Clinical acceptance and dosimetric impact of automatically delineated elective target and organs at risk for head and neck MR-Linac patients

Background: MR-Linac allows for daily online treatment adaptation to the observed geometry of tumor targets and organs at risk (OARs). Manual delineation for head and neck cancer (HNC) patients takes 45-75 minutes, making it unsuitable for online adaptive radiotherapy. This study aims to clinically and dosimetrically validate an in-house developed algorithm which automatically delineates the elective target volume and OARs for HNC patients in under a minute.Methods: Auto-contours were generated by an in-house model with 2D U-Net architecture trained and tested on 52 MRI scans via leave-one-out cross-validation. A randomized selection of 684 automated and manual contours (split half-and-half) was presented to an oncologist to perform a blind test and determine the clinical acceptability. The dosimetric impact was investigated for 13 patients evaluating the differences in dosage for all structures. Results: Automated contours were generated in 8 seconds per MRI scan. The blind test concluded that 114 (33%) of auto-contours required adjustments with 85 only minor and 15 (4.4%) of manual contours required adjustments with 12 only minor. Dosimetric analysis showed negligible dosimetric differences between clinically acceptable structures and structures requiring minor changes. The Dice Similarity coefficients for the auto-contours ranged from 0.66 ± 0.11 to 0.88 ± 0.06 across all structures. Conclusion: Majority of auto-contours were clinically acceptable and could be used without any adjustments. Majority of structures requiring minor adjustments did not lead to significant dosimetric differences, hence manual adjustments were needed only for structures requiring major changes, which takes no longer than 10 minutes per patient.</p

An efficient implementation of massive neutrinos in non-linear structure formation simulations

Massive neutrinos make up a fraction of the dark matter, but due to their large thermal velocities, cluster significantly less than cold dark matter (CDM) on small scales. An accurate theoretical modelling of their effect during the non-linear regime of structure formation is required in order to properly analyse current and upcoming high-precision large-scale structure data, and constrain the neutrino mass. Taking advantage of the fact that massive neutrinos remain linearly clustered up to late times, this paper treats the linear growth of neutrino overdensities in a non-linear CDM background. The evolution of the CDM component is obtained via N-body computations. The smooth neutrino component is evaluated from that background by solving the Boltzmann equation linearised with respect to the neutrino overdensity. CDM and neutrinos are simultaneously evolved in time, consistently accounting for their mutual gravitational influence. This method avoids the issue of shot-noise inherent to particle-based neutrino simulations, and, in contrast with standard Fourier-space methods, properly accounts for the non-linear potential wells in which the neutrinos evolve. Inside the most massive late-time clusters, where the escape velocity is larger than the neutrino thermal velocity, neutrinos can clump non-linearly, causing the method to formally break down. It is shown that this does not affect the total matter power spectrum, which can be very accurately computed on all relevant scales up to the present time.Comment: Version accepted by MNRAS. Implementation available at http://github.com/downloads/sbird/fs-neutrino/kspace-neutrino-2.tar.g

Massive Neutrinos and the Non-linear Matter Power Spectrum

We perform an extensive suite of N-body simulations of the matter power spectrum, incorporating massive neutrinos in the range M = 0.15-0.6 eV, probing the non-linear regime at scales k < 10 hMpc-1 at z < 3. We extend the widely used HALOFIT approximation to account for the effect of massive neutrinos on the power spectrum. In the strongly non-linear regime HALOFIT systematically over-predicts the suppression due to the free-streaming of the neutrinos. The maximal discrepancy occurs at k ~ 1 hMpc-1, and is at the level of 10% of the total suppression. Most published constraints on neutrino masses based on HALOFIT are not affected, as they rely on data probing the matter power spectrum in the linear or mildly non-linear regime. However, predictions for future galaxy, Lyman-alpha forest and weak lensing surveys extending to more non-linear scales will benefit from the improved approximation to the non-linear matter power spectrum we provide. Our approximation reproduces the induced neutrino suppression over the targeted scales and redshifts significantly better. We test its robustness with regard to changing cosmological parameters and a variety of modelling effects.Comment: 12 pages, 6 figures, version accepted by MNRAS. v2: Minor clarifications and corrections, citations added. Code available in CAMB and from http://www.sns.ias.edu/~spb v3: Correct typo in equation A

Variation in migration behaviors used by Arctic Terns (Sterna paradisaea) breeding across a wide latitudinal gradient

Arctic Terns (Sterna paradisaea) share a few routes to undertake the longest annual migrations of any organism. To understand how the wide spatial range of their breeding colonies may affect their migration strategies (e.g., departure date), we tracked 53 terns from five North American colonies distributed across 30° of latitude and 90° of longitude. While birds from all colonies arrived in Antarctic waters at a similar time, terns nesting in the Arctic colonies migrated back north more slowly and arrived to their breeding grounds later than those nesting in the colony farther south. Arrival dates in Antarctic waters coincided with the start of favorable foraging conditions (i.e., increased ocean productivity), and similarly arrival dates at breeding colonies coincided with the start of local favorable breeding conditions (i.e., disappearance of snow and ice). Larger birds followed a more direct southbound migration route than smaller birds. On both southbound and northbound migrations, daily distances traveled declined as time spent in contact with the ocean increased, suggesting a trade-off between resting/foraging and traveling. There was more unexplained variation in behavior among individuals than among colonies, and one individual had a distinctive stop around Brazil. Terns nesting in the Arctic have a narrow time window for breeding that will likely increase with continuing declines in sea ice and snow. Departing Arctic Terns likely have few clues about the environmental conditions they will encounter on arrival, and their response to environmental changes at both poles may be assisted by large individual variation in migration strategy

Atypical functional connectivity during unfamiliar music listening in children with autism

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula.Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning.info:eu-repo/semantics/publishedVersio

A three-country comparison of psychotropic medication prevalence in youth

<p>Abstract</p> <p>Background</p> <p>The study aims to compare cross-national prevalence of psychotropic medication use in youth.</p> <p>Methods</p> <p>A population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0–4, 5–9, 10–14, and 15–19), gender, drug subclass pattern and concomitant use. The data include insured youth aged 0–19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157).</p> <p>Results</p> <p>The annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5–2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth.</p> <p>Conclusion</p> <p>Prominent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.</p

Anatomically realistic ultrasound phantoms using gel wax with 3D printed moulds

Here we describe methods for creating tissue-mimicking ultrasound phantoms based on patient anatomy using a soft material called gel wax. To recreate acoustically realistic tissue properties, two additives to gel wax were considered: paraffin wax to increase acoustic attenuation, and solid glass spheres to increase backscattering. The frequency dependence of ultrasound attenuation was well described with a power law over the measured range of 3 to 10 MHz. With the addition of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to 2.91 dB/cm at 3 MHz and from 6.84 to 26.63 dB/cm at 10 MHz. With solid glass sphere concentrations in the range of 0.025 to 0.9 w/w%, acoustic backscattering consistent with a wide range of ultrasonic appearances was achieved. Native gel wax maintained its integrity during compressive deformations up to 60%; its Young's modulus was 17.4 ± 1.4 kPa. The gel wax with additives was shaped by melting and pouring it into 3D printed moulds. Three different phantoms were constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart atrium phantom, and a placental phantom for minimally-invasive fetal interventions. In the first, nerves and vessels were represented as hyperechoic and hypoechoic tubular structures, respectively, in a homogeneous background. The second phantom comprised atria derived from an MRI scan of a patient with an intervening septum and adjoining vena cavae. The third comprised the chorionic surface of a placenta with superficial fetal vessels derived from an image of a post-partum human placenta. Gel wax is a material with widely tuneable ultrasound properties and mechanical characteristics that are well suited for creating patient-specific ultrasound phantoms in several clinical disciplines

Media reporting of tenofovir trials in Cambodia and Cameroon

BACKGROUND: Two planned trials of pre-exposure prophylaxis tenofovir in Cambodia and Cameroon to prevent HIV infection in high-risk populations were closed due to activist pressure on host country governments. The international news media contributed substantially as the primary source of knowledge transfer regarding the trials. We aimed to characterize the nature of reporting, specifically focusing on the issues identified by media reports regarding each trial. METHODS: With the aid of an information specialist, we searched 3 electronic media databases, 5 electronic medical databases and extensively searched the Internet. In addition we contacted stakeholder groups. We included media reports addressing the trial closures, the reasons for the trial closures, and who was interviewed. We extracted data using content analysis independently, in duplicate. RESULTS: We included 24 reports on the Cambodian trial closure and 13 reports on the Cameroon trial closure. One academic news account incorrectly reported that it was an HIV vaccine trial that closed early. The primary reasons cited for the Cambodian trial closure were: a lack of medical insurance for trial related injuries (71%); human rights considerations (71%); study protocol concerns (46%); general suspicions regarding trial location (37%) and inadequate prevention counseling (29%). The primary reasons cited for the Cameroon trial closure were: inadequate access to care for seroconverters (69%); participants not sufficiently informed of risks (69%); inadequate number of staff (46%); participants being exploited (46%) and an unethical study design (38%). Only 3/23 (13%) reports acknowledged interviewing research personnel regarding the Cambodian trial, while 4/13 (30.8%) reports interviewed researchers involved in the Cameroon trial. CONCLUSION: Our review indicates that the issues addressed and validity of the media reports of these trials is highly variable. Given the potential impact of the media in formulation of health policy related to HIV, efforts are needed to effectively engage the media during periods of controversy in the HIV/AIDS epidemic

Hydrolyzed eggshell membrane immobilized on phosphorylcholine polymer supplies extracellular matrix environment for human dermal fibroblasts

We have found that a water-soluble alkaline-digested form of eggshell membrane (ASESM) can provide an extracellular matrix (ECM) environment for human dermal fibroblast cells (HDF) in vitro. Avian eggshell membrane (ESM) has a fibrous-meshwork structure and has long been utilized as a Chinese medicine for recovery from burn injuries and wounds in Asian countries. Therefore, ESM is expected to provide an excellent natural material for biomedical use. However, such applications have been hampered by the insolubility of ESM proteins. We have used a recently developed artificial cell membrane biointerface, 2-methacryloyloxyethyl phosphorylcholine polymer (PMBN) to immobilize ASESM proteins. The surface shows a fibrous structure under the atomic force microscope, and adhesion of HDF to ASESM is ASESM-dose-dependent. Quantitative mRNA analysis has revealed that the expression of type III collagen, matrix metalloproteinase-2, and decorin mRNAs is more than two-fold higher when HDF come into contact with a lower dose ASESM proteins immobilized on PMBN surface. A particle-exclusion assay with fixed erythrocytes has visualized secreted water-binding molecules around the cells. Thus, HDF seems to possess an ECM environment on the newly designed PMBN-ASESM surface, and future applications of the ASESM-PMBN system for biomedical use should be of great interest