Resolving spatial response heterogeneity in glioblastoma.

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

Lateralisation of nasal cycle is not reflected in the olfactory bulb volumes and cerebral activations.

Nasal cycle (NC) is a rhythmic change of lateralised nasal airflow mediated by the autonomous nervous system. Previous studies reported the dependence of NC dominance or more patent side on handedness and hemispheric cerebral activity. We aimed to investigate firstly the possible lateralised effect of NC on olfactory bulb volume and secondly the association of NC with the lateralised cerebral dominance in terms of olfactory processing. Thirty-five subjects (22 women and 13 men, mean age 26 ± 3 years) participated in the study. NC was ascertained using a portable rhino-flowmeter. Structural and functional brain measurements were assessed using a 3T MR scanner. Vanillin odorant was presented during functional scans using a computer-controlled olfactometer. NC was found to be independent of the olfactory bulb volumes. Also, cerebral activations were found independent of the NC during odorant perception. NC potency is not associated with lateralised structural or functional differences in the cerebral olfactory system.

SAS-PRP Study: A Real-Life Satisfaction Assessment in Patients with Cartilage Lesions of the Knee Treated by Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is a rising therapy treating locomotor system lesions such as knee osteoarthritis. The objective of this study was to evaluate patients' satisfaction 6 to 12 months after a PRP injection for cartilage lesions of their knee under real-life conditions. Patients' satisfaction was assessed by a specific questionnaire named SATMED-Q©, which explores six different dimensions of a given treatment. In addition, pain and function were assessed thanks to VAS pain, WOMAC, and IKDC scores. Responders were identified through the OMERACT-OARSI criteria. We observed excellent satisfaction after a PRP injection with a SATMED-Q© score of 80.81% 6 to 12 months after the procedure. Even when there was no significant improvement in pain and function scores, 52% of the evaluated population fulfilled the OMERACT-OARSI criteria and were considered responders. According to the sub-group analysis, patients with less osteoarthritis damage (i.e., Kellgren-Lawrence grades 1-2) and older study subjects (i.e., >40 years old) with focal chondropathy had benefited most from their PRP injection. Thus, platelet-rich plasma seems to be a well-tolerated and efficient therapy for cartilage lesions of the knee.

Protecting the invisible: Establishing guideline values for copper toxicity to marine microbiomes.

Understanding the rapid responses of marine microbiomes to environmental disturbances is paramount for supporting early assessments of harm to high-value ecosystems, such as coral reefs. Yet, management guidelines aimed at protecting aquatic life from environmental pollution remain exclusively defined for organisms at higher trophic levels. In this study, 16S rRNA gene amplicon sequencing was applied in conjunction with propidium monoazide for cell-viability assessment as a sensitive tool to determine taxon- and community-level changes in a seawater microbial community under copper (Cu) exposure. Bayesian model averaging was used to establish concentration-response relationships to evaluate the effects of copper on microbial composition, diversity, and richness for the purpose of estimating microbiome Hazard Concentration (mHCx) values. Predicted mHC5 values at which a 5 % change in microbial composition, diversity, and richness occurred were 1.05, 0.72, and 0.38 µg Cu L-1, respectively. Threshold indicator taxa analysis was applied across the copper concentrations to identify taxon-specific change points for decreasing taxa. These change points were then used to generate a Prokaryotic Sensitivity Distribution (PSD), from which mHCxdec values were derived for copper, suitable for the protection of 99, 95, 90, and 80 % of the marine microbiome. The mHC5dec guideline value of 0.61 µg Cu L-1, protective of 95 % of the marine microbial community, was lower than the equivalent Australian water quality guideline value based on eukaryotic organisms at higher trophic levels. This suggests that marine microbial communities might be more vulnerable, highlighting potential insufficiencies in their protection against copper pollution. The mHCx values proposed here provide approaches to quantitatively assess the effects of contaminants on microbial communities towards the inclusion of prokaryotes in future water quality guidelines.

Team-based home blood pressure monitoring for blood pressure equity a protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Home Blood Pressure Monitoring (HBPM) that includes a team with a clinical pharmacist is an evidence-based intervention that improves blood pressure (BP). Yet, strategies for promoting its adoption in primary care are lacking. We developed potentially feasible and sustainable implementation strategies to improve hypertension control and BP equity. METHODS: We assessed barriers and facilitators to HBPM and iteratively adapted implementation strategies through key informative interviews and guidance from a multistakeholder stakeholder team involving investigators, clinicians, and practice administration. RESULTS: Strategies include: 1) pro-active outreach to patients; 2) provision of BP devices; 3) deployment of automated bidirectional texting to support patients through education messages for patients to transmit their readings to the clinical team; 3) a hypertension visit note template; 4) monthly audit and feedback reports on progress to the team; and 5) training to the patients and teams. We will use a stepped wedge randomized trial to assess RE-AIM outcomes. These are defined as follows Reach: the proportion of eligible patients who agree to participate in the BP texting; Effectiveness: the proportion of eligible patients with their last BP reading <140/90 (six months); Adoption: the proportion of patients invited to the BP texting; Implementation: patients who text their BP reading ≥10 of days per month; and Maintenance: sustained BP control post-intervention (twelve months). We will also examine RE-AIM metrics stratified by race and ethnicity. CONCLUSIONS: Findings will inform the impact of strategies for the adoption of team-based HPBM and the impact of the intervention on hypertension control and equity. REGISTRATION DETAILS: www. CLINICALTRIALS: gov Identifier: NCT05488795.

Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. METHODS: In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. RESULTS: The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P < 0.001). Concomitantly, the levels of the biomarker angiopoietin-2 rose, showing a strong correlation based on the time points of measurements (r = 0.959, P = 0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of capillary leak were increased. After controlling for common risk factors of edema formation, we found that an increase of 1 ng/mL in angiopoietin-2 was associated with a 0.24L increase in extracellular water (P < 0.001). Angiopoietin-2 showed increased odds for the development of acute kidney injury (OR 1.095 [95% CI 1.032, 1.169]; P = 0.004) and was furthermore associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. Machine learning predicted postoperative complications when capillary leak was added to standard risk factors. CONCLUSIONS: Capillary leak and subsequent edema formation are relevant problems after cardiac surgery. Levels of angiopoietin-2 in combination with extracellular water show promising potential to predict postoperative complications after cardiac surgery. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS No. 00017057), Date of registration 05/04/2019, www.drks.de.

Imaging the WHO 2021 Brain Tumor Classification: Fully Automated Analysis of Imaging Features of Newly Diagnosed Gliomas.

BACKGROUND: The fifth version of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) in 2021 brought substantial changes. Driven by the enhanced implementation of molecular characterization, some diagnoses were adapted while others were newly introduced. How these changes are reflected in imaging features remains scarcely investigated. MATERIALS AND METHODS: We retrospectively analyzed 226 treatment-naive primary brain tumor patients from our institution who received extensive molecular characterization by epigenome-wide methylation microarray and were diagnosed according to the 2021 WHO brain tumor classification. From multimodal preoperative 3T MRI scans, we extracted imaging metrics via a fully automated, AI-based image segmentation and processing pipeline. Subsequently, we examined differences in imaging features between the three main glioma entities (glioblastoma, astrocytoma, and oligodendroglioma) and particularly investigated new entities such as astrocytoma, WHO grade 4. RESULTS: Our results confirm prior studies that found significantly higher median CBV (p = 0.00003, ANOVA) and lower median ADC in contrast-enhancing areas of glioblastomas, compared to astrocytomas and oligodendrogliomas (p = 0.41333, ANOVA). Interestingly, molecularly defined glioblastoma, which usually does not contain contrast-enhancing areas, also shows significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.01309, ANOVA). CONCLUSIONS: This work provides extensive insights into the imaging features of gliomas in light of the new 2021 WHO CNS tumor classification. Advanced imaging shows promise in visualizing tumor biology and improving the diagnosis of brain tumor patients.

Physical and psychosocial impact on peers with HIV co-leading an HIV intervention: A pilot theory-guided case-study.

Objective: To examine longitudinal changes in activation, HIV health outcomes, and social and psychological determinants of adherence to antiretroviral therapy (ART) among peer trainers with HIV. Methods: A multi-method case study. The study population included peers (n = 4) from a randomized controlled trial about peers training patients with HIV (n = 359) to better manage their health. Each peer completed a semi-structured interview that we analyzed using Social Learning Theory (SLT) as a guiding framework. The peers also completed longitudinal surveys about their health after each training cohort (n = 5) over 3-years. Results: Peers reported personal benefits from training others with HIV in self-management. Their self-reported activation, self-efficacy and some health outcomes increased overtime. The peers mentioned SLT principles during their interviews. Generally, the peers enjoyed and benefited from training others with HIV in a group-based learning environment. Conclusion: Our findings suggest peer leadership can serve as a means for empowerment that is effective at both supporting improvements in health outcomes for patients and for themselves, which may be both scalable and sustainable. Innovation: To our knowledge, this is the first mixed-methods study to show reciprocal long-term improvement in health behaviors in a diverse group of peers training others with HIV to self-manage their care.

Thermal and Radiation Stability in Nanocrystalline Cu.

Nanocrystalline metals have presented intriguing possibilities for use in radiation environments due to their high grain boundary volume, serving as enhanced irradiation-induced defect sinks. Their promise has been lessened due to the propensity for nanocrystalline metals to suffer deleterious grain growth from combinations of irradiation and/or elevated homologous temperature. While approaches for stabilizing such materials against grain growth are the subject of current research, there is still a lack of central knowledge on the irradiation-grain boundary interactions in pure metals despite many studies on the same. Due to the breadth of available reports, we have critically reviewed studies on irradiation and thermal stability in pure, nanocrystalline copper (Cu) as a model FCC material, and on a few dilute Cu-based alloys. Our study has shown that, viewed collectively, there are large differences in interpretation of irradiation-grain boundary interactions, primarily due to a wide range of irradiation environments and variability in materials processing. We discuss the sources of these differences and analyses herein. Then, with the goal of gaining a more overarching mechanistic understanding of grain size stability in pure materials under irradiation, we provide several key recommendations for making meaningful evaluations across materials with different processing and under variable irradiation conditions.

Portrait of autosomal recessive diseases in the French-Canadian founder population of Saguenay-Lac-Saint-Jean.

The population of the Saguenay-Lac-Saint-Jean (SLSJ) region, located in the province of Quebec, Canada, is recognized as a founder population, where some rare autosomal recessive diseases show a high prevalence. Through the clinical and molecular study of 82 affected individuals from 60 families, this study outlines 12 diseases identified as recurrent in SLSJ. Their carrier frequency was estimated with the contribution of 1059 healthy individuals, increasing the number of autosomal recessive diseases with known carrier frequency in this region from 14 to 25. We review the main clinical and molecular features previously reported for these disorders. Five of the studied diseases have a potential lethal effect and three are associated with intellectual deficiency. Therefore, we believe that the provincial program for carrier screening should be extended to include these eight disorders. The high-carrier frequency, together with the absence of consanguinity in most of these unrelated families, suggest a founder effect and genetic drift for the 12 recurrent variants. We recommend further studies to validate this hypothesis, as well as to extend the present study to other regions in the province of Quebec, since some of these disorders could also be present in other French-Canadian families.

The Fatigue-Related Symptoms Post-Acute SARS-CoV-2: A Preliminary Comparative Study.

A sizeable sub-group of individuals continue to experience persistent debilitating symptoms post-acute SARS-CoV-2. Although these can vary from person to person, fatigue appears to be the most common symptom. Post-viral fatigue has been documented in conditions such as influenza, infectious mononucleosis and more recently chronic fatigue syndrome (CFS). The current study uses measures that successfully describe the fatigue-related symptoms associated with CFS to investigate the fatigue experienced post-acute SARS-CoV-2. Twenty-six volunteers were recruited from Long COVID support groups active on social media. Data were collected anonymously using an online survey platform. These data were compared to pre-pandemic data from non-fatigued and CFS groups. The post-acute SARS-CoV-2 volunteers reported significantly higher levels of fatigue and cognitive difficulties than the non-fatigued controls. They also report more individual symptoms (such as lack of concentration) and problems with sleep quality. There was a similarity between the post-acute SARS-CoV-2 volunteers and the CFS group in terms of levels of depression, perceived stress, emotional distress and cognitive difficulties. Although this was a small-scale study, it demonstrates the range of symptoms experienced post-acute SARS-CoV-2. In addition, the similarities between this group and CFS suggests the need for further research into the mechanisms at play here, the need to identify those at risk of long-term symptoms and the development of possible interventions.

How to Evaluate Health in All Policies at the Local Level: Methodological Insights Within Municipalities From the WHO French Healthy Cities Network.

BACKGROUND: This article proposes a method for analysing the degree of maturity of Health in All Policies (HiAP) among World Health Organization-French Healthy Cities Network (WHO-FHCN) as part of the GoveRnance for Equity, EnviroNment and Health in the City (GREENH-City) project. We focused on the creation or enhancement of health-promoting environments, and more specifically, public green spaces. METHODS: We conducted a cross-sectional quantitative study guided by the evaluative framework of the HiAP maturity level developed by Storm et al mixed with a qualitative interpretation. A self-administered questionnaire was sent to elected officials and health department officers in the 85 member cities of the WHO-FHCN in 2017. Subsequently 58 cities were included in the analysis, which was based on a multiple correspondence analysis (MCA) and a hierarchical ascending classification (HAC). RESULTS: Thirty-two criteria among a total of 100 were identified and were used to organize the cities into 8 groups which was then reduced to three profiles among the cities: a less advanced HiAP profile, an established HiAP profile and an advanced HiAP profile. This process allows us to identify 4 dimensions that make it possible to evaluate the level of maturity of cities in the HiAP process, namely: (1) the consideration of social inequalities in health and/or health issues in the policies/actions of the sector studied, (2) occasional intersectoral collaboration, ie, one-off initiatives between the health department and others sectors, (3) the existence of joint projects, ie, common projects between two or more sectors, (4) the existence of intersectoral bodies, in this case on the theme of urban green spaces including an intersectoral committee and/or working groups. CONCLUSION: Four dimensions which allow to the measurement of the degree of progress in implementing health-all-policies are proposed. With a view to integrating knowledge into public action, this study carried out under real conditions offers a realistic method to evaluate HiAP.

Racial and oral health disparity associated with perinatal oral health care utilization among underserved US pregnant women.

OBJECTIVE: The study aims to identify specific determinants of dental care utilization during the perinatal period (prenatal and 1-year postnatal) among underserved US women residing in Upstate New York. METHOD AND MATERIALS: The prospective cohort study included 186 low-income US pregnant women. Demographic-socioeconomic parameters and medical-dental conditions were obtained from questionnaires, electronic medical-dental records, and dental examinations. Multivariate regression analyses were used to assess factors associated with perinatal dental care utilization. As an exploratory effort, a separate logistic model assessed factors associated with adverse birth outcomes. RESULTS: The results demonstrated unmet oral health needs among the underserved US pregnant women residing in Upstate New York. Despite an average of 2.7 ± 3.6 untreated decayed teeth per person during pregnancy, only 39.3% and 19.9% utilized prenatal and 1-year postnatal dental care, respectively. Previous dental care utilization was a notable factor contributing to a higher uptake of perinatal dental care at a subsequent period. Prenatal dental care utilization was significantly lower among African American women (odds ratio 0.43 [95% CI 0.19, 0.98], P = .04) and positively associated with dental caries severity (OR 2.40 [1.09, 5.12], P = .03). Postnatal utilization was associated with caries severity (OR 4.70 [1.73, 12.74], P = .002) and prevalent medical conditions (hypertension, diabetes mellitus, and emotional conditions). Pregnant women who achieved prenatal caries-free status had a lower odds of experiencing adverse birth outcomes; however, this was an insignificant finding due to limited adverse birth cases. CONCLUSION: Racial and oral health disparity is associated with perinatal oral health care utilization among underserved US pregnant women in New York. While both prenatal and postnatal dental care utilization was positively associated with oral health status, specifically, postnatal utilization was driven by existing medical conditions such as emotional condition, hypertension, and diabetes mellitus. The results add to existing information on inherent barriers and postulated needs to improve access to perinatal oral care, thereby informing statewide recommendations to maximize utilization. Considering this is a geographically restricted population, the findings are particularly true to this cohort of underserved pregnant women. However, future more robust studies are warranted to assess effective strategies to further improve perinatal dental care utilization among underserved pregnant women.

Improving Automated Glioma Segmentation in Routine Clinical Use Through Artificial Intelligence-Based Replacement of Missing Sequences With Synthetic Magnetic Resonance Imaging Scans.

OBJECTIVES: Although automated glioma segmentation holds promise for objective assessment of tumor biology and response, its routine clinical use is impaired by missing sequences, for example, due to motion artifacts. The aim of our study was to develop and validate a generative adversarial network for synthesizing missing sequences to allow for a robust automated segmentation. MATERIALS AND METHODS: Our model was trained on data from The Cancer Imaging Archive (n = 238 WHO II-IV gliomas) to synthesize either missing FLAIR, T2-weighted, T1-weighted (T1w), or contrast-enhanced T1w images from available sequences, using a novel tumor-targeting loss to improve synthesis of tumor areas. We validated performance in a test set from both the REMBRANDT repository and our local institution (n = 68 WHO II-IV gliomas), using qualitative image appearance metrics, but also segmentation performance with state-of-the-art segmentation models. Segmentation of synthetic images was compared with 2 commonly used strategies for handling missing input data, entering a blank mask or copying an existing sequence. RESULTS: Across tumor areas and missing sequences, synthetic images generally outperformed both conventional approaches, in particular when FLAIR was missing. Here, for edema and whole tumor segmentation, we improved the Dice score, a common metric for evaluation of segmentation performance, by 12% and 11%, respectively, over the best conventional method. No method was able to reliably replace missing contrast-enhanced T1w images. DISCUSSION: Replacing missing nonenhanced magnetic resonance sequences via synthetic images significantly improves segmentation quality over most conventional approaches. This model is freely available and facilitates more widespread use of automated segmentation in routine clinical use, where missing sequences are common.

Continuous clinical improvement of mild-to-moderate seborrheic dermatitis and rebalancing of the scalp microbiome using a selenium disulfide-based shampoo after an initial treatment with ketoconazole.

OBJECTIVE: Scalp seborrheic dermatitis (SD) is a chronic, relapsing, and inflammatory scalp disease. Studies indicate a global bacterial and fungal microbiota shift of scalp SD, as compared to healthy scalp. Ketoconazole and selenium disulfide (SeS2 ) improve clinical signs and symptoms in both scalp dandruff and SD. AIM: The main objective of this study was to investigate the changes in the scalp microbiota diversity and counts in subjects with scalp SD during a two-phase treatment period. MATERIAL AND METHODS: The scalp microbiota and clinical efficacy were investigated in 68 subjects with mild-to-moderate scalp SD after an initial one-month treatment with 2% ketoconazole, and after a 2-month maintenance phase, either with a 1% SeS2 -based shampoo or its vehicle. RESULTS: Thirty one subjects in the active and 37 subjects in the vehicle group participated. Ketoconazole provided an improvement of clinical symptoms (adherent (-1.75 p < 0.05), non-adherent (-1.5, p < 0.05)) flakes and erythema (scores 1.67-0.93, p < 0.001), in an increased fungal diversity and in a significant (p < 0.005) decrease of Malassezia spp. SeS2 provided an additional clinical improvement (-0.8; p = 0.0002 and -0.7; p = 0.0081 for adherent and non-adherent flakes, respectively, at Day 84) compared to the vehicle associated with a low Malassezia spp. count and an additional significant (p < 0.001) decrease of the Staphylococcus spp. level. CONCLUSION: Selenium disulfide provides an additional benefit on the scalp microbiota and in clinical symptoms of SD and dandruff after treatment with ketoconazole. The results confirm the role of Staphylococcus spp. in scalp SD and open possible perspectives for preventing relapses.

First glance at the molecular etiology of hearing loss in French-Canadian families from Saguenay-Lac-Saint-Jean's founder population.

The French-Canadian population of Saguenay-Lac-Saint-Jean is known for its homogenous genetic background. The hereditary causes of hearing loss were previously unexplored in this population. Individuals with hearing loss were referred from the otorhinolaryngology, pediatrics and family physicians' clinics to the medical genetics service at the Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean between June 2015 and March 2021. A regional clinical evaluation strategy was developed. Samples from 63 individuals belonging to 41 families were sent independently to different molecular clinical laboratories and index cases were analyzed through comprehensive multigene panels, with a diagnostic rate of 54%. Sixteen hearing loss causal variants were identified in 12 genes, with eight of these variants not been previously reported in the literature. Recurrent variants were present in four genes, suggesting a possible founder effect, while GJB2 gene variants were scarce. A comprehensive multigene panel approach as part of the proposed clinical evaluation strategy offers a high diagnostic yield for this population.

Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance.

Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET−MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET−MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong's test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.

Toxicity thresholds of nine herbicides to coral symbionts (Symbiodiniaceae).

Over 30 herbicides have been detected in catchments and waters of the Great Barrier Reef (GBR) and their toxicity to key tropical species, including the coral endosymbiotic algae Symbiodiniaceae, is not generally considered in current water quality guideline values (WQGVs). Mutualistic symbionts of the family Symbiodiniaceae are essential for the survival of scleractinian corals. We tested the effects of nine GBR-relevant herbicides on photosynthetic efficiency (ΔF/Fm') and specific growth rate (SGR) over 14 days of cultured coral endosymbiont Cladocopium goreaui (formerly Symbiodinium clade C1). All seven Photosystem II (PSII) herbicides tested inhibited ΔF/Fm' and SGR, with toxicity thresholds for SGR ranging between 2.75 and 320 µg L-1 (no effect concentration) and 2.54-257 µg L-1 (EC10). There was a strong correlation between EC50s for ΔF/Fm' and SGR for all PSII herbicides indicating that inhibition of ΔF/Fm' can be considered a biologically relevant toxicity endpoint for PSII herbicides to this species. The non-PSII herbicides haloxyfop and imazapic did not affect ΔF/Fm' or SGR at the highest concentrations tested. The inclusion of this toxicity data for Symbiodiniaceae will contribute to improving WQGVs to adequately inform risk assessments and the management of herbicides in tropical marine ecosystems.