Evaluating the Impact of an Innovative Integrative Health-Focused Elective in a Doctor of Pharmacy Program.

OBJECTIVE: To assess knowledge and perceptions of integrative health principles. METHODS: This was a retrospective, pre-post observational cohort study evaluating Doctor of Pharmacy students following completion of an innovative elective course that was offered between 2020-2022. This Integrated Health in Pharmacy elective was created at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in the Spring of 2020. The primary objective was to assess student knowledge of integrative health principles. The secondary objective was to assess student confidence and perceptions of integrative health principles. RESULTS: Students completed a pre-course assessment (n = 80/81) and a post-course assessment (n = 73/81). Overall, the mean (SD) performance on the assessment questions increased between the pre-post assessment groups (57.59 [12.98]% vs 65.46 [14.43]%). Survey results indicated that students' perceptions and confidence pertaining to integrative health increased after completing this elective course offering. CONCLUSION: Participation in this innovative elective course was associated with improved knowledge and perceptions of integrative health principles.

Lessons Learned From a Sequential Mixed-Mode Survey Design to Recruit and Collect Data From Case-Control Study Participants: Formative Evaluation.

BACKGROUND: Sequential mixed-mode surveys using both web-based surveys and telephone interviews are increasingly being used in observational studies and have been shown to have many benefits; however, the application of this survey design has not been evaluated in the context of epidemiological case-control studies. OBJECTIVE: In this paper, we discuss the challenges, benefits, and limitations of using a sequential mixed-mode survey design for a case-control study assessing risk factors during the COVID-19 pandemic. METHODS: Colorado adults testing positive for SARS-CoV-2 were randomly selected and matched to those with a negative SARS-CoV-2 test result from March to April 2021. Participants were first contacted by SMS text message to complete a self-administered web-based survey asking about community exposures and behaviors. Those who did not respond were contacted for a telephone interview. We evaluated the representativeness of survey participants to sample populations and compared sociodemographic characteristics, participant responses, and time and resource requirements by survey mode using descriptive statistics and logistic regression models. RESULTS: Of enrolled case and control participants, most were interviewed by telephone (308/537, 57.4% and 342/648, 52.8%, respectively), with overall enrollment more than doubling after interviewers called nonresponders. Participants identifying as female or White non-Hispanic, residing in urban areas, and not working outside the home were more likely to complete the web-based survey. Telephone participants were more likely than web-based participants to be aged 18-39 years or 60 years and older and reside in areas with lower levels of education, more linguistic isolation, lower income, and more people of color. While there were statistically significant sociodemographic differences noted between web-based and telephone case and control participants and their respective sample pools, participants were more similar to sample pools when web-based and telephone responses were combined. Web-based participants were less likely to report close contact with an individual with COVID-19 (odds ratio [OR] 0.70, 95% CI 0.53-0.94) but more likely to report community exposures, including visiting a grocery store or retail shop (OR 1.55, 95% CI 1.13-2.12), restaurant or cafe or coffee shop (OR 1.52, 95% CI 1.20-1.92), attending a gathering (OR 1.69, 95% CI 1.34-2.15), or sport or sporting event (OR 1.05, 95% CI 1.05-1.88). The web-based survey required an average of 0.03 (SD 0) person-hours per enrolled participant and US $920 in resources, whereas the telephone interview required an average of 5.11 person-hours per enrolled participant and US $70,000 in interviewer wages. CONCLUSIONS: While we still encountered control recruitment challenges noted in other observational studies, the sequential mixed-mode design was an efficient method for recruiting a more representative group of participants for a case-control study with limited impact on data quality and should be considered during public health emergencies when timely and accurate exposure information is needed to inform control measures.

Exploring the association of weather variability on Campylobacter - A systematic review.

BACKGROUND: Previous work has found climate change-induced weather variability is suspected to increase the transmission of enteric pathogens, including Campylobacter, a leading cause of bacterial gastroenteritis. While the relationship between extreme weather events and diarrheal diseases has been documented, the specific impact on Campylobacter infections remains underexplored. OBJECTIVE: To synthesize the peer-reviewed literature exploring the effect of weather variability on Campylobacter infections in humans. METHODS: The review included English language, peer-reviewed articles, published up to September 1, 2022 in PubMed, Embase, GEOBASE, Agriculture and Environmental Science Database, and CABI Global Health exploring the effect of an antecedent weather event on human enteric illness caused by Campylobacter (PROSPERO Protocol # 351884). We extracted study information including data sources, methods, summary measures, and effect sizes. Quality and weight of evidence reported was summarized and bias assessed for each article. RESULTS: After screening 278 articles, 47 articles (34 studies, 13 outbreak reports) were included in the evidence synthesis. Antecedent weather events included precipitation (n = 35), temperature (n = 30), relative humidity (n = 7), sunshine (n = 6), and El Niño and La Niña (n = 3). Reviewed studies demonstrated that increases in precipitation and temperature were correlated with Campylobacter infections under specific conditions, whereas low relative humidity and sunshine were negatively correlated. Articles estimating the effect of animal operations (n = 15) found presence and density of animal operations were significantly associated with infections. However, most of the included articles did not assess confounding by seasonality, presence of animal operations, or describe estimates of risk. DISCUSSION: This review explores what is known about the influence of weather events on Campylobacter and identifies previously underreported negative associations between low relative humidity and sunshine on Campylobacter infections. Future research should explore pathogen-specific estimates of risk, which can be used to influence public health strategies, improve source attribution and causal pathways, and project disease burden due to climate change.

Digital health program improves quality of life in rheumatoid arthritis: a retrospective analysis of real-world data.

OBJECTIVES: Sidekick Health launched a 16-week digital support programme for people with rheumatoid arthritis in 2021. The objective of this retrospective analysis was to understand whether quality of life (QoL; sleep quality, energy and stress levels) improved for users engaged with the programme in a real-world setting. METHODS: This analysis included 635 users who engaged with the programme after the first week, out of 1541 who enrolled. Users self-reported QoL up to four times per week on their phones. Survival bias was investigated by comparing pre-post QoL scores of the full analysis set (all users) and the complete case set (programme completers). Users were divided into highly-engaged and less-engaged groups based on the weekly average number of in-app activities by iterative K-means clustering. Mixed models for repeated measures were used to estimate changes in QoL for highly-versus less-engaged groups. RESULTS: Both the full analysis set and the complete case set had significant pre-post improvements in energy and stress; this suggested that survival bias did not have a substantial effect on these real-world data. Both the highly- and less-engaged groups experienced significant longitudinal improvements in all QoL outcomes. Highly-engaged users achieved better scores in energy, stress, and sleep than less-engaged users. Moreover, a significant time-group interaction for sleep showed that highly-engaged users not only had better sleep scores, but also experienced larger improvements over time than less-engaged users. CONCLUSIONS: These findings demonstrate that a 16-week digital support programme improves self-reported QoL measures, supporting the 2021 EULAR recommendations to incorporate digital healthcare into routine practice. Noteworthy is the study's relevance in the context of the increasing importance of patient empowerment in managing chronic diseases.

Geometry and length control of 3D engineered heart tissues using direct laser writing.

Geometry and mechanical characteristics of the environment surrounding the Engineered Heart Tissues (EHT) affect their structure and function. Here, we employed a 3D tissue culture platform fabricated using two-photon direct laser writing with a high degree of accuracy to control parameters that are relevant to EHT maturation. Using this platform, we first explore the effects of geometry based on two distinct shapes: a rectangular seeding well with two attachment sites, and a stadium-like seeding well with six attachment sites that are placed symmetrically along hemicylindrical membranes. The former geometry promotes uniaxial contraction of the tissues; the latter additionally induces diagonal fiber alignment. We systematically increase the length of the seeding wells for both configurations and observe a positive correlation between fiber alignment at the center of the EHTs and tissue length. With increasing length, an undesirable thinning and "necking" also emerge, leading to the failure of longer tissues over time. In the second step, we optimize the stiffness of the seeding wells and modify some of the attachment sites of the platform and the seeding parameters to achieve tissue stability for each length and geometry. Furthermore, we use the platform for electrical pacing and calcium imaging to evaluate the functional dynamics of EHTs as a function of frequency.

Improving occupational health surveillance for enteric infections.

AIMS: Enteric pathogens with a livestock reservoir pose a unique risk to people in occupations with regular contact with animals. However, public health surveillance of occupational exposures is inadequate, with surveillance for occupation typically focusing on the risk of transmission and the need for worker exclusion, rather than workplace exposures. To improve surveillance for occupational zoonoses, the Colorado Integrated Food Safety Center of Excellence convened a group of subject matter experts who developed a set of variables on occupation, industry, and exposures, which were integrated into Colorado's surveillance system in 2017. We evaluated the quality and completeness of these new occupational fields for interviewed cases with laboratory-confirmed zoonotic infections and compared occupations to cases with a non-zoonotic infection (Shigella) and to employment data from the Bureau of Labor Statistics. METHODS AND RESULTS: From March 2017 through December 2019, 3668 domestically acquired, laboratory-confirmed sporadic infections of Campylobacter, Cryptosporidium, Shiga toxin-producing Escherichia coli, and non-typhoidal Salmonella among individuals ≥14 years of age were interviewed by public health. We found asking explicitly about occupational exposure risks and focusing on animal exposures, improved data quality and accuracy. Of the cases who stated that they were employed, 262 (13%) reported working in an occupation with regular animal exposure, and 254 (14%) reported an industry with regular animal exposure. Cases with an animal exposure occupation were more likely to be male and live in a rural or frontier county compared to other occupations. All occupations with regular animal contact were reported at a higher frequency than among Shigella cases or the general population. CONCLUSIONS: Public health efforts, both in occupational health and communicable disease sectors, should be made to improve surveillance for enteric zoonoses and identify opportunities for prevention strategies.

A Prediction Tool to Identify the Causative Agent of Enteric Disease Outbreaks Using Outbreak Surveillance Data.

Information on the causative agent in an enteric disease outbreak can be used to generate hypotheses about the route of transmission and possible vehicles, to guide environmental assessments, and to target outbreak control measures. However, only about 40% of outbreaks reported in the United States include a confirmed etiology. The goal of this project was to identify clinical and demographic characteristics that can be used to predict the causative agent in an enteric disease outbreak and to use these data to develop an online tool for investigators to use during an outbreak when hypothesizing about the causative agent. Using data on enteric disease outbreaks from all transmission routes (animal contact, environmental contamination, foodborne, person-to-person, waterborne, unknown) reported to the U.S. Centers for Disease Control and Prevention, we developed random forest models to predict the etiology of an outbreak based on aggregated clinical and demographic characteristics at both the etiology category (i.e., bacteria, parasites, toxins, viruses) and individual etiology (Clostridium perfringens, Campylobacter, Cryptosporidium, norovirus, Salmonella, Shiga toxin-producing Escherichia coli, and Shigella) levels. The etiology category model had a kappa of 0.85 and an accuracy of 0.92, whereas the etiology-specific model had a kappa of 0.75 and an accuracy of 0.86. The highest sensitivities in the etiology category model were for bacteria and viruses; all categories had high specificities (>0.90). For the etiology-specific model, norovirus and Salmonella had the highest sensitivity and all etiologies had high specificities. When laboratory confirmation is unavailable, information on the clinical signs and symptoms reported by people associated with the outbreak, with other characteristics including case demographics and illness severity, can be used to predict the etiology or etiology category. An online publicly available tool was developed to assist investigators in their enteric disease outbreak investigations.

Competencies for Public Health Professionals and Epidemiologists Who Detect and Investigate Enteric Disease Outbreaks.

OBJECTIVE: Food safety progress depends on the ability of public health agencies to detect and investigate foodborne disease outbreaks. The Integrated Food Safety Centers of Excellence identify and implement best practices and serve as resources for public health professionals who investigate enteric disease outbreaks. To target the needs of this diverse workforce, the Integrated Food Safety Centers of Excellence developed and assessed a professional tier framework and competencies. METHODS: We described the characteristics of public health professionals who investigate enteric disease outbreaks in the epidemiology role in a conceptual tiered framework. We mapped core competencies to each tier and disseminated a survey to practitioners at local (June 2019) and state (August 2018) US public health agencies to evaluate the importance and frequency of each competency. RESULTS: We developed 15 competencies on surveillance, outbreak detection, interview skills, investigation team, specimen testing, data analysis, hypothesis generation, study design, communication, enteric disease biology, control measures, legal authority, quality improvement, environmental health, and reporting to surveillance. The 286 survey respondents selected interview skills, surveillance, control measures, and hypothesis generation as the competencies most important to their work and most frequently performed. CONCLUSION: The Integrated Food Safety Centers of Excellence created the first published workforce framework and competencies for public health professionals who detect and investigate enteric disease outbreaks in the epidemiology role, in collaboration with local, state, and federal public health agencies and national organizations. These tools have been integrated into existing programs and can be used to develop training curricula, assess workforce competency over time, and identify priorities for continuing education and training.

Community exposures among Colorado adults who tested positive for SARS-CoV-2 -A case-control study, March-December 2021.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), is spread primarily through exposure to respiratory droplets from close contact with an infected person. To inform prevention measures, we conducted a case-control study among Colorado adults to assess the risk of SARS-CoV-2 infection from community exposures. METHODS: Cases were symptomatic Colorado adults (aged ≥18 years) with a positive SARS-CoV-2 test by reverse transcription-polymerase chain reaction (RT-PCR) reported to Colorado's COVID-19 surveillance system. From March 16 to December 23, 2021, cases were randomly selected from surveillance data ≤12 days after their specimen collection date. Cases were matched on age, zip code (urban areas) or region (rural/frontier areas), and specimen collection date with controls randomly selected among persons with a reported negative SARS-CoV-2 test result. Data on close contact and community exposures were obtained from surveillance and a survey administered online. RESULTS: The most common exposure locations among all cases and controls were place of employment, social events, or gatherings and the most frequently reported exposure relationship was co-worker or friend. Cases were more likely than controls to work outside the home (adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI): 1.09-1.28) in industries and occupations related to accommodation and food services, retail sales, and construction. Cases were also more likely than controls to report contact with a non-household member with confirmed or suspected COVID-19 (aOR 1.16, 95% CI: 1.06-1.27). CONCLUSIONS: Understanding the settings and activities associated with a higher risk of SARS-CoV-2 infection is essential for informing prevention measures aimed at reducing the transmission of SARS-CoV-2 and other respiratory diseases. These findings emphasize the risk of community exposure to infected persons and the need for workplace precautions in preventing ongoing transmission.

Barriers to stool specimen collection during foodborne and enteric illness outbreak investigations in Arizona and Colorado.

Stool specimen collection during a foodborne or enteric illness outbreak investigation is essential for determining the outbreak etiology and for advancing the epidemiologic understanding of the pathogens and food vehicles causing illness. However, public health professionals face multifaceted barriers when trying to collect stool specimens from ill person during an outbreak investigation. The Colorado Integrated Food Safety Center of Excellence (Colorado IFS CoE) and the Arizona Department of Health Services surveyed local public health agencies (LPHAs) to identify barriers to collecting ≥2 clinical specimens in foodborne and enteric illness outbreaks. The most commonly selected patient-related barrier was that the patient did not think it is important to provide a stool sample because they are well by the time the LPHA follows-up (61%). The most frequently selected outbreak-related barrier was the LPHA did not learn about the outbreak until after symptoms had resolved (61%). Time/personnel not being available for stool collection was the most frequently chosen health department-related barrier (51%). Timing of the outbreak (e.g., on a weekend or holiday) was the most frequently selected transportation-related barrier (51%) to collecting ≥2 stool specimens. Many of the frequently cited barriers in this survey were similar to those previously reported, such as workforce capacity and patient privacy concerns, indicating that these barriers are ongoing. Reducing barriers to stool collection during outbreaks will require efforts led at the national and state levels, such as increased enteric illness program funding, educating public health staff on the importance of specimen collection during every enteric illness outbreak, and providing specimen collection resources to LPHA staff.

Improving Foodborne Disease Surveillance and Outbreak Detection and Response Using Peer Networks-The Integrated Food Safety Centers of Excellence.

CONTEXT: Foodborne disease surveillance and outbreak investigations are foundational to the prevention and control of foodborne disease in the United States, where contaminated foods cause an estimated 48 million illnesses, 128 000 hospitalizations, and 3000 deaths each year. Surveillance activities and rapid detection and investigation of foodborne disease outbreaks require a trained and coordinated workforce across epidemiology, environmental health, and laboratory programs. PROGRAM: Under the 2011 Food Safety Modernization Act, the Centers for Disease Control and Prevention (CDC) was called on to establish Integrated Food Safety (IFS) Centers of Excellence (CoEs) at state health departments, which would collaborate with academic partners, to identify, implement, and evaluate model practices in foodborne disease surveillance and outbreak response and to serve as a resource for public health professionals. IMPLEMENTATION: CDC designated 5 IFS CoEs in August 2012 in Colorado, Florida, Minnesota, Oregon, and Tennessee; a sixth IFS CoE in New York was added in August 2014. For the August 2019-July 2024 funding period, 5 IFS CoEs were designated in Colorado, Minnesota, New York, Tennessee, and Washington. Each IFS CoE is based at the state health department that partners with at least one academic institution. EVALUATION: IFS CoEs have built capacity across public health agencies by increasing the number of workforce development opportunities (developing >70 trainings, tools, and resources), supporting outbreak response activities (responding to >50 requests for outbreak technical assistance annually), mentoring students, and responding to emerging issues, such as changing laboratory methods and the COVID-19 pandemic.

Rolling Helical Microrobots for Cell Patterning.

Microrobots, untethered miniature devices capable of performing tasks at the microscale, have gained significant attention in the fields of robotics and biomedicine. These devices hold immense potential for various industrial and scientific applications, including targeted drug delivery and cell manipulation. In this study, we present a novel magnetic rolling helical microrobot specifically designed for bio-compatible cell patterning. Our microrobot incorporates both open-loop and closed-loop control mechanisms, providing flexible, precise, and rapid control for various applications. Through experiments, we demonstrate the microrobot's ability to manipulate cells by pushing them while rolling and arranging cells into desired patterns. This result is particularly significant as it has implications for diverse biological applications such as tissue engineering and organoid development. Moreover, we showcase the effectiveness of our microrobot in a closed-loop control system, where it successfully follows a predetermined path from an origin to a destination. The combination of cellular manipulation capabilities and trajectory-tracking performance underlines the versatility and potential of our magnetic rolling helical microrobot. The ability to control and navigate the microrobot with high precision opens up new possibilities for advanced biomedical applications. These findings contribute to the growing body of knowledge in microbotics and pave the way for further research and development in the field.

Programmable Modular Acoustic Microrobots.

Microrobots have emerged as promising tools for biomedical and in vivo applications, leveraging their untethered actuation capabilities and miniature size. Despite extensive research on diversifying multi-actuation modes for single types of robots, these tiny machines tend to have limited versatility while navigating different environments or performing specific tasks. To overcome such limitations, self-assembly microstructures with on-demand reconfiguration capabilities have gained recent attention as the future of biocompatible microrobotics, as they can address drug delivery, microsurgery, and organoid development processes. Reversible modular reconfiguration structures require specific arrangements of particles that can assume several shapes when external fields are applied. We show how magnetic interaction can be used to assemble cylindrical microrobots into modular microstructures with different shapes. The motion actuation of the formed microstructure happens due to an external acoustic field, which generates responsive forces in the air bubbles trapped in the inner cavity of the robots. An external magnetic field can also steer these structures. We illustrate these capabilities by assembling the robots into different shapes that can swim and be steered, showing the potential to perform biomedical applications. Furthermore, we confirm the biocompatibility of the cylindrical microrobot used as the building blocks of our microstructure. Exposing Chinese Hamster Ovary cells to our microrobots for 24 hours demonstrates cell viability when in contact with the microrobot.

Potential immunological effects of gender-affirming hormone therapy in transgender people - an unexplored area of research.

There are well-described sex-based differences in how the immune system operates. In particular, cisgender (cis) females have a more easily activated immune system; associated with an increased prevalence of autoimmune diseases and adverse events following vaccinations. Conversely, cis males have a higher threshold for immune activation, and are more prone to certain infectious diseases, such as coronavirus disease (COVID-19). Oestrogen and testosterone have immune-modulatory properties, and it is likely that these contribute to the sexual dimorphism of the immune system. There are also important immune-related genes located on the X chromosome, such as toll-like receptor (TLR) 7/8; and the mosaic bi-allelic expression of such genes may contribute to the state of immune hyperactivation in cis females. The scientific literature strongly suggests that sex-based differences in the functioning of the immune system are related to both X-linked genes and immune modulation by sex hormones. However, it is currently not clear how this impacts transgender (trans) people receiving gender-affirming hormonal therapy. Moreover, it is estimated that in Australia, at least 2.3% of adolescents identify as trans and/or gender diverse, and referrals to specialist gender-affirming care are increasing each year. Despite the improving social awareness of trans people, they remain chronically underrepresented in the scientific literature. In addition, a small number of case studies describe new onset autoimmune disorders in adult trans females following oestrogen use. However, there is currently minimal long-term research with an immunological focus on trans people. Therefore, to ensure the positive health outcomes of trans people, it is crucial that the role of sex hormones in immune modulation is investigated further.

Stressors in forensic organizations: Risks and solutions.

Stressors of many types occur in forensic laboratories, with detrimental effects for individuals, laboratory systems, and casework outcomes. These stressors may be general, affecting the entire laboratory or all cases, or specific, affecting individual examiners or single cases. Stressors affecting individual examiners include: vicarious trauma associated with details of worked cases, nonstandard working hours, fatigue, the monotony of repetitious tasks, fear of errors, and severe backlogs. Policies and laboratory cultures can be put in place to minimize the effects of stressors; however, current forensic organizational responses to these stressors may vary from punitive to collaborative approaches. This article presents several models and case studies that can help inform the creation of positive laboratory policies. A system of discipline-wide centralized error reporting, similar to systems used to reduce fatal mistakes in medicine and aviation, could have the potential to identify areas of concern within forensic science practices.

The need for research-based tools for personnel selection and assessment in the forensic sciences.

The popularity of forensic science television programs has created a hiring challenge for forensic science laboratories. Laboratories receive unprecedented numbers of applicants, yet struggle to identify highly-qualified candidates. Forensic examiners must possess a unique set of knowledge, skills, and abilities (KSAs) plus other characteristics. They must be critical thinkers, detail-oriented, decisive, and self-regulated; be able to communicate clearly and effectively within the laboratory, with customers (typically investigators or attorneys), and in the courtroom; and demonstrate the required core competencies. Currently, no validated instruments, standardized job descriptions, or lists of KSAs exist to aid in forensic science personnel recruitment and assessment, often resulting in high turnover leading to costly new recruitment and training cycles. This article describes how industrial/organizational psychology develops methods and tools to improve workforce selection; describes some tools currently in use in forensic science; and advocates for research and development of better tools for use in forensic science.

Foodborne Illness Outbreaks Reported to National Surveillance, United States, 2009-2018.

Foodborne outbreaks reported to national surveillance systems represent a subset of all outbreaks in the United States; not all outbreaks are detected, investigated, and reported. We described the structural factors and outbreak characteristics of outbreaks reported during 2009-2018. We categorized states (plus DC) as high (highest quintile), middle (middle 3 quintiles), or low (lowest quintile) reporters on the basis of the number of reported outbreaks per 10 million population. Analysis revealed considerable variation across states in the number and types of foodborne outbreaks reported. High-reporting states reported 4 times more outbreaks than low reporters. Low reporters were more likely than high reporters to report larger outbreaks and less likely to implicate a setting or food vehicle; however, we did not observe a significant difference in the types of food vehicles identified. Per capita funding was strongly associated with increased reporting. Investments in public health programming have a measurable effect on outbreak reporting.

Metacognitive insight into cognitive performance in Huntington's disease gene carriers.

Objectives: Insight is an important predictor of quality of life in Huntington's disease and other neurodegenerative conditions. However, estimating insight with traditional methods such as questionnaires is challenging and subjected to limitations. This cross-sectional study experimentally quantified metacognitive insight into cognitive performance in Huntington's disease gene carriers. Methods: We dissociated perceptual decision-making performance and metacognitive insight into performance in healthy controls (n=29), premanifest (n=19) and early-manifest (n=10) Huntington's disease gene carriers. Insight was operationalised as the degree to which a participant's confidence in their performance was informative of their actual performance (metacognitive efficiency) and estimated using a computational model (HMeta-d'). Results: We found that premanifest and early-manifest Huntington's disease gene carriers were impaired in making perceptual decisions compared with controls. Gene carriers required more evidence in favour of the correct choice to achieve similar performance and perceptual impairments were increased in those with manifest disease. Surprisingly, despite marked perceptual impairments, Huntington's disease gene carriers retained metacognitive insight into their perceptual performance. This was the case after controlling for confounding variables and regardless of disease stage. Conclusion: We report for the first time a dissociation between impaired cognition and intact metacognition (trial-by-trial insight) in the early stages of a neurodegenerative disease. This unexpected finding contrasts with the prevailing assumption that cognitive deficits are associated with impaired insight. Future studies should investigate how intact metacognitive insight could be used by some early Huntington's disease gene carriers to positively impact their quality of life.

Engineering a living cardiac pump on a chip using high-precision fabrication.

Biomimetic on-chip tissue models serve as a powerful tool for studying human physiology and developing therapeutics; however, their modeling power is hindered by our inability to develop highly ordered functional structures in small length scales. Here, we demonstrate how high-precision fabrication can enable scaled-down modeling of organ-level cardiac mechanical function. We use two-photon direct laser writing (TPDLW) to fabricate a nanoscale-resolution metamaterial scaffold with fine-tuned mechanical properties to support the formation and cyclic contraction of a miniaturized, induced pluripotent stem cell-derived ventricular chamber. Furthermore, we fabricate microfluidic valves with extreme sensitivity to rectify the flow generated by the ventricular chamber. The integrated microfluidic system recapitulates the ventricular fluidic function and exhibits a complete pressure-volume loop with isovolumetric phases. Together, our results demonstrate a previously unexplored application of high-precision fabrication that can be generalized to expand the accessible spectrum of organ-on-a-chip models toward structurally and biomechanically sophisticated tissue systems.

Using Outbreak Data for Hypothesis Generation: A Vehicle Prediction Tool for Disease Outbreaks Caused by Salmonella and Shiga Toxin-Producing Escherichia coli.

Hypothesis generation about potential food and other exposures is a critical step in an enteric disease outbreak investigation, helping to focus investigation efforts and use of limited resources. Historical outbreak data are an important source of information for hypothesis generation, providing data on common food- and animal-pathogen pairs and other epidemiological trends. We developed a model to predict vehicles for Shiga toxin-producing Escherichia coli and Salmonella outbreaks using demographic and outbreak characteristics from outbreaks in the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System (1998-2019) and Animal Contact Outbreak Surveillance System (2009-2019). We evaluated six algorithmic methods for prediction based on their ability to predict multiple class probabilities, selecting the random forest prediction model, which performed best with the lowest Brier score (0.0953) and highest accuracy (0.54). The model performed best for outbreaks transmitted by animal contact and foodborne outbreaks associated with eggs, meat, or vegetables. Expanding the criteria to include the two highest predicted vehicles, 83% of egg outbreaks were predicted correctly, followed by meat (82%), vegetables (74%), poultry (67%), and animal contact (62%). The model performed less well for fruit and poultry vehicles, and it did not predict any dairy outbreaks. The final model was translated into a free, publicly available online tool that can be used by investigators to provide data-driven hypotheses about outbreak vehicles as part of ongoing outbreak investigations. Investigators should use the tool for hypothesis generation along-side other sources, such as food-pathogen pairs, descriptive data, and case exposure assessments. The tool should be implemented in the context of individual outbreaks and with an awareness of its limitations, including the heterogeneity of outbreaks and the possibility of novel food vehicles.