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Large-eddy simulation (LES) is performed to study the tip vortex flow in a ducted propulsor geometry replicating the experiments of Chesnakas & Jessup (2003, pp. 257–267), Oweis et al. (2006a J. Fluids Engng128, 751–764) and Oweis et al. (2006b J. Fluids Engng128, 751–764). Inception of cavitation in these marine propulsion systems is closely tied to the unsteady interactions between multiple vortices in the tip region. Here LES is used to shed insight into the structure of the tip vortex flow. Simulation results are able to predict experimental propeller loads and show agreement with laser Doppler velocimetry measurements in the blade wake at design advance ratio, $J=0.98$. Results show the pressure differential across the blade produces a leakage vortex which separates off the suction side blade tip upstream of the trailing edge. The separation sheet aft of the primary vortex separation point is shown to take the form of a skewed shear layer which produces a complex arrangement of unsteady vortices corotating and counter-rotating with the primary vortex. Blade tip boundary layer vortices are reoriented to align with the leakage flow and produce instantaneous low-pressure regions wrapping helically around the primary vortex core. Such low-pressure regions are seen both upstream and downstream of the propeller blade trailing edge. The trailing edge wake is found to only rarely have a low-pressure vortex core. Statistics of instantaneous low pressures below the minimum mean pressure are found to be concentrated downstream of the blade’s trailing edge wake crossing over the primary vortex core and continue in excess of 40 % chord length behind the trailing edge. The rollup of the leakage flow duct boundary layer behind the trailing edge is also seen to produce counter-rotating vortices which interact with the primary leakage vortex and contribute to strong stretching events.
Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.
Methods
We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.
Results
Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.
Conclusions
Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.
Gastrointestinal infections significantly impact African low- and middle-income countries, although, accurate data on acute gastrointestinal illness (AGI) for all ages are lacking. This study aimed to describe the epidemiology of AGI in Ethiopia, Mozambique, Nigeria, and Tanzania. A population survey was conducted in one urban and one rural site per country, from 01 October 2020 to 30 September 2021, using web-based and face-to-face tools (n = 4417). The survey tool was adapted from high-income countries, ensuring comparability through an internationally recommended AGI case definition. Ethiopia had the highest AGI incidence (0.87 episodes per person-year), followed by Mozambique (0.58), Tanzania (0.41), and Nigeria (0.34). Age-standardized incidence was highest in Mozambique (1.46) and Ethiopia (1.25), compared to Tanzania (0.58) and Nigeria (0.33). The 4-week prevalence was 6.4% in Ethiopia and 4.3% in Mozambique, compared to 3.1% in Tanzania and 2.6% in Nigeria. AGI lasted an average of 5.3 days in Ethiopia and 3.0 to 3.4 days elsewhere. Children under five had 4.4 times higher AGI odds (95% CI: 2.8, 6.7) than those aged 15-59. The study provides empirical data on the incidence and demographic determinants of AGI in these four countries.
Objectives/Goals: Methicillin-resistant Staphylococcus aureus (MRSA) is a human bacterial pathogen and is classified as a serious threat. MRSA has become resistant to most B-lactam antibiotics (penicillins and cephalosporins). The goal of this study is to identify an antibiotic adjuvant capable of resurrecting B-lactams for the treatment of MRSA infections. Methods/Study Population: A fluorescence-reporter assay was used to screen a compound library. Minimum-inhibitory concentrations were assessed for the compounds against various MSSA and MRSA strains. A common resistance mechanism to B-lactams by MRSA is by the function of the bla operon. One gene in this operon encodes for a B-lactam sensor/signal transducer protein BlaR, the primary target of this study. Inhibition of BlaR by compound 1 (best potentiator of oxacillin) was studied by nano-differential scanning fluorimetry (nanoDSF), surface plasmon resonance (SPR), scanning electron microscopy (SEM), and time-kill assays. Results/Anticipated Results: We identified 80 compound hits from a 1,974-compound NCI library. Twenty-four compounds showed potentiating ability (2- to 4,096-fold decrease in MIC for oxacillin). Seven compounds exhibited melting temperature shifts by nanoDSF of BlaR, indicating binding. SPR determined compound 1 has a binding affinity of 31 micromolar to BlaR-SD. SEM images showed disruption in the S. aureus cell wall on exposure to compound 1 and oxacillin. S. aureus N315 showed 3-log reduction in bacterial count treated with a mixture of compound 1 and oxacillin. Discussion/Significance of Impact: Compound 1 targets BlaR-SD, which restores S. aureus susceptibility to treatment by oxacillin. There are currently few antibiotics available in the clinic capable of treating MRSA infections. The combination hold promise of a treatment option for MRSA.
The need for collaborative and transparent sharing of COVID-19 clinical trial and large-scale observational study data to accelerate scientific discovery and inform clinical practice is critical. Responsible data-sharing requires addressing challenges associated with data privacy and confidentiality, data linkage, data quality, variable harmonization, data formats, and comprehensive metadata documentation to produce a high-quality, contextually rich, findable, accessible, interoperable, and reusable (FAIR) dataset. This communication explores the experiences and lessons learned from sharing National Heart Lung and Blood Institute (NHLBI) COVID-19 clinical trial (including adaptive platform trials) and cohort study datasets through the NHLBI BioData Catalyst® (BDC) ecosystem, focusing on the challenges and successes of harmonizing these datasets for broader research use. Our findings highlight the importance of establishing standardized data formats, adopting common data elements and creating and maintaining robust data governance structures that address common challenges (i.e., data privacy and data-sharing limitations resulting from informed consent). These efforts resulted in a set of comprehensive and interoperable datasets from 5 clinical trials and 13 cohort studies that will enable downstream reuse in analyses and collaborations. The principles and strategies outlined, derived through experience with consortia data, can lay the groundwork for advancing collaborative and efficient data sharing.
We conduct a laboratory experiment among male participants to investigate whether rewarding schemes that depend on work performance—in particular, tournament incentives—induce more stress than schemes that are independent of performance—fixed payment scheme. Stress is measured over the entire course of the experiment at both the hormonal and psychological level. Hormonal stress responses are captured by measuring salivary cortisol levels. Psychological stress responses are measured by self-reported feelings of stress and primary appraisals. We find that tournament incentives induce a stress response whereas a fixed payment does not induce stress. This stress response does not differ significantly across situations in which winners and losers of the tournament are publically announced and situations in which this information remains private. Biological and psychological stress measures are positively correlated, i.e. increased levels of cortisol are associated with stronger feelings of stress. Nevertheless, neither perceived psychological stress nor elevated cortisol levels in a previous tournament predict a subsequent choice between tournaments and fixed payment schemes, indicating that stress induced by incentives schemes is not a relevant criterion for sorting decisions in our experiment. Finally, we find that cortisol levels are severely elevated at the beginning of the experiment, suggesting that participants experience stress in anticipation of the experiment per se, potentially due to uncertainties associated with the unknown lab situation. We call this the novelty effect.
We conduct a laboratory experiment among male participants to investigate whether rewarding schemes that depend on work performance—in particular, tournament incentives—induce more stress than schemes that are independent of performance—fixed payment scheme. Stress is measured over the entire course of the experiment at both the hormonal and psychological level. Hormonal stress responses are captured by measuring salivary cortisol levels. Psychological stress responses are measured by self-reported feelings of stress and primary appraisals. We find that tournament incentives induce a stress response whereas a fixed payment does not induce stress. This stress response does not differ significantly across situations in which winners and losers of the tournament are publicly announced and situations in which this information remains private. Biological and psychological stress measures are positively correlated, i.e., increased levels of cortisol are associated with stronger feelings of stress. Nevertheless, neither perceived psychological stress nor elevated cortisol levels in a previous tournament predict a subsequent choice between tournaments and fixed payment schemes, indicating that stress induced by incentives schemes is not a relevant criterion for sorting decisions in our experiment. Finally, we find that cortisol levels are severely elevated at the beginning of the experiment, suggesting that participants experience stress in anticipation of the experiment per se, potentially due to uncertainties associated with the unknown lab situation. We call this the novelty effect.
Attention deficit/hyperactivity disorder (ADHD) prevalence has increased in the last 10 years, most likely due to increased recognition by clinicians. Even so, an issue with under-diagnostics may persist. Historically ADHD has been described as a male-dominant disorder. However, recent evidence shows that ADHD prevalence is similar between the sexes, but that the related impairment or symptomatology might vary. This study estimated the prevalence of undiagnosed ADHD symptoms (pADHD) and explored the sex-stratified symptomatology and associations with self-perceived health-related quality of life (HRQL) and experience of depressive symptoms.
Methods
This was done in a unique cohort of 50,937 healthy blood donors – individuals who successfully maintain regular commitments despite potential ADHD symptoms. ADHD symptoms were estimated using the Adult ADHD Self-Report Scale (ASRS), health-related quality of life (HRQL) measured using mental and physical component scores (MCS/PCS) estimated based on a 12-item Short-Form Health Survey (SF-12) with a higher score indicating better HRQL, and depressive symptoms were measured using Major Depression Inventory (MDI) with higher score indicating more depressive symptoms.
Results
In total, 3% were classified with pADHD (sex ratio 1:1). pADHD was associated with reduced MCS and PCS, and increased MDI score. Males scored on average higher on inattentive symptoms compared to females, whereas females scored on average higher on hyperactive-impulsive symptoms. Individuals scoring high on the combined inattentive and hyperactive-impulsive ADHD symptom presentation were most likely to be impaired in terms of higher MDI scores and lower PCS when compared to non-ADHD controls.
Conclusions
In conclusion, ADHD symptoms are common in this seemingly healthy and undiagnosed population. Symptom presentations differ between sexes and the type of presentation seems to impact the association with depressive symptoms and level of reduced HRQL.
Chronic headache after aneurysmal subarachnoid hemorrhage (aSAH) remains an ongoing area of investigation, with uncertainty regarding its prevalence and long-term outcomes.
Methods:
A systematic review was conducted across five databases – Medline (Ovid), the Cochrane Central Register of Controlled Trials (Ovid), PsychInfo (Ovid), Embase (Ovid) and Scopus (Elsevier) – to identify all studies investigating the prevalence of chronic headaches after aSAH. A total of five studies were identified and included in our review.
Results:
There were five observational studies (three cohort and two cross-sectional). The overall prevalence of chronic headaches after aSAH ranged from 16.1% to 41%, albeit across a follow-up time frame of 12 months to 7.5 years. Outcome measurements included quantitative pain scores and opioid usage; however, these were inconsistent across studies, and the studies did not address the long-term impacts of chronic headaches on quality of life or their psychosocial implications.
Conclusion:
The prevalence of chronic headache after aSAH is not well-characterized, and long-term outcomes are seldom studied, highlighting a critical gap in the current literature. Longitudinal cohort studies with standardized approaches to ascertain the psychosocial and physiological burden associated with post-aSAH chronic headaches are urgently needed.
Sodium-glucose cotransporter-2 inhibitors reduce cardiovascular outcomes in patients with congestive heart failure and a biventricular circulation. Congestive heart failure in Fontan univentricular circulation is distinctly different. Experience with sodium-glucose cotransporter-2 inhibitors in this group has not yet been well described.
Objectives:
This work describes safety and tolerability of sodium-glucose cotransporter-2 inhibitors in patients with Fontan circulation.
Methods:
Single-centre review of patients with Fontan circulation prescribed a sodium-glucose cotransporter-2 inhibitors for congestive heart failure. Primary outcome was tolerability or need for discontinuation. Secondary outcomes were changes in New York Heart Association class, congestive heart failure hospitalisation, ventricular function, exercise performance, and laboratory values.
Results:
We identified 25 patients with Fontan circulation prescribed an sodium-glucose cotransporter-2 inhibitors, most with a systemic right ventricle. Over a third of subjects had at least moderately reduced baseline ventricular function. Baseline catheterisation showed a mean Fontan pressure of 17.1 ± 3.7 mmHg and pulmonary capillary wedge pressure 11.7 ± 3.2 mmHg at rest; 59% had occult diastolic dysfunction with abnormal pulmonary capillary wedge pressure elevation following volume expansion. Most were on congestive heart failure medications and/or a pulmonary vasodilator prior to sodium-glucose cotransporter-2 inhibitors addition, and three had a congestive heart failure hospitalisation within the previous year. All reported good medication tolerance except one patient was nonadherent to medications and two discontinued sodium-glucose cotransporter-2 inhibitors for perceived side effects. There were no significant differences in secondary outcomes. There was, however, a downward trend of serum brain natriuretic peptide (n = 13) and improved peak VO2 (n = 6), though neither statistically significant (p > 0.05).
Conclusion:
This series, the largest published to date, suggests that sodium-glucose cotransporter-2 inhibitors are safe and tolerable congestive heart failure therapy in Fontan circulation. Further research is warranted to explore therapy in this unique population.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.
Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring brain function by correlating temporal changes in local cerebral blood oxygenation with behavioral measures. fMRI is used to study individuals at single time points, across multiple time points (with or without intervention), as well as to examine the variation of brain function across normal and ill populations. fMRI may be collected at multiple sites and then pooled into a single analysis. This paper describes how fMRI data is analyzed at each of these levels and describes the noise sources introduced at each level.
In the current paper, we review existing tools for solving variable selection problems in psychology. Modern regularization methods such as lasso regression have recently been introduced in the field and are incorporated into popular methodologies, such as network analysis. However, several recognized limitations of lasso regularization may limit its suitability for psychological research. In this paper, we compare the properties of lasso approaches used for variable selection to Bayesian variable selection approaches. In particular we highlight advantages of stochastic search variable selection (SSVS), that make it well suited for variable selection applications in psychology. We demonstrate these advantages and contrast SSVS with lasso type penalization in an application to predict depression symptoms in a large sample and an accompanying simulation study. We investigate the effects of sample size, effect size, and patterns of correlation among predictors on rates of correct and false inclusion and bias in the estimates. SSVS as investigated here is reasonably computationally efficient and powerful to detect moderate effects in small sample sizes (or small effects in moderate sample sizes), while protecting against false inclusion and without over-penalizing true effects. We recommend SSVS as a flexible framework that is well-suited for the field, discuss limitations, and suggest directions for future development.
Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.
Aims
We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.
Method
The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status.
Results
The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls.
Conclusion
Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.
Understanding the processes that give rise to networks gives us a better grasp of why we see the networks we do, where we might expect to find them, and how we might expect them to change over time. One way to achieve this is to create simulated networks. Simulated networks allow us to build networks based on detailed principles. We can then ask how networks derived from these principles behave and, correspondingly, understand how our observed networks may be generated by similar principles. This chapter explores many generative algorithms, including random graphs, small world networks, preferential attachment and acquisition, fitness networks, configuration models, amongst many others.
For any form of communication to make it beyond the category of talking to oneself, at least two individuals must share a common lexicon. Before languages can evolve into more complex forms, there must first be a pragmatic sense in which one individual can communicate a basic idea to another. How might shared lexicons have originated? Standard explorations of language often look in well-connected social groups such as chimpanzees, frequently numbering in the tens of individuals. But we might ask if language perhaps didn’t begin in a more humble arrangement, involving social groups of just two or a few individuals, such as that found in the orangutan? Agent-based models combined with network science offer a way to study this problem. By treating nodes as agents with strict rule-based behavior and edges as opportunities for interaction, agent-based models provide frameworks for studying how behavior and connectivity interact to create emergent phenomenon, such as the evolution of cooperation and cultural change. Here we will explore an agent-based model of the naming game to address how structure influences the emergence of shared lexicons.
What is memory? Scientists have proposed a wide variety of spatial metaphors to understand it. These range from the 2D wax tablets proposed by Plato and Aristotle and subsequently Freud, with his magic writing pad, to the 3D physical spaces that one can walk around inside, such as the subway of Collins and Quillian. If memory has such a spatial structure, then it suggests a simple rule: items in memory can be near or far from one another. Anything with a near-and-far structure lends itself to a network representation. Such spatial structure also lends itself to being in the wrong place at the wrong time: remembering things that never happened and forgetting things that did. This chapter explores how structure facilitates memories and also looks at a specific case of false memory to highlight how modeling the process of spreading activation on networks can enrich our understanding of structure beyond degree.
The false consensus effect is the observation that people tend to overestimate the number of people who share their views. In modern environments we also see growing evidence of greater polarization. For example, according to the Pew Research Center over the past five decades, congressional US Democrat and Republican ideologies have increasingly diverged, with an ever shrinking middle ground. This is appears to also be reflected among US citizens, with a "disappearing center" hastened by growing “anarchist” and “anti-establishment” ideologies. Many have speculated that this polarization is a global phenomenon. The question we pose here is how beliefs and network structure might interact to facilitate both false consensus effects and rising polarization.