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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
OBJECTIVES/GOALS: Access to pediatric subspecialty care varies by sociodemographic factors. Providers for gender diverse youth (GDY) are rare, and GDY face health disparities, stigma, and discrimination. We examined the association between GDY access to medical and mental health care and rurality, race, parental education, and other GDY-specific factors. METHODS/STUDY POPULATION: We surveyed parents of GDY (<18 years old) across the United States. Participants were recruited through online communities and listserves specific to parents of GDY. We determined associations between access to gender-specific medical or mental health providers and rurality, race, parental education, as well as other GDY-specific factors including age, time since telling their parent their gender identity, parent-adolescent communication, parent stress, and gender identity using chi-square or Fisher’s exact tests. We calculated adjusted odds ratios using logistic regression models. RESULTS/ANTICIPATED RESULTS: We surveyed 166 parents and caregivers from 31 states. The majority (73.2%) identified as white, 66.5% had earned a bachelor’s degree or higher, and 7.6% lived in a zip code designated rural by the Federal Office of Rural Health Policy. We found no evidence of association between reported GDY access to medical or mental health care and race, parental education, or rurality. We did find a significant univariate association between access to mental health care and feminine (either female or transfeminine/transfemale) gender identity (p = 0.033, OR 2.60, 95% CI 1.06 – 6.36). After controlling for parent-adolescent communication in a backwards elimination logistic regression model, it was no longer significant (p = 0.137, OR 2.05, 95% CI 0.80 – 5.25). DISCUSSION/SIGNIFICANCE OF IMPACT: Despite rurality, race, and parental education impacting access to pediatric subspecialty care, we failed to find these associations among GDY accessing gender care. There is a need to better understand structural and societal barriers to care for this population including the impact of stigma and discrimination.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.
From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.
All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.
No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.
Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes.
This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013.
Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis.
We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.
We have been interested in the plasmonic properties of alternative conducting materials to metals, such as conducting oxides, and we have recently expanded our studies to include highly correlated oxides, such as vanadium dioxide (VO2) thin films. VO2 exhibits a metal-insulator transition (MIT) just above ambient temperature at ∼ 340K. Interestingly, this transition can be induced thermally, optically or applying electric fields. Across the MIT, the optical properties are completely modified over a broad frequency range. We will present our recent optical investigations on the photon induced transition studies on such films, as well as the surface plasmon resonance (SPR) modulation in nanopatterned Au gratings by the thermally induced MIT in VO2 thin films, addressing possibilities of ultrafast SPR modulation with VO2.
Between 30 and 60% of adults with unipolar or bipolar disorders exhibit
impairments across multiple domains. However, little is known about
impaired functioning in youth with mood disorders.
To examine the prevalence of objective, subjective and observer-rated
disability in a large, representative sample of young people with a
primary mood disorder.
Individuals aged 16–25 years presenting to youth mental health services
for the first time with a primary mood disorder participated in a
systematic diagnostic and clinical assessment. Impairment was assessed
using objective (unemployment or disability payments), observer- (Social
and Occupational Functioning Assessment Scale; SOFAS) and self-rated
measures (role functioning according to the Brief Disability
Of 1241 participants (83% unipolar; 56% female), at least 30% were
functionally impaired on the objective, self-rated and/or observer-rated
measures, with 16% impaired according to all three criteria. Even when
current distress levels were taken into account, daily use of cannabis
and/or nicotine were significantly associated with impairment, with odds
ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders
were related to lower SOFAS scores (OR = 2–5).
Levels of disability were significant, even in those presenting for
mental healthcare for the first time. Functional impairment did not
differ between unipolar and bipolar cases, but some evidence suggested
that females with bipolar disorder were particularly disabled. The
prevalence of comorbid disorders (50%) and polysubstance use (28%) and
their association with disability indicate that more meaningful
indicators of mood episode outcomes should focus on functional rather
than symptom-specific measures. The association between functioning and
nicotine use requires further exploration.
We are conducting a large survey of distant clusters of galaxies using radio sources with bent jets and lobes as tracers. These radio sources are driven by AGN and achieve their bent morphologies through interaction with the surrounding gas found in clusters of galaxies. Based on low-redshift studies, these types of sources can be used to identify clusters very efficiently. We present initial results from our survey of 653 bent-double radio sources with optical hosts too faint to appear in the SDSS. The sample was observed in the infrared with Spitzer, and it has revealed ~200 distant clusters or proto-clusters in the redshift range z ~ 0.7 - 3.0. The sample of bent-doubles contains both quasars and radio galaxies enabling us to study both radiative and kinetic mode feedback in cluster and group environments at a wide range of redshifts.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.