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Rifampicin is a key antibiotic in the treatment of staphylococcal biofilm infections. In this pilot study, we found that patients who received rifampicin for treatment of an orthopaedic-device-related infection (ODRI) were colonized with rifampicin-resistant staphylococci during treatment and this persisted for up to 2 months after cessation of treatment.

Background and purpose: Magnetic resonance imaging (MRI) scans are highly sensitive to acquisition and reconstruction parameters which affect feature stability and model generalizability in radiomic research. This work aims to investigate the effect of image pre-processing and harmonization methods on the stability of brain MRI radiomic features and the prediction performance of radiomic models in patients with brain metastases (BMs). Materials and methods: Two T1 contrast enhanced brain MRI data-sets were used in this study. The first contained 25 BMs patients with scans at two different time points and was used for features stability analysis. The effect of gray level discretization (GLD), intensity normalization (Z-score, Nyul, WhiteStripe, and in house-developed method named N-Peaks), and ComBat harmonization on features stability was investigated and features with intraclass correlation coefficient >0.8 were considered as stable. The second data-set containing 64 BMs patients was used for a classification task to investigate the informativeness of stable features and the effects of harmonization methods on radiomic model performance. Results: Applying fixed bin number (FBN) GLD, resulted in higher number of stable features compare to fixed bin size (FBS) discretization (10 ± 5.5 % higher). `Harmonization in feature domain improved the stability for non-normalized and normalized images with Z-score and WhiteStripe methods. For the classification task, keeping the stable features resulted in good performance only for normalized images with N-Peaks along with FBS discretization. Conclusions: To develop a robust MRI based radiomic model we recommend using an intensity normalization method based on a reference tissue (e.g N-Peaks) and then using FBS discretization.

Background and Purpose: The feasibility of acquiring diffusion-weighted imaging (DWI) images on an MR-Linac for quantitative response assessment during radiotherapy was explored. DWI data obtained with a Spin Echo Echo Planar Imaging sequence adapted for a 0.35 T MR-Linac were examined and compared with DWI data from a conventional 3 T scanner. Materials and Methods: Apparent diffusion coefficient (ADC) measurements and a distortion correction technique were investigated using DWI-calibrated phantoms and in the brains of seven volunteers. All DWI utilized two phase-encoding directions for distortion correction and off-resonance field estimation. ADC maps in the brain were analyzed for automatically segmented normal tissues. Results: Phantom ADC measurements on the MR-Linac were within a 3 % margin of those recorded by the 3 T scanner. The maximum distortion observed in the phantom was 2.0 mm prior to correction and 1.1 mm post-correction on the MR-Linac, compared to 6.0 mm before correction and 3.6 mm after correction at 3 T. In vivo, the average ADC values for gray and white matter exhibited variations of 14 % and 4 %, respectively, for different selections of b-values on the MR-Linac. Distortions in brain images before correction, estimated through the off-resonance field, reached 2.7 mm on the MR-Linac and 12 mm at 3 T. Conclusion: Accurate ADC measurements are achievable on a 0.35 T MR-Linac, both in phantom and in vivo. The selection of b-values significantly influences ADC values in vivo. DWI on the MR-Linac demonstrated lower distortion levels, with a maximum distortion reduced to 1.1 mm after correction.

Abstract Background Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort). Methods Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005–2015) and prospectively (2015–2019) routine care collected data. Results Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70–9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58–34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39–20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors. Conclusions Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course.

In recent years, nuclear medicine has gained great interest, partly due to the success story of [177Lu]Lu-PSMA-617 (PluvictoTM). Still, in-depth preclinical characterization of radiopharmaceuticals mainly happens at centers that allow working with radioactive material. To support the development of novel radiopharmaceuticals, alternative non-radioactive characterization assays are highly desirable. The aim of this study was to demonstrate that inductively coupled plasma mass spectrometry (ICP-MS) associated with a chromatographic system can serve as a surrogate for the classical high-performance liquid chromatography (HPLC)-radiodetector combination for preclinical in vitro characterization of non-radioactive metal-labeled analogs of radiopharmaceuticals. In this proof-of-concept study, we demonstrate the applicability of HPLC–ICP-MS by assessing the stability of 175Lu- and natGa-labeled prostate-specific membrane antigen (PSMA)-targeting peptidomimetics, single domain antibody (sdAb) conjugates, and monoclonal antibody (mAb) conjugates. 175Lu-labeled DOTAGA-conjugated and natGa-labeled NODAGA-conjugated sdAbs and mAbs showed the highest stability with >90% still intact after 24 h. The peptidomime-tics [175Lu]Lu-PSMA-617 and [natGa]Ga-PSMA-11 showed identical in vitro serum stability as it was reported for their corresponding radioligands with >99% intact species after 24 h incubation in mouse serum, demonstrating the reliability of the method. Hence, the established HPLC–ICP-MS methods can support the development of novel radiopharmaceuticals in a classical pharmaceutical setting.

IL-32 is a recently described cytokine that performs a variety of functions under inflammatory conditions. Serum IL-32 has been shown to be elevated in several diseases, including type 2 diabetes, cancer, systemic lupus erythematosus, HIV infection, and atopic diseases including atopic dermatitis. There are nine different isoforms of IL-32, with IL-32γ being the most biologically active one. The following review summarizes the different roles of the various IL-32 isoforms in the context of skin inflammation, with a focus on atopic dermatitis.

Background and purpose: The requirement of computed tomography (CT) for radiotherapy planning may be bypassed by synthetic CT (sCT) generated from magnetic resonance (MR), which has recently led to the clinical introduction of MR-only radiotherapy for specific sites. Further developments are required for abdominal sCT, mostly due to the presence of mobile air pockets affecting the dose calculation. In this study we aimed to overcome this limitation for abdominal sCT at a low field (0.35 T) hybrid MR-Linac. Materials and methods: A retrospective analysis was conducted enrolling 168 patients corresponding to 215 MR-CT pairs. After the exclusion criteria, 152 volumetric images were used to train the cycle-consistent generative adversarial network (CycleGAN) and 34 to test the sCT. Image similarity metrics and dose recalculation analysis were performed. Results: The generated sCT faithfully reproduced the original CT and the location of the air pockets agreed with the MR scan. The dose calculation did not require manual bulk density overrides and the mean deviations of the dose-volume histogram dosimetric points were within 1 % of the CT, without any outlier above 2 %. The mean gamma passing rates were above 99 % for the 2 %/ 2 mm analysis and no cases below 95 % were observed. Conclusions: This study presented the implementation of CycleGAN to perform sCT generation in the abdominal region for a low field hybrid MR-Linac. The sCT was shown to correctly allocate the electron density for the mobile air pockets and the dosimetric analysis demonstrated the potential for future implementation of MR-only radiotherapy in the abdomen.

Background and purpose: The superior tissue contrast of magnetic resonance (MR) compared to computed tomography (CT) led to an increasing interest towards MR-only radiotherapy. For the latter, the dose calculation should be performed on a synthetic CT (sCT). Patient-specific quality assurance (PSQA) methods have not been established yet and this study aimed to assess several software-based solutions. Materials and methods: A retrospective study was performed on 20 patients treated at an MR-Linac, which were selected to evenly cover four subcategories: (i) standard, (ii) air pockets, (iii) lung and (iv) implant cases. The neural network (NN) CycleGAN was adopted to generate a reference sCT, which was then compared to four PSQA methods: (A) water override of body, (B) five tissue classes with bulk densities, (C) sCT generated by a separate NN (pix2pix) and (D) deformed CT. Results: The evaluation of the dose endpoints demonstrated that while all methods A-D provided statistically equivalent results (p = 0.05) within the 2% level for the standard cases (i), only the methods C-D guaranteed the same result over the whole cohort. The bulk densities override was shown to be a valuable method in absence of lung tissue within the beam path. Conclusion: The observations of this study suggested that the use of an additional sCT generated by a separate NN was an appropriate tool to perform PSQA of a sCT in an MR-only workflow at an MR-Linac. The time and dose endpoints requirements were respected, namely within 10 min and 2%.

IntroductionGambling can have serious consequences for many aspects of a person’s life. Yet relatively few people with gambling problems seek help. This study examines the extent to which exclusion from casino venues among other factors may act as a motivator for further help-seeking among casino gamblers (both landbased and remote) with at-risk or disordered gambling behavior. In addition, the barriers that prevent gamblers from accepting help are examined.MethodsGamblers from Swiss casinos completed a written questionnaire twice, at 6-month intervals. The questions included whether they had sought help in the past 6 months.ResultsFor those with a SOGS-R rating of 1 or over (n = 173) at the second survey point, a difference in help-seeking was found between the excluded and non-excluded gamblers (p

Meeting the net zero emission targets set by many states after the Paris Agreement to help keep global warming well below 2°C above pre-industrial levels will require carbon dioxide removal technologies (CDRs). Several moral concerns arise if the contribution of CDRs to achieving net zero is not specified, but such concerns can be met by defining a permissible target for CDRs. This paper proposes a framework for defining the permissible contribution of CDRs to the net zero targets of individual states. The framework identifies three categories of emissions for which the permissibility of CDRs varies depending on the ethical costs of both emission abatement and CDRs. We argue that a) luxury emissions should be reduced without using CDRs; b) emissions for full membership in society should be abated by structural efforts, although using CDRs is permissible, given certain conditions; and c) CDRs are permissible for residual emissions because otherwise net zero targets cannot be reached. [ABSTRACT FROM AUTHOR]

Introduction: Reactivity to daily stressors may change as a function of stressor type and age. However, prior research often excludes older adults or compares them to younger age groups (e.g., younger and middle-aged adults). Recognizing older adults as a heterogeneous population with shifting motivations, this study focused on individuals aged ≥65 years and tested age differences in associations between different types of daily stressors, affect, and physical symptoms. Methods: A total of 108 older adults aged 65–92 years (M = 73.11, SD = 5.92; 58% women) completed daily dairy questionnaires on daily stressors, positive and negative affect, and physical symptoms for 14 consecutive days. Multilevel models were employed, adjusting for sex, age, education, living situation, and day-in-study. Results: Findings revealed age-dependent variations in the associations between daily stressors and affect and physical symptoms. Specifically, external stressors (e.g., finance and traffic stressors) and health stressors were more strongly associated with daily affective states and with overall physical symptoms (respectively) among older age adults. Age did not moderate associations between social stressors and affect or physical symptoms. Conclusion: These findings underscore the heterogeneous nature of older adults’ responses to daily stressors based on stressor type and age. Specifically, the oldest-old might benefit from personalized support for dealing with challenges such as health and financial stressors. [ABSTRACT FROM AUTHOR]

Episodes of solitude (being alone and without social interaction) are common in older age and can relate to decreased well‐being. Identifying everyday resources that help maintain older adults' well‐being in states of solitude is thus important. We investigated associations of daily solitude with subjective and physical well‐being under consideration of time‐savoring (i.e., attending to positive experiences and upregulating positive emotions). 108 older adults aged 65–92 years (M = 73.11, SD = 5.93; 58% women; 85% born in Switzerland) took part in an app‐based daily diary study in 2022. Over 14 consecutive days, participants reported daily solitude, time‐savoring, depressive mood, loneliness, and somatic symptoms in an end‐of‐day diary. Multilevel models revealed that participants reported higher depressive mood and loneliness, but not higher somatic symptoms on days on which they spent more time in solitude than usual. Higher‐than‐usual daily time‐savoring was associated with lower depressive mood, loneliness, and somatic symptoms. Associations of solitude with depressive mood, loneliness, and somatic symptoms were weaker on days on which higher time‐savoring than usual was reported. Findings highlight the potential of everyday time‐savoring as a resource in older adults in the context of increased solitude. [ABSTRACT FROM AUTHOR]

Abstract Non-Technical Summary Climate stabilization requires scaling-up technologies to capture and store carbon. Carbon removal could be very profitable, and some of the agents best placed to benefit are ‘carbon majors’, i.e. fossil fuel companies. We argue that in ordinary circumstances only agents without significant historical climate responsibilities would be entitled to the full benefits from carbon removal. Under non-ideal conditions, carbon majors might be entitled to benefit, provided that no other agent could remove similar quantities of carbon at similar costs. This burden of proof is only likely to be met in countries with poor governance capacities. Technical Summary Climate stabilization requires scaling up technologies to capture and store carbon. Some of the agents best placed to profit from carbon removal are ‘carbon majors’, especially fossil fuel companies. Yet incentivizing carbon majors to undertake carbon removal poses an ethical dilemma: carbon majors have made significant historical contributions to climate change and have significantly benefitted from such contributions without being made to compensate for resulting climate harm. This is why it seems unfair to reward them with additional economic benefits. However, carbon majors possess the technological skills and infrastructure to upscale carbon removal efficiently. We argue that in ordinary circumstances, only agents without significant climate responsibilities would be morally entitled to fully benefit from carbon removal. Yet under non-ideal conditions, it might be permissible to reward carbon majors if no other agent were capable of removing as much carbon at similar costs and on similar timeframes. We believe this argument faces an imposing burden of proof that is only likely to be met in countries with poor governance capacities. In more favorable circumstances, including those of most OECD countries, rewarding carbon majors without having them pay for their historical climate responsibilities remains impermissible. Social Media Summary Rewarding carbon majors to undertake carbon dioxide removal is unjust due to their historical climate responsibilities. Where possible, governments should empower other agents to remove CO2.

Introduction:: Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.