Improving the diagnostic value of lineup rejections.

Erroneous eyewitness identification evidence is likely the leading cause of wrongful convictions. To minimize this error, scientists recommend collecting confidence. Research shows that eyewitness confidence and accuracy are strongly related when an eyewitness identifies someone from an initial and properly administered lineup. However, confidence is far less informative of accuracy when an eyewitness identifies no one and rejects the lineup instead. In this study, I aimed to improve the confidence-accuracy relationship for lineup rejections in two ways. First, I aimed to find the lineup that yields the strongest confidence-accuracy relationship for lineup rejections by comparing the standard, simultaneous procedure used by police worldwide to the novel "reveal" procedure designed by scientists to boost accuracy. Second, I aimed to find the best method for collecting confidence. To achieve this secondary aim, I made use of machine-learning techniques to compare confidence expressed in words to numeric confidence ratings. First, I find a significantly stronger confidence-accuracy relationship for lineup rejections in the reveal than in the standard procedure regardless of the method used to collect confidence. Second, I find that confidence expressed in words captures unique diagnostic information about the likely accuracy of a lineup rejection separate from the diagnostic information captured by numeric confidence ratings. These results inform models of recognition memory and may improve the criminal-legal system by increasing the diagnostic value of a lineup rejection.

RECORD, a high-throughput, customizable system that unveils behavioral strategies leveraged by rodents during foraging-like decision-making.

Translational studies benefit from experimental designs where laboratory organisms use human-relevant behaviors. One such behavior is decision-making, however studying complex decision-making in rodents is labor-intensive and typically restricted to two levels of cost/reward. We design a fully automated, inexpensive, high-throughput framework to study decision-making across multiple levels of rewards and costs: the REward-COst in Rodent Decision-making (RECORD) system. RECORD integrates three components: 1) 3D-printed arenas, 2) custom electronic hardware, and 3) software. We validated four behavioral protocols without employing any food or water restriction, highlighting the versatility of our system. RECORD data exposes heterogeneity in decision-making both within and across individuals that is quantifiably constrained. Using oxycodone self-administration and alcohol-consumption as test cases, we reveal how analytic approaches that incorporate behavioral heterogeneity are sensitive to detecting perturbations in decision-making. RECORD is a powerful approach to studying decision-making in rodents, with features that facilitate translational studies of decision-making in psychiatric disorders.

Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 enhanced osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge produced consistent bone bridging of a critically sized rat femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized to treat a variety of spine disorders.

Feeling the future of eyewitness research.

For decades, eyewitness memory research has had the worthy goal of minimizing the chances that an innocent suspect is falsely identified. However, this is not the only goal. Partial receiver operating characteristic (ROC) curves provide a way to identify lineup procedures that keep the false alarm rate low while also maximizing the hit rate. Recently, there have been attempts to extend the ROC curve into high false alarm rate regions that fair lineups are intentionally designed to avoid. These new full ROCs could provide a way for the police to circumvent the protections offered by fillers in a fair lineup. Moreover, these attempts to extend the ROC curve are not based on a mathematically coherent model of latent diagnostic signals. In this article, we empirically demonstrate how this lack of a solid foundation can lead to dubious conclusions, such as eyewitnesses possessing precognition and being able to reliably identify the person they will see commit a crime in the future.

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine.

Background: Only a subset of individuals who encounter drugs of abuse become habitual users. Aversive subjective effects like coughing and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop a clinically relevant model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigating whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions. Methods: Twenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2 hr/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR). Results: We identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who "overindulge" on their first use and subsequently find self-administration to be aversive. Conclusions: Our novel model mimics real-world variability in initial interactions with drugs of abuse and yields three distinct groups that differ in self-administration patterns and aversive cue valuation.

The thin red line: Blood planning factors and the enduring need for a robust military blood system to support combat operations.

ABSTRACT: Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.

A microfluidic approach to study variations in Chlamydomonas reinhardtii alkaline phosphatase activity in response to phosphate availability.

Algal growth depends strongly on phosphorus (P) as a key nutrient, underscoring the significance of monitoring P levels. Algal species display a sensitive response to fluctuations in P availability, notably through the expression of alkaline phosphatase (AP) when challenged with P-depletion. As such, alkaline phosphatase activity (APA) serves as a valuable metric for P availability, offering insights into how algae utilize and fix available P resources. However, current APA quantification methods lack single cell resolution, while also being time- and reagent consuming. Microfluidics offers a promising cost-effective solution to these limitations, providing a platform for precise single-cell analysis. In this study, a trap-based microfluidic device was integrated with a commercially available AP live stain to study the single cell APA response of a model algae strain, Chlamydomonas reinhardtii, when exposed to different exogenous P levels. A three-step culture-starve-spike process was used to induce APA in cells cultured under two different basal P levels (1 and 21 mM). When challenged with different spiked P levels (ranging from 0.1-41 mM), C. reinhardtii cells demonstrated a highly heterogeneous APA response. Two-way ANOVA confirmed that this response is influenced by both spiked and basal P levels. Utilizing an unsupervised machine learning approach (HDBSCAN), distinct subpopulations of C. reinhardtii cells were identified exhibiting varying levels of APA at the single-cell level. These subpopulations encompass significant groups of individual cells with either notably high or low APA, contributing to the overall behavior of the cohorts. Considerable intrapopulation differences in APA were observed across cohorts with similar average behavior. For instance, while some cohorts exhibited a concentrated distribution around the overall average APA, others displayed subpopulations dispersed across a wider range of APA levels. This underscores the potential bias introduced by analyzing a small number of cells in bulk, which may skew results by overrepresenting extreme behavioral subpopulations. The findings if this study highlight the need for analytical approaches that account for single cell heterogeneity in APA and demonstrate the utility of microfluidics as a well-suited means for such investigations. This study illuminates the complexities of APA regulation at the single cell level, providing crucial insights that advance our understanding of algal phosphorus metabolism and environmental responses.

Polymerase theta is a synthetic lethal target for killing Epstein-Barr virus lymphomas.

Treatment options for Epstein-Barr virus (EBV)-cancers are limited, underscoring the need for new therapeutic approaches. We have previously shown that EBV-transformed cells and cancers lack homologous recombination (HR) repair, a prominent error-free pathway that repairs double-stranded DNA breaks; instead, EBV-transformed cells demonstrate genome-wide scars of the error-prone microhomology-mediated end joining (MMEJ) repair pathway. This suggests that EBV-cancers are vulnerable to synthetic lethal therapeutic approaches that target MMEJ repair. Indeed, we have previously found that targeting PARP, an enzyme that contributes to MMEJ, results in the death of EBV-lymphoma cells. With the emergence of clinical resistance to PARP inhibitors and the recent discovery of inhibitors of Polymerase theta (POLθ), the polymerase essential for MMEJ, we investigated the role of POLθ in EBV-lymphoma cells. We report that EBV-transformed cell lines, EBV-lymphoma cell lines, and EBV-lymphomas in AIDS patients demonstrate greater abundance of POLθ, driven by the EBV protein EBNA1, compared to EBV-uninfected primary lymphocytes and EBV-negative lymphomas from AIDS patients (a group that also abundantly expresses POLθ). We also find POLθ enriched at cellular DNA replication forks and exposure to the POLθ inhibitor Novobiocin impedes replication fork progress, impairs MMEJ-mediated repair of DNA double-stranded breaks, and kills EBV-lymphoma cells. Notably, cell killing is not due to Novobiocin-induced activation of the lytic/replicative phase of EBV. These findings support a role for POLθ not just in DNA repair but also DNA replication and as a therapeutic target in EBV-lymphomas and potentially other EBV-cancers as EBNA1 is expressed in all EBV-cancers.IMPORTANCEEpstein-Barr virus (EBV) contributes to ~2% of the global cancer burden. With a recent estimate of >200,000 deaths a year, identifying molecular vulnerabilities will be key to the management of these frequently aggressive and treatment-resistant cancers. Building on our earlier work demonstrating reliance of EBV-cancers on microhomology-mediated end-joining repair, we now report that EBV lymphomas and transformed B cell lines abundantly express the MMEJ enzyme POLθ that likely protects cellular replication forks and repairs replication-related cellular DNA breaks. Importantly also, we show that a newly identified POLθ inhibitor kills EBV-cancer cells, revealing a novel strategy to block DNA replication and repair of these aggressive cancers.

Perinatal substance use disorder: Examining the impact on adverse pregnancy outcomes.

Objective: Substance use disorder is a growing concern in the USA, especially among pregnant women. This study was undertaken to assess the impact of substance use disorder on adverse pregnancy outcomes using a nationwide sample of inpatient pregnancy hospitalizations in the USA, and to elucidate the influence on each type of adverse pregnancy outcome. Study design: A cross-sectional analysis of inpatient pregnancy hospitalizations in the USA from the Healthcare Cost and Utilization Project National Inpatient Sample from 2016 to 2020 was conducted. International Classification of Diseases - 10th revision and diagnosis-related group codes were used to identify inpatient pregnancy-related delivery hospitalizations with a substance use disorder and/or adverse pregnancy outcomes. Propensity score matching and multiple logistic regression analyses were undertaken to predict the likelihood of adverse pregnancy outcomes among pregnancy hospitalizations with and without substance use disorder. Subgroup analyses were performed to estimate the impact of substance use disorder on each adverse pregnancy outcome. Results: From 3,238,558 hospitalizations, the prevalence of adverse pregnancy outcomes was substantially higher among pregnancy hospitalizations with substance use disorder (35.6 %) compared with pregnancy hospitalizations without substance use disorder (25.1 %, p < 0.001). After matching and model adjustment for sociodemographic covariates, substance use disorder was identified as an independent predictor of adverse pregnancy outcomes [adjusted odds ratio (aOR) 1.47, 95 % confidence interval (CI) 1.45-1.49]. In subgroup analyses based on type of adverse pregnancy outcome, the greatest exposure risks were fetal growth restriction (aOR 1.96, 95 % CI 1.91-2.01), antepartum hemorrhage (aOR 1.79, 95 % CI 1.73-1.85) and preterm birth (aOR 1.65, 95 % CI 1.62-1.68). Conclusion: Patients with substance use disorder are at higher risk of adverse pregnancy outcomes, particularly fetal growth restriction, antepartum hemorrhage and preterm birth.

New Insights on Expert Opinion About Eyewitness Memory Research.

Experimental psychologists investigating eyewitness memory have periodically gathered their thoughts on a variety of eyewitness memory phenomena. Courts and other stakeholders of eyewitness research rely on the expert opinions reflected in these surveys to make informed decisions. However, the last survey of this sort was published more than 20 years ago, and the science of eyewitness memory has developed since that time. Stakeholders need a current database of expert opinions to make informed decisions. In this article, we provide that update. We surveyed 76 scientists for their opinions on eyewitness memory phenomena. We compared these current expert opinions to expert opinions from the past several decades. We found that experts today share many of the same opinions as experts in the past and have more nuanced thoughts about two issues. Experts in the past endorsed the idea that confidence is weakly related to accuracy, but experts today acknowledge the potential diagnostic value of initial confidence collected from a properly administered lineup. In addition, experts in the past may have favored sequential over simultaneous lineup presentation, but experts today are divided on this issue. We believe this new survey will prove useful to the court and to other stakeholders of eyewitness research.

Deep-pelagic fishes: Demographic instability in a stable environment.

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso- and bathy-pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep-pelagic could make deep-pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep-pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep-pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep-pelagic ecosystems. Frequency-based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep-pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep-pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes.

Moral injury, race-related stress and post-traumatic stress disorder in a trauma-exposed Black population.

BACKGROUND: Race-related stress (RRS) is an unrecognized source of moral injury (MI)-or the emotional and/or spiritual suffering that may emerge after exposure to events that violate deeply held beliefs. Additionally, MI has not been explored as a mechanism of risk for post-traumatic stress disorder (PTSD) in trauma-exposed civilians. We examined relations among exposure to potentially morally injurious events (moral injury exposure, MIE), related distress (moral injury distress, MID), and RRS in Black Americans. Potential indirect associations between RRS and PTSD symptoms via MID were also examined. METHODS: Black Americans (n = 228; 90.4% female; Mage = 31.6 years. SDage = 12.8 years) recruited from an ongoing study of trauma completed measures assessing civilian MIE and MID, RRS, and PTSD. Bivariate correlations were conducted with MIE and MID, and mediation analysis with MID, to examine the role of MI in the relationship between RRS and PTSD symptom severity. RESULTS: MIE was significantly correlated with cultural (r = 0.27), individual (r = 0.29), and institutional (r = 0.25) RRS; MID also correlated with cultural (r = 0.31), individual (r = 0.31), and institutional (r = 0.26) RRS (ps < 0.001). We found an indirect effect of RRS on PTSD symptoms via MID (ß = 0.10, p < 0.005). CONCLUSIONS: All types of RRS were associated with facets of MI, which mediated the relationship between RRS and current PTSD symptoms. MI may be a potential mechanism through which RRS increases the risk for PTSD in Black individuals.

Local FK506 delivery induces osteogenesis in in vivo rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 potentiated the effect of low dose BMP-2 to enhance osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge, produced consistent bone bridging of a rat critically-sized femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized either as a standalone treatment or in conjunction with rhBMP to treat a variety of spine disorders.

18-Month-Old with Lethargy and Accelerated Idioventricular Rhythm in Prehospital Setting: A Case Report.

INTRODUCTION: We report a case of accelerated idioventricular rhythm (AIVR) identified by Emergency Medical Services (EMS) monitoring of an infant presenting with lethargy and respiratory distress. Accelerated idioventricular rhythms are rare ventricular rhythms originating from the His-Purkinje system or ventricular myocytes, consisting of >3 monomorphic beats with gradual onset and termination.1 An AIVR is usually well-tolerated and does not require treatment, though sustained arrythmia may induce syncope, and the rhythm has been seen in newborn infants with congenital heart diseases.1 Monitoring ill children with ECG can identify such dysrhythmias in the prehospital setting. CASE REPORT: An 18-month-old male presented to their pediatrician with lethargy and respiratory distress, prompting activation of EMS. The patient was placed on a 4-lead ECG initially revealing monomorphic QRS complexes at a rate of 170 beats per minute (BPM). A 12-lead ECG was interpreted as sinus tachycardia by the paramedics who noted the QRS complexes were "getting taller and shorter" with a stable rapid heart rate. The clinician then noted a consistently wide tachycardia which spontaneously converted to a narrow complex tachycardia. The QRS pattern remained variable, with notation of variable R-wave height. After arrival to the emergency department, pediatric cardiology was consulted and interpreted the prehospital ECG findings as accelerated idioventricular rhythm. The patient experienced multiple occurrences of accelerated idioventricular rhythm during hospitalization without associated hypoxia or decreased perfusion. DISCUSSION: Accelerated idioventricular rhythm is relatively rare entity without underlying cardiac disease and most cases are asymptomatic or benign. In the pediatric population, AIVR is generally related to congenital heart defects, cardiac tumors, and cardiomyopathies. In the prehospital setting, continuous ECG monitoring should be a part of care by Advanced Life Support personnel in children with altered mental status, respiratory distress, unexplained syncope, or suspected arrhythmias and 12 lead ECG should be considered if there is any abnormality noted. While this patient did not experience persisting morbidity from AIVR, the potentially hazardous rhythm would not have been recognized without the astute observation, clinical management and persistent follow up of the prehospital clinicians.

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia.

Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

Comparing Common Risk Assessment Tools to Predict Outcomes in Total Knee Arthroplasty.

BACKGROUND: A number of tools exist to aid surgeons in risk assessment, including the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Index (ECI), and various measures of frailty, such as the Hospital Frailty Risk Score (HFR). While all of these tools have been validated for general use, the best risk assessment tool is still debated. Risk assessment is particularly important in elective surgery, such as total joint arthroplasty. The aim of this study is to compare the predictive power of the CCI, ECI, and HFR in the setting of total knee arthroplasty (TKA). METHODS: All patients who underwent TKA were identified via International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code from the National Readmissions Database, years 2016 to 2019. Patient demographics, perioperative complications, and hospital-associated outcomes were recorded. Receiver operating characteristic (ROC) curves were created and area under the curves (AUCs) evaluated to gauge the predictive capabilities of each risk assessment tool (CCI, ECI, and HFR) across a range of outcomes. RESULTS: A total of 1,930,803 patients undergoing TKA were included in our analysis. For mortality, ECI was most predictive (0.95 AUC), while HFR and CCI were 0.75 and 0.74 AUC, respectively. For periprosthetic fractures, ECI was 0.78 AUC, HFR was 0.68 AUC, and CCI was 0.66 AUC. For joint infections, the ECI was 0.78 AUC, the HFR was 0.63 AUC, and the CCI was 0.62 AUC. For 30-day readmission, ECI was 0.79 AUC, while HFR and CCI were 0.6 AUC. For 30-day reoperation, ECI was 0.69 AUC, while HFR was 0.58 AUC and CCI was 0.56 AUC. CONCLUSIONS: Our analysis shows that ECI is superior to CCI and HFR for predicting 30-day postoperative outcomes following TKA. Surgeons should consider assessing patients using ECI prior to TKA.

Managing Disease-Modifying Antirheumatic Drugs (DMARDs) for Patients Undergoing Elective Spine Surgery: A Pilot Survey.

Introduction: Patients affected by autoimmune pathologies such as rheumatoid arthritis require surgery for various reasons. However, the systemic inflammatory nature of these disease processes often necessitates therapy with disease-modifying antirheumatic drugs (DMARDs). Alteration of these agents in the perioperative period for surgery requires a careful risk-benefit analysis to limit disease flares, infection rates, and secondary revisions. We therefore queried North and South American practices for perioperative management of DMARDs in patients undergoing elective spine surgery. Methods: An institutional review board-approved pilot survey was disseminated to spine surgeons regarding how they managed DMARDs before, during, and after spine surgery. Results: A total of 47 spine surgeons responded to the survey, 37 of whom were neurosurgeons (78.7%) and 10 orthopedic surgeons (21.3%). Of the respondents, 80.9% were from North America, 72.3% were board-certified, 51.1% practiced in academic institutions, and 66.0% performed 50-150 spine surgeries per year. Most respondents consulted a rheumatologist before continuing or withholding a DMARD in the perioperative period (70.2%). As such, a majority of the spine surgeons in this survey withheld DMARDs at an average of 13.8 days before and 19.6 days after spine surgery. Of the spine surgeons who withheld DMARDs before and after spine surgery, the responses were variable with a trend toward no increased risk of postoperative complications. Conclusions: Based on the results of this pilot survey, we found a consensus among spine surgeons to withhold DMARDs before and after elective spine surgery.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry.

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of chemicals of interest that may pose an overall impact on ecological and human health, prioritization strategies must be used to effectively and efficiently highlight chemicals for further investigation. Prioritization can be based on a chemical's physicochemical properties, structure, exposure, and toxicity, in addition to its regulatory status. This Perspective aims to provide a framework for the strategies used for chemical prioritization that can be implemented to facilitate high-quality research and communication of results. These strategies are categorized as either "online" or "offline" prioritization techniques. Online prioritization techniques trigger the isolation and fragmentation of ions from the low-energy mass spectra in real time, with user-defined parameters. Offline prioritization techniques, in contrast, highlight chemicals of interest after the data has been acquired; detected features can be filtered and ranked based on the relative abundance or the predicted structure, toxicity, and concentration imputed from the tandem mass spectrum (MS2). Here we provide an overview of these prioritization techniques and how they have been successfully implemented and reported in the literature to find chemicals of elevated risk to human and ecological environments. A complete list of software and tools is available from https://nontargetedanalysis.org/.