Association of Cortical Lesions With Regional Glutamate, GABA, N-Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region. METHODS: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, N-acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls. Data were collected at a single center between August 2018 and September 2020. Linear mixed-effects models were used to test for associations between metabolite concentrations and cortical lesion volumes within the same MR-spectroscopy voxel. RESULTS: Forty-seven patients with MS (34 RRMS, 13 SPMS; 45.1 ± 12.5 years; 31 women) and 23 healthy controls (44.4 ± 13 years, 15 women) were studied. In patients, higher regional glutamate and lower regional GABA concentrations were associated with larger cortical lesion volume within the MR-spectroscopy voxel [glutamate: 0.61 (95% CI 0.19-1.03) log(mm3), p = 0.005, GABA: -0.71 (-1.24 to -0.18) log(mm3), p = 0.01]. In addition, lower N-acetylaspartate levels [-0.37 (-0.67 to -0.07) log(mm3), p = 0.016] and higher myoinositol levels [0.48 (0.03-0.93) log(mm3), p = 0.037] were associated with a larger regional cortical lesion volume. Furthermore, glutamate concentrations were reduced in patients with SPMS compared with healthy participants [-0.75 (-1.3 to -0.19) mM, p = 0.005] and patients with RRMS [-0.55 (-1.07 to -0.02) mM, p = 0.04]. N-acetylaspartate levels were lower in both patients with RRMS [-0.81 (-1.39 to -0.24) mM, p = 0.003] and SPMS [-1.31 (-2.07 to -0.54) mM, p < 0.001] when compared with healthy controls. Creatine-normalized N-acetylaspartate levels were associated with performance in the 9-hole peg test of the contralateral hand [-0.004 (-0.007 to -0.002) log(s), p = 0.002], and reduced mean creatine-normalized glutamate was associated with increased Expanded Disability Status Scale (R = -0.39, p = 0.02). DISCUSSION: Cortical lesions are associated with local increases in glutamate and a reduction in GABA concentration within the lesional or perilesional tissue. Further studies are needed to investigate the causal relationship between cortical lesions and changes in neurotransmitter concentrations.

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams.

Objective.This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (LET-) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations.Approach.Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (LET-f) and dose-averaged LET (LET-d) were determined. For both quantities, two sub-types of averages were calculated, either considering the contributions from primary and secondary protons or from all protons and heavier, charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE).Main results.All types ofLET-could be assessed with the luminescence detectors. The experimental determination ofLET-fis in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand,LET-dcan present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from theLET-dcalculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy betweenLET-fandLET-d. Assessment of RBE through the experimentally determinedLET-dvalues agrees with independently acquired reference values, indicating that the investigated detectors can determineLET-with sufficient accuracy for proton therapy.Significance.OSLDs, TLDs, and FNTDs can be used to determineLET-and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived fromLET-, OSLDs and TLDs can simultaneously ascertain dose,LET-, and RBE. This makes passive detectors appealing for measurements in phantoms to facilitate validation of clinical treatment plans or experiments related to proton therapy.

Predicting Individual Hearing-Aid Preference From Self-Reported Listening Experiences in Daily Life.

OBJECTIVES: The study compared the utility of two approaches for collecting real-world listening experiences to predict hearing-aid preference: a retrospective questionnaire (Speech, Spatial, and Qualities of Hearing Scale [SSQ]) and in-situ Ecological Momentary Assessment (EMA). The rationale being that each approach likely provides different and yet complementary information. In addition, it was examined how self-reported listening activity and hearing-aid data-logging can augment EMAs for individualized and contextualized hearing outcome assessments. DESIGN: Experienced hearing-aid users (N = 40) with mild-to-moderate symmetrical sensorineural hearing loss completed the SSQ questionnaire and gave repeated EMAs for two wear periods of 2-weeks each with two different hearing-aid models that differed mainly in their noise reduction technology. The EMAs were linked to a self-reported listening activity and sound environment parameters (from hearing-aid data-logging) recorded at the time of EMA completion. Wear order was randomized by hearing-aid model. Linear mixed-effects models and Random Forest models with five-fold cross-validation were used to assess the statistical associations between listening experiences and end-of-trial preferences, and to evaluate how accurately EMAs predicted preference within individuals. RESULTS: Only 6 of the 49 SSQ items significantly discriminated between responses made for the end-of-trial preferred versus nonpreferred hearing-aid model. For the EMAs, questions related to perception of the sound from the hearing aids were all significantly associated with preference, and these associations were strongest in EMAs completed in sound environments with predominantly low SNR and listening activities related to television, people talking, nonspecific listening, and music listening. Mean differences in listening experiences from SSQ and EMA correctly predicted preference in 71.8% and 72.5% of included participants, respectively. However, a prognostic classification of single EMAs into end-of-trial preference with a Random Forest model achieved a 93.8% accuracy when contextual information was included. CONCLUSIONS: SSQ and EMA predicted preference equally well when considering mean differences, however, EMAs had a high prognostic classifications accuracy due to the repeated-measures nature, which make them ideal for individualized hearing outcome investigations, especially when responses are combined with contextual information about the sound environment.

Effects of anti-CD20 therapy on circulating and intrathecal follicular helper T cell subsets in multiple sclerosis.

Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry. CSF Tfh cells were increased in untreated patients. Compared to paired blood samples, CD25- Tfh cells were enriched in CSF in RRMS, but not in controls. Contrast-enhancing brain MRI lesions and IgG index correlated with CSF CD25- Tfh cell frequency in untreated patients with RRMS. Anti-CD20 therapy reduced the numbers of circulating PD1+ Tfh cells and CD25- Tfh cells, and the frequency of CSF CD25- Tfh cells. The study suggests that CD25- Tfh cells are recruited to the CSF in RRMS, associated with focal inflammation, and are reduced by anti-CD20 therapy.

Dosimetric study for breathing-induced motion effects in an abdominal pancreas phantom for carbon ion mini-beam radiotherapy.

BACKGROUND: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation. PURPOSE: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer. METHODS: As a first step, the carbon ion mini-beam pattern was characterized with Monte Carlo simulations. To analyze the impact of breathing-induced organ motion on the dose distribution of a virtual pancreas tumor as target and related OARs, the anthropomorphic Pancreas Phantom for Ion beam Therapy (PPIeT) was irradiated with carbon ions. A mini-beam collimator was used to deliver a spatially fractionated dose distribution. During irradiation, varying breathing motion amplitudes were induced, ranging from 5 to 15 mm. Post-irradiation, the 2D dose pattern was analyzed, focusing on the full width at half maximum (FWHM), center-to-center distance (ctc), and the peak-to-valley dose ratio (PVDR). RESULTS: The mini-beam pattern was visible within OARs, while in the virtual pancreas tumor a more homogeneous dose distribution was achieved. Applied motion affected the mini-beam pattern within the kidney, one of the OARs, reducing the PVDR from 3.78  ± $\pm$  0.12 to 1.478  ± $\pm$  0.070 for the 15 mm motion amplitude. In the immobile OARs including the spine and the skin at the back, the PVDR did not change within 3.4% comparing reference and motion conditions. CONCLUSIONS: This study provides an initial understanding of how breathing-induced organ motion affects spatial fractionation during carbon ion irradiation, using an anthropomorphic phantom. A decrease in the PVDR was observed in the right kidney when breathing-induced motion was applied, potentially increasing the risk of damage to OARs. Therefore, further studies are needed to explore the clinical viability of mini-beam radiotherapy with carbon ions when irradiating abdominal regions.

Extended interval dosing with ocrelizumab in multiple sclerosis.

BACKGROUND: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). METHODS: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included (n = 184). Clinical, radiological, and blood-based biomarker outcomes were evaluated. MRI disease activity, relapses, worsening of neurostatus, and No Evidence of Disease Activity-3 (NEDA-3) were used as a combined endpoint. RESULTS: Out of 184 participants, 107 participants received EID (58.2%), whereas 77 participants received SID (41.8%). The average extension was 9 weeks with a maximum of 78 weeks. When comparing EID to SID, we found higher levels of B-cells, lower serum concentrations of ocrelizumab, and similar levels of age-adjusted NFL and GFAP in the two groups. No difference in NEDA-3 between EID and SID was demonstrated (hazard ratio: 1.174, p = 0.69). Higher levels of NFL were identified in participants with disease activity. Body mass index correlated with levels of ocrelizumab and B-cells. CONCLUSION: Extending one treatment interval of ocrelizumab on average 9 weeks and up to 78 weeks did not result in clinical, radiological, or biomarker evidence of worsening compared with SID.

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Neoehrlichiosis associated with ocrelizumab in a patient with multiple sclerosis: A case report.

OBJECTIVE: To describe a case of neoehrlichiosis, an emerging opportunistic tick-borne infection, in a patient with multiple sclerosis (MS) treated with ocrelizumab. METHODS: This is a case study. RESULTS: Our patient developed clinical infection over several months while on ocrelizumab and was ultimately diagnosed with neoehrlichiosis, caused by the bacteria Neoehrlichia mikurensis. Resolution of symptoms began within a few days after the initiation of antibiotic treatment. CONCLUSION: We describe the first probable case of ocrelizumab-associated neoehrlichiosis in a patient with MS. Clinicians should be aware of this potentially debilitating and life-threatening infection in patients receiving CD20-depleting therapy.

CD11c+ B cells in relapsing-remitting multiple sclerosis and effects of anti-CD20 therapy.

OBJECTIVES: B cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B-cell subsets between controls and patients with untreated and anti-CD20-treated multiple sclerosis. METHODS: We recruited 155 participants for an exploratory cohort comprising peripheral blood and cerebrospinal fluid, and a validation cohort comprising peripheral blood. Flow cytometry was used to characterize B-cell phenotypes and effector functions of CD11c+ atypical B cells. RESULTS: There were no differences in circulating B cells between controls and untreated multiple sclerosis. As expected, anti-CD20-treated patients had a markedly lower B-cell count. Of B cells remaining after treatment, we observed higher proportions of CD11c+ B cells and plasmablasts. CD11c+ B cells were expanded in cerebrospinal fluid compared to peripheral blood in controls and untreated multiple sclerosis. Surprisingly, the proportion of CD11c+ cerebrospinal fluid B cells was higher in controls and after anti-CD20 therapy than in untreated multiple sclerosis. Apart from the presence of plasmablasts, the cerebrospinal fluid B-cell composition after anti-CD20 therapy resembled that of controls. CD11c+ B cells demonstrated a high potential for both proinflammatory and regulatory cytokine production. INTERPRETATION: The study demonstrates that CD11c+ B cells and plasmablasts are less efficiently depleted by anti-CD20 therapy, and that CD11c+ B cells comprise a phenotypically and functionally distinct, albeit heterogenous, B-cell subset with the capacity of exerting both proinflammatory and regulatory functions.

Evaluating Real-World Benefits of Hearing Aids With Deep Neural Network-Based Noise Reduction: An Ecological Momentary Assessment Study.

PURPOSE: Noise reduction technologies in hearing aids provide benefits under controlled conditions. However, differences in their real-life effectiveness are not established. We propose that a deep neural network (DNN)-based noise reduction system trained on naturalistic sound environments will provide different real-life benefits compared to traditional systems. METHOD: Real-life listening experiences collected with Ecological Momentary Assessments (EMAs) of participants who used two premium models of hearing aid are compared. One hearing aid model (HA1) used traditional noise reduction; the other hearing aid model (HA2) used DNN-based noise reduction. Participants reported listening experiences several times a day while ambient SPL, SNR, and hearing aid volume adjustments were recorded. Forty experienced hearing aid users completed a total of 3,614 EMAs and recorded 6,812 hr of sound data across two 14-day wear periods. RESULTS: Linear mixed-effects analysis document that participants' assessments of ambient noisiness were positively associated with SPL and negatively associated with SNR but were not otherwise affected by hearing aid model. Likewise, mean satisfaction with the two models did not differ. However, individual satisfaction ratings for HA1 were dependent on ambient SNR, which was not the case for HA2. CONCLUSIONS: Hearing aids with DNN-based noise reduction resulted in consistent sound satisfaction regardless of the level of background noise compared to hearing aids implementing noise reduction based on traditional statistical models. While the two hearing aid models also differed on other parameters (e.g., shape), these differences are unlikely to explain the difference in how background noise impacts sound satisfaction with the aids. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25114526.

Beam monitor chamber calibration of a synchro-cyclotron high dose rate per pulse pulsed scanned proton beam.

Objective. Ionization chambers, mostly used for beam calibration and for reference dosimetry, can show high recombination effects in pulsed high dose rate proton beams. The aims of this paper are: first, to characterize the linearity response of newly designed asymmetrical beam monitor chambers (ABMC) in a 100-226 MeV pulsed high dose rate per pulse scanned proton beam; and secondly, to calibrate the ABMC with a PPC05 (IBA Dosimetry) plane parallel ionization chamber and compare to calibration with a home-made Faraday cup (FC).Approach. The ABMC response linearity was evaluated with both the FC and a PTW 60019 microDiamond detector. Regarding ionometry-based ABMC calibration, recombination factors were evaluated theoretically, then numerically, and finally experimentally measured in water for a plane parallel ionization chamber PPC05 (IBA Dosimetry) throughkssaturation curves. Finally, ABMC calibration was also achieved with FC and compared to the ionometry method for 7 energies.Main results. Linearity measurements showed that recombination losses in the new ABMC design were well taken into account for the whole range of the machine dose rates. The two-voltage-method was not suitable for recombination correction, but Jaffé's plots analysis was needed, emphasizing the current IAEA TRS-398 reference protocol limitations. Concerning ABMC calibration, FC based absorbed dose estimation and PPC05-based absorbed dose estimation differ by less than 6.3% for the investigated energies.Significance.So far, no update on reference dosimetry protocols is available to estimate the absorbed dose in ionization chambers for clinical high dose rate per pulse pulsed scanned proton beams. This work proposes a validation of the new ABMC design, a method to take into account the recombination effect for ionometry-based ABMC calibration and a comparison with FC dose estimation in this type of proton beams.

A Monte Carlo study on the secondary neutron generation by oxygen ion beams for radiotherapy and its comparison to lighter ions.

Objective.To study the secondary neutrons generated by primary oxygen beams for cancer treatment and compare the results to those from primary protons, helium, and carbon ions. This information can provide useful insight into the positioning of neutron detectors in phantom for future experimental dose assessments.Approach.Mono-energetic oxygen beams and spread-out Bragg peaks were simulated using the Monte Carlo particle transport codesFLUktuierende KAskade, tool for particle simulation, and Monte Carlo N-Particle, with energies within the therapeutic range. The energy and angular distribution of the secondary neutrons were quantified.Main results.The secondary neutron spectra generated by primary oxygen beams present the same qualitative trend as for other primary ions. The energy distributions resemble continuous spectra with one peak in the thermal/epithermal region, and one other peak in the fast/relativistic region, with the most probable energy ranging from 94 up to 277 MeV and maximum energies exceeding 500 MeV. The angular distribution of the secondary neutrons is mainly downstream-directed for the fast/relativistic energies, whereas the thermal/epithermal neutrons present a more isotropic propagation. When comparing the four different primary ions, there is a significant increase in the most probable energy as well as the number of secondary neutrons per primary particle when increasing the mass of the primaries.Significance.Most previous studies have only presented results of secondary neutrons generated by primary proton beams. In this work, secondary neutrons generated by primary oxygen beams are presented, and the obtained energy and angular spectra are added as supplementary material. Furthermore, a comparison of the secondary neutron generation by the different primary ions is given, which can be used as the starting point for future studies on treatment plan comparison and secondary neutron dose optimisation. The distal penumbra after the maximum dose deposition appears to be a suitable location for in-phantom dose assessments.

Evaluation of a phosphate kinetics model in hemodialysis therapy-Assessment of the temporal robustness of model predictions.

In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R2 ) values. When fitted to intradialytic samples only, the median (interquartile range) R2 values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R2 value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.

Observing the primary steps of ion solvation in helium droplets.

Solvation is a ubiquitous phenomenon in the natural sciences. At the macroscopic level, it is well understood through thermodynamics and chemical reaction kinetics1,2. At the atomic level, the primary steps of solvation are the attraction and binding of individual molecules or atoms of a solvent to molecules or ions of a solute1. These steps have, however, never been observed in real time. Here we instantly create a single sodium ion at the surface of a liquid helium nanodroplet3,4, and measure the number of solvent atoms that successively attach to the ion as a function of time. We found that the binding dynamics of the first five helium atoms is well described by a Poissonian process with a binding rate of 2.0 atoms per picosecond. This rate is consistent with time-dependent density-functional-theory simulations of the solvation process. Furthermore, our measurements enable an estimate of the energy removed from the region around the sodium ion as a function of time, revealing that half of the total solvation energy is dissipated after four picoseconds. Our experimental method opens possibilities for benchmarking theoretical models of ion solvation and for time-resolved measurements of cation-molecule complex formation.

A phantom to simulate organ motion and its effect on dose distribution in carbon ion therapy for pancreatic cancer.

Objective. Carbon ion radiotherapy is a promising radiation technique for malignancies like pancreatic cancer. However, organs' motion imposes challenges for achieving homogeneous dose delivery. In this study, an anthropomorphicPancreasPhantom forIon-beamTherapy (PPIeT) was developed to simulate breathing and gastrointestinal motion during radiotherapy.Approach. The developed phantom contains a pancreas, two kidneys, a duodenum, a spine and a spinal cord. The shell of the organs was 3D printed and filled with agarose-based mixtures. Hounsfield Units (HU) of PPIeTs' organs were measured by CT. The pancreas motion amplitude in cranial-caudal (CC) direction was evaluated from patients' 4D CT data. Motions within the obtained range were simulated and analyzed in PPIeT using MRI. Additionally, GI motion was mimicked by changing the volume of the duodenum and quantified by MRI. A patient-like treatment plan was calculated for carbon ions, and the phantom was irradiated in a static and moving condition. Dose measurements in the organs were performed using an ionization chamber and dosimetric films.Main results. PPIeT presented tissue equivalent HU and reproducible breathing-induced CC displacements of the pancreas between (3.98 ± 0.36) mm and a maximum of (18.19 ± 0.44) mm. The observed maximum change in distance of (14.28 ± 0.12) mm between pancreas and duodenum was consistent with findings in patients. Carbon ion irradiation revealed homogenous coverage of the virtual tumor at the pancreas in static condition with a 1% deviation from the treatment plan. Instead, the dose delivery during motion with the maximum amplitude yielded an underdosage of 21% at the target and an increased uncertainty by two orders of magnitude.Significance. A dedicated phantom was designed and developed for breathing motion assessment of dose deposition during carbon ion radiotherapy. PPIeT is a unique tool for dose verification in the pancreas and its organs at risk during end-to-end tests.

Personal dosimetry at the Paul Scherrer Institute.

The Paul Scherrer Institute (PSI) is the largest research institute for natural and engineering sciences in Switzerland. PSI develops, builds and operates complex large research facilities. Every year, >2400 scientists from Switzerland and around the world come to PSI to use the facilities and to carry out experiments. Many areas at PSI are radiation protection areas. Depending on the radiation protection area, the work carried out and the time the users spend in these areas, they have to carry a personal dosemeter. PSI runs an individual monitoring service in compliance with the Swiss legislation on radiological protection and approved by the Swiss Federal Nuclear Safety Inspectorate. The service provides about 35 000 dosemeters per year for the internal and external customers consisting of whole-body dosemeters for photons and neutrons as well as extremity dosemeters. This paper gives an overview on the employed personal dosimetry techniques by the individual monitoring service of PSI, the number of distributed dosemeters for internal and external customers and statistics about the measured doses at PSI over 30 years.

Multilevel Modeling of Gaze From Listeners With Hearing Loss Following a Realistic Conversation.

PURPOSE: There is a need for tools to study real-world communication abilities in people with hearing loss. We outline a potential method for this that analyzes gaze and use it to answer the question of when and how much listeners with hearing loss look toward a new talker in a conversation. METHOD: Twenty-two older adults with hearing loss followed a prerecorded two-person audiovisual conversation in the presence of babble noise. We compared their eye-gaze direction to the conversation in two multilevel logistic regression (MLR) analyses. First, we split the conversation into events classified by the number of active talkers within a turn or a transition, and we tested if these predicted the listener's gaze. Second, we mapped the odds that a listener gazed toward a new talker over time during a conversation transition. RESULTS: We found no evidence that our conversation events predicted changes in the listener's gaze, but the listener's gaze toward the new talker during a silence-transition was predicted by time: The odds of looking at the new talker increased in an s-shaped curve from at least 0.4 s before to 1 s after the onset of the new talker's speech. A comparison of models with different random effects indicated that more variance was explained by differences between individual conversation events than by differences between individual listeners. CONCLUSIONS: MLR modeling of eye-gaze during talker transitions is a promising approach to study a listener's perception of realistic conversation. Our experience provides insight to guide future research with this method.

Daily sound exposure of hearing aids users during COVID-19 pandemic in Europe.

Introduction: This study aimed to investigate the daily sound exposure of hearing aid (HA) users during the COVID-19 pandemic, with a specific focus on the impact of different governance intervention levels. Methods: Modern HA technology was employed to measure and compare the sound exposure of HA users in three distinct periods: pre-pandemic, and two 14-day periods during the pandemic, corresponding to varying levels of governance interventions. The study sample comprised a total of 386 HA users in Europe during the pandemic, with daily sound exposure data collected as part of the main dataset. Results: The results revealed that, during the pandemic, the equivalent continuous sound pressure level (SPL) experienced by HA users decreased, while the signal-to-noise ratio (SNR) increased compared to the pre-pandemic period. Notably, this impact was found to be more pronounced (p < 0.05) when individuals were subjected to stronger governance intervention levels, characterized by lower SPL and higher SNR. Discussion: This study highlights the changes in daily sound exposure experienced by HA users during the COVID-19 pandemic, particularly influenced by the extent of governance interventions that restricted social activities. These findings emphasize the importance of considering the effects of pandemic-related governance measures on the sound environments of HA users and have implications for audiological interventions and support strategies during similar crises.

Implementation of a coagulation component into a phosphate kinetics model in haemodialysis therapy: A tool for detection of clotting problems?

A coagulation component should be considered in phosphate kinetics modelling because intradialytic coagulation of the extracorporeal circuit and dialyser might reduce phosphate removal in haemodialysis. Thus, the objective of this study was to add and evaluate coagulation as an individual linear clearance reduction component to a promising three-compartment model assuming progressive intradialytic clotting. The model was modified and validated on intradialytic plasma and dialysate phosphate samples from 12 haemodialysis patients collected during two treatments (HD1 and HD2) at a Danish hospital ward. The most suitable clearance reduction in each treatment was identified by minimizing the root mean square error (RMSE). The model simulations with and without clearance reduction were compared based on RMSE and coefficient of determination (R2 ) values. Improvements were found for 17 of the 24 model simulations when clearance reduction was added to the model. The slopes of the clearance reduction were in the range of 0.011-0.632/h. Three improvements were found to be statistically significant (|observed z value| > 1.96). A very significant correlation (R2  = 0.708) between the slopes for HD1 and HD2 was found. Adding the clearance reduction component to the model seems promising in phosphate kinetics modelling and might be explained, at least in part, by intradialytic coagulation. In future studies, the model might be developed further to serve as a potentially useful tool for the quantitative detection of clotting problems in haemodialysis. NEW FINDINGS: What is the central question of this study? The aim was to add an intradialytic coagulation component to a modified version of a promising three-compartment phosphate kinetics model. The hypothesis was that circuit and dialyser clotting can be modelled by an individual linear phosphate clearance reduction component during haemodialysis treatment. What is the main finding and its importance? Improvements were found for 17 of 24 model simulations when clearance reduction was added to the model. Thus, the kinetics model seems promising and could be a useful tool for the quantitative detection of clotting problems in haemodialysis patients.

Horizontal Alveolar Ridge Augmentation with Xenogenic Block Grafts Compared with Autogenous Bone Block Grafts for Implant-retained Rehabilitation: a Systematic Review and Meta-Analysis.

Objectives: The objective of the present systematic review and meta-analysis was to test the 0-hypothesis of no difference in implant treatment outcome after horizontal alveolar ridge augmentation with xenogenic block compared with autogenous bone block. Material and Methods: A literature search was conducted using PubMed, Embase and Cochrane Library databases in combination with a hand-search of relevant journals until 25th of January 2022. Comparative and non-comparative studies evaluating horizontal alveolar ridge augmentations with xenogenic blocks were included. Quality and risk of bias were evaluated by Cochrane Collaboration's revised tool and Newcastle-Ottawa scale. Results: Meta-analysis revealed no statistically significant difference in implant survival rate after more than 6 months of functional implant loading (P = 0.71), no difference in alveolar ridge width (P = 0.07) or gain of alveolar ridge width at re-entry (P = 0.13). Non-comparative studies revealed moderate to high short-term implant survival rate and gain in alveolar ridge width, however, complications including dehiscences, graft exposure and graft failure were observed in several studies. Conclusions: No significant difference could be identified in short-term implant treatment outcome following horizontal alveolar ridge augmentation using xenogenic block compared with autogenous bone block with the limited data available. A high incidence of healing complications and implant failures necessitates further investigation, as well as long-term results on implant survival rate.