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It has been shown that excitotoxicity and tau-mediated toxicities are major contributing factors to neuronal death in Alzheimer's disease (AD). The excitatory amino acid transporter 2 (EAAT2 or GLT-1), the major glutamate transporter in the brain that regulates glutamate levels synaptically and extrasynaptically, has been shown to be deficient in AD brains, leading to excitotoxicity and subsequent cell death. Similarly, buildup of neurofibrillary tangles, which consist of hyperphosphorylated tau protein, correlates with cognitive decline and neuronal atrophy in AD. However, common genes and pathways that are critical in the aforementioned toxicities have not been well elucidated. To investigate the impact of glutamate dyshomeostasis and tau accumulation on translational profiles of affected hippocampal neurons, we used mouse models of excitotoxicity and tau-mediated toxicities (GLT-1 -/- and P301S, respectively) in conjunction with BAC-TRAP technology. Our data show that GLT-1 deficiency in CA3 pyramidal neurons leads to translational signatures characterized by dysregulation of pathways associated with synaptic plasticity and neuronal survival, while the P301S mutation induces changes in endocytic pathways and mitochondrial dysfunction. Finally, the commonly dysregulated pathways include impaired ion homeostasis and metabolic pathways. These common pathways may shed light on potential therapeutic targets for ameliorating glutamate and tau-mediated toxicities in AD., Competing Interests: Declaration of competing interest Unrelated to this work, A.C.P. has patents unrelated to this work licensed to Neurobiopharma, LLC, serves on the scientific advisory board of Sinaptica Therapeutics and has served as a consultant to Eisai., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Many studies show that both callous-unemotional (CU) traits (e.g., low empathy, lack of guilt) and cognitive difficulties increase risk for externalizing psychopathology across development. However, other work suggests that some aggression (e.g., relational, proactive) may rely on intact cognitive function, which could vary based on the presence of CU traits. Moreover, no prior research has adequately accounted for common risk factors shared by CU traits, cognitive difficulties, and externalizing problems, which confounds conclusions that can be drawn about their purported relationships. The current study addressed these knowledge gaps by leveraging rigorous propensity matching methods to isolate associations between CU traits and different dimensions of cognitive function and externalizing problems., Methods: Associations between CU traits, cognitive functioning, and externalizing outcomes were tested within dimensional (n = 11,868) and propensity-matched group-based (n = 1,224) models using data from the Adolescent Brain Cognitive Development Study®, with rigorous statistical control for shared sociodemographic risk factors. Cross-sectional outcomes were parent-reported symptoms of conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD). Longitudinal outcomes were child-reported overt and relational aggression., Results: CU traits were uniquely related to more parent-reported CD, ODD, ADHD symptoms, as well as more child-reported aggressive behaviors. Effects of cognitive difficulties were domain specific and were not consistent across dimensional and propensity matched models. There was minimal evidence for divergent associations between CU traits and externalizing outcomes as a function of cognition (i.e., no moderation)., Conclusions: Rigorous control for sociodemographic factors within propensity-matched models establish CU traits as a robust and unique risk factor for externalizing psychopathology, over and above difficulties with cognitive functioning., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Diffusion Spectrum Imaging (DSI) using dense Cartesian sampling of q-space has been shown to provide important advantages for modeling complex white matter architecture. However, its adoption has been limited by the lengthy acquisition time required. Sparser sampling of q-space combined with compressed sensing (CS) reconstruction techniques has been proposed as a way to reduce the scan time of DSI acquisitions. However prior studies have mainly evaluated CS-DSI in post-mortem or non-human data. At present, the capacity for CS-DSI to provide accurate and reliable measures of white matter anatomy and microstructure in the living human brain remains unclear. We evaluated the accuracy and inter-scan reliability of 6 different CS-DSI schemes that provided up to 80% reductions in scan time compared to a full DSI scheme. We capitalized on a dataset of 26 participants who were scanned over eight independent sessions using a full DSI scheme. From this full DSI scheme, we subsampled images to create a range of CS-DSI images. This allowed us to compare the accuracy and inter-scan reliability of derived measures of white matter structure (bundle segmentation, voxel-wise scalar maps) produced by the CS-DSI and the full DSI schemes. We found that CS-DSI estimates of both bundle segmentations and voxel-wise scalars were nearly as accurate and reliable as those generated by the full DSI scheme. Moreover, we found that the accuracy and reliability of CS-DSI was higher in white matter bundles that were more reliably segmented by the full DSI scheme. As a final step, we replicated the accuracy of CS-DSI in a prospectively acquired dataset (n = 20, scanned once). Together, these results illustrate the utility of CS-DSI for reliably delineating in vivo white matter architecture in a fraction of the scan time, underscoring its promise for both clinical and research applications., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca 2+ activity in both sensory and non-sensory cells. Calcium signalling in neonatal OHCs can be modulated by oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca 2+ activity and afferent connectivity during development. Using a genetically encoded Ca 2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm +/+ ) and Ocm knockout (Ocm -/- ) littermates, we found increased spontaneous Ca 2+ activity and upregulation of purinergic receptors in OHCs from Ocm -/- cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibres on Ocm -/- OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca 2+ signalling in the developing cochlea and the maturation of OHC afferent innervation. KEY POINTS: Cochlear outer hair cells (OHCs) exhibit spontaneous Ca 2+ activity during a narrow period of neonatal development. OHC afferent maturation and connectivity requires spontaneous Ca 2+ activity. Oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein, modulates Ca 2+ signals in immature OHCs. Using transgenic mice that endogenously expressed a Ca 2+ sensor, GCaMP6s, we found increased spontaneous Ca 2+ activity and upregulated purinergic receptors in Ocm -/- OHCs. The maturation of afferent synapses in Ocm -/- OHCs was also delayed, leading to an upregulation of ribbon synapses and afferent fibres in Ocm -/- OHCs before hearing onset. We propose that OCM plays an important role in modulating Ca 2+ activity, expression of Ca 2+ channels and afferent innervation in developing OHCs., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Diffusion MRI is the dominant non-invasive imaging method used to characterize white matter organization in health and disease. Increasingly, fiber-specific properties within a voxel are analyzed using fixels. While tools for conducting statistical analyses of fixel-wise data exist, currently available tools support only a limited number of statistical models. Here we introduce ModelArray, an R package for mass-univariate statistical analysis of fixel-wise data. At present, ModelArray supports linear models as well as generalized additive models (GAMs), which are particularly useful for studying nonlinear effects in lifespan data. In addition, ModelArray also aims for scalable analysis. With only several lines of code, even large fixel-wise datasets can be analyzed using a standard personal computer. Detailed memory profiling revealed that ModelArray required only limited memory even for large datasets. As an example, we applied ModelArray to fixel-wise data derived from diffusion images acquired as part of the Philadelphia Neurodevelopmental Cohort (n = 938). ModelArray revealed anticipated nonlinear developmental effects in white matter. Moving forward, ModelArray is supported by an open-source software development model that can incorporate additional statistical models and other imaging data types. Taken together, ModelArray provides a flexible and efficient platform for statistical analysis of fixel-wise data., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8-23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Issue Addressed: There is a need for culturally appropriate methods in the implementation and evaluation of Aboriginal and Torres Strait Islander health programs. A group of Indigenous and non-Indigenous practitioners culturally adapted and applied the Tri-Ethnic Research Centre's Community Readiness Tool (CRT) to evaluate change in community readiness and reflect on its appropriateness., Methods: Aboriginal community-controlled health service staff informed the cultural adaptation of the standard CRT. The adapted CRT was then used at baseline and 12-month follow-up in three remote communities in the Cape York region, Queensland, Australia. Program implementation occurred within a pilot project aiming to influence availability of drinking water and sugary drinks., Results: The adapted CRT was found to be feasible and useful. Overall mean readiness scores increased in two communities, with no change in the third community. CRT interview data were used to develop community action plans with key stakeholders that were tailored to communities' stage of readiness. Considerations for future application of the CRT were the importance of having a pre-defined issue, time and resource-intensiveness of the process, and need to review appropriateness prior to implementation in other regions., Conclusion: The adapted CRT was valuable for evaluating the project and co-designing strategies with stakeholders, and holds potential for further applications in health promotion in remote Aboriginal and Torres Strait Islander communities. SO WHAT?: This project identified benefits of CRT application not reported elsewhere. The adapted CRT adds a practical method to the toolkits of health promotors and evaluators for working in partnership with Aboriginal and Torres Strait Islander communities to address priority concerns., (© 2022 Australian Health Promotion Association.)

The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions that result in inconsistent processing across sessions. Additionally, in large-scale, heterogeneous neuroimaging datasets, hidden variability in metadata is difficult to detect and classify. To address these challenges, we created a Python-based software package titled "Curation of BIDS" (CuBIDS), which provides an intuitive workflow that helps users validate and manage the curation of their neuroimaging datasets. CuBIDS includes a robust implementation of BIDS validation that scales to large samples and incorporates DataLad--a version control software package for data--as an optional dependency to ensure reproducibility and provenance tracking throughout the entire curation process. CuBIDS provides tools to help users perform quality control on their images' metadata and identify unique combinations of imaging parameters. Users can then execute BIDS Apps on a subset of participants that represent the full range of acquisition parameters that are present, accelerating pipeline testing on large datasets., Competing Interests: Declaration of Competing Interest The authors of Curation of BIDS (CuBIDS) declare that they have no competing or conflicting interests., (Copyright © 2022. Published by Elsevier Inc.)

Mapping individual differences in behavior is fundamental to personalized neuroscience, but quantifying complex behavior in real world settings remains a challenge. While mobility patterns captured by smartphones have increasingly been linked to a range of psychiatric symptoms, existing research has not specifically examined whether individuals have person-specific mobility patterns. We collected over 3000 days of mobility data from a sample of 41 adolescents and young adults (age 17-30 years, 28 female) with affective instability. We extracted summary mobility metrics from GPS and accelerometer data and used their covariance structures to identify individuals and calculated the individual identification accuracy-i.e., their "footprint distinctiveness". We found that statistical patterns of smartphone-based mobility features represented unique "footprints" that allow individual identification (p < 0.001). Critically, mobility footprints exhibited varying levels of person-specific distinctiveness (4-99%), which was associated with age and sex. Furthermore, reduced individual footprint distinctiveness was associated with instability in affect (p < 0.05) and circadian patterns (p < 0.05) as measured by environmental momentary assessment. Finally, brain functional connectivity, especially those in the somatomotor network, was linked to individual differences in mobility patterns (p < 0.05). Together, these results suggest that real-world mobility patterns may provide individual-specific signatures relevant for studies of development, sleep, and psychopathology., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derive personalized functional networks across 29 scales in a large sample of youths (n = 693, ages 8-23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling reflect and strengthen a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks are dissociably related to the emergence of executive function. These results suggest that the development of functional brain networks align with and refine a hierarchy linked to cognition., (© 2022. The Author(s).)

Ca 2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca 2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca 2+ signaling in maintaining hearing health. Manipulation of OCM and Ca 2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Climer, Hornak, Murtha, Yang, Cox, Simpson, Le and Simmons.)

The recent and growing focus on reproducibility in neuroimaging studies has led many major academic centers to use cloud-based imaging databases for storing, analyzing, and sharing complex imaging data. Flywheel is one such database platform that offers easily accessible, large-scale data management, along with a framework for reproducible analyses through containerized pipelines. The Brain Imaging Data Structure (BIDS) is the de facto standard for neuroimaging data, but curating neuroimaging data into BIDS can be a challenging and time-consuming task. In particular, standard solutions for BIDS curation are limited on Flywheel. To address these challenges, we developed "FlywheelTools," a software toolbox for reproducible data curation and manipulation on Flywheel. FlywheelTools includes two elements: fw-heudiconv , for heuristic-driven curation of data into BIDS, and flaudit , which audits and inventories projects on Flywheel. Together, these tools accelerate reproducible neuroscience research on the widely used Flywheel platform., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tapera, Cieslak, Bertolero, Adebimpe, Aguirre, Butler, Cook, Davila, Elliott, Linguiti, Murtha, Tackett, Detre and Satterthwaite.)

Issue Addressed: Good nutrition, physical activity and adequate sleep are essential for the healthy growth and development of young children. Due to complex cultural, historical, social factors, Aboriginal and Torres Strait Islander children face additional challenges to optimal health, particularly in remote areas of Australia. 'Learning, Eating, Active Play and Sleep' (LEAPS) was a Queensland-wide professional development program designed to support early childhood education and care (ECEC) educators to implement and reinforce healthy nutrition and physical activity in their services. This article describes the adaptation, implementation and evaluation of LEAPS for remote ECEC settings in Cape York., Methods: An Aboriginal and Torres Strait Islander Reference Group was commissioned to provide advice about the appropriateness of the existing program for Aboriginal and Torres Strait Islander ECEC settings. Based on the advice of the Reference Group, the program was adapted for use in Cape York and was evaluated using the RE-AIM framework and a combination of data sources. Quantitative data provided information about changes to participant knowledge and confidence regarding nutrition and physical activity and in-depth interviews allowed further insights into enablers and challenges for successful program implementation., Conclusion: A tailored LEAPS program increased participants' knowledge and confidence regarding nutrition and physical activity in ECEC settings. The importance of community consultation, building relationships and face-to-face delivery of training were highlighted as key enablers. The evaluation identified a number of challenges relating to competing priorities, limited support for ongoing implementation and adoption of improved practices. SO WHAT?: Poor nutrition and growth in children in remote Aboriginal and Torres Strait Islander communities indicates the need for the ongoing commitment to and investment in nutrition and physical activity across a range of community settings. To achieve success, this requires a dedicated preventative health workforce supporting evidence-informed, coordinated programs driven by community priorities and developed via community development approaches., (© 2020 Australian Health Promotion Association.)

Diffusion weighted imaging (DWI) has advanced our understanding of brain microstructure evolution over development. Recently, the use of multi-shell diffusion imaging sequences has coincided with advances in modeling the diffusion signal, such as Neurite Orientation Dispersion and Density Imaging (NODDI) and Laplacian-regularized Mean Apparent Propagator MRI (MAPL). However, the relative utility of recently-developed diffusion models for understanding brain maturation remains sparsely investigated. Additionally, despite evidence that motion artifact is a major confound for studies of development, the vulnerability of metrics derived from contemporary models to in-scanner motion has not been described. Accordingly, in a sample of 120 youth and young adults (ages 12-30) we evaluated metrics derived from diffusion tensor imaging (DTI), NODDI, and MAPL for associations with age and in-scanner head motion at multiple scales. Specifically, we examined mean white matter values, white matter tracts, white matter voxels, and connections in structural brain networks. Our results revealed that multi-shell diffusion imaging data can be leveraged to robustly characterize neurodevelopment, and demonstrate stronger age effects than equivalent single-shell data. Additionally, MAPL-derived metrics were less sensitive to the confounding effects of head motion. Our findings suggest that multi-shell imaging data and contemporary modeling techniques confer important advantages for studies of neurodevelopment., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To create supportive environments to reduce sugary drink consumption and increase water consumption by partnering with remote Aboriginal and Torres Strait Islander communities in Cape York., Methods: This paper applied qualitative and quantitative methods to evaluate a co-designed multi-strategy health promotion initiative, implemented over 12 months from 2017 to 2018. Outcome measures included changes in community readiness, awareness of the social marketing campaign and changes in drink availability. Changes in store drink sales were measured in one community and compared to sales in a control store., Results: Community readiness to address sugary drink consumption increased in two of the three communities. Awareness of social marketing campaign messaging was high (56-94%). Availability of drinking water increased in all communities. Water sales as a proportion of total drink volume sales increased by 3.1% (p<0.001) while sugary drink volume sales decreased by 3.4% (p<0.001)., Conclusions: A multi-component strategy with strong engagement from local government, community leaders and the wider community was associated with positive changes in community readiness, drink availability and sales. Implications for public health: Partnering with community leaders in the co-design of strategies to create environments that support healthy drink consumption can stimulate local action and may positively affect drink consumption., (© 2019 The Authors.)

Irritability is an important dimension of psychopathology that spans multiple clinical diagnostic categories, yet its relationship to patterns of brain development remains sparsely explored. Here, we examined how transdiagnostic symptoms of irritability relate to the development of structural brain networks. All participants (n = 137, 83 females) completed structural brain imaging with 3 Tesla MRI at two timepoints (mean age at follow-up: 21.1 years, mean inter-scan interval: 5.2 years). Irritability at follow-up was assessed using the Affective Reactivity Index, and cortical thickness was quantified using Advanced Normalization Tools software. Structural covariance networks were delineated using non-negative matrix factorization, a multivariate analysis technique. Both cross-sectional and longitudinal associations with irritability at follow-up were evaluated using generalized additive models with penalized splines. The False Discovery Rate (q < 0.05) was used to correct for multiple comparisons. Cross-sectional analysis of follow-up data revealed that 11 of the 24 covariance networks were associated with irritability, with higher levels of irritability being associated with thinner cortex. Longitudinal analyses further revealed that accelerated cortical thinning within nine networks was related to irritability at follow-up. Effects were particularly prominent in brain regions implicated in emotion regulation, including the orbitofrontal, lateral temporal, and medial temporal cortex. Collectively, these findings suggest that irritability is associated with widespread reductions in cortical thickness and accelerated cortical thinning, particularly within the frontal and temporal cortex. Aberrant structural maturation of regions important for emotional regulation may in part underlie symptoms of irritability.

The differential regulation of COX17, COX19 and COX23 mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was investigated. The NMD pathway regulates mRNAs that aberrantly terminate translation. This includes mRNAs harboring premature translation termination codons and natural mRNAs. Most natural mRNAs regulated by NMD encode fully functional proteins involved in various cellular processes. However, the cause and targeting of most of these mRNAs by the pathway is not understood. Analysis of a set of mRNAs involved in copper homeostasis showed that a subset of these mRNAs function in mitochondrial copper homeostasis. Here, we examined the regulation of COX17, COX19 and COX23 mRNAs by NMD. These mRNAs encode homologous mitochondrial proteins involved in metallation of cytochrome c oxidase. We found that COX17, COX19 and COX23 mRNAs are differentially regulated by NMD depending on environmental copper levels. A long 3'-UTR contributes to the direct regulation of COX19 mRNA by the pathway. Alternatively, COX23 mRNA contains a long 3'-UTR, but is indirectly regulated by the pathway under two conditions tested here. Analysis of the functionality of the NMD targeting features in COX23 mRNA showed that the COX23 3'-UTR is sufficient to trigger NMD. The regulation of mRNAs involved in mitochondrial copper metabolism by NMD is physiologically significant because excess copper enhances growth of NMD mutants on a non-fermentable carbon source. These findings suggest that regulation of mRNAs encoding homologous proteins by NMD can be differential depending on environmental copper levels. Furthermore, these findings suggest copper ion homeostatic mechanisms in the mitochondria occur at the mRNA level via the NMD pathway.

Objective: While the significance of type II endoleaks (T2ELs) on the long-term outcome of endovascular abdominal aneurysm repair (EVAR) to repair abdominal aortic aneurysms (AAAs) is debatable, duplex ultrasonography (DU) parameters have been suggested to be predictive of their closure or persistence. The purpose of this study was to determine which, if any, of these variables was associated with persistent T2EL or increased AAA sac diameter., Methods: Between 1998 and 2009, 278 patients underwent EVAR and post-operative DU surveillance during long-term follow-up (1-11 years) in our accredited non-invasive vascular laboratory by one of three experienced technologists. DU measured intra-sac flow velocity (IFV), spectral doppler waveform (SDW) patterns, post-EVAR sac diameter, and number of T2ELs., Results: T2ELs developed in 14% (38/278) of patients post-EVAR. Fourteen patients had T2ELs that resolved, and sac diameter decreased or remained the same: the average IFV was 42 cm/second; SDW patterns were monophasic in five, biphasic in seven and bidirectional in two; and multiple T2ELs were not present (0%) in any patient. Twelve patients had T2ELs that persisted, but sac diameter decreased or remained the same: the average IFV was 47 cm/second; SDW patterns were monophasic in one, biphasic in five, bidirectional in five, and undetermined in one; and multiple T2ELs were found in 17% (2) of patients. Twelve patients had T2ELs that persisted and were associated with increased sac diameter: the average IFV was 43 cm/second, SDW patterns were monophasic in one, biphasic in two, and bidirectional in nine; and multiple T2ELs were identified in 75% (9) of patients. None of the 38 patients with T2ELs treated with selective surgical or endovascular intervention for enlarging sac diameters (11/12) experienced a ruptured aneurysm., Conclusion: Contrary to previous smaller reports of T2ELs and DU surveillance, parameters such as IFV did not correlate with increased post-EVAR sac diameter. The presence of multiple T2ELs and bidirectional SDW may be the strongest factors predictive of increased sac diameter., (Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Surgical revision of failing peripheral arterial bypass grafts has generally been shown to provide superior patency rates compared to balloon angioplasty. We analyzed whether balloon angioplasty, specifically of peri-anastomotic stenoses (PAS), provided acceptable patency rates, because surgery for these lesions is more difficult and is likely associated with higher complication rates compared to surgical revision of stenoses in the body of a graft., Methods: This is a retrospective review of PAS balloon angioplasties performed at a single institution between January 1, 1999, and September 1, 2005. We report ''primary site patency'' as a stenosis treated by balloon angioplasty, ''revised primary site patency'' as a stenosis treated by repeat balloon angioplasty, and ''secondary site patency'' as an angioplastied stenosis treated surgically or when the graft thrombosed and was revised surgically. All procedures were performed in an endovascular operating room based on duplex scan findings suggesting a significant stenosis., Results: 48 PAS in 33 autologous vein and 15 prosthetic grafts were treated by balloon angioplasty in 42 patients. Mean follow-up was 12 months (range, 1-49 months). Interventions were performed on 22 femoropopliteal grafts (11 proximal, 11 distal), 20 femorotibial grafts (5 proximal, 15 distal), 2 axillofemoral grafts (2 proximal anastomoses), 2 popliteal-pedal grafts (1 proximal, 1 distal), and 1 common iliac-femoral graft (proximal). Life-table analysis revealed 2-year primary, assisted primary, and secondary patency rates of 38%, 58%, and 84%, respectively. No major complications occurred with any endovascular intervention., Conclusion: Balloon angioplasty of PAS resulted in acceptable 2-year assisted primary patency rate of almost 60%. Endovascular intervention avoided repeat incisions in scarred groins, higher rates of nerve injury and infection, significant blood loss, and longer length of hospital stays. We recommend that balloon angioplasty of PAS be attempted before resorting to surgical intervention, especially in cases of hostile anastomotic wounds.

A conceptual model is proposed for the genetic evolution of many human solid tumors that is based on the observations that cancer cells may spontaneously double their chromosome number; that cells with excessive chromosome numbers may be cytogenetically unstable, both losing chromosomes randomly during subsequent cell divisions, and often developing structural abnormalities in the chromosomes that are retained; and that some structural chromosome abnormalities may activate growth-promoting genes. The sequence of tetraploidization with chromosome loss can occur repeatedly in a given tumor. The available evidence supporting the model is reviewed. A computer simulation system that embodies these concepts is described and the model is used to generate distributions of chromosome number/cell under various simulated conditions and in a variety of simulated biological settings. A simulation of the time course of changes in chromosome number per cell that accompany the spontaneous neoplastic transformation of mouse fibroblasts in vitro is described. The best fit to the data was obtained when provision was made for the activation of at least two growth-promoting genes. The conditions for generating discrete aneuploid peaks in cytogenetic and flow cytometric studies were explored; our modeling studies suggest that the activation of a growth promoting gene is required in order to produce a discrete aneuploid peak. Our modeling studies suggest that the overrepresentation of individual oncogene-bearing chromosomes in aneuploid cell lines may require the activation of gene dose-dependent growth-promoting genes and is not likely to occur in cell lines in which at least two copies of each normal chromosome are required for cell survival. Overall, the results obtained using the model are consistent with a wide variety of flow cytometric and cytogenetic studies in human solid tumors.