Hashtags in Plastic Surgery: A Sentiment Analysis of over 1 Million Tweets.

BACKGROUND: Current literature has sparse recommendations that guide social networking practices in plastic surgery. To address this, we used natural language processing and sentiment analysis to investigate the differences in plastic surgery-related terms and hashtags on Twitter. METHODS: Over 1 million tweets containing keywords #plasticsurgery, #cosmeticsurgery, and their non-hashtagged versions plastic surgery and cosmetic surgery were collected from the Twitter Gardenhose feed spanning from 2012 to 2016. We extracted the average happiness/positivity (h-avg) using hedonometrics and created word-shift graphs to determine influential words. RESULTS: The most popular keywords were plastic and cosmetic surgery, comprising more than 90% of the sample. The positivity scores for plastic surgery, cosmetic surgery, #plasticsurgery, and #cosmeticsurgery were 5.72, 6.00, 6.17, and 6.18, respectively. Compared to plastic surgery, the term cosmetic surgery was more positive because it lacked antagonistic words, such as "fake," "ugly," "bad," "fails," and "wrong." For similar reasons, #plasticsurgery and #cosmeticsurgery were more positively associated than their non-hashtagged counterparts. CONCLUSION: Plastic surgery-related hashtags are more positively associated than their non-hashtagged versions. The language associated with such hashtags suggests a different user profile than the public and, given their underutilization, remain viable channels for professionals to achieve their diverse social media goals. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.

Human language reveals a universal positivity bias.

Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, we present evidence of a deep imprint of human sociality in language, observing that (i) the words of natural human language possess a universal positivity bias, (ii) the estimated emotional content of words is consistent between languages under translation, and (iii) this positivity bias is strongly independent of frequency of word use. Alongside these general regularities, we describe interlanguage variations in the emotional spectrum of languages that allow us to rank corpora. We also show how our word evaluations can be used to construct physical-like instruments for both real-time and offline measurement of the emotional content of large-scale texts.

SEROSURVEY, HEMATOLOGY, AND CAUSES OF MORTALITY OF FREE-RANGING AMERICAN MARTENS ( MARTES AMERICANA) IN MICHIGAN.

To better understand the clinical pathology, diseases, and causes of mortality of reintroduced American martens ( Martes americana) in Michigan, a study was conducted from 2011 to 2015 in the Upper and Lower Peninsulas of Michigan. Samples obtained from live trapping ( n = 58) or harvested carcasses ( n = 34) were serologically tested for select pathogens. Antibodies against Toxoplasma gondii and canine distemper virus were detected in 58 and 3.4% of samples, respectively. All samples were seronegative for Leptospira spp. and negative for Dirofilaria immitis antigen. Urine samples tested for Leptospira spp. via immunofluorescent antibody assay ( n = 7), polymerase chain reaction ( n = 6) , or both ( n = 3) were all negative. Parvovirus DNA was detected in 9.1% of small intestine samples ( n = 22) collected from carcasses and in 3.7% of fecal samples ( n = 27) collected during live trapping. Complete blood counts ( n = 64) and serum biochemistries ( n = 63) were obtained from 49 live-trapped martens. Biochemical parameters found to be significantly different ( P < 0.05) between genders were calcium, creatinine, glucose, and phosphorus. There was no significant difference between genders for any hematologic parameter. Significant differences ( P < 0.05) between summer and winter seasons were found in total estimated white blood cell count, neutrophils, lymphocytes, monocytes, alkaline phosphatase, bicarbonate, calcium, creatinine, globulin, glucose, phosphorus, potassium, sodium, and total protein. There was no significant difference in blood cell count or serum biochemistry values between radio-collared ( n = 17) and noncollared ( n = 47) martens. Animals seropositive for T. gondii were found to have significantly higher ( P < 0.05) eosinophil and globulin levels than seronegative animals. The primary natural cause for mortality of radio-collared American martens was predation. Histologic examinations revealed a high percentage (60%) of martens with verminous or granulomatous pneumonia.

Loss of MITF expression during human embryonic stem cell differentiation disrupts retinal pigment epithelium development and optic vesicle cell proliferation.

Microphthalmia-associated transcription factor (MITF) is a master regulator of pigmented cell survival and differentiation with direct transcriptional links to cell cycle, apoptosis and pigmentation. In mouse, Mitf is expressed early and uniformly in optic vesicle (OV) cells as they evaginate from the developing neural tube, and null Mitf mutations result in microphthalmia and pigmentation defects. However, homozygous mutations in MITF have not been identified in humans; therefore, little is known about its role in human retinogenesis. We used a human embryonic stem cell (hESC) model that recapitulates numerous aspects of retinal development, including OV specification and formation of retinal pigment epithelium (RPE) and neural retina progenitor cells (NRPCs), to investigate the earliest roles of MITF. During hESC differentiation toward a retinal lineage, a subset of MITF isoforms was expressed in a sequence and tissue distribution similar to that observed in mice. In addition, we found that promoters for the MITF-A, -D and -H isoforms were directly targeted by Visual Systems Homeobox 2 (VSX2), a transcription factor involved in patterning the OV toward a NRPC fate. We then manipulated MITF RNA and protein levels at early developmental stages and observed decreased expression of eye field transcription factors, reduced early OV cell proliferation and disrupted RPE maturation. This work provides a foundation for investigating MITF and other highly complex, multi-purposed transcription factors in a dynamic human developmental model system.

Genome Modeling System: A Knowledge Management Platform for Genomics.

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

A pattern-matched Twitter analysis of US cancer-patient sentiments.

BACKGROUND: Twitter has been recognized as an important source of organic sentiment and opinion. This study aimed to (1) characterize the content of tweets authored by the United States cancer patients; and (2) use patient tweets to compute the average happiness of cancer patients for each cancer diagnosis. METHODS: A large sample of English tweets from March 2014 through December 2014 was obtained from Twitter. Using regular expression software pattern matching, the tweets were filtered by cancer diagnosis. For each cancer-specific tweetset, individual patients were extracted, and the content of the tweet was categorized. The patients' Twitter identification numbers were used to gather all tweets for each patient, and happiness values for patient tweets were calculated using a quantitative hedonometric analysis. RESULTS: The most frequently tweeted cancers were breast (n = 15,421, 11% of total cancer tweets), lung (n = 2928, 2.0%), prostate (n = 1036, 0.7%), and colorectal (n = 773, 0.5%). Patient tweets pertained to the treatment course (n = 73, 26%), diagnosis (n = 65, 23%), and then surgery and/or biopsy (n = 42, 15%). Computed happiness values for each cancer diagnosis revealed higher average happiness values for thyroid (h_avg = 6.1625), breast (h_avg = 6.1485), and lymphoma (h_avg = 6.0977) cancers and lower average happiness values for pancreatic (h_avg = 5.8766), lung (h_avg = 5.8733), and kidney (h_avg = 5.8464) cancers. CONCLUSIONS: The study confirms that patients are expressing themselves openly on social media about their illness and that unique cancer diagnoses are correlated with varying degrees of happiness. Twitter can be employed as a tool to identify patient needs and as a means to gauge the cancer patient experience.

Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.

Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies.

Modeling human retinal development with patient-specific induced pluripotent stem cells reveals multiple roles for visual system homeobox 2.

Human induced pluripotent stem cells (hiPSCs) have been shown to differentiate along the retinal lineage in a manner that mimics normal mammalian development. Under certain culture conditions, hiPSCs form optic vesicle-like structures (OVs), which contain proliferating progenitors capable of yielding all neural retina (NR) cell types over time. Such observations imply conserved roles for regulators of retinogenesis in hiPSC-derived cultures and the developing embryo. However, whether and to what extent this assumption holds true has remained largely uninvestigated. We examined the role of a key NR transcription factor, visual system homeobox 2 (VSX2), using hiPSCs derived from a patient with microphthalmia caused by an R200Q mutation in the VSX2 homeodomain region. No differences were noted between (R200Q)VSX2 and sibling control hiPSCs prior to OV generation. Thereafter, (R200Q)VSX2 hiPSC-OVs displayed a significant growth deficit compared to control hiPSC-OVs, as well as increased production of retinal pigmented epithelium at the expense of NR cell derivatives. Furthermore, (R200Q)VSX2 hiPSC-OVs failed to produce bipolar cells, a distinctive feature previously observed in Vsx2 mutant mice. (R200Q)VSX2 hiPSC-OVs also demonstrated delayed photoreceptor maturation, which could be overcome via exogenous expression of wild-type VSX2 at early stages of retinal differentiation. Finally, RNAseq analysis on isolated hiPSC-OVs implicated key transcription factors and extracellular signaling pathways as potential downstream effectors of VSX2-mediated gene regulation. Our results establish hiPSC-OVs as versatile model systems to study retinal development at stages not previously accessible in humans and support the bona fide nature of hiPSC-OV-derived retinal progeny.

Altered Mitochondrial Dynamics Contributes to Propofol-induced Cell Death in Human Stem Cell-derived Neurons.

BACKGROUND: Studies in developing animals have shown that anesthetic agents can lead to neuronal cell death and learning disabilities when administered early in life. Development of human embryonic stem cell-derived neurons has provided a valuable tool for understanding the effects of anesthetics on developing human neurons. Unbalanced mitochondrial fusion and fission lead to various pathological conditions including neurodegeneration. The aim of this study was to dissect the role of mitochondrial dynamics in propofol-induced neurotoxicity. METHODS: Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labeling staining was used to assess cell death in human embryonic stem cell-derived neurons. Mitochondrial fission was assessed using TOM20 staining and electron microscopy. Expression of mitochondrial fission-related proteins was assessed by Western blot, and confocal microscopy was used to assess opening time of the mitochondrial permeability transition pore (mPTP). RESULTS: Exposure to 6 h of 20 µg/ml propofol increased cell death from 3.18 ± 0.17% in the control-treated group to 9.6 ± 0.95% and led to detrimental increases in mitochondrial fission (n = 5 coverslips per group) accompanied by increased expression of activated dynamin-related protein 1 and cyclin-dependent kinase 1, key proteins responsible for mitochondrial fission. Propofol exposure also induced earlier opening of the mPTP from 118.9 ± 3.1 s in the control-treated group to 73.3 ± 1.6 s. Pretreatment of the cells with mdivi-1, a mitochondrial fission blocker rescued the propofol-induced toxicity, mitochondrial fission, and mPTP opening time (n = 75 cells per group). Inhibiting cyclin-dependent kinase 1 attenuated the increase in cell death and fission and the increase in expression of activated dynamin-related protein 1. CONCLUSION: These data demonstrate for the first time that propofol-induced neurotoxicity occurs through a mitochondrial fission/mPTP-mediated pathway.

Serologic Survey of Selected Arthropod-Borne Pathogens in Free-Ranging Snowshoe Hares (Lepus americanus) Captured in Northern Michigan, USA.

Snowshoe hares (Lepus americanus) in the Upper Peninsula (UP) of Michigan, USA, occupy the southern periphery of the species' range and are vulnerable to climate change. In the eastern UP, hares are isolated by the Great Lakes, potentially exacerbating exposure to climate-change-induced habitat alterations. Climate change is also measurably affecting distribution and prevalence of vector-borne pathogens in North America, and increases in disease occurrence and prevalence can be one signal of climate-stressed wildlife populations. We conducted a serosurvey for vector-borne pathogens in snowshoe hares that were captured in the Hiawatha National Forest in the eastern UP of Michigan, USA, 2016-2017. The most commonly detected antibody response was to the mosquito-borne California serogroup snowshoe hare virus (SSHV). Overall, 24 (51%) hares screened positive for SSHV antibodies and of these, 23 (96%) were confirmed positive by plaque reduction neutralization test. We found a positive association between seroprevalence of SSHV and live weight of snowshoe hares. Additionally, we detected a significant effect of ecological land type group on seroprevalence of SSHV, with strong positive support for a group representing areas that tend to support high numbers of hares (i.e., acidic mineral containing soils with cedar, mixed swamp conifers, tamarack and balsam fir as common overstory vegetation). We also detected and confirmed antibodies for Jamestown Canyon virus and Silverwater virus in a single hare each. We did not detect antibodies to other zoonotic vector-borne pathogens, including Lacrosse encephalitis virus, West Nile virus, Borrelia burgdorferi, Powassan virus, and Francisella tularensis. These results provide a baseline for future serological studies of vector-transmitted diseases that may increase climate vulnerability of snowshoe hares in the UP of Michigan, as well as pose a climate-related zoonotic risk.

Biosecurity indemnification and attitudes of United States swine producers towards the prevention of an african swine fever outbreak.

Animal disease outbreaks, such as the recent outbreak of African Swine Fever in 2018, are a major concern for stakeholders across the food supply chain due to their potential to disrupt global food security, cause economic losses, and threaten animal welfare. As a result of their transboundary nature, discussions have shifted to preventive measures aimed at protecting livestock while ensuring food security and safety. Emergency assistance has been a critical response option during pandemics. However, this may not be sustainable in the long run because the expectation of government bailout may encourage risk taking behaviours. Our hypothesis is that an indemnity policy that is conditioned on showing biosecurity practices would increase compliance and reduce government expenditure during disease outbreaks. We developed and launched a survey from March to July 2022 targeted at swine producers across the US. From the survey, we examined livestock farmers' attitudes and intentions regarding biosecurity investment and assessed their attitudes towards the purchase of livestock insurance and reporting suspected infected livestock on their farm. We used a partial proportion odds model analysis to examine the model. Our analysis revealed that intention to call a veterinarian, trust in government agencies and risk perception of farmers were instrumental in the willingness to self-invest in biosecurity, purchase livestock insurance, and promptly report infected livestock on their farms. This provides evidence that biosecurity compliance would increase if indemnification was tied to a demonstration of effort to adopt biosecurity practices. We also show that individuals who have been in the industry for a longer period may become complacent and less likely to report outbreaks. Farmers with a higher share of income from their production operations bear a greater risk from their operational income and are more willing to report any suspected infections on their farms. The data suggest that motivating the willingness of farmers to invest in biosecurity while overcoming cost concerns is achievable.

Recurring mutations found by sequencing an acute myeloid leukemia genome.

BACKGROUND: The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known. METHODS: We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome. RESULTS: We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis. CONCLUSIONS: By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis.

Implementation of the Abbott ID Now COVID-19 assay at a tertiary care center: a prospective pragmatic implementation study during the third wave of SARS-CoV-2 in Ontario.

The Abbott ID Now COVID-19 assay is a point-of-care molecular diagnostic tool for the detection of SARS-CoV-2. We prospectively monitored implementation of the assay in a tertiary care hospital emergency department (ED) for the diagnosis of early symptomatic patients. A total of 269 paired nasopharyngeal swabs were tested in parallel with the ID Now and laboratory-based molecular methodologies, 191 of which met selection criteria for testing based on symptoms description and duration. Forty-six and 48 samples were positive for SARS-CoV-2 with the ID Now and reference molecular assays respectively. Percent positive and negative agreement were high (93.8% and 99.6% respectively), as were the sensitivity and specificity (93.8% and 99.5%). ID Now results were available 17.47 hours earlier than qRT-PCR. In symptomatic patients seen in ED within 7 to 10 days of symptoms onset, the ID Now COVID-19 assay allows for rapid and accurate detection of infection.

Flow impacts of hot/cold zone infection control procedures during the COVID-19 pandemic in the emergency department.

BACKGROUND: The COVID-19 pandemic forced emergency departments (EDs) to change operations to minimize nosocomial infection risk. Many EDs cohort patients using provincial screening tools at triage. Despite cohorting, staff exposures occurred in the 'cold zone' due to lack of personal protective equipment (PPE) use with patients deemed low risk, resulting in staff quarantines. The cohorting strategy was perceived to lengthen time to physician initial assessment and ED length of stay times in our ED without protecting staff well enough due to varying PPE use. The objective of this study was to assess the impact of hot/cold zones for patient cohorting during a viral pandemic on ED length of stay. METHODS: We conducted an interrupted time series analysis 3 weeks before and after the removal of hot/cold zone care space cohorting in our ED. In the before period, staff did not routinely wear full PPE to see cold zone patients. After removal, staff wore full PPE to see almost all patients. We collected data on ED length of stay, physician initial assessment times, arrival-to-room times, patient volumes, Canadian Triage Acuity Score (CTAS), admissions, staff hours of coverage, as well as proportions of patients on droplet/contact precautions and COVD-19 positive patients. The primary outcome was median ED length of stay. RESULTS: After the removal of the hot/cold divisions, there was a decrease in the adjusted median ED length of stay by 24 min (95% CI 14; 33). PPE use increased in the after arm of the study. The interrupted time series analysis suggested a decrease in median ED length of stay after removal, although the change in slope and difference did not reach statistical significance. CONCLUSION: Cohorted waiting areas may provide a safety benefit without operational compromise, but cohorting staff and care spaces is likely to compromise efficiency and create delays.

RéSUMé: CONTEXTE: La pandémie de COVID-19 a contraint les services d'urgence (SU) à modifier leur fonctionnement afin de minimiser le risque d'infection nosocomiale. De nombreux SU regroupaient des patients à l'aide d'outils de dépistage provinciaux au triage. Malgré la constitution de cohortes, les expositions du personnel se sont produites dans la "zone froide" en raison du manque d'utilisation d'équipements de protection individuelle (EPI) avec des patients jugés à faible risque, ce qui a entraîné la mise en quarantaine du personnel. Dans notre service d'urgence, la stratégie de cohorte a été perçue comme prolongeant l'évaluation initiale des médecins et la durée du séjour dans le service sans pour autant protéger suffisamment le personnel en raison de l'utilisation variable des EPI. L'objectif de cette étude était d'évaluer l'impact des zones chaudes/froides pour le regroupement de patients lors d'une pandémie virale sur la durée du séjour à l'urgence. MéTHODES: Nous avons réalisé une analyse de séries chronologiques interrompues trois semaines avant et après la suppression de la cohorte d'espace de soins en zone chaude/froide dans nos urgences. Au cours de la période précédente, le personnel ne portait pas systématiquement un EPI complet pour voir les patients des zones froides. Après le retrait, le personnel a porté un EPI complet pour voir presque tous les patients. Nous avons recueilli des données sur la durée du séjour aux urgences, les délais d'évaluation initiale par les médecins, les délais d'arrivée en salle, le volume de patients, L'échelle canadienne de triage et de gravité (ÉTG), les admissions, les heures de couverture du personnel, ainsi que les proportions de patients ayant reçu des précautions contre les gouttelettes et les contacts et de patients positifs au COVD-19. Le critère de jugement principal était la durée médiane du séjour aux urgences. RéSULTATS: Après la suppression des divisions chaudes/froides, la durée médiane ajustée du séjour aux urgences a diminué de 24 minutes (IC à 95 % : 14 ; 33). L'utilisation des EPI a augmenté dans le groupe suivant de l'étude. L'analyse des séries chronologiques interrompues suggère une diminution de la durée médiane de séjour aux urgences après le retrait, bien que le changement de la pente et de la différence n'ait pas atteint la signification statistique. CONCLUSION: Les zones d'attente en cohorte peuvent offrir un avantage en matière de sécurité sans compromis sur le plan opérationnel, mais le regroupement du personnel et des espaces de soins est susceptible de compromettre l'efficacité et de créer des retards.

Assessing strategic, tactical, and operational decision-making and risk in a livestock production chain through experimental simulation platforms.

This paper provides a research summary of a series of serious games and simulations that form the basis of an experimental platform for the study of human decision-making and behavior associated with biosecurity across complex livestock production chains. This platform is the first of its kind to address the challenges associated with scaling micro-behavior of biosecurity decision-making to macro-patterns of disease spread across strategic, tactical and operational levels, capturing the roles that facility managers and front-line workers play in making biosecurity decisions under risk and uncertainty. Informational and incentive treatments are tested within each game and simulation. Behavioral theories are used to explain these findings. Results from serious games in the form of behavioral probability distributions are then used to simulate disease incidence and spread across a complex production chain, demonstrating how micro-level behaviors contribute to larger macro-level patterns. In the case of this study, the propensity to adopt micro-level biosecurity practices are applied to a network percolation disease spread model. By presenting the suite of companion models of behavior and disease spread we are able to capture scaling dynamics of complex systems, and in the process, better understand how individual behaviors impact whole systems.

The Adverse Event Unit (AEU): A novel metric to measure the burden of treatment adverse events.

OBJECTIVE: To design a physician and patient derived tool, the Adverse Event Unit (AEU), akin to currency (e.g. U.S. Dollar), to improve AE burden measurement independent of any particular disease or medication class. PATIENTS/METHODS: A Research Electronic Data Capture (REDCap) online survey was administered to United States physicians with board certification or board eligibility in general neurology, subspecialty neurology, primary care internal medicine or family medicine, subspecialty internal medicine, general pediatrics, and subspecialty pediatrics. Physicians assigned value to 73 AE categories chosen from the Common Terminology Criteria of Adverse Events (CTCAE) relevant to neurologic disorder treatments. An online forced choice survey was administered to non-physician, potential patients, through Amazon Mechanical Turk (MTurK) to weight the severity of the same AE categories. Physician and non-physician data was combined to assign value to the AEU. Surveys completed between 1/2017 and 3/2019. RESULTS: 363 physicians rated the 73 AE categories derived from CTCAE. 660 non-physicians completed forced choice experiments comparing AEs. The AEU provides 0-10, weighted values for the AE categories studied that differ from the ordinal 1-4 CTCAE scale. For example, CTCAE severe diabetes (category 4) is assigned an AEU score of 9. Although non-physician input changed physician assigned AEU values, there was general agreement among physicians and non-physicians about severity of AEs. CONCLUSION: The AEU has promise to be a useful, practical tool to add precision to AE burden measurement in the clinic and in comparative efficacy research with neurology patients. AEU utility will be assessed in planned comparative efficacy clinical trials.

Comparing behavioral risk assessment strategies for quantifying biosecurity compliance to mitigate animal disease spread.

Understanding the impact of human behavior on the spread of disease is critical in mitigating outbreak severity. We designed an experimental game that emulated worker decision-making in a swine facility during an outbreak. In order to combat contamination, the simulation features a line-of-separation biosecurity protocol. Participants are provided disease severity information and can choose whether or not to comply with a shower protocol. Each simulated decision carried the potential for either an economic cost or an opportunity cost, both of which affected their potential real-world earnings. Participants must weigh the risk infection vs. an opportunity cost associated with compliance. Participants then completed a multiple price list (MPL) risk assessment survey. The survey uses a context-free, paired-lottery approach in which one of two options may be selected, with varying probabilities of a high and low risk payouts. We compared game response data to MPL risk assessment. Game risk was calculated using the normalized frequency of biosecurity compliance. Three predominant strategies were identified: risk averse participants who had the highest rate of compliance; risk tolerant participants who had the lowest compliance rate; and opportunists who adapted their strategy depending on disease risk. These findings were compared to the proportion of risk averse choices observed within the MPL and were classified into 3 categories: risk averse, risk tolerant and neutral. We found weak positive correlation between risk measured in our experimental game compared to the MPL. However, risk averse classified participants in the MPL tended to comply with the biosecurity protocol more often than those classified as risk tolerant. We also found that the behavioral risk clusters and categorization via the MPL were significantly, yet weakly associated. Overall, behavioral distributions were skewed toward more risk averse choices in both the MPL and game. However, the MPL risk assessment wasn't a strong predictor for observed game behavior. This may indicate that MPL risk aversion metrics might not be sufficient to capture these simulated, situational risk aversion behaviors. Experimental games have a large potential for expanding upon traditional survey instruments by immersing participants in a complex decision mechanism, and capturing dynamic and evolving behavioral signals.

Connecting livestock disease dynamics to human learning and biosecurity decisions.

The acceleration of animal disease spread worldwide due to increased animal, feed, and human movement has driven a growing body of epidemiological research as well as a deeper interest in human behavioral studies aimed at understanding their interconnectedness. Biosecurity measures can reduce the risk of infection, but human risk tolerance can hinder biosecurity investments and compliance. Humans may learn from hardship and become more risk averse, but sometimes they instead become more risk tolerant because they forget negative experiences happened in the past or because they come to believe they are immune. We represent the complexity of the hog production system with disease threats, human decision making, and human risk attitude using an agent-based model. Our objective is to explore the role of risk tolerant behaviors and the consequences of delayed biosecurity investments. We set up experiment with Monte Carlo simulations of scenarios designed with different risk tolerance amongst the swine producers and we derive distributions and trends of biosecurity and porcine epidemic diarrhea virus (PEDv) incidence emerging in the system. The output data allowed us to examine interactions between modes of risk tolerance and timings of biosecurity response discussing consequences for disease protection in the production system. The results show that hasty and delayed biosecurity responses or slow shifts toward a biosecure culture do not guarantee control of contamination when the disease has already spread in the system. In an effort to support effective disease prevention, our model results can inform policy making to move toward more resilient and healthy production systems. The modeled dynamics of risk attitude have also the potential to improve communication strategies for nudging and establishing risk averse behaviors thereby equipping the production system in case of foreign disease incursions.