Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging.

AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1-5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy.Clinical Trial Registration Number: NCT04899908.Clinical Trial Registration Date: 25/05/2021.

Caregiving While Black: A Novel, Online Culturally Tailored Psychoeducation Course for Black Dementia Caregivers.

BACKGROUND AND OBJECTIVES: Psychoeducation interventions using distance learning modalities to engage caregivers in active learning environments have demonstrated benefits in enhancing caregiving mastery. However, few of these programs have been specifically adapted to develop mastery in Black caregivers. RESEARCH DESIGN AND METHODS: A multimethod approach was carried out to assess Caregiving While Black (CWB), including pre-post surveys and in-depth interviews. This psychoeducation course addresses the cultural realities of caring for a person living with dementia as a Black American. Caregivers engaged in online asynchronous education related to healthcare navigation, home life management, and self-care. Primary (caregiving mastery) and secondary outcomes (anxiety, depression, perceived stress, burden, perceived ability to manage behavioral and psychological symptoms) were assessed at baseline and post-course (10 weeks). RESULTS: Thirty-two Black caregivers from across the United States completed the course within the allotted time frame. Paired sample t test analyses revealed significant reductions in caregiver burden and role strain. Caregiver mastery from baseline to completion increased by 0.45 points with an effect size of 0.26 (Cohen's d). Twenty-nine caregivers participated in an optional post-course interview, and thematic analysis led to the construction of 5 overarching themes: Comfortability with a Culturally Tailored Course; Experiences Navigating the Course Platform; Utility of Course Resources; Time as a Barrier and Facilitator; Familial and Community Engagement. DISCUSSION AND IMPLICATIONS: Pilot findings convey a need to continue creating and receiving feedback on culturally tailored psychoeducation programs for dementia caregivers. The next steps include applying results to fuel the success of the next iteration of CWB.

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification.

Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd3+ cations with higher Z Bi3+. These next-generation nanoparticles are based on the AGuIX® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX® is used as an initial chelation platform to exchange Gd3+ for Bi3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.

Attitudes toward health care needs and utilization of a university health center among LGBT and non-LGBT college students.

Objective: First, to examine general health care attitudes and health care utilization of a University Health Service (UHS) at a large university. Second, to identify differences between LGBT and non-LBGT students. Participants: 2,943 university students were surveyed in Spring 2013; 7.8% LGBT, 67% undergraduate and 65% female. Methods: A cross-sectional mixed-methods online survey to assess health care utilization and attitudes. Results: A majority had utilized UHS and held positive attitudes in general. LGBT students were more likely to: use UHS for ongoing care, mental health, and preventive care; report concerns about utilization (e.g. confidentiality, sensitivity, and discrimination issues); report provider discomfort discussing sexuality; and hold positive attitudes toward the health care needs of LGBT students. Conclusions: University health centers have an important role in student health. Barriers to care should be removed, including perceived discrimination. Student health center staff should be trained on LGBT health issues.

Experiences of Black American Dementia Caregivers During the COVID-19 Pandemic.

Dementia caregivers are responsible for the daily care and management of individuals who are among the most vulnerable to the serious consequences of COVID-19. This qualitative study explores the experience of Black dementia caregivers during the COVID-19 pandemic in the United States. Nineteen Black dementia caregivers were recruited to participate in semi-structured focus groups held in April 2021. Four overarching themes were constructed during analysis: social isolation, decreased well-being, the good and bad of telehealth, and challenges fulfilling health care needs. The results indicate the experience of Black dementia caregivers overlaps with existing literature on the experiences of dementia caregivers of other races during COVID-19. These results can assist in addressing the specific needs and improving the experiences of dementia caregivers in current and future public health crises.

Taking the strain? Police well-being in the COVID-19 era.

Drawing on survey and interview data collected in one police force area, this article considers the varied impacts on police well-being arising during the COVID-19 pandemic. Approximately one-third of police officers surveyed reported feeling less safe in their role during the pandemic, and nearly half suffered increased anxiety. The toll on well-being appears to be most acute for frontline officers and those with caring responsibilities, and is strongly associated with increases in workload. The task of 'repairing' well-being will require detailed and sensitive consideration involving genuine efforts to hear the voices of those who have endured this prolonged tour of duty.

"Falling between the cracks": Experiences of Black dementia caregivers navigating U.S. health systems.

In addition to numerous care responsibilities, family caregivers are expected to navigate health systems and engage in healthcare management tasks on behalf of their persons living with dementia (PLWD). These challenging tasks pose additional difficulties for Black dementia caregivers. Due to the centuries-old, disadvantaged social history of Black Americans, several unique stressors, vulnerabilities, and resources have emerged which inform and affect Black dementia caregivers' experiences and well-being. Focus groups were held with Black caregivers (N = 19) from the United States to explore the unique experiences and perspectives of this population navigating the U.S. health system on behalf of their PLWD. Five overarching themes were constructed during thematic analysis: Forced Advocacy, Poor Provider Interaction, Payor Source Dictates Care, Discrimination, and Broken Health System. Black dementia caregivers unanimously concurred that the health system that they experience in America is "broken." Gaps in the health system can lead to people [as one caregiver passionately expressed] "falling between the cracks," in terms of care, services, and resources needed. Caregivers agreed that class, sex, utilizing public health insurance, and being a "person of color" contribute to their difficulties navigating the health system. Caregivers perceived being dismissed by providers, forcing them to advocate for both themselves and their PLWD. Healthcare providers and researchers can utilize these findings to improve the experiences and healthcare outcomes of Black persons living with dementia and their caregivers. Additionally, these findings can lead to the development of culturally tailored caregiver education programs.

Three-Year Nursing PhD Model Recommendations from the RWJF Future of Nursing Scholars.

BACKGROUND: In response to the 2011 Future of Nursing report, the Robert Wood Johnson Foundation created the Future of Nursing Scholars (FNS) Program in partnership with select schools of nursing to increase the number of PhD-prepared nurses using a 3-year curriculum. METHOD: A group of scholars and FNS administrative leaders reflect on lessons learned for stakeholders planning to pursue a 3-year PhD model using personal experiences and extant literature. RESULTS: Several factors should be considered prior to engaging in a 3-year PhD timeline, including mentorship, data collection approaches, methodological choices, and the need to balance multiple personal and professional loyalties. Considerations, strategies, and recommendations are provided for schools of nursing, faculty, mentors, and students. CONCLUSION: The recommendations provided add to a growing body of knowledge that will create a foundation for understanding what factors constitute "success" for both PhD programs and students. [J Nurs Educ. 2022;61(1):19-28.].

Macrophage interferon regulatory factor 4 deletion ameliorates aristolochic acid nephropathy via reduced migration and increased apoptosis.

Aristolochic acid (AA) is the causative nephrotoxic alkaloid in AA nephropathy, which results in a tubulointerstitial fibrosis. AA causes direct proximal tubule damage as well as an influx of macrophages, although the role of macrophages in pathogenesis is poorly understood. Here, we demonstrate that AA directly stimulates migration, inflammation, and ROS production in macrophages ex vivo. Cells lacking interferon regulatory factor 4 (IRF4), a known regulator of macrophage migration and phenotype, had a reduced migratory response, though effects on ROS production and inflammation were preserved or increased relative to WT cells. Macrophage-specific IRF4-knockout mice were protected from both acute and chronic kidney effects of AA administration based on functional and histological analysis. Renal macrophages from kidneys of AA-treated macrophage-specific IRF4-knockout mice demonstrated increased apoptosis and ROS production compared with WT controls, indicating that AA directly polarizes macrophages to a promigratory and proinflammatory phenotype. However, knockout mice had reduced renal macrophage abundance following AA administration. While macrophages lacking IRF4 can adopt a proinflammatory phenotype upon AA exposure, their inability to migrate to the kidney and increased rates of apoptosis upon infiltration provide protection from AA in vivo. These results provide evidence of direct AA effects on macrophages in AA nephropathy and add to the growing body of evidence that supports a key role of IRF4 in modulating macrophage function in kidney injury.

Gynecologic interstitial brachytherapy curriculum using a low-cost phantom with ultrasound workshop and a treatment planning workshop is effective.

PURPOSE/OBJECTIVE(S): Standardized simulation training geared towards interstitial brachytherapy (IS BT) for gynecologic malignancies is lacking in radiation oncology resident education. We developed and implemented a curriculum for IS BT training with (1) lecture on equipment, workflow, and guidelines, (2) hands-on ultrasound-guided IS BT workshop, and (3) treatment planning workshop. METHODS AND MATERIAL: The cost in materials of each phantom was approximately $66. After a lecture, two alternating workshops were performed. The first session consisted of a hands-on ultrasound-guided IS BT workshop with one resident imaging the phantom with a transabdominal ultrasound probe and the other resident implanting the phantom with needles. A second session consisted of a hands-on treatment planning workshop using BrachyVision and an l-Q spreadsheet with the following objectives: coverage goal, meeting D2cc constraints, and minimizing V200. The primary outcome was improvement in knowledge assessed with Likert-style questions and objective knowledge-based questions (KBQs). RESULTS: Four of the seven medical residents that participated in this curriculum had prior IS BT experience. Residents reported significantly improved knowledge regarding gynecologic IS BT equipment and procedure, evaluating gynecologic anatomy using ultrasound, CT simulation, contouring, and plan review (overall median pre-session subjective score 2 (1) -(3) versus post-session score 4 (3) -(4, p < 0.01). Residents demonstrated improvement in answering KBQs correctly from 44% correct at baseline to 88% after completion of the curriculum (p < 0.01). All residents "Agree" and "Strongly Agree" the session was an effective learning experience. CONCLUSIONS: Residents participating in phantom training with an ultrasound curriculum and a treatment planning session is effective for improving knowledge and skills in IS BT for radiation oncology residents.

Innovation Amid Pandemic: Construction of a COVID-19 Intensive Care Unit Surge Care Delivery Model.

This article details a shared leadership structure and decision-making processes used to construct an innovative and evidence-based care delivery model for safety and optimal outcomes in the intensive care unit during the novel coronavirus (COVID-19) pandemic. Insights into ways professional development practitioners can facilitate changes in care delivery models, support nurses in their professional roles, and contribute to improved patient care outcomes during the COVID-19 pandemic are provided.

Long-Term Follow-Up of Patients With Ventilator-Dependent High Tetraplegia Managed With Diaphragmatic Pacing Systems.

OBJECTIVE: To explore participants' experiences after implantation of a diaphragmatic pacing system (DPS). DESIGN: Cross-sectional, observational study using self-report questionnaires. SETTING: Participants were recruited from 6 Spinal Cord Injury Model System centers across the United States (Craig Hospital, CO; Jefferson/Magee Rehabilitation Hospital, PA; Kessler Rehabilitation Center, NJ; University of Miami, FL; The Shirly Ryan Ability Lab, IL; Shepherd Center, GA). INTERVENTIONS: Not applicable. PARTICIPANTS: Men and women (N=28) with tetraplegia were enrolled in the study between November 2012 and January 2015. MAIN OUTCOME MEASURES: Participants completed self-report questionnaires focused on their DPS usage and mechanical ventilation, as well as their experiences and satisfaction with the DPS. RESULTS: DPS is a well-tolerated and highly successful device to help individuals living with spinal cord injury who are dependent on ventilators achieve negative pressure, ventilator-free breathing. A small percentage of participants reported complications, including broken pacing wires and surgery to replace or reposition wires. CONCLUSIONS: This study provides insight into the usage patterns of DPS and both the potential negative and positive effects that DPS can have on the life of the user. Knowledge gained from this study can provide a foundation for further discussion about the benefits and potential risks of using a DPS to inform an individual's decision to pursue a DPS implant.

Solution-Grown Formamidinium Hybrid Perovskite (FAPbBr3) Single Crystals for α-Particle and γ-Ray Detection at Room Temperature.

Compared with the widely reported MAPbBr3 single crystals, formamidinium-based (FA-based) hybrid perovskites FAPbBr3 (FPB) with superior chemical and structure stability are expected to be more efficient and perform as more reliable radiation detectors at room temperature. Here, we employ an improved inverse temperature crystallization method to grow FPB bulk single crystals, where issues associated with the retrograde solubility behavior are resolved. A crystal growth phase diagram has been proposed, and accordingly, growth parameters are optimized to avoid the formation of NH4Pb2Br5 secondary phase. The resulting FPB crystals exhibit a high resistivity of 2.8 × 109 Ω·cm and high electron and hole mobility-lifetime products (µτ) of 8.0 × 10-4 and 1.1 × 10-3 cm2·V-1, respectively. Simultaneously, the electron and hole mobilities (µ) are evaluated to be 22.2 and 66.1 cm2·V-1·s-1, respectively, based on the time-of-flight technique. Furthermore, a Au/FPB SC/Au detector is constructed that demonstrates a resolvable gamma peak from 59.5 keV 241Am γ-rays at room temperature for the first time. An energy resolution of 40.1% is obtained at 30 V by collecting the hole signals. These results demonstrate the great potential of FAPbBr3 as a hybrid material for γ-ray spectroscopy and imaging.

Anxiety, Depression, and Pain: Considerations in the Treatment of Patients with Uncontrolled Hypertension.

PURPOSE OF REVIEW: The association between mental health, pain, and treatment-resistant hypertension is an important consideration for treating physicians. We review and discuss the connection between conditions of anxiety, depression, and chronic pain and their effect on uncontrolled hypertension. RECENT FINDINGS: There is significant co-occurrence of hypertension with anxiety, depression, and chronic pain which may lead to undertreatment of hypertension and undertreatment of the underlying mental health disorder. The association between mental health and hypertension is complex and is modulated by physiologic and environmental factors. Physicians treating patients with hypertension should be cognizant of the role anxiety, depression, and chronic pain play in treatment efficacy and compliance. Patients undergoing treatment should be screened for mental health disorders at treatment initiation and frequently thereafter to ensure optimal overall health and compliance.

Examining the Effect of Noise on Biosignal Estimates Extracted through Spatio-Temporal Video Processing.

Spatio-temporal video processing has been used to extract subject vital signals from optical video and, more recently, thermal video. Thermal video, in conjunction with spatio-temporal video processing can extract biosignals optical video cannot; namely temperature data, but also biosignals in poor light conditions. Video processing involves many system parameters that can result in false biosignal reporting. This paper aimed to robustly test spatio-temporal processing algorithms and determine patterns with respect to increasing noise levels. Over 500 simulated thermal videos were generated at 29 different signal frequencies representing heart rates. These videos were contaminated with 18 different levels of Gaussian noise and were used as inputs to the algorithmic system. The algorithmic system processed each video at 6 different filter widths. The results were examined individually and as a collective. Individual results were as expected; the processing resulted in an accurate heart rate estimate if the original signal was inside the filter passband. If the signal was outside of the filter passband, the processing simply amplified noise. These same patterns were observed in the cumulative results, in addition to overarching patterns with respect to noise. Two main patterns were observed; a failure threshold was determined and quantified and a pattern of error behavior beyond this threshold was quantified. The failure threshold occurred at a noise variance of approximately 500, and around this parameter value, all detected signal frequencies were approaching 1.5 Hz (90bpm). This study was able to characterize patterns of failure, which helps to prevent future false reporting.

A Critical Examination of Subgroup Analyses: The National Acute Spinal Cord Injury Studies and Beyond.

The use of high-dose methylprednisolone for acute spinal cord injury continues to be a topic of debate. This controversy largely stems from fundamental issues in statistical interpretation of trial data, most notably subgroup analyses. The purpose of this review is to discuss important examples of improper subgroup analysis and encourage better practices in future research.

Long term monitoring of a pressure ulcer risk patient using thermal images.

Patients in an immobile state are susceptible to pressure ulcers, which are localized injuries to the skin and/or underlying tissues due to prolonged pressure. This paper builds upon a body of work examining in-hospital older adult patients at-risk of developing pedal pressure ulcers by examining thermal images of one patient, who was reporting pain in her right foot, over 112 days of a hospital stay. Thermal images of the patient's left and right heels and malleoli were subjected to image processing to remove noise and enhance contrast, region selection and feature extraction to observe changes in temperature over time. Mean intensity within each ROI was extracted, and the difference in temperature between the left and right heels was calculated over time. The resulting temperature pattern was consistent with the physical phenomenon related to ulcer development, intervention and recovery; the right heel was similar in temperature when starting the study and at the end of the study, but was drastically warmer when experiencing erythema and drastically colder when experiencing ischaemia. These results suggest that consistent thermal imaging, in conjunction with image processing may be able to detect the formation of pressure ulcers faster than can be visually observed. Early detection of pressure ulcers is critical in the prevention of pressure ulcers, and is of great importance to any hospital or nursing home.

Comparison of motion-based analysis to thermal-based analysis of thermal video in the extraction of respiration patterns.

Non-contact methods of extracting vital signals has become a popular area of research. This is likely due to the world's aging population and the increased need for long term and remote monitoring. This paper examines and compares the potential for one modality to capture a vital sign, specifically respiration, in the presence of signal abnormalities. This paper compares temperature based-methods to motion-based methods of extracting respiration rate from thermal video of a subject performing computationally difficult respiration tests. The thermal video was subjected to segmentation-based image processing and region tracking to encompass temperature changes over time. All methods were successful in identifying regular breathing and the absence of breathing, but differed in performance identifying hyperventilation and obstructive sleep apnea simulated breathing. The temperature-based method better depicted airflow volume, while the motion-based method better depicted absence of breath and chest movement; neither signal on its own was able to accurately depict OSA breathing. These results suggest that the fusion of information from different physical phenomenon (i.e. motion and temperature) is important here in detecting abnormal breathing patterns, but also in the detection of all vital signals, adding algorithmic robustness in the presence of signal abnormalities.

Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time to Recombinant Tissue Plasminogen Activator.

BACKGROUND: Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA. OBJECTIVE: To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times. METHODS: This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital. RESULTS: Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group ( P < 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% ( P < 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (ßcoefficient -23.5 minutes, 95% confidence interval [95% CI] -38.6 to -8.50 minutes). CONCLUSION: A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.

Find the Hidden Object. Understanding Play in Psychological Assessments.

Standardized psychological assessments are extensively used by practitioners to determine rate and level of development in different domains of ability in both typical and atypical children. The younger the children, the more likely the trials will resemble play activities. However, mode of administration, timing and use of objects involved are constrained. The purpose of this study is to explore what kind of play is play in psychological assessments, what are the expectations about children's performance and what are the abilities supporting the test activities. Conversation Analysis (CA) was applied to the videorecording of an interaction between a child and a practitioner during the administration of the Bayley Scale of Infant and Toddler Development, III edition. The analysis focuses on a 2'07″ long sequence relative to the administration of the test item "Find the hidden object" to a 23 months old child with Down syndrome. The analysis of the sequence shows that the assessor promotes the child's engagement by couching the actions required to administer the item in utterances with marked child-directed features. The analysis also shows that the objects constituting the test item did not suggest to the child a unique course of action, leading to the assessor's modeling of the successful sequence. We argue that when a play frame is activated by an interactional partner, the relational aspect of the activity is foregrounded and the co-player becomes a source of cues for ways in which playing can develop. We discuss the assessment interaction as orienting the child toward a right-or-wrong interpretation, leaving the realm of play, which is inherently exploratory and inventive, to enter that of instructional activities. Finally, we argue that the sequential analysis of the interaction and of the mutual sense-making procedures that partners put in place during the administration of an assessment could be used in the design and evaluation of tests for a finer understanding of the abilities involved.