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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.
The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models.
Methods
A machine learning approach was applied to predict anxiety disorder remission in a large sample of 2114 anxious youth (5–18 years). Potential predictors included demographic, clinical, parental, and treatment variables with data obtained pre-treatment, post-treatment, and at least one follow-up.
Results
All machine learning models performed similarly for remission outcomes, with AUC between 0.67 and 0.69. There was significant alignment between the factors that contributed to the models predicting two target outcomes: remission of all anxiety disorders and the primary anxiety disorder. Children who were older, had multiple anxiety disorders, comorbid depression, comorbid externalising disorders, received group treatment and therapy delivered by a more experienced therapist, and who had a parent with higher anxiety and depression symptoms, were more likely than other children to still meet criteria for anxiety disorders at the completion of therapy. In both models, the absence of a social anxiety disorder and being treated by a therapist with less experience contributed to the model predicting a higher likelihood of remission.
Conclusions
These findings underscore the utility of prediction models that may indicate which children are more likely to remit or are more at risk of non-remission following CBT for childhood anxiety.
Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366
This chapter explores the legislative history of immigration and higher education, shedding light on the challenges faced by undocumented students in the US education system. Using findings from a qualitative study with undocumented students who left higher education, the chapter examines the barriers faced by students that affected their decisions to leave higher education, including financial need, imposter syndrome, and disclosure of identity. It also looks at the impact of interactions with peers, family pressure, and changing campus resources on student persistence. This chapter offers recommendations for support and retention of these students, including guidance during the transition from high school, advising, fostering a sense of community, and direct support services.
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.
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
To develop and internally validate a Free Sugars Screener (FSS) for Australian children aged 2 and 5 years.
Design:
Using data collected from a ninety-nine-item (2-year-olds) and ninety-eight-item (5-year-olds) FFQ in the Study of Mothers’ and Infants’ Life Events affecting oral health (SMILE-FFQ), a regression-based prediction modelling approach was employed to identify a subset of items that accurately estimate total free sugars intake (FSI). The predictors were grams of free sugars (FSg) for individual items in the SMILE-FFQ and child’s age and sex. The outcome variable was total FSI per person. To internally validate the SMILE-FSS items, the estimated FSg was converted to percent energy from free sugars (%EFS) for comparison to the WHO free sugars guideline categories (< 5 %, 5–< 10 % and ≥ 10 %EFS) using cross-classification analysis.
Setting:
Australia.
Participants:
858 and 652 2- and 5-year-old children, respectively, with complete dietary (< 5 % missing) and sociodemographic data.
Results:
Twenty-two and twenty-six items were important in predicting FSI at 2 and 5 years, respectively. Items were similar between ages with more discretionary beverage items (e.g. sugar-sweetened beverages) at 5 years. %EFS was overestimated by 4·4 % and 2·6 %. Most children (75 % and 82 %) were categorised into the same WHO free sugars category with most (87 % and 95 %) correctly identified as having < 10 %EFS in line with the WHO recommendation.
Conclusions:
The SMILE-FSS has good internal validity and can be used in research and practice to estimate young Australian children’s FSI and compare to the WHO free sugars guidelines to identify those ‘at risk’.
Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in addition to penicillin, but evidence to support this is limited. This review assessed the evidence of benefit of metronidazole for the treatment of peritonsillar abscess.
Methods
A systematic review was conducted of the literature and databases including Ovid Medline, Ovid Embase, PubMed and Cochrane library. Search terms included all variations of peritonsillar abscess, penicillin and metronidazole.
Results
Three randomised, control trials were included. All studies assessed the clinical outcomes after treatment for peritonsillar abscess, including recurrence rate, length of hospital stay and symptom improvement. There was no evidence to suggest additional benefit with metronidazole, with studies suggesting increased side effects.
Conclusion
Evidence does not support the addition of metronidazole in first-line management of peritonsillar abscess. Further trials to establish optimum dose and duration schedules of oral phenoxymethylpenicillin would benefit clinical practice.
Since the 1990s, the racial landscape of Spain has dramatically shifted as a result of migration via the entrance of immigrants and the exodus of Spaniards as a result of the global economic crisis. The influx of racialized migrants (and subsequently, citizens) over the last 30 years has led to the development of racist metaphors that reference natural disasters such as floods, avalanches, and seismic phenomena, all of which are events that are becoming more common owing to climate change. In addition, in the media, politics, and cultural production, immigrants of color have been referred to as scum or pollution that restricts the air (i.e., the lives) of good (to be read as white) Spanish citizens. These metaphors refer both materially and symbolically to events associated over the years with threat and destruction in order to promote xenophobic and racist ideologies within the national imaginary. Such discourses have led to violence as in the famous race riots in El Ejido in 2000. These metaphors thereby demonstrate the existence of a necropolitical structure, in which the Spanish State and Spanish society more largely have facilitated a system in which racialized migrants live in constant precarity. These people live, and in many cases, die to sustain Spain’s agricultural and oenological industries, thereby stimulating the national economy. I propose that the narrative of toxicity that is used against immigrants (particularly Black and Arab ones) is actually a projection not only of the Spanish nation state’s fragility as a result of its ecocide domestically, but also of the toxicity it spews abroad by operating as a Fortress Europe nation guided by capitalism. This projection necessitates a dependence on migrants to sustain the national ecosystem in both literal and figurative terms. Thus, given the use of these environmental metaphors and their real-life implications for racialized people, there is a real need for racial justice and environmental justice to go hand in hand.
Various scholars have explored how rampant consumerism in the Global North has subjugated those who live in the Global South. As Srnicek and Williams note:
Capital requires a particular type of surplus population: cheap, docile, and pliable. Without these characteristics, this excess of humanity becomes a problem for capital.
To explore communities’ perspectives on the factors in the social food environment that influence dietary behaviours in African cities.
Design:
A qualitative study using participatory photography (Photovoice). Participants took and discussed photographs representing factors in the social food environment that influence their dietary behaviours. Follow-up in-depth interviews allowed participants to tell the ‘stories’ of their photographs. Thematic analysis was conducted, using data-driven and theory-driven (based on the socio-ecological model) approaches.
Setting:
Three low-income areas of Nairobi (n 48) in Kenya and Accra (n 62) and Ho (n 32) in Ghana.
Participants:
Adolescents and adults, male and female aged ≥13 years.
Results:
The ‘people’ who were most commonly reported as influencers of dietary behaviours within the social food environment included family members, friends, health workers and food vendors. They mainly influenced food purchase, preparation and consumption, through (1) considerations for family members’ food preferences, (2) considerations for family members’ health and nutrition needs, (3) social support by family and friends, (4) provision of nutritional advice and modelling food behaviour by parents and health professionals, (5) food vendors’ services and social qualities.
Conclusions:
The family presents an opportunity for promoting healthy dietary behaviours among family members. Peer groups could be harnessed to promote healthy dietary behaviours among adolescents and youth. Empowering food vendors to provide healthier and safer food options could enhance healthier food sourcing, purchasing and consumption in African low-income urban communities.
High rates of recidivism are reported after paediatric cholesteatoma surgery. Our practice has adapted to include non-echoplanar diffusion-weighted magnetic resonance imaging for the diagnosis of residual or recurrent cholesteatoma. This audit aimed to evaluate the performance of non-echoplanar diffusion-weighted magnetic resonance imaging in our paediatric population.
Methods
A retrospective review was conducted of non-echoplanar diffusion-weighted magnetic resonance imaging scans performed to detect residual disease or recurrence after surgery for cholesteatoma in children from 1 January 2012 to 30 November 2017 in our centre. Follow-up diffusion-weighted magnetic resonance imaging scans were reviewed to 16 August 2019.
Results
Thirty-four diffusion-weighted magnetic resonance imaging scans were included. The sensitivity and specificity values of diffusion-weighted magnetic resonance imaging for detecting post-operative cholesteatoma were 81 per cent and 72 per cent, respectively. Positive predictive and negative predictive values were 72 per cent and 81 per cent, respectively.
Conclusion
Use of diffusion-weighted magnetic resonance imaging is recommended as a replacement for routine second-look surgical procedures in the paediatric population. However, we would caution that patients require close follow up after negative diffusion-weighted magnetic resonance imaging findings.
To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students.
Design:
An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health.
Setting:
Twenty-two higher education institutions.
Participants:
College students (n 17 686) enrolled at one of twenty-two participating universities.
Results:
Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04).
Conclusions:
College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.
Coronavirus disease 2019 was declared a pandemic on 11th March 2020. All non-urgent surgical procedures have been postponed indefinitely. The British Association of Head and Neck Oncology state that only those with treatable head and neck cancer unsuitable for alternative treatment should undergo surgery. This paper details our management of a patient who tested positive for severe acute respiratory syndrome coronavirus-2 days before curative surgery for laryngeal cancer.
Case report
By following British Association of Head and Neck Oncology guidance, a 49-year-old male scheduled for total laryngectomy and bilateral neck dissection for a T3 transglottic squamous cell cancer was pre-operatively identified as an asymptomatic carrier of severe acute respiratory syndrome coronavirus-2. Following 14-day isolation and laboratory proven viral clearance, he underwent successful major surgery. He was managed throughout the peri- and post-operative phases without complications or adverse effects on staff.
Conclusion
With careful planning, previous coronavirus disease 2019 positive status should not prevent an individual from undergoing successful total laryngectomy and bilateral neck dissection in a safe and timely manner during the pandemic.
22q11.2 deletion syndrome (22q11DS) associates with schizophrenia spectrum disorders (SSDs), autism spectrum disorders (ASDs), and other psychiatric disorders, but co-occurrence of diagnoses are not well described.
Methods
We evaluated the co-occurrence of SSDs, ASDs and other axis I psychiatric diagnoses in 31 adolescents and adults with 22q11DS, assessing ASDs using either stringent Collaborative Program for Excellence in Autism (ASD-CPEA) criteria, or less stringent DSM-IV criteria alone (ASD-DSM-IV).
Results
Ten (32%) individuals met criteria for an SSD, five (16%) for ASD-CPEA, and five others (16%) for ASD-DSM-IV. Of those with ASD-CPEA, one (20%) met SSD criteria. Of those with ASD-DSM-IV, four (80%) met SSD criteria. Depressive disorders (8 individuals; 26%) and anxiety disorders (7; 23%) sometimes co-occurred with SSDs and ASDs. SSDs, ASDs, and anxiety occurred predominantly among males and depression predominantly among females.
Conclusions
Individuals with 22q11DS can manifest SSDs in the presence or absence of ASDs and other axis I diagnoses. The results suggest that standard clinical care should include childhood screening for ASDs, and later periodic screening for all axis I diagnoses.
Background: Adults are at risk of being exposed to influenza from many sources. Healthcare personnel (HCP) have the additional risk of being exposed to ill patients.
Objective:
To determine whether HCP were at higher risk than adults working in nonhealthcare roles (non-HCP).
Design:
Prospective cohort study.
Setting:
Acute-care hospitals and other businesses in Toronto, Ontario, Canada.
Methods:
Adults aged 18–69 years were enrolled for 1 or more of the 2010/2011, 2011/2012, and 2012/2013 influenza seasons. Swabs collected during acute respiratory illnesses were tested for influenza and pre- and postseason blood samples were tested for influenza-specific immune response.
Results:
The adjusted odds of influenza were similar for HCP and non-HCP (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.63–2.63). Older adults and those vaccinated against influenza had lower odds, and those who shared their workspace and who used corrective eyewear had higher odds of influenza.
Conclusions:
HCP and other working adults are at similar risk of influenza infection.
Frozen raw breaded chicken products (FRBCP) have been identified as a risk factor for Salmonella infection in Canada. In 2017, Canada implemented whole genome sequencing (WGS) for clinical and non-clinical Salmonella isolates, which increased understanding of the relatedness of Salmonella isolates, resulting in an increased number of Salmonella outbreak investigations. A total of 18 outbreaks and 584 laboratory-confirmed cases have been associated with FRBCP or chicken since 2017. The introduction of WGS provided the evidence needed to support a new requirement to control the risk of Salmonella in FRBCP produced for retail sale.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Observations of the water level in Beaver Lake, an epishelf lake in East Antarctica, show a regular tidal signal that is lagged and attenuated from the tides beneath the adjacent Amery Ice Shelf. The phase lag and amplitude attenuation can be created by a narrow inlet connection between Beaver Lake and the cavity beneath the Amery Ice Shelf. A forced linear damped oscillator is used to determine the inlet dimensions that are required to produce the observed phase lag and amplitude attenuation. The model shows that the observations are consistent with a tidal flow that is restricted by the drag created by flow in the narrow inlet. Analysis shows that the phase lag and amplitude attenuation of the tides in Beaver Lake has increased over the years 1991-2002, probably due to a thickening of the overlying ice shelf. The response is sensitive to subtle variations in the dimensions of the inlet.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
Aims
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Method
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
Results
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
Conclusions
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.