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Major depressive episodes (MDEs) are highly recurrent in clinical samples. However, the course of MDEs and predictors of their endurance are unclear in the general youth population.
Methods
We investigated prospective factors associated with enduring MDE (the presence of 12-month DSM-IV MDE at baseline and 1 year using the Composite International Diagnostic Interview–Screening Scales) in 1,833 participants of a 1-year epidemiological youth cohort study in Hong Kong. Multivariable logistic regression models were used to examine the influences of a range of personal and environmental factors.
Results
At baseline, 13.7% participants had MDEs, among whom 21.1% presented enduring MDEs. More severe symptoms of post-traumatic stress disorder (adjusted odds ratio [aOR] = 5.54, confidence interval [CI] = 2.14–14.38), depression (aOR = 3.92, CI = 1.79–8.62), and generalized anxiety (aOR = 2.27, CI = 1.21–4.25) at baseline were among the strongest associated factors for enduring MDE, with trends of associations observed for psychotic-like experiences (aOR = 1.98, CI = 0.98–4.02) and eating disorder symptoms (aOR = 1.88, CI = 0.90–3.95). Among various types of stressors, only dependent stressors at follow-up showed a clear association with enduring MDE (aOR = 4.22, CI = 1.81–9.83). Those with enduring MDE showed poorer functioning and mental health-related quality of life at follow-up, with only 35.6% having sought any psychiatric/psychological help during the past year.
Conclusions
Detecting comorbid symptoms in those with prior MDEs and reducing the impact of dependent stressors may help reduce their long-term implications. Enhancing the accessibility and acceptability of youth-targeted mental health services would also be crucial to improve help-seeking.
To analyze the correlation between scale of Candida auris clustering and extent of environmental contamination, exploring its implications for improving infection control measures in healthcare settings.
Design:
Retrospective observational study.
Setting:
An acute hospital and a convalescent hospital in Hong Kong.
Patients:
Laboratory confirmed C. auris carriers diagnosed in two hospitals between March and October 2023.
Methods:
C. auris screening was conducted on patients with defined risk factors and through regular surveillance. Environmental samples were collected from high-touch surfaces and air grilles in corresponding wards.
Results:
One-hundred-seventy new C. auris patients were identified, including 65 from nine outbreaks and 105 sporadic cases. Environmental screening from eight outbreaks and 46 sporadic isolated cases was analyzed. The environmental contamination rate was significantly higher in the outbreak group (15.1% vs 2.6%, P < 0.05). Longer outbreak duration (34 vs 7 days, P < 0.05) and a higher median number of affected patients per outbreak (9 vs 5, P = 0.05) were associated with higher contamination rates. Notably, air grille samples had a significantly higher contamination rate than high-touch surfaces in both the outbreak (31.6% vs 10.2%, P < 0.05) and sporadic groups (4.6% vs 1.5%, P < 0.05).
Conclusion:
Prolonged and sizeable C. auris clusterings were linked with more extensive environmental contamination, particularly in air grilles, which are often overlooked during decontamination
These findings underscore the need for enhanced infection control measures, including thorough environmental decontamination of air ventilation systems, to mitigate transmission risks in healthcare settings.
Accurate assessment of an individual’s diet is vital to study the effect of diet on health. Image-based methods, which use images as input, may improve the reliability of dietary assessment. We developed an iOS application that uses computer vision to identify food from images. This study aimed to assess the accuracy of energy intake (EIapp) estimates from the application by comparing them to estimated energy expenditure (EE) and to the EI estimates from a validated dietary assessment tool, the 24-h recall (EIrecall). Participants were recruited from a randomised controlled trial called He Rourou Whai Painga. Participants recorded all intake over 7 d using the application, which provided a mean daily EI; this was compared to the EI estimated by two 24-h recalls. The EI from the application and the recalls were compared to EE, estimated using indirect calorimetry and wrist-worn accelerometry. EI estimates from the application and the 24-h recalls were lower than EE, with a mean bias of -1814 kJ (95% CI -3012 to -615, p = 0.005) and -1715 kJ (95% CI -3237 to -193, p = 0.029), respectively. The mean bias between EI from the application and the 24-h recall was 783 kJ (95% CI -875 to 2441, p = 0.33). This suggests that the EI estimates from the application are comparable to the 24-h recall method, a validated and widely used tool in nutritional research.
The Hector Galaxy Survey is a new optical integral field spectroscopy (IFS) survey currently using the Anglo-Australian Telescope to observe up to 15 000 galaxies at low redshift ($z \lt 0.1$). The Hector instrument employs 21 optical fibre bundles feeding into two double-beam spectrographs, AAOmega and the new Spector spectrograph, to enable wide-field multi-object IFS observations of galaxies. To efficiently process the survey data, we adopt the data reduction pipeline developed for the SAMI Galaxy Survey, with significant updates to accommodate Hector’s dual-spectrograph system. These enhancements address key differences in spectral resolution and other instrumental characteristics relative to SAMI and are specifically optimised for Hector’s unique configuration. We introduce a two-dimensional arc fitting approach that reduces the root-mean-square (RMS) velocity scatter by a factor of 1.2–3.4 compared to fitting arc lines independently for each fibre. The pipeline also incorporates detailed modelling of chromatic optical distortion in the wide-field corrector, to account for wavelength-dependent spatial shifts across the focal plane. We assess data quality through a series of validation tests, including wavelength solution accuracy (1.2–2.7 km s$^{-1}$ RMS), spectral resolution (FWHM of 1.2–1.4 Å for Spector), throughput characterisation, astrometric precision ($\lesssim$ 0.03 arcsec median offset), sky subtraction residuals (1–1.6% median continuum residual), and flux calibration stability (4% systematic offset when compared to Legacy Survey fluxes). We demonstrate that Hector delivers high-fidelity, science-ready datasets, supporting robust measurements of galaxy kinematics, stellar populations, and emission-line properties and provide examples. Additionally, we address systematic uncertainties identified during the data processing and propose future improvements to enhance the precision and reliability of upcoming data releases. This work establishes a robust data reduction framework for Hector, delivering high-quality data products that support a broad range of extragalactic studies.
Non-suicidal self-injury (NSSI) is associated with mental disorders, yet work regarding the direction of this association is inconsistent. We examined the prevalence, comorbidity, time–order associations with mental disorders, and sex differences in sporadic and repetitive NSSI among emerging adults.
Methods
We used survey data from n = 72,288 first-year college students as part of the World Mental Health-International College Student Survey Initiative (WMH-ICS) to explore time–order associations between onset of NSSI and mental disorders, based on retrospective age-of-onset reports using discrete-time survival models. We distinguished between sporadic (1–5 lifetime episodes) and repetitive (≥6 lifetime episodes) NSSI in relation to DSM-5 mood, anxiety, and externalizing disorders.
Results
We estimated a lifetime NSSI rate of 24.5%, with approximately half reporting sporadic NSSI and half repetitive NSSI. The time–order associations between onset of NSSI and mental disorders were bidirectional, but mental disorders were stronger predictors of the onset of NSSI (median RR = 1.94) than vice versa (median RR = 1.58). These associations were stronger among individuals engaging in repetitive rather than sporadic NSSI. While associations between NSSI and mental disorders generally did not differ by sex, repetitive NSSI was a stronger predictor for the onset of subsequent substance use disorders among females compared to males. Most mental disorders marginally increased the risk for persistent repetitive NSSI (median RR = 1.23).
Conclusions
Our findings offer unique insights into the temporal order between NSSI and mental disorders. Further work exploring the mechanism underlying these associations will pave the way for early identification and intervention of both NSSI and mental disorders.
Background: Empiric antibiotic therapy choices and de-escalation practices for the management of febrile neutropenia (FN) can vary. Facility-specific antimicrobial guidelines have an important role in influencing prescription practices for FN and is a foundation of antimicrobial stewardship activities. Methods: This pre-post quality improvement study at the University of Maryland Medical Center (UMMC) Greenebaum Comprehensive Cancer Center evaluated the impact of the implementation of updated institutional FN guidelines. The changes primarily included: 1) removal of meropenem as first-line agent for patients receiving levofloxacin prophylaxis without other risk factors (e.g. history of resistant organism) and 2) de-escalation protocol for low-risk patients (e.g. afebrile, hemodynamically stable). Education of oncology attendings, residents and pharmacists were carried out. We included patients receiving antipseudomonal antibiotics for FN or sepsis as indicated by prescriber (~70% concordance with antimicrobial stewardship review). Sepsis was included because of high rates of observed misclassification for patients with FN. Stem cell transplant patients were excluded. Pre-intervention (04/2021 – 12/2022) and post-intervention (01/2023 – 09/2024) groups were compared for total anti-pseudomonal antibiotic and meropenem-specific days of therapy (DOT) per 1000 days present (DP) and count of unique antibiotic order per 1000 DP. In addition, a sample of antibiotics reviewed by the UMMC antimicrobial stewardship team was assessed for guideline compliance. Means were calculated across quarters for each period and Willcoxon rank sum was used for comparisons (p Results: A total of 3,311 antibiotics were ordered for FN (79%) or sepsis (21%) during the study period. Longitudinal trends and antibiotic type distribution are illustrated in Figures 1 and 2, respectively. DOT per 1000 DP for all antipseudomonal antibiotics was 213 in the pre-intervention group compared to 191 in the post-intervention group (p=0.06). Meropenem DOT per 1000 DP decreased from 105 in the pre-intervention group to 87 in the post-intervention group (p=0.004). Unique antibiotic order per 1000 DP of all antipseudomonal antibiotics remained constant (62 vs. 56, p=0.1), while unique antibiotic order per 1000 DP for meropenem decreased (16 vs. 8, p =0.01). Of the 317 antibiotics reviewed, 130/169 (77%) were guideline compliant in the pre-intervention group and 113/148 (76%) in the post-intervention group. Conclusion: Changes in FN guidelines at the UMMC cancer center led to decreased meropenem use with a nonsignificant decline in all antipseudomonal antibiotics. Additional work is needed to identify barriers to guideline adherence.
Background: Data in adults and older children demonstrate repeat blood cultures (BlCx) are not always necessary. Indications for repeat BlCx include Staphylococcus aureus or yeast in the initial blood culture, or the presence of a central venous catheter (CVC). Blood collection in premature babies can be challenging and there are little data regarding when repeat BlCxs are necessary after an initial positive. The goal of this study is to determine risk factors for persistent bloodstream infection (BSI) to determine when unnecessary blood cultures can be avoided. Methods: The Yale New Haven Children’s Hospital NNICU is a 68-bed level 4 unit. Babies in the NNICU with a positive blood culture from 8/1/16 to 12/31/21 were included. Persistent BSI was defined as a repeat positive BlCx with the same organism >48 hrs. after the original culture. A BlCx > 7 days after the original BlCx was considered a new event. Babies who died within 48 hrs. of the initial culture were excluded. In preliminary analysis we did not distinguish between true BSI and contamination. Data were extracted from the medical record by the Yale Data Analytics Team and by manual chart review. Data were stored in excel for descriptive statistics. Additional statistical analysis in SPSS is on-going to account for multiple variables. Results: 142 babies had a positive BlCx with 122 babies alive at 48 hrs. and included in the study. These 124 babies had 139 positive BlCx growing 145 organisms. Persistent BSI occurred in 17.3% (24/139) of BlCxs. Factors associated with persistence in univariate analyses included the presence of a CVC and recovery of S. aureus. (Table 1) No babies with either streptococcal infection or early onset sepsis had persistent BSI. (Table 1) Additional variables under evaluation in a multiple regression model to determine the probability of persistent BSI include other sources of infection, white blood cell count at the time of BlCx, congenital heart disease, immunosuppressive agents such as steroids and whether empiric antibiotic therapy was appropriate. We will also define probable contaminants and repeat the analyses with and without these BSI episodes. Conclusions: Preliminary analysis shows that neonates have similar risk factors for persistent BSI as adults including the presence of a CVC and the recovery of S. aureus that require repeat BlCx to confirm clearance. For babies with streptococcal infection, repeat BlCx may not be routinely required. Current work is examining additional potential risk factors in multi-variable models.
Helicopter-based shooting using either a .308 semi-automatic rifle or a semi-automatic 12-gauge shotgun is widely used to manage non-native ungulate populations in Australasia, but the animal welfare outcomes of these two firearms have not been robustly compared. We conducted a randomised field study to compare the animal welfare outcomes of helicopter-based shooting of fallow deer (Dama dama) using a shotgun with three types of lead-based shot (Winchester® 00 Buck, 1 Buck or 4 Buck) relative to a .308 rifle with 135-grain lead-based bullets in New South Wales, Australia, in 2023. All deer that were shot at (n = 390) were killed. Time-to-event curves for times from pursuit to first shot, first shot to insensibility, and the sum of these two metrics (‘total time’), were similar among the four ammunition types. The mean number of shots fired per deer was similar across all four ammunition types, but the mean number of wound tracts per deer increased across the four ammunition types with the number of projectiles per cartridge. All deer subjected to post mortem examination had $ \ge $ 1 wound tract or projectile in the thorax. Our study indicates that using a .308 semi-automatic rifle or a 12-gauge semi-automatic shotgun for helicopter-based shooting of non-native deer, when the latter is used at ranges ≤ 30 m, provides similar animal welfare outcomes.
Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
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.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Early Miocene land mammals from eastern North America are exceedingly rare. Over the past several decades a small, but significant, vertebrate fauna has been recovered by paleontologists and citizen scientists from the Belgrade Formation at the Martin Marietta Belgrade Quarry in eastern North Carolina. This assemblage has 12 land mammal taxa, including beaver (Castoridae), stem lagomorph, carnivorans (Mustelidae, Ailuridae), horses (Equidae), rhinoceros (Rhinocerotidae), tapir (Tapiridae), peccary (Tayassuidae), anthracothere (Anthracotheriidae), entelodont (Entelodontidae), and protoceratid (Protoceratidae). Taken together, the biochronology of this Maysville Local Fauna indicates a late Arikareean (Ar3/Ar4) to early Hemingfordian (He1) North American Land Mammal Age (NALMA). This interval, which includes the Runningwater Chronofauna, documents numerous important Holarctic immigrants, including Amphictis, Craterogale, and cf. Menoceras found at this locality. Strontium isotope stratigraphy (SIS) of shark teeth collected in situ from the Belgrade Formation yield an age of 21.4 ± 0.13 Ma, which validates the age of interbedded land mammals within this unit. It also is consistent with the late Arikareean (Ar3/Ar4) biochronology and Aquitanian Neogene marine stage. New SIS analyses of oysters (Striostrea gigantissima) and clams (Chione) from this mine, previously assigned to late Oligocene or Late Miocene, are significantly older (28.0 ± 0.22 Ma and 27.6 ± 0.26 Ma, respectively) than the land mammals. Depending upon stratigraphic interpretations, these may confirm an older marine facies within the Belgrade Formation. This locality is important because of its marine and terrestrial tie-ins that facilitate intercalibration of both NALMAs and Cenozoic marine stages.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.
Objectives/Goals: This poster describes the scientific rationale, needs assessment, programmatic elements, and impact of a community of practice (CoP) focusing on advancing equity in the science and practice of mentorship. Methods/Study Population: In 2023, the University of Wisconsin Institute for Clinical and Translational Research received NIH R13 funding to host a conference, the Science of Effective Mentorship (Asquith, McDaniels, et.al., 2023). Approximately 150 researchers and program leaders from Clinical and Translational Science Awards (CTSA) Hubs and beyond attended. Data were collected before, during, and after the conference, providing the authors with an initial idea of community needs. As a result, a mentorship CoP was formed. In the subsequent 18 months, a steering and advisory committee established a program of virtual, topic-focused virtual events every 3 months as well as a community website, with increasing attendance and utilization. A survey was disseminated after the completion of one year, and a focus group was held during the last virtual gathering. Results/Anticipated Results: The demand for infrastructure to support a national community of practice will be demonstrated. The demographic and positional diversity (e.g. role within a CTSA Hub) will highlight the opportunities of convening this diverse community. Organizational challenges and opportunities will be highlighted. Assessment data will reveal the broad range of needs and interests of participants. Aggregate demographic, professional, and participation data about community of practice members will be shared, as well as the governance and programmatic elements of this community of practice. Evaluation results from the first year of activity will be displayed. Needs for sustainability will be discussed. Discussion/Significance of Impact: CoPs are not new in the CTR space. Membership in a CoP may reduce isolation individuals feel as they negotiate the important work of equity in the biomedical workforce. Members of this community of practice share the expertise and commitment to promoting equity in the biomedical workforce through supporting robust culture of mentorship.
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.
This paper reports an expansion of the English as a second language (L2) component of the Multilingual Eye Movement Corpus (MECO L2), an international database of eye movements during text reading. While the previous Wave 1 of the MECO project (Kuperman et al., 2023) contained English as a L2 reading data from readers with 12 different first language (L1) backgrounds, the newly collected dataset adds eye-tracking data on English text reading from 13 distinct L1 backgrounds (N = 660) as well as participants’ scores on component skills of English proficiency and information about their demographics and language background and use. The paper reports reliability estimates, descriptive statistics, and correlational analyses as means to validate the expansion dataset. Consistent with prior literature and the MECO Wave 1, trends in the MECO Wave 2 data include a weak correlation between reading comprehension and oculomotor measures of reading fluency and a greater L1-L2 contrast in reading fluency than reading comprehension. Jointly with Wave 1, the MECO project includes English reading data from more than 1,200 readers representing a diversity of native writing systems (logographic, abjad, abugida, and alphabetic) and 19 distinct L1 backgrounds. We provide multiple pointers to new venues of how L2 reading researchers can mine this rich publicly available dataset.
Building on the availability of geospatial data, improvements in mapping software, and innovations in spatial statistics, political scientists are increasingly taking geography seriously. As we adopt the tools of geographers, we must also consider the methodological challenges they have identified. We focus on the modifiable areal unit problem (MAUP)—the idea that the size of aggregate spatial units and the location of their borders affect the empirical results we obtain. We first describe the logic of the MAUP, and then demonstrate the MAUP through simulations, showing MAUP-related inconsistency in regression results in randomly generated and real-world data. We identify MAUP concerns, and best practices, in top journals in political science. We conclude by suggesting how scholars may respond in theoretical and empirical terms to concerns about validity and reliability that arise from the MAUP.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.