Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.

In the past decade, there have been substantial changes in diagnostic nomenclature. This study investigated sex differences in attention-deficit/hyperactivity disorder (ADHD) symptom severity based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV(TR), and DSM-5 criteria, separating rating scale and clinical interview data in children and adults with ADHD. PubMed, PsycINFO, and Scopus were searched for published studies (1996–2021) reporting severity of attention, and hyperactivity/impulsivity in males and females. We compared data: (1) across the entire lifespan aggregating rating scale and clinical interview data (51 studies), (2) drawing solely on rating scale data (18 studies), and (3) drawing solely on clinical interview data (33 studies). Fifty-two studies met inclusion criteria comparing data for females (n = 8423) and males (n = 9985) with ADHD across childhood and/or adulthood. In total, 15 meta-analyses were conducted. Pooled data across the lifespan aggregating both rating scale and clinical diagnostic interview data, showed males had significantly more severe hyperactivity/impulsivity symptoms than females. Rating scale data were similar; boys had significantly more severe hyperactivity/impulsivity than girls. In adulthood, men were rated to have significantly more severe inattention than women with no difference in the hyperactivity/impulsivity dimension. All significant differences were of small effect size. No significant sex differences in the severity of symptoms emerged for clinical interview data for children or adults, in contrast. Possible reasons for the discrepancy in findings between rating scales and clinical diagnostic interviews are discussed.

This study investigated the effects of Lacticaseibacillus rhamnosus HN001 supplementation on the architecture and gene expression in small intestinal tissues of piglets used as an animal model for infant humans. Twenty-four 10-d-old entire male piglets (4·3 (sd 0·59) kg body weight) were fed an infant formula (IF) (control) or IF supplemented with 1·3 × 105 (low dose) or 7·9 × 106 (high dose) colony-forming units HN001 per ml of reconstituted formula (n 8 piglets/treatment). After 24 d, piglets were euthanised. Samples were collected to analyse the histology and gene expression (RNAseq and qPCR) in the jejunal and ileal tissues, blood cytokine concentrations, and blood and faecal calprotectin concentrations. HN001 consumption altered (false discovery rate < 0·05) gene expression (RNAseq) in jejunal tissues but not in ileal tissues. The number of ileal goblet cells and crypt surface area increased quadratically (P < 0·05) as dietary HN001 levels increased, but no increase was observed in the jejunal tissues. Similarly, blood plasma concentrations of IL-10 and calprotectin increased linearly (P < 0·05) as dietary HN001 levels increased. In conclusion, supplementation of IF with HN001 affected the architecture and gene expression of small intestine tissue, blood cytokine concentration and frequencies, and blood calprotectin concentrations, indicating that HN001 modulated small intestinal tissue maturation and immunity in the piglet model.

Clinical guidelines recommend device removal for cardiovascular implantable electronic device (CIED) infection management. In this retrospective, nationwide cohort, 60.8% of CIED infections received guideline-concordant care. One-year mortality was higher among those without procedural management (25% vs 16%). Factors associated with receipt of device procedures included pocket infections and positive microbiology.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

Escherichia coli concentration levels in recreational water are used by beach managers to evaluate the risk of gastrointestinal illness among beachgoers. We examined the relationship between specific environmental factors and E. coli concentration in recreational beaches in the Niagara Region. We analysed E. coli geometric means collected from eight beaches from two of the Great Lakes in the Niagara Region in Ontario, between 2011 and 2019. We applied path analysis to evaluate the relationship between the environmental factors and E. coli concentrations, including whether effects were direct or indirect via a mediator. Turbidity was found to be an important mediator for the indirect effect of environmental variables overall and in beach-specific models. Rainfall and streamflow had a positive indirect effect on E. coli via turbidity and a direct effect in five out of seven beach models. Streamflow was also a mediator for the indirect effect of previous day air temperature in five out of seven models. In three subset models, outfall E. coli concentration was a mediator for the effect of the environmental factors. Using a novel methodological approach, this study identifies important relationships and pathways that predict beach E. coli concentration in freshwater beaches located on two of the Great Lakes.

Background: Surgical site infections (SSIs) among cardiothoracic (CT) patients are associated with high rates of morbidity and mortality. Data are limited regarding SSI incidence among pediatric patients undergoing primary reparative procedures for congenital cardiac disease. Published evidence on targeted interventions to prevent pediatric CT-surgery SSI is lacking. We aimed to establish standard metrics for measuring CT-surgery SSI incidence and to implement bundled interventions for SSI prevention. Methods: A dedicated CT-surgery SSI prevention workgroup was established, consisting of hospital leadership, CT surgeons, cardiac critical care unit staff, anesthesia, perfusion, environmental services, instrument sterile processing, risk management, infection prevention and antibiotic stewardship. We created a standard definition for CT-surgery SSI and calculated retrospective SSI rates over a 24-month period (2017–2019). The outcome measured was incidence of CT-surgery SSI per 100 primary cardiac procedures with delayed ( 3 days after primary surgery) or non-delayed chest closure. The difference in proportion of SSI was reported separately for delayed closure and non-delayed closure; statistical significance was tested using a Fisher’s Exact test. We identified many potential improvement opportunities, including gaps in SSI surveillance, poor compliance with daily bathing, inconsistent perioperative antimicrobial prophylaxis, lack of controlled environment for bedside chest closures, and lapses in environmental cleaning. These issues informed the enhanced SSI prevention bundle, which included education on sterility with the operating room (OR) staff. Protocols for care of cardiac patients with delayed chest closures focused on universal daily and preoperative chlorhexidine baths. In addition, the bundle incorporated stringent environmental cleaning interventions including scheduled decluttering of patient rooms and clinical spaces, terminal cleaning of patient rooms prior to returning from the OR, and use of adjunctive ultraviolet light for the daily cleaning of operating rooms and patient rooms at discharge. Results: Surveillance definition of microbiological growth from a clinical sample obtained within 30 days of primary cardiac procedure sufficiently captured all CT-surgery SSIs. Of 551 CT-surgery procedures prior to intervention, 91 (17%) had delayed final operative closures. Prior to the intervention, 16 SSIs were identified from July 2017 – May 2019 for a rate of 2.90 per /100 procedures, and was higher among patients with delayed chest closure 6.59 per /100 procedures (6 SSIs/91 procedures) versus those with primary chest closure 2.17 per /100 procedures (10 SSIs/460 procedures; P = 0.034). Gram-positive organisms, including coagulase coagulase-negative Staphylococci, were most frequently identified as the causative organisms for SSIs. Compliance with bundled intervention, rolled out over a 2-month period, was associated with an immediate decrease in the number of SSIs for primary and delayed chest closures 6SSIs /185 procedures in the initial quarters (August – December 2019) of the post-intervention period. However, this decrease was not reflected in the overall rate (3.24 per /100 procedures) due to fewer procedures performed. Data collection to measure sustainability is ongoing. Conclusions: Bundled interventions targeting skin antisepsis and environmental cleaning may be associated with a decrease in SSIs among pediatric CT-surgery patients. Ongoing surveillance is required to determine sustainability of these interventions.

Funding: None

Disclosures: None

Background: Central-line–associated bloodstream infection (CLABSI) rates have steadily decreased as evidence-based prevention bundles were implemented. Bone marrow transplant (BMT) patients are at increased risk for CLABSI due to immunosuppression, prolonged central-line utilization, and frequent central-line accesses. We assessed the impact of an enhanced prevention bundle on BMT nonmucosal barrier injury CLABSI rates. Methods: The University of Iowa Hospitals & Clinics is an 811-bed academic medical center that houses the only BMT program in Iowa. During October 2018, we added 3 interventions to the ongoing CLABSI prevention bundle in our BMT inpatient unit: (1) a standardized 2-person dressing change team, (2) enhanced quality daily chlorhexidine treatments, and (3) staff and patient line-care stewardship. The bundle included training of nurse champions to execute a team approach to changing central-line dressings. Standard process description and supplies are contained in a cart. In addition, 2 sets of sterile hands and a second person to monitor for breaches in sterile procedure are available. Site disinfection with chlorhexidine scrub and dry time are monitored. Training on quality chlorhexidine bathing includes evaluation of preferred product, application per product instructions for use and protection of the central-line site with a waterproof shoulder length glove. In addition to routine BMT education, staff and patients are instructed on device stewardship during dressing changes. CLABSIs are monitored using NHSN definitions. We performed an interrupted time-series analysis to determine the impact of our enhanced prevention bundle on CLABSI rates in the BMT unit. We used monthly CLABSI rates since January 2017 until the intervention (October 2018) as baseline. Because the BMT changed locations in December 2018, we included both time points in our analysis. For a sensitivity analysis, we assessed the impact of the enhanced prevention bundle in a hematology-oncology unit (March 2019) that did not change locations. Results: During the period preceding bundle implementation, the CLABSI rate was 2.2 per 1,000 central-line days. After the intervention, the rate decreased to 0.6 CLABSI per 1,000 central-line days (P = .03). The move in unit location did not have a significant impact on CLABSI rates (P = .85). CLABSI rates also decreased from 1.6 per 1,000 central-line days to 0 per 1,000 central-line days (P < .01) in the hematology-oncology unit. Conclusions: An enhanced CLABSI prevention bundle was associated with significant decreases in CLABSI rates in 2 high-risk units. Novel infection prevention bundle elements should be considered for special populations when all other evidence-based recommendations have been implemented.

Funding: None

Disclosures: None

Unlike most other countries, in the United States, subnational governments (states) have substantial authority over collective bargaining and union organization laws. Because states compete for business investment and union (dis)organization likely has spillover effects beyond state borders, weak unions in one state may affect union organization in other states. We examine how union decline in one state is associated with union decline in neighboring states, and whether the presence of prounion (left-leaning) governments may limit the spread of union decline. Examining a period of major union decline (1983-2014), we find that union weakness in one state is associated with union weakness in nearby states. We observe that Democratic power in Congress is associated with higher unionization rates, but that liberal state governments have been relatively powerless to stop union decline in this period. These findings have important implications for understanding the historical and contemporary weakness of American unions and for the future of union strength in the United States.

During 2000–07, five giant icebergs (B15A, B15J, B15K, C16 and C25) adrift in the southwestern Ross Sea, Antarctica, were instrumented with global positioning system (GPS) receivers and other instruments to monitor their behavior in the near-coastal environment. The measurements show that collision processes can strongly influence iceberg behavior and delay their progress in drifting to the open ocean. Collisions appear to have been a dominant control on the movement of B15A, the largest of the icebergs, during the 4-year period it gyrated within the limited confines of Ross Island, the fixed Ross Ice Shelf and grounded C16. Iceberg interactions in the near-coastal regime are largely driven by ocean tidal effects which determine the magnitude of forces generated during collision and break-up events. Estimates of forces derived from the observed drift trajectories during the iceberg-collisioninduced calving of iceberg C19 from the Ross Ice Shelf, during the iceberg-induced break-off of the tip of the Drygalski Ice Tongue and the break-up of B15A provide a crude estimate of the stress scale involved in iceberg calving. Considering the total area the vertical face of new rifts created in the calving or break-up process, and not accounting for local stress amplification near rift tips, this estimated stress scale is 104 Pa.

We detail the rewards and barriers to participating in multidisciplinary research (MDR) using a 2011 survey of applied economists at U.S. universities. We compare these findings with an earlier 1993 survey to assess if rewards and barriers have changed over time. Different administrative levels of U.S. universities are sending contradictory signals regarding rewards from MDR. External funding agencies convey positive signals. Although the scope and breadth of questions addressed by applied economists are changing over time, institutional incentives and reward structures are not keeping pace with these changes. Progress toward adapting to new professional demands has been slow.

The Florida Children’s Medical Services (CMS) has a long-standing history of ensuring that providers of multiple paediatric subspecialties abide by the highest standards. The cardiac sub-committee has written quality standard documents that participating programmes must meet or exceed. These standards oversee paediatric cardiology services including surgery, catheterisations, and outpatient services. On April, 2012, the cardiac sub-committee decided to develop similar standards in paediatric electrophysiology. A task force was created and began this process. These standards include a catalogue of required and optional equipment, as well as staff and physician credentials. We sought to establish expectations of procedural numbers by practitioner and facility. The task force surveyed the members of the Pediatric and Congenital Electrophysiology Society. Finding no consensus, the task force is committed to generate the data by requiring that the CMS participating programmes enrol and submit data to the Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT™) Initiative. This manuscript details the work of the Florida CMS Paediatric Electrophysiology Task Force.

Vegetable oils containing stearidonic acid (SDA, 18 : 4n-3) are considered better precursors of long-chain n-3 PUFA (LC n-3 PUFA) than those with only α-linolenic acid (ALA, 18 : 3n-3). The present study re-examined this premise using treatments where added ALA from linseed oil was matched with ALA plus SDA from echium oil. Lambs (n 6) were abomasally infused with saline (control (C), 25 ml), echium oil low (EL, 25 ml), echium oil high (EH, 50 ml), linseed oil low (LL, 25 ml) or linseed oil high (LH, 50 ml) for 4 weeks. The basal ration used was identical across all treatments. EPA (20 : 5n-3) in meat increased from 6·5 mg in the C lambs to 16·8, 17·7, 13·5 and 11·7 (sem 0·86) mg/100 g muscle in the EL, EH, LL and LH lambs, respectively. For muscle DPA (docosapentaenoic acid; 22 : 5n-3), the corresponding values were 14·3, 22·2, 18·6 18·2 and 19·4 (sem 0·57) mg/100 g muscle. The DHA (22 : 6n-3) content of meat was 5·8 mg/100 g in the C lambs and ranged from 4·53 to 5·46 (sem 0·27) mg/100 g muscle in the oil-infused groups. Total n-3 PUFA content of meat (including ALA and SDA) increased from 39 mg to 119, 129, 121 and 150 (sem 12·3) mg/100 g muscle. We conclude that both oil types were effective in enhancing the EPA and DPA, but not DHA, content of meat. Furthermore, we conclude that, when balanced for precursor n-3 fatty acid supply, differences between linseed oil and echium oil in enriching meat with LC n-3 PUFA were of little, if any, nutritional significance.