Practical Considerations for Navigating Withdrawal from the Federal Select Agent Program.

Introduction: Clear guidance is provided by the Federal Select Agent Program (FSAP) to assist registered entities in nearly all facets of compliance with the Federal select agent regulations (7 CFR Part 331; 9 CFR Part 121; 42 CFR Part 73). If a registered entity chooses to discontinue its registration, detailed instructions for registration withdrawal are deeply embedded within a document entitled "eFSAP Form 1 Amendment Instructions," which is found on the FSAP website within the electronic Federal Select Agent Program (eFSAP) Resource Center. Methods: Using the information found within the eFSAP Form 1 Amendment Instructions, as well as extensive written and verbal guidance provided by the lead assigned entity point of contact at the FSAP, we completed the FSAP withdrawal process during a 12-month period between 2022 and 2023. Discussion: This commentary shares our recent professional experiences navigating the FSAP withdrawal process at the University of Texas Health Science Center at Houston (UTHealth Houston). Successes, challenges, and lessons learned are shared so that others planning or considering withdrawing may benefit from our experience. Conclusion: The resources provided for withdrawal within the eFSAP Form 1 Amendment Instructions are relatively basic, and additional details are not currently found in other FSAP guidance documents. Therefore, direct communication and support from the FSAP to the entity Responsible Officials are imperative to ensure a safe, secure, and compliant withdrawal.

Deep-learning-based image segmentation for image-based computational hemodynamic analysis of abdominal aortic aneurysms: a comparison study.

Computational hemodynamics is increasingly being used to quantify hemodynamic characteristics in and around abdominal aortic aneurysms (AAA) in a patient-specific fashion. However, the time-consuming manual annotation hinders the clinical translation of computational hemodynamic analysis. Thus, we investigate the feasibility of using deep-learning-based image segmentation methods to reduce the time required for manual segmentation. Two of the latest deep-learning-based image segmentation methods, ARU-Net and CACU-Net, were used to test the feasibility of automated computer model creation for computational hemodynamic analysis. Morphological features and hemodynamic metrics of 30 computed tomography angiography (CTA) scans were compared between pre-dictions and manual models. The DICE score for both networks was 0.916, and the correlation value was above 0.95, indicating their ability to generate models comparable to human segmentation. The Bland-Altman analysis shows a good agreement between deep learning and manual segmentation results. Compared with manual (computational hemodynamics) model recreation, the time for automated computer model generation was significantly reduced (from ∼2 h to ∼10 min). Automated image segmentation can significantly reduce time expenses on the recreation of patient-specific AAA models. Moreover, our study showed that both CACU-Net and ARU-Net could accomplish AAA segmentation, and CACU-Net outperformed ARU-Net in terms of accuracy and time-saving.

A Means of Codifying Safety Cross-Training Knowledge Expectations for Biosafety Professionals.

Introduction: The health and safety issues encountered by biosafety professionals in the daily conduct of their work is rarely limited solely to potentially infectious pathogens. A basic understanding of the other types of hazards inherent to laboratories is necessary. As such, management of the health and safety program at an academic health institution sought to ensure crosscutting competency for its technical staff, including staff members within the biosafety program. Methods: Using a focus group approach, a team of safety professionals from a variety of specialties developed a list of 50 basic health and safety items that any safety specialist should know, inclusive of basic but important information about biosafety that was considered imperative for staff members to understand. This list was used as the basis for a formal cross-training effort. Results: Staff responded positively to the approach and the associated cross-training, and overall compliance with an array of health and safety expectations was experienced across the institution. Subsequently, the list of questions has been shared broadly with other organizations for their own consideration and use. Discussion/Conclusion: The codification of the basic knowledge expectations for technical staff within a health and safety program at an academic health institution, which includes the biosafety program technical staff, was warmly received and helped establish what information was expected to be known and what issues warranted input from other specialty areas. The cross-training expectations served to expand the health and safety services provided despite resource limitations and organizational growth.

Computerized Differentiation of Growth Status for Abdominal Aortic Aneurysms: A Feasibility Study.

Fast-growing abdominal aortic aneurysms (AAA) have a high rupture risk and poor outcomes if not promptly identified and treated. Our primary objective is to improve the differentiation of small AAAs' growth status (fast versus slow-growing) through a combination of patient health information, computational hemodynamics, geometric analysis, and artificial intelligence. 3D computed tomography angiography (CTA) data available for 70 patients diagnosed with AAAs with known growth status were used to conduct geometric and hemodynamic analyses. Differences among ten metrics (out of ninety metrics) were statistically significant discriminators between fast and slow-growing groups. Using a support vector machine (SVM) classifier, the area under receiving operating curve (AUROC) and total accuracy of our best predictive model for differentiation of AAAs' growth status were 0.86 and 77.50%, respectively. In summary, the proposed analytics has the potential to differentiate fast from slow-growing AAAs, helping guide resource allocation for the management of patients with AAAs.

The Harvard Macy Institute Art Museum-based Health Professions Education Fellowship: Transformational faculty development through the arts.

Museum-based education for health professionals can lead to a variety of important learning outcomes within the domain of skills development, personal insight, perspective-taking and social advocacy. The Harvard Macy Institute's Art Museum-based Health Professions Education Fellowship was designed to develop faculty expertise in art museum-based practices, encourage scholarship, and cultivate a cohesive and supportive community of educators. The Fellowship was piloted from January to May 2019 with twelve interprofessional Fellows. Two in-person experiential sessions were held at Boston-area museums with intervening virtual learning. Fellows were introduced to a variety of approaches used in art museum-based education and developed a project for implementation at their home institution. A qualitative formative evaluation assessed immediate and 6-month post-Fellowship outcomes. Outcomes are reported in four categories: (1) Fellows' personal and professional development; (2) Institutional projects and curriculum development; (3) Community of practice and scholarly advancement of the field; and (4) Development of Fellowship model. A follow-up survey was performed four years after the conclusion of the pilot year, documenting Fellows' significant accomplishments in museum-based education, reflections on the Fellowship and thoughts on the future of the field.

Assessing the Established Competency Categories of the Biosafety, Infection Prevention, and Public Health Professions: A Guide for Addressing Needed Professional Development Training for the Current and Next Pandemic.

A recent series of widespread infectious disease outbreaks has highlighted commonalities and differences between three key professions that operate on the front lines of response in support of research and/or direct healthcare providers: biosafety, infection prevention, and public health. This assessment, which builds upon previous study by the authors, examines the stated professional competency categories for these three areas, highlighting similarities and differences. This assessment is important as these professions are being drawn together in an operational environment driven by the current pandemic and inevitably future disease outbreaks. Cross-training opportunities for the various professions are proposed.

Pivoting the Biosafety Program in Response to COVID-19: Recommendations of Key Services and Tasks to Consider for the Next Pandemic.

Introduction: With the onset of the COVID-19 pandemic, a rapid adjustment of work tasks was necessary for many biosafety programs (and other safety programs) to address drastic shifts in workload demands amid pandemic-related shutdowns and subsequent needs for supporting COVID-19-related safe work protocols, diagnostic testing, research, vaccine development, and so forth. From a program management standpoint, evaluating and understanding these tasks were critically important to ensure that appropriate support and resources were in place, especially during such unprecedented times of rapid change and significant impact to normal life and routine. Methods: Described here are examples of how the biosafety program at The University of Texas Health Science Center at Houston (UTHealth Houston) addressed these challenges. Results: As part of this required pivot, key services and tasks emerged into three distinct categories: (1) those that were temporarily diminished, (2) those that had to continue despite COVID-19 and the associated shutdowns for safety or compliance purposes, and (3) those that dramatically increased in volume, frequency, and novelty. Conclusion: Although the adjustments described were made in situ as the pandemic evolved, the cataloging of these tasks throughout the experience can serve as a template for biosafety programs to plan and prepare for the next pandemic, which will inevitably occur.

Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost Opportunities.

BACKGROUND: Kidney transplantation is associated with the best outcomes for most patients with ESKD. The national Kidney Allocation System prioritizes patients with Estimated Post-Transplant Survival (EPTS) scores in the top 20% for expedited access to optimal deceased donor kidneys. METHODS: We studied adults aged ≥18 years in the United States Renal Data System with top 20% EPTS scores who had been preemptively waitlisted or initiated dialysis in 2015-2017. We evaluated time to waitlist placement, transplantation, and mortality with unadjusted and multivariable survival models. RESULTS: Of 42,445 patients with top 20% EPTS scores (mean age, 38.0 years; 57% male; 59% White patients, and 31% Black patients), 7922 were preemptively waitlisted. Among 34,523 patients initiating dialysis, the 3-year cumulative waitlist placement incidence was 37%. Numerous factors independently associated with waitlisting included race, income, and having noncommercial insurance. For example, waitlisting was less likely for Black versus White patients, and for patients in the lowest-income neighborhoods versus those in the highest-income neighborhoods. Among patients initiating dialysis, 61% lost their top 20% EPTS status within 30 months versus 18% of patients who were preemptively listed. The 3-year incidence of deceased and living donor transplantation was 5% and 6%, respectively, for patients who initiated dialysis and 26% and 44%, respectively, for patients who were preemptively listed. CONCLUSIONS: Many patients with ESKDqualifying with top 20% EPTS status are not placed on the transplant waiting list in a timely manner, with significant variation on the basis of demographic and social factors. Patients who are preemptively listed are more likely to receive benefits of top 20% EPTS status. Efforts to expedite care for qualifying candidates are needed, and automated transplant referral for patients with the best prognoses should be considered. PODCAST: This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_07_30_JASN2020081146.mp3.

An assessment of outpatient clinic room ventilation systems and possible relationship to disease transmission.

BACKGROUND: With healthcare shifting to the outpatient setting, this study examined whether outpatient clinics operating in business occupancy settings were conducting procedures in rooms with ventilation rates above, at, or below thresholds defined in the American National Standards Institute/American Society of Heating, Refrigerating and Air-Conditioning Engineers/American Society for Health Care Engineering Standard 170 for Ventilation in Health Care Facilities and whether lower ventilation rates and building characteristics increase the risk of disease transmission. METHODS: Ventilation rates were measured in 105 outpatient clinic rooms categorized by services rendered. Building characteristics were evaluated as determinants of ventilation rates, and risk of disease transmission was estimated using the Gammaitoni-Nucci model. RESULTS: When compared to Standard 170, 10% of clinic rooms assessed did not meet the minimum requirement for general exam rooms, 39% did not meet the requirement for treatment rooms, 83% did not meet the requirement for aerosol-generating procedures, and 88% did not meet the requirement for procedure rooms or minor surgical procedures. CONCLUSIONS: Lower than standard air changes per hour were observed and could lead to an increased risk of spread of diseases when conducting advanced procedures and evaluating persons of interest for emerging infectious diseases. These findings are pertinent during the SARS-CoV-2 pandemic, as working guidelines are established for the healthcare community.

Facilitators and Barriers to Successful Engagement in a Complex Care Management Program: Patient and Care Manager Perspectives.

Complex care management (CCM) interventions have been developed across the United States to address the challenges of high-need, high-cost patients. Though their heterogeneity makes it challenging to determine their general effectiveness, there are calls in the literature to continue to implement and evaluate them. This article presents CCM patient and care manager perspectives on facilitators and barriers to success in such a program in a safety-net hospital. Our findings suggest that motivated patients, team-based care, and the ability to form trusting, supportive relationships are important contributors to success in a CCM program while patients' own mental health and socioeconomic challenges impede success. Given the relatively short-term nature of most CCM programs and the complicated challenges faced by many CCM patients, this work poses larger questions to consider around the general alignment of the program model to the patient population and the definition of success for CCM programs.

SHORT-TERM EFFECTS OF TRIGGER POINT DRY NEEDLING ON PAIN AND DISABILITY IN SUBJECTS WITH PATELLOFEMORAL PAIN SYNDROME.

BACKGROUND: Patellofemoral pain syndrome (PFPS) is a prevalent knee disorder. A novel yet increasingly popular treatment for PFPS is trigger point dry needling (DN). PURPOSE: The purpose of this study was to determine if DN is more effective at reducing pain and disability than a sham treatment in individuals with PFPS. STUDY DESIGN: Randomized trial. MATERIALS/METHODS: Sixty military health care beneficiaries (36 males) with a clinical diagnosis of PFPS were recruited and completed the study. Subjects underwent a standardized clinical examination and were randomized into a DN or sham treatment group. DN treatment consisted of insertion of an acupuncture-like needle into six sites in the quadriceps femoris muscles of the symptomatic lower extremity based on a palpation examination. The sham grouped received a simulated treatment with a sharp object and needle guide tube without puncturing the skin. Self-reports of pain, disability, and overall status were collected before treatment, immediately after treatment and at 72 hours. Data were analyzed with separate 2x2 repeated measures analysis of variance, with independent variables being Group (DN vs. sham) and Time (pre-treatment vs. immediately post-treatment, and pre-treatment vs. 72 hours). The hypothesis of interest in each case was the Group*Time interaction. The alpha-level was set a priori to .05 using 2-tailed tests. RESULTS: Both groups exhibited a clinically meaningful reduction in pain based on numeric pain rating scale scores immediately post-treatment and at 72 hours, but there was no statistically significant difference between groups (p = 0.219, 0.310). There was no significant difference between groups for any other outcome measures. CONCLUSION: These data suggest that DN treatment is not more effective than a sham DN treatment at reducing short-term pain and disability in individuals with PFPS when used as an isolated treatment approach. LEVEL OF EVIDENCE: 2.

The effects of concussion on rapid picture naming in children.

PRIMARY OBJECTIVE: The purpose of this investigation was to examine children's accuracy and speed when asked to name rapidly images following a concussion. The authors predicted that children with a recent concussion would not differ in accuracy from peers, but would be slower. RESEARCH DESIGN: Children with and without a recent concussion were compared on their accuracy and speed of naming objects, and speed was correlated with time since injury. METHODS AND PROCEDURES: Fifty-eight participants, aged 10-22 years, 32 within one month of concussion and 26 age-matched participants with no history of concussion, rapidly viewed and verbally named 107 illustrations of common objects, and sensitive measures of response time were recorded. MAIN OUTCOMES AND RESULTS: Groups did not differ in rate of accuracy, but children with recent injury responded significantly more slowly. A trajectory of recovery was calculated, providing qualified evidence for a longer timeline of recovery than the typical two-week period. CONCLUSIONS: These findings affirm the presence of this naming latency effect in children, explore the duration of this effect over the course of recovery, and add nuance to inconsistently reported chronic naming deficits following concussion, informing recommendations for return to full academic and recreational participation.

Effect of Repetitive, Subconcussive Impacts on Electrophysiological Measures of Attention.

OBJECTIVES: In this preliminary study, the auditory P3b response, when measured during a visually distracting task, was investigated as an index of change in cognitive function resulting from exposure to subconcussive impacts (SCIs) in collision sports over time. METHODS: Both pre- and postseason P3b responses were examined in seven first-year collegiate-level American football players. Comparisons were made between a group of seven third- and fourth-year players and a control group of seven noncontact athletes. RESULTS: No difference in P3b amplitude was revealed in pre- versus postseason data of the first-year players. Furthermore, no P3b amplitude differences were found when comparing first-year players with controls. P3b amplitudes of third- and fourth-year players versus first-year players were smaller along the midline electrode sites. CONCLUSIONS: Preliminary results suggest exposure to SCIs during the course of a season does not affect brain function negatively, as measured by the P3b response; however, differences between first-year players and the group of third- and fourth-year players suggest that exposure to hundreds of SCIs in multiple seasons leads to changes in brain activation patterns. Subtle effects such as difficulty with attentional resource allocation may develop. Longitudinal studies are necessary before definitive conclusions can be drawn.

The effects of visual distracter complexity on auditory evoked p3b in contact sports athletes.

"Classic" P3b auditory oddball paradigms are insensitive to subtle deficits. An auditory oddball paradigm paired with visual distracters was used to compare football players with history of concussion, football players without history of concussion, and non-contact sport athletes. As hypothesized, increasing complexity of, and attention to, visual distracters reduced P3b amplitude. P3b amplitudes from non-contact athletes were larger than those from football players; however, players with and without a history of concussion were not significantly different. An auditory oddball paradigm with simple visual distracter improves sensitivity to cognitive deficits. Subconcussive impacts may contribute to brain damage frequently attributed to concussions.

Effects of complexity of visual distracters on attention and information processing speed reflected in auditory p300.

OBJECTIVES: The primary aim of this study was to assess the effects of continuous, visual distracters that change systematically in complexity on P300 responses generated by an auditory oddball paradigm. In addition, the type of attention given to the visual distracter was explored. It was hypothesized that P300 amplitudes would be smallest, latencies longest, and changes in scalp distribution greatest when the most complex visual distracter requiring active attention was used versus the simple visual distracter requiring passive attention. DESIGN: Auditory-evoked P300s were collected in a sample of 10 healthy adults (mean age = 19.90 years) using a two-toned oddball paradigm (1500 Hz "frequent" tone, probability of occurrence: 0.88, and 2000 Hz "rare" target tone, probability of occurrence: 0.12). The oddball paradigm was paired with three different visual distracters, increasing in complexity. The simplest was a black fixation cross on a white background that participants were asked to view passively as they performed the auditory task of counting the target stimulus. The second visual distracter increased in complexity by introducing color and motion, as tan and medium pink squares were alternated on the screen. Participants had to actively attend to the alternating squares by looking for a hidden text message while simultaneously counting the target auditory stimulus. The third visual distracter condition increased complexity again by introducing not only color and motion, but also biological relevance as participants viewed a mouth producing nonsense syllables. Participants had to actively attend to the moving mouth to determine what it was producing while simultaneously counting the rare auditory stimulus. RESULTS: The two more complex visual distracters that required active attention caused reductions in auditory-evoked P300 amplitudes relative to those recorded while the participants passively viewed a fixation cross. P300 amplitudes were similar whether the two more complex visual distracters (squares versus mouth) were used. P300 latencies and scalp distribution were not influenced by complexity of, or type of attention to, the visual distracter. Regardless of distracter condition, P300 amplitude was significantly smaller and P300 latency was significantly shorter at frontal sites when compared with central and parietal sites. CONCLUSIONS: Findings indicate that endogenous attentional resource allocation abilities can be effectively monitored through the addition of a complex, visually distracting task to a "classic" auditory P300 paradigm. Biological relevance of the distracting task does not seem to have an effect on the event-related potentials measured in this study, suggesting other aspects, such as whether or not a stimulus contains color or motion, may determine the efficiency of the distracter. Last, by increasing the complexity of, and amount of attention to, a visual distracter while evoking P300s using auditory stimuli, the cognitive load for the normal, healthy listener seems to be increased and the response amplitude subsequently reduced. Evoking P300s under similar conditions from disordered populations with subtle cognitive deficits (e.g., mild traumatic brain injury) may allow for increased diagnostic specificity and sensitivity over that found for P300s to classic, auditory oddball paradigms alone.

Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules.

We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (ß(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptors.

Implementation of cervical cancer prevention services for HIV-infected women in Zambia: measuring program effectiveness.

BACKGROUND: Cervical cancer kills more women in low-income nations than any other malignancy. A variety of research and demonstration efforts have proven the efficacy and effectiveness of low-cost cervical cancer prevention methods but none in routine program implementation settings of the developing world, particularly in HIV-infected women. METHODS: In our public sector cervical cancer prevention program in Zambia, nurses conduct screening using visual inspection with acetic acid aided by digital cervicography. Women with visible lesions are offered same-visit cryotherapy or referred for histologic evaluation and clinical management. We analyzed clinical outcomes and modeled program effectiveness among HIV-infected women by estimating the total number of cervical cancer deaths prevented through screening and treatment. RESULTS: Between 2006 and 2008, 6572 HIV-infected women were screened, 53.6% (3523) had visible lesions, 58.5% (2062) were eligible for cryotherapy and 41.5% (1461) were referred for histologic evaluation. A total of 75% (1095 out of 1462) of patients who were referred for evaluation complied. Pathology results from 65% (715 out of 1095) of women revealed benign abnormalities in 21% (151), cervical intraepithelial neoplasia (CIN) I in 30% (214), CIN 2/3 in 33% (235) and invasive cervical cancer in 16.1% (115, of which 69% were early stage). Using a conditional probability model, we estimated that our program prevented 142 cervical cancer deaths (high/low range: 238-96) among the 6572 HIV-infected women screened, or one cervical cancer death prevented per 46 (corresponding range: 28-68) HIV-infected women screened. CONCLUSION: Our prevention efforts using setting-appropriate human resources and technology have reduced morbidity and mortality from cervical cancer among HIV-infected women in Zambia. Financial support for implementing cervical cancer prevention programs integrated within HIV/AIDS care programs is warranted. Our prevention model can serve as the implementation platform for future low-cost HPV-based screening methods, and our results may provide the basis for comparison of programmatic effectiveness of future prevention efforts.

Functional communication in individuals with chronic severe aphasia using augmentative communication.

Intervention incorporating augmentative and alternative communication (AAC) is often implemented with adults with aphasia, although studies do not always specify the approaches and strategies used. This study examined abilities of three individuals with chronic non-fluent aphasia (NA) using a dynamic display AAC device to enhance communication. The device, Dialect with Speaking Dynamically Pro, was tailored to each participant's skill level using a treatment protocol adapted from Koul, Corwin, and Hayes (2005). The primary caregiver was the spouse. Pre and post-treatment measures revealed improvement in quality and effectiveness of communication for all participants. Improved linguistic and cognitive functioning was observed for two participants. Results are discussed relative to use of a device with other adults with chronic NA.