BurnCare tablet trainer to enhance burn injury care and treatment.

BACKGROUND: Applied Research Associates (ARA) and the United States Army Institute of Surgical Research (USAISR) have been developing a tablet-based simulation environment for burn wound assessment and burn shock resuscitation. This application aims to supplement the current gold standard in burn care education, the Advanced Burn Life Support (ABLS) curriculum. RESULTS: Subject matter experts validate total body surface area (TBSA) identification and analysis and show that the visual fidelity of the tablet virtual patients is consistent with real life thermal injuries. We show this by noting that the error between their burn mapping and the actual patient burns was sufficiently less than that of a random sample population. Statistical analysis is used to confirm this hypothesis. In addition a full body physiology model developed for this project is detailed. Physiological results, and responses to standard care treatment, are detailed and validated. Future updates will include training modules that leverage this model. CONCLUSION: We have created an accurate, whole-body model of burn TBSA training experience in Unreal 4 on a mobile platform, provided for free to the medical community. We hope to provide learners with more a realistic experience and with rapid feedback as they practice patient assessment, intervention, and reassessment.

Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks.

Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations-an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise.

Crosstalk and the evolution of specificity in two-component signaling.

Two-component signaling (TCS) serves as the dominant signaling modality in bacteria. A typical pathway includes a sensor histidine kinase (HK) that phosphorylates a response regulator (RR), modulating its activity in response to an incoming signal. Most HKs are bifunctional, acting as both kinase and phosphatase for their substrates. Unlike eukaryotic signaling networks, there is very little crosstalk between bacterial TCS pathways; indeed, adding crosstalk to a pathway can have disastrous consequences for cell fitness. It is currently unclear exactly what feature of TCS necessitates this degree of pathway isolation. In this work we used mathematical models to show that, in the case of bifunctional HKs, adding a competing substrate to a TCS pathway will always reduce response of that pathway to incoming signals. We found that the pressure to maintain cognate signaling is sufficient to explain the experimentally observed "kinetic preference" of HKs for their cognate RRs. These findings imply a barrier to the evolution of new HK-RR pairs, because crosstalk is unavoidable immediately after the duplication of an existing pathway. We characterized a set of "near-neutral" evolutionary trajectories that minimize the impact of crosstalk on the function of the parental pathway. These trajectories predicted that crosstalk interactions should be removed before new input/output functionalities evolve. Analysis of HK sequences in bacterial genomes provided evidence that the selective pressures on the HK-RR interface are different from those experienced by the input domain immediately after duplication. This work thus provides a unifying explanation for the evolution of specificity in TCS networks.

Senior Medical Student Mock Interview Program in Pediatrics.

OBJECTIVES: Residency interviews play an integral part in medical residency placement. We aimed to develop and evaluate a mock interview program for fourth-year medical students interested in a pediatric specialty. METHODS: A mock interview program for fourth-year medical students interested in pediatrics was developed and implemented. Preinterview quantitative data and postinterview qualitative data were collected. Fifty-nine students completed the program across three consecutive academic years. Preinterview surveys were completed regarding comfort and confidence levels specific to aspects of the interview process. Descriptive analyses were used. In addition, a focus group was held with nine of the participating students to obtain qualitative data via a paper blog process. Themes in student responses were identified through constant comparative analysis. RESULTS: Before the mock interview, students were most uncomfortable with introductory and closing remarks and their confidence levels varied by topic. A thematic analysis of focus group data identified five themes (preparation, stress reduction, interview process familiarity, confidence of skills, and receiving feedback) for which the mock interviews were most helpful. CONCLUSIONS: Implementation of a mock interview program was feasible and acceptable for senior medical students and may improve comfort and confidence levels in the residency interview process. Further longitudinal research is needed.

Phosphatase specificity and pathway insulation in signaling networks.

Phosphatases play an important role in cellular signaling networks by regulating the phosphorylation state of proteins. Phosphatases are classically considered to be promiscuous, acting on tens to hundreds of different substrates. We recently demonstrated that a shared phosphatase can couple the responses of two proteins to incoming signals, even if those two substrates are from otherwise isolated areas of the network. This finding raises a potential paradox: if phosphatases are indeed highly promiscuous, how do cells insulate themselves against unwanted crosstalk? Here, we use mathematical models to explore three possible insulation mechanisms. One approach involves evolving phosphatase KM values that are large enough to prevent saturation by the phosphatase's substrates. Although this is an effective method for generating isolation, the phosphatase becomes a highly inefficient enzyme, which prevents the system from achieving switch-like responses and can result in slow response kinetics. We also explore the idea that substrate degradation can serve as an effective phosphatase. Assuming that degradation is unsaturatable, this mechanism could insulate substrates from crosstalk, but it would also preclude ultrasensitive responses and would require very high substrate turnover to achieve rapid dephosphorylation kinetics. Finally, we show that adaptor subunits, such as those found on phosphatases like PP2A, can provide effective insulation against phosphatase crosstalk, but only if their binding to substrates is uncoupled from their binding to the catalytic core. Analysis of the interaction network of PP2A's adaptor domains reveals that although its adaptors may isolate subsets of targets from one another, there is still a strong potential for phosphatase crosstalk within those subsets. Understanding how phosphatase crosstalk and the insulation mechanisms described here impact the function and evolution of signaling networks represents a major challenge for experimental and computational systems biology.

As I see it: a study of African American pastors' views on health and health education in the black church.

The Black Church is the only institution that has consistently served the interest of African Americans, and there is no other institution in the African American community that rivals its influence (Camara, 2004). The spiritual well-fare, social support, health, and well-being of its people have been one of its main goals. With health disparities of African Americans still at an alarming rate, the Black Church has used informal education as a means to impart knowledge on health, as well as other non-religious and religious topics. One of the avenues least researched within the Black Church is the pastor's perception of its educational role in health and wellness and its efforts to reduce health discrimination and health disparities between African American and European Americans in the U.S. Since social justice appears as a theme and concern in the traditions of many churches, it is only appropriate that, among other things, the Black Church should address the issue of health education and interventions. The purpose of this study was to explore African American pastors' perceptions of the role of the Black Church in providing health care, health education, and wellness opportunities to African Americans. Many pastors reported their church provided some form of health education and/or health screenings. Their perceptions about the important issues facing their congregants versus African Americans in general were quite similar.

Evaluation of an innovative tool for child sexual abuse education.

Child sexual abuse poses a serious threat to public health and is often unreported, unrecognized, and untreated. Prevention, early recognition, and treatment are critically important to reduce long-term effects. Little data are available on effective methods of preventing child sexual abuse. The current research demonstrates a unique approach to promoting awareness and stimulating discussion about child sexual abuse. Qualitative methods have rarely been used to study child sexual abuse prevention. Qualitative inductive analyses of interviews from 20 key informants identified both positive and negative assessments with six emergent themes. The themes revealed inherent tensions in using narrative accounts to represent the complex cultural context within which child sexual abuse occurs. More research is needed, but the program shows potential as a methodology to raise awareness of child sexual abuse.

Crosstalk and competition in signaling networks.

Signaling networks have evolved to transduce external and internal information into critical cellular decisions such as growth, differentiation, and apoptosis. These networks form highly interconnected systems within cells due to network crosstalk, where an enzyme from one canonical pathway acts on targets from other pathways. It is currently unclear what types of effects these interconnections can have on the response of networks to incoming signals. In this work, we employ mathematical models to characterize the influence that multiple substrates have on one another. These models build off of the atomistic motif of a kinase/phosphatase pair acting on a single substrate. We find that the ultrasensitive, switch-like response these motifs can exhibit becomes transitive: if one substrate saturates the enzymes and responds ultrasensitively, then all substrates will do so regardless of their degree of saturation. We also demonstrate that the phosphatases themselves can induce crosstalk even when the kinases are independent. These findings have strong implications for how we understand and classify crosstalk, as well as for the rational development of kinase inhibitors aimed at pharmaceutically modulating network behavior.

Yellow fever vaccine-associated viscerotropic disease.

Yellow fever is a mosquito-transmitted hemorrhagic viral disease that is endemic to tropical regions in South America and Africa. It remains a significant health concern for deploying military personnel, accordingly vaccination is frequently performed on troops. Although the vaccine is generally administered with only minor complications, rare severe complications are also reported. Herein, we report a mild case of yellow fever vaccine-associated viscerotropic disease 4 days after administration of the vaccine. The various complications of the vaccine and their pathogenesis are also reviewed.

Devil in the details: Mechanistic variations impact information transfer across models of transcriptional cascades.

The transcriptional network determines a cell's internal state by regulating protein expression in response to changes in the local environment. Due to the interconnected nature of this network, information encoded in the abundance of various proteins will often propagate across chains of noisy intermediate signaling events. The data-processing inequality (DPI) leads us to expect that this intracellular game of "telephone" should degrade this type of signal, with longer chains losing successively more information to noise. However, a previous modeling effort predicted that because the steps of these signaling cascades do not truly represent independent stages of data processing, the limits of the DPI could seemingly be surpassed, and the amount of transmitted information could actually increase with chain length. What that work did not examine was whether this regime of growing information transmission was attainable by a signaling system constrained by the mechanistic details of more complex protein-binding kinetics. Here we address this knowledge gap through the lens of information theory by examining a model that explicitly accounts for the binding of each transcription factor to DNA. We analyze this model by comparing stochastic simulations of the fully nonlinear kinetics to simulations constrained by the linear response approximations that displayed a regime of growing information. Our simulations show that even when molecular binding is considered, there remains a regime wherein the transmitted information can grow with cascade length, but ends after a critical number of links determined by the kinetic parameter values. This inflection point marks where correlations decay in response to an oversaturation of binding sites, screening informative transcription factor fluctuations from further propagation down the chain where they eventually become indistinguishable from the surrounding levels of noise.

Postoperative 20% albumin vs standard care and acute kidney injury after high-risk cardiac surgery (ALBICS): study protocol for a randomised trial.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgery. Factors such as cardiopulmonary bypass, aortic cross-clamping and surgical stress may precipitate renal hypoperfusion and ischaemia, inflammation and oxidative stress are associated with development of AKI. Albumin's pharmacological properties and widespread availability have the potential to mitigate these factors. However, the effect of albumin on cardiac surgery-associated AKI is unknown. OBJECTIVE: To evaluate the impact of postoperative 20% albumin infusion on kidney function after high-risk cardiac surgery. METHODS: We designed an open-label, multicentre, randomised controlled trial-the ALBICS study (ALBumin Infusion and acute kidney injury following Cardiac Surgery). A total of 590 patients undergoing high-risk cardiac surgery (combined procedure or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) will be enrolled into the study and randomly allocated to receive a postoperative 20% albumin infusion or standard care in a 1:1 ratio, stratified by centre and baseline renal function. The study fluid will be administered upon arrival in intensive care for 15 h. Patients will be followed up until 28 days after surgery or until discharge from the hospital. The primary outcome is the proportion of patients who develop AKI in both groups. Secondary outcomes to be measured are proportions of AKI stage II and III, 28-day mortality, mechanical ventilation time and length of stay in intensive care and hospital. CONCLUSION: This trial aims to determine if a postoperative infusion of concentrated albumin reduces the risk of AKI following high-risk cardiac surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619001355167. Registered on 03 October 2019-retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378383 .

COVID-19 infection data encode a dynamic reproduction number in response to policy decisions with secondary wave implications.

The SARS-CoV-2 virus is responsible for the novel coronavirus disease 2019 (COVID-19), which has spread to populations throughout the continental United States. Most state and local governments have adopted some level of "social distancing" policy, but infections have continued to spread despite these efforts. Absent a vaccine, authorities have few other tools by which to mitigate further spread of the virus. This begs the question of how effective social policy really is at reducing new infections that, left alone, could potentially overwhelm the existing hospitalization capacity of many states. We developed a mathematical model that captures correlations between some state-level "social distancing" policies and infection kinetics for all U.S. states, and use it to illustrate the link between social policy decisions, disease dynamics, and an effective reproduction number that changes over time, for case studies of Massachusetts, New Jersey, and Washington states. In general, our findings indicate that the potential for second waves of infection, which result after reopening states without an increase to immunity, can be mitigated by a return of social distancing policies as soon as possible after the waves are detected.

Improving Preventive Care for Children With Sickle Cell Anemia: A Quality Improvement Initiative.

Sickle cell disease is a complex chronic disorder associated with increased morbidity and early mortality. The Pediatric Quality Measures Program has developed new sickle cell-specific quality measures focused on hydroxyurea (HU) counseling and annual transcranial Doppler (TCD) screening; however, these measures have not been used in a clinical setting to inform quality improvement (QI) efforts. METHODS: From 2017 to 2018, 9 sickle cell subspecialty clinics from the Pacific Sickle Cell Regional Collaborative conducted a year-long QI collaborative focused on improving the percentage of patients with HU counseling and TCD screening based on the new quality measures. After an initial kick-off meeting, the 9 sites participated in monthly conference calls. We used run charts annotated with plan-do-study-act cycle activities to track each site's monthly progress and the overall mean percentage for the entire collaborative. RESULTS: There was an overall improvement in the aggregate HU counseling from 85% to 98% (P < 0.01). For TCD screening, referral frequency changed from 85% to 90% (P = 0.76). For both measures, the variation in frequencies decreased over the year. CONCLUSION: Over 1 year, we found that a regional QI collaborative increased HU counseling. Although referral for TCD screening increased, there was no overall change in TCD completion. Overall, this QI report's findings can help clinicians adopt and implement these quality measures to improve outcomes in children.

Tranexamic Acid in cardiac surgery and postoperative seizures: a case report series.

With the recent withdrawal of the antifibrinolytic aprotinin from the market, tranexamic acid (TxA) has become more widely used. This change has led to increasing concern about the side-effect profile of TxA, particularly the incidence of postoperative seizures. In this case series, we describe 7 patients over an 18-month period who had open-chamber cardiac surgery and developed seizures in the postoperative period. This incidence is increased compared with that of a cohort of patients in the previous 36 months who did not receive TxA (0.66% versus 0%; P < .05). The exact mechanism of TxA-induced seizures is thought to be via inhibition of gamma-aminobutyric acid receptors in neurons. Data from the neurosurgical literature show a well-established link between this antifibrinolytic and seizures. There is now increasing awareness of this association in cardiac surgery, particularly when high TxA doses are used.

Perceptions of intimidation and bullying in dental schools: a multi-national study.

OBJECTIVES: To determine first year dental students' perceptions of intimidation by instructors and bullying by fellow students. METHODS: Data were collected through a cross-sectional survey of first year dental students from seven dental schools representing five countries; one each from Romania, South Africa, Australia and the U.S.A., and three from Malaysia. Self-report questionnaires were administered to participants at least six months after they had commenced their dental degree course during 2005-6. RESULTS: Over a third (34.6%) reported that they had been intimidated or badly treated by their tutors/instructors and 17% reported that they had been bullied or badly treated by their fellow students in the recent past. There were statistically significant differences in reports of intimidation by instructors between the different dental schools. Intimidation by instructors was associated with a history of medication use for stress, anxiety and depression, and perceived stress in the past month. There were no statistically significant variations in reports of bullying by fellow students between different dental schools. Bullying by fellow students was associated with dieting to lose weight, self-reported general health and perceived stress. CONCLUSIONS: This multi-national study highlights that intimidation and bullying is prevalent within dental teaching and training environments. Future research is needed to explore their impact on students' wellbeing and academic progress as well as on patient care. CLINICAL IMPLICATIONS: Dentists are the best recruiters for the profession. If the dental school experience is a negative one it can have significant impact on the future of the profession

Does a novel teaching approach work? A Students' perspective.

BACKGROUND: There is always a call for educational reform and further research to improve educational programs. The continuous development of new educational approaches is a work in progress. Educational strategies like team-based learning, flipped classroom, and lottery-based token economy, were used to develop a novel teaching approach. AIM: This study had two major goals. The first goal was to introduce a novel teaching approach in professional healthcare academies. The second goal was to get an in-depth understanding, from the students' perspective, about the benefits and limitations of this new teaching approach. METHOD: The study was conducted using a qualitative, phenomenological research design. Third and fourth-year nursing students completed reflective journals to describe their personal experience with the new teaching approach at the end of the semester. The students' responses were analyzed and coded using Kember's four-category coding schema for reflective writing, to extract themes using thematic analysis. FINDINGS: Seventy-five students completed and returned their reflective journals. The analysis showed various challenges and facilitators/benefits of the students' experiences. The themes that emerged from the analysis were: lack of exposure vs. a sense of achievement; lack of teamwork skills vs. role fulfillment; working with new people vs. conflict resolution; variation vs. collaboration/creativity; time management vs. constructive competition; wasting resources vs. flexibility, and proactivity/active engagement. These themes summarized why the new teaching approach worked and what barriers students faced with the new assembly. CONCLUSION: Results from the current study demonstrated the great potential of the new teaching approach. Recommendations for future research were also discussed.

Dental students' and faculty members' perceptions of incivility in the classroom.

The purpose of this study was to compare dental students' and faculty members' perceptions of classroom incivility and to determine how many students willingly engage in uncivil behavior in the classroom. A web-based survey research design was used to obtain information regarding uncivil classroom behaviors from dental students and full- and part-time dental faculty members at a midwestern U.S. dental school. Responses were received from sixty-eight dental faculty members and 127 third- and fourth-year students. The perceptions of faculty members about what constitutes uncivil classroom behavior differed from those of students. In fact, of the eighteen questions asked of both groups, statistical differences were found for eleven (61 percent).

Stochastically modeling multiscale stationary biological processes.

Large scale biological responses are inherently uncertain, in part as a consequence of noisy systems that do not respond deterministically to perturbations and measurement errors inherent to technological limitations. As a result, they are computationally difficult to model and current approaches are notoriously slow and computationally intensive (multiscale stochastic models), fail to capture the effects of noise across a system (chemical kinetic models), or fail to provide sufficient biological fidelity because of broad simplifying assumptions (stochastic differential equations). We use a new approach to modeling multiscale stationary biological processes that embraces the noise found in experimental data to provide estimates of the parameter uncertainties and the potential mis-specification of models. Our approach models the mean stationary response at each biological level given a particular expected response relationship, capturing variation around this mean using conditional Monte Carlo sampling that is statistically consistent with training data. A conditional probability distribution associated with a biological response can be reconstructed using this method for a subset of input values, which overcomes the parameter identification problem. Our approach could be applied in addition to dynamical modeling methods (see above) to predict uncertain biological responses over experimental time scales. To illustrate this point, we apply the approach to a test case in which we model the variation associated with measurements at multiple scales of organization across a reproduction-related Adverse Outcome Pathway described for teleosts.

Barriers to Pediatric Sickle Cell Disease Guideline Recommendations.

National guidelines recommend that providers counsel all patients with sickle cell anemia about hydroxyurea (HU) therapy and screen children with sickle cell anemia annually for the risk of stroke with transcranial Doppler (TCD). We surveyed a national convenience sample of sickle cell disease clinicians to assess factors associated with low adherence. Adherence was 46% for TCD screening. Low adherence was associated with a lack of outcome expectancy (eg, a belief that there would be poor patient follow-up to TCD testing; P < .05). Adherence was 72% for HU counseling. Practice barriers (eg, lack of support staff or time) and a lack of agreement with HU recommendations were associated with low adherence (P < .05). This study demonstrates that different types of strategies are needed to improve TCD screening (to address follow-up and access to testing) versus HU counseling (to address physician agreement and practice barriers).

Enhancing communication in dental clinics with linguistically different patients.

The United States is becoming substantially more diverse in its citizenry, with numerous racial and ethnic cultural groups and immigrants living and working in this country. In addition, there has been an increase in the number of languages other than English spoken in homes, as well as an increase in the number of individuals with limited English-speaking abilities. Given the emerging racial, ethnic, and cultural trends in U.S. society, it is important that dental students as future practitioners have knowledge of interpreter services, working with professionally trained interpreters, and the legal responsibilities and requirements of interpretation. The purposes of this study were to 1) describe the role of interpreters in dental health care settings; 2) identify challenges they face; and 3) propose approaches and strategies to improve communication between dental students as future practitioners and non-English-speaking patients. Data were collected through a series of individual in-depth, face-to-face interviews using a semi-structured open-question format and email communications with three key informants who were purposefully selected to participate in this study based on their comprehensive knowledge and experience as interpreters. The qualitative analysis revealed themes or stories related to the following areas of this study: 1) the role of professional interpreters in dental and other health care settings; 2) challenges faced by interpreters and providers working with patients with limited English-speaking ability; and 3) strategies and approaches used to improve communication and address challenges. By understanding the unique interpreting needs of non- or limited English-speaking patients, dental students have an opportunity to broaden their cultural competency skills. Dental schools have an obligation to ensure that students, faculty, and staff know and understand the legal rights of patients and health care providers to communicate effectively when using an interpreter, although having a professionally trained interpreter working in a facility does not end the cultural learning processes needed in a multicultural society.