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Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.
Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.
Methods
This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).
Results
In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.
Conclusions
Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.
OBJECTIVES/GOALS: We designed the Biocascade Exhaled Breath Sampler (BEBS) to characterize viral aerosol shedding among individuals with influenza and other respiratory virus infections. We first aimed to test the BEBS on volunteer COVID-19 cases and report the aerodynamic size distribution of exhaled breath aerosol particles carrying SARS-CoV-2 RNA. METHODS/STUDY POPULATION: From June 15 through December 15, 2022, we recruited 27 PCR-confirmed COVID-19 cases from a college campus and the surrounding community to provide 30-minute breath samples into a well-validated Gesundheit-II (G-II) exhaled breath aerosol sampler. Among these individuals, 17 provided an additional exhaled breath sample into the newly designed BEBS. We quantified samples for viral RNA using reverse transcription digital polymerase chain reaction (RT-dPCR) and determined the viral RNA copies collected within two aerosol size fractions (≤5 µm and >5 µm in diameter) from the G-II, and four aerosol size fractions (<1.15 µm, 1.15–3.2 µm, 3.3–8.2 µm, and >8.2 µm) from the BEBS. RESULTS/ANTICIPATED RESULTS: Individuals with a SARS-CoV-2 Omicron BA.4 or BA.5 infection shed virus in aerosols at an average rate of 7.5x103 RNA copies per 30-minute G-II sample, with 78% of the total RNA in aerosols ≤5 µm in diameter. Among the BEBS samples, 10% of the total viral RNA was detected in aerosols <1.15 µm, 43% in 1.15–3.2 µm, 37% in 3.3–8.2 µm, and 10% in the >8.2 µm size fraction. Based on viral RNA loads, our results indicate that exhaled aerosols ≤3.2 µm contribute the majority of SARS-CoV-2 inhalation exposure. DISCUSSION/SIGNIFICANCE: Our data provide additional evidence that respirable aerosols contribute to the spread of SARS-CoV-2. Thus, our data suggest that mitigation measures designed to reduce infectious aerosol inhalation, such as ventilation and the use of air cleaners and respirators, are needed to control the spread.
Though food insecurity has long been recognised to impact health, population-specific determinants of food insecurity have recently been studied systematically as an important public health concern. Indeed, while immigrant populations face particular challenges to equitable access to the food system, many of these concerns have not been systematically described. To this end, we critically review recent work that demonstrates the importance of transportation and language access as independent determinants of access to food for immigrant populations. Furthermore, we highlight proposals to mitigate barriers to access, including both academic and community-driven approaches to create overlapping institutional commitments for inclusive policymaking that meets the specific needs of diverse populations.
Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.
Methods
After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.
Results
The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.
Conclusions
These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.
Despite the impact of inappropriate prescribing on antibiotic resistance, data on surgical antibiotic prophylaxis in sub-Saharan Africa are limited. In this study, we evaluated antibiotic use and consumption in surgical prophylaxis in 4 hospitals located in 2 geographic regions of Sierra Leone.
Methods:
We used a prospective cohort design to collect data from surgical patients aged 18 years or older between February and October 2021. Data were analyzed using Stata version 16 software.
Results:
Of the 753 surgical patients, 439 (58.3%) were females, and 723 (96%) had received at least 1 dose of antibiotics. Only 410 (54.4%) patients had indications for surgical antibiotic prophylaxis consistent with local guidelines. Factors associated with preoperative antibiotic prophylaxis were the type of surgery, wound class, and consistency of surgical antibiotic prophylaxis with local guidelines. Postoperatively, type of surgery, wound class, and consistency of antibiotic use with local guidelines were important factors associated with antibiotic use. Of the 2,482 doses administered, 1,410 (56.8%) were given postoperatively. Preoperative and intraoperative antibiotic use was reported in 645 (26%) and 427 (17.2%) cases, respectively. The most commonly used antibiotic was ceftriaxone 949 (38.2%) with a consumption of 41.6 defined daily doses (DDD) per 100 bed days. Overall, antibiotic consumption was 117.9 DDD per 100 bed days. The Access antibiotics had 72.7 DDD per 100 bed days (61.7%).
Conclusions:
We report a high rate of antibiotic consumption for surgical prophylaxis, most of which was not based on local guidelines. To address this growing threat, urgent action is needed to reduce irrational antibiotic prescribing for surgical prophylaxis.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Methods
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
Results
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Conclusions
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (
${>}7 \times 10^{10} {\mathrm{M}}_\odot$
) central galaxies at
$0.25 < z <0.35$
in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics (
$0.6-0.8$
arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at
$0.25 < z <0.35$
, as well as hundreds of emission-line sources at
$z < 6$
. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at
$z\approx 0.3$
. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
We compared rotavirus detection patterns before (2001–2006) and after (2008–2015) rotavirus vaccine introduction. We also compared rotavirus detection patterns in odd (2009, 2011, 2013, 2015) and even (2008, 2010, 2012, 2014) years post-vaccine separately. Results of stool rotavirus antigen testing from inpatient, outpatient and emergency department encounters from July 2000 to July 2015 at two paediatric hospital laboratories in Atlanta, Georgia were reviewed. Post-vaccine, rotavirus detection declined (30.2% vs. 13.7% (overall 54.6% decline, P <0.001)), occurred more frequently outside the rotavirus season (19.8% vs. 3.5%; P < 0.001), and was more common among older children (26 vs. 13 median months of age; P < 0.001). During odd years post-vaccine, rotavirus detection was significantly higher than even years (20.2% vs. 6.4%; P < 0.001). Rotavirus detection declined substantially and developed a biennial pattern in the post-vaccine era. The intensity and temporality of rotavirus detection in odd years post-vaccine resembled that observed pre-vaccine, although considerably reduced in magnitude.
It is difficult to control Holotrichia parallela Motschulsky with chemical insecticides due to the larvae's soil-living habit, thus the pest has caused great economic losses in agriculture. In addition, uridine diphosphate-glycosyltransferases (UGTs) catalyze the glycosylation process of a variety of small lipophilic molecules with sugars to produce water-soluble glycosides, and play multiple roles in detoxification, endobiotic modulation, and sequestration in an insect. Some UGTs were found specifically expressed in antennae of Drosophila melanogaster and Spodoptera littoralis, and glucurono-conjugated odorants could not elicit any olfactory signals, suggesting that the UGTs may play roles in odorant inactivation by biotransformation. In the current study, we performed a genome-wide analysis of the candidate UGT family in the dark black chafer, H. parallela. Based on a UGT gene signature and the similarity of these genes to UGT homologs from other organisms, 20 putative H. parallela UGT genes were identified. Bioinformatics analysis was used to predict sequence and structural features of H. parallela UGT proteins, and revealed important domains and residues involved in sugar donor binding and catalysis by comparison with human UGT2B7. Phylogenetic analysis of these 20 UGT protein sequences revealed eight major groups, including both order-specific and conserved groups, which are common to more than one order. Of these 20 UGT genes, HparUGT1265-1, HparUGT3119, and HparUGT8312 were highly (>100-fold change) expressed in antennae, suggesting a possible role in olfactory tissue, and most likely in odorant inactivation and olfactory processing. The remaining UGT genes were expressed in all tissues (head, thorax, abdomen, leg, and wing), indicating that these UGTs likely have different biological functions. This study provides the fundamental basis for determining the function of UGTs in a highly specialized olfactory organ, the H. parallela antenna.
Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.
To explore cross-sectional adherence to cancer prevention recommendations by adults enrolled in a prospective cohort in Alberta, Canada.
Design
Questionnaire data were used to construct a composite cancer prevention adherence score for each participant, based on selected personal recommendations published by the World Cancer Research Fund/American Institute for Cancer Research (2007). Data were self-reported on health and lifestyle, past-year physical activity and past-year FFQ. The scores accounted for physical activity, dietary supplement use, body size, and intakes of alcohol, fruit, vegetables and red meat. Tobacco exposure was also included. Scores ranged from 0 (least adherent) to 7 (most adherent).
Setting
Alberta’s Tomorrow Project; a research platform based on a prospective cohort.
Subjects
Adult men and women (n 24 988) aged 35–69 years recruited by random digit dialling and enrolled in Alberta’s Tomorrow Project between 2001 and 2009.
Results
Of the cohort, 14 % achieved adherence scores ≥5 and 60 % had scores ≤3. Overall adherence scores were higher in women (mean (sd): 3·4 (1·1)) than in men (3·0 (1·2)). The extent of overall adherence was also associated with level of education, employment status, annual household income, personal history of chronic disease, family history of chronic disease and age.
Conclusions
Reported adherence to selected personal recommendations for cancer prevention was low in this cohort of adults. In the short to medium term, these results suggest that more work is required to identify behaviours to target with cancer prevention strategies at a population level. Future work will explore the associations between adherence scores and cancer risk in this cohort.
We present a reconstructed lithologic column compiled from a series of lacustrine outcrops along a tributary of the Nyang River, a major tributary of the Yarlung-Tsangpo in southeast Tibet. The deposits were preserved between terraces at altitudes of 2950–3100 m asl. The stratigraphic record features at least two sets of coarsening-upward sequences depicting episodic aggradation and progradation of a glacially dammed lake related delta. Recognized facies changes illustrate the evolution cycles of depositional environments from pro-delta, delta front, to delta plain. Radiocarbon and optically stimulated luminescence dates reveal an aging-downward trend in stratigraphic order and provide an approximate timeline for the formation of glacially dammed lakes in late Pleistocene. This result reflects that the Zelunglung Glacier had progressively advanced to block the Yarlung-Tsangpo river and the dam materials had stepwise stacked up to an altitude of 3095 m asl during Marine Oxygen Isotope Stages 4 to 2.
Introduction: In order to achieve the best possible outcomes for patients requiring resuscitation (PRRs) in the emergency department (ED), health care providers (HCPs) must provide an efficient, multi-disciplinary and coordinated response. A quality improvement (QI) project was undertaken to improve HCP response to PRRs at two tertiary care hospital EDs in Toronto. Methods: We conducted a before-and-after mixed-method survey to evaluate the perception of the adequacy of HCP response and clarity of HCP role when responding to PRRs. The results were compared using the Chi-square test. Qualitative responses to the first survey were also used to inform the development of the QI project. Through interviews of key stakeholders and with continuous input from front-line ED HCPs, a multi-disciplinary team modified the ED resuscitation protocol. This included standardized pre-hospital communication form with paramedics, ED-wide overhead announcement of ‘Code Resus’, dedicated HCPs assigned to respond to PRRs, and specific duties assigned to each responder. Change initiatives were reinforced through education and posters in the ED. Six months after implementation, a second survey was conducted to evaluate the sustained effects of the intervention. Results: Baseline measures indicated that 16 of 52 (30.8%) nurses surveyed believed their role was often or always apparent to themselves and others when they attended to a PRR (on a 5-point rating scale). This proportion increased to 35 of 55 (63.6%) nurses in the post-implementation survey (p < 0.001). Regarding adequacy of the number of HCPs responding to PRRs, 17 of 39 (43.6%) physicians and 23 of 53 (43.4%) nurses surveyed thought the appropriate number of HCPs responded to PRRs; the remainder thought that there were too few or too many HCPs. In the post-implementation survey, 34 of 41 (82.9%) physicians (p < 0.001) and 36 of 56 (64.3%) nurses (p = 0.029) surveyed felt that the appropriate number of HCPs attended to PRRs. Conclusion: Using a quality improvement approach, we identified and quantified perceived deficiencies in HCP response to PRRs in the ED. Through feedback-based modifications of the ED resuscitation protocol and by engaging HCP stakeholders, change initiatives were implemented to improve HCP response. As a result, this project achieved significant and sustained improvements in HCPs’ perceived response to PRRs.
We summarise recent progress in understanding the star formation activity in early-type galaxies (ETGs), using recent studies that leverage photometry in the rest-frame ultraviolet (UV) wavelengths. While classically thought to be old, passively-evolving systems, recent UV studies have revealed widespread star formation in ETGs, with ~20% of the stellar mass in today's ETGs forming at late epochs (z < 1). A strong correlation is found between the presence of morphological disturbances and blue UV colours, suggesting that the star formation is merger-driven. However, the major merger rate at late epochs is far too low to satisfy the number of disturbed ETGs, indicating that minor mergers drive the star formation in these galaxies over the latter half of cosmic time. Together with the recent literature which suggests that minor mergers may drive the size evolution of massive ETGs, these results highlight the significant role of minor mergers in driving the evolution of massive galaxies in the low and intermediate-redshift Universe.
Peroxisome proliferator activated receptor gamma is a ligand-dependent transcription factor with an important role in insulin resistance and obesity. We investigated the associations between the Pro12Ala polymorphism of this receptor, obstructive sleep apnoea hypopnoea syndrome and hyperlipidaemia risk factors, in a Chinese cohort.
Subjects and methods:
We recruited 420 obstructive sleep apnoea hypopnoea syndrome patients and 190 healthy controls. Genetic analysis was conducted by restriction fragment length polymorphism. The hyperlipidaemia risk in both the study and control groups was analysed.
Results:
Comparison of genotype and allele frequencies revealed no significant differences between patients and controls (p > 0.05). In patients, there was no correlation between genotype and clinical parameters (p > 0.05), apart from a significant association between the Ala12 allele and hyperlipidaemia (odds ratio = 2.181; p = 0.017; 95 per cent confidence interval = 1.133–4.198).
Conclusion:
In this Chinese cohort, the Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma was not associated with obstructive sleep apnoea hypopnoea syndrome, but was associated with increased hyperlipidaemia risk.