Extending insights from LeDoux: using movies to study subjective, clinically meaningful experiences in neuroscience.

Neuroscience research with public health relevance to emotional disorders examines brain-behavior relations. Joe LeDoux's legacy advances these efforts in ways that remain truly unique. While recognized for his basic science research, he also inspires applied researchers, guiding an agenda for clinical scientists: understanding the pathophysiology of altered subjective experiences in emotional disorders.

Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study.

Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood.

Independent replications reveal anterior and posterior cingulate cortex activation underlying state anxiety-attenuated face encoding.

Anxiety involves the anticipation of aversive outcomes and can impair neurocognitive processes, such as the ability to recall faces encoded during the anxious state. It is important to precisely delineate and determine the replicability of these effects using causal state anxiety inductions in the general population. This study therefore aimed to replicate prior research on the distinct impacts of threat-of-shock-induced anxiety on the encoding and recognition stage of emotional face processing, in a large asymptomatic sample ( = 92).

Tuning the potency and selectivity of ImmTAC molecules by affinity modulation.

T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response.

Naloxegol versus Alvimopan for Enhancing Postoperative Recovery following Radical Cystectomy for Bladder Cancer.

Introduction: µ-Opioid-receptor antagonists are a standard component of enhanced recovery after surgery (ERAS) pathways following radical cystectomy (RC) as they reduce ileus and shorten length of stay (LOS). Prior studies have used alvimopan; however, naloxegol is a less expensive medication in the same class. We compared differences in postoperative outcomes between patients receiving alvimopan or naloxegol following RC.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort.

Materials And Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy.

Threat vigilance and intrinsic amygdala connectivity.

A well-documented amygdala-dorsomedial prefrontal circuit is theorized to promote attention to threat ("threat vigilance"). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g.

Anxiety Shapes Amygdala-Prefrontal Dynamics During Movie Watching.

Background: A well-characterized amygdala-dorsomedial prefrontal circuit is thought to be crucial for threat vigilance during anxiety. However, engagement of this circuitry within relatively naturalistic paradigms remains unresolved.

Methods: Using an open functional magnetic resonance imaging dataset (Cambridge Centre for Ageing Neuroscience;  = 630), we sought to investigate whether anxiety correlates with dynamic connectivity between the amygdala and dorsomedial prefrontal cortex during movie watching.

RapidHRV: an open-source toolbox for extracting heart rate and heart rate variability.

Heart rate and heart rate variability have enabled insight into a myriad of psychophysiological phenomena. There is now an influx of research attempting using these metrics within both laboratory settings (typically derived through electrocardiography or pulse oximetry) and ecologically-rich contexts ( wearable photoplethysmography, , smartwatches). However, these signals can be prone to artifacts and a low signal to noise ratio, which traditionally are detected and removed through visual inspection.

Anxiety and amygdala connectivity during movie-watching.

Rodent and human studies have implicated an amygdala-prefrontal circuit during threat processing. One possibility is that while amygdala activity underlies core features of anxiety (e.g.

Treatment in the absence of disease reclassification among men on active surveillance for prostate cancer.

Background: Maintaining men on active surveillance for prostate cancer can be challenging. Although most men who eventually undergo treatment have experienced clinical progression, a smaller subset elects treatment in the absence of disease reclassification. This study sought to understand factors associated with treatment in a large, contemporary, prospective cohort.

NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases.

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, vo and pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus.

NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy.

Background: NKTR-255 is a novel polyethylene glycol-conjugate of recombinant human interleukin-15 (rhIL-15), which was designed to retain all known receptor binding interactions of the IL-15 molecule. We explored the biologic and pharmacologic differences between endogenous IL-15 receptor α (IL-15Rα)-dependent (NKTR-255 and rhIL-15) and IL-15Rα-independent (precomplexed rhIL-15/IL-15Rα) cytokines.

Methods: In vitro pharmacological properties of rhIL-15, NKTR-255 and precomplex cytokines (rhIL-15/IL-15Rα and rhIL-15 N72D/IL-15Rα Fc) were investigated in receptor binding, signaling and cell function.

Titrating the Smell of Fear: Initial Evidence for Dose-Invariant Behavioral, Physiological, and Neural Responses.

It is well accepted that emotional intensity scales with stimulus strength. Here, we used physiological and neuroimaging techniques to ask whether human body odor-which can convey salient social information-also induces dose-dependent effects on behavior, physiology, and neural responses. To test this, we first collected sweat from 36 males classified as low-, medium-, and high-fear responders.

Trait anxiety does not correlate with metacognitive confidence or reminder usage in a delayed intentions task.

Setting external reminders provides a convenient way to reduce cognitive demand and ensure accurate retrieval of information for prospective tasks. Recent experimental evidence has demonstrated that the decision to offload cognitive information to external resources is guided by metacognitive belief, that is, individuals' confidence in their unaided ability. Other work has also suggested a relationship between metacognitive belief and trait anxiety.

Comparison of readmission and early revision rates as a quality metric in total knee arthroplasty using the Nationwide Readmission Database.

Background: After release of the Comprehensive Care for Joint Replacement bundle, there has been increased emphasis on reducing readmission rates for total knee arthroplasty (TKA). The potential for a separate, clinically-relevant metric, TKA revision rates within a year following surgery, has not been fully explored. Based on this, we compared rates and payments for TKA readmission and revision procedures as metrics for improving quality and cost.

Reframing Financial Incentives Around Reducing Readmission After Radical Cystectomy.

Objective: To better understand the financial implications of readmission after radical cystectomy, an expensive surgery coupled with a high readmission rate. Currently, whether hospitals benefit financially from readmissions after radical cystectomy remains unclear, and potentially obscures incentives to invest in readmission reduction efforts.

Materials And Methods: Using a 20% sample of national Medicare beneficiaries, we identified 3544 patients undergoing radical cystectomy from January 2010 to November 2014.

Does overloading cognitive resources mimic the impact of anxiety on temporal cognition?

Anxiety alters how we perceive the world and can alter aspects of cognitive performance. Prominent theories of anxiety suggest that the effect of anxiety on cognition is due to anxious thoughts "overloading" limited cognitive resources, competing with other processes. If this is so, then a cognitive load manipulation should impact performance of a task in the same way as induced anxiety.

Encoding fear intensity in human sweat.

Humans, like other animals, have an excellent sense of smell that can serve social communication. Although ample research has shown that body odours can convey transient emotions like fear, these studies have exclusively treated emotions as , neglecting the question whether emotion can be expressed chemically. Using a unique combination of methods and techniques, we explored a dose-response function: Can fear intensity be in fear sweat? Specifically, fear experience was quantified using multivariate pattern classification (combining physiological data and subjective feelings with partial least-squares-discriminant analysis), whereas a photo-ionization detector quantified volatile molecules in sweat.

Dynamic readmission prediction using routine postoperative laboratory results after radical cystectomy.

Objective: To determine if the addition of electronic health record data enables better risk stratification and readmission prediction after radical cystectomy. Despite efforts to reduce their frequency and severity, complications and readmissions following radical cystectomy remain common. Leveraging readily available, dynamic information such as laboratory results may allow for improved prediction and targeted interventions for patients at risk of readmission.

Characterising 'bounce-back' readmissions after radical cystectomy.

Objective: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions.

Patients And Methods: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge.

Potential Savings in Medicare Part D for Common Urological Conditions.

Introduction: Millions of patients take prescription medications each year for common urological conditions. Generic and brand-name drugs have widely divergent pricing despite similar therapeutic benefit and side effect profiles. We examined prescribing patterns across provider types for generic and brand-name drugs used to treat 3 common urological conditions, and estimated economic implications for Medicare Part D spending.

Role of Post-Acute Care on Hospital Readmission After High-Risk Surgery.

Background: Payment models, including the Hospital Readmissions Reduction Program and bundled payments, place pressures on hospitals to limit readmissions. Against this backdrop, we sought to investigate the association of post-acute care after major surgery and readmission rates.

Methods: We identified patients undergoing high-risk surgery (abdominal aortic aneurysm repair, coronary bypass grafting, aortic valve replacement, carotid endarterectomy, esophagectomy, pancreatectomy, lung resection, and cystectomy) from 2005 to 2010 using the Healthcare Cost and Utilization Project's State Inpatient Database.

Characterising potential bone scan overuse amongst men treated with radical prostatectomy.

Objectives: To characterise bone scan use, and potential overuse, after radical prostatectomy (RP) using data from a large, national integrated delivery system. Overuse of imaging is well documented in the setting of newly diagnosed prostate cancer, but whether overuse persists after RP remains unknown.

Patients And Methods: We identified 12 269 patients with prostate cancer treated with RP between 2005 and 2008 using the Veterans Administration Central Cancer Registry.