Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity.

Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b+CD45+ myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b+CD45+ cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C+MHCII+ macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.

Integrating stakeholder feedback into the design of a peer-delivered primary care wellness program: A rapid qualitative study.

BACKGROUND: Individuals seen in Primary Care with behavioral health concerns who decline behavioral health treatment may benefit from the support of peers (consumers in recovery from behavioral health concerns employed to support other consumers). Whole Health STEPS is a new intervention for Veterans in Primary Care with behavioral health concerns which combines essential elements of peers' role and the Whole Health model using a stepped-care design. We incorporated stakeholder feedback in the Whole Health STEPS design to improve fit with Veterans, peers, and primary care settings. METHODS: We conducted semi-structured qualitative interviews with VA staff using questions derived from the Consolidated Framework for Implementation Research (CFIR). Participants were recruited via a maximum variation strategy across a national sample and interviewed between January 2021-April 2021. The analytic design was a rapid qualitative analysis. Interviews addressed design decisions and potential barriers and facilitators to future implementation. Then, we made adaptations to Whole Health STEPS and catalogued changes using the Framework for Adaptations and Modifications-Enhanced (FRAME). A VA peer conducted the interviews, participated in analyses, assisted with design modifications, and co-wrote this paper. RESULTS: Sixteen staff members from 9 VA primary care peer programs participated (8 peers and 8 supervisors/administrators). Feedback themes included: capitalizing on peer skills (e.g., navigation), ensuring patient-centered and flexible design, and making it easy and efficient (e.g., reducing session length). Understanding the structure of primary care peers' roles and their interactions with other programs helped us identify role conflicts (e.g., overlap with Whole Health Coaches and Health Behavior Coordinators), which led to design modifications to carve out a unique role for Whole Health STEPS. Staff also made recommendations about marketing materials and training tools to support Whole Health STEPS roll out. CONCLUSIONS: Feedback from frontline staff, including peers, in the design process was crucial to identifying essential modifications that would not have been possible after initial trials without re-evaluating efficacy due to the extent of the changes. Whole Health STEPS was adapted to fit within a range of program structures, emphasize peers' unique contributions, and streamline delivery. Lessons learned can be applied to other interventions.

Temperature alone is insufficient to understand hibernation energetics.

Energy conservation has long been a focal point in hibernation research. A long-standing assumption is that ambient temperature (Ta) largely defines the rate of energy expenditure because of well-known relationships between Ta, metabolic rate and frequency of arousal from torpor. Body condition and humidity also affect energy expenditure but are usually considered secondary factors. We held tricolored bats (Perimyotis subflavus) in captivity under multiple environmental conditions to directly compare the importance of Ta, fat mass and humidity for hibernation energy expenditure. Fat mass was the best predictor of female mass loss, followed by Ta and humidity. However, males had less fat and adopted a more energetically conservative hibernation strategy. Our results demonstrate that understanding the evolution of behavior, physiology and ecology of hibernation requires disentangling the relative contributions of multiple drivers of hibernation energetics, and that Ta is not always the most important factor driving energy expenditure.

PTPN11 Gain-of-Function Mutations Affect the Developing Human Brain, Memory, and Attention.

The Ras-MAPK pathway has an established role in neural development and synaptic signaling. Mutations in this pathway are associated with a collection of neurodevelopmental syndromes, Rasopathies; among these, Noonan syndrome (NS) is the most common (1:2000). Prior research has focused on identifying genetic mutations and cellular mechanisms of the disorder, however, effects of NS on the human brain remain unknown. Here, imaging and cognitive data were collected from 12 children with PTPN11-related NS, ages 4.0-11.0 years (8.98 ± 2.33) and 12 age- and sex-matched typically developing controls (8.79 ± 2.17). We observe reduced gray matter volume in bilateral corpus striatum (Cohen's d = -1.0:-1.3), reduced surface area in temporal regions (d = -1.8:-2.2), increased cortical thickness in frontal regions (d = 1.2-1.3), and reduced cortical thickness in limbic regions (d = -1.6), including limbic structures integral to the circuitry of the hippocampus. Further, we find high levels of inattention, hyperactivity, and memory deficits in children with NS. Taken together, these results identify effects of NS on specific brain regions associated with ADHD and learning in children. While our research lays the groundwork for elucidating the neural and behavioral mechanisms of NS, it also adds an essential tier to understanding the Ras-MAPK pathway's role in human brain development.

A library mobile device deployment to enhance the medical student experience in a rural longitudinal integrated clerkship.

OBJECTIVE: Investigators implemented the Rural Information Connection (RIC) project, a library-initiated deployment of iPad Mini 3s for third-year medical students who were enrolled in a seven-month rural longitudinal integrated clerkship (LIC) rotation. The research aims were to determine if devices preloaded with high-quality mobile health apps enhanced the experience and increased access to and awareness of mobile health information resources for the enrolled project participants. METHODS: Nine participants enrolled in this mixed methods research project. Pre- and post-survey and structured learning journals (SLJs) were used for data collection on device and app use. Descriptive statistics and thematic coding analysis included data from seven pre-surveys, nine post-surveys, and sixty-four SLJ prompts. The validated Technology Acceptance Model instrument was also incorporated to gauge the devices' integration into the participants' workflow. RESULTS: The investigation indicated that the iPad Mini 3 and resources were utilized and integrated at varying levels in the participants' workflow. Reported use of health information apps suggests a preference for broad-based information sources rather than specific or specialized information resources. Participants performed several tasks on the device, including seeking background information, educating patients, and managing rotation schedules. Participant reflections indicated positive experiences utilizing the device and health information resources, which enhanced their rural LIC rotations. CONCLUSIONS: The research analysis demonstrates the information-seeking behavior of medical students immersed in a rural environment and indicates an acceptance of mobile technology into the workflow of participants in this project. Mobile device deployments offer great opportunities for librarians to design innovative programming in medical education.

Professional development in evidence-based practice: course survey results to inform administrative decision making.

OBJECTIVE: To understand librarians' evidence-based practice (EBP) professional development needs and assist library administrators with professional development decisions in their own institutions, the study team surveyed past participants of an EBP online course. This study aimed to (1) understand what course content participants found valuable, (2) discover how participants applied their course learning to their work, and (3) identify which aspects of EBP would be beneficial for future continuing education. METHODS: The study team distributed an eighteen-question survey to past participants of the course (2011-2017). The survey covered nontraditional demographic information, course evaluations, course content applications to participants' work, additional EBP training, and EBP topics for future CE opportunities. The study team analyzed the results using descriptive statistics. RESULTS: Twenty-nine percent of course participants, representing different library environments, responded to the survey. Eighty-five percent of respondents indicated that they had prior EBP training. The most valuable topics were searching the literature (62%) and developing a problem, intervention, comparison, outcome (PICO) question (59%). Critical appraisal was highly rated for further professional development. Fifty-three percent indicated change in their work efforts after participating in the course. Ninety-seven percent noted interest in further EBP continuing education. CONCLUSIONS: Survey respondents found value in both familiar and unfamiliar EBP topics, which supported the idea of using professional development for learning new concepts and reinforcing existing knowledge and skills. When given the opportunity to engage in these activities, librarians can experience new or expanded EBP work roles and responsibilities. Additionally, the results provide library administrators insights into the benefit of EBP professional development.

Wellness in Sickness and Health (The W.I.S.H. Project): Advance Care Planning Preferences and Experiences Among Elderly Latino Patients.

OBJECTIVE: To assess advance care planning (ACP) preferences, experiences, and comfort in discussing end-of-life (EOL) care among elderly Latinos. METHODS: Patients aged 60 and older from the Los Angeles County and University of Southern California (LAC+USC) Medical Center Geriatrics Clinic (n = 41) participated in this intervention. Trained staff conducted ACP counseling with participants in their preferred language, which included: (a) pre-counseling survey about demographics and EOL care attitudes, (b) discussion of ACP and optional completion of an advance directive (AD), and (c) post-session survey. RESULTS: Patients were primarily Spanish speaking with an average of 2.7 chronic medical conditions. Most had not previously documented (95%) or discussed (76%) EOL wishes. Most were unaware they had control over their EOL treatment (61%), but valued learning about EOL options (83%). Post-counseling, 85% reported comfort discussing EOL goals compared to 66% pre-session, and 88% elected to complete an AD. Nearly half of patients reported a desire to discuss EOL wishes sooner. CONCLUSIONS: Elderly Latino patients are interested in ACP, given individualized, culturally competent counseling in their preferred language. CLINICAL IMPLICATIONS: Patients should be offered the opportunity to discuss and document EOL wishes at all primary care appointments, regardless of health status. Counseling should be completed in the patient's preferred language, using culturally competent materials, and with family members present if this is the patient's preference. Cultural-competency training for providers could enhance the impact of EOL discussions and improve ACP completion rates for Latino patients.

Natural Course of Co-Occurring PTSD and Alcohol Use Disorder Among Recent Combat Veterans.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur in veterans, yet little is known about the longitudinal course of PTSD and drinking in comorbid populations. This study assessed the natural course of daily alcohol consumption and weekly changes in PTSD symptoms in 112 recent combat veterans over the course of 11 months. Latent class growth mixture modeling was used to classify individuals into distinct classes with similar PTSD symptom and alcohol use growth trajectories. We then investigated theorized predictors of class membership including sociodemographics; pre-, peri-, and postdeployment factors; coping; symptom severity; and number of mental health/substance use appointments attended. Results revealed that most participants had severe and nonremitting PTSD. Trajectories for alcohol use included gradual and drastic declines, and chronic low-level drinking. The use of behavioral health services (odds ratio = 2.47) and fewer current stressors (odds ratio = 0.42) predicted AUD remission. Because little variation was observed in the PTSD course, our study did not observe coordinated fluctuations of PTSD symptoms and heavy drinking. Our findings suggest that treatment impacts the course of AUD and that recent combat veterans who do not seek PTSD treatment may have chronic and severe PTSD symptoms.

NExT: creating an interdisciplinary alliance to diminish informational barriers for public health nursing.

BACKGROUND: Public health nurses (PHNs) are challenged in obtaining opportunities to learn evidence-based practice (EBP). An interdisciplinary alliance was created between health sciences librarians and nurse educators to create a continuing education (CE) opportunity. OBJECTIVE: To measure the effectiveness of CE training for PHNs on the knowledge gained about the EBP process and information resources. METHODS: Ten in-person CE workshops were offered to 69 attendees in rural and urban areas. A pre-test/post-test survey was administered immediately before and after the training that asked participants to rate their perceived knowledge and comfort levels with EBP concepts and resources. RESULTS: Ninety-seven per cent of participants reported the training was a good use of their time. Based on a 5-point Likert scale self-assessment, participants developed new skills (m = 4.06, SD = 0.968) and were able to find evidence-based literature (m = 4.16, SD = 0.980). Participants reported increasing their understanding of EBP concepts and familiarity of information resources. All data were statistically significant at P < 0.001 (95% CI). DISCUSSION: With the interdisciplinary collaboration capitalising on the instructors' disciplinary skill sets, the team was able to create a new effective EBP education intervention for PHNs. CONCLUSION: Public health nurses were able to increase knowledge of EBP concepts and information resources to utilise in practice or grant development.

A Self-Help Crisis Outreach Effort for At-Risk Primary Care Patients: A Pilot Study of Veterans During the COVID-19 Pandemic.

Stressful events can exacerbate symptoms of psychiatric disorders among primary care patients, putting them at increased risk for suicide. In a pilot study that ran from August to December of 2020, researchers evaluated the acceptability and implementation of Managing Emotions in Disaster and Crisis (MEDIC), a self-help intervention designed to assist at-risk primary care patients. A total of 108 at-risk veterans completed baseline and 6-week assessments. Results were promising, with high patient acceptability and engagement along with improvement in all measures of mental illness symptoms from baseline to posttreatment. Self-help interventions like MEDIC may offer a low-burden way for primary care providers to support more patients.

Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling.

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

Failure and delay in treatment-seeking across anxiety disorders.

Anxiety disorders are a significant mental health problem. Despite the availability of effective treatments most sufferers do not seek help. The current study assesses delays in treatment-seeking, failure to seek treatment, and reasons for delaying treatment for individuals with anxiety disorders. Data were drawn from the Collaborative Psychiatric Epidemiological Surveys including 3,805 participants and analyses focused on treatment-seeking variables. Results indicate that individuals with anxiety disorders are less likely to seek treatment from a professional and more likely to experience delays in obtaining both any treatment, and effective treatment, than individuals with other forms of mental illness (in this case unipolar depression or substance use disorders). Deficits in mental health literacy (knowledge and beliefs about mental illness) were commonly endorsed as reasons for having delayed seeking treatment. The current study highlights the importance of improving knowledge about anxiety disorders to improve treatment-seeking.

The Effects of Acute and Repeated Administration of Ketamine on Memory, Behavior, and Plasma Corticosterone Levels in Female Mice.

Ketamine is an anesthetic drug that has recently been approved for the treatment of treatment-resistant depression. Females are diagnosed with Major Depressive Disorder at higher rates than males, yet most of the pre-clinical research on ketamine has been conducted in male subjects. Additionally, the literature on the acute and long-term behavioral and cognitive effects of ketamine shows conflicting results. It is important to examine the acute and long-term cognitive and behavioral effects of ketamine exposure at lower sub-anesthetic doses, as the recreational use of the drug at higher doses is associated with cognitive and memory impairments. The current study examined the effects of acute and repeated ketamine exposure on anxiety-like behavior, novel object recognition memory, depression-like behavior, and plasma corticosterone levels in 20 adult female C57BL/6J mice. Mice were exposed acutely or repeatedly for 10 consecutive days to saline or 15 mg/kg ketamine and behavior was measured in the open field test, novel object recognition test, and the Porsolt forced swim test. Plasma corticosterone levels were measured following behavioral testing. Acute ketamine exposure decreased locomotor activity and increased anxiety-like behavior in the open field test compared to controls, while repeated ketamine exposure impaired memory in the novel object recognition test. There were no effects of acute or repeated ketamine exposure on depression-like behavior in the Porsolt forced swim test or on plasma corticosterone levels. These findings suggest that a subanesthetic dose of ketamine alters behavior and cognition in female mice and the effects are dependent on the duration of exposure.

Implementing evidence-based telephone coaching for health behavior program enrollment: A quality improvement project.

INTRODUCTION: This program evaluation describes the use of implementation facilitation to support uptake of a telephone-based engagement coaching intervention, ACTIVATE, using paraprofessional staff, to support health behavior program enrollment. METHOD: The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework guided the formative evaluation. A mixed-methods approach was used to integrate qualitative (i.e., rapid analysis approach) and quantitative (i.e., descriptive statistics, chi-square test of independence, logistic regression) analyses for each outcome. RESULTS: Most patients (95%; 319 of 335) were offered ACTIVATE, and 82 patients completed ACTIVATE. Delivery with paraprofessional staff was feasible with adaptations for translation from research to a clinical setting, which are described. External facilitation (a form of implementation facilitation) was associated with higher reach. DISCUSSION: Delivery of telephone-based coaching by paraprofessional staff to support health behavior program enrollment was feasible. External facilitation was important to the translation of ACTIVATE from research to clinical practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PET imaging of TREM1 identifies CNS-infiltrating myeloid cells in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that causes substantial morbidity and diminished quality of life. Evidence highlights the central role of myeloid lineage cells in the initiation and progression of MS. However, existing imaging strategies for detecting myeloid cells in the CNS cannot distinguish between beneficial and harmful immune responses. Thus, imaging strategies that specifically identify myeloid cells and their activation states are critical for MS disease staging and monitoring of therapeutic responses. We hypothesized that positron emission tomography (PET) imaging of triggering receptor expressed on myeloid cells 1 (TREM1) could be used to monitor deleterious innate immune responses and disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first validated TREM1 as a specific marker of proinflammatory, CNS-infiltrating, peripheral myeloid cells in mice with EAE. We show that the 64Cu-radiolabeled TREM1 antibody-based PET tracer monitored active disease with 14- to 17-fold higher sensitivity than translocator protein 18 kDa (TSPO)-PET imaging, the established approach for detecting neuroinflammation in vivo. We illustrate the therapeutic potential of attenuating TREM1 signaling both genetically and pharmacologically in the EAE mice and show that TREM1-PET imaging detected responses to an FDA-approved MS therapy with siponimod (BAF312) in these animals. Last, we observed TREM1+ cells in clinical brain biopsy samples from two treatment-naïve patients with MS but not in healthy control brain tissue. Thus, TREM1-PET imaging has potential for aiding in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.

Leveraging Integrated Primary Care to Address Patients' and Families' Unmet Social Needs: Aligning Practice with National Academy of Sciences, Engineering and Medicine Recommendations.

Primary care is well-poised to address unmet social needs that affect health. Integrated primary care is increasingly common and can be leveraged to facilitate identification of practice and clinician-level modifiable characteristics and assist practices to address unmet social needs for patients and families. A recent National Academies of Sciences, Engineering, and Medicine (NASEM)'s consensus report identified 5 critical system-level activities to facilitate the integration of addressing social needs into health care: awareness (ask patients), adjustment (flexible intervention delivery), assistance (intervention to address the social need), alignment (link with community resources), and advocacy (policy change). This article outlines how integrated primary care characteristics, such as routine screening, functional workflows, interprofessional team communication, and patient-centered practices, exemplify the NASEM report's activities and offer robust biopsychosocial tools for addressing social needs. We provide a case to illustrate how these strategies might be used in practice.

Engagement, experience, and satisfaction with peer-delivered whole health coaching for veterans with PTSD: A mixed methods process evaluation.

To describe the process of peer-delivered Whole Health Coaching, a primary care-based intervention in which peers provide patients with individualized support to set and work toward wellness goals. Fifteen primary care Veterans with PTSD participated in peer-delivered Whole Health Coaching during a multiple baseline design study. This is a planned mixed methods concurrent equal status analysis of the process of peer-delivered Whole Health Coaching including patient engagement, patient experience, fidelity to the coaching and peer roles, and patient satisfaction. Data sources were feedback interviews, electronic medical record reviews, self-report assessments, and observer fidelity ratings of session recordings. Qualitative data were used to expand the interpretation of quantitative descriptive data. A rapid assessment approach was used for qualitative analysis. Retention in peer-delivered Whole Health Coaching was 11 of 15 participants, and factors facilitating engagement were peers as providers and flexibility in scheduling/modality of sessions. Peers demonstrated high fidelity to coaching skills, Whole Health Coaching phases and stages, and the peer role. Participants expressed high satisfaction and perceived peer-delivered Whole Health Coaching as helpful with making progress on individualized wellness goals. Results build on the literature describing the expansion of peer services into primary care and implementation of interventions such as wellness coaching. This initial small study suggests that peers can deliver high-quality wellness coaching, and this description of the process can guide the integration of peers doing wellness coaching in similar clinical settings and for future research trials. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Practical and Emotional Peer Support Tailored for Life's Challenges: Personalized Support for Progress Randomized Clinical Pilot Trial in a Veterans Health Administration Women's Clinic.

INTRODUCTION: Women Veterans experience a broad range of stressors (e.g., family, relationship, and financial) and high rates of mental health and physical health conditions, all of which contribute to high levels of stress. Personalized Support for Progress (PSP), an evidence-based intervention, is well suited to support women Veterans with high stress as it involves a card-sort task to prioritize concerns as well as pragmatic and emotional support to develop and implement a personalized plan addressing those concerns. Our aims were to explore the population and context for delivery and evaluate the feasibility, acceptability, and utility of PSP delivered by a peer specialist to complement existing services in a Veterans Health Administration (VHA) Women's Wellness Center. MATERIALS AND METHODS: This randomized controlled pilot trial compared treatment as usual plus PSP to treatment as usual and used the a priori Go/No-Go criteria to establish success for each outcome. We interviewed staff regarding the population and delivery context at a VHA Women's Wellness Center and analyzed interviews using a rapid qualitative approach. For the rapid qualitative analysis, we created templated summaries of each interview to identify key concepts within each a priori theme, reviewed each theme's content across all interviews, and finally reviewed key concepts across themes. We evaluated feasibility using recruitment and retention rates; acceptability via Veteran satisfaction, working relationship with the peer, and staff satisfaction; and utility based on the proportion of Veterans who experienced a large change in outcomes (e.g., stress, mental health symptoms, and quality of life). The Syracuse VA Human Subjects Institutional Review Board approved all procedures. RESULTS: Staff interviews highlight that women Veterans have numerous unmet social needs and concerns common among women which increase the complexity of their care; call for a supportive, consistent, trusting relationship with someone on their health care team; and require many resources (e.g., staff such as social workers, services such as legal support, and physical items such as diapers) to support their needs (some of which are available within VHA but may need support for staffing or access, and some of which are unavailable). Feasibility outcomes suggest a need to modify PSP and research methods to enhance intervention and assessment retention before the larger trial; the recruitment rate was acceptable by the end of the trial. Veteran acceptability of PSP was high. Veteran outcomes demonstrate promise for utility to improve stress, mental health symptoms, and quality of life for women Veterans. CONCLUSIONS: Given the high acceptability and promising outcomes for utility, changes to the design to enhance the feasibility outcomes which failed to meet the a priori Go/No-Go criteria are warranted. These outcomes support future trials of PSP within VHA Women's Wellness Centers.

Shock wave formation from head-on collision of two subsonic vortex rings.

Vortex ring collisions have attracted intense interest in both water and air studies (Baird in Proc R Soc Lond Ser Math Phys Sci 409:59-65, 1987, Poudel et al. in Phys Fluids 33:096105, 2021, Lim and Nickels in Nature 357:225, 1992, New et al. in Exp Fluids 57:109, 2016, Suzuki et al. in Geophys Res Lett 34, 2007, Yan et al. in J Fluids Eng 140:054502, 2018, New et al. in J Fluid Mech 899, 2020, Cheng et al. in Phys Fluids 31:067107, 2019, Hernández and Reyes in 29:103604, 2017, Mishra et al. in Phys Rev Fluids, 2021, Zednikova et al. in Chem Eng Technol 42:843-850, 2019, Kwon et al. in Nature 600:64-69, 2021). These toroidal structures spin around a central axis and travel in the original direction of impulse while spinning around the core until inertial forces become predominant causing the vortex flow to spontaneously decay to turbulence (Vortex Rings, https://projects.iq.harvard.edu/smrlab/vortex-rings ). Previous studies have shown the collision of subsonic vortex rings resulting in reconnected vortex rings, but the production of a shock wave from the collision has not been demonstrated visibly (Lim and Nickels in Nature 357:225, 1992, Cheng et al. in Phys Fluids 31:067107, 2019). Here we present the formation of a shock wave due to the collision of explosively formed subsonic vortex rings. As the vortex rings travel at Mach 0.66 toward the collision point, they begin to trap high pressure air between them. Upon collision, high pressure air was imploded and released radially away from the axis of the collision, generating a visible shock wave traveling through and away from the colliding vortices at Mach 1.22. Our results demonstrate a pressure gradient with high pressure release creating a shock wave. We anticipate our study to be a starting point for more explosively formed vortex collisions. For example, explosives with different velocities of detonation could be tested to produce vortex rings of varying velocities.

Variation within the visually evoked neurovascular coupling response of the posterior cerebral artery is not influenced by age or sex.

Neurovascular coupling (NVC) is the temporal and spatial coordination between local neuronal activity and regional cerebral blood flow. The literature is unsettled on whether age and/or sex affect NVC, which may relate to differences in methodology and the quantification of NVC in small sample-sized studies. The aim of this study was to 1) determine the relative and combined contribution of age and sex to the variation observed across several distinct NVC metrics (n = 125, 21-66 yr; 41 males) and 2) present an approach for the comprehensive systematic assessment of the NVC response using transcranial Doppler ultrasound. NVC was measured as the relative change from baseline (absolute and percent change) assessing peak, mean, and total area under the curve (tAUC) of cerebral blood velocity through the posterior cerebral artery (PCAv) during intermittent photic stimulation. In addition, the NVC waveform was compartmentalized into distinct regions, acute (0-9 s), mid (10-19 s), and late (20-30 s), following the onset of photic stimulation. Hierarchical multiple regression modeling was used to determine the extent of variation within each NVC metric attributable to demographic differences in age and sex. After controlling for differences in baseline PCAv, the R2 data suggest that 1.6%, 6.1%, 1.1%, 3.4%, 2.5%, and 4.2% of the variance observed within mean, peak, tAUC, acute, mid, and late response magnitude is attributable to the combination of age and sex. Our study reveals that variability in NVC response magnitude is independent of age and sex in healthy human participants, aged 21-66 yr.NEW & NOTEWORTHY We assessed the variability within the neurovascular coupling response attributable to age and sex (n = 125, 21-66 yr; 41 male). Based on the assessment of posterior cerebral artery responses to visual stimulation, 0%-6% of the variance observed within several metrics of NVC response magnitude are attributable to the combination of age and sex. Therefore, observed differences between age groups and/or sexes are likely a result of other physiological factors.