. Simultaneously excited slices were separated by half the field of view. Slices intersecting with the liver-lung interface were used as navigator slices. For each navigator slice location, an end-exhale dynamic was automatically identified, and used to derive the self-sorting signal by rigidly registering the remaining dynamics. Navigator slices were sorted into 10 amplitude bins, and the temporal relationship of simultaneously excited slices was used to generate sorted 4D-MRIs for 12 healthy volunteers. The self-sorting signal was validated using an in vivopeak-to-peak motion analysis. The smoothness of the liver-lung interface was quantified by comparing to sagittal cine images acquired directly after the SMS-4D-MRI sequence. To ensure compatibility with the MR-linac radiotherapy workflow, the 4D-MRIs were transformed into 3D mid-position (MidP) images using deformable image registration. Consistency of the deformable vector fields was quantified in terms of the distance discordance metric (DDM) in the body. The SMS-4D-TSE sequence was additionally acquired for 3 lung cancer patients to investigate tumor visibility. SMS-4D-MRI acquisition and processing took approximately 7 min. 4D-MRI reconstruction was possible for 26 out of 27 acquired datasets. Missing data in the sorted 4D-MRIs varied from 4%-26% for the volunteers and varied from 8%-24% for the patients. Peak-to-peak (SD) amplitudes analysis agreed within 1.8 (1.1) mm and 0.9 (0.4) mm between the sorted 4D-MRIs and the self-sorting signals of the volunteers and patients, respectively. Liver-lung interface smoothness was found to be in the range of 0.6-3.1 mm for volunteers. The percentage of DDM values smaller than 2 mm was in the range of 85%-89% and 86%-92% for the volunteers and patients, respectively. Lung tumors were clearly visibility in the SMS-4D-TSE images and MidP images. Two fast SMS-accelerated 4D-MRI sequences were developed resulting in T 2/T 1or T 2weighted contrast. The SMS-4D-MRIs and derived 3D MidP-MRIs yielded anatomically plausible images and good tumor visibility. SMS-4D-MRI is therefore a strong candidate to be used for treatment simulation and daily guidance of thoracic and abdominal MR-guided radiotherapy

Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup

Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1

Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.Peer reviewe

On the feasibility of cardiac substructure sparing in magnetic resonance imaging guided stereotactic lung radiotherapy

Background: Lung stereotactic body radiotherapy (SBRT) has proven an effective treatment for medically inoperable lung tumors, even for (ultra-)central tumors. Recently, there has been growing interest in radiation-induced cardiac toxicity in lung radiotherapy. More specifically, dose to cardiac (sub-)structures (CS) was found to correlate with survival after radiotherapy. Purpose: Our goal is first, to investigate the percentage of patients who require CS sparing in an magnetic resonance imaging guided lung SBRT workflow, and second, to quantify how successful implementation of cardiac sparing would be. Methods: The patient cohort consists of 34 patients with stage II–IV lung cancer who were treated with SBRT between 2017 and 2020. A mid-position computed tomography (CT) image was used to create treatment plans for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) following clinical templates. Under guidance of a cardio-thoracic radiologist, 11 CS were contoured manually for each patient. Dose constraints for five CS were extracted from the literature. Patients were stratified according to their need for cardiac sparing depending on the CS dose in their non-CS constrained MR-linac treatment plans. Cardiac sparing treatment plans (CSPs) were then created and dosimetrically compared with their non-CS constrained treatment plan counterparts. CSPs complied with the departmental constraints and were considered successful when fulfilling all CS constraints, and partially successful if some CS constraints could be fulfilled. Predictors for the need for and feasibility of cardiac sparing were explored, specifically planning target volume (PTV) size, cranio-caudal (CC) distance, 3D distance, and in-field overlap volume histograms (iOVH). Results: 47% of the patients (16 out of 34) were in need of cardiac sparing. A successful CSP could be created for 62.5% (10 out of 16) of these patients. Partially successful CSPs still complied with two to four CS constraints. No significant difference in dose to organs at risk (OARs) or targets was identified between CSPs and the corresponding non-CS constrained MR-linac plans. The need for cardiac sparing was found to correlate with distance in the CC direction between target and all of the individual CS (Mann–Whitney U-test p-values <10 −6). iOVHs revealed that complying with dose constraints for CS is primarily determined by in-plane distance and secondarily by PTV size. Conclusion: We demonstrated that CS can be successfully spared in lung SBRT on the MR-linac for most of this patient cohort, without compromising doses to the tumor or to other OARs. CC distance between the target and CS can be used to predict the need for cardiac sparing. iOVHs, in combination with PTV size, can be used to predict if cardiac sparing will be successful for all constrained CS except the left ventricle

First experimental exploration of real-time cardiorespiratory motion management for future stereotactic arrhythmia radioablation treatments on the MR-linac

Objective.Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive treatment for refractory ventricular tachycardia (VT). The VT isthmus is subject to both respiratory and cardiac motion. Rapid cardiac motion presents a unique challenge. In this study, we provide first experimental evidence for real-time cardiorespiratory motion-mitigated MRI-guided STAR on the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) aimed at simultaneously compensating cardiac and respiratory motions. Approach.A real-time cardiorespiratory motion-mitigated radiotherapy workflow was developed on the Unity MR-linac in research mode. A 15-beam intensity-modulated radiation therapy treatment plan (1 × 25 Gy) was created in Monaco v.5.40.01 (Elekta AB) for the Quasar MRI 4Dphantom (ModusQA, London, ON). A film dosimetry insert was moved by combining either artificial (cos 4, 70 bpm, 10 mm peak-to-peak) or subject-derived (59 average bpm, 15.3 mm peak-to-peak) cardiac motion with respiratory (sin, 12 bpm, 20 mm peak-to-peak) motion. A balanced 2D cine MRI sequence (13 Hz, field-of-view = 400 × 207 mm 2, resolution = 3 × 3 × 15 mm 3) was developed to estimate cardiorespiratory motion. Cardiorespiratory motion was estimated by rigid registration and then deconvoluted into cardiac and respiratory components. For beam gating, the cardiac component was used, whereas the respiratory component was used for MLC-tracking. In-silico dose accumulation experiments were performed on three patient data sets to simulate the dosimetric effect of cardiac motion on VT targets. Main results.Experimentally, a duty cycle of 57% was achieved when simultaneously applying respiratory MLC-tracking and cardiac gating. Using film, excellent agreement was observed compared to a static reference delivery, resulting in a 1%/1 mm gamma pass rate of 99%. The end-to-end gating latency was 126 ms on the Unity MR-linac. Simulations showed that cardiac motion decreased the target's D98% dose between 0.1 and 1.3 Gy, with gating providing effective mitigation. Significance.Real-time MRI-guided cardiorespiratory motion management greatly reduces motion-induced dosimetric uncertainty and warrants further research and development for potential future use in STAR