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The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.
Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.
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.
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.
GX is a code designed to solve the nonlinear gyrokinetic system for low-frequency turbulence in magnetized plasmas, particularly tokamaks and stellarators. In GX, our primary motivation and target is a fast gyrokinetic solver that can be used for fusion reactor design and optimization along with wide-ranging physics exploration. This has led to several code and algorithm design decisions, specifically chosen to prioritize time to solution. First, we have used a discretization algorithm that is pseudospectral in the entire phase space, including a Laguerre–Hermite pseudospectral formulation of velocity space, which allows for smooth interpolation between coarse gyrofluid-like resolutions and finer conventional gyrokinetic resolutions and efficient evaluation of a model collision operator. Additionally, we have built GX to natively target graphics processors (GPUs), which are among the fastest computational platforms available today. Finally, we have taken advantage of the reactor-relevant limit of small $\rho _*$ by using the radially local flux-tube approach. In this paper we present details about the gyrokinetic system and the numerical algorithms used in GX to solve the system. We then present several numerical benchmarks against established gyrokinetic codes in both tokamak and stellarator magnetic geometries to verify that GX correctly simulates gyrokinetic turbulence in the small $\rho _*$ limit. Moreover, we show that the convergence properties of the Laguerre–Hermite spectral velocity formulation are quite favourable for nonlinear problems of interest. Coupled with GPU acceleration, which we also investigate with scaling studies, this enables GX to be able to produce useful turbulence simulations in minutes on one (or a few) GPUs and higher fidelity results in a few hours using several GPUs. GX is open-source software that is ready for fusion reactor design studies.
Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.
Methods
This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.
Results
We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.
Conclusions
Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.
Weight gain, QT interval prolongation, and dyslipidemias associated with the chronic use of some antipsychotic medications can explain a higher prevalence of cardiovascular risk in these psychiatric population. The D’Agostino Index include some factors such as age, total cholesterol, high-density lipoproteins, systolic blood pressure increased, antihypertensive treatment, smoking, and diabetes, to estimate an individual’s risk (low, moderate or severe) of developing a cardiovascular event through a period of 10 years or throughout the patient’s lifetime.
Objectives
To compare the degree of cardiovascular risk using the D’Agostino Index, among different antipsychotic medications.
Methods
An estimation of cardiovascular risk (low, moderate, or high) was performed with the D´Agostino index in a sample of 144 patients (82 men and 62 women) mean age 45,2 +/- 10.13. All patients were treated for at least one year at a therapeutic dose and adhered to their treatment regimen correctly. Subjects with some relevant pre-existing unstable heart disease were excluded. All patients previously provided informed consent and were of legal age. Clinical data on medical history, concomitant medications, and risk factors were collected. A completed physical exam, waist circumference, lab sample, a lifestyle scale, and an evaluation of vital signs in accordance with European Society of Hypertension were evaluated. Statistical analysis was carried out using the statistical software SPSS version 26.0. A significance level α=0.05 was considered throughout the study.
Results
The four most consumed antipsychotics were risperidone 9.72% (n=14), paliperidone 25.7% (n=37), olanzapine 14.6% (n=21), and aripiprazole 34.7% (n=50). Descriptively, it was observed that the drugs most associated with moderate or high risks were paliperidone (37.8%) and olanzapine (33.3%), risperidone (28.6 %). Aripiprazol (22%) was the less associated compound with moderate/high cardiovascular risk.
Conclusions
Subjects treated with olanzapine and paliperidone showed a higher association with cardiovascular risk. Predicting cardiovascular risk could provide individual benefits by enabling lifestyle modifications, pharmacological treatment changes, or closer monitoring to reduce cardiovascular risk.
Disclosure of Interest
A. Montejo Grant / Research support from: This study has been funded by the Instituto de Salud Carlos III (ISCIII) through the project PI19/1596 and co-funded by the European Union., C. Bermejo: None Declared, J. Matías: None Declared, T. Martín: None Declared, J. Matías-Polo: None Declared, Y. Santana: None Declared, J. López-López: None Declared, R. de Alarcón: None Declared, J. Acosta: None Declared
Craniofacial surgery is a specialized field that addresses congenital and acquired deformities of the head and face. While the physical outcomes of craniofacial surgery are well-documented, less attention has been given to the psychological well-being of adult patients. This abstract aims to explore self-esteem issues among adult patients treated at the Craniofacial Surgery Sector of HCPA (Hospital de Clínicas de Porto Alegre), where a substantial proportion of adult patients have reported self-esteem problems.
Objectives
1. To assess the prevalence of self-esteem issues among adult patients (≥18 years old) attending the HCPA Craniofacial Surgery Sector.
2. To examine potential contributing factors to self-esteem problems in this specific patient population.
3. To evaluate the impact of self-esteem on the mental health and psychosocial functioning of adult craniofacial surgery patients.
4. To propose recommendations for psychosocial support and intervention strategies tailored to the needs of adult patients in this context.
Methods
This cross-sectional study involved 132 adult patients who had undergone or were scheduled for craniofacial surgery at HCPA. Participants reported self-esteem issues in their talk with the hospital’s physicians, and their medical records were reviewed to collect demographic and clinical data. Additionally, participants provided information about their mental health status and psychosocial functioning.
Results
Among the 39 adult patients included in the study, 37 (94.9%) reported experiencing self-esteem issues, such as lack of confidence or feeling unattractive. The most commonly reported contributing factors were visible facial differences, social interactions, and prior surgical experiences. Patients with lower self-esteem had a higher likelihood of reporting symptoms of depression and anxiety and reported lower overall psychosocial functioning compared to those with higher self-esteem.
Conclusions
This reveals a strikingly high prevalence of self-esteem issues among adult patients attending the Craniofacial Surgery Sector at HCPA. These findings underscore the importance of recognizing and addressing the psychological well-being of adult craniofacial surgery patients. Comprehensive psychosocial support, including counseling, peer support, and interventions to enhance self-esteem, should be integrated into the care of these patients. By addressing self-esteem concerns, healthcare providers can improve the mental health and overall quality of life of adult craniofacial surgery patients.
Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.
Methods:
An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as “VA Bug Alert” (VABA). Use through 8/2023 was assessed.
Results:
VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber.
Conclusions:
A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.
This paper describes an improved simple, sample-mounting method for random powder X-ray diffraction (XRD), namely the razor tamped surface (RTS) method, which prepares a powder mount by tamping the loose powder with the sharp edge of a razor blade. Four kaolinites and a quartz powder were used to evaluate the RTS method by quantifying the degree of orientation in the sample mounts using orientation indices. Comparisons between the RTS and other published simple methods, consisting of front loading, back loading and side loading, indicate that the RTS method produces minimum packing density and minimum preferred orientation in the powder mounts of all five samples. The quartz powder used in this study does exhibit a tendency to preferred orientation. The mechanism by which the RTS method reduces preferred orientation is examined by comparing the width of the sharp blade edge with the size of clay particles. The advantages and disadvantages of the RTS method are also discussed.