Search

We investigate uncertainty guidance mechanisms to support proton therapy (PT) planning visualization. Uncertainties in the PT workflow pose significant challenges for navigating treatment plan data and selecting the most optimal plan among alternatives. Although guidance techniques have not yet been applied to PT planning scenarios, they have successfully supported sense- and decision-making processes in other contexts. We hypothesize that augmenting PT uncertainty visualization with guidance may influence the intended users’ perceived confidence and provide new insights. To this end, we follow an iterative co-design process with domain experts to develop a visualization dashboard enhanced with distinct level-of-detail uncertainty guidance mechanisms. Our approach classifies uncertainty guidance into two dimensions: degree of intrusiveness and detail-orientation. Our dashboard supports the comparison of multiple treatment plans (i.e., nominal plans with their translational variations) while accounting for multiple uncertainty factors. We subsequently evaluate the designed and developed strategies by assessing perceived confidence and effectiveness during a sense- and decision-making process. Our findings indicate that uncertainty guidance in PT planning visualization does not necessarily impact the perceived confidence of the users in the process. Nonetheless, it provides new insights and raises uncertainty awareness during treatment plan selection. This observation was particularly evident for users with longer experience in PT planning.

Background: Radiochromic silicone-based dosimeters are flexible 3D dosimeters, which at appropriate concentration of leucomalachite green (LMG) and curing agent are dose-rate independent for clinical photon beams. However, their dose response is based on chemical processes that can be influenced by temporal and thermal conditions, impacting measurement stability. Purpose: The aim of this study was to investigate the temporal stability of the dose response of radiochromic dosimeters for different curing times and post-irradiation storage temperatures. Methods: Six cylindrical dosimeters (5 cm diameter, 5 cm length) were produced in a single batch and separated into two groups that were irradiated 72 and 118 h after production. The same photon plan, consisting of two 10 × 1.6 cm 2 opposing fields, was delivered to all dosimeters. After irradiation, the dosimeters were separated into three groups, stored at 5°C, 15°C, and 20°C, and read out for five consecutive days. Results: Storage temperature influenced the measurement stability, and changes in the optical response with time differed between irradiated and non-irradiated parts of the dosimeters. The relative change between signal and background was greater than 10% for all measurements performed 24 h or more after irradiation, except for dosimeters stored at 5°C, which changed by 2%–5% after 24 h. The dosimeter temporal stability was not influenced by curing time. Conclusions: For room temperature storage (15°C and 20°C), readout should take place as soon as possible after irradiation since the background color increased rapidly for both curing times (72 and 118 h), whereas the dosimeters are stored at 5°C, readout can be performed up to 24 h after.

The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the trial. The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the trial.

This study aims to examine the effect of the independent variables of motivation, organizational commitment, and due professional care on the dependent variable of audit quality. The population in this study were all auditors, both junior and senior auditors who worked in 5 public accounting firm in Jakarta with a total of 57 respondents. The sampling technique in this study used the Convenience Sampling Method and the data used in this study was primary data. In this study, the authors use Descriptive Statistical Test, Classical Assumption Tes (normality test, multicollinearity test, heteroscedasticity test), Hypothesis Test (coefficient of determination, t test, f test) and Multiple Linear Regression Analysis to be able to analyze the data used and use SPSS software version 25. Based on the results of research through several tests carried out, it can be concluded that motivation, commitment organization, and due professional care have a positive effect on audit quality. Keywords: Motivation, Organizational Commitment, Due Professional Care, and Audit Quality

Everyone is used to seeing graphs predicting unprecedented growth for the offshore wind industry over the next decades. Whether or not these ambitious goals are achieved remains to be seen, as it will require nothing less than an industrial revolution in offshore construction and installation. Never have such growth projections been backed by a global sense of urgency, but unfortunately, it is not just the growth challenge that has to be met and resolved. Data from insurance companies show a significant growth in financial losses in the offshore wind industry. For an expanding industry, an increase in insurance claims may be a result of the growth, however, even when normalizing the financial losses against industry CAPEX, number of turbines, or installed capacity, worrying trends are seen. For offshore wind to be a viable energy source in the future, the quality of design, installation and operation needs to improve significantly. Furthermore, the industry cannot continue to scale developments until it has overcome some serious reliability issues. In offshore wind, we have seen how an extreme focus on reducing CAPEX in projects has led to low-quality engineering and choice of sub-standard products that are not fit for long-term applications exposed to dynamic loading in marine environments. Standardization is needed, reflecting the best insight, experiences, methods, and tools. Although the challenges were never as extensive in oil and gas as in offshore wind today, the situation still resembles the quality and technology challenges faced by the offshore oil and gas industry some two decades ago. Many of the design challenges that have been overcome in oil and gas have been incorporated into codes, standards, and well-established engineering practices. Seen from a distance, the offshore wind industry experience similar trends. However, with the ongoing rapid growth, the learning and improvement processes need to be accelerated by leveraging the experiences from oil and gas. On the shoulders of a mature offshore industry and today's digital capabilities, standardization and up-scaling of offshore wind have better opportunities than oil & gas had 25 years ago. However, to leverage this opportunity a true life-of-field approach is required.

Supplementary Figure S3. CD147 expression levels in A549 and NCI-H520 cells were determined by flow cytometry using a FITC-labeled mouse anti-human CD147 primary mAb (Becton, Dickinson and Company) and a mouse IgG1 mAb as an isotype control. The results shown are mean values {plus minus} S.D. and are representative of 3 independent experiments.

Supplementary Information. including Materials and methods

Metuzumab is an affinity-optimized and nonfucosylated anti-CD147 human–mouse chimeric IgG1 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). The purpose of this study was to characterize the pharmacokinetics, safety, and antitumor activities of metuzumab in mouse, rat, and monkey. The ADCC activity was assessed by a lactate dehydrogenase release assay. The pharmacokinetics of metuzumab were determined in Sprague–Dawley rats and in cynomolgus monkeys. Single- and repeat-dose toxicology studies of the i.v. administration of high-dose metuzumab were conducted in cynomolgus monkeys. Mice bearing human tumor xenografts were used to evaluate the antitumor efficacy of metuzumab. The ADCC potency of metuzumab was enhanced compared with the nonglycoengineered parental antibody. Metuzumab also effectively inhibited tumor growth in A549 and NCI-H520 xenograft models. In the monkey model, the total clearance of metuzumab decreased with increasing dose. The nonspecific clearance in monkeys was estimated to be 0.53 to 0.92 mL/h/kg. In single- and repeat-dose toxicology studies in cynomolgus monkeys, metuzumab did not induce any distinct or novel adverse findings and was well tolerated at all tested doses. These preclinical safety data facilitated the initiation of an ongoing clinical trial of metuzumab for the treatment of non–small cell lung cancer (NSCLC) in China. Mol Cancer Ther; 14(1); 162–73. ©2014 AACR.

Supplementary Figure Legends

Supplementary Figure S2. Metuzumab has potent ADCC activity with murine PBMCs and macrophages/monocytes. The ability of Metuzumab mediated in vitro ADCC by human PBMCs (hPBMCs), murine PMBCs (mPBMCs), murine NK cells, or murine macrophages/monocytes were measured using LDH release assay. A549 and NCI-H520 cells were used as target cells in a 30:1 effector/target ratio (5:1 when NK cells or macrophages/monocytes were used as effectors). The results are shown as the mean values {plus minus} S.D. and are representative of 6 independent experiments.

Supplementary Table S1-S6. Table S1. Tissue crossreactivity of Metuzumab with different species; Table S2. Immunohistochemical Detection of CD147 by Metuzumab in Human Cancer Arrays; Table S3. Hematology analysis in rat and monkeys treated with Metuzumab in repeated dose toxicity study; Table S4. CD4+ and CD8+ T cell analysis in Cynomolgus monkey treated with Metuzumab in repeated dose toxicity study. Table S5. Clinical chemistry analysis in rats and monkeys treated with Metuzumab in repeated dose toxicity study. Table S6. CD4+ and CD8+ T cell analysis in rats treated with Metuzumab in repeated dose toxicity study.

Supplementary Figure S1. Images of anti-tumor efficacy of Metuzumab in SCID mice bearing A549 (left) and NCI-H520 (right) human lung cancer cell line xenografts.

Background and Purpose: Proton therapy is sensitive to range uncertainties, which typically are accounted for by margins or robust optimization, based on tissue-independent uncertainties. However, range uncertainties have been shown to depend on the specific tissues traversed. The aim of this study was to investigate the differences between range margins based on stopping power ratio (SPR) uncertainties which were tissue-specific (applied voxel-wise) or fixed (tissue-independent or composite). Materials and Methods: Uncertainties originating from imaging, computed tomography (CT) number estimation, and SPR estimation were calculated for low-, medium-, and high-density tissues to quantify the tissue-specific SPR uncertainties. Four clinical treatment plans (four different tumor sites) were created and recomputed after applying either tissue-specific or fixed SPR uncertainties. Plans with tissue-specific and fixed uncertainties were compared, based on dose-volume-histogram parameters for both targets and organs-at-risk. Results: The total SPR uncertainties were 7.0% for low-, 1.0% for medium-, and 1.3% for high-density tissues. Differences between the proton plans with tissue-specific and fixed uncertainties were mainly found in the vicinity of the target. Composite uncertainties were found to capture the tissue-specific uncertainties more accurately than the tissue-independent uncertainties. Conclusion: Different SPR uncertainties were found for low-, medium-, and high-density tissues indicating that range margins based on tissue-specific uncertainties may be more exact than the standard approach of using tissue-independent uncertainties. Differences between applying tissue-specific and fixed uncertainties were found, however, a fixed uncertainty might still be sufficient, but with a magnitude that depends on the body region.

mRNA delivery has shown high application value in the treatment of various diseases, but its effective delivery is still a major challenge at present. Herein, we propose a lantern-shaped flexible RNA origami for mRNA delivery. The origami is composed of a target mRNA scaffold and only two customized RGD-modified circular RNA staples, which can compress the mRNA into nanoscale and facilitate its endocytosis by cells. In parallel, the flexible structure of the lantern-shaped origami allows large regions of the mRNA to be exposed and translated, exhibiting a good balance between endocytosis and translation efficiency. The application of lantern-shaped flexible RNA origami in the context of the tumor suppressor gene, Smad4 in colorectal cancer models demonstrates promising potential for accurate manipulation of protein levels in in vitro and in vivo settings. This flexible origami strategy provides a competitive delivery method for mRNA-based therapies.

BACKGROUND: A frequent consequence of stroke is impaired mental function, which often affects the ability to perform activities and participate in life situation. In occupational therapy practice, performance-based instruments during activity and participation are often used. However, it is important to assess if the instruments used are valid, reliable and responsive.OBJECTIVE: The objective of this systematic review is to investigate measurement properties of performance-based instruments to assess mental function during activity and participation in persons who have survived stroke.MATERIAL AND METHODS: Systematic database searches of PubMed, EMBASE, CINAHL, PsycINFO, and OTseeker will be conducted. COSMIN Risk of Bias checklist will be used to evaluate methodological quality of the included articles. Measurement properties of the included studies will be rated against criteria for good measurement properties. The overall evidence of each measurement property per instrument is graded using a modified GRADE approach.RESULTS: Results will be presented in text and tables.CONCLUSIONS: Conclusion will be drawn up-on the overall evidence to give recommendations on the most suitable instrument.SIGNIFICANCE: It is expected that findings of the review will provide evidence to guide professionals in the selection of a performance-based instruments to measure mental function in practice and research.TRIAL REGISTRATION NUMBER: PROSPERO CRD42018086744.

Radiotherapy is a well-established and important treatment for cancer tumors, and advanced technologies can deliver doses in complex three-dimensional geometries tailored to each patient’s specific anatomy. A 3D dosimeter, based on optically stimulated luminescence (OSL), could provide a high accuracy and reusable tool for verifying such dose delivery. Nanoparticles of an OSL material embedded in a transparent matrix have previously been proposed as an inexpensive dosimeter, which can be read out using laser-based methods. Here, we show that Cu-doped LiF nanocubes (nano-LiF:Cu) are excellent candidates for 3D OSL dosimetry owing to their high sensitivity, dose linearity, and stability at ambient conditions. We demonstrate a scalable synthesis technique producing a material with the attractive properties of a single dosimetric trap and a single near-ultraviolet emission line well separated from visible-light stimulation sources. The observed transparency and light yield of silicone sheets with embedded nanocubes hold promise for future 3D OSL-based dosimetry.

The European Commission approved Slovenia’s recovery and resilience plan (RRP) on 1 July 2021. Although the RRP and the partnership agreement and programmes under cohesion policy funds for 2021–2027 took into consideration Country Specific Recommendations and investment guidance sound strategic priorities set at the national level are lacking. Moreover, proposed projects do not take uneven regional distribution sufficiently into account. While the main focus of the RRP lies on the implementation of the so-called green and digital transitions, it also envisages a number of reforms and investments that directly impact the labour market (training, education and pension reform, for example). The goal of this article is to present the reforms in the context of the European Pillar of Social Rights and the Country Specific Recommendations issued within the European Semester.

Bakgrunnen for denne undersøkelsen var å lære mer om akvakultur sin påvirkning på bentiske arter. Denne oppgaven tar for seg akvakultur sin påvirkning på taskekrabber (Cancer pagurus) i et fjordsystem, sammenlignet med ett kystområde uten påvirkning. Hensikten med undersøkelsen var å undersøke om taskekrabben beiter på fôrspill, og om dette påvirker fettsyresammensetningen i arten. Det ble også vurdert om kjønnsmessige forskjeller har noe å si for påvirkningen. Oppgavens praktiske del baserte seg på felt- og laboratoriearbeid. Det ble høstet taskekrabber fra tre ulike fangstområder lokalisert i Møre og Romsdal. Det første var rett under et oppdrettsanlegg, det andre 2 kilometer fra anlegget og det siste ute ved kysten. Videre ble krabbene behandlet på laboratorium. Her ble disseksjon, fettsyreekstraksjon og analyse av krabbelever gjennomført. Resultatene fra undersøkelsen viste en forhøyning av vegetabilske fettsyrer og en reduksjon av DHA i taskekrabben høstet ved oppdrettsanlegg. Funnene viste at det var kun i hunnkrabbene det kunne påvises signifikante forskjeller i fettsyresammensetningen når man sammenlignet området ved oppdrettsanlegg med de to andre fangstområdene. Resultatene viste også kjønnsmessige forskjeller ved at hunnkrabbene inneholdt mer vegetabilske fettsyrer enn hannkrabbene. Videreføring av arbeidet anbefales for å kartlegge hvilken påvirkning fôrspill kan ha på beitende bentiske arter ved oppdrettsanlegg i fjordsystemer. The background for this study was to learn about aquaculture and its effect on benthic species. This study looks into the influence aquaculture has on the edible crab (Cancer pagurus) in a fjord system, compared to a coastal area that is unaffected. The study also takes into consideration any gender differences the edible crab might have. The aim of the research was to investigate whether edible crab graze on the feed waste from fin-fish aquaculture, and whether it had any effect on the fatty acid profile of the crabs. The practical part of the study was based on field- and laboratory work. Edible crabs were harvested from three different fishing areas located in Møre og Romsdal. The first was located directly under a fin-fish farm, the second area located 2 kilometres away from the fish farm and the last area were located on the unaffected coastal region. In the later stages the crabs were processed in the laboratory, where dissection, fatty acid extraction, and analysis of the crabs hepatopancreas were conducted. The results of the study showed an increase in fatty acids of terrestrial origin and a decrease in the marine fatty acid DHA in the edible crabs harvested near the fin-fish farm. The outcome of the study indicated that significant differences in fatty acid compositions were only observed in female crabs between the area near the fish farm and the other two fishing areas. In addition, the results revealed differences between genders, with the female crab containing more lipids from terrestrial origin than the male crabs. Further research is recommended to assess the impact of feed waste on gazing benthic species near fin-fish aquaculture in fjord systems.

PurposeThe aim of the paper is to identify the causal effect of the COVID-19 induced crisis on students' decisions about their educational plans. The authors hypothesise that students adjusted their decisions by delaying graduation, dropping out or change the field of education because of increased uncertainty about future employment and monetary returns.Design/methodology/approachThe empirical approach is based on a survey done during the first wave of COVID-19 in Slovenia. The probability of dropping out, prolonging or stop-out is designed by applying probit and probit with insturmental variables empirical model.FindingsPrimary orientation towards work increases the probability of dropping out and financial constraints increase the probability of prolonging studies. The same holds after accounting for endogeneity. However, the authors do not find that poor job expectations due to COVID-19 affect students' decisions to prolong, drop-out or stop-out. The authors also find that the primary orientation toward work or study explains the differences in the probability of each outcome that is not influenced by enrolment in a particular field of study.Research limitations/implicationsThe results cannot be read as an objective prediction of the impact of the COVID-19 crisis on college failures. However, the study provides insight into how students' expectations change their intentions to prolong, drop-out, or stop-out during periods of high uncertainty. The extent, to which measured intentions are realised, however, is uncertain.Practical implicationsUnderstanding the response diversity and motives behind students' study decisions represents extremely valuable insights for economic policy. Mapped apprehensions, augmented by heterogeneity in personal and financial characteristics, are relevant for policymakers. In terms of future research, it would be interesting to analyse what changes occurred over a five-year period, specifically which field of study was most affected by students' adjusted plans due to the pandemic.Social implicationsStudents have always been a special group in the labour market. After the initial shock of closing activities, studying online and the drastic decrease in student work due to COVID-19, the decision was made in spring 2020 to continue on the chosen path or not. This paper provides insight into the changing decision students made about their educational plans.Originality/valueThis paper is one of the first to highlight the implications of COVID-19 for the adaptation of student plans in the transition from school-to work in Europe. It departs from the classical literature of college failures, as specific macroeconomic conditions influence students to reconsider their educational decisions. Moreover, the paper also contributes to the rapidly growing literature on the impact of the COVID-19 pandemic on household-level labour market outcomes, particularly with respect to job search and labour supply decisions in general.

Aims: To identify more effective ginsenoside for type 2 diabetes (T2D) and clarify whether the ginsenoside characterizing estrogenic multi-targeted antidiabetic effects. Study Design: Identifying more effective ginsenoside through preclinical evaluation of antidiabetic effects of representative ginsenosides with T2D rat model, and further test pharmacological mechanism underlying the potent antidiabetic effects of the ginsenoside in the same model. Place and Duration of Study: Key laboratory for Pharmacy, Inner Mongolia Medical University, March 2018 to November 2020. Methodology: Used a total of 240 female adult rats. Rat model of T2D induced by high-fat diet fed and streptozotocin. Five tapes of representative ginsenosides (Rb1, Rd, Rg3, Re, Rg1) administrated at low (20 mg/kg daily) and high (40 mg/ kg daily) doses to T2D rats with orally for 4 weeks. Detect testing indexes with biochemical, histological, Quantitative Real-Time PCR, and western blots analysis. Results: Ginsenoside Re (Re), very significantly lowered blood glucose (P

Hydrogen has been seen as a decarbonization enabler for the last few decades, and in the last couple of years, there have been many investments in its production through renewables and use in different industrial applications. It is often researched for energy storage, and combustion is an excellent alternative to recover the energy stored in hydrogen. It might be the most viable alternative, especially when it comes to energy-intensive metal and glass production processes. The utilization of hydrogen as a fuel in these processes would reduce greenhouse gas emissions significantly, considering their share in total emissions. Since these industries already benefit from oxyfuel combustion with traditional fuels for fuel savings, part of the infrastructure already exists for hydrogen oxyfuel combustion. Fuel change is expected to require some minor adjustments other than simply changing the oxidizer; however, each industry has specific points to consider. This chapter investigates metal and glass production processes based on their needs and challenges in using hydrogen oxyfuel combustion for heating. Additionally, possible exhaust gas stream improvements are suggested to recover energy and reduce emissions. Finally, safety aspects of hydrogen and oxygen use are discussed together with the community acceptance of hydrogen use.

Background: The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial. Material and methods: A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30. Results: Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p

Radiochromic silicone-based dosimeters are flexible 3D dosimeters, which at appropriate concentration of leucomalachite green (LMG) and curing agent are dose-rate independent for clinical photon beams. However, their dose response is based on chemical processes that can be influenced by temporal and thermal conditions, impacting measurement stability.The aim of this study was to investigate the temporal stability of the dose response of radiochromic dosimeters for different curing times and post-irradiation storage temperatures.Six cylindrical dosimeters (5 cm diameter, 5 cm length) were produced in a single batch and separated into two groups that were irradiated 72 and 118 hours after production. The same photon plan, consisting of two 10 × 1.6 cmStorage temperature influenced the measurement stability, and changes in the optical response with time differed between irradiated and non-irradiated parts of the dosimeters. The relative change between signal and background was greater than 10% for all measurements performed 24 hours or more after irradiation, except for dosimeters stored at 5 ͦC, which changed by 2-5% after 24 hours. The dosimeter temporal stability was not influenced by curing time.For room temperature storage (15 and 20 ͦC), readout should take place as soon as possible after irradiation since the background colour increased rapidly for both curing times (72 and 118 hours), whereas the dosimeters are stored at 5 ͦC, readout can be performed up to 24 hours after. This article is protected by copyright. All rights reserved.

The European Commission approved Slovenia’s recovery and resilience plan (RRP) on 1 July 2021. Although the RRP and the partnership agreement and programmes under cohesion policy funds for 2021–2027 took into consideration Country Specific Recommendations and investment guidance sound strategic priorities set at the national level are lacking. Moreover, proposed projects do not take uneven regional distribution sufficiently into account. While the main focus of the RRP lies on the implementation of the so-called green and digital transitions, it also envisages a number of reforms and investments that directly impact the labour market (training, education and pension reform, for example). The goal of this article is to present the reforms in the context of the European Pillar of Social Rights and the Country Specific Recommendations issued within the European Semester., Italian Labour Law e-Journal, Vol. 15 No. 1S (2022): Special Issue - The NextGeneration EU in Action: Impact on Social and Labour Policies

The purpose of this study was to observe and determine the effect of the reputation of the auditor and the audit committee on the value of basic materials companies listed on the Indonesia Stock Exchange for the period 2018-2021. This study uses quantitative methods, the sample used is 45 companies using the purpose sampling method, totaling 180 data. The technique used in this research is descriptive statistical technique, classical assumption test, t hypothesis test, f hypothesis test, and coefficient of determination test. Based on the results of the t hypothesis test, it explains that the reputation of the auditor has a significant effect on firm value. While the audit committee does not have a significant effect on firm value. Therefore, it can be said that there is no substantial effect on firm value on the auditor and audit committee reputation variables, either one or both variables.

Background and purpose: A fixed relative biological effectiveness (RBE) of 1.1 (RBE1.1) is used clinically in proton therapy even though the RBE varies with properties such as dose level and linear energy transfer (LET). We therefore investigated if symptomatic brainstem toxicity in pediatric brain tumor patients treated with proton therapy could be associated with a variable LET and RBE. Materials and methods: 36 patients treated with passive scattering proton therapy were selected for a case-control study from a cohort of 954 pediatric brain tumor patients. Nine children with symptomatic brainstem toxicity were each matched to three controls based on age, diagnosis, adjuvant therapy, and brainstem RBE1.1 dose characteristics. Differences across cases and controls related to the dose-averaged LET (LETd) and variable RBE-weighted dose from two RBE models were analyzed in the high-dose region. Results: LETd metrics were marginally higher for cases vs. controls for the majority of dose levels and brainstem substructures. Considering areas with doses above 54 Gy(RBE1.1), we found a moderate trend of 13% higher median LETd in the brainstem for cases compared to controls (P =.08), while the difference in the median variable RBE-weighted dose for the same structure was only 2% (P =.6). Conclusion: Trends towards higher LETd for cases compared to controls were noticeable across structures and LETd metrics for this patient cohort. While case-control differences were minor, an association with the observed symptomatic brainstem toxicity cannot be ruled out.

Background and purpose: Three-dimensional dosimetry of proton therapy (PT) with chemical dosimeters is challenged by signal quenching, which is a lower dose-response in regions with high ionization density due to high linear-energy-transfer (LET) and dose-rate. This study aimed to assess the viability of an empirical correction model for 3D radiochromic silicone-based dosimeters irradiated with spot-scanning PT, by parametrizing its LET and dose-rate dependency. Materials and methods: Ten cylindrical radiochromic dosimeters (Ø50 and Ø75 mm) were produced in-house, and irradiated with different spot-scanning proton beam configurations and machine-set dose rates ranging from 56 to 145 Gy/min. Beams with incident energies of 75, 95 and 120 MeV, a spread-out Bragg peak and a plan optimized to an irregular target volume were included. Five of the dosimeters, irradiated with 120 MeV beams, were used to estimate the quenching correction factors. Monte Carlo simulations were used to obtain dose and dose-averaged-LET (LETd) maps. Additionally, a local dose-rate map was estimated, using the simulated dose maps and the machine-set dose-rate information retrieved from the irradiation log-files. Finally, the correction factor was estimated as a function of LETd and local dose-rate and tested on the different fields. Results: Gamma-pass-rates of the corrected measurements were >94% using a 3%-3 mm gamma analysis and >88% using 2%-2 mm, with a dose deviation of

Focusing on Sarah Waters’s Tipping the Velvet (1998) and Affinity (1999), this article examines how the reader-pleasure afforded by contemporary reimaginings of Victorian lesbianism accommodates the complicated emotional response of shame. Through an investigation of how both texts relate queer experience to shame and what narrative strategies facilitate or induce shame in the reader during their reading experience, this article argues that Waters’s work invites a more sophisticated analysis of shame: one that relates to, and arguably reproduces, the empathetic engagement between the text and the reader. In so doing, this article demonstrates the importance of affect and narrative studies in unpacking the complicated reading pleasure afforded by Waters’s writings and its political potentials.

Medical physics has made considerable contributions to recent advances in radiation oncology. Medical physicists are key players in the clinical and scientific radiation oncology context due to their unique skill sets, flexibility, clinical involvement and intrinsic translational character. The continuing development and widespread adoption of "high-tech" radiotherapy has led to an increased need for medical physics involvement. More recently, our field is rapidly changing towards an era of "precision oncology". These changes have opened new challenges for the definition of the professional and scientific roles and responsibilities of medical physicists. In this paper, we have identified four grand challenges of medical physics in radiation oncology: (1) improving target volume definition, (2) adoption of artificial intelligence and automation, (3) development of predictive models of biological effects for precision medicine, and (4) need for leadership. New visions and suggestions to orientate medical physics to successfully face these new challenges are summarized. We foresee that the scientific and professional challenges of our times are pushing medical physicists to accelerate toward multidisciplinarity. Medical physicists are expected to innovatively drive interactions and collaborations with other specialists outside radiation oncology while the radiation physics core will remain central. Medical physicists will retain strong and pivotal roles in quality, safety and in managing ever more complex technologies. The new challenges will require medical physicists to continuously update skills and innovate education, adapt curricula to include new fields, reinforce multi-disciplinary attitude and spirit of innovation. These challenges require visionary and open leadership, which is able to merge established roles with the exciting new fields where medical physics should increasingly contribute. (C) 2020 Elsevier B.V. All rights reserved.