Sepsis-2.5: Resolving Conflicts Between Payers and Providers
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ABSTRACT:
SUBMITTER: Rodenberg H
PROVIDER: S-EPMC10462079 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Agriculture dominates the planet. Yet it has many environmental costs that are unsustainable, especially as global food demand rises. Here, we evaluate ways in which different parts of the world are succeeding in their attempts to resolve conflict between agriculture and wild nature. We envision that coordinated global action in conserving land most sensitive to agricultural activities and policies that internalise the environmental costs of agriculture are needed to deliver a more sustainable future.
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Project description:Understanding phosphoryl and sulfuryl transfer is central to many biochemical processes. However, despite decades of experimental and computational studies, a consensus concerning the precise mechanistic details of these reactions has yet to be reached. In this work we perform a detailed comparative theoretical study of the hydrolysis of p-nitrophenyl phosphate, methyl phosphate and p-nitrophenyl sulfate, all of which have served as key model systems for understanding phosphoryl and sulfuryl transfer reactions, respectively. We demonstrate the existence of energetically similar but mechanistically distinct possibilities for phosphate monoester hydrolysis. The calculated kinetic isotope effects for p-nitrophenyl phosphate provide a means to discriminate between substrate- and solvent-assisted pathways of phosphate monoester hydrolysis, and show that the solvent-assisted pathway dominates in solution. This preferred mechanism for p-nitrophenyl phosphate hydrolysis is difficult to find computationally due to the limitations of compressing multiple bonding changes onto a 2-dimensional energy surface. This problem is compounded by the need to include implicit solvation to at least microsolvate the system and stabilize the highly charged species. In contrast, methyl phosphate hydrolysis shows a preference for a substrate-assisted mechanism. For p-nitrophenyl sulfate hydrolysis there is only one viable reaction pathway, which is similar to the solvent-assisted pathway for phosphate hydrolysis, and the substrate-assisted pathway is not accessible. Overall, our results provide a unifying mechanistic framework that is consistent with the experimentally measured kinetic isotope effects and reconciles the discrepancies between theoretical and experimental models for these biochemically ubiquitous classes of reaction.
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Project description:We examine the effect of commercial dental insurance concentration on the size of dental practices, the decision of dentists to own a practice, and the choice of dentists to work at a dental management service organization-a type of corporate group practice that has become more prevalent in the United States in recent years. Using 2013-2015 dentist-level data from the American Dental Association, county-level data on firms and employment from the United States Census, and commercial dental insurance market concentration data from FAIR Health®, we find a modest effect of dental insurance market concentration on the size of dental practices. We also find that a higher level of commercial dental insurance market concentration is associated with a dentist's decision not to own a practice. There is inconclusive evidence that higher levels of dental insurance market concentration impact a dentist's decision to affiliate with a dental management service organization. Overall, our findings imply that dentists consolidate in response to increases in concentration among commercial dental insurers.
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Project description:ObjectiveTo evaluate the linkage of claims from the Utah All Payers Claims Database (APCD) and Utah Cancer Registry (UCR).Data sourcesSecondary data from 2013 and 2014 Utah APCD and 2013 UCR cases.Study designThis is a descriptive analysis of the quality of linkage between APCD claims data and cancer registry cases.Data collection/extraction methodsWe used the LinkPlus software to link Utah APCD and UCR data.Principal findingsWe were able to link 82.4 percent (9441/11 453) of the UCR reportable cancer cases with APCD claims. Of those linked, 66 percent were perfect matches.ConclusionsThe quality of identifiers is high, evidence that claims data can potentially supplement cancer registry data for use in research.
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Project description:IntroductionAccurate phylogenetic reconstruction is crucial for understanding evolutionary relationships and biodiversity. Despite advances in molecular systematics, the relationships within Pandanales-which include Cyclanthaceae, Pandanaceae, Stemonaceae, Triuridaceae, and Velloziaceae-remain unresolved. This study aims to clarify these relationships by analyzing transcriptomic and genomic data from these families.MethodsWe analyzed transcriptomic and genomic data from 20 samples representing all five families of Pandanales. Our approach involved assembling 2,668 single-copy orthologous genes (SCOGs) and conducting phylogenetic analyses using both coalescent- and concatenation-based methods, alongside plastid genome data. Additionally, we employed HyDe for gene flow analysis and conducted coalescent simulations and QuIBL analyses to explore sources of phylogenetic conflict. We also investigated whole-genome duplication (WGD) events within Pandanales.ResultsThe phylogenetic analyses produced strongly supported but topologically incongruent trees. Our gene flow analysis suggested that the concatenation-based topology likely reflects the true evolutionary history of Pandanales. We identified two significant ancient gene flow events: one between Velloziaceae and Triuridaceae, and another between Triuridaceae and the C-P clade (Cyclanthaceae + Pandanaceae). Furthermore, we detected five whole-genome duplication (WGD) events, including two that occurred before the Cretaceous-Paleogene boundary in Stemonaceae and Pandanaceae, one in Triuridaceae during the mid-Paleogene, and two within Velloziaceae near the Paleogene-Neogene boundary.DiscussionOur findings indicate that gene flow, rather than incomplete lineage sorting, is the primary source of phylogenetic conflict at certain nodes within Pandanales. The identified WGD events likely played a significant role in facilitating adaptation and diversification under changing environmental conditions. These results not only resolve long-standing phylogenetic conflicts but also enhance our understanding of the mechanisms driving plant diversification within this order.
| S-EPMC11891173 | biostudies-literature
Project description:BackgroundDifferent factors may lead to hepatitis. Among which are liver inflammation and poisoning. We chose two hepatitis models, typical for these two underlying causes. Thus, we aimed to characterize the role of protease-activated receptor 2 (Par2) in liver regeneration and inflammation to reconcile Par2 conflicting role in many damage models, which sometimes aggravates the induced damage and sometimes alleviates it.MethodsWT and knockout (Par2KO) mice were injected with concanavalin A (ConA) to induce immune-mediated hepatitis or with carbon tetrachloride (CCl4) to elicit direct hepatic damage. To distinguish the immune component from the liver regenerative response, we conducted bone marrow (BM) replacements of WT and Par2KO mice and repeated the damage models.ResultsConA injection caused limited damage in Par2KO mice livers, while in the WT mice severe damage followed by leukocyte infiltration was evident. Reciprocal BM replacement of WT and Par2KO showed that WT BM-reconstituted Par2KO mice displayed marked liver damage, while in Par2KO BM-reconstituted WT mice, the tissue was generally protected. In the CCl4 direct damage model, hepatocytes regenerated in WT mice, whereas Par2KO mice failed to recover. Reciprocal BM replacement did not show significant differences in hepatic regeneration. In Par2KO mice, hepatitis was more apparent, while WT recovered regardless of the BM origin.ConclusionsWe conclude that Par2 activation in the immune system aggravates hepatitis and that Par2 activation in the damaged tissue promotes liver regeneration. When we incorporate this finding and revisit the literature reports, we reconciled the conflicts surrounding Par2's role in injury, recovery, and inflammation.
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Project description:As stresses on groundwater resources increase due to growing population and climate change, water litigation, such as the recently decided Mississippi (MS) vs Tennessee (TN) lawsuit, will become more common. In the United States, lawsuits between states can be heard only by the Supreme Court of the United States (SCOTUS). These lawsuits are expensive and lengthy, often requiring highly specialized technical expertise. In the MS vs TN case, the Court unanimously held that an interstate aquifer is subject to equitable apportionment. Although this appears to be a sound resolution, a careful examination of the SCOTUS hearing transcript revealed that the Justices had several egregious misconceptions about the groundwater system. These misconceptions arose in part due to the failure of technical experts to communicate groundwater concepts in understandable terms and in part due to the Justices' lack of expertise in groundwater science. To address these issues, we first explore methods for improving scientific communication in courtrooms. Second, we propose ideas for reforming the legal system and provide compelling arguments for using the lower courts to hear such cases. We also explore the possibility of creating specialized federal water courts to resolve water disputes.
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Project description:ObjectiveProper inflammation resolution is crucial to prevent runaway inflammation during sepsis and reduce sepsis-related mortality/morbidity. Previous studies suggest that deleting TRAM, a key TLR4 signaling adaptor, can reprogram the first inflammatory responder cell-neutrophil from an inflammatory state to a resolving state. In this study, we aim to examine the therapeutic potential of TRAM-deficient neutrophils in vivo with recipient mice undergoing experimental sepsis.Material and methodsWild-type or Tram-/- mice were intraperitoneally injected with cecal slurry to induce either severe or mild sepsis. Phenotypic examinations of sepsis and neutrophil characteristics were examined in vivo and ex vivo. The propagations of resolution from donor neutrophils to recipient cells such as monocytes, T cells, and endothelial cells were examined through co-culture assays in vitro. The efficacies of Tram-/- neutrophils in reducing inflammation were studied by transfusing either wild-type or Tram-/- neutrophils into septic recipient mice.ResultsTram-/- septic mice had improved survival and attenuated injuries within the lung and kidney tissues as compared to wild-type septic mice. Wild-type septic mice transfused with Tram-/- resolving neutrophils exhibited reduced multi-organ damages and improved cellular homeostasis. In vitro co-culture studies revealed that donor Tram-/- neutrophils can effectively propagate cellular homeostasis to co-cultured neighboring monocytes, neutrophils, T cells as well as endothelial cells.ConclusionsNeutrophils with TRAM deletion render effective reprogramming into a resolving state beneficial for ameliorating experimental sepsis, with therapeutic potential in propagating cellular and tissue homeostasis as well as treating sepsis.
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Project description:IntroductionCognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear.MethodsTo further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based event-related potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory theta-burst stimulation-a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)-over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices.ResultsThe results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials ("Gratton effect") that was only accomplished with an intact DLPFC (i.e., following placebo stimulation).DiscussionBecause non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities.
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Project description:BackgroundMeasuring care coordination in administrative data facilitates important research to improve care quality.ObjectiveTo compare shared patient networks constructed from administrative claims data across multiple payers.DesignSocial network analysis of pooled cross sections of physicians treating prevalent colorectal cancer patients between 2003 and 2013.ParticipantsSurgeons, medical oncologists, and radiation oncologists identified from North Carolina Central Cancer Registry data linked to Medicare claims (N = 1735) and private insurance claims (N = 1321).Main measuresProvider-level measures included the number of patients treated, the number of providers with whom they share patients (by specialty), the extent of patient sharing with each specialty, and network centrality. Network-level measures included the number of providers and shared patients, the density of shared-patient relationships among providers, and the size and composition of clusters of providers with a high level of patient sharing.ResultsFor 24.5% of providers, total patient volume rank differed by at least one quintile group between payers. Medicare claims missed 14.6% of all shared patient relationships between providers, but captured a greater number of patient-sharing relationships per provider compared with the private insurance database, even after controlling for the total number of patients (27.242 vs 26.044, p < 0.001). Providers in the private network shared a higher fraction of patients with other providers (0.226 vs 0.127, p < 0.001) compared to the Medicare network. Clustering coefficients for providers, weighted betweenness, and eigenvector centrality varied greatly across payers. Network differences led to some clusters of providers that existed in the combined network not being detected in Medicare alone.ConclusionMany features of shared patient networks constructed from a single-payer database differed from similar networks constructed from other payers' data. Depending on a study's goals, shortcomings of single-payer networks should be considered when using claims data to draw conclusions about provider behavior.
| S-EPMC6816773 | biostudies-literature