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Advancements in VLBI instrumentation, driven by the geodetic community’s goal of achieving positioning accuracy of 1 mm and stability of 0.1 mm/y, have led to the development of new broadband systems. Here, we assess the potential of these new capabilities for space weather monitoring. These enhanced VLBI capabilities were used to investigate interplanetary scintillation (IPS), a phenomenon caused by the scattering of radio waves due to density irregularities in the solar wind. Compact radio sources near the Sun were observed using the AuScope VLBI array in Australia, which consists of 12-meter telescopes at Hobart, Katherine, and Yarragadee. The baseline lengths between these telescopes are approximately 3400 km (Hobart–Katherine), 3200 km (Hobart–Yarragadee), and 2400 km (Katherine–Yarragadee). The observations covered solar elongations from 6.5° to 11.3° and frequencies between 3 and 13 GHz. The study focused on phase scintillation as an indicator of turbulence in the solar wind. As the solar elongation decreased, we observed an increase in the phase scintillation index, consistent with theoretical models. Importantly, the broadband system also detected IPS using relatively weak radio sources. Additionally, the phase scintillation increased with baseline length, in agreement with Kolmogorov turbulence with an index of 11/3. These findings demonstrate the effectiveness of geodetic broadband VLBI in capturing detailed features of the solar wind. This capability enables continuous space weather monitoring and advances our understanding of solar and interplanetary dynamics.
Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.
To compare rates of clinical response in children with Clostridioides difficile infection (CDI) treated with metronidazole vs vancomycin.
Design:
Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2–17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response.
Results:
One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response (P = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin (P = 0.105).
Conclusions:
In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.
Pigmentation and colouration are important to animal fitness. Colourations convey important information and impact predation risk, thermoregulation and mate selection. There are many cases of hypopigmentation across the animal kingdom, and leucism is a common form. We observed a Weddell seal (Leptonychotes weddellii) pup with cream-coloured fur, light skin and white nails multiple times in 2022 in Erebus Bay, Antarctica. The pup was observed 1 year later as a generally healthy yearling. This is the first documentation of a leucistic seal within this well-studied population and the second documentation of such colouration in this species. This seal offers a potential opportunity to observe the effects of hypopigmentation in Antarctic true seals.
Lewy body dementias (LBD) are the second most common dementia. Several genes have been associated with LBD, but little is known about their contributions to LBD pathophysiology. Each gene may transcribe multiple RNA, and LBD brains have extensive RNA splicing dysregulation. Hence, we completed the first transcriptome-wide transcript-level differential expression analysis of post-mortem LBD brains for gaining more insights into LBD molecular pathology that are essential for facilitating discovery of novel therapeutic targets and biomarkers for LBD. We completed transcript-level quantification of next-generation RNA-sequencing data from post-mortem anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) of people with pathology-verified LBD (LBD = 14; Controls = 7) using Salmon. We identified differentially expressed transcripts (DET) using edgeR and investigated their functional implications using DAVID. We performed transcriptome-wide alternative splicing analysis using DRIMseq. We identified 74 DET in ACC and 96 DET in DLPFC after Benjamini-Hochberg false discovery rate (FDR) correction (5%). There were 135 and 98 FDR-corrected alternatively spliced genes in ACC and DLPFC of LBD brains, respectively. Identified DET may contribute to LBD pathology by altering DNA repair, apoptosis, neuroplasticity, protein phosphorylation, and regulation of RNA transcription. We confirm widespread alternative splicing and absence of chronic neuroinflammation in LBD brains. Transcript-level differential expression analysis can reveal specific DET that cannot be detected by gene-level expression analyses. Therapeutic and diagnostic biomarker potential of identified DET, especially those from TMEM18, MICB, MPO, and GABRB3, warrant further investigation. Future LBD blood-based biomarker studies should prioritise measuring the identified DET in small extracellular vesicles.
Entrenched ethnoracial hierarchies that persist alongside formal democratic rules threaten commitments to democracy. Previous research has shown how marginalization and oppression harm minoritized group members, but has rarely considered the potential harm entrenched group-based hierarchies pose for democratic society overall. This paper offers two innovations. First, we argue that ethnoracial hierarchies have society-wide implications. Entrenched systems of ethnoracial marginalization undermine support for democracy and respect for democratic rights, even among members of privileged groups. Second, group consciousness conditions the effects of ethnoracial hierarchy among minoritized group members. Specifically, when minoritized individuals hold a structural dimension of group consciousness, they tend to sustain commitments to democracy. Insights from interviews with Indigenous and Afrodescendant activists and policy makers conducted during field research in Peru facilitate development of these theoretical expectations. Subsequent analysis of survey data cross-nationally throughout Latin America and over time in Bolivia demonstrates that ethnoracial hierarchies are associated with weaker democratic commitments across society, while reducing these hierarchies strengthens support for democracy. Among minoritized group members, however, structural group consciousness helps to mitigate these negative effects. This paper contributes a theoretical framework and empirical evidence concerning the challenges ethnoracial hierarchies pose for democratic commitments not only among those who belong to minoritized groups, but for people across society.
Hypertensive heart disease and hypertrophic cardiomyopathy both lead to left ventricular hypertrophy despite differing in aetiology. Elucidating the correct aetiology of the presenting hypertrophy can be a challenge for clinicians, especially in patients with overlapping risk factors. Furthermore, drugs typically used to combat hypertensive heart disease may be contraindicated for the treatment of hypertrophic cardiomyopathy, making the correct diagnosis imperative. In this review, we discuss characteristics of both hypertensive heart disease and hypertrophic cardiomyopathy that may enable clinicians to discriminate the two as causes of left ventricular hypertrophy. We summarise the current literature, which is primarily focused on adult populations, containing discriminative techniques available via diagnostic modalities such as electrocardiography, echocardiography, and cardiac MRI, noting strategies yet to be applied in paediatric populations. Finally, we review pharmacotherapy strategies for each disease with regard to pathophysiology.
Antisocial personality disorder (ASPD) is a mental condition in which a person exhibits a pattern of repeated disregard for and violation of others’ rights. The Diagnostic and Statistical Manual of Mental Disorders (DSM) provides the framework for diagnosing ASPD. The prevalence rate of ASPD is high in prisons. Genetics, epigenetics, neuroscience, sociology, epidemiology, psychology, and other behavioral science fields have attempted to find a primary etiology. Despite decades of research, the precise etiology of ASPD has not been found, and its pathophysiology remains a complex question. The interaction between genes and the environment appears to be a significant factor in the development of ASPD. Brain imaging in subjects with ASPD has revealed structural brain changes in those with ASPD. Individuals with ASPD are challenging to manage for health care providers because of their complicated clinical presentation, high comorbidity of medical and mental disorders, lack of licensed pharmacotherapies for ASPD, and increased utilization of healthcare resources. ASPD requires tremendous effort from treating clinicians. Clinicians can successfully manage individuals with ASPD if they remain aware of the unique challenges of these patients while thoughtfully applying available research.
Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.
Methods
Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.
Results
Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.
Conclusions
Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.
We present the case of 53-year-old woman with a late diagnosis of an right pulmonary artery-left atrium fistula who underwent transcatheter device closure using multi-modality imaging for pre-procedural planning and procedural guidance.
The maintenance of cross-cultural variation and arbitrary traditions in human populations is a key question in cultural evolution. Conformist transmission, the tendency to follow the majority, was previously considered central to this phenomenon. However, recent theory indicates that cognitive biases can greatly reduce its ability to maintain traditions. Therefore, we expanded prior models to investigate two other ways that cultural variation can be sustained: payoff-biased transmission and norm reinforcement. Our findings predict that both payoff-biased transmission and reinforcement can enhance conformist transmission's ability to maintain traditions. However, payoff-biased transmission can only sustain cultural variation if it is functionally related to environmental factors. In contrast, norm reinforcement readily generates and maintains arbitrary cultural variation. Furthermore, reinforcement results in path-dependent cultural dynamics, meaning that historical traditions influence current practices, even though group behaviours have changed. We conclude that environmental variation probably plays a role in functional cultural traditions, but arbitrary cultural variation is more plausibly due to the reinforcement of norm compliance.
Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.
Methods
We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.
Results
FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.
Conclusions
Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
Advances in comparative ageing research strongly depend on data quality and quantity. Across the world, zoos and aquariums gather data on the physiology, morphology, health and demography of the animals under their care to facilitate their management. Many of these data are hosted in a centralized database, the Species360 Zoological Information Management System (ZIMS). As of 2022, ZIMS held records on ~10 million individuals across 22,000 species and over 1200 member institutions, with historical animal records dating back to the mid-1800s. These millions of age-specific data could enable analyses testing hypotheses at individual and species levels and between species with vastly different life history strategies. This chapter summarizes the diversity of questions (ranging from evolutionary theories to mechanistic hypotheses) for ageing research that could be addressed using data from zoo and aquarium populations. In addition, many of these studies could inform the management and conservation of animals, not only in zoos and aquariums, but also in the wild.
We evaluated one of the first secure large language models approved for protected health information, for identifying central line-associated bloodstream infections (CLABSIs) using real clinical notes. Despite no pretraining, the model demonstrated rapid assessment and high sensitivity for CLABSI identification. Performance would improve with access to more patient data.
COVID-19 changed the epidemiology of community-acquired respiratory viruses. We explored patterns of respiratory viral testing to understand which tests are most clinically useful in the postpandemic era.
Methods:
We conducted a retrospective observational study of discharge data from PINC-AI (formerly Premier), a large administrative database. Use of multiplex nucleic acid amplification respiratory panels in acute care, including small (2–5 targets), medium (6–11), and large panels (>11), were compared between the early pandemic (03/2020–10/2020), late pandemic (11/2020–4/2021), and prepandemic respiratory season (11/2019 - 02/2020) using ANOVA.
Results:
A median of 160.5 facilities contributed testing data per quarter (IQR 155.5–169.5). Prepandemic, facilities averaged 103 respiratory panels monthly (sd 138), including 79 large (sd 126), 7 medium (sd 31), and 16 small panels (sd 73). Relative to prepandemic, utilization decreased during the early pandemic (62 panels monthly/facility; sd 112) but returned to the prepandemic baseline by the late pandemic (107 panels monthly/facility; sd 211). Relative to prepandemic, late pandemic testing involved more small panel use (58 monthly/facility, sd 156) and less large panel use (47 monthly/facility, sd 116). Comparisons among periods demonstrated significant differences in overall testing (P < 0.0001), large panel use (P < 0.0001), and small panel use (P < 0.0001).
Conclusions:
Postpandemic, clinical use of respiratory panel testing shifted from predominantly large panels to predominantly small panels. Factors driving this change may include resource availability, costs, and the clinical utility of targeting important pathogenic viruses instead of testing “for everything.”
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
The circadian timing system regulates many aspects of metabolic physiology, including the postprandial response to meals(1). Experimental inversion of circadian and behavioural rhythms by 12 hours adversely effects markers of metabolic health(2). We investigated effects of a more modest 5hour delay in behavioural cycles.
Fourteen participants completed an 8-day in-patient laboratory protocol, with controlled sleepwake opportunities, light-dark cycles, and diet. The 5-hour delay in behavioural cycles was induced by delaying sleep opportunity. We measured: melatonin to confirm central circadian phase; fasting markers and postprandial metabolism; energy expenditure; subjective sleepiness; and appetite, throughout the waking period.
After the phase delay, there was slower gastric emptying at breakfast, lower fasting plasma glucose, higher postprandial plasma glucose and triglycerides, and lower thermic effect of feeding. Any changes were abolished or attenuated within 48-72 hours. Further, we show no difference in 16 h waking energy expenditure.
These data extend our previous findings, which showed no time-of-day effect on energy expenditure in healthy adults.