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Abstract Background data Computed Tomography (CT) is the gold standard for cervical spine (c-spine) evaluation. Magnetic resonance imaging (MRI) emerges due to its increasing availability and the lack of radiation exposure. However, MRI is costly and time-consuming, questioning its role in the emergency department (ED). This study investigates the added the value of an additional MRI for patients presenting with a c-spine injury in the ED. Methods We conducted a retrospective monocenter cohort study that included all patients with neck trauma presenting in the ED, who received imaging based on the NEXUS criteria. Spine surgeons performed a full-case review to classify each case into “c-spine injured” and “c-spine uninjured”. Injuries were classified according to the AO Spine classification. We assessed patients with a c-spine injury detected by CT, who received a subsequent MRI. In this subset, injuries were classified separately in both imaging modalities. We monitored the treatment changes after the additional MRI to evaluate characteristics of this cohort and the impact of the AO Spine Neurology/Modifier modifiers. Results We identified 4496 subjects, 2321 were eligible for inclusion and 186 were diagnosed with c-spine injuries in the retrospective case review. Fifty-six patients with a c-spine injury initially identified through CT received an additional MRI. The additional MRI significantly extended (geometric mean ratio 1.32, p

Abstract Introduction and objectives Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery. Patients and methods From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy. Results All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%. Conclusion The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

Abstract Purpose The aim of this study is to determine the validity of consumer grade step counter devices during the early recovery period after knee replacement surgery. Methods Twenty-three participants wore a Fitbit Charge or Apple Watch Series 4 smart watch and performed a walking test along a 50-metre hallway. There were 9 males and 14 females included in the study with an average age of 68.5 years and BMI of 32. Each patient wore both the Fitbit Charge and Apple Watch while completing the walking test and an observer counted the ground truth value using a thumb-push tally counter. This test was repeated pre-operatively with no gait aid, immediately post operatively with a walker, at 6 weeks follow up with a cane and at 6 months with no gait aid. Bland-Altman plots were performed for all walking tests to compare the agreement between measurement techniques. Results Mean overall agreement of step count for pre-operative and at 6 months for subjects walking without gait aids was excellent for both the Apple Watch vs. actual and Fitbit vs. actual with bias values ranging from − 0.87 to 1.36 with limits of agreement (LOA) ranging between − 10.82 and 15.91. While using a walker both devices showed extremely little agreement with the actual step count with bias values between 22.5 and 24.37 with LOA between 11.7 and 33.3. At 6 weeks post-op while using a cane, both the Apple Watch and Fitbit devices had a range of bias values between − 2.8 and 5.73 with LOA between − 13.51 and 24.97. Conclusions These devices show poor validity in the early post operative setting, especially with the use of gait aids, and therefore results should be interpreted with caution.

Introduction: Evidence-based medicine (EBM) is a critical skill for physicians, and EBM competency has been shown to increase implementation of best medical practices, reduce medical errors, and increase patient-centered care. Like any skill, EBM must be practiced, receiving iterative feedback to improve learners’ comprehension. Having residents document patient interactions in logbooks to allow for residency program review, feedback, and documentation of competency has been previously described as a best practice within emergency medicine (EM) to document practice-based learning (PBL) competency. Quantifying how residents use the information they query, locate, evaluate, and apply while providing direct patient care can measure the efficacy of EBM education and provide insight into more efficient ways of providing medical care. Methods: Practice-based learning logs were surveys created to record resident EBM activity on-shift and were placed into our residency management software program. Residents were required to submit 3–5 surveys of EBM activity performed during a 28-day rotation during which additional information was sought. This study included all PBL logs completed by EM residents from June 1, 2013–May 11, 2020. Using qualitative methodology, a codebook was created to analyze residents’ free-text responses to the prompt: “Based on your research, would you have done anything differently?” The codebook was designed to generate a three-digit code conveying the effect of the researched information on the patient about whom the log was written, as well as whether the information would affect future patient care and whether these decisions were based on scientific evidence. Results: A total of 10,574 logs were included for primary analysis. In total, 1,977 (18.7%) logs indicated that the evidence acquired through research would affect future patient care. Of these, 392 (3.7%) explicitly stated that the EBM activity conducted as part of our project led to real-time changes in patient care in the ED and would change future management of patients as well. Conclusion: We present a proof of concept that PBL log activity can lead to integration of evidence-based medicine into real-time patient care. While a convenience sample, our cohort recorded evidence of both lifelong learning and application to patient care.

This study investigates the impact of emotionalizing sound design on driving behaviour, focusing on the effect of an acoustic stimulus that varies from positive to negative/threatening based on the vehicle’s time headway (THW). Our primary goal was to explore how this sound influences driving durations within specific THW ranges and the mean THW itself. The experiment utilized a control group and a within-participant setting across simulated driving scenarios. The statistical analysis showed mixed results. While participants in the control group setup did not demonstrate significant reductions in the durations of driving in lower THW ranges, a modest but significant increase in mean THW was observed when the emotionalizing sound was active. However, within-participant comparisons showed both a significant decrease in the duration of driving at lower THWs and an increase in mean THW when the negative stimulus was active, suggesting the stimulus’ effectiveness in promoting safer driving habits. These findings highlight the potential of emotionalizing sound design to influence driver behaviour towards maintaining safer distances, although the impact appears to diminish at higher THW ranges. Future research should further investigate the characteristics of sounds that effectively modify driving behaviour, aiming for broader applications in traffic safety.

Abstract Type IV pili are filamentous appendages found in most bacteria and archaea, where they can support functions such as surface adhesion, DNA uptake, aggregation, and motility. In most bacteria, PilT-family ATPases disassemble adhesion pili, causing them to rapidly retract and produce twitching motility, important for surface colonization. As archaea do not possess PilT homologs, it was thought that archaeal pili cannot retract and that archaea do not exhibit twitching motility. Here, we use live-cell imaging, automated cell tracking, fluorescence imaging, and genetic manipulation to show that the hyperthermophilic archaeon Sulfolobus acidocaldarius exhibits twitching motility, driven by retractable adhesion (Aap) pili, under physiologically relevant conditions (75 °C, pH 2). Aap pili are thus capable of retraction in the absence of a PilT homolog, suggesting that the ancestral type IV pili in the last universal common ancestor (LUCA) were capable of retraction.

Abstract Amongst the major types of archaeal filaments, several have been shown to closely resemble bacterial homologues of the Type IV pili (T4P). Within Sulfolobales, member species encode for three types of T4P, namely the archaellum, the UV-inducible pilus system (Ups) and the archaeal adhesive pilus (Aap). Whereas the archaellum functions primarily in swimming motility, and the Ups in UV-induced cell aggregation and DNA-exchange, the Aap plays an important role in adhesion and twitching motility. Here, we present a cryoEM structure of the Aap of the archaeal model organism Sulfolobus acidocaldarius. We identify the component subunit as AapB and find that while its structure follows the canonical T4P blueprint, it adopts three distinct conformations within the pilus. The tri-conformer Aap structure that we describe challenges our current understanding of pilus structure and sheds new light on the principles of twitching motility.

Rubber production is a labour-intensive process. In order to reduce the needed number of workers and the waste of material, the level of digitalisation should be increased. One part of the production is the extrusion to produce gaskets and similar objects. An automated observation of the continuous rubber extrudate enables an early intervention in the production process. In addition to chemical monitoring, the geometrical observation of the extrudate is an important aspect of the quality control. For this purpose, we use laser triangulation sensors (LTS) at the beginning and the end of the cooling phase of the extrudate after the extrusion. The LTS acquire two-dimensional profiles at a constant frequency. To combine these profiles into a three-dimensional model of the extrudate, the movement of the extrudate has to be tracked. Since the extrudate is moved over a conveyor belt, the conveyor belt can be tracked by a stereo camera system to deduce the movement of the extrudate. For the correct usage of the tracking, the orientation between the LTS and the stereo camera system needs to be known. A calibration object that considers the different data from the LTS and the camera system was developed to determine the orientation. Afterwards, the orientation can be used to combine arbitrary profiles. The measurement setup, consisting of the LTS, the stereo camera system and the conveyor belt, is explained. The development of the calibration object, the algorithm for evaluating the orientation data and the combination of the LTS profiles are described. Finally, experiments with real extrusion data are presented to validate the results and compare three variations of data evaluation. Two use the calculated orientation, but have different tracking approaches and one without any orientation necessary.

Abstract The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Abstract Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering.

This study examined principal perspectives on barriers and strengths or assets associated with the delivery of school mental health services in their school and considered whether the common determinants that principals identify vary by geographic locales (i.e., city, suburban, town, and rural). Participants were 638 principals from across the four locale categories. Principals completed open-ended survey questions that addressed perceived barriers and strengths or assets with the delivery of school mental health. Thematic analysis was conducted of principal responses. There were differences in the most common barriers principals identified across locale. For example, principals in suburban areas identified lack of personnel, principals in cities identified a lack of a shared understanding about mental and behavioral health and associated services, and principals in towns and rural areas identified financial concerns as primary barriers in addressing student mental health needs. Across all four locales, the most common stated strength or asset in schools was having school-based mental and behavioral health personnel and resources. Implications for practice and future research are discussed.

Background: What is redundancy? While most studies confirm that redundancy is harmful to learning, there are two theoretical approaches to redundancy. The first understands redundancy as a contentual overlap that puts demand on the limited cognitive capacities of the learner. The second understands redundancy as an ineffective combination of sources leading to an overload of the limited working memory modalities. Aims: Since these theoretical differences are rarely acknowledged in operation, this study proposes a classification of two distinct types of redundancy to compare these experimentally to investigate their possible main and interaction effects. The first type, content redundancy, is concerned with the contentual overlap of information. The second type, modal redundancy, is concerned with the modalities in which the information is displayed. Methods: We used these two types of redundancy as factors in a 2 × 2 within-subject design, in which we experimentally compared their effects. Sample: University students (N = 46) learned from specifically designed domain-general material which aimed to observe redundancy effects without interference from confounding variables. Results: The results show that content redundancy increases learning outcomes and decreases cognitive load, while modal redundancy decreases learning outcomes and increases cognitive load. Conclusion: On the theoretical level, these findings confirm the usefulness to distinguish content redundancy from modal redundancy. On the practical level, the empirical findings of the different effects of the two types of redundancy provide educators with important insights that can improve the design of multimedia learning materials.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor (Oxtr) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species (n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.

Hydrothermal vents emit hot fluids enriched in energy sources for microbial life. Here, we compare the ecological and biogeochemical effects of hydrothermal venting of two recently discovered volcanic seamounts, Polaris and Aurora of the Gakkel Ridge, in the ice-covered Central Arctic Ocean. At both sites, persistent hydrothermal plumes increased up to 800 m into the deep Arctic Ocean. In the two non-buoyant plumes, rates of microbial carbon fixation were strongly elevated compared to background values of 0.5–1 μmol m−3 day−1 in the Arctic deep water, which suggests increased chemoautotrophy on vent-derived energy sources. In the Polaris plume, free sulfide and up to 360 nM hydrogen enabled microorganisms to fix up to 46 μmol inorganic carbon (IC) m−3 day−1. This energy pulse resulted in a strong increase in the relative abundance of SUP05 by 25% and Candidatus Sulfurimonas pluma by 7% of all bacteria. At Aurora, microorganisms fixed up to 35 μmol IC m−3 day−1. Here, metal sulfides limited the bioavailability of reduced sulfur species, and the putative hydrogen oxidizer Ca. S. pluma constituted 35% and SUP05 10% of all bacteria. In accordance with this data, transcriptomic analysis showed a high enrichment of hydrogenase-coding transcripts in Aurora and an enrichment of transcripts coding for sulfur oxidation in Polaris. There was neither evidence for methane consumption nor a substantial increase in the abundance of putative methanotrophs or their transcripts in either plume. Together, our results demonstrate the dominance of hydrogen and sulfide as energy sources in Arctic hydrothermal vent plumes.

The neutron-rich rare isotope 190W is discussed as a candidate for a prolate-oblate transitional nucleus with maximum γ-softness. The collectivity of this isotope is assessed for the first time by the measurement of the reduced E2 transition probability of its first 2+ state to the ground state. The experiment employed the FAst TIming Array (FATIMA), comprised of 36 LaBr3(Ce) scintillators, which was part of the DESPEC setup at GSI, Darmstadt. The 41+ and 21+ states of 190W were populated subsequently to the decay of its 127(12) μs isomeric Jπ=10− state. The mean lifetime of the 21+ state was determined to be τ=274(28) ps, which corresponds to a B(E2;21+→01+) value of 95(10) W.u. The results motivated a revision of previous calculations within an energy-density functional-based interacting boson model-2 approach, yielding E2 transition properties and spectroscopic quadrupole moments for tungsten isotopes. From comparison to theory, the new data suggest that 190W is at the transition from prolate to oblate structure along the W isotopic chain, which had previously been discussed as a nuclear shape-phase transition.

Aqueous processing of lithium (ion) battery cathodes based on Ni‐rich layered oxides like LiNi0.83Co0.12Mn0.05O2 (NCM) can reduce costs, increase sustainability, and pave the way for F‐free, e.g., biopolymeric binders, however, the degradation of water‐sensitive Ni‐rich NCM remains a challenge. Besides strategies like NCM coatings and processing additives, customized binders can be performance‐decisive via impacting both, electrode processing aspects (paste viscosity, particle dispersibility, etc.) and chemical interactions with NCM surface, though, a distinction between these two impacting factors is difficult given their mutual influences. For this reason, a bifunctional binder system is chosen in this work, i.e., highly viscous xanthan and low viscous pullulan, both polysaccharides known from the food industry, which realize constant viscosity and processing, finally enabling systematic investigation of binder modifications (here pullulan) with various side groups. In fact, while the rate performance remains constant, suggesting a similar composite network with comparable electronic and ionic conductivities, the modified binders affect the NCM||graphite cycle life, where a higher substitution degree of carboxymethylated pullulan can even compete with N‐methyl‐2‐pyrrolidone/polyvinylidene difluoride state‐of‐the‐art system at conventional upper charge voltage (4.2 V); while at 4.5 V water‐reasoned NCM damages get obvious, as seen by enhanced electrode cross‐talk via transition metal deposition on anode.

Introduction Professional caregivers’ perspectives on dementia and on people living with dementia (PlwD) can influence their feelings, judgements and behaviours in work situations, for example, how they think about symptoms, disease progression and the impact on a person’s quality of life. Their individual dementia mindset, which can be investigated with the 12-item Dementia Mindset Scale (DMS), might influence job satisfaction, work-related well-being and person-centred care. The aim of the proposed replication study is to confirm the results of the original study of the DMS and to test whether a malleable mindset is correlated with higher levels of caregiver education, dementia-specific professional experience/competence and dementia knowledge.Methods and analysis Professional caregivers in residential care facilities for older persons who work directly with PlwD will be asked to answer an anonymous web-based online survey. The survey encompasses five standardised questionnaires: the DMS, the Dementia Knowledge Assessment Scale, the Oldenburg Burnout Inventory, the Job-related Affective Well-being Scale and the Sense of Competence in Dementia Care Staff Scale. In addition, job satisfaction, the educational background, professional experience and work situation are surveyed. For replication, the analyses will re-evaluate the psychometric properties (structural validity, model fit, internal consistency and predictive validity) by applying descriptive statistics, regression analysis, confirmatory factor analysis and correlation analysis. The additional analyses will use descriptive statistics, regression analysis and correlation analysis. Rasch analysis will be used to rank the difficulty of the items.Ethics and dissemination This study was approved by the ethics committee of the German Society of Nursing Science (ID number 23-004). No personal information will be gathered. The results of the study will be distributed nationally and internationally through peer-reviewed academic journals, conferences, institutional websites and journals for nursing care practice.

Ion channels and cytoskeletal proteins in the cardiac dyad play a critical role in maintaining excitation-contraction (E-C) coupling and provide cardiac homeostasis. Functional changes in these dyad proteins, whether induced by genetic, epigenetic, metabolic, therapeutic, or environmental factors, can disrupt normal cardiac electrophysiology, leading to abnormal E-C coupling and arrhythmias. Animal models and heterologous cell cultures provide platforms to elucidate the pathogenesis of arrhythmias for basic cardiac research; however, these traditional systems do not truly reflect human cardiac electro-pathophysiology. Notably, patients with the same genetic variants of inherited channelopathies (ICC) often exhibit incomplete penetrance and variable expressivity which underscores the need to establish patient-specific disease models to comprehend the mechanistic pathways of arrhythmias and determine personalized therapies. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) inherit the genetic background of the patient and reflect the electrophysiological characteristics of the native cardiomyocytes. Thus, iPSC-CMs provide an innovative and translational pivotal platform in cardiac disease modeling and therapeutic screening. In this review, we will examine how patient-specific iPSC-CMs historically evolved to model arrhythmia syndromes in a dish, and their utility in understanding the role of specific ion channels and their functional characteristics in causing arrhythmias. We will also examine how CRISPR/Cas9 have enabled the establishment of patient-independent and variant-induced iPSC-CMs-based arrhythmia models. Next, we will examine the limitations of using human iPSC-CMs with respect to in vitro arrhythmia modeling that stems from variations in iPSCs or toxicity due to gene editing on iPSC or iPSC-CMs and explore how such hurdles are being addressed. Importantly, we will also discuss how novel 3D iPSC-CM models can better capture in vitro characteristics and how all-optical platforms provide non-invasive and high- throughput electrophysiological data that is useful for stratification of emerging arrhythmogenic variants and drug discovery. Finally, we will examine strategies to improve iPSC-CM maturity, including powerful gene editing and optogenetic tools that can introduce/modify specific ion channels in iPSC-CMs and tailor cellular and functional characteristics. We anticipate that an elegant synergy of iPSCs, novel gene editing, 3D- culture models, and all-optical platforms will offer a high-throughput template to faithfully recapitulate in vitro arrhythmogenic events necessary for personalized arrhythmia monitoring and drug screening process.

IntroductionAmong hyperthermophilic organisms, in vivo protein localization is challenging due to the high growth temperatures that can disrupt proper folding and function of mostly mesophilic-derived fluorescent proteins. While protein localization in the thermophilic model archaeon S. acidocaldarius has been achieved using antibodies with fluorescent probes in fixed cells, the use of thermostable fluorescent proteins for live imaging in thermophilic archaea has so far been unsuccessful. Given the significance of live protein localization in the field of archaeal cell biology, we aimed to identify fluorescent proteins for use in S. acidocaldarius.MethodsWe expressed various previously published and optimized thermostable fluorescent proteins along with fusion proteins of interest and analyzed the cells using flow cytometry and (thermo-) fluorescent microscopy.ResultsOf the tested proteins, thermal green protein (TGP) exhibited the brightest fluorescence when expressed in Sulfolobus cells. By optimizing the linker between TGP and a protein of interest, we could additionally successfully fuse proteins with minimal loss of fluorescence. TGP-CdvB and TGP-PCNA1 fusions displayed localization patterns consistent with previous immunolocalization experiments.DiscussionThese initial results in live protein localization in S. acidocaldarius at high temperatures, combined with recent advancements in thermomicroscopy, open new avenues in the field of archaeal cell biology. This progress finally enables localization experiments in thermophilic archaea, which have so far been limited to mesophilic organisms.

Background Unfavorable clinical outcomes in patients with acute ischemic stroke caused by large‐vessel occlusions despite successful reperfusion have been associated with poor venous outflow. The objective of this study is to assess the relationship between prolonged venous transit (PVT), a novel perfusion imaging surrogate for poor venous outflow, and likelihood of favorable clinical recovery. Methods In this retrospective review of prospectively collected data of consecutive patients (2017–2022) with successfully reperfused, anterior circulation acute ischemic stroke caused by large‐vessel occlusions, we assessed the association between PVT+, defined as time to maximum ≧10‐second timing delays within either the posterior superior sagittal sinus, torcula, or both regions on pretreatment perfusion imaging, and favorable clinical outcomes defined as 90‐day modified Rankin Scale score of 0 to 2. Patients were dichotomized into PVT+ and PVT− for analysis. Multivariable logistic regression analyses for favorable recovery were performed with demographic variables and stroke characteristics. Results A total of 127 consecutive patients (median age, 71 [interquartile range 61—77] years; 59.1% women) were included, and 40 of 127 (31.5%) were PVT+. PVT+ (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07–0.81]; P = 0.02) and advanced age (aOR, 0.92 [95% CI, 0.88–0.97]; P = 0.01) were significantly associated with the primary outcome. Conclusion PVT+ was associated with a lower likelihood of achieving favorable clinical recovery in successfully reperfused patients with acute ischemic stroke caused by large vessel occlusion. PVT may serve as a clinically useful adjunctive imaging parameter.

Introduction: Intensive care unit (ICU) patients exhibit erratic blood glucose (BG) fluctuations, including hypoglycemic and hyperglycemic episodes, and require exogenous insulin delivery to keep their BG in healthy ranges. Glycemic control via glycemic management (GM) is associated with reduced mortality and morbidity in the ICU, but GM increases the cognitive load on clinicians. The availability of robust, accurate, and actionable clinical decision support (CDS) tools reduces this burden and assists in the decision-making process to improve health outcomes. Clinicians currently follow GM protocol flow charts for patient intravenous insulin delivery rate computations.Methods: We present a mechanistic model-based control algorithm that estimates the optimal intravenous insulin rate to keep BG within a target range; the goal is to develop this approach for eventual use within CDS systems. In this control framework, we employed a stochastic model representing BG dynamics in the ICU setting and used the linear quadratic Gaussian control methodology to develop a controller.Results: We designed two experiments, one using virtual (simulated) patients and one using a real-world retrospective dataset. Using these, we evaluated the safety and efficacy of this model-based glycemic control methodology. The presented controller avoids hypoglycemia and hyperglycemia in virtual patients, maintaining BG levels in the target range more consistently than two existing GM protocols. Moreover, this methodology could theoretically prevent a large proportion of hypoglycemic and hyperglycemic events recorded in a real-world retrospective dataset.Discussion: The current version of the methodology shows potential usefulness in GM of ICU patients. However, it is limited to a subgroup of the ICU patient population, who are fed through and enteral tube and delivered intravenous insulin. After extending to a broader ICU patient population who can consume oral nutrition and are delivered subcutaneous insulin for GM, the methodology could be tested with pilot studies and clinical trials for eventual use as a CDS tool.

Background: The protocols and therapeutic guidance established for treating traumatic brain injury (TBI) in neurointensive care focus on managing cerebral blood flow (CBF) and brain tissue oxygenation based on pressure signals. The decision support process relies on assumed relationships between cerebral perfusion pressure (CPP) and blood flow, pressure-flow relationships (PFRs), and shares this framework of assumptions with mathematical intracranial hemodynamics models. These foundational assumptions are difficult to verify, and their violation can impact clinical decision-making and model validity.Methods: A hypothesis- and model-driven method for verifying and understanding the foundational intracranial hemodynamic PFRs is developed and applied to a novel multi-modality monitoring dataset.Results: Model analysis of joint observations of CPP and CBF validates the standard PFR when autoregulatory processes are impaired as well as unmodelable cases dominated by autoregulation. However, it also identifies a dynamical regime -or behavior pattern-where the PFR assumptions are wrong in a precise, data-inferable way due to negative CPP-CBF coordination over long timescales. This regime is of both clinical and research interest: its dynamics are modelable under modified assumptions while its causal direction and mechanistic pathway remain unclear.Conclusion: Motivated by the understanding of mathematical physiology, the validity of the standard PFR can be assessed a) directly by analyzing pressure reactivity and mean flow indices (PRx and Mx) or b) indirectly through the relationship between CBF and other clinical observables. This approach could potentially help to personalize TBI care by considering intracranial pressure and CPP in relation to other data, particularly CBF. The analysis suggests a threshold using clinical indices of autoregulation jointly generalizes independently set indicators to assess CA functionality. These results support the use of increasingly data-rich environments to develop more robust hybrid physiological-machine learning models.

Background: Troponin is a biomarker of myocardial injury and death but has not been well studied after pediatric heart transplants. The objective of this analysis is to describe the distribution and clinical determinants of serum troponin measured in the first week after pediatric heart transplantation. Methods: We included all patients who underwent heart transplantation at Seattle Children’s Hospital between 2012 and 2016. Serum Troponin-I (TnI) was measured daily in the first week after transplant. We described the distribution of serum TnI, and examined the relationship between peak TnI with known pre- peri-operative risk factors for myocardial injury including etiology of heart failure, ischemia time, and donor to recipient characteristics. Logistic regression models were used to test the association between peak TnI with incidence of death or rejection and formation of donor-specific antibodies (DSA) within 1 year. Adjusted models included age, HF etiology, crossmatch status, and panel reactive antibodies. Results: During the study period, 86 transplants were performed on 83 unique individuals. Serum TnI peaked at a median of 0.9 days after transplantation. In adjusted models, higher peak TnI was associated with death and/or rejection within 1-year post-transplant (odds ratio [95% confidence interval]: 1.10 [1.02, 1.19]). Peak TnI was not associated with de-novo DSA formation in adjusted models (OR [95%CI]: 1.01 [0.94, 1.09]). Post-transplant length of stay in the intensive care unit was positively correlated with peak TnI (r = 0.36, p