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Abstract As part of a continued search for more efficient anti-HIV-1 drugs, we are focusing on the possibility that small molecules could efficiently inhibit HIV-1 replication through the restoration of p53 and p21WAF1 functions, which are inactivated by HIV-1 infection. Here we describe the molecular mechanism of 9-aminoacridine (9AA) mediated HIV-1 inhibition. 9AA treatment resulted in inhibition of HIV LTR transcription in a specific manner that was highly dependent on the presence and location of the amino moiety. Importantly, virus replication was found to be inhibited in HIV-1 infected cell lines by 9AA in a dose-dependent manner without inhibiting cellular proliferation or inducing cell death. 9AA inhibited viral replication in both p53 wildtype and p53 mutant cells, indicating that there is another p53 independent factor that was critical for HIV inhibition. p21WAF1 is an ideal candidate as p21WAF1 levels were increased in both p53 wildtype and p53 mutant cells, and p21WAF1 was found to be phosphorylated at S146, an event previously shown to increase its stability. Furthermore, we observed p21WAF1 in complex with cyclin T1 and cdk9 in vitro, suggesting a direct role of p21WAF1 in HIV transcription inhibition. Finally, 9AA treatment resulted in loss of cdk9 from the viral promoter, providing one possible mechanism of transcriptional inhibition. Thus, 9AA treatment was highly efficient at reactivating the p53 – p21WAF1 pathway and consequently inhibiting HIV replication and transcription.

Abstract It has been demonstrated that the p53 pathway plays an important role in HIV-1 infection. Previous work from our lab has established a model demonstrating how p53 could become inactivated in HIV-1 infected cells through binding to Tat. Subsequently, p53 was inactivated and lost its ability to transactivate its downstream target gene p21/waf1. P21/waf1 is a well-known cdk inhibitor (CKI) that can lead to cell cycle arrest upon DNA damage. Most recently, the p21/waf1 function was further investigated as a molecular barrier for HIV-1 infection of stem cells. Therefore, we reason that the restoration of the p53 and p21/waf1 pathways could be a possible theraputical arsenal for combating HIV-1 infection. In this current study, we show that a small chemical molecule, 9-aminoacridine (9AA) at low concentrations, could efficiently reactivate p53 pathway and thereby restoring the p21/waf1 function. Further, we show that the 9AA could significantly inhibit virus replication in activated PBMCs, likely through a mechanism of inhibiting the viral replication machinery. A mechanism study reveals that the phosphorylated p53ser15 may be dissociated from binding to HIV-1 Tat protein, thereby activating the p21/waf1 gene. Finally, we also show that the 9AA-activated p21/waf1 is recruited to HIV-1 preintegration complex, through a mechanism yet to be elucidated.

Presents the case of a 69-year-old man with progressive cognitive dysfunction. Symptoms including pulsatile tinnitus, migraine with aura, blurred vision, and slurred speech; Abnormal pattern of flow voids in the region of the right transverse sinus showing on the brain magnetic resonance imaging; Angiography showing a dural arteriovenous fistula of the right transverse sinus and torcula, with occlusion of the right sigmoid sinus.

The article presents several letters in response to the assistance provided by New England Bureau of Education in recommending teachers for Superintendent of Schools in November 1881.

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin, exhibit significantly higher antimalarial potency than their parent compounds (1). However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH) is the major activating enzyme of multiple lipophilic ester prodrugs. Surprisingly, this enzyme is taken up by the malaria parasite, Plasmodium falciparum , where it localizes to the parasite cytoplasm and retains enzymatic activity. Using a novel fluorogenic ester library, we characterize the structure activity relationship of APEH, and compare it to that of P. falciparum esterases. We show that parasite-internalized APEH plays an important role in the activation of substrates with branching at the alpha carbon, in keeping with its exopeptidase activity. Our findings highlight a novel mechanism for antimicrobial prodrug activation, relying on a host-derived enzyme to yield activation at a microbial target. Mutations in prodrug activating enzymes are a common mechanism for antimicrobial drug resistance (2-4). Leveraging an internalized host enzyme would circumvent this, enabling the design of prodrugs with higher barriers to drug resistance.

Over the past 50 years, there has been a marked increase in diseases like dengue fever, chikungunya, and Zika. The World Mosquito Program (WMP) has developed an approach that, instead of attempting to eliminate vector species, introduces Wolbachia into native Aedes aegypti populations through the release of Wolbachia -infected mosquitoes. Using this approach, a randomized controlled study recently demonstrated a 77% reduction in dengue across a treatment area within Yogyakarta, Indonesia. Existing release methods use the ground-based release of mosquito eggs or adults that are labor-intensive, are logistically challenging to scale up, and can be restrictive in areas where staff safety is a concern. To overcome these limitations, we developed a fully automated mosquito dosing release system that released smaller cohorts of mosquitoes over a wide area and integrated it into an uncrewed aerial vehicle. We established the effectiveness of this system using an aerial mark, release, and recapture approach. We then demonstrated that using only the aerial release method, we can establish Wolbachia infection in a naive Ae. aegypti population. In both cases, the use of aerial releases demonstrated comparable outcomes to ground-based releases without the required labor or risk. These two trials demonstrated the feasibility of using an aerial release approach for large-scale mosquito releases.

Background: High daily doses of pancreatic enzyme replacement therapy (PERT) were historically associated with risk of fibrosing colonopathy (FC) in people with cystic fibrosis (pwCF), leading to development of PERT dosing guidelines and reformulated products. This study quantified incidence of FC in pwCF treated with PERT following those measures., Methods: This large prospective cohort study included eligible pwCF enrolled in the Cystic Fibrosis Foundation Patient Registry with ≥1 clinic visit in 2012-2014 and follow-up through 2020. Data on PERT exposure, demographics, and medical history were collected. Clinical data, imaging, and histopathology of suspected cases were examined by an independent adjudication panel of physicians familiar with this complication., Results: Base Study Population included 26,025 pwCF who contributed 155,814 person-years [mean (SD) 6.0 (2.0) years] of follow-up. Over 7.8 years, 29 pwCF had suspected FC; three cases were confirmed by adjudication, 22 cases were confirmed as not FC, and four cases were indeterminate. There were 22,161 pwCF exposed to any PERT, with mean PERT use time of 5.583 person-years and mean daily dose of 8328 U lipase per kg per day. All three confirmed cases and four indeterminate cases of FC occurred during current use of PERT. Incidence rates per 1000 person-years exposed were 0.0242 (95 % CI [0.0050, 0.0709]) for confirmed FC and 0.0566 (95 % CI [0.0227, 0.1166]) for indeterminate or confirmed FC., Conclusions: The incidence of FC in pwCF is very low in the era of current treatment guidelines and more stringent quality standards for PERT products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Stephanie E. Chiuve and Lino Rodrigues Jr are full-time employees of AbbVie Inc., which marketed one of the pancreatic enzymes included in the study. They hold stock and stock options. Their work on this study was done as part of their employment. At the time of this study, Daniel Fife was a full-time employee of Janssen Research & Development, LLC, which marketed one of the pancreatic enzymes included in the study and held stock and stock options. As an employee, he received travel support and pension rights from Johnson & Johnson, the parent company of Janssen Research & Development. His work on this study was done as part of his employment. He has since retired from Janssen Research & Development, LLC. During the time of the study, he was on the board of directors of the International Society for Pharmacoepidemiology (ISPE) and was the Industry Council Chair of ISPE. Gerhard Leitz is a full-time employee of Janssen Research & Development, LLC, which marketed one of the pancreatic enzymes included in the study and holds stock and stock options. His work on this study was done as part of his employment. Craig Peterson is a full-time employee of VIVUS LLC., which marketed one of the pancreatic enzymes included in this study. At the time of this study, he held stock and stock options in VIVUS LLC., and his work on this study was done as part of his employment. Amanda Rennig and Neil M. Campbell are employed by Digestive Care, Inc., which marketed one of the pancreatic enzymes included in this study. At the time of this study, they did not hold stock or stock options in Digestive Care, Inc., and their work on this study was done as part of their employment. Dennis Decktor is a full-time employee (initially a contract employee) of Nestle, which marketed one of the pancreatic enzymes included in this study. His work on this study was done as part of his employment. Christopher Dowd was employed by the Cystic Fibrosis Foundation during the time of the study, which was paid by all the sponsors to conduct the study. Bruce C. Marshall was employed by the Cystic Fibrosis Foundation during the time of the study, which was paid by all the sponsors to conduct the study. Drucy Borowitz was a consultant for the Cystic Fibrosis Foundation during the development of the study and served as the chair of the Adjudication Committee for which her employer, Jacobs School of Medicine and Biomedical Sciences, received compensation. In 2016, she became an employee for the Cystic Fibrosis Foundation and her work on this study was done as part of her employment. As of 2020, she is no longer an employee or consultant to the Cystic Fibrosis Foundation. She received consulting fees as a member of a scientific advisory board for Synspira Therapeutics. The active members of the Adjudication Committee and the third-party reviewers of radiology and pathology were: Drucy Borowitz, MD, Sarah Jane Schwarzenberg, MD, John Stevens, MD, Maria Mascarenhas, MBBS, Bruce Pawel, MD, J. Michael Zerin, MD, Boaz Karmazyn, MD, F. Glen Seidel, MD. The medical monitor for this study was Christopher H. Goss, MD, MSc. This study was managed by Cystic Fibrosis Foundation Therapeutics (CFFT) and the Therapeutics Development Network Coordinating Center (TDNCC). It was conducted within the CFF-accredited care center network with guidance, input, review, and approval by the sponsors, including development of materials; recruitment, training, and management of sites; and data management and analysis. An independent adjudication committee was formed to validate the diagnosis of FC based on a prospective case definition and decision rules. The CFFT identified the panel of experts and mediated the adjudication process., (Copyright © 2023. Published by Elsevier B.V.)

Blue cone monochromacy (BCM) is a rare X-linked retinal disease characterized by the absence of L- and M-opsin in cone photoreceptors, considered a potential gene therapy candidate. However, most experimental ocular gene therapies utilize subretinal vector injection which would pose a risk to the fragile central retinal structure of BCM patients. Here we describe the use of ADVM-062, a vector optimized for cone-specific expression of human L-opsin and administered using a single intravitreal (IVT) injection. Pharmacological activity of ADVM-062 was established in gerbils, whose cone-rich retina naturally lacks L-opsin. A single IVT administration dose of ADVM-062 effectively transduced gerbil cone photoreceptors and produced a de novo response to long-wavelength stimuli. To identify potential first-in-human doses we evaluated ADVM-062 in non-human primates. Cone-specific expression of ADVM-062 in primates was confirmed using ADVM-062.myc, a vector engineered with the same regulatory elements as ADVM-062. Enumeration of human OPN1LW.myc-positive cones demonstrated that doses ≥3 × 10 10 vg/eye resulted in transduction of 18%-85% of foveal cones. A Good Laboratory Practice (GLP) toxicology study established that IVT administration of ADVM-062 was well tolerated at doses that could potentially achieve clinically meaningful effect, thus supporting the potential of ADVM-062 as a one-time IVT gene therapy for BCM., Competing Interests: Declaration of interests K.H., D.C., J.N., C.D., P.S., K.O.B., M.R., B.S., C.M.G., B.E.R., and R.N.G. are current or previous employees of Adverum Biotechnologies and hold stock grants. J.V.H. is a paid consultant of Adverum Biotechnologies., (Copyright © 2023 Adverum Biotechnologies Inc. Published by Elsevier Inc. All rights reserved.)

Background: Intraoperative angiography (IOA) has been shown to be a useful adjunct in surgical treatment of cerebral aneurysms. However, its use can be limited by hybrid operating room availability. On the other hand, the use of C-arm fluoroscopy can add challenges to IOA during navigation of the aortic arch and selection of the great vessels. We aimed to describe a simple method of IOA that can be applied during surgery of paraclinoid aneurysms and can be performed in a normal operating room without the need to navigate the aortic arch., Methods: In patients undergoing surgery for paraclinoid aneurysms with need for cervical carotid artery exposure, IOA was performed using a single plane C-arm fluoroscopy unit after direct puncture of the carotid artery., Results: Five patients were included: 2 with subarachnoid hemorrhage, 2 with unruptured aneurysm and history of subarachnoid hemorrhage, and 1 with unruptured aneurysm. There were 2 internal carotid blister aneurysms, 2 ophthalmic artery aneurysms, and 1 superior hypophyseal artery aneurysm. IOA was performed using direct carotid puncture through the neck incision required for proximal control. In all cases, intraoperative images were of sufficient quality to determine the completeness of aneurysm occlusion as well as parent and branching vessel patency. There were no postoperative infarctions and no complications related to IOA., Conclusions: IOA using direct carotid puncture can be performed in a standard operating room with the use of a C-arm, eliminating the need to catheterize the great vessels of the aortic arch., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Due to the COVID-19 pandemic, there was an uptake of telehealth in cystic fibrosis care. Previous studies show disparities in telehealth use based on socioeconomic status (SES). We aimed to: (1) understand telehealth use and perceptions and (2) identify the facilitators and barriers to telehealth use among people with CF and their families (PwCF) from diverse racial/ethnic and socioeconomic backgrounds., Methods: We conducted an analysis of the 2020 Cystic Fibrosis State of Care surveys completed by PwCF (PFSoC), CF Care Programs (SoC1) and the CF Foundation Patient Registry (CFFPR)., Results: A total of 424 PwCF and 286 programs responded to the PFSoC and SoC1. Among PwCF, 90% self-identified as White, 6% as Hispanic/Latino, and 2% as Black. Racial/ethnic minorities were less likely to have had a telehealth visit (p=.015). This difference was pronounced among the Hispanic/Latino population (p<.01). Telehealth use did not differ by health insurance and was similarly offered independent of financial status. Compared to PwCF who denied financial constraints, those who reported financial difficulties found telehealth more difficult to use (p=.018) and were less likely to think that their concerns (p=.010) or issues that mattered most to them (p=.020) were addressed during telehealth. Programs perceived lack of technology, language barriers, and home conditions as barriers to telehealth in vulnerable populations., Conclusion: PFSoC and SoC1 identified differences in telehealth use and care perceptions by ethnicity, race, and socioeconomic characteristics. Further studies are needed to understand how telehealth can change access to CF care in diverse subpopulations., Competing Interests: Declaration of Competing Interest While I received grant support from CFF and private pharmaceutical companies, I have no conflict of interest to report related to this manuscript., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cystic fibrosis (CF) programs and people with CF (PwCF) employed various monitoring methods for virtual care during the COVID-19 pandemic. This paper characterizes experiences with remote monitoring across the U.S. CF community., Methods: The CF Foundation (CFF) sponsored distribution of home spirometers (April 2020 to May 2021), surveys to PwCF and CF programs (July to September 2020), and a second program survey (April to May 2021). We used mixed methods to explore access, use, and perspectives regarding the use of remote monitoring in future care., Results: By October 2020, 13,345 spirometers had been distributed, and 19,271 spirometers by May 2021. Programs (n=286) estimated proportions of PwCF with home devices increased over seven months: spirometers (30% to 70%), scales (50% to 70%), oximeters (5% to 10%) with higher estimates in adult programs for spirometers and oximeters. PwCF (n=378) had access to scales (89%), followed by oximeters (48%) and spirometers (47%), often using scales and oximeters weekly, and spirometers monthly. Over both surveys, some programs had no method to collect respiratory specimens for cultures associated with telehealth visits (47%, n=132; 41%, n=118). Most programs (81%) had a process for phlebotomy associated with a telehealth visit, primarily through off-site labs. Both PwCF and programs felt future care should advance remote monitoring and recommended improvements for access, training, and data collection systems., Conclusions: PwCF and programs experienced unprecedented access to remote monitoring and raised its importance for future care. Improvements to current systems may leverage these shared experiences to augment future care models., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: The COVID-19 pandemic forced cystic fibrosis (CF) care programs to rapidly shift from in-person care delivery to telehealth. Our objective was to provide a qualitative exploration of facilitators and barriers to: 1) implementing high-quality telehealth and 2) navigating reimbursement for telehealth services., Methods: We used data from the 2020 State of Care CF Program Survey (n=286 U.S. care programs) administered in August-September to identify two cohorts of programs, with variation in telehealth quality (n=12 programs) and reimbursement (n=8 programs). We conducted focus groups and semi-structured interviews with CF program directors and coordinators in December 2020, approximately 9 months from onset of the pandemic. We used the Consolidated Framework for Implementation Research to identify facilitators and barriers of implementation, and inductive thematic analysis to identify facilitators and barriers of reimbursement., Results: Factors differentiating programs with greater and lower perceived telehealth quality included telehealth characteristics (perceived advantage over in-person care, cost, platform quality); external influences (needs and resources of those served by the CF program), characteristics of the CF program (compatibility with workflows, relative priority, available resources); characteristics of team members (individual stage of change), and processes for implementation (engaging patients and teams). Reimbursement barriers included documentation to optimize billing; reimbursement of multi-disciplinary team members, remote monitoring, and telephone-only telehealth; and lower volume of patients., Conclusions: A number of factors are associated with successful implementation and reimbursement of telehealth. Future efforts should provide guidance and incentives that support telehealth delivery and infrastructure, share best practices across CF programs, and remove barriers., (Copyright © 2021. Published by Elsevier B.V.)

Background: Novel therapies have dramatically changed cystic fibrosis (CF) and innovative care delivery systems are needed to meet future patient needs. Telehealth has been shown to be an efficient and desirable form of care delivery. The COVID-19 pandemic caused a rapid shift to telehealth, and this presented a unique opportunity to study facilitators, barriers, and satisfaction with this mode of care delivery. We aim to report survey methods, demographics and telehealth use among CF care programs, patients, and families during the pandemic., Methods: CF programs completed two surveys between July 29 and September 18, 2020, and between April 19 and May 19, 2021. Patients and families completed a similar survey between August 31 and October 30, 2020. The surveys addressed topics assessing the pandemic's financial impact, telehealth modes and experiences, licensure and reimbursement issues, health screening, and remote monitoring. Quantitative data were analyzed with descriptive statistics and were compared to the CF Foundation Patient Registry., Results: Most programs (278 at timepoint one and 274 at timepoint two) provided telehealth during the pandemic. The percent of visits containing either telephone or video components changed from 45% to 25% over the time periods. Additionally, 424 patients and families from various ages and backgrounds responded to the survey and 81% reported having a telehealth visit., Conclusions: The pandemic accelerated telehealth adoption and these datasets are a valuable source for exploring telehealth barriers and facilitators, the quality-of-care experience, financial and workforce implications, the impact on underrepresented populations, and implications for coverage and reimbursement., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cystic fibrosis (CF) care programs in the United States rapidly adopted telehealth during the COVID-19 pandemic. Understanding factors that promote or impede telehealth will inform planning for future telehealth-enabled care models., Methods: Adult, pediatric, and affiliate CF care programs in the United States (n = 287) were surveyed twice eight months apart in 2020-2021 about telehealth use. Programs were asked to describe barriers to and promoters of telehealth., Results: Ninety-seven percent of programs provided telehealth services. In the first CF Care Program State of Care Survey (SoC1), programs estimated that 57% of patients exclusively received in-person care, 36% of patients received telehealth by phone/computer with video, and 8% of patients received telephone-only care. In the second CF Care Program State of Care Survey (SoC2), programs estimated that 80% of visits were in-person and 15% were via audio and video telehealth. Pediatric programs (21%) were less likely than adult (37%) or affiliate (41%) programs to recommend telehealth (p = 0.007). All programs ranked lack of internet access as the highest barrier to patient engagement with telehealth. Promoters of telehealth were increased accessibility and avoidance of infection transmission. Top ranked changes to improve telehealth were expanded provision of remote monitoring devices and technology access. Similar proportions of program types anticipated institutional telehealth expansion., Conclusion: During the COVID-19 pandemic, CF programs in the United States identified factors to improve future care delivery via telehealth. Targeting specific barriers and promoters will improve the use and quality of telehealth throughout the care center network., (Copyright © 2021. Published by Elsevier B.V.)

Background: During the COVID-19 pandemic, CF centers shifted to a telehealth delivery model. Our study aimed to determine how people with CF (PwCF) and their families experienced telehealth and assessed its quality and acceptability for future CF care., Methods: The CF Patient and Family State of Care Survey (PFSoC) was fielded from August 31-October 30, 2020. The PFSoC explored themes of overall telehealth quality, ease of use, desirability, and preference for a future mix of in-person and telehealth care. Demographic covariates considered included: gender, age, CFTR modulator status, and region of residence., Results: 424 PwCF and parents of PwCF responded (47% parents). Most (81%) reported a telehealth visit which included a MD/APP and nurse team members. 91% found telehealth easy to use, and 66% reported similar/higher quality than in-person care. One-third (34%) reported the highest desire for future telehealth care, with 45% (n =212) desiring 50% or more of visits conducted via telehealth. Adults were more likely than parents to report highest desire for future telehealth (64% vs. 36%). Respondents who perceived telehealth as similar/higher quality were more likely to desire future telehealth compared to those who perceived telehealth as lower quality (96% vs. 50%). Mixed methods analysis revealed themes affecting perceptions of telehealth., Conclusions: PwCF desire for future telehealth was influenced by perception of quality and age. Several themes emerged that need to be explored as telehealth is adapted into the CF chronic care model, especially when thinking about integration into pediatric care., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background and Purpose: AVFs of the foramen magnum region, including fistulas of the marginal sinus and condylar veins, have complex arterial supply, venous drainage, symptoms, and risk features that are not well-defined. The purpose of this study was to present the angioarchitectural and clinical phenotypes of a foramen magnum region AVF from a large, single-center experience., Materials and Methods: We retrospectively reviewed cases from a 10-year neurointerventional data base. Arterial and venous angioarchitectural features and clinical presentation were extracted from the medical record. Venous drainage patterns were stratified into 4 groups as follows: type 1 = unrestricted sinus drainage, type 2 = sinus reflux (including the inferior petrosal sinus), type 3 = reflux involving sinuses and cortical veins, and type 4 = restricted cortical vein outflow or perimedullary congestion., Results: Twenty-eight patients (mean age, 57.9 years; 57.1% men) had 29 foramen magnum region AVFs. There were 11 (37.9%) type 1, nine (31.0%) type 2, six (20.7%) type 3, and 3 (10.3%) type 4 fistulas. Pulsatile tinnitus was the most frequent symptom (82.1%), followed by orbital symptoms (31.0%), subarachnoid hemorrhage (13.8%), cranial nerve XII palsy (10.3%), and other cranial nerve palsy (6.9%). The most frequent arterial supply was the ipsilateral ascending pharyngeal artery (93.1% ipsilateral, 55.5% contralateral), vertebral artery (89.7%), occipital artery (65.5%), and internal carotid artery branches (48.3%)., Conclusions: We present the largest case series of foramen magnum region AVFs to date and show that clinical features relate to angioarchitecture. Orbital symptoms are frequent when sinus reflux is present. Hemorrhage was only observed in type 3 and 4 fistulas., (© 2021 by American Journal of Neuroradiology.)

Activating variants in the platelet-derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next-generation sequencing-based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB-activating variants through literature search. The conditions caused by PDGFRB-activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant-related phenotypes are present. Whole-body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6- to 12-month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted., (© 2021 Wiley Periodicals LLC.)

Background: Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs. This article describes a project of the Clinical Trials Transformation Initiative (CTTI) intended to help clinical trials researchers determine when a registry could potentially serve as the platform for the conduct of a clinical trial., Methods: Through a review of registry-embedded clinical trials and commentaries, semi-structured interviews with experts, and a multi-stakeholder expert meeting, the project team addressed how to identify and describe essential registry characteristics, practices, and processes required to for conducting embedded clinical trials intended for regulatory submissions in the United States., Results: Recommendations, suggested practices, and decision trees that facilitate the assessment of whether a registry is suitable for embedding clinical trials were developed, as well as considerations for the design of new registries. Essential registry characteristics include relevancy, robustness, reliability, and assurance of patient protections., Conclusions: The project identifies a clear role for registries in creating a sustainable and reusable infrastructure to conduct clinical trials. Adoption of these recommendations will facilitate the ability to perform high-quality and efficient prospective registry-based clinical trials.

Background and Purpose: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA., Materials and Methods: Thirty-five color-coded parametric DSA images of 34 brain AVMs were analyzed by 4 neuroradiologists with experience in interventional neuroradiology. Hemodynamic features assessed included MTT of the AVM and TTP of the dominant feeding artery and draining vein. Agreement among the 4 raters was assessed using the intraclass correlation coefficient., Results: The interrater reliability among the 4 raters was poor (intraclass correlation coefficient = 0.218; 95% CI, 0.062-0.414; P value = .002) as it related to MTT assessment. When the analysis was limited to cases in which the raters selected the same image to analyze and selected the same primary feeding artery and the same primary draining vein, interrater reliability improved to fair (intraclass correlation coefficient  = 0.564; 95% CI, 0.367-0.717; P  < .001)., Conclusions: Interrater reliability in deriving color-coded parametric DSA measurements such as MTT is poor so minor differences among raters may result in a large variance in MTT and TTP results, partly due to the sensitivity and 2D nature of the technique. Reliability can be improved by defining a standard projection, feeding artery, and draining vein for analysis., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast., Materials and Methods: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study., Results: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P  = .04)., Conclusions: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: Arterial access is a technical consideration of mechanical thrombectomy that may affect procedural time, but few studies exist detailing the relationship of anatomy to procedural times and patient outcomes. We sought to investigate the respective impact of aortic arch and carotid artery anatomy on endovascular procedural times in patients with large-vessel occlusion., Materials and Methods: We retrospectively reviewed imaging and medical records of 207 patients from 2 academic institutions who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion from January 2015 to July 2018. Preintervention CTAs were assessed to measure features of the aortic arch and ipsilateral great vessel anatomy. These included the cranial-to-caudal distance from the origin of the innominate artery to the top of the aortic arch and the takeoff angle of the respective great vessel from the arch. mRS scores were calculated from rehabilitation and other outpatient documentation. We performed bootstrap, stepwise regressions to model groin puncture to reperfusion time and binary mRS outcomes (good outcome, mRS ≤ 2)., Results: From our linear regression for groin puncture to reperfusion time, we found a significant association of the great vessel takeoff angle ( P = .002) and caudal distance from the origin of the innominate artery to the top of the aortic arch ( P = .05). Regression analysis for the binary mRS revealed a significant association with groin puncture to reperfusion time ( P < .001)., Conclusions: These results demonstrate that patients with larger takeoff angles and extreme aortic arches have an association with longer procedural times as approached from transfemoral access routes., (© 2020 by American Journal of Neuroradiology.)

We evaluated cause of injury and quantified levels of three potential mycoplasmal pathogens ( Mycoplasma agassizii , Mycoplasma testudineum , and an emydid mycoplasma) in three-toed box turtles ( Terrapene carolina triunguis ) from the greater St. Louis, Missouri, US area, brought to and housed at the Wildlife Rescue Center (Ballwin, Missouri, US) in 2015 and 2016. We created a probebased quantitative PCR (qPCR) assay for the emydid mycoplasma, with a similar specificity and sensitivity as the existing qPCR assays for M. agassizii and M. testudineum . All three microbes have been implicated in the development of upper respiratory tract disease in turtles and tortoises. We assessed whether signs of respiratory disease, sex, type of trauma, or treatment (administration of antibiotics) affected the presence of pathogens. We found that the most common types of injury experienced by turtles ( n =85) were due to motor vehicles and other types of machinery, and that injuries due to motor vehicles were the most severe. We found a 61% prevalence of emydid mycoplasm a ( n =28) but M. agassizii or M. testudineum were not detected. Prevalence of disease and antibiotic treatment was too low to statistically relate to levels of mycoplasma. Sex and type of trauma were not associated with levels of emydid mycoplasma. The box turtle population we sampled did not experience signs of respiratory disease due to the fairly widespread prevalence of emydid mycoplasma. However, mycoplasmal diseases can be pathogen load-dependent. The qPCR we designed can be used to assess levels of emydid mycoplasma in other emydid species, populations, and individuals, in which there might be a positive association between the microbe and expression of respiratory disease.

Purpose: The purpose of this study was to report trends, complications, and costs associated with endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR). Methods: Using Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes, patients who had open versus endoscopic carpal tunnel release (CTR) were identified retrospectively in the PearlDiver database from both the Medicare and Humana (a private payer health insurance) populations from 2005 to 2014. These groups were then evaluated for postoperative complications, including wound infection within 90 days, wound dehiscence within 90 days, and intraoperative median nerve injury. We also used the data output for each group to compare the cost of the 2 procedure types. Data were analyzed via the Student t test. Statistical significance was set at P < .05. Results: A significantly lower percentage of patients in the endoscopic CTR group had a postoperative infection (5.21 vs 7.97 per 1000 patients per year, P < .001; 7.36 vs 11.23 per 1000 patients per year, P < .001) and wound dehiscence (1.58 vs 2.87 per 1000 patients per year, P < .001; 2.14 vs 3.73 per 1000 patients per year, P < .05) than open CTR group in the Medicare and Humana populations, respectively. Median nerve injury occurred 0.59/1000 ECTRs versus 1.69/1000 OCTRs (Medicare) and 1.96/1000 ECTRs versus 3.72/1000 OCTRs (Humana). Endoscopic CTR cost was more than open CTR for both the Medicare population ($1643 vs $1015 per procedure, P < .001) and Humana population ($1928 vs $1191 per procedure, P < .001). Conclusions: In both the Medicare and private insurance patient populations, endoscopic CTR is associated with fewer postoperative complications than open CTR, but is associated with greater expenses.

Appropriate segregation within manufacturing facilities is required by regulators and utilized by manufacturers to ensure that the final product has not been contaminated with (a) adventitious viruses, (b) another pre-/postviral clearance fraction of the same product, or (c) another product processed in the same facility. However, there is no consensus on what constitutes appropriate facility segregation to minimize these risks. In part, this is due to the fact that a wide variety of manufacturing facilities and operational practices exist, including single-product and multiproduct manufacturing, using traditional segregation strategies with separate rooms for specific operations that may use stainless steel or disposable equipment to more modern ballroom-style operations that use mostly disposable equipment (i.e., pre- and postviral clearance manufacturing operations are not physically segregated by walls). Further, consensus is lacking around basic definitions and approaches related to facility segregation. For example, given that several unit operations provide assurance of virus clearance during downstream processing, how does one define pre- and postviral clearance and at which point(s) should a viral segregation barrier be introduced? What is a "functionally closed" system? How can interventions be conducted so that the system remains functionally closed? How can functionally closed systems be used to adequately isolate a product stream and ensure its safety? To address these issues, the member companies of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) have conducted a facility segregation project with the following goals: define "pre- and postviral clearance zones" and "pre- and postviral clearance materials"; define "functionally closed" manufacturing systems; and identify an array of facility segregation approaches that are used for the safe and effective production of recombinant biologics as well as plasma products. This article reflects the current thinking from this collaborative endeavor. LAY ABSTRACT: Operations in biopharmaceutical manufacturing are segregated to ensure that the final product has not been contaminated with adventitious viruses, another fraction of the same product, or with another product from within the same facility. Yet there is no consensus understanding of what appropriate facility segregation looks like. There are a wide variety of manufacturing facilities and operational practices. There are existing facilities with separate rooms and more modern approaches that use disposable equipment in an open ballroom without walls. There is also no agreement on basic definitions and approaches related to facility segregation approaches. For example, many would like to claim that their manufacturing process is functionally closed, yet exactly how a functionally closed system may be defined is not clear. To address this, the member companies of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) have conducted a project with the goal of defining important manufacturing terms relevant to designing an appropriately segregated facility and identifying different facility segregation approaches that are used for the safe and effective production of recombinant biologics as well as plasma products., (© PDA, Inc. 2019.)

Hyperkalemia is common in patients with heart failure or chronic kidney disease, particularly those taking renin-angiotensin-aldosterone system inhibitors, and can cause arrhythmias and sudden cardiac death. The most widely used treatment, sodium polystyrene sulfonate (SPS), limits gastrointestinal potassium absorption, but has poor palatability. RDX7675 (RDX227675) is the calcium salt of a reengineered polystyrene sulfonate-based resin with improved palatability over SPS. The pharmacodynamic effects and safety of RDX7675 were assessed in a phase 1, single-center, randomized, active-controlled study. Healthy volunteers received nominal active doses of RDX7675 4.6 g twice a day (BID), 4.6 g 3 times a day (TID), 6.9 g BID, 13.7 g daily (QD), 9.2 g TID, or 13.7 g BID (n = 12 each), or equivalent doses of SPS (n = 3 each), for 4 days. RDX7675 dosing increased stool potassium excretion and decreased urinary potassium excretion from baseline. Stool potassium excretion increased by up to 1481 mg/day with RDX7675 (6.9 g BID), and urinary potassium excretion decreased by up to 939 mg/day (13.7 g BID). Similar levels of potassium excretion were observed using QD, BID, or TID dosing of a 13.7 g total daily RDX7675 dose. Few adverse events were reported. In conclusion, repeated oral dosing with RDX7675 over 4 days reduced potassium absorption in healthy volunteers; the results support QD dosing of RDX7675 in future clinical studies., (© 2018, The American College of Clinical Pharmacology.)

As we celebrate the 70th birthday of the NHS, Clare Price-Dowd reflects on the pioneers of nursing and how leadership in the NHS, and in nursing, has changed over time, and shares some thoughts about the future.

Aim: To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori ( H. pylori )-infected patients in Ireland., Methods: DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori -infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. cagA and vacA genotypes were investigated using PCR., Results: Primary, secondary and overall resistance rates for clarithromycin were 50.5% ( n = 53/105), 78.3% ( n = 47/60) and 60.6% ( n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2% ( n = 16/105) and 28.3% ( n = 17/60) and 20% ( n = 33/165), respectively. Resistance to both antibiotics was 12.4% ( n = 13/105) in treatment-naïve patients, 25% ( n = 15/60) in those previously treated and 17% ( n = 28/165) overall. A cagA -positive genotype was detected in 22.4% ( n = 37/165) of patient samples. The dominant vacA genotype was S1/M2 at 44.8% ( n = 74/165), followed by S2/M2 at 26.7% ( n = 44/165), S1/M1 at 23.6% ( n = 39/165) and S2/M1 at 4.8% ( n = 8/165). Primary clarithromycin resistance was significantly lower in cagA -positive strains than in cagA -negative strains [32% ( n = 8/25) vs 56.3% ( n = 45/80) P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, [41% ( n = 32/78) vs 77.8% ( n = 21/27) P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status., Conclusion: Genotypic H. pylori clarithromycin resistance is high and cagA -negative strains are dominant in our population. Less virulent ( cagA -negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance., Competing Interests: Conflict-of-interest statement: None to declare.

In her final blog, Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, discusses what good communication means and the difference this can make to patients.

There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

We hope that all nurses are committed to what they do, but what does that really mean? Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, explores why commitment is fundamental for a nurse.

Background and Purpose: Although intracranial dural arteriovenous fistulas are principally supplied by dural branches of the external carotid, internal carotid, and vertebral arteries, they can also be fed by pial arteries that supply the brain. We sought to determine the frequency of neurologic deficits following treatment of intracranial dural arteriovenous fistulas with and without pial artery supply., Materials and Methods: One hundred twenty-two consecutive patients who underwent treatment for intracranial dural arteriovenous fistulas at our hospital from 2008 to 2015 were retrospectively reviewed. Patient data were examined for posttreatment neurologic deficits; patients with such deficits were evaluated for imaging evidence of cerebral infarction. Data were analyzed with multivariable logistic regression., Results: Of 122 treated patients, 29 (23.8%) had dural arteriovenous fistulas with pial artery supply and 93 (76.2%) had dural arteriovenous fistulas without pial arterial supply. Of patients with pial artery supply, 4 (13.8%) had posttreatment neurologic deficits, compared with 2 patients (2.2%) without pial artery supply ( P = .04). Imaging confirmed that 3 patients with pial artery supply (10.3%) had cerebral infarcts, compared with only 1 patient without pial artery supply (1.1%, P = .03). Increasing patient age was also positively associated with pial supply and treatment-related complications., Conclusions: Patients with dural arteriovenous fistulas supplied by the pial arteries were more likely to experience posttreatment complications, including ischemic strokes, than patients with no pial artery supply. The approach to dural arteriovenous fistula treatment should be made on a case-by-case basis so that the risk of complications can be minimized., (© 2017 by American Journal of Neuroradiology.)

Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, discusses the importance of candour in her latest blog on the '6Cs of nursing', and the need for honesty and openness in patient care.

Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, Leeds, explores what courage means to her in the fourth blog in her '6 Cs of nursing' series.

In this third blog in the series, Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, Leeds, discusses the importance of having both confident and competent nurses delivering care.

In her second blog in the series, Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, Leeds, talks about the importance of care in nurses' day-to-day lives, both for patients and colleagues.

When mum had a fall and was taken to hospital, nobody was looking for anything life-threatening. But in a matter of days, things went desperately wrong and she died from an abdominal tumour that had gone undetected.

The spontaneous growth of cloud condensation nuclei (CCN) into cloud droplets under supersaturated water vapour conditions is described by classic Köhler theory. This spontaneous activation of CCN depends on the interplay between the Raoult effect, whereby activation potential increases with decreasing water activity or increasing solute concentration, and the Kelvin effect, whereby activation potential decreases with decreasing droplet size or increases with decreasing surface tension, which is sensitive to surfactants. Surface tension lowering caused by organic surfactants, which diminishes the Kelvin effect, is expected to be negated by a concomitant reduction in the Raoult effect, driven by the displacement of surfactant molecules from the droplet bulk to the droplet-vapour interface. Here we present observational and theoretical evidence illustrating that, in ambient air, surface tension lowering can prevail over the reduction in the Raoult effect, leading to substantial increases in cloud droplet concentrations. We suggest that consideration of liquid-liquid phase separation, leading to complete or partial engulfing of a hygroscopic particle core by a hydrophobic organic-rich phase, can explain the lack of concomitant reduction of the Raoult effect, while maintaining substantial lowering of surface tension, even for partial surface coverage. Apart from the importance of particle size and composition in droplet activation, we show by observation and modelling that incorporation of phase-separation effects into activation thermodynamics can lead to a CCN number concentration that is up to ten times what is predicted by climate models, changing the properties of clouds. An adequate representation of the CCN activation process is essential to the prediction of clouds in climate models, and given the effect of clouds on the Earth's energy balance, improved prediction of aerosol-cloud-climate interactions is likely to result in improved assessments of future climate change.

In the first instalment in a series of blogs, Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, Leeds, talks about her personal experience of compassionate nursing and discusses why it is so important in the NHS.

Rationale: The Cystic Fibrosis Foundation Patient Registry (CFFPR) is an ongoing patient registry study that collects longitudinal demographic, clinical, and treatment information about persons with cystic fibrosis (CF) in the United States. CF is a life-shortening genetic disorder that occurs in approximately 1 in 3,500 births in the United States. High-quality observational data is important for clinical research, quality improvement, and clinical management., Objectives: To describe the data collection, patient population, and key limitations of the CFFPR., Methods: Inclusion criteria for the CFFPR include diagnosis with CF or a CFTR-associated disorder, care at an accredited care center program, and provision of informed consent. Data from clinic visits and hospitalizations are collected through a secure website. Loss to follow-up and generalizability were examined using several methods. The accuracy of CFFPR data was evaluated with an audit of 2012 CFFPR data compared to the medical record., Measurements and Main Results: Since 1986, the CFFPR contains the records of 48,463 individuals with CF. Participation among individuals seen at accredited care centers is high, and loss to follow-up is low. An audit of 2012 CFFPR data suggests that the CFFPR contains 95% of clinic visits and 90% of hospitalizations found in the medical record for these patients, and nearly all of the audited fields were highly accurate., Conclusions: Registries such as the CFFPR are important tools for research, clinical care, and tracking incidence, mortality and population trends.

In the endovascular treatment of cerebral arteriovenous malformations, ethanol sclerotherapy is seldom used due to safety concerns. However, when limited reflux of an embolic agent is permissible or when there is a long distance to the target, ethanol may be preferable. We reviewed 10 patients with 14 cerebral AVM feeding artery aneurysms or intranidal aneurysms treated with intra-arterial ethanol sclerotherapy at our institution between 2005 and 2014. All patients presented with acute intracranial hemorrhage. Thirteen of 14 aneurysms were treated primarily with 60%-80% ethanol into the feeding artery. Complete target feeding artery and aneurysm occlusion was seen in all cases; 8/13 (62%) were occluded by using ethanol alone. No retreatments or recurrences were seen. One permanent neurologic deficit (1/13, 7.7%) and no deaths occurred. In a subset of ruptured cerebral AVMs, ethanol sclerotherapy of feeding artery aneurysms and intranidal aneurysms can be performed with a high degree of technical success and a low rate of complication., (© 2016 by American Journal of Neuroradiology.)

Background and Purpose: A minority of intracranial dural arteriovenous fistulas progress with time. We sought to determine features that predict progression and define outcomes of patients with progressive dural arteriovenous fistulas., Materials and Methods: We performed a retrospective imaging and clinical record review of patients with intracranial dural arteriovenous fistula evaluated at our hospital., Results: Of 579 patients with intracranial dural arteriovenous fistulas, 545 had 1 fistula (mean age, 45 ± 23 years) and 34 (5.9%) had enlarging, de novo, multiple, or recurrent fistulas (mean age, 53 ± 20 years; P = .11). Among these 34 patients, 19 had progressive dural arteriovenous fistulas with de novo fistulas or fistula enlargement with time (mean age, 36 ± 25 years; progressive group) and 15 had multiple or recurrent but nonprogressive fistulas (mean age, 57 ± 13 years; P = .0059, nonprogressive group). Whereas all 6 children had fistula progression, only 13/28 adults (P = .020) progressed. Angioarchitectural correlates to chronically elevated intracranial venous pressures, including venous sinus dilation (41% versus 7%, P = .045) and pseudophlebitic cortical venous pattern (P = .048), were more common in patients with progressive disease than in those without progression. Patients with progressive disease received more treatments than those without progression (median, 5 versus 3; P = .0068), but as a group, they did not demonstrate worse clinical outcomes (median mRS, 1 and 1; P = .39). However, 3 young patients died from intracranial venous hypertension and intracranial hemorrhage related to progression of their fistulas despite extensive endovascular, surgical, and radiosurgical treatments., Conclusions: Few patients with dural arteriovenous fistulas follow an aggressive, progressive clinical course despite treatment. Younger age at initial presentation and angioarchitectural correlates to venous hypertension may help identify these patients prospectively., (© 2015 by American Journal of Neuroradiology.)

Background and Purpose: Intracranial hemorrhage is the most serious outcome for brain arteriovenous malformations. This study examines associations between venous characteristics of these lesions and intracranial hemorrhage., Materials and Methods: Statistical analysis was performed on a prospectively maintained data base of brain AVMs evaluated at an academic medical center. DSA, CT, and MR imaging studies were evaluated to classify lesion side, drainage pattern, venous stenosis, number of draining veins, venous ectasia, and venous reflux. Logistic regression analyses were performed to identify the association of these angiographic features with intracranial hemorrhage of any age at initial presentation., Results: Exclusively deep drainage (OR, 3.42; 95% CI, 1.87-6.26; P < .001) and a single draining vein (OR, 1.98; 95% CI, 1.26-3.08; P = .002) were associated with hemorrhage, whereas venous ectasia (OR, 0.52; 95% CI, 0.34-0.78; P = .002) was inversely associated with hemorrhage., Conclusions: Analysis of venous characteristics of brain AVMs may help determine their prognosis and thereby identify lesions most appropriate for treatment., (© 2015 by American Journal of Neuroradiology.)

Recent studies have shown that young adults significantly reduce their gait speed and weave more when texting while walking. Previous research has not examined the simultaneous dual-task effects on texting performance, therefore, the attention prioritization strategy used by young adults while texting and walking is not currently known. Moreover, it is not known whether laboratory-based studies accurately reflect texting and walking performance in the real world. This study compared dual-task interference during texting and walking between laboratory and real-world settings, and examined the ability of young adults to flexibly prioritize their attention between the two tasks in each environment. Texting and walking were assessed in single-task and three dual-task conditions (no-priority, gait-priority, texting-priority) in the lab and a University Student Center, in 32 healthy young adults. Dual-task effects on gait speed, texting speed, and texting accuracy were significant, but did not significantly differ between the two environments. Young adults were able to flexibly prioritize their attention between texting and walking, according to specific instruction, and this ability was not influenced by environmental setting. In the absence of instructions, young adults prioritized the texting task in the low-distraction environment, but displayed more equal focus between tasks in the real world. The finding that young adults do not significantly modify their texting and walking behavior in high-distraction environments lends weight to growing concerns about cell phone use and pedestrian safety., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Purpose: The imaging characteristics and modes of presentation of brain AVMs may vary with patient age. Our aim was to determine whether clinical and angioarchitectural features of brain AVMs differ between children and adults., Materials and Methods: A prospectively collected institutional data base of all patients diagnosed with brain AVMs since 2001 was queried. Demographic, clinical, and angioarchitecture information was summarized and analyzed with univariable and multivariable models., Results: Results often differed when age was treated as a continuous variable as opposed to dividing subjects into children (18 years or younger; n = 203) versus adults (older than 18 years; n = 630). Children were more likely to present with AVM hemorrhage than adults (59% versus 41%, P < .001). Although AVMs with a larger nidus presented at younger ages (mean of 26.8 years for >6 cm compared with 37.1 years for <3 cm), this feature was not significantly different between children and adults (P = .069). Exclusively deep venous drainage was more common in younger subjects when age was treated continuously (P = .04) or dichotomized (P < .001). Venous ectasia was more common with increasing age (mean, 39.4 years with ectasia compared with 31.1 years without ectasia) and when adults were compared with children (52% versus 35%, P < .001). Patients with feeding artery aneurysms presented at a later average age (44.1 years) than those without such aneurysms (31.6 years); this observation persisted when comparing children with adults (13% versus 29%, P < .001)., Conclusions: Although children with brain AVMs were more likely to come to clinical attention due to hemorrhage than adults, venous ectasia and feeding artery aneurysms were under-represented in children, suggesting that these particular high-risk features take time to develop., (© 2014 by American Journal of Neuroradiology.)