Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis

Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy

Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A block aperture module was integrated into VPMC. VPMC was validated by an opensource code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 cc). Finally, 3 patients were selected for robust optimization with aperture blocks using VPMC. Results: In the water phantoms, 3D gamma passing rate (2%/2mm/10%) between VPMC and MCsquare were 99.71$\pm$0.23%. In the patient geometries, 3D gamma passing rates (3%/2mm/10%) between VPMC/MCsquare and RayStation MC were 97.79$\pm$2.21%/97.78$\pm$1.97%, respectively. The calculation time was greatly decreased from 112.45$\pm$114.08 seconds (MCsquare) to 8.20$\pm$6.42 seconds (VPMC), both having statistical uncertainties of about 0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 seconds. Conclusion: VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.Comment: 3 tables, 3 figure

Clinical commissioning of intensity-modulated proton therapy systems: Report of AAPM Task Group 185

Proton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system\u27s multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components. Also included in the commissioning process are the x-ray computed tomography scanner calibration for proton stopping power, the radiotherapy treatment planning system, and corresponding portions of the treatment management system. This commissioning report focuses exclusively on intensity-modulated scanning systems, presenting details of how to perform the commissioning of the proton therapy and ancillary systems, including the required proton beam measurements, treatment planning system dose modeling, and the equipment needed

Consensus Statement on Proton Therapy in Mesothelioma

Purpose: Radiation therapy for mesothelioma remains challenging, as normal tissue toxicity limits the amount of radiation that can be safely delivered to the pleural surfaces, especially radiation dose to the contralateral lung. The physical properties of proton therapy result in better sparing of normal tissues when treating the pleura, both in the postpneumonectomy setting and the lung-intact setting. Compared with photon radiation, there are dramatic reductions in dose to the contralateral lung, heart, liver, kidneys, and stomach. However, the tissue heterogeneity in the thorax, organ motion, and potential for changing anatomy during the treatment course all present challenges to optimal irradiation with protons. Methods: The clinical data underlying proton therapy in mesothelioma are reviewed here, including indications, advantages, and limitations. Results: The Particle Therapy Cooperative Group Thoracic Subcommittee task group provides specific guidelines for the use of proton therapy for mesothelioma. Conclusions: This consensus report can be used to guide clinical practice, insurance approval, and future research

The influence of the viewpoint in a self-avatar on body part and self-localization

The goal of this study is to determine how a self-avatar in virtual reality, experienced from different viewpoints on the body (at eye- or chest-height), might influence body part localization, as well as self-localization within the body. Previous literature shows that people do not locate themselves in only one location, but rather primarily in the face and the upper torso. Therefore, we aimed to determine if manipulating the viewpoint to either the height of the eyes or to the height of the chest would influence self-location estimates towards these commonly identified locations of self. In a virtual reality (VR) headset, participants were asked to point at sev- eral of their body parts (body part localization) as well as "directly at you" (self-localization) with a virtual pointer. Both pointing tasks were performed before and after a self-avatar adaptation phase where participants explored a co-located, scaled, gender-matched, and animated self-avatar. We hypothesized that experiencing a self-avatar might reduce inaccuracies in body part localization, and that viewpoint would influence pointing responses for both body part and self-localization. Participants overall pointed relatively accurately to some of their body parts (shoulders, chin, and eyes), but very inaccurately to others, with large undershooting for the hips, knees, and feet, and large overshooting for the top of the head. Self-localization was spread across the body (as well as above the head) with the following distribution: the upper face (25%), the up- per torso (25%), above the head (15%) and below the torso (12%). We only found an influence of viewpoint (eye- vs chest-height) during the self-avatar adaptation phase for body part localization and not for self-localization. The overall change in error distance for body part localization for the viewpoint at eye-height was small (M = –2.8 cm), while the overall change in error distance for the viewpoint at chest-height was significantly larger, and in the upwards direction relative to the body parts (M = 21.1 cm). In a post-questionnaire, there was no significant difference in embodiment scores between the viewpoint conditions. Most interestingly, having a self-avatar did not change the results on the self-localization pointing task, even with a novel viewpoint (chest-height). Possibly, body-based cues, or memory, ground the self when in VR. However, the present results caution the use of altered viewpoints in applications where veridical position sense of body parts is required

Long term aging of Selenide glasses: Evidence of sub-Tg endotherms and pre-Tg exotherms

Long term aging is studied on several families of chalcogenide glasses including the Ge-Se, As-Se, Ge-P-Se and Ge-As-Se systems. Special attention is given to the As-Se binary, a system that displays a rich variety of aging behavior intimately tied to sample synthesis conditions and the ambient environment in which samples are aged. Calorimetric (Modulated DSC) and Raman scattering experiments are undertaken. Our results show all samples display a sub-Tg endotherm below Tg in glassy networks possessing a mean coordination number r in the 2.25 < r < 2.45 range. Two sets of AsxSe1-x samples aged for 8 years were compared, set A consisted of slow cooled samples aged in the dark, and set B consisted of melt quenched samples aged at laboratory environment. Samples of set B in the As concentration range, 35% < x < 60%, display a pre-Tg exotherm, but the feature is not observed in samples of set A. The aging behavior of set A presumably represents intrinsic aging in these glasses, while that of set B is extrinsic due to presence of light. The reversibility window persists in both sets of samples but is less well defined in set B. These findings contrast with a recent study by Golovchak et al., which finds the onset of the reversibility window moved up to the stoichiometric composition (x = 40%). Here we show that the upshifted window is better understood as resulting due to demixing of As4Se4 and As4Se3 molecules from the backbone, i.e., Nanoscale phase separation (NSPS). We attribute sub-Tg endotherms to compaction of the flexible part of networks upon long term aging, while the pre-Tg exotherm to NSPS. Finally, the narrowing and sharpening of the reversibility window upon aging is interpreted as the slow 'self-organizing' stress relaxation of the phases just outside the Intermediate phase.Comment: In press - J. of Physics: Condensed Matte

Distributed, Collaborative Virtual Reality Application for Product Development with Simple Avatar Calibration Method

In this work we present a collaborative virtual reality application for distributed engineering tasks, including a simple avatar calibration method. Use cases for the application include CAD review, ergonomics analyses or virtual training. Full-body avatars are used to improve collaboration in terms of co-presence and embodiment. Through a calibration process, scaled avatars based on body measurements can be generated by users from within the VR application. We demonstrate a simple, yet effective method for measuring the human body which requires off-the-shelf VR devices only. Tracking only the user’s head and hands, we use inverse kinematics for avatar motion reconstruction