Search

BACKGROUND Challenges exist with heterotaxy due to the complexity of heart disease, abnormal venous connections, and infection risks. This study aims to understand heart transplant outcomes for children with heterotaxy. METHODS All children with congenital heart disease listed for transplant from 1993 to 2018 were included. Those with and without heterotaxy were compared. Waitlist outcomes and survival post-listing and transplant were analyzed. Post-transplant risk factors were identified using multiphase parametric hazard modeling. RESULTS There were 4814 children listed, of whom 196 (4%) had heterotaxy. Heterotaxy candidates were older (5.8 ± 5.7 vs 4.2 ± 5.5 years, p < 0.01), listed at a lower urgency status (29.8% vs 18.4%, p < 0.01), more commonly single ventricle physiology (71.3% vs 59.2%, p < 0.01), and less often supported by mechanical ventilation (22% vs 29.1%, p < 0.05) or extracorporeal membrane oxygenation (3.6% vs 7.5%, p < 0.05). There were no differences in waitlist outcomes of transplant, death, or removal. Overall, post-transplant survival was worse for children with heterotaxy: one-year survival 77.2% vs 85.1%, with and without heterotaxy, respectively. Heterotaxy was an independent predictor for early mortality in the earliest era (1993-2004), HR 2.09, CI 1.16-3.75, p = 0.014. When stratified by era, survival improved with time. Heterotaxy patients had a lower freedom from infection and from severe rejection, but no difference in vasculopathy or malignancy. CONCLUSIONS Mortality risk associated with heterotaxy is mitigated in the recent transplant era. Early referral may improve waitlist outcomes for heterotaxy patients who otherwise have a lower status at listing. Lower freedom from both infection and severe rejection after transplant in heterotaxy highlights the challenges of balancing immune suppression.

A novel method of producing fluorine-18 for Positron emission tomography (PET) scan applications is evaluated theoretically. The method is based upon the 3He(d,p)4He nuclear reaction from which the protons produced are used to produce fluorine-18 via the 18O(p,n)18F reaction. The potential advantage of such a system over cyclotron-based production is of lower input beam energy, which may lower the cost of the system and potentially allow for onsite production. Two theoretical designs were investigated. The first utilizes a helium-3 beam incident on a deuterated plastic target such as Mylar which is backed with an oxygen-18 heavy-water (H2O18) target. The second design utilizes a super-heavy-water (D2O18) target effectively combining both targets into one. Theoretical yield calculations were performed for both designs and the practicalities, primarily those of thermal and target degradation effects were assessed. To produce sufficient fluorine-18 yield a 1 MeV helium-3 beam at 100 mA was simulated. For this beam it was calculated that 310 MBq of fluorine-18 activity, as required to scan a 74 kg patient would be generated in a 69 min or an 18 min production run for the Mylar and super-heavy-water systems respectively. The simulated beam is at 100 kW power and without significant cooling would vaporize the target materials with the melting point of Mylar and boiling point of water calculated to be breached within 0.41 μs and 0.45 μs from beam-on. To achieve sufficient fluorine-18 yield the helium-3 beam power had to be increased to impractical levels making the systems technically infeasible.

Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit-safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. Methods: A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. Findings: Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit-safety balances remain better than those of the noncannabinoid drugs. Interpretation: The benefit-safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain.

BACKGROUND The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 ( n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease , and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin . Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events , including major bleeding, were reduced in the PSS group. CONCLUSIONS The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

The majority of cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction approaches based on machine learning aim to separate those subpopulations in a sample and reconstruct their evolutionary history. However, current approaches are entirely data-driven and agnostic to evolutionary theory. We demonstrate that systematic errors occur in the analysis if evolution is not accounted for, and this is exacerbated by multi-sampling of the same tumor. We present a novel approach for model-based tumor subclonal reconstruction (MOBSTER) that combines machine learning with theoretical population genetics. Using public whole-genome sequencing data from 2,606 samples from different cohorts, new data and synthetic validation, we show this method is more robust and accurate than current techniques in single sample, multi-region and longitudinal data. This approach minimizes the confounding factors of non-evolutionary methods, leading to more accurate recovery of the evolutionary history of human cancers.

Accurate quantification of absorbed radiation dose is important for safe and effective delivery of radiation therapy. An important aspect to this is reference dosimetry, which is performed under reference conditions specified by international codes of practice. Such measurements are usually performed in a water phantom. In the Sun Nuclear Corporation (SNC) three‐dimensional (3D) scanner water tank system the detector holder is fixed to a horizontal metallic drive rail (MDR) which is in close proximity to the active volume of the detector. In this project, the dosimetric effects of the MDR on reference dosimetry were investigated for MV photons, MeV electrons, and kV photons by comparing reference dosimetry measurements in the SNC 3D scanner against similar measurements in a Standard Imaging (SI) one‐dimensional (1D) tank and against measurements in the SNC 3D scanner with an additional, custom‐made spacer placed beneath the chamber holder to increase the chamber ‐ MDR separation. A second experiment investigated the difference in chamber reading dependent on chamber to MDR separation by fixing the chamber in the tank independently of the MDR and successively moving the MDR vertically to alter the separation. The results showed that measurements in the SNC 3D scanner agree with both SI 1D tank and SNC 3D scanner with spacer to within ±0.3% for MV photons, ±0.1% for electrons and ±1.2% for kV photons within the calculated setup uncertainty. The second experiment showed that the contribution of backscatter from the MDR was significant if the distance between MDR and chamber was reduced below the chamber's designed position in the SNC 3D scanner. The exception was for kV photons where the contribution of backscatter from the MDR was measured to be 0.5% at the designed distance. Further investigation would be useful for kV photons, where the experiment showed relatively large measurement uncertainties.

International audience; In this paper we investigate the effect of Carbon ion implantation in Ge$_2$ Sb$_2$ Te$_5$ based Phase-Change Memory (PCM) targeting reliability improvement in 4kb memory arrays. We show how ion implantation by beam line allows to localize the Carbon in a specific volume of the active layer, demonstrating that a low C concentration (lower than 5 at. %) can be achieved with a high control thanks to dose monitoring. We evidence an outstanding improvement of the PCM cell performances, in both single devices and 4kb arrays, such as programming window widening and reduced variability of electrical parameters. We support our findings by TEM/EDS analyses demonstrating the healing effects of C ion implantation on interfaces and on retarding the phase-change layer segregation mechanisms.

Cardiac endothelial cells respond to both ischemia and therapeutic ultrasound; the proteomic changes underlying these responses are unknown. This data article provides raw and processed data resulting from our global, unbiased phosphoproteomics investigation conducted on primary mouse cardiac endothelial cells exposed to ischemia (2-hour oxygen glucose deprivation) and ultrasound (250 kHz, 1.2 MPa) in vitro [1]. Proteins were extracted from cell lysates and enriched phosphopeptides were analyzed with a high mass accuracy liquid chromatrography (LC) - tandem mass spectrometry (MS/MS) proteomic platform, yielding multiple alterations in both total protein levels and phosphorylation events in response to ischemic injury and ultrasound. This dataset can be used as a reference for future studies on the cardiac endothelial response to ischemia and the mechanistic underpinnings of the cellular response to ultrasound, with the potential to yield clinically relevant therapeutic targets.

GPR39, a member of the ghrelin family of G protein-coupled receptors, is zinc-responsive and contributes to the regulation of diverse neurovascular and neurologic functions. Accumulating evidence suggests a role as a homeostatic regulator of neuronal excitability, vascular tone, and the immune response. We review GPR39 structure, function, and signaling, including constitutive activity and biased signaling, and summarize its expression pattern in the central nervous system. We further discuss its recognized role in neurovascular, neurological, and neuropsychiatric disorders.

To evaluate the efficacy of neurobehavioural rehabilitation (NbR) programmes, services should employ valid, reliable assessment tools; the ability to detect change on repeated assessment is a particular requirement. The United Kingdom Rehabilitation Outcomes Collaborative (UKROC) requires neurorehabilitation services to collect data using a standardized basket of measures, but the responsiveness and usefulness of using these in the context of NbR remains unknown. Anonymous data collected at two assessments for 123 people were examined using multiple methods to determine responsiveness of four outcome measures routinely used in NbR (HoNOS-ABI, FIM + FAM UK, MPAI-4, SASNOS). Predictive validity of two measures of rehabilitation complexity (RCS-E, SRS) regarding the extent of difference scores on these outcome measures at reassessment was also determined. All four outcome measures demonstrated responsiveness, with higher levels for SASNOS and MPAI-4 when only participants categorized as "most likely to change" at first assessment were analyzed. Predictive validity of the RCS-E and SRS in estimating the extent of change was variable. SRS was only predictive of improvement on the MPAI-4 whilst RCS-E was not predictive at all. Recommendations are made regarding ideal characteristics of NbR outcome measures, along with the need to develop measures of rehabilitation complexity specifically conceptualized for these programmes.

BACKGROUND Learning networks have emerged in medicine as a novel organizational structure that contains elements of quality improvement, education, and research with the goal of effecting rapid improvements in clinical care. In this article, the concept of a learning network is defined and highlighted in the field of pediatric heart failure and transplantation. METHODS Learning networks are defined, with particular attention paid to the recent creation of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) for children with heart failure and those being supported with ventricular assist devices (VAD). RESULTS The mission, goals, and organizational structure of ACTION are described, and recent initiatives promoted by ACTION are highlighted, such as stroke reduction initiatives, practice harmonization protocols, and use of ACTION data to support the recent US Food and Drug Administration approval of newer VAD for pediatric patients. CONCLUSIONS The learning network, exemplified by ACTION, is distinguished from traditional clinical research collaboratives by contributions in research, quality improvement, patient-reported outcomes, and education, and serves as an effective vehicle to drive clinical improvement in the care of children with advanced heart failure.

Patients present to primary care physicians with musculoskeletal complaints more often than they do for upper respiratory infections, hypertension, or diabetes. Despite this, instruction in musculoskeletal medicine for internal medicine residents represents less than 1% of their total didactic and clinical education time. We recognize the immense breadth of knowledge and skill required to train residents in the practice of internal medicine. This curriculum guideline defines a recommended training strategy, and supplies relevant resources, to improve musculoskeletal education among internal medicine residents to optimize patient care. This curriculum guideline was created by internists who are sports medicine specialists. Sports medicine physicians promote overall health and well-being while providing expertise in acute and chronic musculoskeletal conditions, as well as how disease affects exercise and using exercise as medicine for people with chronic disease.

Myocardial infarction and subsequent therapeutic interventions activate numerous intracellular cascades in every constituent cell type of the heart. Endothelial cells produce several protective compounds in response to therapeutic ultrasound, under both normoxic and ischemic conditions. How endothelial cells sense ultrasound and convert it to a beneficial biological response is not known. We adopted a global, unbiased phosphoproteomics approach aimed at understanding how endothelial cells respond to ultrasound. Here, we use primary cardiac endothelial cells to explore the cellular signaling events underlying the response to ischemia-like cellular injury and ultrasound exposure in vitro. Enriched phosphopeptides were analyzed with a high mass accuracy liquid chromatrography (LC) - tandem mass spectrometry (MS/MS) proteomic platform, yielding multiple alterations in both total protein levels and phosphorylation events in response to ischemic injury and ultrasound. Application of pathway algorithms reveals numerous protein networks recruited in response to ultrasound including those regulating RNA splicing, cell-cell interactions and cytoskeletal organization. Our dataset also permits the informatic prediction of potential kinases responsible for the modifications detected. Taken together, our findings begin to reveal the endothelial proteomic response to ultrasound and suggest potential targets for future studies of the protective effects of ultrasound in the ischemic heart.

Background: In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems. Aims: Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes. Outcomes: Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions. Conclusions: There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.

Background Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions. Materials and methods Healthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1. Results All subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects, though systemic NEFA and carnitine levels reflected fasted and fed states. Conclusion The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism.

Background: Ischemic stroke is a leading cause of morbidity and mortality. Efficacy of current thrombolytic and endovascular therapies are not uniform in all patients, and depends on age, stroke severity and diabetic status. This is in part attributed to impaired microvascular reperfusion, which limits the benefit from large-vessel recanalization. Microvascular blood flow is regulated by a number of molecules including the P450 eicosanoids which are arachidonic acid-derived lipid signaling molecules whose levels are known to be altered during stroke. We have recently identified GPR39 as a dual sensor for two vasoactive P450 eicosanoids: the dilator 14,15-epoxyeicosatrienoate (EET) and constrictor 15-hydroxyeicosatetranoate (HETE). GPR39 is expressed in arteriolar vascular smooth muscle cells and peri-capillary pericytes. Thus, GPR39 is uniquely positioned to sense the balance of vasoactive eicosanoids and modulate microvascular blood flow during and following stroke. To investigate the role of GPR39 in stroke, we have generated a global GPR39 knock-out (KO) mouse via CRISPR/Cas9 deletion of the receptor’s first exon, eliminating expression of GPR39. We tested the hypothesis that GPR39 KO mice sustain larger infarcts after transient focal cerebral ischemia compared to wild-type (WT) littermates with intact GPR39. Methods: A 60-min middle cerebral artery occlusion (MCAO) was induced in 3-month old male and female mice using a silicone coated filament introduced through an external carotid stump under isoflurane anesthesia. A total of 15 KO (8 males, 7 females) and 8 WT (4 males and 4 females) mice were used for the study. Brains were harvested at 24 hours of reperfusion, sliced coronally in 2-mm segments, sections stained with triphenyltetrazolium chloride ( TTC ), and infarcted areas measured after accounting for edema. Results: Hemispheric infarct was 44.7% ± 3.31% in male GPR39 KO mice compared to 34.7% ± 5.23% in WT male littermates (mean ± sem, p=0.07). In females, infarct size was 30.3% ± 5.58% in GPR39 KO mice compared to 33.9% ± 1.45% in WT littermates (p = 0.34). Conclusions: Our preliminary results suggest that GPR39 plays a sexually-dimorphic protective role in ischemic stroke, and that GPR39 may serve as a therapeutic target in stroke.

Therapeutic mammaplasty (TM) may be an alternative to mastectomy, but few well designed studies have evaluated the success of this approach or compared the short-term outcomes of TM with mastectomy with or without immediate breast reconstruction (IBR). Data from the national iBRA-2 and TeaM studies were combined to compare the safety and short-term outcomes of TM and mastectomy with or without IBR.The subgroup of patients in the TeaM study who underwent TM to avoid mastectomy were identified, and data on demographics, complications, oncology and adjuvant treatment were compared with those of patients undergoing mastectomy with or without IBR in the iBRA-2 study. The primary outcome was the percentage of successful breast-conserving procedures in the TM group. Secondary outcomes included postoperative complications and time to adjuvant therapy.A total of 2916 patients (TM 376; mastectomy 1532; mastectomy and IBR 1008) were included in the analysis. Patients undergoing TM were more likely to be obese and to have undergone bilateral surgery than those having IBR. However, patients undergoing mastectomy with or without IBR were more likely to experience complications than the TM group (TM: 79, 21·0 per cent; mastectomy: 570, 37·2 per cent; mastectomy and IBR: 359, 35·6 per cent; P 0·001). Breast conservation was possible in 87·0 per cent of patients who had TM, and TM did not delay adjuvant treatment.TM may allow high-risk patients who would not be candidates for IBR to avoid mastectomy safely. Further work is needed to explore the comparative patient-reported and cosmetic outcomes of the different approaches, and to establish long-term oncological safety.La mamoplastia terapéutica (therapeutic mammaplasty, TM) puede ser una alternativa a la mastectomía, pero hay pocos estudios bien diseñados que hayan evaluado el éxito de esta estrategia o hayan comparado los resultados a corto plazo de la TM con la mastectomía con o sin (+/-) reconstrucción mamaria inmediata (immediate breast reconstruction, IBR). Para comparar la seguridad y los resultados a corto plazo de la TM y la mastectomía +/- IBR se combinaron los datos de los estudios nacionales iBRA-2 y TeaM. MÉTODOS: En el estudio TeaM se identificó el subgrupo de pacientes al que se realizó una TM para evitar la mastectomía y se compararon los datos demográficos, las complicaciones, los resultados oncológicos y el tratamiento adyuvante con las pacientes sometidas a mastectomía +/- IBR del estudio iBRA-2. La variable principal fue el porcentaje de éxito de la cirugía conservadora de mama en el grupo TM. Las variables secundarias fueron las complicaciones postoperatorias y el intervalo de tiempo hasta el inicio del tratamiento adyuvante.Se incluyeron en el análisis 2.916 pacientes (TM n = 376; mastectomía n = 1.532; IBR n = 1.008). La TM era más frecuente en pacientes obesas o en las sometidas a cirugía bilateral en comparación con las pacientes con IBR. Sin embargo, las pacientes sometidas a una mastectomía +/- IBR tenían más probabilidades de desarrollar complicaciones que las del grupo TM (TM n = 79, 21,0%; mastectomía n = 570, 37,2%; mastectomía y IBR n = 359, 35,6%; P 0,001). La conservación de la mama fue posible en el 87% de las pacientes con TM y el procedimiento no retrasó el inicio del tratamiento adyuvante. CONCLUSIÓN: La TM puede permitir que pacientes de alto riesgo que no serían candidatas a IBR eviten la mastectomía de una forma segura. Se necesitan más trabajos para comparar los resultados percibidos por las pacientes y los estéticos de las diferentes estrategias terapéuticas y establecer la seguridad oncológica a largo plazo.

No abstract available

Alignment of the On‐Board Imager (OBI) X‐ray tube is important for ensuring imaging to treatment isocenter coincidence, which in turn is important for accurate Image Guided Radiotherapy (IGRT). Varian introduced a new X‐ray tube alignment procedure for the TrueBeam linac in software version 2.5 MR2 as part of the machine performance check (MPC) application. This study evaluated the new procedure against conventional methods and examined the clinical significance of X‐ray tube misalignment. Long term stability and short term repeatability of MPC tube alignment was assessed as well as sensitivity of the method to setup error. Standard quality assurance tests expected to be sensitive to tube misalignment were performed before and after tube alignment. These tests included: IsoCal verification; MPC kV imager offset; Winston‐Lutz: kV imaging to treatment/radiation isocenter coincidence; CBCT image QA using the Catphan phantom; and OBI image geometric accuracy and center pixel alignment. Tube alignment measurements were performed with MPC, the two‐plate method, and wire‐on‐faceplate method. The X‐ray tube was then realigned by approximately 1.01 mm in the tangential plane based upon MPC and the tube alignment and standard quality assurance measurements were repeated. The time taken for each tube alignment method was estimated. The MPC method of tube alignment was found to be repeatable, insignificantly sensitive to phantom setup error and quick and simple to perform. The standard QA tests were generally insensitive to the tube alignment change, possibly because of the IsoCal correction. However, reduction in the magnitude of IsoCal correction and MPC kV imager offset was recorded after tube alignment. There was also apparent improvement in CBCT image uniformity. The MPC procedure is recommended for X‐ray tube alignment.

Beam steering is the process of calibrating the angle and translational position with which a linear accelerator's (linac's) electron beam strikes the x‐ray target with respect to the collimator rotation axis. The shape of the dose profile is highly dependent on accurate beam steering and is essential for ensuring correct delivery of the radiotherapy treatment plan. Traditional methods of beam steering utilize a scanning water tank phantom that makes the process user‐dependent. This study is the first to provide a methodology for both beam angle steering and beam translational position steering based on EPID imaging of the beam and does not require a phantom. Both the EPID‐based beam angle steering and beam translational steering methods described have been validated against IC Profiler measurement. Wide field symmetry agreement was found between the EPID and IC Profiler to within 0.06 ± 0.14% (1 SD) and 0.32 ± 0.11% (1 SD) for flattened and flattening‐filter‐free (FFF) beams, respectively. For a 1.1% change in symmetry measured by IC Profiler the EPID method agreed to within 0.23%. For beam translational position steering, the EPID method agreed with IC Profiler method to within 0.03 ± 0.05 mm (1 SD) at isocenter. The EPID‐based methods presented are quick to perform, simple, accurate and could easily be integrated with the linac, potentially via the MPC application. The methods have the potential to remove user variability and to standardize the process of beam steering throughout the radiotherapy community.

The success of participatory marine governance arrangements is influenced by the levels of trust that exist between decision-makers and diverse stakeholder groups within the community. While the benefits of high levels of trust among these groups is well established, specific approaches to building trust remain largely unknown. The aim of this study is to understand the extent to which scientific research programs can enhance trust among marine protected area (MPA) managers and community members via an evaluation of the Ningaloo Research Program - a large-scale program of marine research in the Ningaloo Marine Park. Results from a survey of 125 local residents show that community members along the Ningaloo coast believe that scientific research is important for the management of the marine park, and strongly support government investment in scientific research in the region. Results also suggest that science undertaken through the Ningaloo Research Program has increased the extent to which community members trust local managers, which study participants believe has led to improved social and environmental outcomes in the region. Finally, additional opportunities are identified to maintain and further enhance trust between community members and MPA managers, via targeted communication and engagement programs that account for different personality ‘types’. In particular, the establishment of citizen science programs might further build trust. These results suggest that scientific research could be used as a means to increase trust among decision-makers and community members when coupled with an effective communication and outreach program, thus enhancing the success of participatory marine governance arrangements.

Purpose We sought to evaluate the association between early-onset cardiac allograft vasculopathy (CAV) [ Methods Data from the Pediatric Heart Transplant Society (PHTS) for pediatric ( Results Over a median follow-up period of 4.1 (IQR 1.3 - 8.3) years, angiographic evidence of CAV was identified in 17% (885/5,075) of patients, 28% (252/885) of which were early-onset CAV. Compared to those who developed CAV >10 years post HT, patients with early-onset CAV were older at transplant (8.3 +/- 6.2 vs. 3.8 +/- 4.8 years, p Conclusion Following diagnosis, the progression of CAV & graft survival was similar for patients with early-onset CAV compared with CAV at other time points. These findings suggest that early-onset CAV does not necessarily represent a more aggressive phenotype of disease.

Modern day Stereotactic treatments require high geometric accuracy of the delivered treatment. To achieve the required accuracy the IGRT imaging isocenter needs to closely coincide with the treatment beam isocenter. An influence on this isocenter coincidence and on the spatial positioning of the beam itself is the alignment of the treatment beam focal spot with collimator rotation axis. The positioning of the focal spot is dependent on the linac beam steering and on the stability of the monitor chamber and beam steering servo system. As such, there is the potential for focal spot misalignment and this should be checked on a regular basis. Traditional methods for measuring focal spot position are either indirect, inaccurate, or time consuming and hence impractical for routine use. In this study a novel, phantomless method has been developed using the EPID (Electronic Portal Imaging Device) that utilizes the different heights of the MLC and jaws. The method has been performed on four linear accelerators and benchmarked against an alternate ion chamber‐based method. The method has been found to be reproducible to within ±0.012 mm (1 SD) and in agreement with the ion chamber‐based method to within 0.001 ± 0.015 mm (1 SD). The method could easily be incorporated into a departmental routine linac QA (Quality Assurance) program.

Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT.Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included. Patients were classified into two groups: pCR and no-or-incomplete response (NR). Polymerase chain reaction was used to evaluate gene expression. Omnibus testing was applied to overall gene expression differences between groups, and log-rank tests compared individual genes.Eleven pCR and eighteen NR patients were analyzed. Combined expression profiles were significantly different between pCR and NR groups (p 0.01). The gene CCL28 was over-expressed in pCR patients (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3 was under-expressed in pCR (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031).EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response.

Summary There's a strong case for making social and emotional learning (SEL) skills and competencies a central feature of elementary school. Children who master SEL skills get along better with others, do better in school, and have more successful careers and better mental and physical health as adults. But evidence from the most rigorous studies of elementary-school SEL programs is ambiguous. Some studies find few or no effects, while others find important and meaningful effects. Or studies find effects for some groups of students but not for others. What causes such variation isn't clear, making it hard to interpret and act on the evidence. What are the sources of variation in the impacts of SEL programs designed for the elementary years? To find out, Stephanie Jones, Sophie Barnes, Rebecca Bailey, and Emily Doolittle examine how the theories of change behind 11 widely used school-based SEL interventions align with the way those interventions measure outcomes. Their central conclusion is that what appears to be variation in impacts may instead stem from imprecise program targets misaligned with too-general measures of outcomes. That is to say, program evaluations often fail to measure whether students have mastered the precise skills the programs seek to impart. The authors make three recommendations for policy makers, practitioners, and researchers. The first is that we should focus more on outcomes at the teacher and classroom level, because teachers' own social-emotional competency and the quality of the classroom environment can have a huge effect on students' SEL. Second, because the elementary years span a great many developmental and environmental transitions, SEL programs should take care to focus on the skills appropriate to each grade and age, rather than taking a one-size-fits-all approach. Third, they write, measurement of SEL skills among children in this age range should grow narrower in focus but broader in context and depth. www.futureofchildren.org Research has shown that during the elementary school years, social and emotional skills are related to positive academic, social, and mental health outcomes. For example, correlational studies show that classrooms function more effectively and student learning increases when children can focus their attention, manage negative emotions, navigate relationships with peers and adults, and persist in the face of difficulty. (1) Children who effectively manage their thinking, attention, and behavior are also more likely to have better grades and higher standardized test scores. (2) Children with strong social skills are more likely to make and sustain friendships, initiate positive relationships with teachers, participate in classroom activities, and be positively engaged in learning. (3) Indeed, social and emotional skills in childhood have been tied to important life outcomes 20 to 30 years later, including job and financial security, as well as physical and mental health. (4) This compelling evidence suggests that there's a strong case for making such non-academic skills and competencies a central feature of schooling, both because of their intrinsic value to society and, from a pragmatic standpoint, because they may help to reduce achievement and behavior gaps and mitigate exposure to stress. (5) But what do we know about efforts designed to improve and support social and emotional skills in the elementary years? The evidence from gold-standard studies--in which one group is randomly assigned to receive an intervention while another is not--is ambiguous. What works, for whom it works, and under what conditions often varies. For example, we've seen largescale national studies that find small or no effects from interventions designed for the elementary school years, and many individual studies that find important and meaningful effects. (6) What causes such variation isn't clear, making it hard to interpret and act on the evidence. …

Objectifs La dysautonomie familiale (FD) est une polyneuropathie hereditaire rare sensitive et autonomique. Il n’existe a ce jour aucune donnee sur la frequence et les caracteristiques des dysfonctions vesicosphincteriennes chez les patients atteints de FD. L’objectif de cette etude etait d’evaluer la frequence et les caracteristiques des dysfonctions vesicosphincteriennes chez les patients atteints de FD. Methodes Tous les patients avec une FD confirmee genetiquement ayant consulte consecutivement dans un centre de reference de la FD entre novembre 2017 et septembre 2018 ont ete inclus dans une etude prospective. Tous les patients remplissaient le jour de leur consultation les questionnaires suivants : IPSS (/35), IPSS-qol (/6), ICIQ-UI-SF (/21) et Qualiveen-SF. Tous les patients avaient le jour de la consultation une mesure du residu post-mictionnel (RPM). La charge anticholinergique etait calculee au moyen de l’Anticholinergic Drug Scale (ADS) et le handicap moteur evalue au moyen du score Brief Ataxia Rating Scale (BARS). Resultats Quarante-cinq patients ont ete inclus : 22 hommes, 23 femmes, dont l’âge moyen etait 24,3 ± 13,1 ans. Le RPM moyen etait de 54,2 ± 13,1 mL et 5 patients (11,1 %) avaient un RPM > 100 mL. Tous les questionnaires suggeraient que les patients etaient peu symptomatiques sur le plan urinaire avec un IPSS moyen a 4,5 ± 4,1, un IPSS-qol moyen a 1,3 ± 1,5, un ICIQ-UI SF moyen a 1,9 ± 3, et un Qualiveen-SF moyen a 0,3 ± 0,3. Le RPM n’etait associe statistiquement a aucun score symptome. Parmi les 15 patients qui avaient eu une echographie renovesicale recent, un avait une hydronephrose (6,7 %). Deux patients avaient un antecedent d’infections urinaires (4,6 %). Les patients avec un RPM > 100 mL avaient une charge anticholinergique plus elevee et un handicap moteur plus severe (ADS 4,2 vs 1,3, p = 0,02) (BARS 19,8 vs 13,2, p = 0,03). Conclusion Bien que peu symptomatique sur le plan urinaire, 11 % des patients atteints de FD presentaient une retention vesicale chronique. Les patients avec une retention vesicale chronique avaient une charge anticholinergique plus elevee et un handicap moteur plus important.

Purpose The obesity epidemic has afflicted children of all ages with heart transplant (HT) recipients at significant risk compared to their pediatric counterpart. This study is the first large scale study to evaluate the prevalence of obesity in pediatric HT recipients and its effects on cardiac allograft vasculopathy (CAV) and graft survival. Methods We evaluated pediatric HT recipients (age 2 years) and weight/length z score >95%ile (WHO guidelines; age Results 4756 pediatric HT patients (pts) met study criteria (mean age at 1 year post-HT = 6.7 ± 6.2 yrs; 44.6% female; 69.5% White). At HT, 56% had a normal weight, 10% were overweight, 11% were obese and 23% were underweight. Overall, ∼60% had normal BMI that remained consistent up to 15 years post-HT (56-69%). For obese pts at HT, there was an increased risk for CAV development (HR 1.5, p = 0.002) and graft loss (HR 1.3, p = 0.001), see Figure. The risk of CAV development remained significant for obese pts at 5 years post-HT (p Conclusion Only 60% of pediatric HT recipients had ideal BMI at 1 year and 5 year follow up. Obesity at HT predicts an increased risk of CAV and graft loss. Exploring metabolic risk factors that lead to CAV development and graft loss are important. Healthy lifestyle interventions pre-HT and during HT follow up may potentially reduce morbidity and mortality.

Purpose A predictive linac quality assurance system based on the output of the Machine Performance Check (MPC) application was developed using statistical process control and autoregressive integrated moving average forecast modeling. The aim of this study is to demonstrate the feasibility of predictive quality assurance based on MPC tests that allow proactive preventative maintenance procedures to be carried out to better ensure optimal linac performance and minimize downtime. Method and Materials Daily MPC data were acquired for a total of 490 measurements. The initial 85% of data were used in prediction model learning with the autoregressive integrated moving average technique and in calculating upper and lower control limits for statistical process control analysis. The remaining 15% of data were used in testing the accuracy of the predictions of the proposed system. Two types of prediction were studied, namely, one‐step‐ahead values for predicting the next day's quality assurance results and six‐step‐ahead values for predicting up to a week ahead. Results that fall within the upper and lower control limits indicate a normal stage of machine performance, while the tolerance, determined from AAPM TG‐142, is the clinically required performance. The gap between the control limits and the clinical tolerances (as the warning stage) provides a window of opportunity for rectifying linac performance issues before they become clinically significant. The accuracy of the predictive model was tested using the root‐mean‐square error, absolute error, and average accuracy rate for all MPC test parameters. Results The accuracy of the predictive model is considered high (average root‐mean‐square error and absolute error for all parameters of less than 0.05). The average accuracy rate for indicating the normal/warning stages was higher than 85.00%. Conclusion Predictive quality assurance with the MPC will allow preventative maintenance, which could lead to improved linac performance and a reduction in unscheduled linac downtime.

The characteristics of the focal spot of the linear accelerator (linac) play a role in determining the resulting dose distribution within the patient, and hence probability of treatment success. A direct measurement of focal spot position is not recommended by AAPM Task Group 142, but factors influenced by focal spot position, such as beam symmetry and isocentre position, are. Traditional methods of measuring focal spot position are time consuming and can only be performed at gantry 0°. The presented method has been proposed using a phantom of novel design to accurately measure the position of the focal spot relative to the collimator’s axis of rotation (CAX) at any gantry angle, and to measure the intra-fraction movement of the focal spot relative to the mean position during treatment. The method was reproducible to within 0.012 mm/0.029 mm (mean/max) for the three Varian linacs tested. The focal spot position was shown to deviate from the CAX by up to 0.386 mm during gantry rotation. The focal spot position was more unstable at the start of treatment, with the worst performing linac having an initial displacement of up to 0.15 mm from its mean position before stabilizing to within 0.01 mm after 3 s. The method proposed is a beneficial addition to the quality assurance (QA) schedule of any clinic, allowing quick determination of source position and movement at any gantry angle. Measurement of focal spot allows the possibility of fine-tuning the electron beam steering system to improve the standard of the photon beam and of stereotactic treatments.

BACKGROUND: Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction-breast reconstruction with implants or expanders at the time of mastectomy-but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques.METHODS: In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281.FINDINGS: Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8-10) experienced implant loss, 372 (18%, 16-20) required re-admission to hospital, and 370 (18%, 16-20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23-27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (INTERPRETATION: Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction.FUNDING: National Institute for Health Research, Association of Breast Surgery, and British Association of Plastic, Reconstructive and Aesthetic Surgeons.

In this paper, we investigate the influence of negative gate stress on threshold voltage V TH instabilities in GaN-on-Si devices. This study has been carried out by using ultra-fast Measurement-Stress-Measurement (MSM) procedure on GaN-on-Si E-mode MOSc-HEMTs (Enhancement-mode MOS-channel HEMTs) for different gate lengths L G . NBTI transients at different temperatures and complementary ToF-SIMS analysis reveal the influence of two trap populations involved on V TH instabilities, both of them are related to the C N acceptor traps. The first one is close to the interface between GaN and Al 2 O 3 gate oxide due to N-vacancies induced by the dry etching process, the second one is likely to be related to GaN:C layer. NBTI transients also exhibit a dependence with L G , which is consistent with the E-field distribution of the gate region obtained by TCAD simulations at different gate stress voltages, and confirm the proximity of a C N trap population to the gate oxide.

As a response to the environmentally and socially destructive practices of post-war mechanization and intensification, the concept of sustainable agriculture has become prominent in research, policy, and practice. Sustainable agriculture aims to balance the economic, environmental, and social aspects of farming, creating a resilient farming system in the long-term. Over the last few decades, various concepts have been used in research and policy to encourage the adoption of sustainable practices. Within such a congested space, this paper assesses the value of ‘integrated farm management’ as a concept for the promotion of sustainable agriculture. The concept is the subject of renewed policy interest in England and Wales and it is also being promoted in Europe. Previous research, however, has suggested that integrated farm management may not be well understood or widely practised. There are also criticisms that it can be impractical and poorly differentiated from similar ideas. As such, renewed insights are required into how useful the concept might be for encouraging sustainable agriculture. Using a mixed methods approach, we gathered the views of farmers, farm advisors, and industry representatives about integrated farm management in England and Wales, and interpreted these through a theoretical framework to judge the strength of the concept. Overall, the general principles of Integrated Farm Management were found to be coherent and familiar to most of our respondents. However, the concept performed poorly in terms of its resonance, simplicity of message, differentiation from other similar terms and theoretical utility. We reflect on our findings in the context of other ways to promote sustainable agriculture, drawing out messages for policy and knowledge exchange in England and Wales, as well as elsewhere.

Purpose Lack of both relevant clinical trials and real-world data (RWD) make it difficult to assess the effectiveness of any intervention in pediatric ventricular assist devices (VADs) population. Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry offers a means to capture RWD outside of traditional clinical trials. ACTION registry has introduced a standardized blinded adjudication process to provide VAD related adverse events (AEs) data with improved consistency and reliability. This study reviews the outcomes of the process at the end of its first year. Methods The ACTION adjudication committee, comprised of experts in the field, reviews all critical adverse events, including neurological dysfunction (ND), device malfunctions (DM) and events that lead to death, on a quarterly basis. The committee also reviews a randomly selected subset (15%) of major bleeding (MB) and major infection (MI). Pre-adjudication reports are sent to the centers to upload source documents to a secure portal. Documents are de-identified by the Data Coordinating Center (DCC) and are shared with the chair and two assigned adjudication reviewers. Each AE is presented by the assigned reviewers at a virtual meeting followed by a period of discussion and final adjudication. Committee recommendations are sent as post-adjudication reports to make necessary changes to the AE data entered in registry. Results Total of 658 AEs were reported in the registry through June 2020. Thus far, 182 (28%) AEs were adjudicated (59 Neuro AE, 48 events leading to death, 37 DM, and 38 randomly selected from other AEs). Majority of AEs [150 (82%)] were adjudicated as classified, however, 25 (14%) were classified as non-AEs (DMs = 22, MB = 2, ND = 1). Eight (4.5%) reported events were reclassified in different categories (MI = 2, ND = 4, Events leading to cause of death = 2). As a result of this process, 34 additional events (Events leading to cause of death = 21; Stroke = 4; Other neurological events = 3; Bleeding = 4; Infection = 1; Device malfunction = 1) were identified by the committee that were not originally reported to the registry. Conclusion ACTION adjudication process identified 18% misclassified and ∼5% unreported events, highlighting limitations of any registry data. However, an expert-led adjudication process with a follow-up DCC to site communications and training has the potential to improve the quality of RWD.

Purpose Several centers have considered the potential benefits of atrial inflow cannulation to provide mechanical circulatory support (MCS) among pediatric patients with small or restrictive ventricles particularly in those with potential for myocardial recovery. Limited pediatric data are available on contemporary outcomes of atrial cannulation. We sought to describe the characteristics, complications, and outcomes of children supported with atrial cannulation using the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) ventricular assist device (VAD) database. Methods Data were collected from the ACTION VAD database for all patients who underwent VAD implantation via atrial cannulation from 8/16/2012 to 9/8/2020. Patient characteristics, VAD types, complications, and outcomes were analyzed. Results Forty-one patients met the study criteria with 52 implants. Median age was 3.6 years (range 0.02 - 25.32), weight 13.6 kg (2.7-106), and BSA 0.6 (0.15 - 2.2). Diagnoses included dilated cardiomyopathy (42%), congenital heart disease (37%), transplant graft dysfunction (7%), restrictive and hypertrophic cardiomyopathies (5% each). VAD indications were bridge to decision (42%), bridge to transplant (42%), and bridge to recovery (17%). Eighty-four percent of patients were INTERMACS 1 or 2, 44% were on ECMO, and 63% were mechanically ventilated. Devices utilized included Berlin Heart Excor (40%), paracorporeal continuous flow devices (38%), Heartware (19%) and one Heartmate 3. Median support duration was 43.5 days (range 0-307). Overall mortality was 22%. Twenty patients (49%) were successfully transplanted, 7 (17%) recovered, and 5 (12%) are still alive on the device. Adverse events included major bleeding (24%), stroke (12%), sepsis (10%), right heart failure requiring RVAD (5%), and one instance of pump thrombosis. Conclusion Atrial cannulation in pediatric MCS can be performed across a variety of anatomic substrates and age ranges with outcomes and complication rates that are comparable to left ventricular cannulation strategies. This method may be advantageous in certain circumstances including patients with small or restrictive ventricles, potential for myocardial recovery, or multiple prior sternotomies to minimize surgical dissection. Further studies are needed to delineate the ideal patient population and benefits of varying atrial cannulation techniques.

Pediatric heart transplantation has additional and unique aspects from standard pediatric heart surgery and adult heart transplantation. The purpose of this article is to review pediatric heart transplantation and special surgical considerations. The methods used by the authors involved reviewing the literature and surgical techniques surrounding this patient population and procedure. The article presents a general review of the topic including the history, current state, surgical approaches, post-operative management, and outcomes in this patient population.

Multileaf collimator (MLC) positions should be precisely and independently measured as a function of gantry angle as part of a comprehensive quality assurance (QA) program for volumetric‐modulated arc therapy (VMAT). It is also ideal that such a QA program has the ability to relate MLC positional accuracy to patient‐specific dosimetry in order to determine the clinical significance of any detected MLC errors. In this work we propose a method to verify individual MLC trajectories during VMAT deliveries for use as a routine linear accelerator QA tool. We also extend this method to reconstruct the 3D patient dose in the treatment planning system based on the measured MLC trajectories and the original DICOM plan file. The method relies on extracting MLC positions from EPID images acquired at 8.41 fps during clinical VMAT deliveries. A gantry angle is automatically tagged to each image in order to obtain the MLC trajectories as a function of gantry angle. This analysis was performed for six clinical VMAT plans acquired at monthly intervals for three months. The measured trajectories for each delivery were compared to the MLC positions from the DICOM plan file. The maximum mean error detected was 0.07 mm and a maximum root‐mean‐square error was 0.8 mm for any leaf of any delivery. The sensitivity of this system was characterized by introducing random and systematic MLC errors into the test plans. It was demonstrated that the system is capable of detecting random and systematic errors on the range of 1–2 mm and single leaf calibration errors of 0.5 mm. The methodology developed in the work has potential to be used for efficient routine linear accelerator MLC QA and pretreatment patient‐specific QA and has the ability to relate measured MLC positional errors to 3D dosimetric errors within a patient volume. PACS number(s): 87.55.Qr

In volumetric‐modulated arc therapy (VMAT) treatment delivery perfect beam symmetry is assumed by the planning system. This study aims to test this assumption and present a method of measuring time‐resolved beam symmetry measurement during a VMAT delivery that includes extreme variations of dose rate and gantry speed. The Sun Nuclear IC Profiler in gantry mount was used to measure time‐resolved in‐plane and cross‐plane profiles during plan delivery from which symmetry could be determined. Time‐resolved symmetry measurements were performed throughout static field exposures at cardinal gantry angles, conformal arcs with constant dose rate and gantry speed, and during a VMAT test plan with gantry speed and dose rate modulation. Measurements were performed for both clockwise and counterclockwise gantry rotation and across four Varian 21iX linacs. The symmetry was found to be generally constant throughout the static field exposures to within 0.3% with an exception on one linac of up to 0.7%. Agreement in symmetry between cardinal angles was always within 1.0% and typically within 0.6%. During conformal arcs the results for clockwise and counterclockwise rotation were in agreement to within 0.3%. Both clockwise and counterclockwise tended to vary in similar manner by up to 0.5% during arc consistent with the cardinal gantry angle static field results. During the VMAT test plan the symmetry generally was in agreement with the conformal arc results. Greater variation in symmetry was observed in the low‐dose‐rate regions by up to 1.75%. All results were within clinically acceptable levels using the tolerances of NCS Report 24 (2015). PACS number(s): 87.55.Qr

To accurately measure the concentrations of atmospheric gasses, especially the gasses with low concentrations, strong absorption features must be accessed. Each molecular species or constituent has characteristic mid-infrared absorption features by which either column content or range resolved concentrations can be measured. Because of these characteristic absorption features the mid infrared spectral region is known as the fingerprint region. However, as noted by the Decadal Survey, mid-infrared solid-state lasers needed for DIAL systems are not available. The primary reason is associated with short upper laser level lifetimes of mid infrared transitions. Energy gaps between the energy levels that produce mid-infrared laser transitions are small, promoting rapid nonradiative quenching. Nonradiative quenching is a multiphonon process, the more phonons needed, the smaller the effect. More low energy phonons are required to span an energy gap than high energy phonons. Thus, low energy phonon materials have less nonradiative quenching compared to high energy phonon materials. Common laser materials, such as oxides like YAG, are high phonon energy materials, while fluorides, chlorides and bromides are low phonon materials. Work at NASA Langley is focused on a systematic search for novel lanthanide-doped mid-infrared solid-state lasers using both quantum mechanical models (theoretical) and spectroscopy (experimental) techniques. Only the best candidates are chosen for laser studies. The capabilities of modeling materials, experimental challenges, material properties, spectroscopy, and prospects for lanthanide-doped mid-infrared solid-state laser devices will be presented.

Purpose The initial project of ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is focused on improving stroke rates in patients implanted with a ventricular assist devices (VAD) in participating centers. The initial interventions targeted improving communication, anticoagulation, and blood pressure management. We sought to describe the characteristics and outcomes of patients implanted with intracorporeal, continuous flow VADs (cfVAD). Methods The ACTION registry was used to determine the stroke frequency in cfVAD implanted patients between April 2018 and September 2019, the time from development of the quality improvement bundle to the present. Results Sixty two patients (33 Heartmate3 [HM3] and 29 Heartware [HVAD]) were identified (Table). The majority had dilated cardiomyopathy (76%). Of the 12 (20%) patients with congenital heart disease (CHD), 9 (75%) had single ventricle (SV) physiology. The HM3 patients were older (16.5 yr vs 12.8 yr) and larger (64.2 kg vs 51.9 kg) than the HVAD patients. No significant difference was observed in diagnosis, duration of support, device strategy, or clinical outcome. One patient (2%) experienced a stroke during 6,920 days of support. Forty of the 45 (89%) patients to reach a clinical endpoint experienced a positive outcome (transplant or explant for recovery) while 17 (27%) patients remain on device. Conclusion The stroke rate is low and survival good among patients implanted with an intracorporeal cfVAD at ACTION centers using the clinical protocols developed within the network. The HVAD is currently being used more frequently in younger and smaller patients. There has been an appreciable increase in the number and frequency of implants in patients with CHD, especially SV disease, as compared to previous reports. Future efforts within ACTION will focus on improving clinical outcomes as devices are increasingly used at individual centers and as the number of VAD-supported patients with congenital heart disease continues to grow.

Dyslipidemia in the pediatric heart transplant (HT) population carries significant risk for developing cardiac allograft vasculopathy (CAV), one of the primary reasons for heart retransplantation (retx). This large-scale pediatric study sought to evaluate the prevalence of dyslipidemia and its