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Introduction: Tissue diagnoses of breast cancer are made by pathologists, who generally do not interact with patients directly. A patient's diagnosis and related information is generally delivered second-hand by a treating clinician. As pathologists are able to explain how a diagnosis of breast cancer is made on a biopsy, and why and how malignant diseases are different from “normal” tissue, a patient-pathologist consultation may be a valuable option for educating the patient. In our study, we evaluate the value, if any, patient-pathologist consultations may have for patients with a diagnosis of breast cancer. Methods: Patients with a diagnosis of invasive breast carcinoma or ductal carcinoma in-situ (DCIS) were recruited to participate in a free, one-on-one patient-pathologist consultation. During the consultation, information within the patient's pathology report, breast cancer-related pathogenesis and terms, and breast biomarker immunohistochemistry were discussed. The patient was able to review their own specimen slides with the pathologist. Pre- and post-consultation surveys were administered to measure the patient’s perceived knowledge of terminology related to their diagnosis, their anxiety regarding their understanding of their diagnosis, whether they were able to mentally picture their tumor, and to measure overall satisfaction. Results: Twenty (20) female patients were recruited into the study, with a median age of 58 years. Thirteen (13) of the 20 patients (65%) had a diagnosis of invasive carcinoma (10 invasive ductal carcinoma (IDC), 2 invasive lobular carcinoma (ILC), and 1 both IDC and ILC), and 7 patients (35%) had a diagnosis of ductal carcinoma in-situ (DCIS). Pre- and post-consultation survey data showed significant increases in the patients’ perceived understanding of medical terminology related to their diagnosis following the consultation, decreases in perceived anxiety related to the understanding of their diagnosis following the consultation, and patients reported that they were able to mentally picture their tumor (Table 1). With regard to general satisfaction with the consultation, all patients believed meeting with a pathologist was valuable, and all would recommend the consultation to a family member or friend with a breast cancer diagnosis. Free-text comments were provided by 9 patients, which showed with favorable comments. Discussion and Limitations: Our results suggest that patient-pathologist consultation may be valuable to breast cancer patients. Following the consultation, patients reported less anxiety regarding the understanding of their diagnosis, were able to mentally picture their tumor, and reported a better understanding of medical terminology related to their diagnosis. There were several limitations to our study. Most consultations were provided by a single pathologist with fellowship training in breast pathology. Secondly, we had a small sample size and all participants were female. Finally, the surveys could only measure patient's short-term perception of perceived knowledge gains or lessened anxiety regarding their understanding of their diagnosis. Aside from these limitations, we feel patient-pathologist consultation for breast cancer patients, if included as part of their care, would help demystify their diagnosis and further empower the patient by increasing their knowledge of their diagnosis. Table 1.Pre- and Post-consultation Survey DataQuestion NumberQuestionPre-consultationPost-consultationp1Understanding of medical terminology related to diagnosis4 [4-7]9 [8-9] Citation Format: Catherine T Stoos, Kate A. Hunley, Laurrie Cronin, Ryan Walters. The value of patient-pathologist consultation for breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-15-01.

We aimed to study the efficacy of cardiac magnetic resonance imaging (CMR) and intracoronary optical coherence tomography (OCT) in detecting the etiology of myocardial infarction with non-obstructive coronary arteries (MINOCA). A systematic search was conducted in PubMed, Medline, and Cochrane databases. Search terms used: Myocardial infarction, Coronary angiography, Normal coronary arteries, CMR, and OCT. Inclusion criteria was fulfilled by 18 studies. Meta-analysis was performed with 15 studies. A total of 2697 patients were included. The mean age of all the patients was 51.5 and 56.4% were men. CMR established diagnosis in 74% of the patients; 29% had acute myocarditis, 18% had true myocardial infarction and 12% had takotsubo cardiomyopathy. Combining OCT with CMR was better at finding the etiology than either modality individually. The findings of this study conclude that CMR is integral in identifying the etiology of MINOCA. Coupling OCT and CMR is better than either technique individually at finding the cause.

Background: Readmissions have a significant economic impact on the healthcare burden of atrial fibrillation (AF). Health Related Social Needs (HRSN) contribute to poor outcomes including readmissions. Differences in readmission rates related to sex are unclear. Methods: Data were abstracted from the 2016 to 2018 National Readmission Database (NRD). The primary outcome was all-cause 30-day readmission following discharge for index AF. We identified HRSN (employment, family, housing, psychosocial, and socioeconomic status [SES]) using ICD-10 codes. Using multivariable logistic regression models, we evaluated whether the association between HRSN and readmission differed between males and females. Results: We identified 614,520 AF hospitalizations, which included 51% female and 49% male. The overall readmissions rate was 14.5% (95% CI: 14.4%, 14.6%). The adjusted odds of readmissions in the presence of housing, family, or psychosocial HRSN were statistically higher for males compared to females (all interaction p < .05), whereas the association between readmission and employment and SES were statistically similar. Overall, the strongest association with readmission was observed for housing (Table 1). Conclusion: Males with housing, family, and psychosocial HRSN have a higher risk of readmissions for AF . Further study is needed to address why these sex-based disparities exist and what interventions that impact HRSN may result in improved outcomes.

Objectives. Evaluate the health impact of a novel financial education and coaching program in single mothers of low-income in Omaha, Nebraska. Methods. Employed, single mothers earning no more than 200% of the 2017 Federal Poverty Level (n = 345) enrolled in the study between April 2017 and August 2020 and were randomized to receive a novel financial education and coaching program, the Financial Success Program (FSP) or no intervention control. Demographics, biometrics, financial strain, health behaviors and healthcare utilization were assessed at baseline and the 12-month study visits. Results. Participants who completed the FSP demonstrated significantly reduced financial strain, an increased rate of smoking cessation, and a reduction in avoidance of medical care due to cost compared to participants in the control group. Conclusions. The FSP represents an effective model in promoting economic stability in vulnerable individuals through a reduction in financial strain. Health behavior changes including an increased rate of smoking cessation were demonstrated within the first 12 months of intervention.

Study Objective The primary objective was to compare carbon dioxide (CO2) absorption rates in patients undergoing gynecologic laparoscopy with a standard versus valveless insufflation system (AirSeal; ConMed, Utica, NY) at intra-abdominal pressures (IAPs) of 10 and 15 mm Hg. Secondary objectives were assessment of surgeons’ visualization of the operative field, anesthesiologists’ ability to maintain adequate end-tidal CO2 (etCO2), and patients’ report of postoperative shoulder pain. Design A randomized controlled trial using an equal allocation ratio into 4 arms: standard insufflation/IAP 10 mm Hg, standard insufflation/IAP 15 mm Hg, valveless insufflation/IAP 10 mm Hg, and valveless insufflation/IAP 15 mm Hg. Setting Single tertiary care academic institution. Patients Women ≥ 18 years old undergoing nonemergent conventional or robotic gynecologic laparoscopic surgery. Interventions A standard or valveless insufflation system at IAPs of 10 or 15 mm Hg. Measurements and Main Results One hundred thirty-two patients were enrolled and randomized with 33 patients per group. There were 84 robotic cases and 47 conventional laparoscopic cases. CO2 absorption rates (mL/kg*min) did not differ across groups with mean rates of 4.00 ± 1.3 in the valveless insufflation groups and 4.00 ± 1.1 in the standard insufflation groups. The surgeons’ rating of overall visualization of the operative field on a 10-point Likert scale favored the valveless insufflation system (median visualization, 9.0 ± 2.0 cm and 9.5 ± 1.8 cm at 10 and 15 mm Hg, respectively) over standard insufflation (7.0 ± 3.0 cm and 7.0 ± 2.0 cm at 10 and 15 mm Hg, respectively; p .05). Conclusion CO2 absorption rates, anesthesiologists’ ability to maintain adequate etCO2, and postoperative shoulder pain did not differ based on insufflation system type or IAP. Surgeons’ rating of visualization of the operative field was significantly improved when using the valveless over the standard insufflation system.

Objective: To assess 30-day readmission rates and mortality at readmission in nonagenarians following primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI). Background: There is limited contemporary data exploring the 30-day readmission rates and mortality in nonagenarians (age greater than 90 years) with STEMI following pPCI when compared to no pPCI. Methods: We utilized the National Readmissions Database (NRD) from 2010 to 2018 to identify nonagenarians hospitalized with STEMI. We divided the total cohort into two groups based on pPCI status. We analyzed 30-day readmission rates, mortality at the time of readmission, and causes of readmissions in both study cohorts. Results: Between 2010-2018, an estimated 37,363 STEMI hospitalizations were identified in nonagenarians, of which 12,062 (32.3%) included pPCI and 25,301 (67.7%) had no pPCI. Compared to pPCI cohort, no pPCI had more women (69.8% vs 36.7%), higher elixhauser comorbidity index (13% vs 8%), palliative care consultation (12.6% vs 3.4%), and nursing home placement (48% vs 33.3%) (all p Conclusion: In nonagenarians with STEMI, pPCI during index hospitalization is associated with slightly higher 30-day readmissions but significantly lower mortality at the time of readmission. Given the remarkable mortality benefit with pPCI, further research is necessary to risk stratify and optimize readmission rates following STEMI in nonagenarians.

Background: Myocardial Infarction with Non-Obstructive Coronary arteries (MINOCA) is defined as acute Myocardial Infarction (MI) despite the absence of severe coronary artery stenosis on angiography (i.e., stenosis severity Methods: A systematic search was made in PubMed, Medline and Cochrane database. Search terms used: Myocardial infarction, Coronary angiography, Normal coronary arteries, CMR, and OCT. Inclusion criteria was fulfilled by 18 studies. Meta-analysis and meta-regression was performed with 14 studies due to increased heterogeneity. Results: A total of 2474 patients were included in the meta-analysis. The mean age of all the patients was 51.5 and 56.4% were men. CMR was able to establish diagnosis in 74% of the patients; 30.4% had AM, 21.3% had true MI and 12% had TCM. Upon meta-regression the demographic variables, cardiovascular risk factors, troponin levels and C-reactive protein levels did not have any association with AM or MI. Incorporation of OCT with CMR was better at finding the etiology than either modalities individually. Conclusion: CMR is integral in finding the cause of MINOCA. Coupling coronary OCT and CMR is better than either techniques alone at identifying the etiology.

Background: Previous studies have reported sex-specific differences in the presentation, mechanisms, and outcomes of acute myocardial infarction (AMI). Objective: To assess differences in the incidence and in-hospital outcomes of left ventricular (LV) aneurysm complicating AMI in women and men. Methods: We used the National Inpatient Sample database (NIS) from 2000 to 2017, to identify adult hospitalizations with a primary diagnosis of AMI and concomitant LV aneurysm. Incidence and trends in in-hospital mortality, complications, length of stay and costs were analyzed in women and men. Results: A total of 16,334 AMI hospitalizations with LV aneurysm were identified including 6,994 (42.8%) women and 9,340 (57.2%) men. Women had a higher incidence of LV aneurysm compared to men (0.16% vs. 0.14%; p Conclusions: In this large population-based cohort study, women had a slightly higher incidence but dramatically higher in-hospital mortality associated with LV aneurysm complicating AMI compared to men. Further research is necessary to validate strategies to ensure that women receive guideline-directed therapy for AMI and LV aneurysm to address the sex disparity in mortality.

Introduction: Pericarditis is a relatively common cause of chest pain and is the most common pericardial syndrome in clinical practice. Pericardiectomy is the treatment of choice for patients with chronic or recurrent pericarditis refractory to medical therapy. However, perioperative morbidity and mortality rates for pericardiectomy remain high. Several factors, such as etiology, duration of disease, patient functional status, and operator/center experience, can impact outcomes. Objectives: In this study, we explore the national trends in perioperative complication rates, in-hospital mortality, readmission rates, and impact of center volumes on these endpoints in patients undergoing pericardiectomy. Methods: Using the Nationwide Readmissions Database (NRD), we identified patients who underwent isolated pericardiectomy from 2010 to 2018. Year-over-year trends in mortality and readmission rates were assessed using orthogonal polynomial contrasts, with non-linear trends evaluated as needed. Multivariable logistic regression models were constructed to identify independent predictors of mortality and readmission. All analyses accounted for NRD sampling design and were performed using the SAS v. 9.4 with a p < .05 to indicate statistical significance. Results: A total of 23,230 hospitalizations for pericardiectomy were identified during the study period. Median age was 59 years and 44% were female. In-hospital mortality was 5.3%, median length of stay was 7 days, and 18% were readmitted within 30 days. While rates were relatively consistent early on, between 2015 and 2018, there was a slight increase in the hospitalizations for pericardiectomy, decrease in in-hospital mortality and an uptick in 30 day all-cause readmission rates. Advanced age, higher comorbidity index, and lower annual facility pericardiectomy volume were independent predictors of in-hospital mortality. Conclusion: Isolated pericardiectomy rates have remained largely constant with relatively small changes in in-hospital mortality and 30-day readmission rates over the last decade. Advanced age, facility pericardiectomy volume, and the Elixhauser Comorbidity Index are independent predictors of surgical mortality.

Introduction Cognitive processing therapy (CPT) is a recommended first-line psychotherapy treatment for veterans with PTSD. Veterans with PTSD are at higher risk for sleep disorders including obstructive sleep apnea (OSA), and there is evidence that OSA can exacerbate PTSD and vice versa. Several studies have shown that CPAP use is associated with improvement in PTSD symptoms. CPT is an effective, yet time and resource intensive treatment option, making it critical to identify potential health factors impacting its efficacy. This retrospective chart analysis of veterans diagnosed with OSA and PTSD evaluated the effect of CPAP adherence on response to CPT. Methods Medical records of patients seen in a VA Health Care System were reviewed to identify veterans diagnosed with OSA and PTSD that received between 1-12 sessions of CPT with documented weekly PTSD Checklist for DSM-5 (PCL-5) scores, Patient Health Questionnaire-9 (PHQ-9) scores, and were issued a CPAP machine for OSA. Data collected included demographics, CPAP adherence (mean CPAP use, % days with greater than 4 hrs./night of CPAP use, mean residual apnea hypopnea index, mask leak), and PTSD symptoms (PCL-5 and PHQ-9 scores). For each outcome, we estimated a linear mixed-effects model; models for PCL-5 allowed heterogeneous residual variances for each veteran. Results This study identified 25 veterans receiving CPT for PTSD with access to a CPAP machine for OSA. The median age of patients was 43 years, median BMI was 35.6, and median residual AHI was 2.4. Patients received CPT for a median duration of 11.0 weeks. There was significant improvement in weekly PCL-5 and PHQ-9 scores over the course of CPT (both p < .001). CPAP adherence of at least 4 hrs./night for ≥70% of days did not significantly impact PCL-5 and PHQ-9 scores during CPT. Residual AHI and mask leak were not associated with PTSD symptoms during CPT. Conclusion While CPAP nonadherence appears to be a potential contributing factor to the reduced effectiveness of evidence-based treatments for veterans with PTSD, our study revealed significant improvement in PTSD symptoms during CPT regardless of CPAP adherence. Given the retrospective nature and small sample size of this study, further research is needed to expand on these findings. Support (If Any)

To evaluate pituitary function in men with a low screening prostate-specific antigen (PSA) of ≤0.1 ng/mL and test the hypothesis that low PSA is associated with hypogonadism alone or other hormone deficiency.This was a case-control study evaluating the rates of hypogonadism and low insulin-like growth factor (IGF)-1 in a cohort of men with low or normal screening PSA level. Sixty-four men40 years old without known prostate disease were divided into a low-PSA group (PSA ≤0.1 ng/mL) and normal-PSA group (PSA 1 to 4 ng/mL). Hormonal evaluation included total testosterone, prolactin, luteinizing hormone, follicle-stimulating hormone, IGF-1, growth hormone, thyroid-stimulating hormone, free thyroxine, morning cortisol, and adrenocorticotropic hormone. The difference between each patient's observed IGF-1 and the IGF-1 age-specific lower limit was calculated. The odds ratios (ORs) for having hypogonadism and associated 95% confidence intervals (CIs) were calculated using the Cochran-Mantel-Haenszel test.The rate of hypogonadism was significantly higher in the low-PSA group (n = 44) compared with the normal-PSA control group (n = 20) (45.5% vs. 15.0%; OR, 4.7; 95% CI, 1.2 to 18.4; P = .027). The total testosterone in the low-PSA group was significantly lower compared with the control group (181.7 ng/dL vs. 263.7 ng/dL; P = .008). IGF-1 values were below their lower bound in 18.6% of subjects in the low-PSA group, compared with 0% in the control group.Men with low PSA have significantly higher rates of hypogonadism and low IGF-1 compared with those with normal PSA. In such men, we recommend hormonal evaluation to exclude associated pituitary dysfunction.BMI = body mass index; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; PSA = prostate-specific antigen; T2DM = type 2 diabetes mellitus; VA-NWIHCS = VA-Nebraska Western Iowa Health Care System.

Introduction: Pseudomonas aeruginosa (PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. A systematic review and meta-analysis were performed to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults.Methods: Comprehensive literature searches of Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed without time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed.Results: A total of 368 articles were screened, and 6 studies involving 338 total patients were included in the meta-analysis. Upon evaluation of methodological quality, 2 studies were rated good, 3 fair, and 1 poor. A meta-analysis of 3 studies demonstrates FQ monotherapy is associated with significantly improved survival compared to BL monotherapy for patients with PA bacteremia (OR, 3.65; 95% CI, 1.27-10.44; p=.02). A meta-analysis of 3 studies demonstrates FQ monotherapy is associated with equivalent bacteriological eradication compared to BL monotherapy for PA pneumonia or skin and soft tissue infection (RD, 0.07; 95% CI, -0.09 to 0.24; p=.39).Conclusion: The meta-analyses demonstrate FQ monotherapy significantly improves survival in PA bacteremia and is associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations.

Introduction To describe the risks of chronic kidney disease (CKD) progression in patients with obstructive sleep apnea (OSA) Methods In this retrospective case control study; patients with CKD and OSA compared to patients with CKD without OSA who followed up at Creighton University Hospital Clinic. Data retrieved from Electronic Medical Records: demographics, time of diagnosis severity of OSA , apnea hypopnea index, severity of chronic kidney disease using serum creatinine and CKD -EPI equation for glomerular filtration rate cut offs. Patient’s kidney function was followed up for 10 years from their diagnosis of OSA. Worsening kidney function is defined on the basis of laboratory values including estimaed GFR( eGFR) and serum creatinine as well as Kidney Diseases Outcome Quality Initiative (KDOQI) 2002 definition and staging. We calculated the mean and SD when appropriate. P values less than 0.05 were considered statistically significant. Results 269 patients without OSA included in the study. 416 patients with mild OSA, 343 with moderate OSA and 225 with severe OSA mean (SD) age 46.6 (16.3), 52.9(13.5), 56.9(14.1) and 55.3(15.1) years respectively; 59.1, 56.5, 39.1 and 35.6% were females respectively. CKD stage 1 42.8, 26.9, 26.5 and 28.9% respectively. Stage 246.5, 56.3, 54.2 and 46.7% respectively. Stage 3 10.7, 16.9, 19.2 and 24.3% respectivelyPatient’s renal functions who had CKD stage 2 or 3 with mild., moderate and severe OSA got worse in 21.2,31.5 and 26.7% respectively. compared to 13.1% with no sleep apnea.(p Conclusion Patients with OSA and CKD are more likely to have worsening renal function compared to patients without OSA and this association may depend on severity of both CKD and OSA. Support (If Any)

Background Pseudomonas aeruginosa (PA) is a leading cause of healthcare-associated infections, including pneumonia, bloodstream infections, and surgical site infections around the world. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. Here, we report a systematic review and meta-analysis to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults. Methods Comprehensive literature searches of Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed in April 2019 without time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed (Figure 1). Results A total of 368 articles were screened, and 6 studies were included in the meta-analysis. Upon evaluation of methodological quality, 2 studies were rated good, 3 fair, and 1 poor (Table 1). A meta-analysis of 3 cohort studies demonstrates FQ monotherapy for PA bacteremia is associated with increased survival compared to BL monotherapy (OR, 3.65; 95% CI, 1.27–10.44; p=.02; Figure 2). A meta-analysis of 3 randomized control studies demonstrates FQ monotherapy for PA pneumonia and skin and soft tissue infection is not significantly associated with increased bacteriological eradication compared to BL monotherapy (RD, 0.07; 95% CI, -0.09 to 0.24; p=.39; Figure 3). Conclusion The data appear to suggest FQ monotherapy is significantly associated with increased survival in PA bacteremia and associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations. Disclosures All Authors: No reported disclosures

Introduction: Variant detection in circulating tumor DNA (ctDNA) provides an unprecedented opportunity to study the mutational landscape of cancers with minimal patient invasiveness. Meanwhile, new variants providing information about drug response and disease prognosis are being rapidly discovered. Therefore, to fully harness the power of ctDNA variant detection it is critical to be able to rapidly modify the set of variants targeted in an assay. Here we present a platform for next generation sequencing-based ctDNA assays that allows researchers to readily customize their panel targets. Methods: Anchored Multiplex PCR (AMP™) is a molecular biology technique that allows for near infinite modularity of assay targets while maintaining variant detection sensitivity. In order to ensure assay specificity, AMP utilizes molecular barcoded adapters (MBC) to uniquely label input molecules prior to amplification, enabling post-sequencing error correction. This increases analytical sensitivity by reducing background noise. We also developed bioinformatics methods, which allow the characterization of position-specific error levels. By combining molecular barcode-based error correction and error profile characterization, we can reliably detect low frequency variants with high specificity. Results: We tested the modularity of the AMP ctDNA platform by creating ctDNA panels targeting either 6 kb of cancer variant hotspots or 34 kb of tumor suppressors plus the same 6kb of cancer hotspots (40 kb total target sequence). We then prepared and sequenced libraries using ctDNA-like inputs containing important cancer variants at low allele fractions (AF). We used these data to characterize the noise inherent in AMP library preparation and Illumina sequencing. We then performed a power analysis to measure the lowest AF at which we could detect variants at each target position given the noise level and sequencing coverage. Our results show that we can confidently detect variants with an AF of less than 0.18% in 50% of bases and 0.47% in 95% of bases covered in the 6kb panel. Variant detection sensitivity remained consistent over the 6kb of hotspot targets in the context of the 40kb panel (50% of bases powered to detect 0.17% AF variants and 95% powered to detect 0.45% variants). Across the full 40kb of the larger panel we had statistical power to call 0.23% AF variants at 50% of target bases and to call 0.56% variants at 95% of target bases. These data demonstrate that ctDNA panels can maintain assay performance upon panel modifications. Conclusions: The modular nature of AMP ctDNA panels allows for endless combinations of targeted genes to maximize detection sensitivity in relevant regions while also maintaining assay performance. Our experience with AMP assays indicates that the range in the number of targets that can be included in a panel is quite large, allowing broad implementation of the assays developed on the AMP platform. Citation Format: Matt Egleston, Paula Roberts, Ian Hoskins, Aaron Garnett, Laura Griffin, Abel Licon, Ryan Walters. Development of a Highly Customizable Platform for Variant Detection in Circulating Tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 413.

Cell penetrating peptides facilitate efficient intracellular uptake of diverse materials ranging from small contrast agents to larger proteins and nanoparticles. However, a significant impediment remains in the subsequent compartmentalization/endosomal sequestration of most of these cargoes. Previous functional screening suggested that a modular peptide originally designed to deliver palmitoyl-protein thioesterase inhibitors to neurons could mediate endosomal escape in cultured cells. Here, we detail properties relevant to this peptide’s ability to mediate cytosolic delivery of quantum dots (QDs) to a wide range of cell-types, brain tissue culture and a developing chick embryo in a remarkably non-toxic manner. The peptide further facilitated efficient endosomal escape of large proteins, dendrimers and other nanoparticle materials. We undertook an iterative structure-activity relationship analysis of the peptide by discretely modifying key components including length, charge, fatty acid content and their order using a comparative, semi-quantitative assay. This approach allowed us to define the key motifs required for endosomal escape, to select more efficient escape sequences, along with unexpectedly identifying a sequence modified by one methylene group that specifically targeted QDs to cellular membranes. We interpret our results within a model of peptide function and highlight implications for in vivo labeling and nanoparticle-mediated drug delivery by using different peptides to co-deliver cargoes to cells and engage in multifunctional labeling.

Soil from George Town, Grand Cayman Island, yielded the bacteriophage Belinda, isolated on Bacillus thuringiensis DSM 350. We present here the analysis of the complete genome sequence of 162,308 bp, with 298 predicted genes. The genome also contains three tRNA genes. Belinda belongs to the C1 cluster of Bacillus phages.

This paper seeks to evaluate the effect of the upcoming 2010 UK Feed-in Tariff (UK FIT) on decentralised small wind-energy installations at the household and building level in urban locations. It is projected that the UK FIT will stimulate an unprecedented surge in building-mounted turbine installation. The tariff amount must stimulate incentive but mitigate the likelihood of distortions in the competitive electricity market. To analyse these issues, measured energy output from sites in the Warwick Wind Trials Project (WWTP) is converted into revenue in a net-present-value (NPV) framework for assessing commercial purchases of small wind systems. Variances in project variables are examined through NPV simulations using Monte Carlo analysis to capture permutations of small wind-project performance in the UK—with and without the UK FIT. Our research concludes that the proposed tariff amount of 30.5 p/kWh will not significantly boost the economic attractiveness of mildly selective (WWTP-based) sites in the UK. Furthermore, the fixed-tariff rate ( £ /kWh generated) could cause inefficiencies applied across uneven wind-resource distribution. The results of this study suggest further examination of policy related to micro-generation, in particular decentralised small wind projects.

Background There are currently no well-defined, evidence-based guidelines for management of end-stage heart failure in patients over 65, and the decisions to use mechanical circulatory support with left ventricular assist device (LVAD), either as a bridge to transplantation or destination therapy, or isolated heart transplantation (HTx) remain controversial. We aimed to compare the outcomes after the implementation of three heart replacement strategies in this high-risk population. Methods We conducted a retrospective cohort study of all patients between the ages of 65 and 72 receiving a continuous-flow LVAD as bridge to transplantation or destination therapy or isolated HTx at our center between 2005 and 2012. The patients were stratified according to treatment strategy into three groups: group D (destination LVAD, n = 23), group B (bridge to transplantation LVAD, n = 43), and group H (HTx alone, n = 47). The primary outcomes of interest were survival to discharge and 2-year overall survival. Results The patients in group D were significantly older, had a higher prevalence of ischemic cardiomyopathy, and had a higher pulmonary vascular resistance than did patients in groups B or H. There were no significant differences between groups in survival to discharge (87% D vs 83.7% B vs 87.2% H, p = 0.88) or 2-year overall survival (75.7% D vs 68.7% B vs 80.9% H, log-rank p = 0.47). The incidence rates of readmission were 1.1 events/patient·year in group D and 0.5 events/patient·year in group H. Conclusions There was no significant difference in perioperative, short-term, and medium-term survival between the treatment groups. However, the LVAD patients had a higher incidence of readmission. Larger trials are needed to refine differences in long-term survival, quality of life, and resource utilization for elderly patients requiring heart replacement therapy.

We have previously shown that CdSe/ZnS core/shell luminescent semiconductor nanocrystals or QDs (quantum dots) coated with PEG [poly(ethylene glycol)]-appended DHLA (dihydrolipoic acid) can bind AcWG(Pal)VKIKKP9GGH6 (Palm1) through the histidine residues. The coating on the QD provides colloidal stability and this peptide complex uniquely allows the QDs to be taken up by cultured cells and readily exit the endosome into the soma. We now show that use of a polyampholyte coating [in which the neutral PEG is replaced by the negatively heterocharged CL4 (compact ligand)], results in the specific targeting of the palmitoylated peptide to neurons in mature rat hippocampal slice cultures. There was no noticeable uptake by astrocytes, oligodendrocytes or microglia (identified by immunocytochemistry), demonstrating neuronal specificity to the overall negatively charged CL4 coating. In addition, EM (electron microscopy) images confirm the endosomal egress ability of the Palm1 peptide by showing a much more disperse cytosolic distribution of the CL4 QDs conjugated to Palm1 compared with CL4 QDs alone. This suggests a novel and robust way of delivering neurotherapeutics to neurons.

Glyoxalase 1 (Glo1) has been implicated in anxiety-like behavior in mice and in multiple psychiatric diseases in humans. We used mouse Affymetrix exon arrays to detect copy number variants (CNV) among inbred mouse strains and thereby identified a approximately 475 kb tandem duplication on chromosome 17 that includes Glo1 (30,174,390-30,651,226 Mb; mouse genome build 36). We developed a PCR-based strategy and used it to detect this duplication in 23 of 71 inbred strains tested, and in various outbred and wild-caught mice. Presence of the duplication is associated with a cis-acting expression QTL for Glo1 (LOD>30) in BXD recombinant inbred strains. However, evidence for an eQTL for Glo1 was not obtained when we analyzed single SNPs or 3-SNP haplotypes in a panel of 27 inbred strains. We conclude that association analysis in the inbred strain panel failed to detect an eQTL because the duplication was present on multiple highly divergent haplotypes. Furthermore, we suggest that non-allelic homologous recombination has led to multiple reversions to the non-duplicated state among inbred strains. We show associations between multiple duplication-containing haplotypes, Glo1 expression and anxiety-like behavior in both inbred strain panels and outbred CD-1 mice. Our findings provide a molecular basis for differential expression of Glo1 and further implicate Glo1 in anxiety-like behavior. More broadly, these results identify problems with commonly employed tests for association in inbred strains when CNVs are present. Finally, these data provide an example of biologically significant phenotypic variability in model organisms that can be attributed to CNVs.

Objective: Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control. Method: Through the use of an eventrelated design, 25 patients with firstepisode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-level-dependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control. Results: Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. Significant correlations were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning. Conclusions: These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia.