Potential Difference Research Articles

Validation of an alternative technique for RQ estimation in anesthetized pigs

BackgroundRespiratory quotient (RQ) is an important variable when assessing metabolic status in intensive care patients. However, analysis of RQ requires cumbersome technical equipment. The aim of the current study was to examine a simplified blood gas-based method of RQ assessment, using Douglas bag measurement of RQ (Douglas-RQ) as reference in a laboratory porcine model under metabolic steady state. In addition, we aimed at establishing reference values for RQ in the same population, thereby generating data to facilitate further research.MethodsRQ was measured in 11 mechanically ventilated pigs under metabolic steady state using Douglas-RQ and CO-oximetry blood gas analysis of pulmonary artery and systemic carbon dioxide and oxygen content. The CO-oximetry data were used to calculate RQ (blood gas RQ). Paired recordings with both methods were made once in the morning and once in the afternoon and values obtained were analyzed for potential significant differences.ResultsThe average Douglas-RQ, for all data points over the whole day, was 0.97 (95%CI 0.95–0.99). The corresponding blood gas RQ was 0.95 (95%CI 0.87–1.02). There was no statistically significant difference in RQ values obtained using Douglas-RQ or blood gas RQ for all data over the whole day (P = 0.43). Bias was − 0.02 (95% limits of agreement ± 0.3). Douglas-RQ decreased during the day 1.00 (95%CI 0.97–1.03) vs 0.95 (95%CI 0.92–0.98) P < 0.001, whereas the decrease was not significant for blood gas RQ 1.02 (95%CI 0.89–1.16 vs 0.87 (0.80–0.94) P = 0.11.ConclusionRQ values obtained with blood gas analysis did not differ statistically, compared to gold standard Douglas bag RQ measurement, showing low bias but relatively large limits of agreement, when analyzed for the whole day. This indicates that a simplified blood gas-based method for RQ estimations may be used as an alternative to gold standard expired gas analysis on a group level, even if individual values may differ. In addition, RQ estimated with Douglas bag analysis of exhaled air, was 0.97 in anesthetized non-fasted pigs and decreased during prolonged anesthesia.

Challenges and approaches to calibrating patient phenotype as evidence for cancer gene variant classification under ACMG/AMP guidelines.

Since first publication of the American College of Medical Genetics and Genomics/Association for Medical Pathology (ACMG/AMP) variant classification guidelines, additional recommendations for application of certain criteria have been released (https://clinicalgenome.org/docs/), to improve their application in the diagnostic setting. However, none have addressed use of the PS4 and PP4 criteria, capturing patient presentation as evidence towards pathogenicity. Application of PS4 can be done through traditional case-control studies, or "proband counting" within or across clinical testing cohorts. Review of the existing PS4 and PP4 specifications for Hereditary Cancer Gene Variant Curation Expert Panels revealed substantial differences in the approach to defining specifications. Using BRCA1, BRCA2 and TP53 as exemplar genes, we calibrated different methods proposed for applying the "PS4 proband counting" criterion. For each approach, we considered limitations, non-independence with other ACMG/AMP criteria, broader applicability, and variability in results for different datasets. Our findings highlight inherent overlap of proband-counting methods with ACMG/AMP frequency codes, and the importance of calibration to derive dataset-specific code weights that can account for potential between-dataset differences in ascertainment and other factors. Our work emphasizes the advantages and generalizability of logistic regression analysis over simple proband-counting approaches to empirically determine the relative predictive capacity and weight of various personal clinical features in the context of multigene panel testing, for improved variant interpretation. We also provide a general protocol, including instructions for data formatting and a web-server for analysis of personal history parameters, to facilitate dataset-specific calibration analyses required to use such data for germline variant classification.

N26 Disease outcomes and patient’s perspectives after switching biologics from intravenous to subcutaneous administration. A real-world experience in a tertiary IBD-unit

Abstract Background Since 2022, subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) became available. This study aims to assess patients’ perspectives on potential switch to SC administration. Methods A prospective observational, nurse-led study was performed at the Ghent University Hospital. Patients treated with IV IFX or VDZ, deemed suitable by the treating physician based on the DIAMOND multi-stakeholder position statement of the Belgian IBD Research and Development group (BIRD), were offered switch to SC administration between 01/01/2022-30/06/2023. Participants were asked to fill out questionnaires regarding personal perspective on a potential switch to SC administration. Data was collected using REDCap®. Descriptive and univariate analyses were performed with Excel ®. The study was approved by the Ethical committee of UZ Ghent (ONZ-2022-0296). Results In total 404 patients receiving IV IFX or VDZ were identified within the inclusion period. Of those, 196 received 8-weekly treatment. After screening by the treating physician, 157 patients met the inclusion criteria of whom 84 agreed to participate (Figure 1). Questionnaires were filled out completely by 70 of the included patients. Fourty patients were treated with VDZ (57.1%) and 42.9% with IFX. Fourty-three patients (61.40%) had Crohn’s disease, 26 (37.1 %) had ulcerative colitis and 1 (1.4 %) indeterminate colitis. Fifteen patients (21.4%) had previous experience with SC self-injections. Thirty-four participants (48.6%) chose to switch to SC administration of their current treatment, 36 refused (51.4%). In general, patients were aware of the possibility to switch to SC administration before entering the study as 71% knew this formulation was available. Main information channels were: treating physician (56%) and/or IBD nurse (58%). Univariate analyses comparing switchers versus non-switchers are shown in Table 1. Patients who refused switch were more concerned about potential adverse events (agree: 61.1% vs 23.5%), loss of response (agree: 41.4% vs 11.4%) or incompliance (agree: 47.2% vs 14.7%) with SC formulations. Furthermore, the associated physician visit at the IV-administration unit was deemed more important to non-switchers (agree: 88.9% vs 55.9%). Patients who switched were less concerned about potential differences in healthcare costs (disagree: 70.6 vs 36.1%) and felt that regular visits to the IV-administration unit had big impact on QoL (agree: 64.7% vs 11.2%). Conclusion Patient’s perspectives differed significantly between those who chose to switch to SC IFX/VDZ and those who remained under the IV formulation. This should be considered when discussing treatment options with the patients and confirms the importance of patient engagement in managing IBD.

Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number

Mitochondrial DNA copy number (mtDNA-CN) is a biomarker for mitochondrial dysfunction associated with several diseases. Previous genome-wide association studies (GWAS) have been performed to unravel underlying mechanisms of mtDNA-CN regulation. However, the identified gene regions explain only a small fraction of mtDNA-CN variability. Most of this data has been estimated from microarrays based on various pipelines. In the present study we aimed to (1) identify genetic loci for qPCR-measured mtDNA-CN from three studies (16,130 participants) using GWAS, (2) identify potential systematic differences between our qPCR derived mtDNA-CN measurements compared to the published microarray intensity-based estimates, and (3) disentangle the nuclear from mitochondrial regulation of the mtDNA-CN phenotype. We identified two genome-wide significant autosomal loci associated with qPCR-measured mtDNA-CN: at HBS1L (rs4895440, p = 3.39 × 10–13) and GSDMA (rs56030650, p = 4.85 × 10–08) genes. Moreover, 113/115 of the previously published SNPs identified by microarray-based analyses were significantly equivalent with our findings. In our study, the mitochondrial genome itself contributed only marginally to mtDNA-CN regulation as we only detected a single rare mitochondrial variant associated with mtDNA-CN. Furthermore, we incorporated mitochondrial haplogroups into our analyses to explore their potential impact on mtDNA-CN. However, our findings indicate that they do not exert any significant influence on our results.

The influence of soil organic matter content and substance lipophilicity on the toxicity of pesticides to the earthworm Eisenia andrei

To account for potential differences in bioavailability (and toxicity) due to different soil organic matter (OM) contents in natural and artificial soil (AS), in the current European environmental risk assessment (ERA) a correction factor (CF) of 2 is applied to toxicity endpoints for so called lipophilic pesticides (i.e. log Kow > 2) generated from laboratory tests with soil invertebrates. However, the appropriateness of a single CF is questioned. To improve the accuracy of ERA, this study investigated the influence of soil OM content on the toxicity to the earthworm Eisenia andrei of five active substances used in pesticides covering a wide range of lipophilicity. Laboratory toxicity tests were performed in AS containing 10 %, 5 % and 2.5 % peat, and a natural LUFA 2.2 soil (4.5 % OM), assessing effects on survival, biomass change and reproduction. Pesticide toxicity differed significantly between soils. For all pesticides, toxicity values (LC50, EC50) strongly correlated with soil OM content in AS (r2 > 0.82), with toxicity decreasing with increasing OM content. Obtained regression equations were used to calculate the toxicity at OM contents of 10.0 % and 5.0 %. Model-estimated toxicity between these soils differed by factors of 1.9–3.6, and 2.1–3.2 for LC50 and EC50 values, respectively. No clear relationships between pesticide lipophilicity and toxicity-OM relationships were observed: the toxicity of non-lipophilic and lipophilic pesticides was influenced by OM content in a similar manner. The results suggest that the CF of 2 may not be appropriate as it is based on incorrect assumptions regarding the relationships between lipophilicity, OM content and toxicity. Further research should be conducted to understand the mechanistic link between toxicity and soil OM content to better define more chemically and ecologically appropriate CFs for ERA.

Comparative analysis of proximal humerus fracture management in elderly patients: complications of open reduction and internal fixation by shoulder surgeons and non-shoulder surgeons-a retrospective study.

Open reduction and internal fixation (ORIF) with a locking plate is a popular surgical treatment for proximal humeral fractures (PHF). This study aimed to assess the occurrence of complications in elderly patients with PHF treated surgically using ORIF with a locking plate and to investigate the potential differences between patients treated by shoulder surgeons and non-shoulder surgeons. A retrospective study was conducted using a single-center database to identify patients aged ≥70 years who underwent ORIF for PHF between January 1, 2011, and December 31, 2021. Data on the Neer classification, follow-up, occurrence of avascular necrosis of the humeral head, implant failure, and revision surgery were also collected. Statistical analyses were performed to calculate the overall frequency of complications according to the Neer classification. The rates of implant failure, avascular osteonecrosis, and revision surgery were 15.7%, 4.8%, and 15.7%, respectively. Complications were more common in patients with Neer three- and four-part fractures. Although the difference between surgeries performed by shoulder surgeons and non-shoulder surgeons did not reach statistical significance, the rate of complications and the need for revision surgery were nearly two-fold higher in the latter group. PHF are highly prevalent in the elderly population. However, the ORIF surgical approach, as demonstrated in this study, is associated with a considerable rate of complications. Surgeries performed by non-shoulder surgeons had a higher rate of complications and a more frequent need for revision surgery. Future studies comparing surgical treatments and their respective complication rates are crucial to determine the optimal therapeutic options. Level of evidence: III.

P1019 "Totality-of-the-evidence" of proposed ustekinumab biosimilar SB17"

Abstract Background SB17 is a proposed biosimilar to Stelara [ustekinumab reference product (UST-RP)], which is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. In accordance with regulatory guidelines, "totality-of-the-evidence" proofs similarity between a proposed biosimilar and its reference product and includes analytical, non-clinical and clinical data.1, 2 SB17 is under review by regulatory agencies to be approved as ustekinumab biosimilar. The proposed justification for extrapolation of indications for SB17 was justified based on "totality-of-the-evidence" (i) MoA of ustekinumab binding to p40 subunit of IL-12/23, which has been associated with immune-mediated diseases, including approved indications of UST-RP (ii) overall data from the comparability comparison to UST-RP using analytical methods showing similar molecular structure and in vitro function (iii) PK studies showing similar exposure, and PD studies in healthy subject and (iv) efficacy and safety (including immunogenicity) based on studies in patients with moderate-to-severe psoriasis (PsO). The phase III study was conducted in ustekinumab-naïve patients with PsO as the most sensitive design to assess potential differences in efficacy and the risk of immunogenicity. The objective of this report is to describe the biosimilarity of SB17 to UST-RP with regard to potential extrapolation from PsO to other indications. Methods Analytical comparability of SB17 to UST-RP was assessed in ELISA binding assays. PK equivalence, efficacy, safety, tolerability, and immunogenicity similarity were assessed in clinical trials of healthy subjects and PsO patients. Results In the analytical assessment, SB17 was highly similar to the EU- and US-UST-RP in overall critical and non-critical quality attributes. Evaluation of IL-12 and IL-23 neutralization and binding activities, MoA-related biological activities, showed similarity between SB17, EU-, and US-UST-RP. 3 In a phase I study, SB17 and EU- and US-UST-RP had similar PK and comparable safety, tolerability, and immunogenicity (Table 1).4 In a phase III study of 503 patients with moderate to severe PsO, SB17 had equivalent efficacy and comparable safety and immunogenicity to UST-RP up to Week 28 (Table 1).5 Conclusion With similar target binding and PK and confirmed similarity in efficacy and safety for PsO patients, SB17 is proposed to be highly similar to UST-RP in physicochemical, non-clinical, and clinical similarity studies. "Totality-of-the-evidence" data for SB17 supports its extrapolation to UST-RP indications.

Longitudinal Influence of Prescribed Antidepressants on Fecal and Oral Microbiomes Among Veterans With Major Depressive Disorder.

The purpose of this study was to evaluate the influence of a new course of antidepressant monotherapy on gut and oral microbiomes and the relationship to depressive symptoms. Longitudinal microbiome samples obtained from 10 U.S. veterans were analyzed. Baseline samples were taken before a new course of antidepressant monotherapy (either switching from a previous treatment or starting a new treatment). Targeted genomic sequencing of the microbiome samples was used to analyze changes in taxonomy and diversity across participants, medications, and medication class. Associations between these changes and Patient Health Questionnaire-9 (PHQ-9) scores were analyzed. Taxonomic variability was observed across participants, with the individual being the main microbial community driver. In terms of the fecal microbiome, antidepressants were associated with shifts toward Bacteroides being less abundant and Blautia, Pseudomonas, or Faecalibacterium being more abundant. Likewise, the composition of the oral microbiome was variable, with individual participants being the primary drivers of community composition. In the oral samples, the relative abundance of Haemophilus decreased after antidepressants were started. Increases in Blautia and decreases in Bacteroides were associated with lower PHQ-9 scores. Antidepressants were found to influence fecal and oral microbiomes such that a new course of antidepressant monotherapy was associated with taxonomic alterations toward healthier states in both fecal and oral microbiomes, which were associated with decreases in depressive symptoms. Additional longitudinal research is required to increase understanding of microbiomes and symptom-based changes, with a particular focus on potential differences between medication classes and underlying mechanisms.

Awareness of the impact of sex and gender in the disease risk and outcomes in hematology and medical oncology-a survey of Swiss clinicians.

Although male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients. To evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022. We collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate). While most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research. Our findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care.

Atopic dermatitis and stress: A functional magnetic resonance imaging study of female patients with atopic dermatitis using an arithmetic task

AbstractBackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, dry skin and persistent itch. AD may worsen due to psychological stress. However, little is known about the neural correlates that mediate the interaction between psychological stress and AD.ObjectivesTo identify the possible difference in brain activation during arithmetic‐task induced stress in patients with AD versus healthy controls (HC) as well as the link between the brain response and clinical and psychodemographic parameters.MethodsA cohort of 29 AD female patients and 23 matched HC were recruited to investigate the potential difference in functional magnetic resonance imaging (fMRI) response to a block‐designed arithmetic paradigm. Both the HC and AD subjects were evaluated regarding their psychological traits, and for the AD subjects also their clinical characteristics, including stress indicators such as heart rate and salivary cortisol. We employed both univariate and multivariate statistical methods to analyse the blood oxygen level dependent (BOLD) fMRI response of the subjects to the block‐designed arithmetic paradigm.Results(1) Compared with HC subjects, the AD patients depict less deactivation in the default mode network including right angular gyrus, bilateral temporal pole and temporal lobe in response to the arithmetic task. (2) The BOLD fMRI response amplitude in the right postcentral gyrus and inferior parietal lobule is positively correlated with the stress susceptibility scores in the AD subjects, whereas the trend was the opposite of this for the HC subjects. (3) The activation in the postcentral gyrus also shows a correlation with the degree of itch in the AD patients.ConclusionsThe BOLD fMRI measurements based on an arithmetic paradigm can provide useful insight into altered brain processing and its association with psychological traits and clinical characteristics in subjects with AD. Psychological stress exacerbates brain activities for the AD subjects in the motor, somatosensory association cortex, perception and sensory integration processing. The postcentral gyrus might be of particular interest for itch and stress.

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

BackgroundElectronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance.MethodsFive-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively.ResultsExposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN.ConclusionExposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.

Seasonal variability drives differences in the structure of the calanoid copepod community in two contrasting regions of the Gulf of Mexico

Abstract Calanoid copepods (CC) are key contributors to the biological carbon pump and pelagic trophic dynamics. The deep-water regions of Perdido and the Bay of Campeche in the western and southern Gulf of Mexico (GM), respectively, differ in hydrography and productivity, leading to potential differences in copepod biomass and community structure. Zooplankton (0-200 m) were collected from the shelf edge to the deep-water region during the winter and summer autumn 2016. Calanoids contributed 38-60% of total zooplankton biomass and 55-70% of overall copepod abundance. The Bay of Campeche had the highest total zooplankton biovolume (287±120 ml 1000 m−3) and total mean copepod abundance (CC and non-calanoids ~146,000 ind. 1000 m−3) during summer-autumn, likely resulting from cross-shelf nutrient transport fueling local productivity. Adult females dominated calanoid numerical abundance (43-50%), thus suggesting a high reproductive potential. Cluster analysis showed differences between seasons (~40% dissimilarity) but not regions. Environmental conditions explained 22% of the variability in community composition; the winter assemblage was significantly related to oxygen concentrations, whereas the summer-autumn community was related to warmer conditions and higher integrated chlorophyll-a concentrations. The CC community responded to seasonal changes more than regionally related hydrographic differences, with likely implications for organic matter cycling and export.

Implementation of Cyclical Processes in the Moisture Electricity Generation for Continuous Operation

The article presents the results of a study on the generation of electricity using porous Ca6H2O19Si6 structures as an example during moisture adsorption. It has been determined that the potential difference at the contacts of a single‐layer structure of compacted Ca6H2O19Si6 particles depends on the time of formation of the potential‐determining and diffusion layers and processes that destroy the diffusion layer or prevent its formation can increase the efficiency of moisture electric generator. The concept for creating the moisture electric generators based on multilayer structures, which may allow the use of such structures as moisture electric generators for continuous operation under constant external conditions, has been proposed.

Reward Learning as a Potential Mechanism for Improvement in Schizophrenia Spectrum Disorders Following Cognitive Remediation: Protocol for a Clinical, Nonrandomized, Pre-Post Pilot Study.

Cognitive impairment is common with schizophrenia spectrum disorders. Cognitive remediation (CR) is effective in improving global cognition, but not all individuals benefit from this type of intervention. A better understanding of the potential mechanism of action of CR is needed. One proposed mechanism is reward learning (RL), the cognitive processes responsible for adapting behavior following positive or negative feedback. It is proposed that the structure of CR enhances RL and motivation to engage in increasingly challenging tasks, and this is a potential mechanism by which CR improves cognitive functioning in schizophrenia. Our primary objective is to examine reward processing in individuals with schizophrenia before and after completing CR and to compare this with a group of matched clinical controls. We will assess whether RL mediates the relationship between CR and improved cognitive function and reduced negative symptoms. Potential differences in social RL and nonsocial RL in individuals with schizophrenia will also be investigated and compared with a healthy matched control group. We propose a clinical, nonrandomized, pre-post pilot study comparing the impact of CR on RL and neurocognitive outcomes. The study will use a combination of objective and subjective measures to assess neurocognitive, psychiatric symptoms, and neurophysiological domains. A total of 40 individuals with schizophrenia spectrum disorders (aged 18-35 years) will receive 12 weeks of CR therapy (n=20) or treatment as usual (n=20). Reward processing will be evaluated using a reinforcement learning task with 2 conditions (social reward vs nonsocial reward) at baseline and the 12-week follow-up. Functional magnetic resonance imaging responses will be measured during this task. To validate the reinforcement learning task, RL will also be assessed in 20 healthy controls, matched for age, sex, and premorbid functioning. Mixed-factorial ANOVAs will be conducted to evaluate treatment group differences. For the functional magnetic resonance imaging analysis, computational modeling will allow the estimation of learning parameters at each point in time, during each task condition, for each participant. We will use a variational Bayesian framework to measure how learning occurred during the experimental task and the subprocesses that underlie this learning. Second-level group analyses will examine how learning in patients differs from that observed in control participants and how CR alters learning efficiency and the underlying neural activity. As of September 2023, this study has enrolled 15 participants in the CR group, 1 participant in the treatment-as-usual group, and 11 participants in the healthy control group. Recruitment is expected to be completed by September 2024. Data analysis is expected to be completed and published in early 2025. The results of this study will contribute to the knowledge of CR and RL processes in severe mental illness and the understanding of the systems that impact negative symptoms and cognitive impairments within this population. DERR1-10.2196/52505.

Coalescence sum rule and the electric charge- and strangeness-dependences of directed flow in heavy ion collisions

The rapidity-odd directed flows (v1) of identified hadrons are expected to follow the coalescence sum rule when the created matter is initially in parton degrees of freedom and then hadronizes through quark coalescence. A recent study has considered the v1 of produced hadrons that do not contain u or d constituent quarks. It has constructed multiple hadron sets with a small mass difference but given difference in electric charge Δq and strangeness ΔS between the two sides, where a nonzero and increasing Δv1 with Δq has been proposed to be a consequence of electromagnetic fields. In this study, we examine the consequence of coalescence sum rule on the Δv1 of the hadron sets in the absence of electromagnetic fields. We find that in general Δv1≠0 for a hadron set with nonzero Δq and/or ΔS due to potential v1 differences between u¯ and d¯ and between s and s¯ quarks. We further propose methods to extract the coefficients for the Δq- and ΔS-dependences of the direct flow difference, where a nonzero constant term would indicate the breaking of the coalescence sum rule. The extraction methods are then demonstrated with transport model results.

Insights from an extensive triaxial testing campaign on a shale for comparative site characterization of a deep geological repository

Several boreholes were drilled for site comparison of a deep geological repository (DGR) in Northern Switzerland. The main target of the exploration program was the >100m thick Opalinus Clay, the designated host rock encountered at approximately 450 to 1000 m depth in three different sites. This contribution focuses on the evaluation of geomechanical properties and the deformation behavior from the triaxial testing campaign, both aspects relevant to construction and the assessment of the long-term safety of a DGR. Some 140 triaxial tests were performed on cores from seven different boreholes to evaluate potential differences in material properties by depth and geographic location. Core sampling, preparation chain, and testing protocols were validated before the campaign, and three laboratories were commissioned to perform the tests. A comparison of basic properties from cores used for triaxial testing with a much larger database of complementary core analyses and geophysical logging demonstrates that the performed tests cover the range of expected material properties. Limited to no differences in strength and stiffness are detected from cores at different depths and sites. Despite a relatively large variation in bulk mineralogy of the formation (e.g. clay-mineral content varying between 35 and 75 wt%), the strength values of Opalinus Clay vary only moderately, with equivalent (calculated) unconfined compressive strengths of 21 ± 5 MPa, for loading directions parallel or perpendicular to bedding. This contrasts with the results of Opalinus Clay from the Rock Laboratory at Mont Terri, where the effect of material composition was more relevant. Assuming a Mohr-Coulomb-type failure law, the transition from peak to post-peak strength comes at the expense of cohesion, and only a small reduction of the shear strength angle. Hence the burial history, tectonic overprint, and current depth mainly control the intact properties by additional cohesion, whereas the post-peak behavior is mainly controlled by bulk mineralogy.

Crime Risk and Depression Differentially Relate to Aspects of Sleep in Patients with Major Depression or Social Anxiety.

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social-ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have been under-researched in terms of internalizing conditions. Therefore, the current study comprised participants diagnosed with major depression (n = 24) or social anxiety (n = 35). Sleep measures included actigraphic variables (i.e., total sleep time, waking after sleep onset, sleep onset latency) and subjective sleep quality. Geocoding was used to assess nationally-normed crime risk exposure at the person level (e.g., murder, assault) and property level (e.g., robbery, burglary). Analyses consisted of independent t-tests to evaluate potential differences between diagnostic groups. To examine relationships, multiple regressions were used with internalizing symptoms, crime risk, and age as independent variables and sleep measures as the dependent variable. The t-test results revealed that groups differed in symptoms and age but not sleep or neighborhood crime. Regression results revealed crime risk positively corresponded with sleep onset latency but no other sleep measures. Also, only depression positively corresponded with total sleep time. Preliminary findings suggest exposure to crime and depression relate differentially to facets of sleep in individuals with internalizing conditions.

2000 Cause of death amongst frail and non-frail older people post-hospital admission in northern Tanzania

Abstract Introduction Verbal autopsy (VA) is a tool used to determine cause of death (COD) in regions lacking routine medical certification. Automated algorithms are widely used to interpret VA data. This study aimed to investigate potential differences in COD between frail and non-frail older people in northern Tanzania. Method This work forms part of a longitudinal study investigating the clinical outcomes of 308 consecutive adults aged ≥60 years following admission to four hospitals in northern Tanzania. Frailty status was established on admission using the Clinical Frailty Scale (CFS) and dichotomised with CFS ≥5 indicating frailty. For participants who passed away in the 10-12 months following admission, VA data were collected through telephone interview using the 2022 World Health Organization (WHO) VA instrument. COD estimates were established using the SmartVA-Analyze program, implementing the Tariff 2.0 Method. Results After a mean follow-up period of 10.8 (±0.9) months, VA data were available for 69 participants. At admission screening, 51 (73.9%) were frail, while 18 (26.1%) were non-frail. SmartVA produced COD estimates for 42 (60.9%) participants, while 27 (39.1%) remained undetermined. Cause Specific Mortality Fractions (CSMFs) for non-communicable disease were higher for those with frailty than the non-frail group (70.6% vs. 54.0%, respectively). An undetermined COD was more likely in those with frailty. Of the 27 undetermined COD, 22 (81.5%) were attributed to frail individuals and 5 (18.5%) to non-frail. These undetermined COD represent 43.1% of frailty-related deaths and 27.8% of non-frailty-related deaths. Conclusions Older people with frailty living in Tanzania are more likely to die from non-communicable diseases compared to non-frail older people. Although employing SmartVA to analyse VA data from this population was feasible, it faced challenges ascribing COD to all participants. This limitation may be due to the multi-morbidity often present in older populations where multiple factors combine to cause mortality.

Irradiation Spillover Effect in Photo‐Assisted Ion Batteries: Overcoming Size Limits for Solar Utilization

AbstractPhoto‐assisted ion batteries demonstrate remarkable potential for portable and decentralized solar energy utilization, due to their profound capacity enhancement under irradiation accompanied by promoted discharge voltages. However, ion batteries in practice are highly compact with limited surface area for irradiation. Overcoming the size limit for irradiation is a challenge. Herein, an irradiation spillover effect in photo‐assisted ion batteries is demonstrated, that is the impact of irradiation on the battery is not restrained within the irradiated area but can spillover the whole electrode. This phenomenon is a consequence of the light‐induced potential difference between irradiated and unirradiated regions, leading to selective ion insertion. Irradiated regions favored H+ insertion due to light‐induced proton‐coupled electron transfer, while unirradiated regions preferred Zn2+ insertion. Consequently, the capacity enhancement remains unaffected by halving the irradiated area. This study overcomes the irradiation size limit for photo‐assisted ion batteries and encourages highly integrated photo‐assisted ion batteries for practice application.

A Cohort of 469 Mayer-Rokitansky-Küster-Hauser Syndrome Patients-Associated Malformations, Syndromes, and Heterogeneity of the Phenotype.

The Mayer-Rokitansky-Küster-Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.