High spatial resolution inorganic scintillator detector for high energy X-ray beam at small field irradiation

International audiencePurpose: Small fielddosimetry for radiotherapy is one of the major challenges due to the size of most dosimeters,e.g. sufficient spatial resolution, accurate dose distribution and energy dependency of the detector. In this context, the purpose of this research is to develop a small size scintillating detector targeting small field dosimetry and compare its performance with other commercial detectors. Method: An inorganic scintillator detector (ISD) of about 200 μm outer diameter was developed and tested through different small fields dosimetric characterization under high energy photons (6 MV and 15 MV) delivered by an Elekta Linear Accelerator (LINAC). PDD and beam profile measurements were compared using dosimeters from PTW namely, microdiamond and PinPoint 3D detector. A background fiber method has been considered to quantifyand eliminate the minimal Cerenkov effect from the total optical signal magnitude. Measurements were performed inside a water phantom under IAEA Technical reports series recommendations (IAEA TRS 381 and TRS 483). Results:Small fields ranging from 3 x 3 cm2, down to 0.5 x 0.5 cm2 were sequentiallymeasured using the ISD and commercial dosimeters, and a good agreement was obtained among all measurements. The result also shows that, scintillating detector has good repeatabilityand reproducibility of the output signal with maximum deviation of 0.26% and 0.5% respectively. The Full Width Half Maximum (FWHM) was measured 0.55 cm for the smallest available square size field of 0.5 x 0.5 cm2, where the discrepancy of 0.05 cm is dueto the scattering effects inside the water and convolution effect between field and detector geometries. Percentage Depth Dose (PDD) factor dependence variation with water depth exhibits nearly the same behavior for all tested detectors. The ISD allows to perform dose measurements at a very high accuracy from low (50 cGy/min) to high dose rates (800 cGy/min) and found to be independent of dose rate variation. The detection system also showed an excellent linearity with dose; hence calibration was easily achieved. Conclusions: The developed detector can be used to accurately measure the delivered dose at small field during the treatment of small volume tumors. The author’s measurement shows that despite using a non-water equivalent detector, the detector can be a powerful candidate for beam characterization and quality assurance in e.g., radiosurgery, Intensity Modulated Radiotherapy (IMRT), and brachytherapy. Our detector can provide real-time dose measurement and good spatial resolution with immediate readout, simplicity, flexibility, and robustness

Active Learning for Auditory Hierarchy

Much audio content today is rendered as a static stereo mix: fundamentally a fixed single entity. Object-based audio envisages the delivery of sound content using a collection of individual sound ‘objects’ controlled by accompanying metadata. This offers potential for audio to be delivered in a dynamic manner providing enhanced audio for consumers. One example of such treatment is the concept of applying varying levels of data compression to sound objects thereby reducing the volume of data to be transmitted in limited bandwidth situations. This application motivates the ability to accurately classify objects in terms of their ‘hierarchy’. That is, whether or not an object is a foreground sound, which should be reproduced at full quality if possible, or a background sound, which can be heavily compressed without causing a deterioration in the listening experience. Lack of suitably labelled data is an acknowledged problem in the domain. Active Learning is a method that can greatly reduce the manual effort required to label a large corpus by identifying the most effective instances to train a model to high accuracy levels. This paper compares a number of Active Learning methods to investigate which is most effective in the context of a hierarchical labelling task on an audio dataset. Results show that the number of manual labels required can be reduced to 1.7% of the total dataset while still retaining high prediction accuracy

Soundscape assessment: Towards a validated translation of perceptual attributes in different languages

The recently published ISO/TS 12913-2:2018 standard aims to provide researchers and practitioners around the world with a reliable questionnaire for soundscape characterization. The ISO Technical Specifications report protocols and attributes grounded in the soundscape literature, but only includes an English version. The applicability and reliability of these attributes in non-English speaking regions remains an open question, as research investigating translations of soundscape attributes is limited. To address this gap, an international collaboration was initiated with soundscape researchers from all over the world. Translation into 15 different languages, obtained through focus groups and panels of experts in soundscape studies, are proposed. The main challenges and outcomes of this preliminary exercise are discussed. The long-term objective is to validate the proposed translations using standardized listening experiments in different languages and geographical regions as a way to promote a widespread use of the soundscape attributes, both in academia and practice, across locations, populations and languages

Rapid HIV disease progression following superinfection in an HLA-B*27:05/B*57:01-positive transmission recipient.

BACKGROUND: The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expressing both HLA-B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads for more than a decade of follow up. The other progressed to AIDS in < 3 years. RESULTS: The rapid progressor was the recipient within a known transmission pair, enabling virus sequences to be tracked from transmission. Progression was associated with a 12% Gag sequence change and 26% Nef sequence change at the amino acid level within 2 years. Although next generation sequencing from early timepoints indicated that multiple CD8+ cytotoxic T lymphocyte (CTL) escape mutants were being selected prior to superinfection, < 4% of the amino acid changes arising from superinfection could be ascribed to CTL escape. Analysis of an HLA-B*27:05/B*57:01 non-progressor, in contrast, demonstrated minimal virus sequence diversification (1.1% Gag amino acid sequence change over 10 years), and dominant HIV-specific CTL responses previously shown to be effective in control of viraemia were maintained. Clonal sequencing demonstrated that escape variants were generated within the non-progressor, but in many cases were not selected. In the rapid progressor, progression occurred despite substantial reductions in viral replicative capacity (VRC), and non-progression in the elite controller despite relatively high VRC. CONCLUSIONS: These data are consistent with previous studies demonstrating rapid progression in association with superinfection and that rapid disease progression can occur despite the relatively the low VRC that is typically observed in the setting of multiple CTL escape mutants

Differential immunodominance hierarchy OF CD8+ T cell responses in HLA-B*27:05 AND B*27:02-mediated control of HIV-1 infection

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV

Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection

The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex