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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Intensive longitudinal data (ILD) collected in mobile health (mHealth) studies contain rich information on the dynamics of multiple outcomes measured frequently over time. Motivated by an mHealth study in which participants self-report the intensity of many emotions multiple times per day, we describe a dynamic factor model that summarizes ILD as a low-dimensional, interpretable latent process. This model consists of (i) a measurement submodel—a factor model—that summarizes the multivariate longitudinal outcome as lower-dimensional latent variables and (ii) a structural submodel—an Ornstein–Uhlenbeck (OU) stochastic process—that captures the dynamics of the multivariate latent process in continuous time. We derive a closed-form likelihood for the marginal distribution of the outcome and the computationally-simpler sparse precision matrix for the OU process. We propose a block coordinate descent algorithm for estimation and use simulation studies to show that it has good statistical properties with ILD. Then, we use our method to analyze data from the mHealth study. We summarize the dynamics of 18 emotions using models with one, two, and three time-varying latent factors, which correspond to different behavioral science theories of emotions. We demonstrate how results can be interpreted to help improve behavioral science theories of momentary emotions, latent psychological states, and their dynamics.
Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.
Aims
We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.
Method
We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.
Results
The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.
Conclusions
Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
The EMT-ATG achieved a significant milestone with its inaugural deployment during the SIDS4 Conference in Antigua. The EMT2030 strategy and Global Health Emergency Corps (GHEC) approach underscore the importance of collaborative leadership and joint efforts among all the networks to provide a comprehensive response.
Objectives:
The primary objective of the deployment was to ensure the health and safety of SIDS4 conference attendees through a coordinated and effective emergency medical response. It also aimed to demonstrate the capability of small island countries to establish and deploy fully operational and self-sufficient EMTs in coordination with other rapid response capacities, fostering a model of collaborative leadership.
Method/Description:
Training programs, conducted in collaboration with PAHO, focused on disaster response, triage, and mass casualty management. PAHO capacity building included the procurement of medical equipment, establishment of mobile medical units, and enhancement of communication systems for seamless coordination.
In preparation for deployment, ATG-EMT conducted simulation exercises and drills which involved various stakeholders, including local health authorities, security agencies, prehospital EMS, public health rapid response teams, and community volunteers.
Results/Outcomes:
The successful deployment of ATG-EMT during the SIDS4 Conference demonstrated the team’s capability to provide high-quality medical care and support at a high-profile international event. This contributed to the health and safety of over 4,500 delegates.
Conclusion:
The deployment highlights the importance of continuous training, robust capacity building, meticulous preparation in developing an effective emergency medical response system and serves as a model for small island countries aiming to enhance their disaster response capabilities.
Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials.
Methods
Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old (N=21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder.
Results
The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience.
Conclusions
The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.
The success of deep brain stimulation (DBS) relies on applying carefully titrated therapeutic stimulation at specific targets. Once implanted, the electrical stimulation parameters at each electrode contact can be modified. Iteratively adjusting the stimulation parameters enables testing for the optimal stimulation settings. Due to the large parameter space, the currently employed empirical testing of individual parameters based on acute clinical response is not sustainable. Within the constraints of short clinical visits, optimization is particularly challenging when clinical features lack immediate feedback, as seen in DBS for dystonia and depression and with the cognitive and axial side effects of DBS for Parkinson’s disease. A personalized approach to stimulation parameter selection is desirable as the increasing complexity of modern DBS devices also expands the number of available parameters. This review describes three emerging imaging and electrophysiological methods of personalizing DBS programming. Normative connectome-base stimulation utilizes large datasets of normal or disease-matched connectivity imaging. The stimulation location for an individual patient can then be varied to engage regions associated with optimal connectivity. Electrophysiology-guided open- and closed-loop stimulation capitalizes on the electrophysiological recording capabilities of modern implanted devices to individualize stimulation parameters based on biomarkers of success or symptom onset. Finally, individual functional MRI (fMRI)-based approaches use fMRI during active stimulation to identify parameters resulting in characteristic patterns of functional engagement associated with long-term treatment response. Each method provides different but complementary information, and maximizing treatment efficacy likely requires a combined approach.
Validated yes/no vocabulary tests that measure bilinguals’ language proficiency based on vocabulary knowledge have been widely used in psycholinguistic research. However, it is unclear what aspects of test takers’ vocabulary knowledge are employed in these tests, which makes the interpretation of their scores problematic. The present study investigated the contribution of bilinguals’ form-meaning knowledge to their item accuracy on a Malay yes/no vocabulary test. Word knowledge of Malay first- (N = 80) and second-language (N = 80) speakers were assessed using yes/no, meaning recognition, form recognition, meaning recall and form recall tests. The findings revealed that 59% of the variance in the yes/no vocabulary test score was explained by the accuracy of the meaning recognition, form recognition and meaning recall tests. Importantly, the item analysis indicated that yes/no vocabulary tests assess primarily knowledge of form recognition, supporting its use as a lexical proficiency measure to estimate bilinguals’ receptive language proficiency.
Interprofessional teams in the pediatric cardiac ICU consolidate their management plans in pre-family meeting huddles, a process that affects the course of family meetings but often lacks optimal communication and teamwork.
Methods:
Cardiac ICU clinicians participated in an interprofessional intervention to improve how they prepared for and conducted family meetings. We conducted a pretest–posttest study with clinicians participating in huddles before family meetings. We assessed feasibility of clinician enrollment, assessed clinician perception of acceptability of the intervention via questionnaire and semi-structured interviews, and impact on team performance using a validated tool. Wilcoxon rank sum test assessed intervention impact on team performance at meeting level comparing pre- and post-intervention data.
Results:
Totally, 24 clinicians enrolled in the intervention (92% retention) with 100% completion of training. All participants recommend cardiac ICU Teams and Loved ones Communicating to others and 96% believe it improved their participation in family meetings. We exceeded an acceptable level of protocol fidelity (>75%). Team performance was significantly (p < 0.001) higher in post-intervention huddles (n = 30) than in pre-intervention (n = 28) in all domains. Median comparisons: Team structure [2 vs. 5], Leadership [3 vs. 5], Situation Monitoring [3 vs. 5], Mutual Support [ 3 vs. 5], and Communication [3 vs. 5].
Conclusion:
Implementing an interprofessional team intervention to improve team performance in pre-family meeting huddles is feasible, acceptable, and improves team function. Future research should further assess impact on clinicians, patients, and families.
Seed genebanks must maintain collections of healthy seeds and regenerate accessions before seed viability declines. Seed shelf life is often characterized at the species level; however, large, unexplained variation among genetic lines within a species can and does occur. This variation contributes to unreliable predictions of seed quality decline with storage time. To assess variation of seed longevity and aid in timing regeneration, ten varieties of pea (Pisum sativum L.), chickpea (Cicer arietinum L.) and lentil (Lens culinaris Medikus subsp. culinaris) from the Australian Grains Genebank were stored at moderate temperature (20°C) and moisture (7–11% water, relative humidity [RH] ~30%) and deterioration was assessed by yearly germination tests for 20 years. Decline in germination was fit to a sigmoidal model and the time corresponding to 50% germination (P50) was used to express seed longevity for each genetic line. The feasibility of using RNA fragmentation to assess changed seed health was measured using RNA integrity number (RIN) from RNA extracted from seeds that were stored for 13 and 20 years. Seed lots of legume grains that maintained high survival throughout the 20 years (i.e. they aged slower than other lines) had higher RIN than samples that degraded faster. RIN was lower in embryonic axes compared with cotyledons in the more deteriorated samples, perhaps indicating that axes exhibit symptoms of ageing sooner than cotyledons. Overall, RIN appears to be associated with longevity indicators of germination for these legumes and indicating that RIN decline can be used to assess ageing rate, which is needed to optimize viability monitoring.
This study aimed to determine the feasibility of using Chat Generative Pre-trained Transformer (ChatGPT) (https://chatgpt.com) as a patient resource for paediatric otolaryngology conditions and assess the quality of responses generated by ChatGPT when compared with information available on the internet.
Method
ChatGPT responses to common paediatric otolaryngology conditions were compared with top internet pages for readability (Flesch Reading Ease score, word count), expediency (time taken to generate response), validity (comparison of recommendations to the American Academy of Otolaryngology Head and Neck Surgery guidelines) and consistency (changes in recommendations based on question variation).
Results
ChatGPT was more expeditious in generating responses with fewer words, albeit with higher reading scores. When compared with accredited guidelines, there was no difference in validity between these sources (internet sources and ChatGPT). Consistent responses were obtained with question variation.
Conclusion
ChatGPT may be a valuable source for patients and families in providing valid information comparable to internet materials.
Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation.
Aims
To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions.
Method
We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs).
Results
Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins.
Conclusions
These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.
Rinsing only with water or washing with soap and water are common methods of skin decontamination for skin contaminated during a chemical hazard release. The null hypothesis was that a 15-minute water irrigation (decontamination method 1) would not be superior to decontamination using a microfiber towel, followed by a wet wipe (Signature Select Softly Flushable Tissue Better Living Brands LLC, Pleasanton, CA), followed by using another microfiber towel (decontamination method 2).
Methods
A simulated contaminant (Magic Fluorescent Glow Paint for Face and Body, iLC Shenzhen Fulimei Technology Co. LTD, Shenzhen, the People’s Republic of China) was applied to the dorsal skin of each subject’s forearms. Then, photographs of these subject’s skin were taken before and after decontamination of the simulated contaminant by using either decontamination method 1 or 2. Each of the subjects underwent both decontamination methods in separate trials, with each subject using one forearm for decontamination method 1 and their other forearm for decontamination method 2. Discrete points of contamination were quantified on the photographs that were taken with the skin illuminated by ambient visible light or ultraviolet light (395nm, Roceei ultraviolet flashlight, China).
Results
Under visible light, no residual contamination was seen by inspecting photographs taken after decontaminating with either method. Under ultraviolet light, less visible contamination was seen by inspecting photographs taken after decontaminating with method 1 than after decontaminating with method 2.
Conclusion
In this study, skin decontamination with water irrigation was superior to skin decontamination without water irrigation.
We recently showed that adherence to the Mediterranean diet increased the proportion of plasma n-3 PUFA, which was associated with an improved intestinal barrier integrity. In the present exploratory analysis, we assessed faecal fatty acids in the same cohort, aiming to investigate possible associations with intestinal barrier integrity. Women from the Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) randomised controlled trial, characterised by an impaired intestinal barrier integrity, followed either a Mediterranean diet (intervention group, n 33) or a standard diet (control group, n 35). At baseline (BL), month 3 (V1) and month 12 (V2), plasma lipopolysaccharide-binding protein, faecal zonulin and faecal fatty acids were measured. In the intervention group, faecal proportions of palmitoleic acid (16:1, n-7) and arachidonic acid (20:4, n-6) decreased, while the proportion of linoleic acid (18:2, n-6) and α linoleic acid (18:3, n-3) increased (BL-V1 and BL-V2, all P < 0·08). In the control group, faecal proportions of palmitic acid and arachidic acid increased, while the proportion of linoleic acid decreased (BL-V1, all P < 0·05). The decrease in the proportion of palmitoleic acid correlated with the decrease in plasma lipopolysaccharide-binding protein (ΔV1-BL r = 0·72, P < 0·001; ΔV2-BL r = 0·39, P < 0·05) and correlated inversely with adherence to the Mediterranean diet (Mediterranean diet score; ΔV1-BL r = –0·42, P = 0·03; ΔV2-BL r = -0·53, P = 0·005) in the intervention group. Our data show that adherence to the Mediterranean diet induces distinct changes in the faecal fatty acid composition. Furthermore, our data indicate that the faecal proportion of palmitoleic acid, but not faecal n-3 PUFA, is associated with intestinal barrier integrity in the intervention group.
Seismic imaging in 3-D holds great potential for improving our understanding of ice sheet structure and dynamics. Conducting 3-D imaging in remote areas is simplified by using lightweight and logistically straightforward sources. We report results from controlled seismic source tests carried out near the West Antarctic Ice Sheet Divide investigating the characteristics of two types of surface seismic sources, Poulter shots and detonating cord, for use in both 2-D and 3-D seismic surveys on glaciers. Both source types produced strong basal P-wave and S-wave reflections and multiples recorded in three components. The Poulter shots had a higher amplitude for low frequencies (<10 Hz) and comparable amplitude at high frequencies (>50 Hz) relative to the detonating cord. Amplitudes, frequencies, speed of source set-up, and cost all suggested Poulter shots to be the preferred surface source compared to detonating cord for future 2-D and 3-D seismic surveys on glaciers.
Despite major advancements in surgery and anesthesia, the risk of mortality following cardiac and non-cardiac surgery remains high and is frequently associated with perioperative organ dysfunction. Neurological derangements range from brief postoperative delirium to postoperative cognitive dysfunction to perioperative stroke with associated impact on quality of life and mortality. Major adverse cardiac events and arrhythmias play a significant role in adverse clinical outcomes following all surgical procedures. GI dysfunction represents one of the more common complications following surgery, while hepatic dysfunction remains infrequent but largely uninvestigated. Perioperative endocrine dysfunction consists of both hyperglycemia and hypoglycemia, both of which can have significant effects on perioperative course and recovery. Postoperative pulmonary complications remain one of the more common perioperative complications depending on patient-related and surgical factors. Perioperative acute kidney injury is common in the perioperative setting. This chapter briefly explores the impact of cardiac and non-cardiac surgery on individual organ systems and some of the effects of these perturbations on perioperative morbidity and mortality.
European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.
OBJECTIVES/GOALS: The objective of this study is to assess the feasibility and preliminary impact of a physiotherapy protocol for developing an individualized home-based physical activity program to increase physical activity (PA) levels in sedentary older adults with Type II Diabetes Mellitus (T2DM) living in Puerto Rico (PR). METHODS/STUDY POPULATION: This will be a pilot study with two phases. In phase 1, we will design a novel patient-centered home-based PA program protocol for adults ≥65 years with T2DM based on the Information-Motivation-Behavioral Skills model. Its content validity will be assessed through focus groups with 10 experts and 10 older adults and analyzed using a directed content analysis. Phase 2 we will be program implementation using a one-group, repeated measures design with 12 adults ≥65 years with T2DM. PA levels will be assessed by recording active minutes with a Fitbit. Risk of falls, balance, strength, and physical function will be assessed through standardized tests validated for this population. Statistical analysis will include descriptive statistics, comparisons via chi-square/Fisher’s exact test, and non-parametric tests. RESULTS/ANTICIPATED RESULTS: We expect to recruit a minimum of 12 participants and to administer the program for 12 weeks at a frequency of two visits per week. We anticipate that implementing and supervising the home-based PA protocol will be feasible as determined by recruitment and retention rates, patients’ satisfaction, and compliance with the program. We also expect that this protocol will increase physical activity levels, improve general strength, balance, physical function, and reduce the risk of falls in sedentary older adults with T2DM. DISCUSSION/SIGNIFICANCE: As the third cause of death in PR, T2DM represents a public health challenge. An effective home-based PA program may decrease morbidity and mortality rates in older adults by increasing PA and functional health. This study will provide data for planning a randomized controlled trial to assess its effectiveness in the outcomes of interest.