Using OR Black Box Technology to Determine Quality Improvement Outcomes for In-situ Timeout and Debrief Simulation.

OBJECTIVE: The purpose of this study was to determine quality improvement outcomes following the pilot implementation of an in-situ simulation designed to enhance surgical safety checklist performance. BACKGROUND: OR Black Box (ORBB) technology allows near real-time assessment for surgical safety checklist performance. Before our study, timeout quality was 73.3%, compliance was 99.9%, and engagement was 89.7% (n=1993 cases); Debrief Quality was 76.0%, compliance was 66.9%, and engagement was 66.7% (n=1842 cases). METHODS: This IRB-approved study used prospective convergent multi-methods. During 2 months, a 15-minute in-situ simulation, incorporating rapid cycle deliberate practice, was implemented for OR teams. ORBB analytics generated Timeout and Debrief scores for actual operations performed by surgeons who participated in simulation (Sim-group) versus those who did not (No-sim group) over 6 months, including 2 months pre-intervention, during-intervention, and post-intervention. Inductive content analysis was performed based on simulation discussions to determine team member perspectives. RESULTS: Thirty simulations with 163 interprofessional participants were conducted. ORBB data from 1570 cases were analyzed. Scores were significantly better for the Sim-group compared with the No-sim group for debrief quality (84% vs. 79% P<0.001, during-intervention), compliance (73% vs. 66%, P<0.001, post-intervention), and engagement (80% vs. 73%, P=0.012, during-intervention). There were no between-group differences for Timeout scores. Thematic analysis identified 2 primary categories: "culture of safety" and "policy." CONCLUSIONS: This simulation-based QI intervention created a psychologically safe training environment for OR teams. The novel use of ORBB technology facilitated outcome analysis and showed significantly better Debrief scores for simulation-trained surgeons compared with nontrained surgeons.

The dissection of a despotic society: exploration, dominance and hormonal traits.

Naked mole-rats (Heterocephalus glaber) live in large colonies with one breeding female (queen), one to three breeding males (BMs) and the remainder are non-reproductive subordinates. The animals have a linear dominance rank with the breeders at the top of the hierarchy. We investigated how dominance rank in naked mole-rats differs with exploration (the propensity to explore a novel environment) and related endocrine markers. Exploration behaviour, faecal progestagen metabolite (fPM), faecal glucocorticoid metabolite (fGCM), faecal androgen metabolite (fAM) and plasma prolactin concentrations were quantified in breeding, high-, middle- and low-ranked females and males from five naked mole-rat colonies. There were no significant differences between the dominance rank and exploration behaviour. Interestingly, the queens and high-ranking females had higher fGCM and fAM concentrations compared with middle- and low-ranked females. The queens had significantly higher fPM concentrations than all other ranked females, since they are responsible for procreation. In the males, the BMs had higher fGCM concentrations compared with high- and low-ranked males. In addition, BMs and middle-ranking males had overall higher prolactin levels than all other ranked males, which could be linked to cooperative care. Overall, the results suggest that physiological reproductive suppression is linked to high dominance rank.

Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125.

Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. Using an Fcγ receptor-mediated NK cell activation assay, we show that ascites from ovarian cancer patients potently inhibits NK cell activation. Part of the inhibitory activity is mediated by CA125, a mucin 16 fragment shed from ovarian cancer tumors. Moreover, transcriptional analyses by RNA sequencing reveal upregulation of genes involved in multiple metabolic pathways but downregulation of genes involved in cytotoxicity and signaling pathways in NK cells purified from ovarian cancer patient ascites. Transcription of genes involved in cytotoxicity pathways are also downregulated in NK cells from healthy donors after in vitro treatment with ascites or with a CA125-enriched protein fraction. These results show that ascites and CA125 inhibit antitumor activity of NK cells at transcriptional levels by suppressing expression of genes involved in NK cell activation and cytotoxicity. Our findings shed light on the molecular mechanisms by which ascites inhibits the activity of NK cells and suggest possible approaches to reactivate NK cells for ovarian cancer immunotherapy.

Broad Electronic Modulation of Two-Dimensional Metal-Organic Frameworks over Four Distinct Redox States.

Two-dimensional (2D) inorganic materials have emerged as exciting platforms for (opto)electronic, thermoelectric, magnetic, and energy storage applications. However, electronic redox tuning of these materials can be difficult. Instead, 2D metal-organic frameworks (MOFs) offer the possibility of electronic tuning through stoichiometric redox changes, with several examples featuring one to two redox events per formula unit. Here, we demonstrate that this principle can be extended over a far greater span with the isolation of four discrete redox states in the 2D MOFs LixFe3(THT)2 (x = 0-3, THT = triphenylenehexathiol). This redox modulation results in 10,000-fold greater conductivity, p- to n-type carrier switching, and modulation of antiferromagnetic coupling. Physical characterization suggests that changes in carrier density drive these trends with relatively constant charge transport activation energies and mobilities. This series illustrates that 2D MOFs are uniquely redox flexible, making them an ideal materials platform for tunable and switchable applications.

Mimicking biological stress-strain behaviour with synthetic elastomers.

Despite the versatility of synthetic chemistry, certain combinations of mechanical softness, strength, and toughness can be difficult to achieve in a single material. These combinations are, however, commonplace in biological tissues, and are therefore needed for applications such as medical implants, tissue engineering, soft robotics, and wearable electronics. Present materials synthesis strategies are predominantly Edisonian, involving the empirical mixing of assorted monomers, crosslinking schemes, and occluded swelling agents, but this approach yields limited property control. Here we present a general strategy for mimicking the mechanical behaviour of biological materials by precisely encoding their stress-strain curves in solvent-free brush- and comb-like polymer networks (elastomers). The code consists of three independent architectural parameters-network strand length, side-chain length and grafting density. Using prototypical poly(dimethylsiloxane) elastomers, we illustrate how this parametric triplet enables the replication of the strain-stiffening characteristics of jellyfish, lung, and arterial tissues.

Highly socially vulnerable communities exhibit disproportionately increased viral loads as measured in community wastewater.

Wastewater surveillance has proven to be a useful tool for evidence-based epidemiology in the fight against the SARS-CoV-2 virus. It is particularly useful at the population level where acquisition of individual test samples may be time or cost-prohibitive. Wastewater surveillance for SARS-CoV-2 has typically been performed at wastewater treatment plants; however, this study was designed to sample on a local level to monitor the spread of the virus among three communities with distinct social vulnerability indices in Shreveport, Louisiana, located in a socially vulnerable region of the United States. Twice-monthly grab samples were collected from September 30, 2020, to March 23, 2021, during the Beta wave of the pandemic. The goals of the study were to examine whether: 1) concentrations of SARS-CoV-2 RNA in wastewater varied with social vulnerability indices and, 2) the time lag of spikes differed during wastewater monitoring in the distinct communities. The size of the population contributing to each sample was assessed via the quantification of the pepper mild mottle virus (PMMoV), which was significantly higher in the less socially vulnerable community. We found that the communities with higher social vulnerability exhibited greater viral loads as assessed by wastewater when normalized with PMMoV (Kruskal-Wallis, p < 0.05). The timing of the spread of the virus through the three communities appeared to be similar. These results suggest that interconnected communities within a municipality experienced the spread of the SARS-CoV-2 virus at similar times, but areas of high social vulnerability experienced more intense wastewater viral loads.

The Operating Room Black Box: Understanding Adherence to Surgical Checklists.

OBJECTIVE: We report for the first time the use of the Operating Room Black Box (ORBB) to track checklist compliance, engagement, and quality. BACKGROUND: Implementation of operative checklists is associated with improved outcomes. Compliance is difficult to monitor. Most studies report either no assessment of checklist compliance or deployed in-person short-term assessment. The ORBB a novel artificially intelligence-driven data analytic platform affords the opportunity to assess checklist compliance without disrupting surgical workflow. METHODS: This was a retrospective review of prospectively collected ORBB data. Operative cases included elective surgery at a quaternary referral center. Cases were analyzed as prepolicy change (first 9 months) or as a postpolicy change (last 9 months). Measures of checklist compliance, engagement, and quality were assessed. RESULTS: There were 3879 cases that were performed and monitored for checklist compliance between August 15, 2020, and February 20, 2022. The overall scores for compliance, engagement, and quality were 81%, 84%, and 67% respectively. When broken down by phase, the scores for time-out were compliance 100%, engagement 98%, and quality 61%. Scores for the debrief phase were 81% for compliance, 98% for engagement, and 66% for quality. After a hospital policy change, the debrief scores improved significantly (85%; P <0.001 for compliance, 88%; P <0.001 for engagement and 71%; P <0.001 for quality). CONCLUSIONS: ORBB provides the unprecedented ability to assess not only compliance with surgical safety checklists but also engagement and quality. Utilization of this technology allows the assessment of compliance in near real time and to accurately address safety threats that may arise from noncompliance.

Plasma oxidative stress in reproduction of two eusocial African mole-rat species, the naked mole-rat and the Damaraland mole-rat.

One of the most prominent life-history trade-offs involves the cost of reproduction. Oxidative stress has been proposed to be involved in this trade-off and has been associated with reduced life span. There is currently an unclear relationship between oxidative cost and the reproduction-longevity trade-off. The current study, using a non-lethal and minimally invasive (only a single blood sample and no euthanasia) method, investigated whether an oxidative cost (oxidative stress) to reproduction would be apparent in two long-lived eusocial mole-rats, the naked mole-rat (NMR), Heterocephalus glaber, and the Damaraland mole-rat (DMR), Fukomys damarensis, where breeding colony members live longer than non-breeder conspecifics. We measured the direct redox balance in plasma by measuring the oxidative stress index (OSI) based on the ratio of total oxidant status and total antioxidant activity in breeders and non-breeders of both sexes, in the two species. NMR had significantly higher OSI between breeders and non-breeders of each sex, whereas DMR showed no significant differences except for total antioxidant capacity (TAC). The mode of reproductive suppression and the degree of reproductive investment in NMR may explain to some degree the redox balance difference between breeders and non-breeders. DMR show minimal physiological changes between breeders and non-breeders except for the mode of reproduction, which may explain some variations in TAC and TOS values, but similar OSI between breeders and non-breeders.

Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes.

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.

Chemo- and Regioselective Functionalization of Isotactic Polypropylene: A Mechanistic and Structure-Property Study.

Polyolefins represent a high-volume class of polymers prized for their attractive thermomechanical properties, but the lack of chemical functionality on polyolefins makes them inadequate for many high-performance engineering applications. We report a metal-free postpolymerization modification approach to impart functionality onto branched polyolefins without the deleterious chain-coupling or chain-scission side reactions inherent to previous methods. The identification of conditions for thermally initiated polyolefin C-H functionalization combined with the development of new reagents enabled the addition of xanthates, trithiocarbonates, and dithiocarbamates to a variety of commercially available branched polyolefins. Systematic experimental and kinetic studies led to a mechanistic hypothesis that facilitated the rational design of reagents and reaction conditions for the thermally initiated C-H xanthylation of isotactic polypropylene (iPP) within a twin-screw extruder. A structure-property study showed that the functionalized iPP adheres to polar surfaces twice as strongly as commercial iPP while demonstrating similar tensile properties. The fundamental understanding of the elementary steps in amidyl radical-mediated polyolefin functionalization provided herein reveals key structure-reactivity relationships for the design of improved reagents, while the demonstration of chemoselective and scalable iPP functionalization to realize a material with improved adhesion properties indicates the translational potential of this method.

Repeated sublethal freshwater exposures reduce the amoebic gill disease parasite, Neoparamoeba perurans, on Atlantic salmon.

Freshwater bathing is one of the main treatment options available against amoebic gill disease (AGD) affecting multiple fish hosts in mariculture systems. Prevailing freshwater treatments are designed to be long enough to kill Neoparamoeba perurans, the ectoparasite causing AGD, which may select for freshwater tolerance. Here, we tested whether using shorter, sublethal freshwater treatment durations are a viable alternative to lethal ones for N. perurans (2-4 hr). Under in vitro conditions, gill-isolated N. perurans attached to plastic substrate in sea water lifted off after ≥2 min in freshwater, but survival was not impacted until 60 min. In an in vivo experiment, AGD-affected Atlantic salmon Salmo salar subjected daily to 30 min (sublethal to N. perurans) and 120 min (lethal to N. perurans) freshwater treatments for 6 days consistently reduced N. perurans cell numbers on gills (based on qPCR analysis) compared to daily 3 min freshwater or seawater treatments for 6 days. Our results suggest that targeting cell detachment rather than cell death with repeated freshwater treatments of shorter duration than typical baths could be used in AGD management. However, the consequences of modifying the intensity of freshwater treatment regimes on freshwater tolerance evolution in N. perurans populations require careful consideration.

Solvent-free, supersoft and superelastic bottlebrush melts and networks.

Polymer gels are the only viable class of synthetic materials with a Young's modulus below 100 kPa conforming to biological applications, yet those gel properties require a solvent fraction. The presence of a solvent can lead to phase separation, evaporation and leakage on deformation, diminishing gel elasticity and eliciting inflammatory responses in any surrounding tissues. Here, we report solvent-free, supersoft and superelastic polymer melts and networks prepared from bottlebrush macromolecules. The brush-like architecture expands the diameter of the polymer chains, diluting their entanglements without markedly increasing stiffness. This adjustable interplay between chain diameter and stiffness makes it possible to tailor the network's elastic modulus and extensibility without the complications associated with a swollen gel. The bottlebrush melts and elastomers exhibit an unprecedented combination of low modulus (∼100 Pa), high strain at break (∼1,000%), and extraordinary elasticity, properties that are on par with those of designer gels.

Yoga-based Psychotherapy Groups for Boys Exposed to Trauma in Urban Settings.

BACKGROUND: Children who experience abuse and neglect and are exposed to adverse life events are at risk of developing emotional and behavioral problems. They may display variable internalizing and externalizing symptoms, such as posttraumatic stress, depression, anxiety, low self-esteem, and aggression. Yoga may be able to regulate body-brain pathways that cause stress following traumatic experiences, thereby reducing adverse mental and physical sequelae. OBJECTIVE: The objective of this preliminary study is to examine changes in functioning following meetings of a yoga-based psychotherapy group (YBPG) for boys with a history of interpersonal trauma exposure. METHODS/DESIGN: The study was a prospective, intervention cohort study. SETTING: The study occurred at an urban-based mental health center focusing on treatment of children exposed to interpersonal trauma in their communities and families. PARTICIPANTS: Participants were 10 boys, aged 8-12 y, who primarily were African-Americans (70%) and who had a history of trauma. INTERVENTION: The YBPG was a 12-wk, yoga-based, group therapy, integrated with mental health treatment that was trauma informed and evidence-based. OUTCOME MEASURES: Measures of attendance and interpersonal functioning-the Behavioral and Emotional Rating Scale 2 (BERS-2) and patient satisfaction surveys-were collected. The pre- and post-YBPG, paired t test; Wilcoxon's signed rank test; and effect sizes were calculated to assess change in interpersonal functioning following the YBPG, as reported by the parents and children. RESULTS: The BERS-2 scores yielded clinically and statistically significant mean improvements on the parents' ratings of participants' (1) Interpersonal Strength, Intrapersonal Strength, and Family Involvement scores, with mean improvements on those subscales being 1.4 (P=.007), 1.9 (P=.012), and 1.4 (P=.045) points, respectively; and (2) Strength Index scores, with a mean improvement of 8.7 (P=.004). The effect size was in the large range. In addition to significant improvements posttreatment, the parents' mean rating score of their children's functioning was closer but still lower than the children's self-reports on all subscales. The attendance rate for the YBPG was among the highest for group therapies at the center. CONCLUSIONS: The study provided preliminary evidence for the feasibility of YBPG as an effective intervention for boys exposed to trauma in urban settings.

Enhancing scaffold-free spheroid models: 3D cell bioprinting method for metastatic HSC3-Oral squamous carcinoma cell line.

3D in vitro systems offer advantages over the shortcomings of two-dimensional models by simulating the morphological and functional features of in vivo-like environments, such as cell-cell and cell-extracellular matrix interactions, as well as the co-culture of different cell types. Nevertheless, these systems present technical challenges that limit their potential in cancer research requiring cell line- and culture-dependent standardization. This protocol details the use of a magnetic 3D bioprinting method and other associated techniques (cytotoxicity assay and histological analysis) using oral squamous cell carcinoma cell line, HSC3, which offer advantages compared to existing widely used approaches. This protocol is particularly timely, as it validates magnetic bioprinting as a method for the rapid deployment of 3D cultures as a tool for compound screening and development of heterotypic cultures such as co-culture of oral squamous cell carcinoma cells with cancer-associated fibroblasts (HSC3/CAFs).

Environmental health and household demographics impacting biosand filter maintenance and diarrhea in Guatemala: an application of structural equation modeling.

In rural health development practice, engineers and scientists must recognize the complex interactions that influence individuals' contact with disease-causing pathogens and understand how household habits may impact the adoption and long-term sustainability of new technology. The goal of this study was to measure the effect of various environmental health factors and household demographics on the operation and maintenance of the Biosand filter (Centre for Affordable Water and Sanitation Technology, Calgary, Alberta, Canada) and diarrhea health burden in the region. In July and August 2010, randomized household surveys (n = 286) were completed in rural Guatemala detailing water access, sanitation availability, hygiene practice, socio-economic status, education level, filter operation and maintenance, and diarrhea health burden of the home. A hypothesized structural equation model was developed based on a review of published research and tested using the surveyed data. Model-derived parameter estimates indicated that: (a) proper personal hygiene practices significantly promote proper filter operation and maintenance; and (b) higher household education level, proper filter operation and maintenance, and improved water supply significantly reduce diarrhea health burden. Additionally, a high level of unexplained variance in diarrhea indicated the filter, though protective of health, is not the only factor influencing diarrhea.

Validation of Enzyme Immunoassays via an Adrenocorticotrophic Stimulation Test for the Non-Invasive Quantification of Stress-Related Hormone Metabolites in Naked Mole-Rats.

Small size in mammals usually restricts long-term, frequent monitoring of endocrine function using plasma as a matrix. Thus, the non-invasive monitoring of hormone metabolite concentrations in excreta may provide an invaluable approach. The aim of the current study was to examine the suitability of enzyme immunoassays (EIAs) for monitoring responses to stressors in the naked mole-rat (Heterocephalus glaber, NMR) using urine and feces as hormone matrices. A saline control administration, and a high- and low-dose adrenocorticotropic hormone (ACTH) challenge were performed on six male and six female disperser morph NMRs. The results revealed that a 5α-pregnane-3ß,11ß,21-triol-20-one EIA detecting glucocorticoid metabolites (GCMs) with a 5α-3ß-11ß-diol structure is the most suitable assay for measuring concentrations in male urine samples, whereas an 11-oxoaetiocholanolone EIA detecting GCMs with a 5ß-3α-ol-11-one structure appears the most suitable EIA for quantifying GCMs in female urine. An 11-oxoaetiocholanolone EIA detecting 11,17 dioxoandrostanes was the most suitable EIA for quantifying GCMs in the feces of both sexes. There were sex-related differences in response to the high- and low-dose ACTH challenge. We recommend using feces as a more suitable matrix for non-invasive GCM monitoring for NMRs which can be valuable when investigating housing conditions and other welfare aspects.

Non-Invasive Quantification of Faecal and Urine Reproductive Hormone Metabolites in the Naked Mole-Rat (Heterocephalus glaber).

The naked mole-rat (Heterocephalus glaber) occurs in colonies with a distinct dominance hierarchy, including one dominant, breeding female (the queen), 1-3 breeding males, and non-reproductive subordinates of both sexes that are reproductively suppressed while in the colony. To non-invasively evaluate reproductive capacity in the species, we first had to examine the suitability of enzyme immunoassays (EIAs) for determining progestogen and androgen metabolite concentrations in the naked mole-rat, using urine and faeces. A saline control and gonadotrophin-releasing hormone (GnRH) were administered to twelve (six males and six females) naked mole-rats which were previously identified as dispersers and housed singly. The results revealed that urine is possibly not an ideal matrix for progestogen and androgen metabolite quantification in naked mole-rats as no signal was detected in the matrix post GnRH administration. A 5α-Progesterone EIA and an Epiandrosterone EIA were identified as suitable for quantifying faecal progesterone metabolites (fPMs) and faecal androgen metabolites (fAMs) in males and females, respectively. The results suggest that there are individual variations in baseline fPM and fAM concentrations, and only two out of six females and no males exhibited an increase in fPM concentrations greater than 100% (-20% SD) post GnRH administration. Conversely, only four out of six females and three out of six males had an increase in fAM concentrations greater than 100% (-20% SD) following GnRH administration. These results imply that some naked mole-rat individuals have a reduced reproductive capacity even when they are separated from the queen.

Unraveling two distinct polymorph transition mechanisms in one n-type single crystal for dynamic electronics.

Cooperativity is used by living systems to circumvent energetic and entropic barriers to yield highly efficient molecular processes. Cooperative structural transitions involve the concerted displacement of molecules in a crystalline material, as opposed to typical molecule-by-molecule nucleation and growth mechanisms which often break single crystallinity. Cooperative transitions have acquired much attention for low transition barriers, ultrafast kinetics, and structural reversibility. However, cooperative transitions are rare in molecular crystals and their origin is poorly understood. Crystals of 2-dimensional quinoidal terthiophene (2DQTT-o-B), a high-performance n-type organic semiconductor, demonstrate two distinct thermally activated phase transitions following these mechanisms. Here we show reorientation of the alkyl side chains triggers cooperative behavior, tilting the molecules like dominos. Whereas, nucleation and growth transition is coincident with increasing alkyl chain disorder and driven by forming a biradical state. We establish alkyl chain engineering as integral to rationally controlling these polymorphic behaviors for novel electronic applications.

Retention and Predictors of Attrition Among People Living With HIV on Antiretroviral Therapy in Guinea: A 13-Year Historical Cohort Study in Nine Large-Volume Sites.

Objectives: The objective of this study was to estimate the retention rate of patients in an ART program and identify the predictors of attrition. Methods: This was a historical cohort study of HIV patients who started ART between September 2007 and April 2020, and were followed up on for at least 6 months in nine large-volume sites. Kaplan Meier techniques were used to estimate cumulative retention and attrition probabilities. Cox proportional hazards models were used to identify predictors of attrition. Results: The cumulative probability of retention at 12 and 24 months was 76.2% and 70.2%, respectively. The attrition rate after a median follow-up time of 3.1 years was 35.2%, or an incidence of 11.4 per 100 person-years. Having initiated ART between 2012 and 2015; unmarried status; having initiated ART with CD4 count <100 cells/µL; and having initiated ART at an advanced clinical stage were factors significantly associated with attrition. Conclusion: The retention rate in our study is much lower than the proposed national target (90%). Studies to understand the reasons for loss to follow-up are needed.