Statistically learned associations among objects bias attention.

A growing body of research suggests that semantic relationships among objects can influence the control of attention. There is also some evidence that learned associations among objects can bias attention. However, it is unclear whether these findings are due to statistical learning or existing semantic relationships. In the present study, we examined whether statistically learned associations among objects can bias attention in the absence of existing semantic relationships. Participants searched for one of four targets among pairs of novel shapes and identified whether the target was present or absent from the display. In an initial training phase, each target was paired with an associated distractor in a fixed spatial configuration. In a subsequent test phase, each target could be paired with the previously associated distractor or a different distractor. In our first experiment, the previously associated distractor was always presented in the same pair as the target. Participants were faster to respond when this distractor was present on target-present trials. In our second experiment, the previously associated distractor was presented in a different pair than the target in the test phase. In this case, participants were slower to respond when this distractor was present on both target-present and target-absent trials. Together, these findings provide clear evidence that statistically learned associations among objects can bias attention, analogous to the effects of semantic relationships on attention.

Psilocybin-assisted therapy and HIV-related shame.

As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of - 5.5 (- 6.5, - 3.5) points from baseline to 3-months follow-up (Z = - 2.6, p = 0.009, r = - 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.

Relating distractor suppression to problematic drinking behavior.

BACKGROUND: Impaired cognitive control has been linked to weakened self-regulatory processes underlying compulsive substance intake. Previous research has provided evidence for impaired task performance in substance-abusing groups during Stroop and Go/No-Go tasks. Mechanisms of distractor suppression in visual search might also involve overlapping regulatory components that support goal-directed behavior by resolving the attentional competition between distractors and the target of search. However, the efficiency of learning-dependent distractor suppression has not been examined in the context of drug abuse and a direct comparison between cognitive control and distractor suppression is lacking. METHOD: A total of 84 participants were assigned either to the heavy drinking group (ALC, n = 42) or the control group (CTL, n = 42) based on self-reported substance use. Participants completed the Alcohol Use Disorders Identification Test (AUDIT) and Barratt Impulsiveness Scale (BIS). After that, participants completed a computerized version of the Stroop task, Go/No-go task, and a visual search task measuring learning-dependent distractor suppression. RESULTS: The Stroop effect and the frequency of no-go errors did not differ between groups. However, learned distractor suppression was significantly blunted in the ALC group compared to the control group. Across participants, performance on the Stroop and Go/No-go task were correlated, while the magnitude of distractor suppression was related to neither. CONCLUSIONS: Our findings support a divergence of mechanistic processes underlying cognitive control and attentional control, and demonstrate impaired learning-dependent distractor suppression in heavy drinkers relative to a control group. Impaired distractor suppression offers new insight into why drug cues can be difficult to ignore.

Protocol to evaluate the effectiveness of a virtual-reality-based behavioral intervention in enhancing sensory responses to real-world warning.

Habituation to signals that warn of a potential danger in high-risk work environments is a critical causal factor of workplace accidents. Such habituation is hard to measure in a real-world setting, and no existing intervention can effectively curb it. Here, we present a protocol to enhance workers' sensory responses to frequently encountered warnings at workplaces using a virtual-reality-based behavioral intervention. We describe steps for performing a virtual reality experiment and an electroencephalography (EEG) experiment with human participants. For complete details on the use and execution of this protocol, please refer to Kim et al.1.

An examination of the motivation to manage distraction.

Individuals exhibit limited awareness of when their attention is captured by salient but irrelevant stimuli, and it has long been argued that involuntary attentional capture by such stimuli is minimally disruptive to information processing. Yet, robust mechanisms of distractor suppression are hypothesized to support the control of attention, which presumably serve in the interest of managing distraction. In the present study, I examine whether participants are aware of the cost of distraction with respect to task performance, and whether they are motivated to manage this cost even when it is effortful to do so. Across three experiments, participants were willing to exert physical effort in order to reduce the frequency with which they encountered physically salient distractors, and in a fourth experiment tended to prefer trials with fewer distractors when given a choice over distractor frequency. Importantly, the amount of physical effort exerted varied as a function of the degree to which task-irrelevant distractors impaired search performance, suggesting that people are sensitive to the cost of distraction.

Absorption pharmacokinetics and feasibility of intranasal dexmedetomidine in patients under general anaesthesia.

BACKGROUND: The use of intranasal dexmedetomidine is hampered by a limited understanding of its absorption pharmacokinetics. METHODS: We examined the pharmacokinetics and feasibility of intranasal dexmedetomidine administered in the supine position to adult patients undergoing general anaesthesia. Twenty-eight patients between 35 and 80 years of age, ASA 1-3 and weight between 50 and 100 kg, who underwent elective unilateral total hip or knee arthroplasty under general anaesthesia were recruited. All patients received 100 µg of intranasal dexmedetomidine after anaesthesia induction. Six venous blood samples (at 0, 5, 15, 45, 60, 240 min timepoints from dexmedetomidine administration) were collected from each patient and dexmedetomidine plasma concentrations were measured. Concentration-time profiles after nasal administration were pooled with earlier data from a population analysis of intravenous dexmedetomidine (n = 202) in order to estimate absorption parameters using nonlinear mixed effects. Peak concentration (CMAX) and time (TMAX) were estimated using simulation (n = 1000) with parameter estimates and their associated variability. RESULTS: There were 28 adult patients with a mean (SD) age of 66 (8) years and weight of 83 (10) kg. The mean weight-adjusted dose of dexmedetomidine was 1.22 (0.15) µg kg-1. CMAX 0.273 µg L-1 was achieved at 98 min after intranasal administration (TMAX). The relative bioavailability of dexmedetomidine was 80% (95% CI 75-91%). The absorption half-time (TABS = 120 min; 95% CI 90-147 min) was slower than that in previous pharmacokinetic studies on adult patients. Perioperative haemodynamics of all patients remained stable. CONCLUSIONS: Administration of intranasal dexmedetomidine in the supine position during general anaesthesia is feasible with good bioavailability. This administration method has slower absorption when compared to awake patients in upright position, with consequent concentrations attained after TMAX for several hours.

A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices.

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half-time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.

Perceptions on and roadblocks to implementation of standardized nomenclature in radiation oncology: A survey from TG-263U1.

PURPOSE: AAPM Task Group No. 263U1 (Update to Report No. 263 - Standardizing Nomenclatures in Radiation Oncology) disseminated a survey to receive feedback on utilization, gaps, and means to facilitate further adoption. METHODS: The survey was created by TG-263U1 members to solicit feedback from physicists, dosimetrists, and physicians working in radiation oncology. Questions on the adoption of the TG-263 standard were coupled with demographic information, such as clinical role, place of primary employment (e.g., private hospital, academic center), and size of institution. The survey was emailed to all AAPM, AAMD, and ASTRO members. RESULTS: The survey received 463 responses with 310 completed survey responses used for analysis, of whom most had the clinical role of medical physicist (73%) and the majority were from the United States (83%). There were 83% of respondents who indicated that they believe that having a nomenclature standard is important or very important and 61% had adopted all or portions of TG-263 in their clinics. For those yet to adopt TG-263, the staffing and implementation efforts were the main cause for delaying adoption. Fewer respondents had trouble adopting TG-263 for organs at risk (29%) versus target (44%) nomenclature. Common themes in written feedback were lack of physician support and available resources, especially in vendor systems, to facilitate adoption. CONCLUSIONS: While there is strong support and belief in the benefit of standardized nomenclature, the widespread adoption of TG-263 has been hindered by the effort needed by staff for implementation.  Feedback from the survey is being utilized to drive the focus of the update efforts and create tools to facilitate easier adoption of TG-263.

Restricting angles of incidence to improve super resolution in time reversal focusing that uses metamaterial properties of a resonator array.

Focusing waves with a spatial extent smaller than a half wavelength (i.e., super resolution or sub diffraction limit) is possible using resonators placed in the near field of time reversal (TR) focusing. While a two-dimensional (2D) Helmholtz resonator array in a three-dimensional reverberant environment has limited ability to produce a high-resolution spatial focus in the TR focusing of audible sound, it is shown that acoustic waves propagating out-of-plane with the resonator array are not as strongly affected by the smaller effective wavelength induced by the resonator array, partially negating the effect of the resonators. A physical 2D waveguide is shown to limit the out-of-plane propagation, leading to improved resolution. It is also shown that post processing using an orthogonal particle velocity decomposition of a spatial scan of the focusing can filter out-of-plane particle motion in the near field of the array, which bypasses the effect of the unwanted third spatial dimension of propagation. The spatial resolution in a reverberant environment is shown to improve in the presence of a 2D Helmholtz resonator array and then further improve by adding a 2D waveguide. The resolution among the resonator array is better still without using a waveguide and instead using the partial-pressure reconstruction.

Framework of the strengths and challenges of clinically integrated trials: An expert panel report.

The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems. The operational and design features of clinically integrated trials include a focused scope, simplicity in design and requirements, the leveraging of existing data structures, and patient participation in the entire trial process. These features are designed to minimize barriers to participation and trial execution and reduce additional research burdens for participants and clinicians alike. Broad adoption and scalability of clinically integrated trials are dependent, in part, on continuing regulatory, healthcare system, and payer support. This analysis presents a framework of the strengths and challenges of clinically integrated trials and is based on a multidisciplinary expert "Think Tank" panel discussion that included representatives from patient populations, academia, non-profit funding agencies, the U.S. Food and Drug Administration, and industry.

Online vs in-person delivery of preclinical coursework: A retrospective cohort study evaluating National Board of Chiropractic Examiners performance.

OBJECTIVE: To evaluate the association between basic science curriculum delivery method with other academic and demographic factors on National Board of Chiropractic Examiners (NBCE) part I pass rates. METHODS: This was a retrospective cohort study of students from 3 campuses of 1 chiropractic institution who matriculated in 2018 or 2020. COVID-19 regulations required online delivery of a basic science curriculum for students in the 2020 cohorts, whereas students in the 2018 cohorts experienced a traditional classroom delivery. A general linear model estimated odds ratios for passing NBCE part I, comparing individual online cohorts with the combined classroom cohort while adjusting for academic and demographic variables. RESULTS: A total of 968 students were included, 55% from the classroom cohort. The spring 2020 cohort had the fewest students with bachelors' degrees (59%) and more students with high in-program grade point averages (GPA; 61%) along with the lowest estimated odds ratio [0.80 (95% CI: 0.73-0.87)] for passing vs the classroom cohort. The fall 2020 cohort had significantly higher odds [1.06 (95% CI: 1.00-1.03)] of passing vs the classroom cohort. Additional predictors included main campus matriculation, white ethnicity, bachelors' degree, no alternative admission status, and in-program GPA. Students with high in-program GPA (vs low) had a 36% increased odds of passing. CONCLUSION: Compared to the classroom cohort, the spring 2020 cohort had the lowest odds while the fall 2020 cohort had the highest odds of passing part I. In-program GPA had the highest association with passing. These results provide information on how curriculum delivery impacts board exam performance.

Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

BACKGROUND AND OBJECTIVES: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 µg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection. METHODS: Fifty paediatric patients (aged 4 days to 16 years) were studied after undergoing cardiac surgery supported by CPB. Data from 29 premature neonates (23-28 weeks' postmenstrual age) treated for prophylaxis of low systemic blood flow were available for a pooled pharmacokinetic analysis. Population parameters were estimated using non-linear mixed effects modelling (NONMEM 7.5.1). RESULTS: There were 369 milrinone measurements available for analysis. A one-compartment model with zero-order input and first-order elimination was used to describe milrinone disposition. Population parameters were clearance 17.8 L/70 kg [95% CI 15.8-19.9] and volume 20.4 L/h/70 kg [95% CI 17.8-22.1]. Covariates included size, postmenstrual age and renal function for clearance, and size and postnatal age for volume. Milrinone clearance is reduced by 39.5% [95% CI 24.0-53.7] immediately after bypass, and recovers to baseline clearance with a half-time of 12.0 h [95% CI 9.7-15.2]. Milrinone volume was 2.07 [95% CI 1.87-2.27] times greater at birth than the population standard and decreased over the first days of life with a half-time of 0.977 days [95% CI 0.833-1.12]. CONCLUSION: Milrinone is predominately renally eliminated and so renal function is an important covariate describing variability in clearance. Increasing clearance over time likely reflects increasing cardiac output and renal perfusion due to milrinone and return to baseline following CPB.

Pediatric anesthesia in Australia and New Zealand and health inequity among First Nations and Maori children.

Australia and New Zealand are two countries in the Southern Pacific region. They share many pediatric anesthesia similarities in terms of medical organizational systems, education, training, and research, however there are important differences between the two nations in relation to geography, the First Nations populations and the history of colonization. While the standards for pediatric anesthesia and the specialty training requirements are set by the Australian and New Zealand College of Anesthetists and the Society for Pediatric Anesthesia in New Zealand and Australia, colonization has created distinct challenges that each nation now faces in order to improve the anesthetic care of its pediatric population. Australia generally has a high standard of living and good access to health care; disparities exist for First Nations People and for those living in rural or remote areas. Two influences have shaped training within New Zealand over the past 40 years; establishment of a national children's hospital in 1990 and, more importantly, acknowledgement that the First Nations people of New Zealand (Maori) have suffered because of failure to recognize their rights consequent to establishing a partnership treaty between Maori and the British Crown in 1840. Health inequities among Maori in New Zealand and First Nations People in Australia have implications for the health system, culturally appropriate approaches to treatment, and the importance of having an appreciation of First Nations people's history and culture, language, family structure, and cultural safety. Trainees in both countries need to be adequately supported in these areas in order for the sub-specialty of pediatric anesthesia to develop further and improve the anesthetic and surgical outcomes of our children.

Illumination of understudied ciliary kinases.

Cilia are cellular signaling hubs. Given that human kinases are central regulators of signaling, it is not surprising that kinases are key players in cilia biology. In fact, many kinases modulate ciliogenesis, which is the generation of cilia, and distinct ciliary pathways. Several of these kinases are understudied with few publications dedicated to the interrogation of their function. Recent efforts to develop chemical probes for members of the cyclin-dependent kinase like (CDKL), never in mitosis gene A (NIMA) related kinase (NEK), and tau tubulin kinase (TTBK) families either have delivered or are working toward delivery of high-quality chemical tools to characterize the roles that specific kinases play in ciliary processes. A better understanding of ciliary kinases may shed light on whether modulation of these targets will slow or halt disease onset or progression. For example, both understudied human kinases and some that are more well-studied play important ciliary roles in neurons and have been implicated in neurodevelopmental, neurodegenerative, and other neurological diseases. Similarly, subsets of human ciliary kinases are associated with cancer and oncological pathways. Finally, a group of genetic disorders characterized by defects in cilia called ciliopathies have associated gene mutations that impact kinase activity and function. This review highlights both progress related to the understanding of ciliary kinases as well as in chemical inhibitor development for a subset of these kinases. We emphasize known roles of ciliary kinases in diseases of the brain and malignancies and focus on a subset of poorly characterized kinases that regulate ciliary biology.

Filtering distractors is costly.

To find a target in visual search, it is often necessary to filter out task-irrelevant distractors. People find the process of distractor filtering effortful, exerting physical effort to reduce the number of distractors that need to be filtered on a given search trial. Working memory demands are sufficiently costly that people are sometimes willing to accept aversive heat stimulation in exchange for the ability to avoid performing a working memory task. The present study examines whether filtering distractors in visual search is similarly costly. The findings reveal that individuals are sometimes willing to accept an electric shock in exchange for the ability to skip a single trial of visual search, increasingly so as the demands of distractor filtering increase. This was true even when acceptance of shock resulted in no overall time savings, although acceptance of shock was overall infrequent and influenced by a plurality of factors, including boredom and curiosity. These findings have implications for our understanding of the mental burden of distractor filtering and why people seek to avoid cognitive effort more broadly.

Mobilizing data during a crisis: Building rapid evidence pipelines using multi-institutional real world data.

The COVID-19 pandemic generated tremendous interest in using real world data (RWD). Many consortia across the public and private sectors formed in 2020 with the goal of rapidly producing high-quality evidence from RWD to guide medical decision-making, public health priorities, and more. Experiences were gathered from five large consortia on rapid multi-institutional evidence generation during the COVID-19 pandemic. Insights have been compiled across five dimensions: consortium composition, governance structure and alignment of priorities, data sharing, data analysis, and evidence dissemination. The purpose of this piece is to offer guidance on building large-scale multi-institutional RWD analysis pipelines for future public health issues. The composition of each consortium was largely influenced by existing collaborations. A central set of priorities for evidence generation guided each consortium, however different approaches to governance emerged. Challenges surrounding limited access to clinical data due to various contributors were overcome in unique ways. While all consortia used different methods to construct and analyze patient cohorts ranging from centralized to federated approaches, all proved effective for generating meaningful real-world evidence. Actionable recommendations for clinical practice and public health agencies were made from translating insights from consortium analyses. Each consortium was successful in rapidly answering questions about COVID-19 diagnosis and treatment despite all taking slightly different approaches to data sharing and analysis. Leveraging RWD, leveraged in a manner that applies scientific rigor and transparency, can complement higher-level evidence and serve as an important adjunct to clinical trials to quickly guide policy and critical care, especially for a pandemic response.