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Abstract: MODIS is a major instrument for NASA’s Earth Observing System (EOS) missions. It is currently operating on-board the EOS Terra and Aqua spacecraft, launched in December 1999 and May 2002, respectively. The MODIS instrument was developed with improvements over heritage sensors in terms of its spectral, spatial, and temporal resolutions, and with more stringent calibration requirements. It makes observations in 36 spectral bands covering wavelengths from 0.41 to 14.4μm and at three nadir spatial resolutions: 250m, 500m, and 1km. Together Terra and Aqua MODIS have produced more than 10 years of global data sets that have significantly helped scientists worldwide to better understand the Earth as an interacting system and the impacts on this system due to human related activities. In order to maintain on-orbit calibration and data product quality, MODIS was built with a complete set of on-board calibrators (OBCs), including a solar diffuser (SD), a solar diffuser stability monitor (SDSM), a blackbody (BB), a deep space view (SV) port, and a spectro-radiometric calibration assembly (SRCA). In this paper, we provide a brief description of both Terra and Aqua MODIS on-orbit operation and calibration activities and present results of on-orbit radiometric, spatial, and spectral characterization. Examples of short-term stability and long-term response changes are illustrated using observations made with the on-board calibrators. On-orbit performance parameters, including detectors noise characterization, are also compared to pre-launch design specifications. [Copyright &y& Elsevier]

In the eastern United States large amounts of smoke emitted from both wildfires and prescribed fires affect the regional air quality and long-term climate and may have an impact on public health. Satellite remote sensing is an effective approach for detecting and monitoring the smoke plume. The spectral characteristics of smoke plume are measurably different from those of other cover types, such as vegetation, cloud, snow, and so on. A multi-threshold method has been developed for detecting smoke plumes with eight MODIS spectral bands based on the analysis of spectral characteristics of different cover types. A series of tests are applied to all pixels in one granule (5-min measurements) to filter out non-smoke pixels step by step with water masking. At each step, specific thresholds are utilized. The results have been validated with true color images for a number of cases from different areas and time, showing that the algorithm works well except for a few missing or incorrect identified smoke pixels. [ABSTRACT FROM AUTHOR]

The Moderate Resolution Imaging Spectroradiometer (MODIS) protoflight model onboard the National Aeronautics and Space Administration's Earth Observing System Terra spacecraft has been in operation for over five years since its launch in December 1999. It makes measurements using 36 spectral bands with wavelengths from 0.41 to 14.5 μm. Bands 1–19 and 26 with wavelengths below 2.2 μm, the reflective solar bands (RSBs), collect daytime reflected solar radiance at three nadir spatial resolutions: 0.25 km (bands 1–2), 0.5 km (bands 3–7), and 1 km (bands 8–19 and 26). Bands 20–25 and 27–36, the thermal emissive bands, collect both daytime and nighttime thermal emissions, at 1-km nadir spatial resolution. The MODIS spectral characterization was performed prelaunch at the system level. One of the MODIS onboard calibrators, the Spectroradiometric Calibration Assembly (SRCA), was designed to perform on-orbit spectral characterization of the MODIS RSB. This paper provides a brief overview of MODIS prelaunch spectral characterization, but focuses primarily on the algorithms and results of using the SRCA for on-orbit spectral characterization. Discussions are provided on the RSB center wavelength measurements and their relative spectral response retrievals, comparisons of on-orbit results with those from prelaunch measurements, and the dependence of center wavelength shifts on instrument temperature. For Terra MODIS, the center wavelength shifts over the past five years are less than 0.5 nm for most RSBs, indicating excellent stability of the instrument's spectral characteristics. Similar spectral performance has also been obtained from the Aqua MODIS (launched in May 2002) SRCA measurements. [ABSTRACT FROM AUTHOR]

Background: Investigating the link between serum neurofilament protein (sNfL) levels and depression remains an area of limited understanding. This study explores the correlation in US adults and employs Mendelian randomization (MR) to ascertain causality., Methods: Our cross-sectional study analyzed data from participants aged 20 and above in the National Health and Nutrition Examination Survey (2013-2014). We employed a weighted multiple logistic regression model to examine the relationship between ln (sNfL) and depression. Restricted cubic splines (RCS) were used to visualize non-linear relationships. Stratified analyses examined associations between ln(sNfL) and depression in different subgroups. Subsequently, we conducted a two-sample bidirectional Mendelian randomization (MR) to assess the causal relationship between sNfL and depression. The inverse variance-weighted (IVW) method was utilized as the primary analysis., Results: Among 1765 participants (mean age 45.19 years; 49.37 % male), 166 had depression with a Patient Health Questionnaire (PHQ-9) score ≥ 10. After adjusting for covariates, a positive correlation remained between sNfL and depression (OR 1.511, 95 % CI: 1.050-2.175). RCS curves indicated a non-linear association, with a turning point at 2.76 pg/ml. Stratified analyses revealed positive correlations in specific subgroups, with interactions involving age, race, family income, recreational activity, and ln(sNfL). MR using IVW found no significant causal relationship between sNfL and depression genetically (OR = 0.956, 95 % CI: 0.878-1.042), with reverse analysis yielding similar results (OR = 0.897, 95 % CI: 0.756-1.065)., Conclusions: This cross-sectional study highlights a significant correlation between ln(sNfL) and depression. However, MR results indicate no causal relationship between sNfL and depression., Competing Interests: Declaration of competing interest The authors of the study confirm that there are no commercial or financial relationships that might be seen as having a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: APP report grants from Metabiota Inc outside the submitted work. J.S. and Columbia University declare partial ownership of SK Analytics. No other authors have competing interests to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Drug-induced thrombocytopenia (DIT) deserves both clinical and research attention for the serious clinical consequences and high prevalence of the condition. The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with thrombocytopenia events. A disproportionality analysis of DIT was conducted using reports submitted to FARES from January 2004 to December 2022. Both the information component (IC) and reporting odds ratio (ROR) algorithms were applied to identify an association between target drugs and DIT events. A total of 15,940,383 cases were gathered in FAERS, 168,657 of which were related to DIT events. The top 50 drugs ranked by number of cases and ranked by signal strength were documented. The top 5 drugs ranked by number of cases were lenalidomide (10,601 cases), niraparib (3726 cases), ruxolitinib (3624 cases), eltrombopag (3483 cases), and heparin (3478 cases). The top 5 drugs ranked by signal strength were danaparoid (ROR 37.61, 95%CI 30.46-46.45), eptifibatide (ROR 34.75, 95%CI 30.65-39.4), inotersen (ROR 34.00, 95%CI 29.47-39.23), niraparib (ROR 30.53, 95%CI 29.42-31.69), and heparin (ROR 28.84, 95%CI 27.76-29.97). The top 3 involved drug groups were protein kinase inhibitors, antimetabolites, and monoclonal antibodies and antibody-drug conjugates. The current comprehensive pharmacovigilance study identified more drugs associated with thrombocytopenia. Although the mechanisms of DIT have been elucidated for some drugs, others still require further investigation., (© 2023, The American College of Clinical Pharmacology.)

Background: Wu-Mei-Wan (WMW), a traditional Chinese medicine (TCM) formula, has a good effect on the treatment of obesity and has been proven helpful to promote the metabolism of adipose tissue. However, its underlying mechanism remains to be studied. This study aims to explore the potential pharmacological mechanism of WMW in the treatment of obesity., Methods: Network pharmacology was used to sort out the relationship between WMW putative targets and obesity-related drug targets or disease targets, which indicated the mechanism of WMW in treating obesity from two aspects of clinical drugs approved by the Food and Drug Administration (FDA) and obesity-related diseases. Databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), PubChem, DrugBank, DisGeNET, and Genecards were used to collect information about targets. String platform was used to convert the data into gene symbol of "homo sapiens", and perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. With the Human Protein Reference Database (HPRD) as background data, Cytoscape 3.6.0 software was used to construct a new protein-protein interaction (PPI) network. Mechanism diagrams of key pathways were obtained from the KEGG database. AutoDock Vina software was used to conduct molecular docking verification., Results: The number of targets in the overlap between WMW putative targets and obesity-related drug targets accounted for more than 50% of the latter, and HTR3A, SLC6A4, and CYP3A4 were core targets. In obesity-related disease targets-WMW putative targets PPI network, the Th17 cell differentiation pathway, and the IL-17 signaling pathway were key pathways, and the 1st module and the 7th module were central function modules that were highly associated with immunity and inflammation. Molecular docking verified that STAT3, TGFB1, MMP9, AHR, IL1B, and CCL2 were core targets in the treatment of WMW on obesity., Conclusion: WMW has similar effects on lipid and drug metabolism as the current obesity-related drugs, and is likely to treat obesity by inhibiting Th17 cell differentiation and alleviating metabolic inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To study the indication for therapeutic plasma exchange (TPE) and related complications in children admitted to the pediatric intensive care unit., Methods: A retrospective analysis was performed on the medical records of the children who received TPE in the Pediatric Intensive Care Unit, Hunan Children's Hospital, from March 2015 to March 2021. The indication for TPE and related complications were analyzed and compared with the American Society for Apheresis (ASFA) indication categories., Results: A total of 405 TPE treatment sessions were performed for 196 children, among whom 76 children (38.8%) also received continuous renal replacement therapy and 147 children (75.0%) survived. The children with neurological diseases had the highest survival rate of 93.1% (27/29). The top three indications for TPE were hematologic diseases (61/196, 31.1%), sepsis with multiple organ dysfunction (41/196, 20.9%), and liver diseases (36/196, 18.4%). The children with hematologic diseases received the highest number of 129 TPE treatment sessions. The subjects with ASFA category Ⅲ indications accounted for the highest proportion of 76.5% (150/196), followed by those with ASFA category Ⅰ indications (11.2%, 22/196), ASFA category Ⅱ indications (7.1%, 14/196), and unknown category (5.1%, 10/196), and no ASFA category Ⅳ indications were observed. The incidence rate of TPE complications was 12.3% (50/405), and the most common complications were pipeline coagulation (4.2%, 17/405) and hypotension (3.7%, 15/405). No serious adverse events were observed., Conclusions: TPE can be safely used for the treatment of critically ill children with indications in an experienced pediatric intensive care unit.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model., Competing Interests: ST, CS, MQ, LM, RB, KS, EH, LC, JL, JK, HH, MK, KT, SW, LS, KR, JL, JD, JK, EL, JP, AH, DK, MC, JD, KM, XX, AP, AV, AS, PP, SV, AA, BL, BK, JO, MO, GH, BH, JC, AV, MM, SH, PB, DM, SC, RP, DJ, JT, MG, TY, SP, JH, RS, MB, MJ, CV No competing interests declared, JL has served as an expert witness on cases where the likely length of the pandemic was of issue, JS and Columbia University disclose partial ownership of SK Analytics. Discloses consulting for BNI, MR reports stock ownership in Becton Dickinson & Co, which manufactures medical equipment used in COVID testing, vaccination, and treatment

Background: Testicular torsion is an acute scrotal disease requiring urgent management, and the COVID-19 pandemic has been demonstrated to lead to poor outcomes for this disease. Presently, many people tend to seek health information via YouTube. This study aims to quantitatively assess the quality of English YouTube video content as an information source of testicular torsion., Methods: In this cross-sectional study, a search was performed with the search term "testicular torsion" on YouTube, and the first 100 videos listed by relevance were selected for our analysis. Duplicate, non-English, videos without audio and surgical videos were excluded. Video features (duration, number of days online, views, likes, comments), source of the video, and author's country were collected. Each video included in the study was assessed using DISCERN and Journal of the American Medical Association (JAMA) Benchmark Criteria. A correlation analysis was performed considering video features, video source, DISCERN scores and JAMA scores., Results: A total of 66 videos were included and analyzed. The most common video content was general information, including etiology, symptoms, and treatment. The majority of videos were from education and training websites (30%), physicians (23%), and independent users (21%). The mean DISCERN and JAMA scores were 36.56 and 2.68, respectively. According to DISCERN, the quality of video uploaded by physicians was relatively high ( P < 0.001), and the quality of video uploaded by independent users was relatively low ( P < 0.001). The JAMA score had no relevance to the video source ( P = 0.813). The correlation between the video features, DISCERN and JAMA scores was controversial by different assessment methods., Conclusions: Despite most of the videos on YouTube being uploaded by medical or education-related authors, the overall quality was poor. The misleading, inaccurate and incomplete information may pose a health risk to the viewers, especially during the COVID-19 pandemic. Much effort needs to be undertaken to improve the quality of health-related videos regarding testicular torsion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bai, Pan, Zhao, Chen, Liu and Fu.)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

(1) Background: Increasing evidence indicates that lipid metabolism may influence the concentration of prostate-specific antigen (PSA). However, the association between triglycerides and PSA remains unclear and complicated. Hence, we evaluated the correlation between triglycerides and PSA based on the U.S. National Health and Nutrition Examination Survey (NHANES) database. (2) Methods: A total of 2910 participants out of 41,156 participants fit into our study after conducting the screening from the 2003 to 2010 NHANES survey. Serum triglycerides were the independent variable of our study, and PSA was the dependent variable; (3) Results: In our study, the average age of chosen participants was 59.7 years (±12.7). After adjusting for covariates, the result indicated that for each additional unit of serum triglyceride (mg/dL), the PSA concentrations were reduced by 0.0043 ng/mL (-0.0082, -0.0005) with a statistical difference. Furthermore, we used machine learning of the XGBoost model to determine the relative importance of selected variables as well as constructed a smooth curve based on the fully adjusted model to investigate the possible linear relationship between the triglyceride and PSA concentrations. (4) Conclusions: The serum triglyceride is independently and negatively correlated with PSA among American males, which may make it hard to detect asymptomatic prostate cancer and diagnose at an advance stage with higher triglycerides due to detection bias.

Background: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission., Methods: Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA., Results: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review., Conclusions: The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

BACKGROUND: High-deductible health plans (HDHPs) are characterized by higher deductibles and lower monthly premiums compared with a typical health plan. HDHPs may reduce, or delay, needed care, which will ultimately lead to poorer access to care for chronically affected participants. OBJECTIVES: To (1) investigate the HDHP enrollment trend and (2) determine the effects of HDHPs on financial access problems for individuals with self-reported cognitive impairment. METHODS: Data between 2010 and 2018 were obtained from the National Health Interview Survey (NHIS). Individuals with cognitive impairment were identified if they were limited by memory difficulties. Problems regarding financial access to health care were assessed based on 6 survey questions from the Centers for Disease Control and Prevention. Multivariable logistic regressions were implemented to evaluate the effects of HDHPs. RESULTS: This study identified 1,148 individuals with cognitive impairment, representing 3.9 million individuals in the United States from 2010 to 2018. A nearly 2-fold increase in HDHP enrollment with cognitive impairment was observed from 2010 (20.9%) to 2018 (41.9%). This increase is similar to that reported for noncognitively impaired individuals. After controlling for possible confounding variables, cognitively impaired individuals with HDPHs were more likely to have overall financial access difficulties compared with those without HDHPs (OR = 1.17, 95% CI = 0.88-1.56, P = 0.271), but this likelihood was not statistically significant. CONCLUSIONS: HDHPs are intended to support effective care options and reduce health care costs. However, our research found that among individuals with cognitive impairment, those with HDHPs experienced some financial access problems, such as affording medical care, follow-up care, and specialists, than those without HDHPs, indicating that HDHPs might have unintended consequences for health care usage. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest or financial interests to disclose.

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally 1-7 . Although a limited number of SARS-CoV-2 introductions were reported in January and February 2020 (refs. 8,9 ), the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening 10 , left many countries vulnerable to unmitigated, cryptic transmission. Here we use a global metapopulation epidemic model to provide a mechanistic understanding of the early dispersal of infections and the temporal windows of the introduction of SARS-CoV-2 and onset of local transmission in Europe and the USA. We find that community transmission of SARS-CoV-2 was likely to have been present in several areas of Europe and the USA by January 2020, and estimate that by early March, only 1 to 4 in 100 SARS-CoV-2 infections were detected by surveillance systems. The modelling results highlight international travel as the key driver of the introduction of SARS-CoV-2, with possible introductions and transmission events as early as December 2019 to January 2020. We find a heterogeneous geographic distribution of cumulative infection attack rates by 4 July 2020, ranging from 0.78% to 15.2% across US states and 0.19% to 13.2% in European countries. Our approach complements phylogenetic analyses and other surveillance approaches and provides insights that can be used to design innovative, model-driven surveillance systems that guide enhanced testing and response strategies., (© 2021. The Author(s).)

Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ML has provided advice on COVID-19 free of charge to Janssen, Astra-Zeneca, Pfizer, and COVAXX (United Biomedical), as well as to the nonprofit One Day Sooner. ML has received consulting income or honoraria from Merck, Pfizer, Bristol Meyers Squibb, and Sanofi, and institutional research support from Pfizer.

Spatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here with a group of older adults (n = 56, 58-80 (67.9±5.2) year old, 31 females, 18.7±3.6 years of education), we provide evidence supporting the notion that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD), and the impairment is detectable using a double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the double cue spatial IOR paradigm may be useful in detecting MCI and early AD., Competing Interests: The authors have declared that no competing interests exist.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katriona Shea reports receipt of two National Science Foundation (NSF) COVID-19 RAPID awards, and a Huck Institutes of the Life Sciences Coronavirus Research Seed Grant. Rebecca Borchering reports funding from an NSF COVID-19 RAPID award. Katharine Tallaksen, Kaitlin Rainwater-Lovett, Laura Asher, Luke C. Mullany, Molly E. Gallagher, Matt Kinsey, Richard F. Obrecht, and Lauren Shin report funding from the U.S. Department of Health and Human Services (HHS), Office of the Assistant Secretary for Preparedness and Response to the Johns Hopkins Applied Physics Laboratory. Matteo Chinazzi reports grants from the National Institutes of Health (NIH), the Council of State and Territorial Epidemiologists (CSTE), and Metabiota to Northeastern University. Ana Pastore y Piontti reports funding from Metabiota, Inc. to Northeastern University and royalties from Springer Publishing. Joseph Lemaitre reports funding from the Swiss National Science Foundation, State of California, HHS, and the Department of Homeland Security (DHS). Kyra H. Grantz reports support from the California Department of Public Health, Johns Hopkins Bloomberg School of Public Health, NIH, and travel support from the World Health Organization (WHO). Elizabeth Lee and Claire Smith report support from the California Department of Public Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins Health System, HHS, and DHS, and computing resources from Amazon Web Services, Johns Hopkins University Modeling and Policy Hub, and the Office of the Dean at the Johns Hopkins Bloomberg School of Public Health. Justin Lessler reports support from DHHS, DHS, California Institute of Technology, NIH, honorarium from the American Association for Cancer Research, personal fees for expert testimony from Paul, Weiss, Rifkind, Wharton & Garrison, LLP. Lindsay Keegan reports support from the State of California, and NIH, a University of Utah Immunology, Inflammation, and Infectious Disease Seed Grant, and a scholarship from the University of Washington Summer Institute in Statistics and Modeling of Infectious Diseases. Lucie Contamin, John Levander, Jessica Salerno, and Willem Gijsbert van Panhuis report a National Institute of General Medical Sciences grant. Ajitesh Srivastava reports a grant from the National Science Foundation. Michael C. Runge reports stock ownership in Becton Dickinson & Co., which manufactures medical equipment used in COVID testing, vaccination, and treatment. Alessandro Vespignani reports grants from NIH, NSF, WHO, CSTE, Metabiota Inc., Templeton Foundation, Scientific Interchange Foundation, Bill & Melinda Gates Foundation; royalties from Cambridge University Press, World Scientific, Springer Publishing, and Il Saggiatore; consulting fees from Human Technopole Foundation, Institute for Scientific Interchange Foundation, honorarium for lecture module at University of Washington; Scientific Advisory Board member of the Institute for Scientific Interchange Foundation, Italy, Supervisory Board member of the Human Technopole Foundation, Italy; and gifts to Northeastern University from the McGovern Foundation, the Chleck Foundation, the Sternberg Family, J. Pallotta, and Google Cloud research credits for COVID-19 from Google. Akhil Sai Peddireddy, Pyrros A. Telionis, Anil Vullikanti, Jiangzhuo Chen, Benjamin Hurt, Brian D. Klahn, Bryan Lewis, James Schlitt, Joseph Outten, Lijing Wang, Madhav Marathe, Patrick Corbett, Przemyslaw Porebski, and Srinivasan Venkatramanan report institutional support from the National Science Foundation, Expeditions, NIH, the U.S. Department of Defense, Virginia Department of Health, Virginia Department of Emergency Management, University of Virginia (internal seed grants), and Accuweather. No other potential conflicts of interest were disclosed.

The US Food and Drug Administration (FDA) has been actively promoting the use of real-world data (RWD) in drug development. RWD can generate important real-world evidence reflecting the real-world clinical environment where the treatments are used. Meanwhile, artificial intelligence (AI), especially machine- and deep-learning (ML/DL) methods, have been increasingly used across many stages of the drug development process. Advancements in AI have also provided new strategies to analyze large, multidimensional RWD. Thus, we conducted a rapid review of articles from the past 20 years, to provide an overview of the drug development studies that use both AI and RWD. We found that the most popular applications were adverse event detection, trial recruitment, and drug repurposing. Here, we also discuss current research gaps and future opportunities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Since December 2020, the Minnesota Department of Health (MDH) Public Health Laboratory has been receiving 100 specimens per week (50 from each of two clinical partners) with low cycle threshold (Ct) values for routine surveillance for SARS-CoV-2, the virus that causes COVID-19. On January 25, 2021, MDH identified the SARS-CoV-2 variant P.1 in one specimen through this surveillance system using whole genome sequencing, representing the first identified case of this variant in the United States. The P.1 variant was first identified in travelers from Brazil during routine airport screening in Tokyo, Japan, in early January 2021 (1). This variant has been associated with increased transmissibility (2), and there are concerns that mutations in the spike protein receptor-binding domain might disrupt both vaccine-induced and natural immunity (3,4). As of February 28, 2021, a total of 10 P.1 cases had been identified in the United States, including the two cases described in this report, followed by one case each in Alaska, Florida, Maryland, and Oklahoma (5)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background and Objectives: It is unclear whether the prognostic significance of the 8th American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system for non-small-cell lung cancer (NSCLC) is applicable to lung cancer as a second primary malignancy (LCSPM). This study used a population-based database to evaluate this relationship., Methods: Patients diagnosed with second primary lung cancer after a nonpulmonary malignancy were identified from the Surveillance, Epidemiology and End Results (SEER) registry from 2004 to 2015. Cumulative incidence function (CIF) and multivariable CIF regression analyses were performed to estimate the difference in disease-specific mortality (DSM) among different TNM stages., Results: Our cohort included 2687 patients from the SEER database. After CIF analysis, although rates of 1-year, 3-year, and 5-year DSM trended higher with increasing TNM stages, the DSM curves overlapped for many subcategories. In a multivariable regression analysis, hazards ratios (HRs) for subcategories of stage Ι demonstrated no significant difference compared with the reference stage ΙA1 ([ΙA2 HR = 1.120; 95% confidence interval [CI], 0.477-2.626]; [ΙA3 HR = 1.762; 95% CI, 0.752-4.126]; [ΙB HR = 2.003; 95% CI, 0.804-4.911]). The following HRs trended higher for increasing TNM stages but with overlapping CIs among adjacent stage groupings., Conclusion: The 8th edition AJCC TNM staging system fails to provide accurate prognostic value for LCSPM., (© 2020 Wiley Periodicals, Inc.)

Background: Unemployment has been reported to be associated with an increased risk of mortality. While most available studies focused on the effects of temporary unemployment on mortality, it remains unclear whether similar trends can be found in subjects who were never employed or are retirement. Therefore, this study examined the associations between temporary unemployment, never employed and retirement, integrating the risk of all-cause and cause-specific mortality in US adults., Methods: Data from the National Health Interview Survey from 2001 to 2013 Linked Mortality files through 31 December 2015 were used. A total of 282 364 participants aged 18 to 65 years were included. Their employment status was categorised into four groups: employed, never employed, temporary unemployed and retired., Results: During the mean follow-up time of 8.2 years, 12 645 subjects died from a variety of causes. Compared with employed participants, temporary unemployed, never employed or retired participants faced an increased risk of mortality for all-cause (temporary unemployed HR 1.76, 95% CI 1.67 to 1.86; never employed HR 1.63, 95% CI 1.47 to 1.81; retired HR 1.27, 95% CI 1.17 to 1.37). Cause-specific mortality analysis showed that compared with employed participants, temporary unemployed or never employed participants faced a significantly increased risk of mortality from cancer, cardiovascular disease, chronic lower respiratory disease, diabetes and kidney disease., Conclusion: This study showed that retired, temporary unemployed and never employed participants aged 18 to 65 years were strongly associated with higher mortality, indicating that both temporary and long-term unemployment are associated with a higher risk of mortality and adversely affect longevity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To discuss the research progress in the field of coronavirus (CoVs) treatment based on the visualization analysis of knowledge graph., Methods: The related literatures in the field of CoVs treatment were retrieved from the establishment of Web of Science core collection database to February 15th, 2020, and the literature analysis tool of Web of Science database was used to count the annual trend of published literatures. The VOSviewer software was used to analyze the relationship among countries, institutions, authors, clustering and density of subject words. The HistCite software was used to screen important documents and to draw the evolution process of hot spots. The CiteSpace software was used to analyze the breakout points of subject words, so as to find the front and hot spots in this field., Results: A total of 1 747 data were retrieved, with the exception of 17 duplicate data, and 1 730 data were retained for visualization analysis. In terms of literature volume, the literatures on CoVs therapy rose after 2003 and 2012, and the number of published literatures had remained high since 2014. In terms of countries, the main countries that carried out the research on the treatment of CoVs were the United States (n = 613), China (n = 582), Germany (n = 122), Canada (n = 99), etc., and the cooperation among countries was close. In terms of institutions, the number of papers issued by Chinese Academy of Sciences in the field of CoVs treatment ranked first (n = 82), followed by University of Hong Kong of China (n = 74) and Chinese University of Hong Kong of China (n = 58), followed by National Institute of Allergy and Infectious Diseases (n = 37), and the cooperation among various institutions was close. In terms of literature authors, there were two high-yielding authors in the United States [Ralph S. Baric (n = 21) and Kuochen Chou (n = 17)], two Chinese authors [Yuen Kwok-yung (n = 17) and Jiang Shibo (n = 16)] and one Dutch author [Eric J. Snijder (n = 17)]. In terms of the cluster analysis of authors, the authors were closely related in reverse genetics, respiratory infection, receptor binding domain, etc., and the 15 top-cited papers came mainly from China, the United States, Netherlands and other countries, and the literature content represented the frontiers and hot spots in different periods. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation. The main subject words were divided into three main categories, namely, CoVs epidemiology, basic research and drug development, in which basic research and drug development were strongly correlated. In the subject words breakthrough analysis, there were time-related breakthrough points in 1991, 1996 and 2002, and the "diagnosis" and "sequence" were continuous hot spots., Conclusions: Through the visualization analysis of knowledge graph, the development trend and hot spots of CoVs therapy research could be well observed. In this study, the degree of attention in the field of CoVs treatment showed periodic changes, related to the outbreak of new CoVs, and the country, institutions and the author were closely related. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation in order to develop new targets of drug.

Pharmaceutical companies are relying more often on external sources of innovation to boost their discovery research productivity. However, more in-depth knowledge about how external innovation may translate to successful product launches is still required in order to better understand how to best leverage the innovation ecosystem. We analyzed the pre-approval publication histories for FDA-approved new molecular entities (NMEs) and new biologic entities (NBEs) launched by 13 top research pharma companies during the last decade (2006-2016). We found that academic institutions contributed the majority of pre-approval publications and that publication subject matter is closely aligned with the strengths of the respective innovator. We found this to also be true for candidate drugs terminated in Phase 3, but the volume of literature on these molecules is substantially less than for approved drugs. This may suggest that approved drugs are often associated with a more robust dataset provided by a large number of institutes. Collectively, the results of our analysis support the hypothesis that a collaborative research innovation environment spanning across academia, industry and government is highly conducive to successful drug approvals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pure breed dogs of Western origin are increasingly more popular in China as is a need to differentiate breeds and individual dogs for personal and forensic reasons. Research on genetic diversities of the canine population in China is rarely conducted. In this study, genetic distributions and forensic efficiencies of 19 canine STR loci in Labrador Retriever population from China were evaluated by using one available commercial canine kit in China. This panel was used to genetically define 214 Labrador Retrievers in China, as an example of one of the most important Western breeds and to compare them with Labrador Retrievers from America based on three overlapping STR loci. Moreover, genetic relationship analyses between Labrador Retriever population and two reference populations in America were performed. All 19 STR loci were polymorphic and conformed to Hardy-Weinberg equilibrium in the studied population. The STR panel was able to discern individual dogs with a high degree of accuracy. Breed-wide genetic heterozygosity comparisons based on present and published allele frequencies revealed that the studied population had the lower genetic heterozygosity than canine populations in America. Principal component analysis among Labrador Retriever population and other reference populations showed that the studied Labrador Retrievers were genetically close to the retriever breeds in America. Population genetic structure analyses among these canine breeds further revealed genetic differentiations between the studied Labrador Retriever population and other compared breeds. In conclusion, these STR loci had relatively high forensic values in Labrador Retriever population in China, which could be employed for individual identification and kinship testing.

Purpose: Acute esophagitis is common after thoracic radiation therapy (TRT) given with chemotherapy for limited-stage small-cell lung cancer (LS SCLC). Although twice-daily TRT to 45 Gy in 30 fractions is considered standard, some clinicians are reluctant to use this schedule because of its perceived impracticality and risk of severe esophagitis. We reviewed a single-institution experience with severe (grade ≥ 3) esophagitis after TRT with chemotherapy for LS SCLC., Patients and Methods: A total of 504 patients were identified as having received TRT (≥45 Gy) with platinum-containing chemotherapy for LS SCLC at MD Anderson Cancer Center in 1987 through 2012. Patients with complete or good partial response were offered prophylactic cranial irradiation. Esophagitis was scored retrospectively with the Common Terminology Criteria for Adverse Events, V3.0. Clinical variables were analyzed for possible association with acute grade ≥ 3 esophagitis., Results: At a median follow-up time of 23.9 months (range, 1.2-240.8 months), 103 (20%) patients had experienced grade ≥ 3 esophagitis. In univariate analysis, TRT dose ≥ 60 Gy was the only factor associated with severe esophagitis (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.02-3.30; P = .043); use of twice-daily TRT was not (OR, 0.96; 95% CI, 0.61-1.52; P = .867). The significance of TRT to ≥ 60 Gy was maintained in multivariate Cox regression analysis adjusted for tumor size (OR, 1.91; 95% CI, 1.05-3.46; P = .034)., Conclusions: TRT to ≥ 60 Gy predicted acute severe esophagitis, but twice-daily fractionation did not. Standard-dose 45-Gy twice-daily TRT should not be avoided for fear of severe esophagitis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although lots of genes have been revealed to relate to sporadic amyotrophic lateral sclerosis (sALS), its genetic mechanisms still need to be further explored. We aimed to search the novel genetic factors of sALS and assess their contribution. We constructed an integrative dataset based on the 3227 subsignificant genes (P value < 0.01) from two sALS-related genome-wide association studies (GWAS) (the US and Irish studies). A significant replication between both studies was confirmed by the gene set enrichment analysis in the integral level (P value < 10 -4 ). Using the pathway overrepresentation analysis, we revealed the 34 shared Gene Ontology (GO) biological processes from the two independent studies (P value < 0.01). Among these pathways, the nervous system developmental pathway (NSD function, GO:0007399) was further supported by the previously reported genes related to sALS (P value = 3.28e-12). Importantly, four of 17 NSD-function-related target genes (disrupted-in-schizophrenia-1 (DISC1), CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case-control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles.

Objectives Whether racial/ethnic differences in prevalence/reporting of sleep disorders exist in pregnant women/women of child-bearing age is unknown. Study objectives were to estimate prevalence of sleep disorders and to examine racial/ethnic differences in sleep disorders, reporting of sleep issues, and amount of sleep among women of child-bearing age (15-44 years) in the US. Methods Through a secondary analysis of the National Health and Nutrition Examination Survey 2005-2010 (3175 non-pregnant, 432 pregnant women in main analysis), prevalence of sleep disorders, reporting of sleep disorders to a physician/health professional, and amount of sleep were estimated overall, by pregnancy status, and by race/ethnicity stratified by pregnancy status. Racial/ethnic differences in reporting of trouble sleeping by pregnancy status were examined using univariate and multivariate logistic regression. Results Prevalence of diagnosed sleep disorders among women of childbearing age was 4.9 % [3.9 % pregnant; 5.1 % non-pregnant (p < 0.01)]. Significantly fewer pregnant and non-pregnant minority women reported adequate sleep (7-8 h) than non-Hispanic white (white) women (p < 0.05). Among non-pregnant women, odds of report of trouble sleeping were significantly higher for white compared to black (aOR 0.47 [95 % CI 0.36, 0.61]) or Mexican-American women (aOR 0.29 [95 % CI 0.21, 0.41]); non-pregnant minority women were also significantly less likely to report trouble sleeping than white women when controlling for amount of sleep. Among pregnant women, these same trends were found. Discussion Compared to white women, minority women, despite reporting less adequate sleep, are less likely to report trouble sleeping, providing evidence of an important health disparity., Competing Interests: The authors declare that they have no conflict of interest.

Background: Assisted reproductive technology has been reported to account for a disproportionate higher number of low birthweight infants, even in singleton births. Low birthweight infants occur from preterm birth, decreased intrauterine growth, or both. It is unclear whether infants conceived by in vitro fertilization (IVF) have a reduced intrauterine growth rate or intrauterine growth restriction. Growth-restricted newborns have higher perinatal morbidity and are at increased risk for adult-onset illnesses. To date, there are no national standards for birthweight percentiles by gestational week, allowing for fetal growth assessment of singletons conceived by assisted reproductive technology in the United States., Objective: The objective of the study was to establish US singleton IVF reference standards using birthweight percentiles by gestational age for singleton live births resulting from IVF in the United States., Study Design: We studied birthweight by completed weeks of gestation for 93,443 singleton IVF births reported to the Society for Assisted Reproductive Technologies, 2006-2010. The third to 97th birthweight percentiles per completed week of gestation for weeks between 24 and 42 were calculated and were compared with recently published birthweight percentiles by gestational age for 3,812,730 US singleton births in 2011., Results: Smoothed birthweight for gestational age charts and curves were created for all US IVF singletons and female-male singletons from 24 to 42 weeks. Over the span of 31-41 weeks of gestation, the 10th, 50th, and 90th birthweight percentile values of IVF singletons were comparable with recently published birthweight percentile values of US singletons. At 40 completed weeks of gestation, the 10th, 50th, and 90th birthweight percentiles of all IVF singletons were 3078, 3506, and 4053 g, as compared with corresponding 3005, 3499, and 4057 g of US singletons. The 10th, 50th, and 90th birthweight percentile values for female and male IVF singletons were also comparable with US female and male singletons., Conclusion: Birthweight percentiles per completed week of gestation of IVF and US singletons are approximately equal from 31 until 41 completed weeks, suggesting that intrauterine growth is not reduced in IVF singleton infants., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Among natural conceptions, advanced maternal age (≥ 35 years) is associated with an increased risk of preterm birth. However, few studies have specifically examined this association in births resulting from in vitro fertilisation (IVF)., Methods: A retrospective cohort study was conducted in 97288 singleton and 40961 twin pregnancies resulting from fresh non-donor IVF cycles using 2006-10 data from the Society for Assisted Reproductive Technology Clinic Online Reporting System., Results: Rates of very early preterm (<28), early preterm (<32), and preterm birth (<37 completed weeks) decreased with increasing maternal age in both singleton and twin births (PTrend <0.01). With women aged 30-34 years as the reference, those aged <30 years were at an increased risk of all types of preterm births. The adjusted odd ratio (95% confidence interval [CI]) for very early preterm birth, early preterm birth, and preterm birth in women aged 25-29 years were 1.3 [95% CI 1.1, 1.5], 1.2 [95% CI 1.1, 1.4], and 1.1 [95% CI 1.02, 1.2] in singletons. This increased risk of preterm births among younger women was even more significant in twin births. However, women aged ≥ 35 years were not at an increased risk of any type of preterm births in both singleton and twin births., Conclusions: In contrast to natural conception, advanced maternal age is not associated with an increased risk of preterm births in pregnancies conceived by IVF. Women who seek IVF treatments before 30 years old are at higher risk of all stages of preterm births., (© 2014 John Wiley & Sons Ltd.)

Background: Nomograms for prostate and colorectal cancer are included in the Surveillance, Epidemiology, and End Results (SEER) Cancer Survival Calculator, under development by the National Cancer Institute. They are based on the National Cancer Institute's SEER data, coupled with Medicare data, to estimate the probabilities of surviving or dying from cancer or from other causes based on a set of patient and tumor characteristics. The nomograms provide estimates of survival that are specific to the characteristics of the tumor, age, race, gender, and the overall health of a patient. These nomograms have been internally validated using the SEER data. In this paper, we externally validate the nomograms using data from Kaiser Permanente Colorado., Methods: The SEER Cancer Survival Calculator was externally validated using time-dependent area under the Receiver Operating Characteristic curve statistics and calibration plots for retrospective cohorts of 1102 prostate cancer and 990 colorectal cancer patients from Kaiser Permanente Colorado., Results: The time-dependent area under the Receiver Operating Characteristic curve statistics were computed for one, three, five, seven, and 10 year(s) postdiagnosis for prostate and colorectal cancer and ranged from 0.77 to 0.89 for death from cancer and from 0.72 to 0.81 for death from other causes. The calibration plots indicated a very good fit of the model for death from cancer for colorectal cancer and for the higher risk group for prostate cancer. For the lower risk groups for prostate cancer (<10% chance of dying of prostate cancer in 10 years), the model predicted slightly worse prognosis than observed. Except for the lowest risk group for colorectal cancer, the models for death from other causes for both prostate and colorectal cancer predicted slightly worse prognosis than observed., Conclusions: The results of the external validation indicated that the colorectal and prostate cancer nomograms are reliable tools for physicians and patients to use to obtain information on prognosis and assist in establishing priorities for both treatment of the cancer and other conditions, particularly when a patient is elderly and/or has significant comorbidities. The slightly better than predicted risk of death from other causes in a health maintenance organization (HMO) setting may be due to an overall healthier population and the integrated management of disease relative to the overall population (as represented by SEER)., (Published by Oxford University Press 2014.)

Background: West Nile virus (WNV) infection is associated with acute morbidity and mortality in adults and children. Information on the effects of maternal WNV illness during pregnancy on early childhood development is limited. This study was designed to examine the relationship between maternal WNV illness during pregnancy and birth and developmental outcomes at age 3 years., Methods: Mother-child participants were identified using a national surveillance registry for women with WNV illness during pregnancy. Maternal and infant health data and relevant family characteristics were obtained through medical record reviews and maternal questionnaires. All infants received ophthalmologic examinations. Child development was evaluated at age 3 years using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III)., Results: As a group, the children's (N = 11) birth weight, head circumference, and infant ophthalmologic examination results were within age expectations; one child was born preterm (gestational age 36 weeks). Mean (SD) age at the time of Bayley-III testing was 36.7 (3.8) months. The group's mean performance on the Bayley-III was at or above age level in all domains, but one child showed a mild delay in the Adaptive domain. The variability observed in this sample (1/53 [1.9%] Domain scores < -2.0 SDs) was consistent with expectations based upon the distribution of Bayley-III Domain scores in the general population., Conclusion: Maternal WNV infection does not appear to be associated with global developmental delays in young children. These results are preliminary, however, and require confirmation in future research., (© 2014 Wiley Periodicals, Inc.)

Objective: To determine the contribution of monozygotic twining to in vitro fertilization multiple births., Study Design: We performed a retrospective analysis of the incidence of monozygotic twining in multiple births resulting from fresh embryo transfers using 2006-2010 data from the Society for Reproductive Technology Clinic Outcome Reporting System., Results: The number of embryos transferred were fewer than the number of births in 0.5% (223/40950) of twin, 29% (659/2289) of triplet, and 64% (43/67) of quadruplet births resulting from transfer of fresh embryos from 2006 to 2010. In 2010, 37% of triplets and 100% of quadruplet births occurred when fewer than 3 and fewer than 4 embryos respectively were transferred., Conclusion: Monozygotic twinning plays a key role in the development of triplet and quadruplet pregnancies achieved through in vitro fertilization., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To analyze the effects of preconception maternal height and weight on the risk of preterm singleton and twin births resulting from in vitro fertilization (IVF)., Study Design: We performed a retrospective cohort analysis of the incidence of very early preterm birth (VEPTB), early preterm birth (EPTB), and preterm birth (PTB), before 28, 32, and 37 completed weeks, respectively, in 60,232 singleton and 24,111 twin live births using 2008-2010 live birth outcome data from the Society for Reproductive Technology Clinic Outcome Reporting System., Result: Maternal obesity is associated with significantly increased risk of VEPTB, EPTB, and PTB in pregnancies conceived by IVF. For morbidly obese women (body mass index ≥35) with singletons, rates of VEPTB, EPTB, and PTB were 1.7%, 3.6%, and 16.4%, with adjusted risk ratios (aRRs) and 95% confidence levels (CIs) of 2.6 (1.8-3.6), 2.2 (1.8-2.6), and 1.5 (1.4-1.7) using corresponding rates for normal body mass index (95% CI, 18.6-24.9) as referent. For morbidly obese women with twins, rate of VEPTB and EPTB were 6.5% and 12.5%, with aRRs and 95% CIs of 2.4 (1.8-3.0) and 1.5 (1.3-1.8). For singletons, the rate of PTB for short stature women (<150 cm) was 14.2%, as compared with 11.8% in those women with height ranging between 160-167 cm (referent), with aRRs and 95% CIs of 1.2 (1.0-1.4)., Conclusion: Preconception maternal obesity and short stature are associated with significantly increased risk of VEPTB and early preterm singleton and twin births in pregnancies resulting from IVF., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: The objective of the study was to examine racial and ethnic differences in preterm births in infants conceived by in vitro fertilization (IVF)., Study Design: A retrospective cohort study was conducted of 97,288 singleton and 40,961 twin pregnancies resulting from fresh, nondonor IVF cycles using 2006-2010 data from the Society for Assisted Reproductive Technology Clinic Online Reporting System., Results: Rates of very early preterm (<28 weeks), early preterm (<32 weeks), and preterm birth (<37 completed weeks) varied across racial and ethnic groups in both singleton and twin pregnancies. In singletons, with white women as the referent, after adjustment of confounding variables, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of very early preterm birth, early preterm birth, and preterm birth in black women were 4.8 (95% CI, 4.1-5.7), 3.9 (95% CI, 3.4-4.4), and 2.1 (95% CI, 1.9-2.3). Hispanic women had a significantly lower rate of preterm births as compared with black women and similar or slightly higher rates as compared with white women. Native American women were not at an increased risk of any types of preterm births; Asian women were at a reduced risk of preterm twin births (adjusted OR, 0.8; 95% CI, 0.7-0.9)., Conclusion: There exist notable racial and ethnic disparities in preterm births in infants conceived by IVF, suggesting that mechanisms other than socioeconomic disparities contribute to this difference., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To explore the economic burden and quality of life of vulvodynia in the United States., Methods: We conducted a web-based survey from 2009 to 2010. Patients who responded to a National Vulvodynia Association advertisement completed the survey every month, recording their own costs and their employers' payments related to vulvodynia in the previous month. A total of 302 patients entered data for at least 1 month and among them, 97 patients had completed data for 6 months. We used multiple imputation to generate values for unobserved cost components. For insurance payments, we also extracted the average insurance payments for direct healthcare services relating to vulvodynia from a commercial insurance database. The total costs were disaggregated into direct healthcare costs, direct non-healthcare costs and indirect costs. We also assessed patients' quality of life by using Euro QOL 5 dimensions (EQ-5D) in a follow-up survey., Results: The total costs in 6 months were $8862.40 per patient, of which $6043.34 (68.19%) were direct healthcare costs, $553.81 (6.25%) were direct non-healthcare costs and $2265.25 (25.56%) were indirect costs. Based on the reported prevalence range of 3-7% in the US, our analysis yielded an annual national burden ranging from $31 to $72 billion in the US. However, the estimate should be viewed with caution as our study sample was non-probability. The average EQ-5D score was 0.74 ± 0.19 in vulvodynia patients., Conclusion: Vulvodynia is associated with a huge economic burden to both individuals and society. It is also related to a relatively low quality of life.

Objective: To examine the effect of height, weight, and body mass index (BMI) on the risk of preterm birth of singleton and twin pregnancies conceived by vitro fertilization (IVF)., Design: Retrospective cohort study using 2006-2008 data from the Society for Reproductive Technology Clinic Outcome Reporting System (SART CORS)., Setting: SART-associated assisted reproductive technology programs., Patient(s): 56,556 singleton and 23,804 twin live births resulting from fresh nondonor IVF cycles., Intervention(s): None., Main Outcome Measure(s): Rates of very early preterm (VEPTB; <28 weeks), very preterm (VPTB; <32 weeks), and preterm birth (<37 weeks) births., Result(s): In both singleton and twin births, increased maternal height was associated with a decreased risk of preterm birth. Maternal overweight and obesity were associated with significantly increased risk of VEPTB and VPTB in twin pregnancies. For very obese women (BMI > 35 kg/m(2)) twins were associated with a threefold increased risk of VEPTB (6.1% vs. 2.0%) and a twofold increased risk of VPTB (11.5% vs. 5.9%) compared with women of normal weight (BMI 18.4-24.9 kg/m(2))., Conclusion(s): Obesity and short stature significantly increase the risk of VEPTB and VPTB in twins conceived by IVF., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Several large randomized controlled clinical trials failed to find that standard periodontal therapy during pregnancy reduces the incidence of adverse pregnancy outcomes (eg, preterm birth and low birthweight). However, treating periodontal disease during pregnancy may be too late to reduce the inflammation that is related to the adverse pregnancy outcomes. Moreover, periodontal treatment during pregnancy can cause bacteremia, which itself may initiate the pathway leading to the adverse pregnancy outcomes. Finally, the periodontal treatments provided during pregnancy are not always effective in preventing the progression of periodontal disease during pregnancy. Pregnancy may not be an appropriate period for periodontal intervention(s). We hypothesize that periodontal treatment before pregnancy may reduce the rates of adverse pregnancy outcomes. Future randomized controlled trials are needed to test if treating periodontal disease in the prepregnancy period reduces the rate of adverse pregnancy outcomes., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Post-treatment attention problems experienced by pediatric cancer survivors have been described as similar to symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) experienced in physically healthy children. Accordingly, the objectives of this study were to: (a) estimate the rate of occurrence of ADHD and secondary ADHD (SADHD) in a sample of pediatric cancer survivors, (b) compare the rate of ADHD/SADHD among survivors to the prevalence of ADHD in the general population, and (c) examine clinical correlates of ADHD/SADHD in this sample., Procedure: Survivors of pediatric ALL or brain tumor (n = 100) participated in an assessment of attention including a Computerized Performance Measure [Conners' Continuous Performance test-II (CPT-II)], parent and self-report measures (Conners 3), and a structured diagnostic interview for ADHD and other psychological disorders [Diagnostic Interview for Children and Adolescents-IV (DICA-IV)]., Results: Binomial tests revealed that the rate of ADHD/SADHD in our sample (9%) was significantly greater than the lower limits of ADHD prevalence among children in the US (3%; P < 0.001), while no difference was identified compared to the upper limits of ADHD prevalence (7%; P > 0.05). Many additional survivors (>25% of the sample) obtained clinical elevations on Conners 3 scales but did not meet ADHD/SADHD criteria., Conclusions: Attentional deficits experienced by pediatric cancer survivors do not appear to resemble the clinical presentation of ADHD or SADHD. Many survivors with cognitive and behavioral difficulties related to attention were not identified using this diagnostic approach. Findings offer needed clarification to guide researchers and clinicians in conceptualizing, assessing, and intervening on attentional late effects., (Copyright © 2011 Wiley-Liss, Inc.)

After Hurricane Katrina, the number of reported cases of West Nile neuroinvasive disease (WNND) sharply increased in the hurricane-affected regions of Louisiana and Mississippi. In 2006, a >2-fold increase in WNND incidence was observed in the hurricane-affected areas than in previous years.

Background: There is limited information on risk factors for treatment-related pneumonitis in esophageal cancer patients., Aim of the Study: To determine factors associated with treatment-related pneumonitis in esophageal cancer patients treated with definitive chemoradiotherapy., Materials and Methods: We retrospectively reviewed clinical data from esophageal cancer patients treated with definitive chemoradiotherapy from 2000 to 2003. Demographic, clinical, and treatment-related data were collected for all patients. The time to occurrence of grade > or =2 pneumonitis was calculated from the end of radiotherapy. Univariate analyses were performed to determine the existence of any association between patient demographic, clinical, or treatment characteristics and pneumonitis., Results: In total, 96 patients were included in the study with a median follow-up of 8 months (range, <1-48 months). Among them, 23 patients also received an average of two cycles of systemic chemotherapy before the initiation of concurrent chemoradiation. The incidence of grade > or =2 pneumonitis was 22% at 1 year. Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade > or =2 pneumonitis (p = 0.003), with the 1-year incidence of grade > or =2 pneumonitis for patients with and without systemic chemotherapy being 49 and 14%, respectively. No other clinical or dosimetric factors investigated were associated with the risk of grade > or =2 pneumonitis., Conclusions: Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade > or =2 pneumonitis, suggesting that induction chemotherapy may have sensitized the lung tissue to radiation damage in esophageal cancer patients.

Mexican-American women have similar low socio-economic status as compared to Non-Hispanic Blacks. However, Mexican-American women have consistently been shown to have a lower rate of low birth weight births as compared to Non-Hispanic Blacks and similar to Non-Hispanic Whites. This phenomenon is referred to as the "Mexican paradox", and the explanation for this is still unclear. We used data from the third US National Health and Nutrition Examination Survey (NHANES III) to compare the rate of periodontal disease in Non-Hispanic Black, Non-Hispanic White and Mexican-American pregnant and non-pregnant women. We found that Mexican-American women have a lower rate of periodontal disease before and during pregnancy when compared to Non-Hispanic Blacks. Since periodontal disease has been associated with an increased risk of preterm birth and low birth weight, we hypothesize that the lower prevalence of periodontal disease before and during pregnancy among Mexican-American women may contribute to the "Mexican paradox".

Objective: To evaluate the effect of fetal position on 1) second-stage labor duration and 2) indicators of maternal and neonatal morbidity., Methods: A retrospective cohort study was conducted using a database from a previously reported randomized clinical trial. The data set includes 210 women with the fetus in a posterior position, 200 women with the fetus in a transverse position, and 1,198 women with the fetus in an anterior position. Mean durations of the second stage of labor for different fetal positions were compared using Tukey studentized test. A multivariate logistic regression model was performed to examine the determinants of prolonged second-stage duration (>or= 3 hours). Kaplan-Meier survival curves were used to graph and compare the duration of the second stage of labor for spontaneous delivery according to the fetal position at full dilatation and study group., Results: Fetal malposition at full dilatation was associated with a significantly increased risk of instrumental vaginal delivery, cesarean delivery, oxytocin administration before full cervical dilatation, episiotomy, severe perineal laceration, and maternal blood loss of more than 500 mL (all P values < .01). Compared with the occiput anterior positions, there were significant differences in the duration of the second stage of labor, with a mean of 3.1 hours (95% confidence interval [CI] 3.0-3.2) for occiput anterior positions, 3.6 hours (95% CI 3.3-3.9) for occiput transverse positions (P < .05), and 3.8 hours (95% CI 3.5-4.1) for occiput posterior positions (P < .05) in the delayed pushing group. For the early pushing group, means were 2.2 hours (95% CI 2.1-2.3) for occiput anterior positions, 2.5 hours (95% CI 2.3-2.8) for occiput transverse positions (P < .05), and 3.0 hours (95% CI 2.7-3.3) for occiput posterior positions (P < .05)., Conclusion: Fetal malposition at full dilatation results in a higher risk of prolonged second stage of labor and increases maternal morbidity indicators., Level of Evidence: II-2.

Because of inconsistent findings among case-control studies on the relationship between IUD use and the risk of ectopic pregnancy, a meta-analysis of published literature was conducted. From 1977 through 1994, 19 publications regarding 16 studies of ectopic pregnancy and IUD use were found by MEDLINE and manual search. The odds ratio (ORs) of ectopic pregnancy with current and past IUD use in each study were pooled. A quality score system was developed to assess each study. Funnel plot was used to assess potential publication biases. For current IUD use, when cases were compared to pregnant controls, there was an increased risk of ectopic pregnancy (pooled OR: 10.63, 95% confidence interval (CI): 7.66-14.74); when cases were compared to non-pregnant controls, there was no risk of ectopic pregnancy (pooled OR: 1.06, 95% CI: 0.91-1.24). Past IUD use could mildly increase the risk of ectopic pregnancy (pooled OR: 1.40, 95% CI: 1.23-1.59). Selecting pregnant or non-pregnant women as controls, however, did not affect the OR estimates of past IUD use. Current IUD use does not increase the risk of the ectopic pregnancy. However, a pregnancy with an IUD in situ is more often an ectopic one than a pregnancy with no IUD. Past IUD use could mildly elevate the risk of ectopic pregnancy.