A comprehensive evaluation of emergency department utilization by patients with cirrhosis.

BACKGROUND: Emergency Department (ED) based care is required for cirrhosis management, yet the burden of cirrhosis-related ED healthcare utilization (HCU) is understudied. We aimed to describe ED utilization within a statewide health system and compare the outcomes of high ED use (HEDU) versus non-HEDU in individuals with cirrhosis. METHODS: We retrospectively reviewed charts of adults with cirrhosis who presented to any of 16 EDs within the Indiana University Health system in 2021. Patient characteristics, features of the initial ED visit, subsequent 90-day healthcare use, and 360-day outcomes were collected. Multivariable logistic regression models were used to identify predictors HEDU status which was defined as ≥2 ED visits within 90 days after the index ED visit. RESULTS: There were 2124 eligible patients (mean age 61.3 years, 53% male, and 91% White). Major etiologies of cirrhosis were alcohol (38%), MASH (27%), and viral hepatitis (21%). Cirrhosis was newly diagnosed in the ED visit for 18.4%. Most common reasons for ED visits were abdominal pain (21%), shortness of breath (19%), and ascites/volume overload (16%). Of the initial ED visits 20% (n=424) were potentially avoidable. The overall 90-day mortality was 16%. Within 90 days, there were 366 HEDU (20%). Notable variables independently associated with HEDU were MELD-Na (aOR=1.044, 95% CI 1.005-1.085), prior ED encounter (aOR=1.520, 95% CI 1.136-2.034), and avoidable initial ED visit (aOR=1.938, 95% CI 1.014-3.703). CONCLUSIONS: Abdominal pain, shortness of breath, and ascites/fluid overload are the common presenting reasons for ED visits for patients with cirrhosis. Patients with cirrhosis presenting to the ED experience a 90-day mortality rate of 16%, and among those who initially visited the ED, 20% were HEDU. We identified several variables independently associated with HEDU. Our observations pave the way for developing interventions to optimize the care of patients with cirrhosis presenting to the ED and to lower repeated ED visits.

A mesoscale connectome of the mouse brain.

Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.

Eye tracking and audio sensors to evaluate surgeon's non-technical skills: An empirical study.

Non-Technical Skills (NTS) of medical teams are currently measured using subjective and resource-intensive ratings given by experts. This study explores if objective NTS assessment approaches with eye-tracking and audio sensors can measure teamwork and communication skills in surgery. Eight surgeons participated in a simulated two-phase surgical scenario developed to assess their NTS. Sensor-based audio, eye tracking and video data were collected and analyzed along with rating from the NOTSS scale. Different levels of communication were detected by the sensor data during the two phases of the simulated surgery. Sensor data detected leadership qualities among surgeons based on speech metrics, and eye tracking offered additional evidence about gaze patterns related to NTS. This objective approach to NTS measurement captured differences in communication in greater detail as opposed to a single collective rating obtained using current assessment tools.

Hemodynamic profiles by non-invasive monitoring of cardiac index and vascular tone in acute heart failure patients in the emergency department: External validation and clinical outcomes.

BACKGROUND: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes. METHODS: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k = 3 profiles each). The VC was subgrouped de novo into three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone. Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome. RESULTS: The VC had median age 60 years (interquartile range {49-67}), and was 45% (n = 116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p = 0.001, R2 = 0.159). A difference was not detected between profiles in the VC vs. the DC (p = 0.59, R2 = 0.016). VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (p<0.05). No significant differences between profiles were observed for other clinical variables or the 3 clinical risk scores. CONCLUSIONS: Hemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicated de novo in an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.

Operating in a Multisensory Context: Assessing the Interplay Between Multisensory Reaction Time Facilitation and Inter-sensory Task-switching Effects.

Individuals respond faster to presentations of bisensory stimuli (e.g. audio-visual targets) than to presentations of either unisensory constituent in isolation (i.e. to the auditory-alone or visual-alone components of an audio-visual stimulus). This well-established multisensory speeding effect, termed the redundant signals effect (RSE), is not predicted by simple linear summation of the unisensory response time probability distributions. Rather, the speeding is typically faster than this prediction, leading researchers to ascribe the RSE to a so-called co-activation account. According to this account, multisensory neural processing occurs whereby the unisensory inputs are integrated to produce more effective sensory-motor activation. However, the typical paradigm used to test for RSE involves random sequencing of unisensory and bisensory inputs in a mixed design, raising the possibility of an alternate attention-switching account. This intermixed design requires participants to switch between sensory modalities on many task trials (e.g. from responding to a visual stimulus to an auditory stimulus). Here we show that much, if not all, of the RSE under this paradigm can be attributed to slowing of reaction times to unisensory stimuli resulting from modality switching, and is not in fact due to speeding of responses to AV stimuli. As such, the present data do not support a co-activation account, but rather suggest that switching and mixing costs akin to those observed during classic task-switching paradigms account for the observed RSE.

Cortex-wide Changes in Extracellular Potassium Ions Parallel Brain State Transitions in Awake Behaving Mice.

Brain state fluctuations modulate sensory processing, but the factors governing state-dependent neural activity remain unclear. Here, we tracked the dynamics of cortical extracellular K+ concentrations ([K+]o) during awake state transitions and manipulated [K+]o in slices, during visual processing, and during skilled motor execution. When mice transitioned from quiescence to locomotion, [K+]o increased by 0.6-1.0 mM in all cortical areas analyzed, and this preceded locomotion by 1 s. Emulating the state-dependent [K+]o increase in cortical slices caused neuronal depolarization and enhanced input-output transformation. In vivo, locomotion increased the gain of visually evoked responses in layer 2/3 of visual cortex; this effect was recreated by imposing a [K+]o increase. Elevating [K+]o in the motor cortex increased movement-induced neuronal spiking in layer 5 and improved motor performance. Thus, [K+]o increases in a cortex-wide state-dependent manner, and this [K+]o increase affects both sensory and motor processing through the dynamic modulation of neural activity.

Auditory sensory memory span for duration is severely curtailed in females with Rett syndrome.

Rett syndrome (RTT), a rare neurodevelopmental disorder caused by mutations in the MECP2 gene, is typified by profound cognitive impairment and severe language impairment, rendering it very difficult to accurately measure auditory processing capabilities behaviorally in this population. Here we leverage the mismatch negativity (MMN) component of the event-related potential to measure the ability of RTT patients to decode and store occasional duration deviations in a stream of auditory stimuli. Sensory memory for duration, crucial for speech comprehension, has not been studied in RTT.High-density electroencephalography was successfully recorded in 18 females with RTT and 27 age-matched typically developing (TD) controls (aged 6-22 years). Data from seven RTT and three TD participants were excluded for excessive noise. Stimuli were 1 kHz tones with a standard duration of 100 ms and deviant duration of 180 ms. To assess the sustainability of sensory memory, stimulus presentation rate was varied with stimulus onset asynchronies (SOAs) of 450, 900, and 1800 ms. MMNs with maximum negativity over fronto-central scalp and a latency of 220-230 ms were clearly evident for each presentation rate in the TD group, but only for the shortest SOA in the RTT group. Repeated-measures ANOVA revealed a significant group by SOA interaction. MMN amplitude correlated with age in the TD group only. MMN amplitude was not correlated with the Rett Syndrome Severity Scale. This study indicates that while RTT patients can decode deviations in auditory duration, the span of this sensory memory system is severely foreshortened, with likely implications for speech decoding abilities.

Identification of genes that promote or inhibit olfactory memory formation in Drosophila.

Genetic screens in Drosophila melanogaster and other organisms have been pursued to filter the genome for genetic functions important for memory formation. Such screens have employed primarily chemical or transposon-mediated mutagenesis and have identified numerous mutants including classical memory mutants, dunce and rutabaga. Here, we report the results of a large screen using panneuronal RNAi expression to identify additional genes critical for memory formation. We identified >500 genes that compromise memory when inhibited (low hits), either by disrupting the development and normal function of the adult animal or by participating in the neurophysiological mechanisms underlying memory formation. We also identified >40 genes that enhance memory when inhibited (high hits). The dunce gene was identified as one of the low hits and further experiments were performed to map the effects of the dunce RNAi to the α/ß and γ mushroom body neurons. Additional behavioral experiments suggest that dunce knockdown in the mushroom body neurons impairs memory without significantly affecting acquisition. We also characterized one high hit, sickie, to show that RNAi knockdown of this gene enhances memory through effects in dopaminergic neurons without apparent effects on acquisition. These studies further our understanding of two genes involved in memory formation, provide a valuable list of genes that impair memory that may be important for understanding the neurophysiology of memory or neurodevelopmental disorders, and offer a new resource of memory suppressor genes that will aid in understanding restraint mechanisms employed by the brain to optimize resources.

Dopamine is required for learning and forgetting in Drosophila.

Psychological studies in humans and behavioral studies of model organisms suggest that forgetting is a common and biologically regulated process, but the molecular, cellular, and circuit mechanisms underlying forgetting are poorly understood. Here we show that the bidirectional modulation of a small subset of dopamine neurons (DANs) after olfactory learning regulates the rate of forgetting of both punishing (aversive) and rewarding (appetitive) memories. Two of these DANs, MP1 and MV1, exhibit synchronized ongoing activity in the mushroom body neuropil in alive and awake flies before and after learning, as revealed by functional cellular imaging. Furthermore, while the mushroom-body-expressed dDA1 dopamine receptor is essential for the acquisition of memory, we show that the dopamine receptor DAMB, also highly expressed in mushroom body neurons, is required for forgetting. We propose a dual role for dopamine: memory acquisition through dDA1 signaling and forgetting through DAMB signaling in the mushroom body neurons.