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Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO) and intravenous (IV) routes on maximum plasma concentration (Cmax), the time to maximum concentration (Tmax), return of spontaneous circulation (ROSC), and time to ROSC in a hypovolemic cardiac arrest model.Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7), IO tibia (n=7), cardiopulmonary resuscitation (CPR) + defibrillation (n=7), and a control group that received just CPR (n=7). Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using high-performance liquid chromatography.Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0) but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031) and IV compared to the CPR-only group (p=0.001). There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031) and IO compared to the CPR-only group (p=0.001). There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127). There was no significant difference in Cmax between the IO and IV groups (p=0.079). The mean ± standard deviation of Cmax of the IO group was 58,709 ± 25,463pg/mL compared to the IV group, which was 106,198 ± 62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084). There were no significant differences in odds of ROSC between the tibial IO and IV groups.Conclusion: Prompt access to the vascular system using the IO route can circumvent the interruption in treatment observed with attempting conventional IV access. The IO route is an effective modality for the treatment of hypovolemic cardiac arrest and may be considered first line for rapid vascular access.

BackgroundCellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. Here, we perform methylome analysis of actively dividing and deeply senescent normal human epithelial cells.ResultsWe identify senescence-associated differentially methylated positions (senDMPs) from multiple experiments using cells from one donor. We find that human senDMP epigenetic signatures are positively and significantly correlated with both cancer and ageing-associated methylation dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, which are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that a single senDMP signature can be effectively reversed in a newly-developed protocol of transient senescence reversal.ConclusionsThe senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that may lead to cancer and age-related diseases in humans.

Connectionist architectures constitute a popular method for modelling animal associative learning processes in order to glean insights into the formation of cognitive capacities. Such approaches (based on purely feedforward activity) are considered limited in their ability to capture relational cognitive capacities. Pavlovian learning value-based models, being not based purely on fully connected feedforward structure, have demonstrated learning capabilities that often mimic those of ‘higher’ relational cognition. Capturing data using such models often reveals how associative mechanisms can exploit structure in the experimental setting, so that ‘explicit’ relational cognitive capacities are not, in fact, required. On the other hand, models of relational cognition, implemented as neural networks, permit formation and retrieval of relational representations of varying levels of complexity. The flexible processing capacities of such models are, however, are subject to constraints as to how offline relational versus online (real-time, real-world) processing may be mediated. In the current article, we review the potential for building a connectionist-relational cognitive architecture with reference to the representational rank view of cognitive capacity put forward by Halford et al. Through interfacing system 1-like (connectionist/associative learning) and system 2-like (relational-cognition) computations through a bidirectional affective processing approach, continuity between Halford et al’s cognitive systems may be operationalized according to real world/online constraints. By addressing i) and ii) in this manner, this paper puts forward a testable unifying framework for system 1-like and system 2-like cognition.

IMPORTANCE: Reduction in emergency department (ED) use is frequently viewed as a potential source for cost savings. One consideration has been to deny payment if the patients diagnosis upon ED discharge appears to reflect a nonemergency condition. This approach does not incorporate other clinical factors such as chief complaint that may inform necessity for ED care. OBJECTIVE: To determine whether ED presenting complaint and ED discharge diagnosis correspond sufficiently to support use of discharge diagnosis as the basis for policies discouraging ED use. DESIGN, SETTING, AND PARTICIPANTS: The New York University emergency department algorithm has been commonly used to identify nonemergency ED visits. We applied the algorithm to publicly available ED visit data from the 2009 National Hospital Ambulatory Medical Care Survey (NHAMCS) for the purpose of identifying all primary care-treatable visits. The 2009 NHAMCS data set contains 34,942 records, each representing a unique ED visit. For each visit with a discharge diagnosis classified as primary care treatable, we identified the chief complaint. To determine whether these chief complaints correspond to nonemergency ED visits, we then examined all ED visits with this same group of chief complaints to ascertain the ED course, final disposition, and discharge diagnoses. MAIN OUTCOMES AND MEASURES: Patient demographics, clinical characteristics, and disposition associated with chief complaints related to nonemergency ED visits. RESULTS: Although only 6.3% (95% CI, 5.8%-6.7%) of visits were determined to have primary care-treatable diagnoses based on discharge diagnosis and our modification of the algorithm, the chief complaints reported for these ED visits with primary care-treatable ED discharge diagnoses were the same chief complaints reported for 88.7% (95% CI, 88.1%-89.4%) of all ED visits. Of these visits, 11.1% (95% CI, 9.3%-13.0%) were identified at ED triage as needing immediate or emergency care; 12.5% (95% CI, 11.8%-14.3%) required hospital admission; and 3.4% (95% CI, 2.5%-4.3%) of admitted patients went directly from the ED to the operating room. CONCLUSIONS AND RELEVANCE: Among ED visits with the same presenting complaint as those ultimately given a primary care-treatable diagnosis based on ED discharge diagnosis, a substantial proportion required immediate emergency care or hospital admission. The limited concordance between presenting complaints and ED discharge diagnoses suggests that these discharge diagnoses are unable to accurately identify nonemergency ED visits.

ImportanceReduction in emergency department (ED) use is frequently viewed as a potential source for cost savings. One consideration has been to deny payment if the patient's diagnosis upon ED discharge appears to reflect a "nonemergency" condition. This approach does not incorporate other clinical factors such as chief complaint that may inform necessity for ED care.ObjectiveTo determine whether ED presenting complaint and ED discharge diagnosis correspond sufficiently to support use of discharge diagnosis as the basis for policies discouraging ED use.Design, setting, and participantsThe New York University emergency department algorithm has been commonly used to identify nonemergency ED visits. We applied the algorithm to publicly available ED visit data from the 2009 National Hospital Ambulatory Medical Care Survey (NHAMCS) for the purpose of identifying all "primary care-treatable" visits. The 2009 NHAMCS data set contains 34,942 records, each representing a unique ED visit. For each visit with a discharge diagnosis classified as primary care treatable, we identified the chief complaint. To determine whether these chief complaints correspond to nonemergency ED visits, we then examined all ED visits with this same group of chief complaints to ascertain the ED course, final disposition, and discharge diagnoses.Main outcomes and measuresPatient demographics, clinical characteristics, and disposition associated with chief complaints related to nonemergency ED visits.ResultsAlthough only 6.3% (95% CI, 5.8%-6.7%) of visits were determined to have primary care-treatable diagnoses based on discharge diagnosis and our modification of the algorithm, the chief complaints reported for these ED visits with primary care-treatable ED discharge diagnoses were the same chief complaints reported for 88.7% (95% CI, 88.1%-89.4%) of all ED visits. Of these visits, 11.1% (95% CI, 9.3%-13.0%) were identified at ED triage as needing immediate or emergency care; 12.5% (95% CI, 11.8%-14.3%) required hospital admission; and 3.4% (95% CI, 2.5%-4.3%) of admitted patients went directly from the ED to the operating room.Conclusions and relevanceAmong ED visits with the same presenting complaint as those ultimately given a primary care-treatable diagnosis based on ED discharge diagnosis, a substantial proportion required immediate emergency care or hospital admission. The limited concordance between presenting complaints and ED discharge diagnoses suggests that these discharge diagnoses are unable to accurately identify nonemergency ED visits.

PurposeTo assess structural, functional, and visual behavioral relationships in mutant rhodopsin transgenic (Tg) rats and to determine whether early optokinetic tracking (OKT) visual experience, known to permanently elevate visual thresholds in normal rats, can enhance vision in rats with photoreceptor degeneration.MethodsEight lines of pigmented Tg rats and RCS rats were used in this study. OKT thresholds were tested at single ages (1, 2, 3, 4, and 6 months) in naïve groups of rats, or daily in groups that began at eye-opening (P15) or 10 days later (P25). Electroretinogram (ERG) response amplitudes were recorded after OKT testing, and outer nuclear layer (ONL) thickness measurements were then obtained.ResultsOKT thresholds, when measured at a single time point in naïve Tg lines beginning at P30, did not decline until months after significant photoreceptor loss. Daily testing of Tg lines resulted mostly with OKT thresholds inversely related to photoreceptor degeneration, with rapid degenerations resulting in sustained OKT thresholds for long periods despite the rapid photoreceptor loss. Slower degenerations resulted in rapid decline of thresholds, long before the loss of most photoreceptors, which was even more pronounced when daily testing began at eye opening. This amplified loss of function was not a result of testing-induced damage to the rod or cone photoreceptors, as ERG amplitudes and ONL thicknesses were the same as untested controls.ConclusionsThe unexpected lack of correlation of OKT testing with photoreceptor degeneration in the Tg rats emphasizes the need in behavioral therapeutic studies for careful analysis of visual thresholds of experimental animals prior to therapeutic intervention.