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Background: Real-time review of frozen sections underpins the quality of Mohs surgery. There is an unmet need for low-cost techniques that can improve Mohs surgery by reliably corroborating cancerous regions of interest and surgical margin proximity. Objective: To test that deep learning models can identify nonmelanoma skin cancer regions in Mohs frozen section specimens. Methods: Deep learning models were developed on archival images of focused microscopic views (FMVs) containing regions of annotated, invasive nonmelanoma skin cancer between 2015 and 2018, then validated on prospectively collected images in a temporal cohort (2019-2021). Results: The tile-based classification models were derived using 1423 focused microscopic view images from 154 patients and tested on 374 images from 66 patients. The best models detected basal cell carcinomas with a median average precision of 0.966 and median area under the receiver operating curve of 0.889 at 100x magnification (0.943 and 0.922 at 40x magnification). For invasive squamous cell carcinomas, high median average precision of 0.904 was achieved at 100x magnification. Limitations: Single institution study with limited cases of squamous cell carcinoma and rare nonmelanoma skin cancer. Conclusion: Deep learning appears highly accurate for detecting skin cancers in Mohs frozen sections, supporting its potential for enhancing surgical margin control and increasing operational efficiency.

Abstract A common approach to monitoring the status of physical and biological systems is through the regular measurement of various system parameters. Changes in a system’s underlying dynamics manifest as changes in the behaviour of the observed time series. For example, the transition from healthy cardiac activity to ventricular fibrillation results in erratic dynamics in measured electrocardiogram (ECG) signals. Identifying these transitions—change point detection—can be valuable in preparing responses to mitigate the effects of undesirable system changes. Here, we present a data-driven method of detecting change points using a phase space approach. Delay embedded trajectories are used to construct an ‘attractor network’, a discrete Markov-chain representation of the system’s attractor. Once constructed, the attractor network is used to assess the level of surprise of future observations where unusual movements in phase space are assigned high surprise scores. Persistent high surprise scores indicate deviations from the attractor and are used to infer change points. Using our approach, we find that the attractor network is effective in automatically detecting the onset of ventricular fibrillation (VF) from observed ECG data. We also test the flexibility of our method on artificial data sets and demonstrate its ability to distinguish between normal and surrogate time series.

Introduction: The relative contributions of aortic and carotid artery stiffness on cognitive impairment and dementia remain unknown. We examined the associations of aortic and carotid artery stiffness with cerebrovascular disease markers, cognition, and dementia subtypes in a memory clinic cohort. Methods: 272 participants underwent applanation tonometry, carotid ultrasonography, 3T brain MRI, and neuropsychological assessment. Aortic stiffness parameters (carotid-femoral pulse wave velocity, aortic augmentation index, and aortic pulse pressure) were obtained with applanation tonometry whilst carotid artery stiffness parameters (β-index, pressure-strain elastic modulus, and pulse- wave velocity-β) were assessed by carotid ultrasonography, from which composite scores for aortic and carotid artery stiffness were calculated. Brain magnetic resonance images were graded for cerebrovascular disease markers, including white matter hyperintensities (WMH), lacunes, cerebral microbleeds, cortical infarcts, and stenosis. Cognition was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network harmonization battery in order to classify participants as having no cognitive impairment, cognitive impairment no dementia, or dementia subtyped as Alzheimer disease and vascular dementia. Results: After considering both aortic and carotid artery stiffness in the same regression models, carotid artery stiffness remained independently and significantly associated with WMH (β=0.78, p

Mass migration and migrant death at the U.S. southern border highlight the disconnectedness of the systems for transnational decedent identifications. Death investigation cases in Texas face delays and barriers at all stages of an investigation. Additionally, fragmentation of DNA databases exacerbate challenges in comparing genetic samples from unidentified human remains (UHR) and families of the missing. We sought to pilot alternative workflows for processing UHR and family reference samples (FRS) for the identification of probable migrant decedents. Primarily using Rapid DNA, but also accredited non-CODIS DNA laboratories, the piloted approaches were conducted in parallel to existing medicolegal workflows under the relevant case jurisdictional guidance. Our data show that Rapid DNA is a valid path for anthropology laboratories to support identification hypotheses and that accredited non-CODIS forensic and genetic laboratories also can support families to identify remains, especially when families reside outside of the United States.

Objectives: Singapore experienced two major outbreaks of chikungunya in 2008-09 and 2013-14. Despite repeated virus introductions, fresh local outbreaks have not emerged after 2014. The present study reviews the success of chikungunya control in Singapore, despite repeated introduction of virus strains, presence of competent vectors and an immunologically naïve population. Methods: Chikungunya virus (CHIKV) sequences (421 envelope 1 genes and 56 polyproteins) were analysed to distinguish the indigenous virus groups from 2008 to 2020. Vector surveillance data was used to incriminate the vector/s associated with local outbreaks. The population exposure to CHIKV was determined by assessing the seroprevalence status in three cohorts of sera collected in 2009 (n=2,008), 2013 (n=2,000) and 2017 (n=3,615). Results: Four distinct groups of CHIKV of East, Central and South African genotype have mainly circulated since 2008, transmitted primarily by Aedes albopictus. The age weighted CHIKV IgG prevalence rates were low (1-5%) and showed a non-significant increase from 2009 to 2013, but a significant decrease in 2017. In contrast, the prevalence of CHIKV neutralising antibodies in the population increased significantly from 2009 to 2013, with no significant change in 2017, but the levels remained below 2%. Conclusions: The evidence suggested that surveillance and vector control strategies implemented were robust to avert severe epidemics, despite repeated introduction of virus strains, presence of competent vectors and an immunologically naïve population.

Introduction: Nitazoxanide is an oral anti-parasitic agent that has been found to have broad antiviral activity. Its role in the treatment of viral gastroenteritis is not well-studied. Given the worldwide prevalence of viral gastroenteritis, particularly in developing nations, a systematic review of this topic would be valuable. Methods: A formal literature search with the assistance of a reference librarian included randomized controlled trials, cohort studies, case-control studies, and case reports. Studies were included if they pertained to nitazoxanide use for viral gastroenteritis and excluded if nitazoxanide was used for parasitic or other viral illnesses. Results: Based on inclusion and exclusion criteria, 5 randomized controlled trials (2 in Egypt and 1 each in Peru, India, and Bolivia) were included in the systematic review. Four of the studies enrolled children only; one study included adults. All studies noted a statistically significant reduction in time from the first dose of nitazoxanide to resolution of illness (approximately one to 2 days) in patients compared to the receiving placebos (approximately 3 days). There were 9 case series or reports on nitazoxanide use for viral gastroenteritis in immunocompromised hosts; of these, only one case reported a noticeable effect of nitazoxanide in reducing symptom duration and severity. Conclusion: Despite the limited number of studies and the potential risk of bias introduced by the funding source, a benefit of nitazoxanide in reducing duration of illness from viral gastroenteritis was demonstrated for immunocompetent children. Randomized controlled trials are needed to elucidate the role of nitazoxanide for treating viral gastroenteritis in immunocompromised hosts.

Introduction: Immigrants to the United States who return home to visit friends and relatives (VFRs) have high rates of travel-related infections. The data on VFR utilization of pre-travel health care is inadequate. The objective of this study was to describe the travel patterns and adherence to pre-travel recommendations of VFRs.Methods: This retrospective study compared pre-travel health care utilization between VFR and non-VFR patients in one travel clinic from 2012-2013. Study investigators reviewed patients’ electronic medical records for demographic data, travel characteristics, and rates of immunizations and preventive medication prescriptions (i.e. antimalarial prophylaxis and antibiotics for traveler’s diarrhea). Categorical variables were compared using chi-square tests. Multivariate logistic regression was used to model adjusted associations of VFR with completion of pre-travel recommendations.Results: VFRs (n = 393) were younger than non-VFRs (n = 1680), more often required interpreters for language translation, and more commonly had government insurance coverage than non-VFRs. VFRs were more likely to travel to lower-income countries in Africa, Asia, and the Middle East. VFRs had longer durations of travel: 51% for >4 weeks vs. 21% for non-VFRs (P < 0.0001). VFRs were less likely to complete tetanus, polio, and rabies vaccinations, but more likely to complete measles, mumps, and rubella vaccinations. Only the association with the rabies vaccination remained significant after adjustment (OR [95% CI] = 0.3 [0.1, 0.8]).Conclusion: VFRs had longer travel durations and lower rates of vaccine completion than non-VFRs. More research is needed to understand this disparity and to promote changes in practice.

Nucleic acid amplification tests (NAATs) are recommended by the CDC for detection of Chlamydia trachomatis (Ct) urogenital infections. Current commercial NAATs require technical expertise and sophisticated laboratory infrastructure, are time-consuming and expensive, and do not differentiate the lymphogranuloma venereum (LGV) strains that require a longer duration of treatment than non-LGV strains. The multiplexed microfluidic PCR-based assay presented in this work simultaneously interrogates 13 loci to detect Ct and identify LGV and non-LGV strain-types. Based on amplified fragment length polymorphisms, the assay differentiates LGV, ocular, urogenital, and proctocolitis clades, and also serovars L1, L2, and L3 within the LGV group. The assay was evaluated in a blinded fashion using 95 clinical swabs, with 76 previously reported as urogenital Ct-positive samples and typed by ompA genotyping and/or Multi-Locus Sequence Typing. Results of the 13-plex assay showed that 51 samples fell within urogenital clade 2 or 4, 24 samples showed both clade 2 and 4 signatures, indicating possible mixed infection, gene rearrangement, or inter-clade recombination, and one sample was a noninvasive trachoma biovar (either a clade 3 or 4). The remaining 19 blinded samples were correctly identified as LGV clade 1 (3), ocular clade 3 (4), or as negatives (12). To date, no NAAT assay can provide a point-of-care applicable turnaround time for Ct detection while identifying clinically significant Ct strain types to inform appropriate treatment. Coupled with rapid DNA processing of clinical swabs (approximately 60 minutes from swab-in to result-out), the assay has significant potential as a rapid POC diagnostic for Ct infections.

Studies of the energy return on investment (EROI) for oil production generally rely on aggregated statistics for large regions or countries. In order to better understand the drivers of the energy productivity of oil production, we use a novel approach that applies a detailed field-level engineering model of oil and gas production to estimate energy requirements of drilling, producing, processing, and transporting crude oil. We examine 40 global oilfields, utilizing detailed data for each field from hundreds of technical and scientific data sources. Resulting net energy return (NER) ratios for studied oil fields range from ≈2 to ≈100 MJ crude oil produced per MJ of total fuels consumed. External energy return (EER) ratios, which compare energy produced to energy consumed from external sources, exceed 1000:1 for fields that are largely self-sufficient. The lowest energy returns are found to come from thermally-enhanced oil recovery technologies. Results are generally insensitive to reasonable ranges of assumptions explored in sensitivity analysis. Fields with very large associated gas production are sensitive to assumptions about surface fluids processing due to the shifts in energy consumed under different gas treatment configurations. This model does not currently include energy invested in building oilfield capital equipment (e.g., drilling rigs), nor does it include other indirect energy uses such as labor or services.

BACKGROUND: The intentional release of Bacillus anthracis in the United States in 2001 has heightened concern about the use of pathogenic microorganisms in bioterrorism attacks. Many of the deadliest bacteria, including the Class A Select Agents Bacillus anthracis, Francisella tularensis, and Yersinia pestis, are highly infectious via the pulmonary route when released in aerosolized form. Hence, rapid, sensitive, and reliable methods for detection of these biothreats and characterization of their potential impact on the exposed population are of critical importance to initiate and support rapid military, public health, and clinical responses. METHODOLOGY/PRINCIPAL FINDINGS: We have developed microfluidic multiplexed PCR and sequencing assays based on the simultaneous interrogation of three pathogens per assay and ten loci per pathogen. Microfluidic separation of amplified fluorescently labeled fragments generated characteristic electrophoretic signatures for identification of each agent. The three sets of primers allowed significant strain typing and discrimination from non-pathogenic closely-related species and environmental background strains based on amplicon sizes alone. Furthermore, sequencing of the 10 amplicons per pathogen, termed "Rapid Focused Sequencing," allowed an even greater degree of strain discrimination and, in some cases, can be used to determine virulence. Both amplification and sequencing assays were performed in microfluidic biochips developed for fast thermal cycling and requiring 7 µL per reaction. The 30-plex sequencing assay resulted in genotypic resolution of 84 representative strains belonging to each of the three biothreat species. CONCLUSIONS/SIGNIFICANCE: The microfluidic multiplexed assays allowed identification and strain differentiation of the biothreat agents Bacillus anthracis, Francisella tularensis, and Yersinia pestis and clear discrimination from closely-related species and several environmental background strains. The assays may be extended to detect a large number of pathogens, are applicable to the evaluation of both environmental and clinical samples, and have the potential to be applied in military, public health, and clinical diagnostic settings.

Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted diseases (STD) worldwide. While commercial nucleic acid amplification tests (NAAT) are available for Ct, none are rapid or inexpensive enough to be used at the point-of-care (POC). Towards the first Ct POC NAAT, we developed a microfluidic assay that simultaneously interrogates nine Ct loci in 20 minutes.Endocervical samples were selected from 263 women at high risk for Ct STDs (∼35% prevalence). A head-to-head comparison was performed with the Roche-Amplicor NAAT. 129 (49.0%) and 88 (33.5%) samples were positive by multiplex and Amplicor assays, respectively. Sequencing resolved 71 discrepant samples, confirming 53 of 53 positive multiplex samples and 12 of 18 positive Amplicor samples. The sensitivity and specificity were 91.5% and 100%, and 62.4% and 95.9%, respectively, for multiplex and Amplicor assays. Positive and negative predictive values were 100% and 91%, and 94.1% and 68.6%, respectively.This is the first rapid multiplex approach to Ct detection, and the assay was also found to be superior to a commercial NAAT. In effect, nine simultaneous reactions significantly increased sensitivity and specificity. Our assay can potentially increase Ct detection in globally diverse clinical settings at the POC.

Multiple locus sequence typing (MLST) has become a central genotyping strategy for analysis of bacterial populations. The scheme involves de novo sequencing of 6-8 housekeeping loci to assign unique sequence types. In this work we adapted MLST to a rapid microfluidics platform in order to enhance speed and reduce laboratory labor time.Using two integrated microfluidic devices, DNA was purified from 100 Bacillus cereus soil isolates, used as a template for multiplex amplification of 7 loci and sequenced on forward and reverse strands. The time on instrument from loading genomic DNA to generation of electropherograms was only 1.5 hours. We obtained full-length sequence of all seven MLST alleles from 84 representing 46 different Sequence Types. At least one allele could be sequenced from a further 15 strains. The nucleotide diversity of B. cereus isolated in this study from one location in Rockville, Maryland (0.04 substitutions per site) was found to be as great as the global collection of isolates.Biogeographical investigation of pathogens is only one of a panoply of possible applications of microfluidics based MLST; others include microbiologic forensics, biothreat identification, and rapid characterization of human clinical samples.

The existing dataset for visual dialog comprises multiple rounds of questions and a diverse range of image contents. However, it faces challenges in overcoming visual semantic limitations, particularly in obtaining sufficient context from visual and textual aspects of images. This paper proposes a new visual dialog dataset called Diverse History-Dialog (DS-Dialog) to address the visual semantic limitations faced by the existing dataset. DS-Dialog groups relevant histories based on their respective Microsoft Common Objects in Context (MSCOCO) image categories and consolidates them for each image. Specifically, each MSCOCO image category consists of top relevant histories extracted based on their semantic relationships between the original image caption and historical context. These relevant histories are consolidated for each image, and DS-Dialog enhances the current dataset by adding new context-aware relevant history to provide more visual semantic context for each image. The new dataset is generated through several stages, including image semantic feature extraction, keyphrase extraction, relevant question extraction, and relevant history dialog generation. The DS-Dialog dataset contains about 2.6 million question-answer pairs, where 1.3 million pairs correspond to existing VisDial’s question-answer pairs, and the remaining 1.3 million pairs include a maximum of 5 image features for each VisDial image, with each image comprising 10-round relevant question-answer pairs. Moreover, a novel adaptive relevant history selection is proposed to resolve missing visual semantic information for each image. DS-Dialog is used to benchmark the performance of previous visual dialog models and achieves better performance than previous models. Specifically, the proposed DSDialog model achieves an 8% higher mean reciprocal rank (MRR), 11% higher R@1%, 6% higher R@5%, 5% higher R@10%, and 8% higher normalized discounted cumulative gain (NDCG) compared to LF. DS-Dialog also achieves approximately 1 point improvement on R@k, mean, MRR, and NDCG compared to the original RVA, and 2 points improvement compared to LF and DualVD. These results demonstrates the importance of the relevant semantic historical context in enhancing the visual semantic relationship between textual and visual representations of the images and questions. [ABSTRACT FROM AUTHOR]