Adaptable, turn-on maturation (ATOM) fluorescent biosensors for multiplexed detection in cells.

A grand challenge in biosensor design is to develop a single-molecule, fluorescent protein-based platform that can be easily adapted to recognize targets of choice. Here, we created a family of adaptable, turn-on maturation (ATOM) biosensors consisting of a monobody (circularly permuted at one of two positions) or a nanobody (circularly permuted at one of three positions) inserted into a fluorescent protein at one of three surface loops. Multiplexed imaging of live human cells coexpressing cyan, yellow and red ATOM sensors detected biosensor targets that were specifically localized to various subcellular compartments. Fluorescence activation involved ligand-dependent chromophore maturation with turn-on ratios of up to 62-fold in cells and 100-fold in vitro. Endoplasmic reticulum- and mitochondria-localized ATOM sensors detected ligands that were targeted to those organelles. The ATOM design was validated with three monobodies and one nanobody inserted into distinct fluorescent proteins, suggesting that customized ATOM sensors can be generated quickly.

"It Is A Purposefully Ambiguous Term": Examining Emerging Adults' Definitions of Hooking Up and How They Vary by Sex/Gender and Educational Background.

The majority of past work on hooking up among emerging adults uses a researcher-led definition and often uses college student samples. The purpose of this study was to qualitatively examine participant-led definitions of hooking up using a large sample (N = 701) of college-attending and non-college emerging adults. Most definitions included behaviors (91.7%), a partner type (64.3%), and references to commitment (69.2%). However, considerable variation in definitions within these categories was identified, in particular with reference to commitment. In our sample, definitions attended to what a hook "is" and "is not" as it relates to commitment. Hookup characteristics were also discussed in definitions, including frequency of hooking up, decision making, sexual health and safety, and purposes for hookups. Participants regularly referenced other common terms in relation to hooking up, including one-night stands, casual sex, no strings attached, and friends with benefits. For some, hookups were similar to these other types of casual sex experiences, whereas for others hooking up was distinct. We also quantitatively examined proportional differences in definitional categories and sub-categories based on sex/gender (men vs. women) and educational background (college-attending vs. non-college). Although some proportional differences were found, in general men and women and college-attending and non-college emerging adults defined hookups in similar ways. Programming focused on emerging adult romantic and sexual relationship education would benefit from addressing these subtle, but meaningful variations, as individuals enact hookup scripts based on how they define their encounters. Future opportunities for research to integrate both researcher-led and participant-led definitions of hooking up are discussed.

Clinical utility of measuring CD4+ T follicular cells in patients with immune dysregulation.

Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation. Patients with infections, active malignancy, or any history of transplantation were excluded. In 238 healthy controls, median cTfh percentages (range 4.8%-6.2%) were comparable among age groups, sexes, races, and ethnicities, apart from a significantly lower percentages in children less than 1 year of age (median 2.1%, CI: 0.4%-6.8, p < 0.0001). Among 130 patients with over 40 immune regulatory disorders, a cTfh percentage exceeding 12% had 88% sensitivity and 94% specificity for differentiating disorders with adaptive immune cell dysregulation from those with predominantly innate cell defects. This threshold had a sensitivity of 86% and specificity of 100% for active autoimmunity and normalized with effective treatment. cTfh percentages exceeding 12% distinguish autoimmunity from autoinflammation, thereby differentiating two endotypes of immune dysregulation with overlapping symptoms and different therapies.

Ventricular arrhythmias following balloon-expandable transcatheter pulmonary valve replacement in the native right ventricular outflow tract.

BACKGROUND: Ventricular arrhythmia incidence in children and adolescents undergoing transcatheter pulmonary valve replacement (TPVR) within the native right ventricular outflow tract (nRVOT) is unknown. We sought to describe the incidence, severity, and duration of ventricular arrhythmias and identify associated risk factors in this population. METHODS: This was a retrospective cohort study of 78 patients <21 years of age who underwent TPVR within the nRVOT. Patients were excluded for pre-existing ventricular arrhythmia or antiarrhythmic use. Study variables included surgical history, valve replacement indication, valve type/size, and ventricular arrhythmia. Univariable logistic regression models were used to evaluate factors associated with ventricular arrhythmias, followed by subset analyses. RESULTS: Nonsustained ventricular arrhythmia occurred in 26/78 patients (33.3%). The median age at the procedure was 10.3 years (interquartle range [IQR]: 6.5, 12.8). Compared with other nRVOT types, surgical repair with transannular patch was protective against ventricular arrhythmia incidence: odds ratio (OR): 0.35 (95% confidence interval [CI], 0.13-0.95). Patient weight, valve type/size, number of prestents, and degree of stent extension into the RVOT were not associated with ventricular arrhythmia occurrence. Beta blocker was started in 16/26 (61.5%) patients with ventricular arrhythmia. One additional patient was lost to follow-up. The median beta blocker duration was 46 days (IQR 42, 102). Beta blocker was discontinued in 10 patients by 8-week follow-up and in the remaining four by 9 months. CONCLUSIONS: Though common after balloon-expandable TPVR within the nRVOT, ventricular arrhythmias were benign and transient. Antiarrhythmic medications were successfully discontinued in the majority at 6- to 8-week follow-up, and in all patients by 20 months.

Impact of COVID-19 on percutaneous coronary intervention utilization and mortality in New York.

BACKGROUND: COVID-19 has disrupted the care of all patients, and little is known about its impact on the utilization and short-term mortality of percutaneous coronary intervention (PCI) patients, particularly nonemergency patients. METHODS: New York State's PCI registry was used to study the utilization of PCI and the presence of COVID-19 in four patient subgroups ranging in severity from ST-elevation myocardial infarction (STEMI) to elective patients before (December 01, 2018-February 29, 2020) and during the COVID-19 era (March 01, 2020-May 31, 2021), as well as to examine the impact of different COVID severity levels on the mortality of different types of PCI patients. RESULTS: Decreases in the mean quarterly PCI volume from the prepandemic period to the first quarter of the pandemic ranged from 20% for STEMI patients to 61% for elective patients, with the other two subgroups having decreases in between these values. PCI quarterly volume rebounds from the prepandemic period to the second quarter of 2021 were in excess of 90% for all patient subgroups, and 99.7% for elective patients. Existing COVID-19 was rare among PCI patients, ranging from 1.74% for STEMI patients to 3.66% for elective patients. PCI patients with COVID-19 and acute respiratory distress syndrome (ARDS) who were not intubated, and PCI patients with COVID-19 and ARDS who were either intubated or were not intubated because of Do Not Resuscitate//Do Not Intubate status had higher risk-adjusted mortality ([adjusted ORs = 10.81 [4.39, 26.63] and 24.53 [12.06, 49.88], respectively]) than patients who never had COVID-19. CONCLUSIONS: There were large decreases in the utilization of PCI during COVID-19, with the percentage of decrease being highly sensitive to patient acuity. By the second quarter of 2021, prepandemic volumes were nearly restored for all patient subgroups. Very few PCI patients had current COVID-19 throughout the pandemic period, but the number of PCI patients with a COVID-19 history increased steadily during the pandemic. PCI patients with COVID-19 accompanied by ARDS were at much higher risk of short-term mortality than patients who never had COVID-19. COVID-19 without ARDS and history of COVID-19 were not associated with higher mortality for PCI patients as of the second quarter of 2021.

Egg viability and egg mass underlie immune tradeoffs and differences between urban and rural lizard egg yolk physiology.

Urbanization can cause innumerable abiotic and biotic changes that have the potential to influence the ecology, behavior, and physiology of native resident organisms. Relative to their rural conspecifics, urban Side-blotched Lizard (Uta stansburiana) populations in southern Utah have lower survival prospects and maximize reproductive investment via producing larger eggs and larger clutch sizes. While egg size is an important predictor of offspring quality, physiological factors within the egg yolk are reflective of the maternal environment and can alter offspring traits, especially during energetically costly processes, such as reproduction or immunity. Therefore, maternal effects may represent an adaptive mechanism by which urban-dwelling species can persist within a variable landscape. In this study, we assess urban and rural differences in egg yolk bacterial killing ability (BKA), corticosterone (CORT), oxidative status (d-ROMs), and energy metabolites (free glycerol and triglycerides), and their association with female immune status and egg quality. Within a laboratory setting, we immune challenged urban lizards via lipopolysaccharide injection (LPS) to test whether physiological changes associated with immune system activity impacted egg yolk investment. We found urban females had higher mite loads than rural females, however mite burden was related to yolk BKA in rural eggs, but not urban eggs. While yolk BKA differed between urban and rural sites, egg mass and egg viability (fertilized vs. unfertilized) were strong predictors of yolk physiology and may imply tradeoffs exist between maintenance and reproduction. LPS treatment caused a decrease in egg yolk d-ROMs relative to the control treatments, supporting results from previous research. Finally, urban lizards laid a higher proportion of unfertilized eggs, which differed in egg yolk BKA, CORT, and triglycerides in comparison to fertilized eggs. Because rural lizards laid only viable eggs during this study, these results suggest that reduced egg viability is a potential cost of living in an urban environment. Furthermore, these results help us better understand potential downstream impacts of urbanization on offspring survival, fitness, and overall population health.

Interfascicular Anatomy of the Motor Branch of the Ulnar Nerve: A Cadaveric Study.

PURPOSE: The motor branch of the ulnar nerve contains fascicles that innervate the intrinsic musculature of the hand. This cadaveric study aimed to describe the organization and consistency of the internal topography of the motor branch of the ulnar nerve. METHODS: Five fresh-frozen cadaveric specimens with an average age of 74 years (range, 65-88 years) were dissected. The ulnar nerve was exposed and transfixed to the underlying tissues to maintain its orientation throughout the dissection. The dorsal cutaneous branch (DCB) and the volar sensory branch were identified and reflected to expose the motor branch. The fascicles to the first dorsal interosseus (FDI), flexor pollicis brevis, and abductor digiti minimi (ADM) were identified. Internal neurolysis was performed distal to proximal to identify the interfascicular arrangement of these fascicles within the motor branch. The organization of these fascicles was noted, and the branch points of the DCB, FDI, and ADM were measured relative to the pisiform using a handheld electronic caliper. RESULTS: The internal topography of the motor branch was consistent among all specimens. Proximal to the pisiform, the arrangement from radial to ulnar was as follows: volar sensory branch, flexor pollicis brevis, FDI/intrinsic muscles, ADM, and DCB. The position of these branches remained consistent as the deep motor branch curved radially within the palm and traveled to the terminal musculature. The locations of the average branch points of the FDI, ADM, and DCB with respect to the pisiform were as follows: FDI, 4.6 cm distal (range, 4.1-4.9 cm), 4.5 cm radial (range, 4.1-4.9 cm); ADM, 0.65 cm distal (range, 0.3-1.1 cm), 0.7 cm radial (range, 0.3-1.1 cm), DCB, 7.7 cm proximal (range, 4.2-10.1 cm), and 0.4 cm ulnar (range, 0.3-0.8 cm). CONCLUSIONS: The internal topography of the ulnar nerve motor branch was consistent among the specimens studied. The topography of the motor branches was maintained as the motor branch turns radially within the palm. CLINICAL RELEVANCE: This study provides further understanding of the internal topography of the ulnar nerve motor branch at the wrist level.

Strength Comparison of Fibrin Glue and Suture Constructs in Upper Extremity Peripheral Nerve Coaptations: An In Vitro Study.

PURPOSE: To compare in vitro failure loads of nerve coaptations using fibrin glue alone, a suture alone, and a combination of fibrin glue and a suture. METHODS: The median, radial, and ulnar nerves of 15 fresh-frozen cadaveric upper extremity specimens (45 nerves in total) were dissected in vitro and transected 5 cm proximal to the wrist crease to simulate an injury requiring coaptation. Three coaptation techniques were used: fibrin glue alone, a suture alone, and a suture augmented with fibrin glue. The load to failure of each repair was measured using a linear servo-actuator with an in-line force sensor. The results were analyzed using 2-way repeated measures analysis of variance tests and pairwise comparisons with Bonferroni correction. RESULTS: Both the nerve coaptation technique and the specific nerve that was repaired had a significant effect on failure load. Suture-glue repair had the highest load to failure, 11.2 ± 2.9 N, and significantly increased the load to failure by 2.9 ± 1.7 N compared with glue repair alone. There was no significant difference between suture-glue repair and suture repair alone or between glue repair alone and suture repair alone. CONCLUSIONS: In this in vitro cadaveric model, nerve injury coaptation using both a suture and fibrin glue resulted in the strongest repair. The addition of fibrin glue may provide some benefit when used to augment suture repair, but when used in isolation, it is inferior to combined suture-and-glue constructs. CLINICAL RELEVANCE: Combined suture-and-glue nerve coaptations might be useful in the early postoperative period in increasing nerve repair strength and potentially reducing rupture rates.

Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). METHODS: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. RESULTS: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. CONCLUSIONS: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.

Glucose tolerance of iguanas is affected by high-sugar diets in the lab and supplemental feeding by ecotourists in the wild.

There is great interspecific variation in the nutritional composition of natural diets, and the varied nutritional content is physiologically tolerated because of evolutionarily based balances between diet composition and processing ability. However, as a result of landscape change and human exposure, unnatural diets are becoming widespread among wildlife without the necessary time for evolutionary matching between the diet and its processing. We tested how a controlled, unnatural high glucose diet affects glucose tolerance using captive green iguanas, and we performed similar glucose tolerance tests on wild Northern Bahamian rock iguanas that are either frequently fed grapes by tourists or experience no such supplementation. We evaluated both short and longer-term blood glucose responses and corticosterone (CORT) concentrations as changes have been associated with altered diets. Experimental glucose supplementation in the laboratory and tourist feeding in the wild both significantly affected glucose metabolism. When iguanas received a glucose-rich diet, we found greater acute increases in blood glucose following a glucose challenge. Relative to unfed iguanas, tourist-fed iguanas had significantly lower baseline CORT, higher baseline blood glucose, and slower returns to baseline glucose levels following a glucose challenge. Therefore, unnatural consumption of high amounts of glucose alters glucose metabolism in laboratory iguanas with short-term glucose treatment and free-living iguanas exposed to long-term feeding by tourists. Based on these results and the increasing prevalence of anthropogenically altered wildlife diets, the consequences of dietary changes on glucose metabolism should be further investigated across species, as such changes in glucose metabolism have health consequences in humans (e.g. diabetes).

Characterization of buried interfaces using Ga Kα hard X-ray photoelectron spectroscopy (HAXPES).

The extension of X-ray photoelectron spectroscopy (XPS) to measure layers and interfaces below the uppermost surface requires higher X-ray energies and electron energy analysers capable of measuring higher electron kinetic energies. This has been enabled at synchrotron radiation facilities and by using lab-based instruments which are now available with sufficient sensitivity for measurements to be performed on reasonable timescales. Here, we detail measurements on buried interfaces using a Ga Kα (9.25 keV) metal jet X-ray source and an EW4000 energy analyser (ScientaOmicron GmbH) in the Henry Royce Institute at the University of Manchester. Development of the technique has required the calculation of relative sensitivity factors (RSFs) to enable quantification analogous to Al Kα XPS, and here we provide further substantiation of the Ga Kα RSF library. Examples of buried interfaces include layers of memory and energy materials below top electrode layers, semiconductor heterostructures, ions implanted in graphite, oxide layers at metallic surfaces, and core-shell nanoparticles. The use of an angle-resolved mode enables depth profiling from the surface into the bulk, and is complemented with surface-sensitive XPS. Inelastic background modelling allows the extraction of information about buried layers at depths up to 20 times the photoelectron inelastic mean free path.

Are the Developmental Features of Emerging Adulthood Associated with Willingness to Engage in Consensually Nonmonogamous Relationships?

The purpose of this study was to examine whether the developmental features of emerging adulthood were associated with willingness to engage in consensually nonmonogamous (CNM) relationships. All participants (N = 792) were English speaking emerging adults (ages 18-25) residing in the USA. About half were attending college, whereas the other half had no college experience. After controlling for a number of variables (i.e., college status, sex/gender, sexual orientation, sexual identity exploration, sexual identity commitment, and casual sex attitudes), greater perceptions of emerging adulthood as a time of identity exploration and feeling in between were negatively associated with willingness to engage in CNM relationships. Also, greater perceptions of emerging adulthood as a time of experimentation/possibilities was positively associated with willingness to engage in CNM. Although our final model explained 33.5% of the variance in willingness to engage in CNM relationships, perceptions of the developmental features of emerging adulthood accounted for just 4.2% of the variance explained. Future research on CNM relationships and relationship education for emerging adults are discussed.

Genetic Architecture and Molecular Neuropathology of Human Cocaine Addiction.

We integrated genomic and bioinformatic analyses, using data from the largest genome-wide association study of cocaine dependence (CD; n = 6546; 82.37% with CD; 57.39% male) and the largest postmortem gene-expression sample of individuals with cocaine use disorder (CUD; n = 36; 51.35% with CUD; 100% male). Our genome-wide analyses identified one novel gene (NDUFB9) associated with the genetic predisposition to CD in African-Americans. The genetic architecture of CD was similar across ancestries. Individual genes associated with CD demonstrated modest overlap across European-Americans and African-Americans, but the genetic liability for CD converged on many similar tissue types (brain, heart, blood, liver) across ancestries. In a separate sample, we investigated the neuronal gene expression associated with CUD by using RNA sequencing of dorsal-lateral prefrontal cortex neurons. We identified 133 genes differentially expressed between CUD case patients and cocaine-free control subjects, including previously implicated candidates for cocaine use/addiction (FOSB, ARC, KCNJ9/GIRK3, NR4A2, JUNB, and MECP2). Differential expression analyses significantly correlated across European-Americans and African-Americans. While genes significantly associated with CD via genome-wide methods were not differentially expressed, two of these genes (NDUFB9 and C1qL2) were part of a robust gene coexpression network associated with CUD involved in neurotransmission (GABA, acetylcholine, serotonin, and dopamine) and drug addiction. We then used a "guilt-by-association" approach to unravel the biological relevance of NDUFB9 and C1qL2 in the context of CD. In sum, our study furthers the understanding of the genetic architecture and molecular neuropathology of human cocaine addiction and provides a framework for translating biological meaning into otherwise obscure genome-wide associations.SIGNIFICANCE STATEMENT Our study further clarifies the genetic and neurobiological contributions to cocaine addiction, provides a rapid approach for generating testable hypotheses for specific candidates identified by genome-wide research, and investigates the cross-ancestral biological contributions to cocaine use disorder/dependence for individuals of European-American and African-American ancestries.

Energy expenditure across immune challenge severities in a lizard: consequences for innate immunity, locomotor performance and oxidative status.

Reptiles, like other vertebrates, rely on immunity to defend themselves from infection. The energetic cost of an immune response is liable to scale with infection severity, prompting constraints on other self-maintenance traits if immune prioritization exceeds energy budget. In this study, adult male side-blotched lizards (Uta stansburiana) were injected with saline (control) or high (20 µg g-1 body mass) or low (10 µg g-1 body mass) concentrations of lipopolysaccharide (LPS) to simulate bacterial infections of discrete severities. The costs and consequences of the immune response were assessed through comparisons of change in resting metabolic rate (RMR), energy metabolites (glucose, glycerol, triglycerides), innate immunity (bactericidal ability), sprint speed and oxidative status (antioxidant capacity, reactive oxygen metabolites). High-LPS lizards had the lowest glucose levels and greatest sprint reductions, while their RMR and bactericidal ability were similar to those of control lizards. Low-LPS lizards had elevated RMR and bactericidal ability, but glucose levels and sprint speed changes between those of high-LPS and control lizards. Levels of glycerol, triglycerides, reactive oxygen metabolites and antioxidant capacity did not differ by treatment. Taken together, energy expenditure for the immune response varies in a non-linear fashion with challenge severity, posing consequences for performance and self-maintenance processes in a reptile.

Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use.

BACKGROUND: Rodent paradigms and human genome-wide association studies (GWAS) on drug use have the potential to provide biological insight into the pathophysiology of addiction. METHODS: Using GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP heritability of these gene-sets using four large human GWAS: (1) alcoholic drinks per week, (2) problematic alcohol use, (3) cigarettes per day, and (4) smoking cessation. We benchmarked our findings with curated human alcohol and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWAS (e.g., height). RESULTS: The rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance-use GWAS, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits. CONCLUSION: Our results suggest that rodent gene expression studies can help to identify genes that contribute to the heritability of some substance use traits in humans, yet there was less specificity than expected. We outline various limitations, interpretations, and considerations for future research.

Meanings Ascribed to Sex and Commitment Among College-Attending and Non-College Emerging Adults: A Replication and Extension.

The purpose of this study was to examine how meanings ascribed to sex and commitment vary based on educational background, gender, and other correlates using a large sample of college-attending and non-college emerging adults (ages 18-25; N = 669). Findings from our content analysis replicated previous research by identifying meanings focused on commitment (47.8%), flexibility (22.7%), and recreation (17.8%). We also found two additional meanings focused on finding a sexual connection (termed Connectors; 9.1%) and using sex to test relationship compatibility (termed Testers; 2.5%), which were not found in previous studies on sex and commitment. A greater proportion of women than men were in the Committers group, whereas a greater proportion of men than women were in the Recreationers group. A greater proportion of heterosexual than sexual minority participants were in the Committers group, whereas a greater proportion of sexual minority than heterosexual participants were in the Flexibles and Testers groups. A greater proportion of those in committed relationships than those in casual or no relationships were in the Committers group, whereas a greater proportion of those in casual relationships than those in committed or no relationships were in the Recreationers group. Those in the Recreationers group reported the greatest average number of hookup partners in the last 12 months (compared to all others), and those in the Recreationers and Testers groups reported the greatest average number of lifetime sexual partners (compared to all others). Implications for future research and sexual health education for emerging adults are discussed.

Confirmatory radiographs have limited utility following ultrasound-guided tunneled femoral central venous catheter placements by interventional radiology.

BACKGROUND: Ultrasonography may reliably visualize both appropriately positioned and malpositioned femoral-approach catheter tips. Radiography may be used to confirm catheter tip position after placement, but its utility following intraprocedural ultrasound (US) catheter tip verification is unclear. OBJECTIVES: To report the utility of confirmatory radiographs after US-guided tunneled femoral central venous catheter (CVC) placements by interventional radiology in pediatric patients. MATERIALS AND METHODS: A total of 484 pediatric patients underwent bedside US-guided tunneled femoral CVC placements in an intensive care setting at a single tertiary children's hospital between Jan. 1, 2016, and April 20, 2020. Technical success, adverse events, post-procedure radiographic practices and inter-modality catheter tip concordance were recorded. All radiographs were performed within 12 h of catheter placement. RESULTS: The mean patient age was 175±508 days (range: 1 day to 19 years), including 257 (53.1%) males and 227 (46.9%) females. Of the 484 attempted placements, 472 (97.5%) were primary placements. Four hundred eighty-one (99.4%) placements were technically successful. There were three (0.6%) technical failures due to previously undiagnosed iliofemoral venous occlusive disease. Five (1.0%) adverse events occurred. Radiographs were obtained within 12 h of CVC placement in 171 (35.3%) patients, in 120 (70.2%) of whom the indication was recent catheter placement. All 171 (100%) post-placement radiographs showed catheter tip location concordance with the intra-procedural US. In one (0.2%) patient, in whom there was nonvisualization of a guidewire and clinical concern for malposition during US-guided placement, post-procedure radiographs, coupled with multiplanar venography, demonstrated inadvertent paravertebral venous plexus catheter placement. CONCLUSION: The concordance between intra-procedural US and confirmatory post-procedure radiographs of CVC placements by interventional radiology obviates the need for routine radiographs. Radiographs may be obtained in instances of proceduralist uncertainty or clinical concern.

Comparison of two cortical measures of binaural hearing acuity.

OBJECTIVE: Multiple studies have demonstrated binaural hearing deficits in the aging and those with hearing loss. Consequently, there is great interest in developing efficient clinical tests of binaural hearing acuity to improve diagnostic assessments and to assist clinicians when fitting binaural hearing aids and/or cochlear implants. DESIGN: Two cortical measures of interaural phase difference sensitivity, the acoustic change complex (ACC) and interaural phase modulation following response (IPM-FR), were compared on three metrics using five different stimulus interaural phase differences (IPDs; 0°, ±22.5°, ±45°, ±67.5° and ±90°). These metrics were scalp topography, time-to-detect, and input-output characteristics. STUDY SAMPLE: Ten young, normal-hearing listeners. RESULTS: Scalp topography qualitatively differed between ACC and IPM-FR. The IPM-FR demonstrated better time-to-detect performance on smaller (±22.5° and ±45°) but not larger (67.5°, and ±90°) IPDs. Input-output characteristics of each response were similar. CONCLUSIONS: The IPM-FR may be a faster and more efficient tool for assessing neural sensitivity to subtle IPD changes. However, the ACC may be useful for research or clinical questions concerned with the topographic representation of binaural cues.

Sex differences in the treatment and outcomes of patients hospitalized with ST-elevation myocardial infarction.

OBJECTIVES: To compare mortality for women and men hospitalized with ST-elevation myocardial infarction (STEMI) by age and revascularization status. BACKGROUND: There is little information on the mortality of men and women not undergoing revascularization, and the impact of age on relative male-female mortality needs to be revisited. METHODS AND RESULTS: An observational database of 23,809 patients with STEMI presenting at nonfederal New York State hospitals between 2013 and 2015 was used to compare risk-adjusted inhospital/30-day mortality for women and men and to explore the impact of age on those differences. Women had significantly higher mortality than men overall (adjusted odds ratio [AOR] = 1.15, 95% CI [1.04, 1.28]), and among patients aged 65 and older. Women had lower revascularization rates in general (AOR = 0.64 [0.59, 0.69]) and for all age groups. Among revascularized STEMI patients, women overall (AOR = 1.30 [1.10, 1.53]) and over 65 had higher mortality than men. Among patients not revascularized, women between the ages of 45 and 64 had lower mortality (AOR = 0.68 [0.48, 0.97]). CONCLUSIONS: Women with STEMI, and especially older women, had higher inhospital/30-day mortality rates than their male counterparts. Women had higher mortality among revascularized patients, but not among patients who were not revascularized.

Assessment of repeat target lesion percutaneous coronary intervention as a quality measure for public reporting and general quality assessment for PCIs.

BACKGROUND: Target lesion percutaneous coronary intervention (TLPCI) within 1 year of PCI has been proposed by critics of public reporting of short-term mortality as an alternative measure for PCI reporting. METHODS: New York's PCI registry was used to identify 1-year repeat TLPCI and 1-year repeat TLPCI/mortality for patients discharged between December 1, 2013 and November 30, 2014. Significant independent predictors of the outcomes were identified. Hospital and cardiologist risk-adjusted outcomes were calculated, and outlier status and correlations of risk-adjusted rates were examined for the three outcomes. RESULTS: The adverse outcome rates were 1.30, 4.21, and 8.97% for in-hospital/30-day mortality, 1-year repeat TLPCI, and 1-year repeat TLPCI/mortality. There were many commonalities but also many differences in significant predictors of the outcomes. Hospital and cardiologist risk-adjusted 1-year repeat TLPCI rates and repeat TLPCI/mortality rates were poorly correlated with risk-adjusted in-hospital/30-day mortality rates (eg, Spearman R = -.16 [p = .23] and .27 [p = .04], respectively, for hospital 1-year repeat TLPCI vs. in-hospital/30-day mortality). Many more providers were found to have significantly higher and lower rates for repeat TLPCI than for short-term mortality. CONCLUSIONS: Hospital and cardiologist quality assessments are very different for TLPCI and repeat TLPCI/mortality than they are for short-term mortality. Repeat TLPCI/mortality rates are highly correlated with repeat TLPCI rates, but outlier providers differ. More study of repeat TLPCI and all the patient, cardiologist, and hospital factors associated with it may be required before using it as a supplement to, or in lieu of, short-term mortality in public reporting of PCI outcomes.