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First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
OBJECTIVES/SPECIFIC AIMS: (1) Assess if the total duration of EEG suppression during a protocolized exposure to general anesthesia predicts cognitive performance in multiple cognitive domains immediately following emergence from anesthesia. (2) Assess if the total duration of EEG suppression in the same individuals predicts the rate of cognitive recovery in a three-hour period following emergence from anesthesia. METHODS/STUDY POPULATION: This was a non-specified substudy of NCT01911195, a multicenter investigation taking place at the University of Michigan, University of Pennsylvania, and Washington University in St. Louis. 30 healthy volunteers aged 20-40 years were recruited to receive general anesthesia. Participants in the anesthesia arm were anesthetized for three hours at isoflurane levels compatible with surgery (1.3 MAC). Multichannel sensor nets were used for EEG acquisition during the anesthetic exposure. EEG suppression was detected through automated voltage-thresholded classification of 2-second signal epochs, with concordance assessed across sensors. Following return of responsiveness to verbal commands, participants completed up to three hours of serial cognitive tests assessing executive function, reaction time, cognitive throughput, and working memory. Non-linear mixed effects models will be used to estimate the initial cognitive deficit and the rate of cognitive recovery following anesthetic exposure; these measures of cognitive function will be assessed in relation to total duration of suppression during anesthesia. RESULTS/ANTICIPATED RESULTS: Participants displayed wide variability in the total amount of suppression during anesthesia, with a median of 31.2 minutes and range from 0 minutes to 115.2 minutes. Initial analyses suggest that greater duration of burst suppression had a weak relationship with participants’ initial cognitive deficits upon return of responsiveness from anesthesia. Model generation of rate of recovery following anesthetic exposure is pending, but we anticipate this will also have a weak relationship with burst suppression. DISCUSSION/SIGNIFICANCE OF IMPACT: In healthy adults receiving a standardized exposure to anesthesia without surgery, burst suppression appears to be a poor predictor of post-anesthesia cognitive task performance. This suggests that burst suppression may have limited utility as a predictive marker of post-operative cognitive functioning, particularly in young adults without significant illness.
Investigate short- and long-term effects of Superstorm Sandy on multiple morbidities among the elderly.
We examined emergency department visits; outpatient visits; and hospital admissions for cardiovascular disease (CVD), respiratory disease, and injury among residents residing in 8 affected counties immediately, 4 months, and 12 months following Superstorm Sandy. Control groups were defined as visits/admissions during the identical time window in the 5 years before (2007-2011) and 1 year after (2013-2014) the storm in affected and nonaffected counties in New York. We performed Poisson regression to test whether there was an association of increased visits/admissions for periods following Superstorm Sandy while controlling for covariates.
We found that the risk for CVD, respiratory disease, and injury visits/admissions was more than twice as high immediately, 4 months, and 12 months after the storm than it was in the control periods. Women were at greater risk at all time periods for CVD (risk ratio [RR], 2.04) and respiratory disease (RRs: 1.89 to 1.92). Whites had higher risk for CVD, respiratory disease, and injury than other racial groups during each period.
We observed increases in CVD, respiratory disease, and injury up to a year following Superstorm Sandy. Findings demonstrate the need to incorporate short- and long-term health effects into public health recovery. (Disaster Med Public Health Preparedness. 2019;13:28-32)
Strong strain-mediated magnetoelectric (ME) coupling in magnetic/ferroelectric heterostructures has great potential for different high-frequency multiferroic devices. In this article, we present the most recent progress in integrated multiferroic devices. Integrated magnetic tunable inductors with a wide operation frequency range, integrated nonreciprocal bandpass filters with dual magnetic and electric-field tunability based on magnetostatics surface waves, and novel radio-frequency nanomechanical ME resonators with pico-Tesla sensitivity for direct current magnetic fields are presented. Finally, a new antenna miniaturization mechanism, acoustically actuated nanomechanical ME antennas, which can successfully miniaturize the size by 1–2 orders, is introduced. With the advantages of high magnetic field sensitivity, highest antenna gain among all nanoscale antennas at similar frequency, integrated capability with complementary metal oxide semiconductor technology, and ground-plane immunity from metallic surfaces and the human body, ME antennas have a bright future for biomedical applications, wearable antennas, and the Internet of Things due to their unique and particular properties.
Hospitals may implement admission screening cultures and may review transfer documentation to identify patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) to implement isolation precautions; however, outcomes and logistical considerations have not been well described.
At an academic hospital in Chicago, we retrospectively studied the implementation and outcomes of CRE admission screening from 2013 to 2016 during 2 periods. During period 1, we implemented active CRE rectal culture screening for all adults patients admitted to intensive care units (ICUs) and for those transferred from outside facilities to general wards. During period 2, screening was restricted only to adults transferred from outside facilities. For a subset of transferred patients who were previously reported to the health department as CRE positive, we reviewed transfer paperwork for appropriate documentation of CRE.
Overall, 11,757 patients qualified for screening; rectal cultures were performed for 8,569 patients (73%). Rates of CRE screen positivity differed by period, previous facility type (if transferred), and current inpatient location. A higher combined CRE positivity rate was detected in the medical and surgical ICUs among period 2 patients (3.3%) versus all other ward-period comparisons (P<.001). Among 13 transferred patients previously known to be CRE colonized, appropriate CRE transfer documentation was available for only 4 patients (31%).
Active screening for CRE is feasible, and screening patients transferred from outside facilities to the medical or surgical ICU resulted in the highest screen positivity rate. Furthermore, CRE carriage was inconsistently documented in transfer paperwork, suggesting that admission screening or enhanced inter-facility communication are needed to improve the identification of CRE-colonized patients.
Thermocapillary dewetting of liquids and molten films has recently emerged as a viable alternative to conventional microprocessing methods. As this thermal gradient-induced mechanism is universal, it can be applied to any material. This work explores the sequential dewetting of materials with varying melting points, including polymers and metals, to create aligned morphologies. The variation in melting point allows for the dewetting of single layers at a time or mobility-limited simultaneous dewetting. As a result, a variety of multimaterial structures can be produced with built-in alignment, such as arrays of concentric circles, lines with periodic segmentation, or islands on holes. This approach employs photothermal methods to induce the necessary thermal gradient, manipulating several variables in order to influence the consequent structures. Adjusting laser power and light intensity allows for the control of temperature for selective dewetting of films; altering beam size and exposure time affects the extent of dewetting in terms of diameter size; overlap effects and simultaneous dewetting can result in complex architectures. This controlled writing of patterns also presents a technique to create both masks at low temperatures for conductive multilayers as well as templates for electrospray deposition.
Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)–impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results.
To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin.
Prospective, randomized 2-center study with blinded assessment.
PARTICIPANTS AND SETTING
Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016.
Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non–antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C).
In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001).
In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined.
Because antibacterial history is difficult to obtain, especially when the exposure occurred at an outside hospital, we assessed whether infection-related diagnostic billing codes, which are more readily available through hospital discharge databases, could infer prior antibacterial receipt.
Retrospective cohort study.
This study included 121,916 hospitalizations representing 78,094 patients across the 3 hospitals.
We obtained hospital inpatient data from 3 Chicago-area hospitals. Encounters were categorized as “infection” if at least 1 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code indicated a bacterial infection. From medication administration records, we categorized antibacterial agents and calculated total therapy days using Centers for Disease Control and Prevention (CDC) definitions. We evaluated bivariate associations between infection encounters and 3 categories of antibacterial exposure: any, broad spectrum, or surgical prophylaxis. We constructed multivariable models to evaluate adjusted risk ratios for antibacterial receipt.
Of the 121,916 inpatient encounters (78,094 patients) across the 3 hospitals, 24% had an associated infection code, 47% received an antibacterial, and 13% received a broad-spectrum antibacterial. Infection-related ICD-9-CM codes were associated with a 2-fold increase in antibacterial administration compared to those lacking such codes (RR, 2.29; 95% confidence interval [CI], 2.27–2.31) and a 5-fold increased risk for broad-spectrum antibacterial administration (RR, 5.52; 95% CI, 5.37–5.67). Encounters with infection codes had 3 times the number of antibacterial days.
Infection diagnostic billing codes are strong surrogate markers for prior antibacterial exposure, especially to broad-spectrum antibacterial agents; such an association can be used to enhance early identification of patients at risk of multidrug-resistant organism (MDRO) carriage at the time of admission.
Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.
We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.
Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain–symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.
Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain–symptom mediators.
To determine the impact of recurrent Clostridium difficile infection (RCDI) on patient behaviors following illness.
Using a computer algorithm, we searched the electronic medical records of 7 Chicago-area hospitals to identify patients with RCDI (2 episodes of CDI within 15 to 56 days of each other). RCDI was validated by medical record review. Patients were asked to complete a telephone survey. The survey included questions regarding general health, social isolation, symptom severity, emotional distress, and prevention behaviors.
In total, 119 patients completed the survey (32%). On average, respondents were 57.4 years old (standard deviation, 16.8); 57% were white, and ~50% reported hospitalization for CDI. At the time of their most recent illness, patients rated their diarrhea as high severity (58.5%) and their exhaustion as extreme (30.7%). Respondents indicated that they were very worried about getting sick again (41.5%) and about infecting others (31%). Almost 50% said that they have washed their hands more frequently (47%) and have increased their use of soap and water (45%) since their illness. Some of these patients (22%–32%) reported eating out less, avoiding certain medications and public areas, and increasing probiotic use. Most behavioral changes were unrelated to disease severity.
Having had RCDI appears to increase prevention-related behaviors in some patients. While some behaviors are appropriate (eg, handwashing), others are not supported by evidence of decreased risk and may negatively impact patient quality of life. Providers should discuss appropriate prevention behaviors with their patients and should clarify that other behaviors (eg, eating out less) will not affect their risk of future illness.
OBJECTIVES/SPECIFIC AIMS: Understand the immunomodulatory effects of anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (G-CSF) on type 1 diabetes patients using samples and in the preclinical model, the nonobese diabetic mouse. METHODS/STUDY POPULATION: Flow cytometry analysis of phase 1 peripheral blood samples treatment of nonobese diabetic mouse with ATG and GCSF and flow cytometry analysis of immune organs (spleen, lymph nodes, blood, bone marrow). RESULTS/ANTICIPATED RESULTS: Changes in both innate and adaptive immune cell subsets including plasmacytoid dendritic cells, naive, memory, effector CD4+ and CD8+ T-cells, and CD4+ T-regulatory cells and CD8+ T-regulatory cells DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding of immune cell targets for immunotherapy in new-onset type 1 diabetes patients.
Little is known about the joint mental health effects of air pollution and tobacco smoking in low- and middle-income countries.
To investigate the effects of exposure to ambient fine particulate matter pollution (PM2.5) and smoking and their combined (interactive) effects on depression.
Multilevel logistic regression analysis of baseline data of a prospective cohort study (n=41785). The 3-year average concentrations of PM2.5 were estimated using US National Aeronautics and Space Administration satellite data, and depression was diagnosed using a standardised questionnaire. Three-level logistic regression models were applied to examine the associations with depression.
The odds ratio (OR) for depression was 1.09 (95% CI 1.01–1.17) per 10 μg/m3 increase in ambient PM2.5, and the association remained after adjusting for potential confounding factors (adjusted OR = 1.10, 95% CI 1.02–1.19). Tobacco smoking (smoking status, frequency, duration and amount) was also significantly associated with depression. There appeared to be a synergistic interaction between ambient PM2.5 and smoking on depression in the additive model, but the interaction was not statistically significant in the multiplicative model.
Our study suggests that exposure to ambient PM2.5 may increase the risk of depression, and smoking may enhance this effect.
To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients.
Multicenter, matched case-control study.
Four LTACHs in Chicago, Illinois.
Each case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay.
From June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01–1.04; P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06–4.77; P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01–1.29; P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure.
Higher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population.
Lithium sulfur (Li–S) batteries have the potential to provide higher energy storage density at lower cost than conventional lithium ion batteries. A key challenge for Li–S batteries is the loss of sulfur to the electrolyte during cycling. This loss can be mitigated by sequestering the sulfur in nanostructured carbon–sulfur composites. The nanoscale characterization of the sulfur distribution within these complex nanostructured electrodes is normally performed by electron microscopy, but sulfur sublimates and redistributes in the high-vacuum conditions of conventional electron microscopes. The resulting sublimation artifacts render characterization of sulfur in conventional electron microscopes problematic and unreliable. Here, we demonstrate two techniques, cryogenic transmission electron microscopy (cryo-TEM) and scanning electron microscopy in air (airSEM), that enable the reliable characterization of sulfur across multiple length scales by suppressing sulfur sublimation. We use cryo-TEM and airSEM to examine carbon–sulfur composites synthesized for use as Li–S battery cathodes, noting several cases where the commonly employed sulfur melt infusion method is highly inefficient at infiltrating sulfur into porous carbon hosts.
Exocytosis is the fundamental process by which cells communicate with each other. The events that lead up to the fusion of a vesicle loaded with chemical messenger with the cell membrane were the subject of a Nobel Prize in 2013. However, the processes occurring after the initial formation of a fusion pore are very much still in debate. The release of chemical messenger has traditionally been thought to occur through full distention of the vesicle membrane, hence assuming exocytosis to be all or none. In contrast to the all or none hypothesis, here we discuss the evidence that during exocytosis the vesicle-membrane pore opens to release only a portion of the transmitter content during exocytosis and then close again. This open and closed exocytosis is distinct from kiss-and-run exocytosis, in that it appears to be the main content released during regular exocytosis. The evidence for this partial release via open and closed exocytosis is presented considering primarily the quantitative evidence obtained with amperometry.
We aimed to evaluate residence in evacuation areas (storm areas) as a risk factor for food and waterborne disease (FWBD) associated with Hurricane Sandy flooding.
We captured 9601 incident outpatient and inpatient FWBD hospital discharge diagnoses for residents of the greater New York City area. We used Poisson or negative binomial regression models to compare the covariate-adjusted risk for a FWBD diagnosis, pre-Sandy (10/28-11/09, 2001-2011) vs. post-Sandy (10/28-11/09, 2012), for residents of “storm” and “non-storm” areas.
Outpatient FWBD risk was lower for storm area residents after Hurricane Sandy (risk ratio [RR]=0.58, 95% confidence interval [CI]: 0.46-0.74), and varied by age, sex, and county. However, storm area residents 65 years of age or older experienced higher risk after Hurricane Sandy (RR=2.16, 95% CI: 1.11-4.19), albeit based on few cases. Inpatient FWBD risk was lower for non-storm area residents after Hurricane Sandy (RR=0.79, 95% CI: 0.66-0.95), and varied by age, race, and county, although there was no significant change for storm area residents (RR=0.86, 95% CI: 0.69-1.08). Those ≥65 years of age were also at lower risk for inpatient FWBD diagnosis, yet the effect was weaker for storm area (RR=0.89, 95% CI: 0.67-1.18) than for non-storm area residents (RR=0.68, 95% CI: 0.52-0.89).
Hurricane preparation, mitigation, and response activities in the greater New York City area may have led to “protective” effects for FWBD. (Disaster Med Public Health Preparedness. 2016;10:503–511)
Many young adolescents are embedded in neighborhoods, schools, and homes where alcohol and drugs are frequently used. However, little is known about (a) how witnessing others' substance use affects adolescents in their daily lives and (b) which adolescents will be most affected. The current study used ecological momentary assessment with 151 young adolescents (ages 11–15) to examine the daily association between witnessing substance use and antisocial behavior across 38 consecutive days. Results from multilevel logistic regression models indicated that adolescents were more likely to engage in antisocial behavior on days when they witnessed others using substances, an association that held when substance use was witnessed inside the home as well as outside the home (e.g., at school or in their neighborhoods). A significant Gene × Environment interaction suggested that the same-day association between witnessing substance use and antisocial behavior was significantly stronger among adolescents with, versus without, the dopamine receptor D4 seven repeat (DRD4-7R) allele. The implications of the findings for theory and research related to adolescent antisocial behavior are discussed.
We present the results of two 2.3 μm near-infrared (NIR) radial velocity (RV) surveys to detect exoplanets around 36 nearby and young M dwarfs. We use the CSHELL spectrograph (R ~ 46,000) at the NASA InfraRed Telescope Facility (IRTF), combined with an isotopic methane absorption gas cell for common optical path relative wavelength calibration. We have developed a sophisticated RV forward modeling code that accounts for fringing and other instrumental artifacts present in the spectra. With a spectral grasp of only 5 nm, we are able to reach long-term radial velocity dispersions of ~20–30 m s−1 on our survey targets.