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Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the rise. Common ocular signs and symptoms associated with EE include conjunctival injection, ocular pain, and reduced visual acuity. On clinical examination, a history of prior or coexisting systemic infections, symptoms (e.g., fever, malaise), and localizing features may be noted. Clinical diagnosis is often challenging, resulting in critical delays that contribute to a poor prognosis. Blood cultures and ocular fluid samples can aid in conforming causative pathogen(s), after which empirical antibiotic therapy, both systemic and intravitreal, should be instated. The use of steroids to suppress inflammation remains controversial. Surgical options include pars plana vitrectomy. Overall prognosis varies depending on host and pathogen factors, and early diagnosis and initiation of appropriate treatment are crucial.

Inflammatory cytokines perturb hematopoietic stem cell (HSC) homeostasis and modulate the fitness of neoplastic HSC clones in mouse models. However, the study of cytokines in human hematopoiesis is challenging due to the concerted activities of multiple cytokines across physiologic and pathologic processes. To overcome this limitation, we leveraged serial bone marrow samples from patients with CALR-mutated myeloproliferative neoplasms who were treated with recombinant interferon-alpha (IFNa). We interrogated baseline and IFNa-treated CD34+ stem and progenitor cells using single-cell multi-omics platforms that directly link, within the same cell, the mutation status, whole transcriptomes and immunophenotyping or chromatin accessibility. We identified a novel IFNa-induced inflammatory granulocytic progenitor defined by expression and activities of RFX2/3 and AP-1 transcription factors, with evidence supporting a direct differentiation from HSCs. On the other hand, IFNa also induced a significant B-lymphoid progenitor expansion and proliferation, associated with enhanced activities of PU.1 and its co- regulator TCF3, as well as decreased accessibility of megakaryocytic-erythroid transcription factor GATA1 binding sites in HSCs. In the neoplastic hematopoiesis, the lymphoid expansion was constrained by a preferential myeloid skewing of the mutated cells, linked with increased myeloid proliferation and enhanced CEBPA and GATA1 activities compared to wildtype cells. Further, IFNa caused a downregulation of the TNFa signaling pathway, with downregulation of NFKB and AP-1 transcription factors. Thus, IFNa simultaneously initiated both – pro-inflammatory and anti- inflammatory – cell states within the same hematopoiesis, and its phenotypic impact varied as a function of the underlying HSC state and mutation status.

Objective:To investigate hospital room and patient-level risk factors associated with increased risk of healthcare-facility–onset Clostridioides difficile infection (HO-CDI).Design:The study used a retrospective cohort design that included patient data from the institution’s electronic health record, existing surveillance data on HO-CDI, and a walk-through survey of hospital rooms to identify potential room-level risk factors. The primary outcome was HO-CDI diagnosis.Setting:A large academic medical center.Patients and participants:All adult patients admitted between January 1, 2015, and December 31, 2016 were eligible for inclusion. Prisoners were excluded. Patients who only stayed in rooms that were not surveyed were excluded.Results:The hospital room survey collected room-level data on 806 rooms. Included in the study were 17,034 patients without HO-CDI and 251 with HO-CDI nested within 535 unique rooms. In this exploratory study, room-level risk factors associated with the outcome in the multivariate model included wear on furniture and flooring and antibiotic use by the prior room occupant. Hand hygiene devices and fixed in-room computers were associated with reduced odds of a HO-CDI. Differences between hospital buildings were also detected. The only individual patient factors that were associated with increased odds of HO-CDI were antibiotic use and comorbidity score.Conclusion:Combining a hospital-room walk-through data collection survey, EHR data, and CDI surveillance data, we were able to develop a model to investigate room and patient-level risks for HO-CDI.

Background Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. Methods The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention–recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. Results Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. Conclusions This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

People with different ancestries inherit different risks and encounter different environmental exposures resulting in different somatic profiles. A lack of knowledge about ancestry-specific alterations is a major barrier to implementing precision medicine, leading to inequities in genetic testing, targeted treatment and clinical trial design for cancer patients from the underserved populations. However, a limited number of cancer cases from non-European populations have been sequenced in research setting, and paired normal samples are often not collected in routine clinical care. Here, we inferred African (AFR), South Asian (SAS), East Asian (EAS), American (AMR) and European (EUR) ancestry from comprehensive genomic profiling (CGP) of over 200,000 tumors at Foundation Medicine and identified 18717, 8588, 6594 patients with significant proportions of AFR, AMR, EAS ancestry, respectively. Using logistic regressions with age of diagnosis, gender and tumor mutation burden (TMB) as covariates, we identified 165 ancestry-associated genes across 14 common cancer types. We found that in colorectal cancer, KRAS (OR=1.5, FDR corrected p=4x10-44) and APC (OR=1.4, FDR corrected p=1x10-16) mutations were enriched in patients with AFR ancestry, whereas BRAF mutations were depleted in both AFR (OR=0.5, FDR corrected p=5x10-24) and EAS (OR=0.6, FDR corrected p=6x10-5) patients. CDK12 mutations were enriched in both AFR (OR=1.6, FDR corrected p=2x10-4) and EAS (OR=3.1, FDR corrected p=2x10-7) prostate cancer patients. For patients with AMR ancestry, increased mutation frequency was observed in SETD2 in pancreatic cancer (OR=3.4, FDR corrected p=1x10-4), and VHL in renal clear cell carcinoma (OR=1.9, FDR corrected p=2x10-4). For renal cell carcinoma patients with AFR ancestry, mutations in NF2 were enriched (OR=2.5, FDR =8x10-6). In GBM, TERT alterations were associated with EUR ancestry (OR=1.3, FDR corrected p=0.003). Interestingly, TMB-high status was associated with EUR ancestry in melanoma (OR=5.9, p=6x10-36) and anti-correlated with AFR ancestry in endometrial carcinoma (OR=0.7, p=1x10-6). Our large-scale ancestry analysis characterized the somatic landscape of non-European cancer patients. Future directions include quantifying the germline heritability of identified ancestry-associated mutations using a local ancestry risk score (LRS). Citation Format: Jian Carrot-Zhang, Justin New, Amy Xie, Garrett Frampton. Genomic analysis of patients across continental ancestry groups [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C016.

To investigate hospital room and patient-level risk factors associated with increased risk of healthcare-facility-onset Clostridioides difficile infection (HO-CDI).The study used a retrospective cohort design that included patient data from the institution's electronic health record, existing surveillance data on HO-CDI, and a walk-through survey of hospital rooms to identify potential room-level risk factors. The primary outcome was HO-CDI diagnosis.A large academic medical center.All adult patients admitted between January 1, 2015, and December 31, 2016 were eligible for inclusion. Prisoners were excluded. Patients who only stayed in rooms that were not surveyed were excluded.The hospital room survey collected room-level data on 806 rooms. Included in the study were 17,034 patients without HO-CDI and 251 with HO-CDI nested within 535 unique rooms. In this exploratory study, room-level risk factors associated with the outcome in the multivariate model included wear on furniture and flooring and antibiotic use by the prior room occupant. Hand hygiene devices and fixed in-room computers were associated with reduced odds of a HO-CDI. Differences between hospital buildings were also detected. The only individual patient factors that were associated with increased odds of HO-CDI were antibiotic use and comorbidity score.Combining a hospital-room walk-through data collection survey, EHR data, and CDI surveillance data, we were able to develop a model to investigate room and patient-level risks for HO-CDI.

The focus of this project was on formulating a model and decision support tool to aid in the decision to build and maintain an Air Traffic Control Tower (ATCT). An important aspect of air travel are ATCTs, towers that help facilitate communication between the airport system and airplanes ascending and descending. ATCTs bring economic, safety, and efficiency benefits to airports and nearby communities. Currently, the Federal Aviation Administration (FAA) uses a document outlining a benefit-cost ratio for building a new tower, with tower funding provided if the ratio is greater than 1. However, the current policy lacks a comprehensive and systematic assessment of factors that influence both costs and benefits to operators and the region.To address these issues, we started by speaking with air traffic stakeholders and then began to collect data from a variety of aviation datasets. Based on the collected data, we identified economy, safety, and efficiency as our three areas of focus. With this data, we were able to compute the similarity, using hierarchical clustering, of a given airport to currently towered airports based on data from the economy, safety, and efficiency sources. We then built an interactive interface to display these similarities and provide information for airports to contact the similar airports.

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19.MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20–February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing.ResultsAmong the 12 patients, median age was 53 years (range: 21–68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients.ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

Simple Summary Immunotherapy has prompted a dramatic change in the management of head and neck squamous cell carcinoma (HNSCC), but the percentage of patients benefiting from treatment is limited to 20% or less. The application of precision oncology to HNSCC introduces the potential for the emergence of biomarkers that may predict a response to immunotherapy and assist with the selection of patients that may benefit from treatment with an immune checkpoint inhibitors. In this retrospective study, the results of tumor mutational burden and programmed death ligand-1 measurements from HNSCC tumors were evaluated independently for their associations with demographics, risk factors, disease characteristics, survival, and response to ICI. Results of this study are expected to assist in laying the groundwork for creating a framework in which PD-L1 and TMB coexist with other variables to predict response to ICI on an individual level. Abstract Failure to predict response to immunotherapy (IO) limited its benefit in the treatment of head and neck squamous cell cancer (HNSCC) to 20% of patients or less. Biomarkers including tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) were evaluated as predictors of response to IO, but the results are inconsistent and with a lack of standardization of their methods. In this retrospective study, TMB and PD-L1 were measured by commercially available methodologies and were correlated to demographics, outcome, and response to PD-1 inhibitors. No correlation was found between TMB and PD-L1 levels. High TMB was associated with smoking and laryngeal primaries. PD-L1 was significantly higher in African Americans, patients with earlier stage tumors, nonsmokers, and nonethanol drinkers. Patients with high TMB fared better in univariate and multivariate survival analysis. No correlation was found between PD-L1 expression and prognosis. There was a statistically significant association between PFS and response to IO and TMB. There was no association between response to ICI and PD-L1 in this study, possibly affected by variations in the reporting method. Further studies are needed to characterize the biomarkers for IO in HNSCC, and this study supports further research into the advancement of TMB in prospective studies.

Accompanying the constant development of data mining technology and neural network, the application of computer technology in energy consumption prediction of large public buildings is the trend of green buildings and intelligent life in the field of engineering. In this paper, a new energy consumption prediction algorithm based on MLR-BP is proposed, which solves the issue of current energy consumption algorithm: the massive amount of calculation and the low prediction accuracy. Firstly, factors that affect building energy consumption are categorized as external factors (meteorological factors) and internal factors. In addition, the multiple linear regression is used to model the external factors, and the influencing factors with high correlation are screened out. Then, the selected external factors and internal factors are combined into the training of BP neural network to obtain a new energy consumption prediction model. The simulation results show that in comparison with the BP neural network, the proposed prediction algorithm in this paper can predict the building energy consumption more accurately.

Many investors need to make long-term asset class forecasts for planning and portfolio construction purposes. We examine the empirical performance of two different approaches to forecasting future ten-year equity returns: a regression methodology using CAPE and a more traditional “building block” approach. The regression approach produces estimates that are poor predictors of subsequent actual returns. The “building block” approach (BBA) outperforms the regression methodology (in terms of root mean squared error) with the repricing component helping to capture periods of poor equity returns. A high CAPE value is not necessarily cause for alarm and changes in asset allocation. If an investor plans to use a methodology that over time will prove more accurate, then the historical record is more supportive of the BBA approach, with or without a repricing component based on current P/E.

Some investors have been surprised by the duration of the current stock market rally and, until just recently, the very low level of equity market volatility (e.g., VIX). However, many are concerned about the possibility of market volatility spikes. We investigate asset class performance before, during, and after volatility events. Specifically, how do stocks and bonds perform during such events? Is asset class performance leading into an event different than after the event? We first define two types of volatility events: “spikes” and “post peaks”. A volatility spike event is a significant sudden increase in volatility, and we measure asset class performance while “the dust is flying.” In contrast, a volatility post peak event is a period of high volatility that is followed by volatility returning to its pre-peak level, and we measure asset class performance “after the dust has settled.” While both types of events are of interest to investors, some investors may act at the onset of a volatility event (i.e., a spike), whereas others may wait until market volatility has calmed down (i.e., after the peak). We examine 26 volatility spike events, and 25 post peak events, across a 68-year span, in a variety of market environments. History shows that while spike events produce large negative returns for equities and credit bonds (with positive returns for Treasuries), markets recover relatively quickly, approximately by the seventh month following the spike month. For post peak events, we focus attention on asset class performance after the dust has settled, not around the peak volatility event itself. The increase in volatility and accompanying equity and credit market declines may be unnerving to some investment committees. These investors may wish to wait until the “dust settles” – either out of caution or time needed for deliberation – before re-examining their investment strategy. History shows that once the dust has settled, equity and credit markets tend to perform well, often better than before the volatility event. The evidence from both types of volatility events suggests that the damage from volatility events is transitory and is likely to be repaired after a reasonable period. These results provide support for investment committees who intend to “stay the course,” and possibly re-balance with increased allocations to risky assets.

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

Chronic aspiration of gastric fluid potentially plays a central role in the pathogenesis of obliterative bronchiolitis, which is often associated with chronic pulmonary allograft failure. It remains unknown whether pharmaceutical-induced increases in gastric pH might effectively prevent any putative pulmonary injury associated with chronic aspiration.To test the hypothesis that neutralization of gastric fluid would affect the development of aspiration-associated obliterative bronchiolitis, an established rat lung transplant model (WKY-to-F344) was utilized. Pulmonary allograft recipients were subjected to eight weekly aspirations of gastric fluid at pH 2.5 (low-pH), gastric fluid at pH 7.4 (neutralized-pH), or saline as a control.Histologic analysis revealed that the fraction of airways affected with lesions consistent with obliterative bronchiolitis was 0.55 ± 0.08 (mean ± SEM) in rats receiving aspiration with low-pH gastric fluid, 0.49 ± 0.07 in animals receiving neutralized-pH gastric fluid, and 0.07 ± 0.05 in rats receiving normal saline only. The difference between groups receiving gastric fluid, regardless of pH, was significantly different from the saline control (P 0.0001), whereas the difference between the groups receiving low-pH gastric fluid and neutralized-pH gastric fluid was not significant (P = 0.75).Effective management of gastroesophageal reflux disease in lung transplant recipients should probably include more than neutralization of gastric fluid.

Background & Aims Reshape Duo is a saline-filled dual, integrated intragastric balloon (IGB) approved by the Food and Drug Administration for weight loss in patients with obesity. In a prospective, randomized trial, obese patients who received the balloon had significantly greater percent excess weight loss (%EWL) compared with patients treated with diet and exercise alone. However, there are limited data on the real-world efficacy of the Reshape balloon. Methods We performed a retrospective study of data collected from 2 academic centers and 5 private practices in which all patients paid for the IGB and follow-up visits out of pocket. The IGB was removed after 6 months. We collected data (demographic, medical, and laboratory) from 202 adults (mean age 47.8 ± 10.8 years; 83% female) with a baseline mean body mass index of 36.8 + 8.4 kg/m2 who had IGB insertion for weight loss therapy, along with counselling on lifestyle modifications focused on diet and exercise. Primary outcomes were percent total body weight loss (%TBWL) and %EWL at 1, 3, 6, 9, and 12 months after the procedure. Results Mean %TBWL at 1, 3, 6, 9 and 12 months was 4.8 ± 2.4%, 8.8 ± 4.3%, 11.4 ± 6.7%, 13.3 ± 7.8%, and 14.7 ± 11.8%, respectively. Data were available from 101 patients at 6 months and 12 patients at 12 months; 60.4% of patients achieved more than 10% TBWL and 55.4% had more than 25% EWL. Seventeen patients (8.4%) had esophageal tears during balloon insertion, with no intervention required. Thirteen patients (6.4%) had their IGB removed before the end of the 6-month treatment period. Nausea, vomiting, and abdominal pain were the most common adverse effects, occurring in 149 (73.8%), 99 (49%), and 51 (25.2%) patients. In one patient, the IGB migrated distally leading to small intestinal obstruction requiring surgical removal. Conclusion In a retrospective analysis of real-world patients who received the Reshape Duo IGB, we found it to be a safe and efficacious endoscopic method for producing weight loss, with most patients achieving greater than 10% TBWL at 6 months.