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The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.

Haptic feedback of gripping forces during robotassisted surgery can benefit the surgical outcome by means of reduced forces applied to the tissue. A custom-designed haptic user interface allows to control four degrees of freedom of the instrument’s endeffector and to display gripping forces. System-centered evaluation is performed to assess its capability of displaying feedback with high mechanical bandwidth. In addition, the perception of gripping forces is evaluated using task-centered methods. Two tasks were performed by ten participants to assess the perceived feedback regarding size and stiffness of grasped objects. Maximum feedback forces of 4.3N and a mechanical bandwidth of 73.5 Hz are achieved. Tests with participants showed promising results regarding the discrimination of size and stiffness of grasped objects.

Building on scholarship on the mediatization of organizations, we propose a conception of the social media orientation of organizational leaders and apply it to higher education. Based on an online survey of 276 leaders of Swiss higher education institutions, we show that social media platforms have made their way into university management and communication but are still not as important as news media. The study discusses differences between university types and uses the literature on new public management to derive influencing factors.

Increasing patient safety during operations is an inevitable topic in anaesthesiology. The cockpit strategy presented by Vogelsang et al. addresses this issue with elements such as closed loop communication and the use of checklists. In this paper, the use of checklists is taken up further. An AR application is presented that augments checklists for anaesthesia induction into the user’s field of view. The application is to be implemented in teaching and help prospective physicians to internalise the workflows in anaesthesiology more quickly and sustainably. A working prototype has been created and loaded onto the HoloLens 2. The prototype is being assessed and evaluated by an anaesthetist. The feedback will be included into the following development steps. The application will be further adapted to the needs and requirements of the users. In order to evaluate the usability and the user experience, students and medical professionals should test and evaluate the application repeatedly.

The global shortage of healthcare staff has led to high workloads and subsequent risks to patient well-being. One of the professions affected is that of the scrub nurse. Robotic scrub nurse systems have the potential to reduce workload and to assist in handling surgical instruments. Existing approaches mostly use two-finger grippers or electromagnetic grippers. However, it is assumed that a granular jamming gripper is more suitable for handling various surgical instruments, regardless of material and shape. A gripping unit based on a granular jamming gripper and attached to a robotic arm is presented. For evaluation, six surgical instruments were repeatedly gripped and transported. The granular jamming gripper was found to be suitable for picking up and transferring most instruments, however, handling very flat instruments turned out to be challenging.

Possibilities of applying automated content analysis in journalism studies include, for example, machine learning to identify topics in journalistic coverage or measuring news diffusion via automated approaches. But how have computational methods been applied thus far? And what are consequences of the “computational turn” in communication science, especially concerning interdisciplinarity? Based on a systematic literature review, this article summarizes the use of automated content analysis in journalism studies. Results illustrate an increasing use of the method by communication scientists, as yet another indicator of methodological interdisciplinarity in communication science. However, there is little evidence of an increase in theoretical interdisciplinarity: Studies relying on computational methods do not increasingly refer to theories from other disciplines. With respect to practical interdisciplinarity, for instance collaborations, our discipline is by no means becoming more interdisciplinary. Instead, we find a shift in favor of technical disciplines. At least up to now, the “computational turn” in communication science should thus not be equated with an “interdisciplinary turn.”

In conventional laparoscopy, the field of view of the surgeon is limited. Angled laparoscopes enable the observation of surrounding structures, however, to change the viewing perspective on a specific object, permanent repositioning and rotation of the shaft is required. In this paper, a demonstrator of a steerable flexible laparoscope is presented, enabling the user to intuitively adjust the perspective onto an object by means of a single control element. The laparoscope provides a viewing angle of ± 50° at 50 mm working distance. In first tests, the presented laparoscope showed advantages regarding intuitiveness of the control, easier handling, and improved depth perception.

During laparoscopic procedures, the surgeon's view of the situs, and thus her or his performance, is dependent on the skills of the camera assistant. The surgeon lacks control over his own field of view and there is a high potential for reducing mental load and workflow issues. In this paper, a research setup of a 360° laparoscopic imaging system is presented and evaluated. The system consists of a 360° camera and a head-mounted display, through which the surgeon can inspect the situs. In a user test, the system showed advantages over a conventional laparoscope regarding orientation in the situs, intuitiveness of operation, and faster task completion.

Accurate measurement of interaction forces during robot-assisted surgery requires compact force sensing modalities in the surgical tools, thus might add considerable cost to the setup. Measuring the motor current to estimate gripping forces, is an advantageous approach since no expensive force sensor is needed. In this paper, a mechanical interface is presented, which allows actuating conventional articulated instruments for robot-assisted surgery. The interface features the estimation of static gripping forces at the instrument’s tip based on the motor current. The evaluation shows reproducible results, and the current-based approach seems to be a cost-efficient way to estimate gripping forces.

When a structural element, like a column, is evaluated for resistance using the finite element method or analytical calculation, all parameters related to the resistance side and action effect are treated as deterministic. Nevertheless, in probabilistic analyses, these parameters are regarded as random variables, which are defined using various distributions like the normal distribution, log-normal distribution, beta, or gamma distribution. Monte Carlo Simulation (MCS) and Latin Hypercube Sampling (LHS) are two sampling methods widely used for generating random samples from statistical distribution. The number of samples generated influences the accuracy of the sampling methods especially the Monte Carlo Simulation; generally speaking, the more samples generated, the more accurate the results and this also implies a significant amount of work and computation time. Consequently, the purpose of this paper is to compare the two sampling methods for the reliability assessment of the resistance of the composite column to flexural buckling under compression force.

Light hypernuclei containing one or two Λ baryons are the subject of an ongoing experimental campaign aiming to study the spectrum of these systems, as well as the 2 and 3-body interaction between Λ hyperons and nucleons. Here we shortly review the theoretical study of these systems within the framework of baryonic effective field theory.

Lattice quantum chromodynamics calculations of multi-baryon systems with physical quark masses could bridge the gap between nuclear physics and its fundamental theory. Such calculations are performed on a finite grid, and thus extrapolation of finite-volume numerical results to the physical-relevant free-space quantities is needed. A common approach for the extrapolation utilizes the two-body Lüscher formula and its generalization to larger systems. To understand better the accuracy of this approach we study here two model systems, bosonic and fermionic. The few-body systems are solved with the stochastic variational method in a periodic box, and the extrapolated values are compared to those calculated directly in free space.

Background: Intimate partner violence (IPV) and violence against children are global issues with severe consequences. Intersections shared by the 2 forms of violence have led to calls for joint programming efforts to prevent both IPV and violence against children. Parenting programs have been identified as a key entry point for addressing multiple forms of family violence. Building on the IPV prevention material that has been integrated into the parenting program ParentText, a digital parenting chatbot, this pilot study seeks to explore parents' engagement with the IPV prevention content in ParentText and explore preliminary changes in IPV., Objective: This study aimed to assess parents' and caregivers' level of engagement with the IPV prevention material in the ParentText chatbot and explore preliminary changes in experiences and perpetration of IPV, attitudes toward IPV, and gender-equitable behaviors following the intervention., Methods: Caregivers of children aged between 0 and 18 years were recruited through convenience sampling by research assistants in Cape Town, South Africa, and by UNICEF (United Nations Children's Fund) Jamaica staff in 3 parishes of Jamaica. Quantitative data from women in Jamaica (n=28) and South Africa (n=19) and men in South Africa (n=21) were collected electronically via weblinks sent to caregivers' phones using Open Data Kit. The primary outcome was IPV experience (women) and perpetration (men), with secondary outcomes including gender-equitable behaviors and attitudes toward IPV. Descriptive statistics were used to report sociodemographic characteristics and engagement outcomes. Chi-square tests and 2-tailed paired dependent-sample t tests were used to investigate potential changes in IPV outcomes between pretest and posttest., Results: The average daily interaction rate with the program was 0.57 and 0.59 interactions per day for women and men in South Africa, and 0.21 for women in Jamaica. The rate of completion of at least 1 IPV prevention topic was 25% (5/20) for women and 5% (1/20) for men in South Africa, and 21% (6/28) for women in Jamaica. Exploratory analyses indicated significant pre-post reductions in overall IPV experience among women in South Africa (P=.01) and Jamaica (P=.01) and in men's overall harmful IPV attitudes (P=.01) and increases in men's overall gender-equitable behaviors (P=.02) in South Africa., Conclusions: To the best of our knowledge, this is the first pilot study to investigate user engagement with and indicative outcomes of a digital parenting intervention with integrated IPV prevention content. Study findings provide valuable insights into user interactions with the chatbot and shed light on challenges related to low levels of chatbot engagement. Indicative results suggest promising yet modest reductions in IPV and improvements in attitudes after the program. Further research using a randomized controlled trial is warranted to establish causality., (©Moa Schafer, Jamie Lachman, Paula Zinser, Francisco Antonio Calderón Alfaro, Qing Han, Chiara Facciola, Lily Clements, Frances Gardner, Genevieve Haupt Ronnie, Ross Sheil. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.01.2025.)

Simulation-based education is a widely used teaching technique in healthcare education. Simulation can provide a rich learning environment for caregivers at all levels. Creating simulation-based scenarios is a systematic, evidence-based, learner-centered process that requires skill and expertise. There are 11 known criteria of best practice in simulation design. Using best practices in simulation scenario design development can provide the bedrock for learners to engage in clinical practice with competency, confidence, and caring. Examples and suggestions are provided to guide readers to create quality, learner-centered simulation scenarios using the Healthcare Simulation Standards of Best Practice: Simulation Design., Competing Interests: Disclosure The authors have no financial or commercial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source., Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies., Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH)., Exposures: Demographic, perioperative, and disease-related variables., Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites., Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage., Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.

Background: Aortic arch measurements provide a framework for surgical decision-making in neonatal aortic coarctation, specifically in the determination of approach for arch repair by lateral thoracotomy vs median sternotomy. The purpose of this study was to evaluate our experience with transthoracic echocardiography (TTE) and computed tomography angiography (CTA) in the preoperative evaluation of infants with aortic coarctation, specifically comparing arch dimensions as a function of imaging modality., Methods: Imaging data were reviewed for all infants undergoing surgical repair of aortic coarctation at our institution from 2012 to 2022. Infants with both TTE and CTA evaluations were included. Aortic measurements were compared at predefined anatomic regions including ascending aorta, proximal arch, distal arch, and isthmus., Results: During the study period, 372 infants underwent surgical coarctation repair; 72 (19.4%) infants had TTE and CTA arch evaluations preoperatively. Significant discrepancies between imaging modalities were defined by poor correlation coefficients and absolute measurement differences and were most prominent in the proximal aortic arch (R 2  = 0.23 [-4.4 to 3.2 mm]) and isthmus regions (R 2  = 0.11 [-4.2 to 1.7 mm]). Improved correlation was demonstrated in the ascending aorta (R 2  = 0.63) and distal aortic arch (R 2  = 0.54)., Conclusions: Significant variability exists between TTE- and CTA-derived aortic measurements in infants with coarctation, with proximal arch measurements demonstrating the poorest correlation. This anatomic location represents a commonly used arch region for the determination of approach for repair of neonatal aortic coarctation. Thus, these findings have important implications for current preoperative surgical decision-making paradigms and future prospective study to minimize the risk of residual or recurrent arch obstruction., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Operating room (OR) traffic disrupts airflow and increases particle count, which predisposes patients to surgical site infections, particularly in longer surgeries with hardware placement. The aim of this study is to evaluate the rate of traffic during neurosurgical procedures, as well as reasons for and perceptions of OR traffic., Methods: This is a single-center, multimethod study monitoring neurosurgical OR traffic through direct observation, automated monitoring, and interviews. Traffic was observed between the skin incision and closure. Personal interviews with OR teams including surgeons, anesthesia, and nurses were conducted to evaluate their perceptions of the frequency of OR traffic and reasons for OR traffic., Results: Direct observation reported OR door opening an average of 18 times, with 20 people entering or exiting per hour. The exact reason for traffic was not verified in all traffic cases and was able to be confirmed in only a third of the cases. Automated monitoring resulted in an average of 31 people entering or exiting the OR per hour. The procedure length was significantly associated with the number of people entering or exiting the OR per hour (P < .0001). Interviews highlighted that OR teams reported traffic to be significantly lower than observed and automated monitoring results, with approximately <6 people entering or exiting per hour., Conclusions: OR traffic is higher than staff expected, and updated processes are required to reduce the number of times the OR door opens. Implementing automated observation of OR traffic could reduce the OR traffic and the risk for surgical site infection., (Copyright © 2024. Published by Elsevier Inc.)

While allowing for rapid recruitment of large samples, online psychiatric and neurodevelopmental research relies heavily on participants' self-report of neuropsychiatric symptoms, foregoing the rigorous clinical characterization of laboratory settings. Autism spectrum disorder (ASD) research is one example where the clinical validity of such an approach remains elusive. Here, we compared participants characterized online via self-reports against in-person participants evaluated by clinicians. Despite having comparable self-reported autism symptoms, the online high-trait group reported significantly more social anxiety and avoidant behavior than in-person ASD subjects. Within the in-person sample, there was no relationship between self-rated and clinician-rated autism symptoms, suggesting these approaches may capture different aspects of ASD. The online high-trait and in-person ASD participants also differed in their behavior in well-validated social decision-making tasks: the in-person group perceived having less social control and acted less affiliative towards virtual characters. Our study aimed to draw comparisons at three levels: methodological platform (online versus in-person), symptom measurement (self- versus clinician-report), and social behavior. We identified a lack of agreement between self- and clinician-rated measures of symptoms and divergent social tendencies in groups ascertained by each method, highlighting the need for differentiation between in-person versus online samples in autism research., Competing Interests: Additional Declarations: There is NO Competing Interest.

As transcranial ultrasound stimulation (TUS) advances as a precise, non-invasive neuromodulatory method, there is a need for consistent reporting standards to enable comparison and reproducibility across studies. To this end, the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST) formed a subcommittee of experts across several domains to review and suggest standardised reporting parameters for low intensity TUS, resulting in the guide presented here. The scope of the guide is limited to reporting the ultrasound aspects of a study. The guide and supplementary material provide a simple checklist covering the reporting of: (1) the transducer and drive system, (2) the drive system settings, (3) the free field acoustic parameters, (4) the pulse timing parameters, (5) in situ estimates of exposure parameters in the brain, and (6) intensity parameters. Detailed explanations for each of the parameters, including discussions on assumptions, measurements, and calculations, are also provided., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EM has acted as a consultant for BrainBox Ltd. JFA holds 5 patents on transcranial ultrasound and had research support from Insightec within the last 3 years. MS is a consultant to Brainsonix Corp., co-inventor on several patents in tFUS, and is a member of the US Technical Advisory Group to the IEC responsible for diagnostic ultrasound output regulation. BET is a developer of and holds a financial interest in the commercially available k-Plan treatment planning software. LV is a member of the scientific board of the Brainbox Initiative. KBP has acted as a consultant for Attune Neurosciences and has had research support from MR Instruments and General Electric within the last 3 years., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Molecular docking is a key technique in various fields like structural biology, medicinal chemistry, and biotechnology. It is widely used for virtual screening during drug discovery, computer-assisted drug design, and protein engineering. A general molecular docking process consists of the target and ligand selection, their preparation, and the docking process itself, followed by the evaluation of the results. However, the most commonly used docking software provides no or very basic evaluation possibilities. Scripting and external molecular viewers are often used, which are not designed for an efficient analysis of docking results. Therefore, we developed InVADo, a comprehensive interactive visual analysis tool for large docking data. It consists of multiple linked 2D and 3D views. It filters and spatially clusters the data, and enriches it with post-docking analysis results of protein-ligand interactions and functional groups, to enable well-founded decision-making. In an exemplary case study, domain experts confirmed that InVADo facilitates and accelerates the analysis workflow. They rated it as a convenient, comprehensive, and feature-rich tool, especially useful for virtual screening.

Introduction and Objectives: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications., Materials and Methods: Chart review of 1200 LT patients from 2002-2020 was performed. Postmenopausal women were defined as women over 51 and compared to a control group of men over 51. Prevalence of LT indications was determined. Subgroup analysis assessed cardiovascular disease risk. BMI and ASCVD risk scores were calculated at the time of LT and after 1 year., Results: 510 patients met the inclusion criteria: 189 (37.1%) women and 321 (62.9%) men. The most common indication was NASH for women (26.5%, p<0.001) and alcohol-related cirrhosis for men (23.1%). 53 men and 46 women underwent subgroup analysis. There was no significant difference in BMI or ASCVD 10-year risk post-LT between sexes. MI occurred more in men (n=9.17%) than women (n=1, 2%, p=0.015), with no significant differences in CAD, CHF, or stroke. LT complications occurred less in men (n=5.9%) than women (n=20, 43%, p=0.0001)., Conclusions: Postmenopausal women were significantly more likely to have NASH as an indication for LT than men. Postmenopausal women had greater weight gain and more noncardiac complications than men. Women did not have increased cardiovascular outcomes, ASCVD risk, or mortality. Diet education and weight control in postmenopausal women with existing risk factors for NASH should be encouraged to modulate health outcomes., Competing Interests: Declaration of interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: MemorialCare Medical Group (MCMG) designed and implemented an advanced health care practitioner (AHP)-led home-visit primary care program to address the needs of a frail older adult population, who struggled with arriving for in-office care. We sought to perform a preliminary analysis to determine the program's efficacy. Methods: We conducted a retrospective review of patients enrolled in the program through tabulation of total costs of care, inpatient visits (IPVs), emergency department visits (EDVs), and 30-day readmissions (30DRs) 1-year pre-enrollment and postenrollment. Results: For the prior year and postyear windows, per-member per-month total cost of care decreased 21.4% ($5,883.44-$4,622.31), reflecting a gross savings of $2,693,480.32. Mean IPVs (2.42-1.56), EDVs (1.53-0.93), and 30DRs (0.27-0.13) were reduced. Conclusions: Initial analysis of an AHP-led in-home primary care program for frail seniors shows promise for improved outcomes with a clear decrease in the total cost of care.

Background: Intimate partner violence (IPV) is a serious public health issue which experienced a sharp incline during the onset of COVID-19. Increases in other forms of violence, such as violence against children (VAC), have also been linked to the pandemic, and there have been calls for greater prevention efforts that tackle both forms of violence concurrently. The COVID-19 crisis has highlighted the urgent need for evidence-based and scalable violence prevention interventions that target multiple forms of family violence. Parenting programmes have shown promising results in preventing various forms of family violence, including IPV and VAC, and have recently experienced an expansion in delivery, with digital intervention formats growing. This paper describes the development and evaluation of the IPV prevention content designed and integrated into ParentText, a chatbot parenting intervention adapted from Parenting for Lifelong Health programmes., Methods: The ParentText IPV prevention content was developed using the Six Steps in Quality Intervention Development (6SQuID) framework. This involved targeted literature searches for key studies to identify causal factors associated with IPV and determining those with greatest scope for change. Findings were used to develop the intervention content and theory of change. Consultations were held with academic researchers (n = 5), practitioners (n = 5), and local community organisations (n = 7), who reviewed the content. A formative evaluation was conducted with parents in relationships (n = 96) in Jamaica to better understand patterns in user engagement with the intervention and identify strategies to further improve engagement., Results: Using the 6SQuID model, five topics on IPV prevention were integrated into the ParentText chatbot. Text-messages covering each topic, including additional materials such as cartoons and videos, were also developed. The formative evaluation revealed an average user-engagement length of 14 days, 0.50 chatbot interactions per day, and over half of participants selected to view additional relationship content., Conclusions: This article provides a unique contribution as the first to integrate IPV prevention content into a remotely delivered, digital parenting intervention for low-resource settings. The findings from this research and formative evaluation shed light on the promising potential of chatbots as scalable and accessible forms of violence prevention, targeting multiple types of family violence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: We sought to improve utilization of a sepsis care bundle and decrease 3- and 30- day sepsis-attributable mortality, as well as determine which care elements of a sepsis bundle are associated with improved outcomes., Methods: Children's Hospital Association formed a QI collaborative to Improve Pediatric Sepsis Outcomes (IPSO) (January 2017-March 2020 analyzed here). IPSO Suspected Sepsis (ISS) patients were those without organ dysfunction where the provider "intended to treat" sepsis. IPSO Critical Sepsis (ICS) patients approximated those with septic shock. Process (bundle adherence), outcome (mortality), and balancing measures were quantified over time using statistical process control. An original bundle (recognition method, fluid bolus < 20 min, antibiotics < 60 min) was retrospectively compared with varying bundle time-points, including a modified evidence-based care bundle, (recognition method, fluid bolus < 60 min, antibiotics < 180 min). We compared outcomes using Pearson χ-square and Kruskal Wallis tests and adjusted analysis., Results: Reported are 24 518 ISS and 12 821 ICS cases from 40 children's hospitals (January 2017-March 2020). Modified bundle compliance demonstrated special cause variation (40.1% to 45.8% in ISS; 52.3% to 57.4% in ICS). The ISS cohort's 30-day, sepsis-attributable mortality dropped from 1.4% to 0.9%, a 35.7% relative reduction over time (P < .001). In the ICS cohort, compliance with the original bundle was not associated with a decrease in 30-day sepsis-attributable mortality, whereas compliance with the modified bundle decreased mortality from 4.75% to 2.4% (P < .01)., Conclusions: Timely treatment of pediatric sepsis is associated with reduced mortality. A time-liberalized care bundle was associated with greater mortality reductions., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Glomerular filtration rate (GFR) is a key measure of kidney function but often inaccurately ascertained by serum creatinine and cystatin C in pediatrics. In this pilot trial, we evaluated the relationship between GFR calculated by using phase-contrast MRI (PC-MRI) biomarkers and GFR by 125 I-iothalamate clearance in youth undergoing bone marrow transplantation (BMT)., Methods: A total of twenty-one pediatric BMT candidates (8-21 years of age) were recruited for a research kidney PC-MRI. After completion of 125 I-iothalamate clearance, same-day PC-MRI measurements were completed of the kidney circulation without a gadolinium-based contrast agent. MRI included a non-contrast balanced-SSFP-triggered angiography to position ECG-gated breath-held 2D PC-MRI flow measurements (1.2 × 1.2 × 6 mm 3 ). A multivariate model of MRI biomarkers estimating GFR (GFR-MRI) was selected using the elastic net approach., Results: The GFR-MRI variables selected by elastic net included average heart rate during imaging (bpm), peak aorta flow below the kidney artery take-offs (ml/s), average kidney artery blood flow, average peak kidney vein blood flow, and average kidney vein blood flow (ml/s). The GFR-MRI model demonstrated strong agreement with GFR by 125 I-iothalamate (R 2  = 0.65), which was stronger than what was observed with eGFR by the full age spectrum and Chronic Kidney Disease in Children under 25 (CKiD U25) approaches., Conclusion: In this pilot study, noninvasive GFR-MRI showed strong agreement with gold standard GFR in youth scheduled for BMT. Further work is needed to evaluate whether non-contrast GFR-MRI holds promise to become a superior alternative to eGFR and GFR by clearance techniques. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: The purpose of this phenomenological study is to understand mothers' lived pregnancy experiences during the COVID-19 pandemic., Design: A qualitative, phenomenological study SETTING: Participants completed the demographic survey online and semi-structured interviews, via video conferencing between November and December 2021 PARTICIPANTS: A sample of 28 mothers who were pregnant during the COVID-19 pandemic participated in the study., Methods and Results: An inductive, thematic approach was used to analyze the data. Two central themes and eight subthemes emerged from the six-phase thematic analysis. The first central theme, Depth of Knowledge About COVID-19, included the following subthemes: 1) Vaccines and 2) Uncertainty for Exposure. The second central theme, Impacts of COVID-19, had six subthemes: 1) Types of Support Received, 2) COVID-19 Restrictions, 3) Childcare, 4) Mental Health, 5) Spending More Time at Home, and 6) Isolation., Conclusions: Findings of this study revealed mothers experienced a significant amount of stress and anxiety related to the coronavirus pandemic during their pregnancy., Implications for Practice: Our findings highlight the need to provide pregnant mothers comprehensive care, including mental health services, adequate access to social support, and providing clear information regarding COVID-19 vaccination and its impacts on pregnancy., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In synaptic molecular communication (MC), the activation of postsynaptic receptors by neurotransmitter (NTs) is governed by a stochastic reaction-diffusion process. This randomness of synaptic MC contributes to the randomness of the electrochemical downstream signal in the postsynaptic cell, called postsynaptic membrane potential (PSP). Since the randomness of the PSP is relevant for neural computation and learning, characterizing the statistics of the PSP is critical. However, the statistical characterization of the synaptic reaction-diffusion process is difficult because the reversible bi-molecular reaction of NTs with receptors renders the system nonlinear. Consequently, there is currently no model available which characterizes the impact of the statistics of postsynaptic receptor activation on the PSP. In this work, we propose a novel statistical model for the synaptic reaction-diffusion process in terms of the chemical master equation (CME). We further propose a novel numerical method which allows to compute the CME efficiently and we use this method to characterize the statistics of the PSP. Finally, we present results from stochastic particle-based computer simulations which validate the proposed models. We show that the biophysical parameters governing synaptic transmission shape the autocovariance of the receptor activation and, ultimately, the statistics of the PSP. Our results suggest that the processing of the synaptic signal by the postsynaptic cell effectively mitigates synaptic noise while the statistical characteristics of the synaptic signal are preserved. The results presented in this paper contribute to a better understanding of the impact of the randomness of synaptic signal transmission on neuronal information processing.

Background: Cannabis is one of the most widely used substances in the world, with usage trending upward in recent years. However, although the psychiatric burden associated with maladaptive cannabis use has been well established, reliable and interpretable biomarkers associated with chronic use remain elusive. In this study, we combine large-scale functional magnetic resonance imaging with machine learning and network analysis and develop an interpretable decoding model that offers both accurate prediction and novel insights into chronic cannabis use., Methods: Chronic cannabis users (n = 166) and nonusing healthy control subjects (n = 124) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic users and nonusers based on whole-brain functional connectivity. Network analysis was used to identify the most predictive regions and communities., Results: We obtained high (∼80% out-of-sample) accuracy across 4 different classification models, demonstrating that task-evoked connectivity can successfully differentiate chronic cannabis users from nonusers. We also identified key predictive regions implicating motor, sensory, attention, and craving-related areas, as well as a core set of brain networks that contributed to successful classification. The most predictive networks also strongly correlated with cannabis craving within the chronic user group., Conclusions: This novel approach produced a neural signature of chronic cannabis use that is both accurate in terms of out-of-sample prediction and interpretable in terms of predictive networks and their relation to cannabis craving., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The primary aims of this study were to compare in patients with esophageal or esophagogastric junction cancers the potential of 68 Ga-NODAGA-RGD PET/CT with that of 18 F-FDG PET/CT regarding tumoral uptake and distribution, as well as histopathologic examination., Methods: Ten 68 Ga-NODAGA-RGD and ten 18 F-FDG PET/CT were performed in nine prospectively included participants (1 woman; aged 58 ± 8.4 y, range 40-69 y). Maximum SUV (SUV max ) and metabolic tumor volumes (MTV) were calculated. The Mann-Whitney U test and Spearman correlation analysis (ρ) were used., Results: 68 Ga-NODAGA-RGD PET/CT detected positive uptake in 10 primary sites (8 for primary tumors and 2 for local relapse suspicion), 6 lymph nodes and 3 skeletal sites. 18 F-FDG PET/CT detected positive uptake in the same sites but also in 16 additional lymph nodes and 1 adrenal gland. On a lesion-based analysis, SUV max of 18 F-FDG was significantly higher than those of 68 Ga-NODAGA-RGD (4.9 [3.7-11.3] vs. 3.2 [2.6-4.2] g/mL, p = 0.014). Only one participant showed a higher SUV max in an osseous metastasis with 68 Ga-NODAGA-RGD as compared to 18 F-FDG (6.6 vs. 3.9 g/mL). Correlation analysis showed positive correlation between 18 F-FDG and 68 Ga-NODAGA-RGD PET parameters (ρ = 0.56, p = 0.012 for SUV max , ρ = 0.78, p < 0.001 for lesion-to-background ratios and ρ = 0.58, p = 0.024 for MTV). We observed that 18 F-FDG uptake was homogenous inside all the confirmed primary sites (n = 9). In contrast, 68 Ga-NODAGA-RGD PET showed more heterogenous uptake in 6 out of the 9 confirmed primary sites (67%), seen mostly in the periphery of the tumor in 5 out of the 9 confirmed primary sites (56%), and showed slight extensions into perilesional structures in 5 out of the 9 confirmed primary sites (56%)., Conclusions: In conclusion, 68 Ga-NODAGA-RGD has lower potential in the detection of esophageal or esophagogastric junction malignancies compared to 18 F-FDG. However, the results suggest that PET imaging of integrin α v β 3 expression may provide complementary information and could aid in tumor diversity and delineation., Trial Registration: Trial registration: NCT02666547. Registered January 28, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02666547 ., (© 2023. The Author(s).)

Introduction: Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addiction remain unclear., Methods: We developed a novel stop-signal functional magnetic resonance imaging task where the stop-signal reaction time (SSRT-a classical inhibitory control measure) was tested under different salience conditions (modulated by drug, food, threat, or neutral words) in individuals with cocaine use disorder (CUD; n = 26) versus demographically matched healthy control participants (n = 26)., Results: Despite similarities in drug cue-related SSRT and valence and arousal word ratings between groups, dorsolateral prefrontal cortex (dlPFC) activity was diminished during the successful inhibition of drug versus food cues in CUD and was correlated with lower frequency of recent use, lower craving, and longer abstinence (Z > 3.1, P < 0.05 corrected)., Discussion: Results suggest altered involvement of cognitive control regions (e.g. dlPFC) during inhibitory control under a drug context, relative to an alternative reinforcer, in CUD. Supporting the iRISA model, these results elucidate the direct impact of drug-related cue reactivity on the neural signature of inhibitory control in drug addiction., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transcranial ultrasound stimulation (TUS) has been shown to be a safe and effective technique for non-invasive superficial and deep brain stimulation. Safe and efficient translation to humans requires estimating the acoustic attenuation of the human skull. Nevertheless, there are no international guidelines for estimating the impact of the skull bone. A tissue independent, arbitrary derating was developed by the U.S. Food and Drug Administration to take into account tissue absorption (0.3 dB/cm-MHz) for diagnostic ultrasound. However, for the case of transcranial ultrasound imaging, the FDA model does not take into account the insertion loss induced by the skull bone, nor the absorption by brain tissue. Therefore, the estimated absorption is overly conservative which could potentially limit TUS applications if the same guidelines were to be adopted. Here we propose a three-layer model including bone absorption to calculate the maximum pressure transmission through the human skull for frequencies ranging between 100 kHz and 1.5 MHz. The calculated pressure transmission decreases with the frequency and the thickness of the bone, with peaks for each thickness corresponding to a multiple of half the wavelength. The 95th percentile maximum transmission was calculated over the accessible surface of 20 human skulls for 12 typical diameters of the ultrasound beam on the skull surface, and varies between 40% and 78%. To facilitate the safe adjustment of the acoustic pressure for short ultrasound pulses, such as transcranial imaging or transcranial ultrasound stimulation, a table summarizes the maximum pressure transmission for each ultrasound beam diameter and each frequency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)