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Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
To investigate the concordance between Australian government guidelines for classifying the healthiness of foods across various public settings.
Design:
Commonly available products in Australian food service settings across eight food categories were classified according to each of the seventeen Australian state and territory food classification guidelines applying to public schools, workplaces and healthcare settings. Product nutrition information was retrieved from online sources. The level of concordance between each pair of guidelines was determined by the proportion of products rated at the same level of healthiness.
Setting:
Australia.
Participants:
No human participants.
Results:
Approximately half (56 %) of the 967 food and drink products assessed were classified as the same level of healthiness across all fifteen ‘traffic light’-based systems. Within each setting type (e.g. schools), pairwise concordance in product classifications between guidelines ranged from 74 % to 100 %. ‘Vegetables’ (100 %) and ‘sweet snacks and desserts’ (78 %) had the highest concordance across guidelines, while ‘cold ready-to-eat foods’ (0 %) and ‘savoury snacks’ (23 %) had the lowest concordance. In addition to differences in classification criteria, discrepancies between guidelines arose from different approaches to grouping of products. The largest proportion of discrepancies (58 %) were attributed to whether products were classified as ‘Red’ (least healthy) or ‘Amber’ (moderately healthy).
Conclusions:
The results indicate only moderate concordance between all guidelines. National coordination to create evidence-based consistency between guidelines would help provide clarity for food businesses, which are often national, on how to better support community health through product development and reformulation.
Wetlands in hypersaline environments are especially vulnerable to loss and degradation, as increasing coastal urbanization and climate change rapidly exacerbate freshwater supply stressors. Hypersaline wetlands pose unique management challenges that require innovative restoration perspectives and approaches that consider complex local and regional socioecological dynamics. In part, this challenge stems from multiple co-occurring stressors and anthropogenic alterations, including estuary mouth closure and freshwater diversions at the catchment scale. In this article, we discuss challenges and opportunities in the restoration of hypersaline coastal wetland systems, including management of freshwater inflow, shoreline modification, the occurrence of concurrent or sequential stressors, and the knowledge and values of stakeholders and Indigenous peoples. Areas needing additional research and integration into practice are described, and paths forward in adaptive management are discussed. There is a broad need for actionable research on adaptively managing hypersaline wetlands, where outputs will enhance the sustainability and effectiveness of future restoration efforts. Applying a collaborative approach that integrates best practices across a diversity of socio-ecological settings will have global benefits for the effective management of hypersaline coastal wetlands.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Epilepsy is one of the most common serious brain illness, with symptoms influenced by multiple risk factors and a strong genetic predisposition, rather than having a single expression and cause¹. Neuropsychiatric symptoms in epilepsy can encompass manifestations such as mood alterations, anxiety, sleep disturbances, psychosis, and behavioral disorders. While the motor and sensory manifestations of epileptic seizures are widely recognized, neuropsychiatric symptoms accompanying epilepsy are often underestimated. Therefore, it is essential to understand the most prevalent epidemiological profile of these patients to improve the diagnosis and management of these symptoms.
Objectives
Our goal was to evaluate the neuropsychiatric behavior of epilepsy patients in Brazilian over the past 3 years through hospitalization data in order to outline an epidemiological and behavioral profile.
Methods
A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals simultaneously diagnosed with epilepsy, schizotypal and delusional disorders, and mood disorders in all five regions of Brazil (South, Southeast, Midwest, North, and Northeast) between February 2020 and December 2022. Data from January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of care, age range, gender, and ethnicity of the patients.
Results
The analysis covers the years 2020 to 2022, totaling 503,045 hospitalizations. In 2022, the highest number of cases occurred (≈ 37.55%), followed by 2021 (≈ 33.62%) and 2020 (≈ 28.81%). Urgent hospitalizations represented ≈ 90.85% of the total. The most affected age group was 30 to 39 years old (≈ 18.30%). Men were more affected than women (≈ 52.03% and ≈ 47.96%, respectively), and Caucasians accounted for ≈ 36.07% of the hospitalizations. The average length of stay was 19.1 days, and the mortality rate was 1.4%.
Conclusions
Thus, there is a gradual and annual increase in the number of hospitalizations during the observed period. While there is a minimal disparity between the affected genders, it is evident that the profile of male, caucasian, and adult patients is the most prevalent. Moreover, the predominantly urgent nature of hospitalizations points to an alarming scenario regarding this issue. From the analysis of the data obtained in the study, there is a clear need for interventions capable of reducing the prevalence of hospitalizations for neuropsychiatric symptoms in epilepsy patients in Brazil.
Neuropsychiatric disorders are the leading cause of disability worldwide, as seen in cases such as depression, anxiety, bipolar mood disorder and schizophrenia, which can be developed or exacerbated by the use of psychoactive substances. Most mental disorders have an early onset, often leading to early and/or permanent disability, increasing the need and cost of healthcare. Therefore, it is necessary to improve the identification of the epidemiological profile of these cases in the South of Brazil in order to enhance the diagnosis and reduce the costs associated with managing these disorders.
Objectives
The present study aimed to analyze statistical data regarding hospitalizations related to mental disorders caused by the use of psychoactive substances and alcohol in the southern region of Brazil, highlighting the pathological scenario and identifying the most prevalent profiles of these disorders in this region.
Methods
A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals diagnosed with mental and behavioral disorders due to the use of psychoactive substances and alcohol in the states of the Southern region of Brazil (Paraná, Santa Catarina, and Rio Grande do Sul) between February 2020 and December 2022. Data of January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of the care, age range, gender, and ethnicity of the patients.
Results
The study covers the years 2020 to 2022, indicating a total of 81,608 hospitalizations, with the year 2022 having the highest number of cases (≈ 37.13%), followed by 2021 (≈ 33.30%) and 2020 (≈ 29.55%). The states with the highest number of hospitalizations were Rio Grande do Sul (≈ 54.90%), Paraná (≈ 29.29%), and Santa Catarina (≈ 15.79%). Urgent hospitalizations accounted for ≈ 87.29% of the total. The most affected age group was 30 to 39 years old (≈ 25.61%). Men were more affected than women (≈ 81.70% and ≈ 18.28%, respectively). Caucasians accounted for ≈ 64.29% of the hospitalizations. The average length of stay was 20.8 days, and the mortality rate was 0.32%.
Conclusions
There is a clear increase in the number of hospitalizations related to mental disorders caused by the use of psychoactive substances in the period from 2020 to 2022 in the southern region of Brazil, with the highest number of cases in the state of Rio Grande do Sul. The most affected population consisted of Caucasian men aged 30 to 39 years old. Furthermore, these results may be related to the increasing trend of psychoactive substance use among the Brazilian population and also the COVID-19 pandemic, which led to a period of underreporting due to social isolation.
In recent years, mental health has gained prominence in public health, prompting thorough investigations into psychiatric condition trends. This study conducts a comprehensive epidemiological analysis of hospitalizations for Schizophrenia, Schizotypal, and Delirium Disorders in Rio Grande do Sul (RS) over the past five years. By revealing these patterns, it enhances our understanding of regional mental health dynamics and offers insights for intervention strategies, resource planning, and improved mental healthcare. The ultimate goal is to advance more effective and accessible mental healthcare in RS and beyond.
Objectives
This study aims to analyze the prevalence and epidemiological profile of hospitalizations due to psychiatric disorders to assist in the diagnosis and outcome of affected patients.
Methods
A cross-sectional, descriptive, retrospective, and quantitative study was conducted regarding hospitalizations for Schizophrenia, Schizotypal Disorders, and Delirium in the state of RS between January 2018 and November 2022. Data were collected from the Department of Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, focusing on the nature of care, age group, gender, and ethnicity of the patients. The information was aggregated over the five-year period based on the four mentioned descriptors and subsequently analyzed to establish a profile of hospitalizations during that period.
Results
The analysis spans from 2018 to 2022, encompassing a total of 28,345 hospitalizations. In 2019, there was the highest number of cases (22.21%), followed by 2018 (21.08%). Urgent care admissions constituted 85.34% of the total. The age group most affected was 35 to 39 years (11.8%). Men were more affected than women (60.18%), and the majority of hospitalizations were among the Caucasian ethnicity (75.12%). The average length of stay was 23.7 days, and the mortality rate stood at 0.26%.
Conclusions
The increasing trend in hospitalizations, peaking in 2019, highlights the need for preventive measures. Urgent admissions (85.34%) underscore the demand for accessible mental health resources. Men in the 35 to 39 age group are disproportionately affected, suggesting specific risk factors. The predominance of Caucasian ethnicity emphasizes the need for culturally sensitive care. A longer average length of stay (23.7 days) underscores treatment complexity, while a low mortality rate (0.26%) signals effective medical care. In essence, these findings inform tailored mental health policies to enhance service quality and prioritize patient-centered approaches.
In recent years, there has been an increase in the prevalence of illicit use of fentanyl and other opioids in the United States population. This has led to an increase in medical, psychopathological and abuse-associated comorbidity, an increase in deaths and a decrease in the age of consumption, and has become a serious emerging problem in young people.
We present the case of an 18-year-old woman from the United States who recently settled in Spain and started a follow-up in Mental Health due to opioid and other substance abuse problems.
Objectives
To address the growing problem surrounding the illicit use of fentanyl and opioids as drugs of abuse based on the presentation of the clinical case mentioned above.
Methods
Bibliographic search and description of a clinical case of a patient under follow-up by Mental Health at the “Hospital Clínico Universitario de Valladolid”.
Results
An 18-year-old woman from the United States who has been living with her father in Spain since the summer of 2023, having moved to Spain due to problems related to substance abuse.
With no previous medical or surgical history and with a history of follow-up in Mental Health in her country of origin for depressive symptomatology, dysfunctional personality traits and abuse of different toxic substances since adolescence.
After a brief and erratic follow-up in Psychiatry for anxious-depressive symptoms reactive to a complex and conflictive relationship with his mother and marked academic difficulties during the first years of adolescence, at the age of 15 he started using cannabis and alcohol, thus beginning a period marked by relationships with marginalized sectors of the population, substance abuse and school failure.
As his cannabis consumption intensified, he began to consume fentanyl prescribed to his mother, as well as other opioids to which he had access illegally, for which reason he had to be admitted twice to detoxification centers without results, which is why his family finally decided to move him to Spain.
Conclusions
In recent years, fentanyl abuse has become a serious public health problem that is mainly centered in the young population.
High levels of impulsivity and lack of frustration tolerance predispose to the use of illicit substances for elusive purposes.
Substance abuse carries with it not only an important organic comorbidity, but also a marked socio-familial and economic repercussion.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
Medical researchers are increasingly prioritizing the inclusion of underserved communities in clinical studies. However, mere inclusion is not enough. People from underserved communities frequently experience chronic stress that may lead to accelerated biological aging and early morbidity and mortality. It is our hope and intent that the medical community come together to engineer improved health outcomes for vulnerable populations. Here, we introduce Health Equity Engineering (HEE), a comprehensive scientific framework to guide research on the development of tools to identify individuals at risk of poor health outcomes due to chronic stress, the integration of these tools within existing healthcare system infrastructures, and a robust assessment of their effectiveness and sustainability. HEE is anchored in the premise that strategic intervention at the individual level, tailored to the needs of the most at-risk people, can pave the way for achieving equitable health standards at a broader population level. HEE provides a scientific framework guiding health equity research to equip the medical community with a robust set of tools to enhance health equity for current and future generations.
With the efflorescence of palaeoscientific approaches to the past, historians have been confronted with a wealth of new evidence on both human and natural phenomena, from human disease and migration to landscape change and climate. These new data require a rewriting of our narratives of the past, questioning what constitutes an authoritative historical source and who is entitled to recount history to contemporary societies. Humanities-based historical inquiry must embrace this new evidence, but to do so historians need to engage with it critically, just as they do with textual and material sources. This article highlights the most vital methodological issues, ranging from the spatiotemporal scales and heterogeneity of the new evidence to the new roles attributed to quantitative methods and the place of scientific data in narrative construction. It considers areas of study where the palaeosciences have “intruded” into fields and subjects previously reserved for historians, especially socioeconomic, climate, and environmental history. The authors argue that active engagement with new approaches is urgently needed if historians want to contribute to our evolving understanding of the challenges of the Anthropocene.
Montmorillonite-based catalysts were compared with an acidic ion-exchange resin of the type used industrially for the production of methyl t-butyl ether (MTBE) from methanol and isobutene or t-butanol. When 1,4-dioxan was used as solvent, Al3+-exchanged montmorillonites had about half the efficiency of the resin Amberlyst 15 at 60°C; they were, however, about twice as efficient at this temperature at Ti3+-montmorillonite or K10, a commercially available acid-treated bentonite. Montmorillonite exchanged with Chlorhydrol solutions to give interlayer [Al13O4(OH)2(H2O)12]7+ ions and pillared clays derived from such materials were poor catalysts, as was K306, a more drastically acid-treated bentonite- based commercial catalyst. Freeze-drying of the Al3+-clay before reaction to produce a more open, porous structure had no effect on its catalytic efficiency. The activation energy for the reaction of isobutene and methanol in dioxan was 44 kj/mole for an Al3+-clay catalyst compared with 25 kJ/mole for reactions catalyzed by Amberlyst 15. With no solvent (as in industrial processes), the rates of reaction were considerably slower for both the clay- and resin-catalyzed reactions. As has been found previously for resin-catalyzed reactions using stoichiometric amounts or an excess of methanol, the rate was proportional to the isobutene concentration, and the rate-determining step appeared to be protonation of the alkene. The performance of the Al3+-clay catalyst was increased by reducing the water content of the clay. In most reactions the clay catalysts were equilibrated at 12% relative humidity. Exposure of the clay to a low vacuum (10−1 torr) before use increased its catalytic activity from 50 to 60% of that of Amberlyst 15.
The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.
Methods
We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.
Results
In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.
Conclusion
Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.
Helium or neopentane can be used as surrogate gas fill for deuterium (D2) or deuterium-tritium (DT) in laser-plasma interaction studies. Surrogates are convenient to avoid flammability hazards or the integration of cryogenics in an experiment. To test the degree of equivalency between deuterium and helium, experiments were conducted in the Pecos target chamber at Sandia National Laboratories. Observables such as laser propagation and signatures of laser-plasma instabilities (LPI) were recorded for multiple laser and target configurations. It was found that some observables can differ significantly despite the apparent similarity of the gases with respect to molecular charge and weight. While a qualitative behaviour of the interaction may very well be studied by finding a suitable compromise of laser absorption, electron density, and LPI cross sections, a quantitative investigation of expected values for deuterium fills at high laser intensities is not likely to succeed with surrogate gases.
To present validation evidence for the first eight cognitive measures available through Mobile Toolbox (MTB). These measures use a remote self-administered platform to assess language, working memory, episodic memory, executive function, and processing speed.
Participants and Methods:
We used two separate samples, recruited as part of a larger study, to validate MTB measures. Sample I, comprised of 92 English-speaking adults ages 18-85, was used to assess internal consistency and construct validity. Participants were first administered “gold standard” cognitive measures (Wechsler Memory Scale-IV Verbal Paired Associates I and II; Wechsler Adult Intelligence Scale-IV Symbol Search, Digit Span, Coding, and Letter-Number Sequencing; Delis-Kaplan Executive Function System Color-Word Interference Test, Peabody Picture Vocabulary Test, Wechsler Individual Achievement Test-4 Spelling, and the Wisconsin Card Sorting Test), after which they completed MTB (pre-loaded on a study-provided smartphone) on their own. Internal consistency was evaluated using measure-appropriate indices (split-half reliability, Cronbach’s alpha or IRT-based indices). Pearson correlation coefficients between MTB tests and measures of similar constructs were used to evaluate concurrent validity. For two tests with timing-dependent scores, Arrow Matching and Shape-Color Sorting, separate analyses were performed for iOS and Android devices. Sample II, with 1,120 English-speaking participants ages 18-90, was used to evaluate age-related change. Participants completed MTB measures remotely on their own smartphones, in a preset order, within a 14-day period. Spearman correlation coefficients, corrected for education, were calculated to evaluate relationships between age and test scores.
Results:
Sample I participants were 67% female, 52% white, 99% non-Hispanic; average age=48 (SD= 17). Education was: < high school (1%); high school (55%); some college (21%); college (15%); graduate degree (8%). Internal consistency estimates ranged from 0.81 to 0.99. Pearson correlations between MTB and external measures ranged from 0.41 to 0.86 (all p < .01). Of the timed tests, only Shape-Color sorting showed significant score differences between Android and iOS devices. Sample II was 57% female, 13% Hispanic, 72% white, mean age = 45 (SD = 21). Education distribution was: < high school (2%); high school (34%); some college (34%), college (20%); graduate degree (11%). Measures of executive function (r = -0.50; r=-0.57) and processing speed (r= -0.61) showed the expected negative correlation with age (all p <0.001). Negative correlations, although weaker, were also seen on measures of working memory (r=-0.2) and episodic memory (r=-0.2, r=-0.37; p.<.001). Vocabulary performance improved with age (r=0.4; p<.001), while spelling scores remained stable (r=0.09).
Conclusions:
Initial studies support the validity and reliability of the first eight MTB cognitive measures in two diverse samples. MTB tests showed satisfactory construct validity, as demonstrated by the associations between MTB and well-established tests. Furthermore, most MTB measures correlated with age in the expected directions. Executive function, processing speed and memory typically decrease with age and this decrease was reflected in MTB test performance. In contrast, spelling and vocabulary, typically preserved as we age, did not decrease in our sample. Our results support the use of MTB in cognitive aging research.
Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:
High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:
Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:
Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.
Methods:
This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.
Results:
Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).
Conclusions:
Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
The curse of dimensionality confounds the comprehensive evaluation of computational structural mechanics problems. Adequately capturing complex material behavior and interacting physics phenomenon in models can lead to long run times and memory requirements resulting in the need for substantial computational resources to analyze one scenario for a single set of input parameters. The computational requirements are then compounded when considering the number and range of input parameters spanning material properties, loading, boundary conditions, and model geometry that must be evaluated to characterize behavior, identify dominant parameters, perform uncertainty quantification, and optimize performance. To reduce model dimensionality, global sensitivity analysis (GSA) enables the identification of dominant input parameters for a specific structural performance output. However, many distinct types of GSA methods are available, presenting a challenge when selecting the optimal approach for a specific problem. While substantial documentation is available in the literature providing details on the methodology and derivation of GSA methods, application-based case studies focus on fields such as finance, chemistry, and environmental science. To inform the selection and implementation of a GSA method for structural mechanics problems for a nonexpert user, this article investigates five of the most widespread GSA methods with commonly used structural mechanics methods and models of varying dimensionality and complexity. It is concluded that all methods can identify the most dominant parameters, although with significantly different computational costs and quantitative capabilities. Therefore, method selection is dependent on computational resources, information required from the GSA, and available data.
Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.