Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis.

BACKGROUND: Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. METHODS: Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019. RESULTS: Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01). CONCLUSION: SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Nationwide Incidence and Trends in Central Retinal Arterial Occlusion Management: A 5000-Patient Analysis.

Central retinal artery occlusion (CRAO) is a rare and visually debilitating vascular condition characterized by sudden and severe vision loss. CRAO is a compelling target for intravenous alteplase (tPA) and endovascular mechanical thrombectomy (MT) due to pathophysiological similarities with acute ischemic stroke; however, the utility of these interventions in CRAO remains dubious due to limited sample sizes and potential risks. To assess usage and outcomes of tPA and MT in CRAO, we queried the National Inpatient Sample database using International Classification of Disease, Ninth and Tenth edition for patients with CRAO and acute ischemic stroke between 2010 and 2019. Our cohort of 5009 CRAO patients were younger with higher rates of obesity, hypertension, long-term anticoagulant use, and tobacco use compared to acute ischemic stroke patients. CRAO patients had lower rates of tPA administration (3.41% vs 6.21%) and endovascular MT (0.38% vs 1.31%) but fewer complications, including deep vein thrombosis, pneumonia, urinary tract infection, acute kidney injury, and acute myocardial infarction (all P < 0.01). CRAO patients had lower rates of poor functional outcome (31.74% vs 58.1%) and in-hospital mortality (1.2% vs 5.64%), but higher rates of profound blindness (9.24% vs 0.58%). A multivariate regression showed no relationship between tPA and MT and profound blindness, although the limited sample size of patients receiving interventions may have contributed to this apparent insignificance. Further investigation of larger patient cohorts and alternative treatment modalities could provide valuable insights for revascularization therapies in CRAO to optimize visual restoration and clinical outcomes.

Ultra-Early Hemostatic Therapy for Acute Intracerebral Hemorrhage: An Updated Review.

Intracerebral hemorrhage (ICH) is the second most common type of stroke, accounting for approximately 10-20% of all strokes, and is linked to severe neurological disability and death. Since the most accurate predictor of outcome in patients with ICH is hematoma volume, there is a great need for pharmacologic therapy that can reduce hematoma expansion and resultant mass effect and edema. This is especially critical within the ultra-early window of 3-4 hours after the presentation. Hemostatic therapies are exceptionally important for those patients taking antiplatelet or anticoagulant medications to reverse the effects of these medications and therefore prevent hematoma expansion. Furthermore, the recent publication of the 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage by the American Heart Association/American Stroke Association, the first update to the guidelines since 2012, underscores the importance of optimizing anticoagulation reversal for this population. The purpose of this selective, nonsystematic review is to examine current literature regarding the use of hemostatic therapies in ICH, with particular attention paid to antiplatelet, anticoagulation, and antifibrinolytic therapies.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

Frailty as a Predictor of Outcomes in Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using "Subarachnoid hemorrhage AND frailty" and "subarachnoid hemorrhage AND frail" as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients (p < 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model (p < 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients.

Neuroendovascular Surgery Applications in Craniocervical Trauma.

Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions.

The gut-brain connection: Inflammatory bowel disease increases risk of acute ischemic stroke.

OBJECTIVES: Chronic inflammation of the gastrointestinal tract is a hallmark of inflammatory bowel disease (IBD). This increased inflammation is thought to induce a hypercoagulable state that increases the risk for stroke. However, few studies have examined the association between IBD and acute ischemic stroke (AIS). Thus, this study aims to investigate the incidence, treatments, complications, and outcomes of AIS in patients with IBD. MATERIALS & METHODS: ICD-9-CM and ICD-10-CM codes were used to query the National Inpatient Sample for AIS and IBD diagnosis. Baseline demographics, clinical characteristics, complications, treatments, and outcomes were assessed through descriptive statistics, multivariate regression, and propensity score matching (PSM) analysis. Acute stroke severity was assessed using the National Institute of Heath's Stroke Severity Score (SSS) as a template. RESULTS: 1,609,817 patients were diagnosed with AIS between 2010 through 2019. 7468 (0.46%) had concomitant diagnoses of IBD. AIS patients with IBS were younger, more likely to be white and female, but less likely to be obese. Although IBD patients had comparable stroke severities (p = 0.64) to their non-IBS counterparts, they received stroke intervention at statistically different rates than their non-IBD counterparts. Additionally, IBD patients had higher rates of in-hospital complications (p < 0.01) and longer lengths of stay (LOS) (p < 0.01). CONCLUSIONS: IBD patients develop AIS at a younger age with similar rates of stroke severity to their non-IBD counterparts, but receive higher rates of tissue plasminogen activator administration and decreased rates of mechanical thrombectomy. Our research shows that patients with IBD are at risk for AIS at an earlier age and are more likely to have complications. This underlies a connection between IBD and a hypercoagulable state that could predispose patients to AIS.

Enhancing measures of ESE to incorporate aspects of place: Personal reputation and place-based social legitimacy.

We argue that existing measures of entrepreneurial self-efficacy (ESE) are underspecified in the context of tight-knit communities, where personal reputation plays a major role. We propose a new place-based ESE dimension that measures assessment by individuals of their ability to elicit respect from their community. This integral ESE component points to the very meaning of entrepreneurship in highly relational contexts. Although our enhanced ESE measure incorporates some influences of place, other aspects, such as geographical context, continue to moderate the relationship between ESE and entrepreneurial aptitude. We conclude with a discussion of the relevance and utility of this enhanced measure.

Effect of Behaviorally Designed Gamification With Social Incentives on Lifestyle Modification Among Adults With Uncontrolled Diabetes: A Randomized Clinical Trial.

Importance: Gamification is increasingly being used to promote healthy behaviors. However, it has not been well tested among patients with chronic conditions and over longer durations. Objective: To test the effectiveness of behaviorally designed gamification interventions to enhance support, collaboration, or competition to promote physical activity and weight loss among adults with uncontrolled type 2 diabetes. Design, Setting, and Participants: A 4-arm randomized clinical trial with a 1-year intervention was conducted from January 23, 2017, to January 27, 2020, with remotely monitored intervention. Analyses were conducted between February 10 and October 6, 2020. Participants included 361 adults with type 2 diabetes with hemoglobin A1c levels greater than or equal to 8% and body mass index greater than or equal to 25. Interventions: All participants received a wearable device, smart weight scale, and laboratory testing. Participants in the control group received feedback from their devices but no other interventions. Participants in the gamification arms conducted goal setting and were entered into a 1-year game designed using insights from behavioral economics with points and levels for achieving step goals and weight loss targets. The game varied by trial arm to promote either support, collaboration, or competition. Main Outcomes and Measures: Co-primary outcomes included daily step count, weight, and hemoglobin A1c level. Secondary outcome was low-density lipoprotein cholesterol level. Intention-to-treat analysis was used. Results: Participants had a mean (SD) age of 52.5 (10.1) years; hemoglobin A1c level, 9.6% (1.6%); daily steps, 4632 (2523); weight, 107.4 kg (20.8 kg); and body mass index, 37.1 (6.6). Of the 361 participants, 202 (56.0%) were women, 143 (39.6%) were White, and 185 (51.2%) were Black; with 87 (24.1%) randomized to control; 92 (25.4%) randomized to gamification with support and intervention; 95 (26.3%) randomized to gamification with collaboration; and 87 (24.1%) randomized to gamification with competition. Compared with the control group over 1 year, there was a significant increase in mean daily steps from baseline among participants receiving gamification with support (adjusted difference relative to control group, 503 steps; 95% CI, 103 to 903 steps; P = .01) and competition (606 steps; 95% CI, 201 to 1011 steps; P = .003) but not collaboration (280 steps; 95% CI, -115 to 674 steps; P = .16). All trial arms had significant reductions in weight and hemoglobin A1c levels from baseline, but there were no significant differences between any of the intervention arms and the control arm. There was only 1 adverse event reported that may have been related to the trial (arthritic knee pain). Conclusions and Relevance: Among adults with uncontrolled type 2 diabetes, a behaviorally designed gamification intervention in this randomized clinical trial significantly increased physical activity over a 1-year period when designed to enhance either support or competition but not collaboration. No differences between intervention and control groups were found for other outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02961192.

Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction.

Goal-directed behaviors are essential for normal function and significantly impaired in neuropsychiatric disorders. Despite extensive associations between genetic mutations and these disorders, the molecular contributions to goal-directed dysfunction remain unclear. We examined mice with constitutive and brain region-specific mutations in Neurexin1α, a neuropsychiatric disease-associated synaptic molecule, in value-based choice paradigms. We found Neurexin1α knockouts exhibited reduced selection of beneficial outcomes and impaired avoidance of costlier options. Reinforcement modeling suggested that this was driven by deficits in updating and representation of value. Disruption of Neurexin1α within telencephalic excitatory projection neurons, but not thalamic neurons, recapitulated choice abnormalities of global Neurexin1α knockouts. Furthermore, this selective forebrain excitatory knockout of Neurexin1α perturbed value-modulated neural signals within striatum, a central node in feedback-based reinforcement learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in value-modulated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

Data Augmentation and Pretraining for Template-Based Retrosynthetic Prediction in Computer-Aided Synthesis Planning.

This work presents efforts to augment the performance of data-driven machine learning algorithms for reaction template recommendation used in computer-aided synthesis planning software. Often, machine learning models designed to perform the task of prioritizing reaction templates or molecular transformations are focused on reporting high-accuracy metrics for the one-to-one mapping of product molecules in reaction databases to the template extracted from the recorded reaction. The available templates that get selected for inclusion in these machine learning models have been previously limited to those that appear frequently in the reaction databases and exclude potentially useful transformations. By augmenting open-access data sets of organic reactions with explicitly calculated template applicability and pretraining a template-relevance neural network on this augmented applicability data set, we report an increase in the template applicability recall and an increase in the diversity of predicted precursors. The augmentation and pretraining effectively teaches the neural network an increased set of templates that could theoretically lead to successful reactions for a given target. Even on a small data set of well-curated reactions, the data augmentation and pretraining methods resulted in an increase in top-1 accuracy, especially for rare templates, indicating that these strategies can be very useful for small data sets.

Usability of Wearable Devices to Remotely Monitor Sleep Patterns Among Patients With Ischemic Heart Disease: Observational Study.

BACKGROUND: There is growing interest in using wearable devices to remotely monitor patient behaviors. However, there has been little evaluation of how often these technologies are used to monitor sleep patterns over longer term periods, particularly among more high-risk patients. OBJECTIVE: The goal of the research was to evaluate the proportion of time that patients with ischemic heart disease used wearable devices to monitor their sleep and identify differences in characteristics of patients with higher versus lower use. METHODS: We evaluated wearable device data from a previously conducted clinical trial testing the use of wearable devices with personalized goal-setting and financial incentives. Patients with ischemic heart disease established a sleep baseline and were then followed for 24 weeks. The proportion of days that sleep data was collected was compared over the 24 weeks and by study arm. Characteristics of patients were compared to groups with high, low, or no sleep data. RESULTS: The sample comprised 99 patients with ischemic heart disease, among which 79% (78/99) used the wearable device to track their sleep. During the 6-month trial, sleep data were collected on 60% (10,024/16,632) of patient-days. These rates declined over time from 77% (4292/5544) in months 1 and 2 to 58% (3188/5544) in months 3 and 4 to 46% (2544/5544) in months 5 and 6. Sleep data were collected at higher rates among the intervention group compared with control (67% vs 55%, P<.001). In the main intervention period (months 3 and 4), patients with higher rates of sleep data were on average older (P=.03), had a history of smoking (P=.007), and had higher rates of commercial health insurance (P=.03). CONCLUSIONS: Among patients with ischemic heart disease in a physical activity trial, a high proportion used wearable devices to track their sleep; however, rates declined over time. Future research should consider larger evaluations coupled with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02531022; https://clinicaltrials.gov/ct2/show/NCT02531022.

Remotely Monitored Gamification and Social Incentives to Improve Glycemic Control Among Adults With Uncontrolled Type 2 Diabetes (iDiabetes): Protocol for a Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes is a significant cause of morbidity and mortality in the United States. Lifestyle modifications including increasing physical activity and losing weight have been demonstrated to improve glycemic control. However, most patients struggle to make these changes. Many stakeholders are interested in using gamification and social incentives to increase engagement in healthy behaviors. However, these approaches often do not appropriately leverage insights from behavioral economics that could be used to address predictable barriers to behavior change. OBJECTIVE: This study aimed to describe the protocol for the Influencing DIabetics to Adapt Behaviors related to Exercise and weighT by Enhancing Social incentives (iDiabetes) trial, which aimed to evaluate the effectiveness of gamification interventions that leverage insights from behavioral economics to enhance supportive, competitive, or collaborative social incentives to improve glycemic control, promote weight loss, and increase physical activity among overweight and obese adults with type 2 diabetes. METHODS: We are conducting a one-year four-arm randomized controlled trial of 361 overweight and obese patients with type 2 diabetes and a glycated hemoglobin (HbA1c) level ≥8.0. Wireless weight scales and wearable devices are provided to remotely monitor weight and physical activity and transmit data to the study team. Patients are recruited by email, following which they establish a baseline measure of weight, daily step count, HbA1c level, and low-density lipoprotein cholesterol level and then repeat these measures at 6 and 12 months. The control arm receives no other interventions. Patients randomized to one of the three intervention arms are entered into a game designed using insights from behavioral economics to enhance supportive, competitive, or collaborative social incentives. To examine predictors of strong or poor performance, participants completed validated questionnaires on a range of areas including their personality, risk preferences, and social network. RESULTS: Enrollment of 361 patients was completed in January 2019. Results are expected in 2020. CONCLUSIONS: The iDiabetes trial represents a scalable model to remotely monitor the daily health behaviors of adults with type 2 diabetes. Results from this trial will help provide insights into how to improve management of patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02961192; https://clinicaltrials.gov/ct2/show/NCT02961192. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14180.

Effectiveness of Behaviorally Designed Gamification Interventions With Social Incentives for Increasing Physical Activity Among Overweight and Obese Adults Across the United States: The STEP UP Randomized Clinical Trial.

Importance: Gamification, the use of game design elements in nongame contexts, is increasingly being used in workplace wellness programs and digital health applications. However, the best way to design social incentives in gamification interventions has not been well examined. Objective: To assess the effectiveness of support, collaboration, and competition within a behaviorally designed gamification intervention to increase physical activity among overweight and obese adults. Design, Setting, and Participants: This 36-week randomized clinical trial with a 24-week intervention and 12-week follow-up assessed 602 adults from 40 states with body mass indexes (calculated as weight in kilograms divided by height in meters squared) of 25 or higher from February 12, 2018, to March 17, 2019. Interventions: Participants used a wearable device to track daily steps, established a baseline, selected a step goal increase, were randomly assigned to a control (n = 151) or to 1 of 3 gamification interventions (support [n = 151], collaboration [n = 150], and competition [n = 150]), and were remotely monitored. The control group received feedback from the wearable device but no other interventions for 36 weeks. The gamification arms were entered into a 24-week game designed using insights from behavioral economics with points and levels for achieving step goals. No gamification interventions occurred during follow-up. Main Outcomes and Measures: The primary outcome was change in mean daily steps from baseline through the 24-week intervention period. Results: A total of 602 participants (mean [SD] age, 39 [10] years; mean [SD] body mass index, 30 [5]; 427 [70.9%] male) were included in the study. Compared with controls, participants had a significantly greater increase in mean daily steps from baseline during the intervention in the competition arm (adjusted difference, 920; 95% CI, 513-1328; P < .001), support arm (adjusted difference, 689; 95% CI, 267-977; P < .001), and collaboration arm (adjusted difference, 637; 95% CI, 258-1017; P = .001). During follow-up, physical activity remained significantly greater in the competition arm than in the control arm (adjusted difference, 569; 95% CI, 142-996; P = .009) but was not significantly greater in the support (adjusted difference, 428; 95% CI, 19-837; P = .04) and collaboration (adjusted difference, 126; 95% CI, -248 to 468; P = .49) arms than in the control arm. Conclusions and Relevance: All 3 gamification interventions significantly increased physical activity during the 24-week intervention, and competition was the most effective. Physical activity was lower in all arms during follow-up and only remained significantly greater in the competition arm than in the control arm. Trial Registration: ClinicalTrials.gov identifier: NCT03311230.

Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making.

Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.

A manikin-based evaluation of a teaching modality for ultrasound-guided infraclavicular longitudinal in-plane axillary vein cannulation in comparison with ultrasound-guided internal jugular vein cannulation: A pilot study.

BACKGROUND AND AIMS: Ultrasound (US)-guided infraclavicular approach for axillary vein (AXV) cannulation has gained popularity in the last decade. MATERIAL AND METHODS: In this manikin study, we evaluated the feasibility of a training model for teaching AXV cannulation. The learning pattern with this technique was assessed among attending anesthesiologists and residents in training. RESULTS: A faster learning pattern was observed for AXV cannulation among the attending anesthesiologists and residents in training, irrespective of their prior experience with US. It was evident that a training modality for this technique could be easily established with a phantom model and that hands-on training motivates trainees to embrace US-based central venous cannulation. CONCLUSION: A teaching model for US-guided infraclavicular longitudinal in-plane AXV cannulation can be established using a phantom model. A focused educational program would result in an appreciable change in preference in embracing US-based cannulation techniques among residents.

Effects of galactosylation in immunoglobulin G from all-atom molecular dynamics simulations.

Explicit water atomistic molecular dynamics simulations (200 ns, ∼330,000 atoms) were performed to study the effects of galactosylation in the Fc domain of immunoglobulin G1. Two glycoforms were simulated to observe changes in protein-carbohydrate interactions and carbohydrate structure. A high degree of flexibility was observed in the small hinge region of the protein, while large domains remained stable. The hinge region flexibility allowed both translation and rotation of the domains relative to each other, resulting in a large number of possible conformations available. The distributions of rotational orientations between the Fab1 and Fab2 domains showed that while these domains are able to orient themselves rather freely pointing in space they rotated in unison to remain rotationally oriented at specific angles. Additionally, removing specific terminal galactose residues increased the mobility of the carbohydrate, resulting in different protein-carbohydrate interactions. Glycosylation has been suggested as a route to improve the aggregation resistance of monoclonal antibodies for therapeutic treatments to aid the immune system. The results presented here may provide insight into the search for IgG molecules with increased aggregation resistance to be used as monoclonal antibodies.

The long lost IUD.

While evaluating a 65 year old white female as an outpatient for upper gastrointestinal bleeding, an intrauterine device (IUD) was found in her right lower quadrant on a scout film of the abdomen. She was status post total abdominal hysterectomy (TAH). A review of the literature was very sparse on how to manage this issue. Of the 24 articles noted on an EBSCO literature search, only 5 were remotely relevant to this patient, and 4 had no English translation. None of the articles dealt with what to do with an IUD found more than 35 years after insertion. Up to Date did not have any reference to a "lost IUD", only information on the IUD and contraception.