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There is a paucity of research examining the patterning of socioeconomic disadvantages and mental health problems across multiple generations. The significance of research on multigenerational processes is based on a concern with if and how (dis)advantages are generated and sustained across generations, and how socioeconomic, mental health, and gender inequalities evolve over a longer period of time.
The current study therefore aimed to investigate the interconnected transmissions of socioeconomic disadvantages and mental health problems from grandparents to grandchildren through the parents, as well as the extent to which these transmissions differ according to lineage (i.e., through matrilineal/patrilineal descent) and grandchild gender.
Drawing on the Stockholm Birth Cohort Multigenerational Study, the sample included 21,416 unique lineages by grandchild gender centered around cohort members born in 1953 (parental generation) as well as their children (grandchild generation) and their parents (grandparental generation). Based on local and national register data, socioeconomic disadvantages were operationalized as low income, and mental health problems as psychiatric disorders. A series of path models based on structural equation modelling were applied to estimate the associations between low income and psychiatric disorders across generations and for each lineage-G2 gender combination.
We found a multigenerational transmission of low income through the patriline to grandchildren. Psychiatric disorders were transmitted through both the patriline and matriline, but only to grandsons. The patriline-grandson transmission of psychiatric disorders was partially operated via low income of the fathers. Furthermore, grandparents’ psychiatric disorders influenced their children’s and grandchildren’s income.
We conclude that there is evidence of transmissions of socioeconomic disadvantages and mental health problems across three generations, although these transmissions differ by lineage and grandchild gender. Our findings further highlight that grandparents’ mental health problems could cast a long shadow on their children’s and grandchildren’s socioeconomic outcomes, and that socioeconomic disadvantages in the intermediate generation may play an important role for the multigenerational transmission of mental health problems.
As an effective drag reduction and thermal protection technology, the opposing jet can guarantee the flight safety of the hypersonic vehicle. In this paper, the jet mode transition is realised by controlling the total jet pressure ratio value (PR) with a function. The jet mode transition from the long penetration mode (LPM) to the short penetration mode (SPM) uses an increasing function. However, the jet mode transition from SPM to LPM uses a decreasing function. The flow field reconstruction process of a two-dimensional axisymmetric blunt body model in the hypersonic flow is studied when the jet mode transition between SPM and LPM changes into each other. The flow field structures and wall parameters of the LPM and SPM transition processes are obtained. The results indicate that the drag and Stanton number both decrease in the transition stage from LPM to SPM, and this is beneficial for the improvement of the drag reduction and thermal protection effect. The peak values of drag and Stanton number fall by 36.39% and 46.40%, respectively. When the jet mode transforms from SPM to LPM, the Stanton number increases, and the drag force first increases and then decreases. However, the final drag reduction effect is not obvious. With the increase in the change rate of the total pressure ratio of the two jet transformation modes, the jet mode transition time is advanced, and the flow field changes more violently.
Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.
Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.
The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.
Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
OBJECTIVES/GOALS: SGLT2i therapy is currently a cornerstone in heart failure with preserved ejection fraction (HFpEF) therapy. Similarly, H2S has been shown to be beneficial in preclinical models of heart failure. With this in mind, we sought to investigate the effects of the SGLT2i and H2S donor therapy alone or in combination in a rodent model of cardiometabolic HFpEF. METHODS/STUDY POPULATION: Male C57BL/6N mice (9 weeks of age) were fed a high fat, Western diet (HFD) and received L-NG-Nitro arginine methyl ester (L-NAME) in the drinking water (0.5 g/L) to induce HFpEF. At 5 weeks, animals were randomized to either control, H2S donor (SG-1002, 90 mg/kg/d, P.O), Empagliflozin (155 mg/L, P.O), or the combination of SG-1002 and Empagliflozin for an additional 5 weeks while being maintained on HFD and L-NAME. Echocardiography, left ventricular invasive LV and systemic hemodynamics, and exercise capacity testing were performed to assess cardiovascular disease severity. Fasted glucose, circulating triglyceride and cholesterol content were similarly measured to quantify key clinical metabolic parameters. H2S and its metabolite, sulfane sulfur, were quantified to assure adequate H2S donation. RESULTS/ANTICIPATED RESULTS: Administration of SG-1002 restored H2S and sulfane sulfur to normal circulating levels. All treatment groups exhibited similar improvements in LV diastolic dysfunction as measured by E/E’and LVEDP. Combination therapy significantly improved exercise capacity whereas the monotherapy groups did not. Treatment with SG-1002 decreased fasting glucose and circulating cholesterol while all treatment groups displayed decreased circulating triglycerides and body weight compared to HFpEF control. DISCUSSION/SIGNIFICANCE: These data indicate that restoring H2S or treatment with an SGLT2i in this preclinical HFpEF model attenuates pathology. Combination of both drugs exhibited greater benefit than either monotherapy in important HFpEF parameters such as exercise capacity. Further studies are underway to characterize the benefits observed from combination therapy.
OBJECTIVES/GOALS: Ocular graft versus host disease (oGVHD) affects ~50% of individuals after an allogeneic hematopoietic stem cell transplant for treating blood cancers. OGVHD results in severe dry eye disease and decreased vision. Quantifying specific cytokine changes in tears may reveal biomarkers and future treatment targets for patients with oGVHD. METHODS/STUDY POPULATION: The goal of this study is to determine if cytokines can be measured in tears with the Isoplexis platform. This pilot validation study evaluates the tears of a patient with oGVHD utilizing the Isoplexis platform. The Isoplexis has specific advantages for tear samples including high-throughput analysis, and small sample requirements, but has yet to be validated in tears. A sample from normal and oGVHD patient tears were collected for comparison. Samples were analyzed on two separate backgrounds–standard Bovine Serum Albumin (BSA) background and artificial tears (ATs). The negative control was ATs and positive control was a concentrated cytokine solution. Analysis of 22 cytokines was performed. RESULTS/ANTICIPATED RESULTS: Analysis of 22 cytokines was performed. As expected, the cytokine levels of the ATs alone were below the limit of detection (LOD). The oGVHD patient tears showed elevated TNF-alpha, TNF-beta, perforin, MIP-1a, MIP-1β, MCP-1, IL2, IL4, IL5, IL-7A, IL9, IL-13, IL-15, IFN-γ, granzyme B, and GM-CSF with ATS background, but no cytokines above the LOD in the BSA background plate. The control tears had elevated IP-10. The elevated cytokines for the oGVHD patient corresponded to symptom severity and clinical findings. DISCUSSION/SIGNIFICANCE: These results suggest that using ATs as the background with the Isoplexis platform improves the sensitivity to detect tear cytokines. Findings of elevated IL-7A and GM-CSF in tears parallels literature findings for oGVHD. Further evaluation of samples will continue to validate the Isoplexis multiplex assay for tear cytokine analyses.
This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.
A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.
Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).
Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.
Computerized-adaptive testing (CAT) may increase reliability or reduce respondent burden for assessing patient-reported outcomes compared with static short forms (SFs). We compared CAT versus SF administration of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric measures in pediatric inflammatory bowel disease (IBD).
Participants completed 4-item CAT, 5- or 6-item CAT, and 4-item SF versions of the PROMIS Pediatric measures. We compared average T-scores, intra-class correlations (ICCs), floor and ceiling effects, and standard error of measurement (SEM) across forms, along with mean effect sizes between active versus quiescent IBD disease activity groups.
Average PROMIS T-scores across forms were <3 points (minimally important difference) of each other. All forms correlated highly with each other (ICCs ≥0.90) and had similar ceiling effects, but the CAT-5/6 had lower floor effects. The CAT-5/6 had lower SEM than the CAT-4 and SF-4, and the CAT-4 had a lower SEM than the SF-4. Mean effect sizes were similar across forms when contrasting disease activity groups.
The CAT and SF forms produced similar score results, but the CAT had better precision and lower floor effects. Researchers should consider PROMIS pediatric CAT if they anticipate that their sample will skew toward symptom extremes.
As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.
An analytical model is developed to study the sound produced by the interaction between shock and instability waves in two-dimensional supersonic jet flows. The jet is considered to be of vortex-sheet type and two-dimensional Euler equations are linearized to determine the governing equations for shock and instability waves and their interaction. Pack's model is used to describe shock waves, while instability waves are calculated using spatial stability analysis. The interaction between shock and instability waves can be solved analytically by performing Fourier transform and subsequently using the method of steepest descent. Sound produced by the interaction between the instability wave and a single shock cell is studied first, after which that due to a number of cells follows. We find that the model developed in this study can correctly predict the frequencies of the fundamental screech tone and its first and second harmonics. We show that the predicted sound directivity, even from a single shock cell, is in good agreement with experimental data. In particular, this model shows the strongest noise emission close to the upstream direction but the emitted noise starts to rapidly decay as the observer angle approaches $180^\circ$, which is in accordance with experimental results; this suggests that the effective noise from a single shock cell is far from of the monopole type as assumed in the classical Powell's model. We find that the noise directivity is very sensitive to the local growth rate of the instability waves and the noise is generated primarily through the Mach wave mechanism.
Limited studies provide direct evidence of Clonorchis sinensis adults in the early stage of gallbladder stone formation. Our current research systematically studied 33 gallbladder stones resembling adult worms and shed light on the definite connection of C. sinensis infection with concomitant cholelithiasis. A total of 33 gallbladder stones resembling adult C. sinensis worms were systematically analysed. Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray energy spectrometry were used to analyse the composition and microstructure. Meanwhile, a histopathological examination of the stone was carried out. The 33 gallbladder stones resembling adult C. sinensis worms included nine calcium carbonate (CaCO3) stones, 12 bilirubinate stones and 12 mixed stones. Clonorchis sinensis eggs were found in 30 cases, including all CaCO3 and mixed stones. Parasite tissues were detected in 12 cases, which were mainly CaCO3 stones or bilirubinate–CaCO3 mixed stones. The outer layer of stones was wrapped with 12.88% calcium salt, as revealed by X-ray energy spectrometry, while surprisingly, many C. sinensis eggs were found in the inner part of these stones. Based on our current findings, we concluded that calcification and packaging occurred after C. sinensis adult entrance into the gallbladder, subsequently leading to the early formation of CaCO3 or bilirubinate–CaCO3 mixed gallbladder stones. This discovery highlights definite evidence for C. sinensis infection causing gallbladder stones.
In this paper, sliding panels are used to increase the bending stiffness of the classic corrugated flexible skin, and the corresponding application procedure for aircraft structures is developed. After the conceptual design of the corrugated flexible skin with sliding panels is proposed, the analytical models to calculate the equivalent tensile and bending properties are investigated. At the same time, its flexibility in the corrugation direction and the load-bearing capacity (is proportional to the bending stiffness) in the direction perpendicular to corrugation are studied by numerical simulation and experiment. The application procedure is established based on geometric analysis and strain definition, and according to this procedure, the corrugated flexible skin with sliding panels is applied to the drooping leading edge to eliminate the gap on the upper skin. The results show that the corrugated flexible skin with sliding panels has more bending stiffness than the classic corrugated flexible skin in the direction perpendicular to corrugation while maintaining the deform ability in the corrugation direction, and the application procedure is effective and can be applied to other parts of the aircraft structure.
Many data-driven patient risk stratification models have not been evaluated prospectively. We performed and compared the prospective and retrospective evaluations of 2 Clostridioides difficile infection (CDI) risk-prediction models at 2 large academic health centers, and we discuss the models’ robustness to data-set shifts.
Mood episodes in bipolar disorder (BD) are still identified with subjective retrospective reports and scales. Digital biomarkers, such as actigraphy, heart rate variability, or ElectroDermal activity (EDA) have demonstrated their potential to objectively capture illness activity.
To identify physiological digital signatures of illness activity during acute episodes of BD compared to euthymia and healthy controls (HC) using a novel wearable device (Empatica´s E4).
A pragmatic exploratory study. The sample will include 3 independent groups totalizing 60 individuals: 36 BD inpatients admitted due to severe acute episodes of mania (N=12), depression (N=12), and mixed features (N=12), will wear the E4-device at four timepoints: the acute phase (T0), treatment response (T1), symptoms remission (T2) and during euthymia (T3; outpatient follow-up). 12 BD euthymic outpatients and 12 HC will be asked to wear the E4-device once. Data pre-processing included average downsampling, channel time-alignment in 2D segments, 3D-array stacking of segments, and random shuffling for training/validation sets. Finally, machine learning algorithms will be applied.
A total of 10 patients and 5 HC have been recruited so far. The preliminary results follow the first differences between the physiological digital biomarkers between manic and depressive episodes. 3 fully connected layers with 32 hidden units, ectified linear activation function (ReLU) activation, 25% dropout rate, significantly differentiated a manic from a depressive episode at different timepoints (T0, T1, T2).
New wearables technologies might provide objective decision-support parameters based on digital signatures of symptoms that would allow tailored treatments and early identification of symptoms.
Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.
To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.
RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.
A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.
RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.