Topological insights into the neural basis of flexible behavior.

It is widely accepted that there is an inextricable link between neural computations, biological mechanisms, and behavior, but it is challenging to simultaneously relate all three. Here, we show that topological data analysis (TDA) provides an important bridge between these approaches to studying how brains mediate behavior. We demonstrate that cognitive processes change the topological description of the shared activity of populations of visual neurons.

Relationship Between Anifrolumab Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Moderate to Severe Systemic Lupus Erythematosus.

This study aimed to elucidate the pharmacokinetic/pharmacodynamic and pharmacodynamic/efficacy relationships of anifrolumab, a type I interferon receptor antibody, in patients with moderate to severe systemic lupus erythematosus. Data were pooled from the randomized, 52-week, placebo-controlled TULIP-1 and TULIP-2 trials of intravenous anifrolumab (150 mg/300 mg, every 4 weeks for 48 weeks). Pharmacodynamic neutralization was measured with a 21-gene type I interferon gene signature (21-IFNGS) in patients with high IFNGS.

Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus.

Objectives: To characterize the relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with moderate to severe SLE despite standard therapy, using pooled data from two phase 3 trials.

Methods: TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks). For the exposure-response analysis, BILAG-based Composite Lupus Assessment (BICLA) or SLE Responder Index [SRI(4)] response rates at week 52 in each quartile/tertile of average anifrolumab serum concentration (Cave) were compared for anifrolumab and placebo in all-comers, patients who completed treatment, and IFN gene signature (IFNGS)-high patients who completed treatment, using average marginal effect logistic regression.

Life-Threatening Bleeding in Children: A Prospective Observational Study.

Objectives: The purpose of our study was to describe children with life-threatening bleeding.

Design: We conducted a prospective observational study of children with life-threatening bleeding events.

Setting: Twenty-four childrens hospitals in the United States, Canada, and Italy participated.

Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study.

Background: 300 mg of intravenous anifrolumab every 4 weeks added to standard-of-care treatment for patients with systemic lupus erythematosus (SLE) reduced disease activity and glucocorticoid requirement in a previous phase 3 trial. Because patients might find subcutaneous administration more convenient than intravenous delivery, we aimed to evaluate the pharmacokinetics, pharmacodynamics, safety, and efficacy of subcutaneous anifrolumab in patients with SLE, active skin disease, and a high type I interferon gene signature.

Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 2 study was done at 12 hospitals and outpatient clinics in Hungary, South Korea, Poland, and the USA.

Outpatient Opioid Prescriptions are Associated With Future Substance Use Disorders and Overdose Following Adolescent Trauma.

Objective: This study aims to determine if outpatient opioid prescriptions are associated with future SUD diagnoses and overdose in injured adolescents 5 years following hospital discharge.

Summary Of Background Data: Approximately, 1 in 8 adolescents are diagnosed with an SUD and 1 in 10 experience an overdose in the 5 years following injury. State laws have become more restrictive on opioid prescribing by acute care providers for treating pain, however, prescriptions from other outpatient providers are still often obtained.

Operative Traumatic Aortic Injuries at an Urban Pediatric Hospital.

Purpose: Limited data are available describing the long-term results of pediatric patients undergoing aortic repair secondary to trauma. Therefore, this descriptive investigation was completed to abrogate this deficit.

Methods: A retrospective review of an urban level 1 pediatric trauma database maintained at a high-volume dedicated children's hospital between 2008-2018 was completed to capture all cases of severe traumatic aortic injury and associated demographics, mechanisms, injury severity, treatment, and clinical outcomes.

Traumatic abdominal wall hernias in children: A case for early exploration.

Purpose: Traumatic abdominal wall hernia (TAWH) is a rare consequence of blunt abdominal trauma (BAT). We examined a series of patients suffering TAWH to evaluate its frequency, rate of associated concurrent intraabdominal injuries (CAI) and correlation with CT, management and outcomes.

Methods: A Level 1 pediatric trauma center trauma registry was queried for children less than 18 years old suffering TAWH from BAT between 2009 and 2019.

Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration.

Supraphysiologic doses of bone morphogenetic protein-2 (BMP-2) are used clinically to promote bone formation in fracture nonunions, large bone defects, and spinal fusion. However, abnormal bone formation (i.e.

Bringing Depth and Meaning to Perinatal Quality Improvement by Partnering With Patients.

The quality of maternal care in the United States has garnered attention as the public has been made aware of outcome data and stories of patients' experiences. Calls to action from national leaders include a focus on evidence-based clinical practice and on interventions that meaningfully include patients and their families in their own care and in identifying promising practices to fill existing gaps. This article provides a look at the methods to identify needs from the patient and family perspective to help improve the quality of maternal care.

A rapid method for determining protein diffusion through hydrogels for regenerative medicine applications.

Hydrogels present versatile platforms for the encapsulation and delivery of proteins and cells for regenerative medicine applications. However, differences in hydrogel cross-linking density, polymer weight content, and affinity for proteins all contribute to diverse diffusion rates of proteins through hydrogel networks. Here, we describe a simple method to accurately measure protein diffusion through hydrogels, within a few hours and without the use of large amounts of protein.

Trends in pediatric-adjusted shock index predict morbidity in children with moderate blunt injuries.

Purpose: Trending the pediatric-adjusted shock index (SIPA) after admission has been described for children suffering severe blunt injuries (i.e., injury severity score (ISS) ≥ 15).

Long-term prescription opioid utilization, substance use disorders, and opioid overdoses after adolescent trauma.

Background: Injured adolescents have a 56% increased risk of developing a substance use disorder (SUD) within 3 years of their injury. The transition from medical prescription opioid use to nonmedical use in adolescent trauma patients has not been longitudinally studied long-term. The aim of this study is to describe 5-year patterns of opioid use in a cohort of injured adolescents as well as the proportion of patients experiencing overdose and SUD diagnoses.

Pediatric Handlebar Injuries: More Than Meets the Abdomen.

Objectives: Injuries associated with bicycles can generally be categorized into 2 types: injuries from falling from/off bicycles and injuries from striking the bicycle. In the second mechanism category, most occur as a result of children striking their body against the bicycle handlebar. The purpose of this study was to evaluate the presentation, body location, injury severity, and need for intervention for pediatric handlebar injuries at a single level one pediatric trauma center and contrast these against other bicycle-related injuries in children.

Assessing outpatient follow-up care compliance, complications, and sequelae in children hospitalized for isolated traumatic abdominal injuries.

Background: Currently there is limited knowledge on compliance with follow-up care in pediatric patients after abdominal trauma. The Indiana Network for Patient Care (INPC) is a large regional health information exchange with both structured clinical data (e.g.

Long-term outcomes after pediatric peripheral revascularization secondary to trauma at an urban level I center.

Objective: The purpose of this investigation was to determine our limb-related contemporary pediatric revascularization perioperative and follow-up outcomes after major blunt and penetrating trauma.

Methods: A retrospective review was performed of a prospectively maintained pediatric trauma database spanning January 2010 to December 2017 to capture all level I trauma activations that resulted in a peripheral arterial revascularization procedure. All preoperative, intraoperative, and postoperative continuous variables are reported as a mean ± standard deviation; categorical variables are reported as a percentage of the population of interest.

The Evolving Surgeon Image.

The stereotype of the abrasive, technically gifted white male surgeon is ubiquitous among members of the public and the medical profession. Yet modern surgeons are far more diverse and socially adept than the stereotype suggests. While the stereotype is largely a relic of days gone by, it continues to influence patients' expectations and surgeons' interactions with their clinical colleagues.

Safety, tolerability and pharmacokinetics of subcutaneous and intravenous anifrolumab in healthy volunteers.

Objectives: To compare the pharmacokinetics (PK), safety and tolerability of subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon receptor monoclonal antibody in development for SLE, in healthy volunteers.

Methods: In this Phase I randomised, placebo-controlled study, 30 adults were assigned to three treatment cohorts (anifrolumab 300 mg SC (n=6), anifrolumab 300 mg intravenous (n=6), anifrolumab 600 mg SC (n=6)) and placebo (n=4/cohort). Serial blood samples were collected up to Day 84 to measure anifrolumab concentrations and antidrug antibodies (ADAs).

The National Network of State Perinatal Quality Collaboratives: A Growing Movement to Improve Maternal and Infant Health.

State Perinatal Quality Collaboratives (PQCs) are networks of multidisciplinary teams working to improve maternal and infant health outcomes. To address the shared needs across state PQCs and enable collaboration, Centers for Disease Control and Prevention (CDC), in partnership with March of Dimes and perinatal quality improvement experts from across the country, supported the development and launch of the National Network of Perinatal Quality Collaboratives (NNPQC). This process included assessing the status of PQCs in this country and identifying the needs and resources that would be most useful to support PQC development.

The National Network of State Perinatal Quality Collaboratives: A Growing Movement to Improve Maternal and Infant Health.

State Perinatal Quality Collaboratives (PQCs) are networks of multidisciplinary teams working to improve maternal and infant health outcomes. To address the shared needs across state PQCs and enable collaboration, Centers for Disease Control and Prevention, in partnership with March of Dimes and perinatal quality improvement experts from across the country, supported the development and launch of the National Network of PQCs National Network of Perinatal Quality Collaboratives (NNPQC). This process included assessing the status of PQCs in this country and identifying the needs and resources that would be most useful to support PQC development.

A programmable platform for sub-second multichemical dynamic stimulation and neuronal functional imaging in C. elegans.

Caenorhabditis elegans (C. elegans) is a prominent model organism in neuroscience, as its small stereotyped nervous system offers unique advantages for studying neuronal circuits at the cellular level. Characterizing temporal dynamics of neuronal circuits is essential to fully understand neuronal processing.

Trends in pediatric adjusted shock index predict morbidity and mortality in children with severe blunt injuries.

Purpose: The utility of measuring the pediatric adjusted shock index (SIPA) at admission for predicting severity of blunt injury in pediatric patients has been previously reported. However, the utility of following SIPA after admission is not well described.

Methods: The trauma registry from a level-one pediatric trauma center was queried from January 1, 2010 to December 31, 2015.