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The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future. STATEMENT OF SIGNIFICANCE: The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Recent clinical studies have reported that heart failure with preserved ejection fraction (HFpEF) can be divided into two phenotypes based on the range of ejection fraction (EF), namely HFpEF with higher EF and HFpEF with lower EF. These phenotypes exhibit distinct left ventricle (LV) remodelling patterns and dynamics. However, the influence of LV remodelling on various LV functional indices and the underlying mechanics for these two phenotypes are not well understood. To address these issues, this study employs a coupled finite element analysis (FEA) framework to analyse the impact of various ventricular remodelling patterns, specifically concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH), with and without LV wall thickening on LV functional indices. Further, the geometries with a moderate level of remodelling from each pattern are subjected to fibre stiffening and contractile impairment to examine their effect in replicating the different features of HFpEF. The results show that with severe CR, LV could exhibit the characteristics of HFpEF with higher EF, as observed in recent clinical studies. Controlled fibre stiffening can simultaneously increase the end-diastolic pressure (EDP) and reduce the peak longitudinal strain (e ll ) without significant reduction in EF, facilitating the moderate CR geometries to fit into this phenotype. Similarly, fibre stiffening can assist the CH and 'EH with wall thickening' cases to replicate HFpEF with lower EF. These findings suggest that potential treatment for these two phenotypes should target the bio-origins of their distinct ventricular remodelling patterns and the extent of myocardial stiffening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cardiovascular function is regulated by a short-term hemodynamic baroreflex loop, which tries to maintain arterial pressure at a normal level. In this study, we present a new multiscale model of the cardiovascular system named MyoFE. This framework integrates a mechanistic model of contraction at the myosin level into a finite-element-based model of the left ventricle pumping blood through the systemic circulation. The model is coupled with a closed-loop feedback control of arterial pressure inspired by a baroreflex algorithm previously published by our team. The reflex loop mimics the afferent neuron pathway via a normalized signal derived from arterial pressure. The efferent pathway is represented by a kinetic model that simulates the net result of neural processing in the medulla and cell-level responses to autonomic drive. The baroreflex control algorithm modulates parameters such as heart rate and vascular tone of vessels in the lumped-parameter model of systemic circulation. In addition, it spatially modulates intracellular Ca 2+ dynamics and molecular-level function of both the thick and the thin myofilaments in the left ventricle. Our study demonstrates that the baroreflex algorithm can maintain arterial pressure in the presence of perturbations such as acute cases of altered aortic resistance, mitral regurgitation, and myocardial infarction. The capabilities of this new multiscale model will be utilized in future research related to computational investigations of growth and remodeling., Competing Interests: Declaration of competing interest None of the authors have any commercial or other interest that are in conflict with the integrity of this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cryoballoon ablation (CBA) is a cryo-energy based minimally invasive treatment procedure for patients suffering from left atrial (LA) fibrillation. Although this technique has proved to be effective, it is prone to reoccurrences and some serious thermal complications. Also, the factors affecting thermal distribution at the pulmonary vein-antrum junction that are critical to the treatment success is poorly understood. Computer modeling of CBA can resolve this issue and help understand the factors affecting this treatment. To do so, however, numerical challenges associated with the simulation of advection-dominant transport process must be resolved. Here, we describe the development of a thermal-hemodynamics computational framework to simulate incomplete occlusion in a patient-specific LA geometry during CBA. The modeling framework uses the finite element method to predict hemodynamics, thermal distribution, and lesion formation during CBA. An incremental pressure correction scheme is used to decouple velocity and pressure in the Navier-Stokes equation, whereas several stabilization techniques are also applied to overcome numerical instabilities. The framework was implemented using an open-source FE library (FEniCS). We show that model predictions of the hemodynamics in a realistic human LA geometry match well with measurements. The effects of cryoballoon position, pulmonary vein blood velocity and mitral regurgitation on lesion formation during CBA was investigated. For a -70 0 C cryoballoon temperature, the model predicts lesion formation for gaps less than 2.5 mm and increasing efficiency of CBA for higher balloon tissue contact areas. The simulations also predict that lesion formation is not sensitive to variation in pulmonary vein blood velocity and mitral regurgitation. The framework can be applied to optimize CBA in patients for future clinical studies., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The commonly observed inverse relationship between dissolved organic carbon (DOC) and nitrate (NO 3 - ) concentrations in aquatic systems can be explained by stoichiometric and thermodynamic principles regulating microbial assimilation and dissimilation processes. However, the interactive effects of human activities and dissolved oxygen (DO) on the DOC and DIN (dissolved inorganic nitrogen, mainly composed of NO 3 - -N and NH 4 + -N) relations are not well identified, particularly in subtropical small mountainous rivers (SMRs). Here, we investigated the exports and relations of DOC-DIN in 42 Taiwan SMRs under different anthropogenic disturbances. Results showed that the island-wide mean concentrations of the three solutes in streams are generally low, yet the abundant rainfall and persistent supply contrarily lead to disproportional high DOC and DIN yields. The inverse DOC-NO 3 - -N relation does not appear under well‑oxygenated conditions, regardless of low or high human disturbance. However, a significant inverse relationship between DOC-NO 3 - -N would emerge in highly-disturbed watersheds under low-oxygenated conditions (mean annual DO <6.5 mg L -1 ), where excess N accumulates as NH 4 + -N rather than NO 3 - -N. The controlling mechanism of DOC-DIN relations would shift from energetic constraints to redox constraints in low-oxygenated conditions. Although riverine concentrations of DOC, NO 3 - -N, and NH 4 + -N could be elevated by human activities, the transition of DOC-DIN relation pattern is directly linked to DO availability. Understanding the mechanism that drives CN coupling is critical for assessing the ecosystem function in the delivery and retention of DOC and DIN in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors have no competing interests or other interests that might be perceived to influence the results and/or discussion reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) medications are highly effective at reducing HIV transmission despite their underutilization. Pharmacists can be involved in HIV PrEP management through collaborative practice agreements (CPAs)., Objectives: This study aimed to (1) describe the development of a CPA for a pharmacist-led HIV PrEP service within an outpatient primary care clinic and (2) describe the growth of the HIV PrEP CPA service after implementation., Practice Description: The service was developed and implemented within a network of 7 outpatient general internal medicine (GIM) clinics associated with a large academic medical center. Pharmacists are embedded in the clinics and provide care alongside an interprofessional team., Practice Innovation: An HIV PrEP CPA was developed and implemented by primary care pharmacists to increase access to HIV PrEP therapy through pharmacist-led visits. The pharmacist-led visits were piloted at one site before expanding to the other primary care clinics., Evaluation Methods: Data were analyzed using an electronic health record-generated report that included all patients prescribed HIV PrEP medications by a GIM primary care provider (PCP) within the last year. The report was generated before the start of the intervention in October 2021 and again in May 2022. Retrospective chart review was then used to identify prescribing patterns and referrals to the pharmacy HIV PrEP CPA., Results: Seven months after the start of the HIV PrEP CPA, 122 patients were prescribed HIV PrEP by a GIM PCP. Thirty-four patients (27.9%) were newly started on HIV PrEP by a GIM PCP since the beginning of the initiative. A total of 53 patient referrals (43.4%) were placed to the pharmacy team. Five of the 7 GIM clinics have established pharmacist-led HIV PrEP services., Conclusion: This report describes the successful development and implementation of a pharmacist-led HIV PrEP CPA in Ohio., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The scleractinian coral-associated symbiotic algae Symbiodiniaceae plays an important role in bleaching tolerance and coral resilience. In this study, coral-associated Symbiodiniaceae communities of 14 reef sites of Perhentian and Redang Islands Marine Parks (Malaysia, South China Sea) were characterized using the high-throughput next-generation amplicon sequencing on the ITS2 rDNA marker to inventory the Symbiodiniaceae diversity from a healthy tropical reef system and to generate a baseline for future studies. A total of 64 coral-Symbiodiniaceae associations were characterized in 18 genera (10 families) of scleractinian corals using the SymPortal analytical framework. The results revealed the predominance of Symbiodiniaceae genera Cladocopium (average 82%) and Durusdinium (18%), while Symbiodinium, Breviolum, Fugacium, and Gerakladium were found as minor groups (<0.01%). Of the 39 Cladocopium and Durusdinium major ITS2 sequences, 14 were considered dominant/sub-dominant, with C3u as the predominant type (63.3%), followed by D1 (15%), C27 (10.1%), and C15 (6.9%). A total of 19 and 13 Cladocopium and Durusdinium ITS2-type profiles were detected across the coral species, respectively. Symbiodiniaceae diversity and richness recorded in this study were higher when compared to other reefs in the proximity. With the increasing coral-Symbiodiniaceae associations archived, the database would provide a baseline to assess the changes of Symbiodiniaceae communities in the coral hosts and to explore the potential adaptive roles of this coral-algal association., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Early identification can improve outcomes for children with autism spectrum disorder (ASD). We sought to assess changes in early ASD identification over time and by co-occurring intellectual disability (ID) and race/ethnicity., Method: Using data for 2002-2016 from a biennial population-based ASD surveillance program among 8-year-old children in the United States, we defined identification as a child's earliest recorded ASD diagnosis or special education eligibility. Unidentified children had characteristics meeting the ASD surveillance case definition but no recorded identification by age 8 years. We calculated median age at identification among identified children, median age at identification including unidentified children, and cumulative incidence of identification by age 48 months., Results: ASD identification by age 48 months was 4 times (95% CI: 3.6-4.3) as likely in 2016 as in 2002, with the largest increases among children without ID. Median age at ASD identification among identified children decreased 3 months during this time. Children of every race/ethnicity were more likely to be identified over time. There were racial disparities stratified by ID: in 2016, Black and Hispanic children without ID were less likely to be identified with ASD than were White children (both groups risk ratio: 0.7; 95% CI: 0.5-0.8), but Black children were 1.5 times (95% CI: 1.3-1.9) as likely as White children to be identified with ASD and ID., Conclusion: Substantial progress has been made to identify more children with ASD early, despite minimal decrease in median age at diagnosis. Considerable disparities remain in early ASD identification by race/ethnicity and co-occurring intellectual disability., (Published by Elsevier Inc.)

Background: Large-scale quarantine facilities staffed with non-healthcare workers (NHCW) were instrumental in preventing community spread of COVID-19 (coronavirus disease of 2019). The objective of this study was to determine the effectiveness of a newly developed procedural skills training framework in ensuring personal protective equipment (PPE) compliance of PPE-naïve NHCWs., Methods: We developed a PPE procedural skills training framework for NHCWs using the Learn, See, Practice, Prove, Do, and Maintain (LSPPDM) framework and international guidelines on PPE for healthcare workers. The NHCWs underwent PPE training using this framework, conducted by a team of Infection Prevention nurses, prior to being stationed within the CCF. Effectiveness of the LSPPDM PPE training framework was assessed using: 1) competency assessment scores for NHCWs, 2) PPE compliance rates from daily audit findings, and, 3) healthcare-associated COVID-19 infection rates of NHCWs., Results: A total of 883 NHCWs had completed the PPE training and demonstrated competency in PPE compliance, fulfilling 100% of the checklist requirements. Mean PPE compliance of all NHCWs during the 11-week study period was noted to be >96%. The post-implementation improvement was statistically significant when the compliance was expressed in 3-days blocks) and in bed management staff (P = < 0.05). None of the 883 NHCWs who underwent PPE training via the LSPPDM framework were diagnosed with healthcare-associated COVID-19 infection., Conclusion: An evidence-based skills training framework is effective in PPE training of large numbers of NHCWs, resulting in high compliance of appropriate PPE use and prevention of healthcare-associated COVID-19 infection., (Copyright © 2021 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an established treatment for left bundle branch block (LBBB) resulting in mechanical dyssynchrony. Approximately 1/3 of patients with CRT, however, are non-responders. To understand factors affecting CRT response, an electromechanics-perfusion computational model based on animal-specific left ventricular (LV) geometry and coronary vascular networks located in the septum and LV free wall is developed. The model considers contractility-flow and preload-activation time relationships, and is calibrated to simultaneously match the experimental measurements in terms of the LV pressure, volume waveforms and total coronary flow in the left anterior descending and left circumflex territories from 2 swine models under right atrium and right ventricular pacing. The model is then applied to investigate the responses of CRT indexed by peak LV pressure and (dP/dt) max at multiple pacing sites with different degrees of perfusion in the LV free wall. Without the presence of ischemia, the model predicts that basal-lateral endocardial region is the optimal pacing site that can best improve (dP/dt) max by 20%, and is associated with the shortest activation time. In the presence of ischemia, a non-ischemic region becomes the optimal pacing site when coronary flow in the ischemic region fell below 30% of its original value. Pacing at the ischemic region produces little response at that perfusion level. The optimal pacing site is associated with one that optimizes the LV activation time. These findings suggest that CRT response is affected by both pacing site and coronary perfusion, which may have clinical implication in improving CRT responder rates., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring., Methods: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy., Results: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD., Conclusions: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Microstructural changes in the pulmonary arteries associated with pulmonary arterial hypertension (PAH) is not well understood and characterized in humans. To address this issue, we developed and applied a patient-specific inverse finite element (FE) modeling framework to characterize mechanical and structural changes of the micro-constituents in the proximal pulmonary arteries using in-vivo pressure measurements and magnetic resonance images. The framework was applied using data acquired from a pediatric PAH patient and a heart transplant patient with normal pulmonary arterial pressure, which serves as control. Parameters of a constrained mixture model that are associated with the structure and mechanical properties of elastin, collagen fibers and smooth muscle cells were optimized to fit the patient-specific pressure-diameter responses of the main pulmonary artery. Based on the optimized parameters, individual stress and linearized stiffness resultants of the three tissue constituents, as well as their aggregated values, were estimated in the pulmonary artery. Aggregated stress resultant and stiffness are, respectively, 4.6 and 3.4 times higher in the PAH patient than the control subject. Stress and stiffness resultants of each tissue constituent are also higher in the PAH patient. Specifically, the mean stress resultant is highest in elastin (PAH: 69.96, control: 14.42 kPa-mm), followed by those in smooth muscle cell (PAH: 13.95, control: 4.016 kPa-mm) and collagen fibers (PAH: 13.19, control: 2.908 kPa-mm) in both the PAH patient and the control subject. This result implies that elastin may be the key load-bearing constituent in the pulmonary arteries of the PAH patient and the control subject., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups., Objective: Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators., Methods: We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator., Results: Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0-16.5) among males and 7.7 (95% CI, 7.2-8.2) among females. ID prevalence was 17.7 (95% CI, 16.6-18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1-13.0), among Hispanic; 8.6 (95% CI, 7.1-10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5-8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES., Conclusions: ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Published by Elsevier Inc.)

Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1 (NPM1)-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54% to 90% in clinical trials; however, a subset of patients progressed within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation and knockout screens in ALCL cell lines, combined with RNA sequencing data derived from ALK inhibitor-relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of interleukin 10 receptor subunit alpha (IL10RA). Elevated IL10RA expression rewires the STAT3 signaling pathway, bypassing otherwise critical phosphorylation by NPM1-ALK. IL-10RA expression does not correlate with response to standard chemotherapy in pediatric patients, suggesting that a combination of crizotinib and chemotherapy could prevent ALK inhibitor resistance-specific relapse., (© 2020 by The American Society of Hematology.)

Background: Evidence about injury management and outcomes in children with autism spectrum disorder (ASD) is limited., Method: Cross-sectional analyses included children aged 30-68 months with at least one medically attended injury. Standardized diagnostic instruments determined ASD cases. Parent-reported injury treatments and outcomes were examined in ASD cases (n = 224) versus developmental delays/disorders (DD) (n = 188) and population (POP) (n = 267) controls, adjusting for child and family characteristics using logistic regression., Results: Injury characteristics were similar between groups. Most children (82.5%) had emergency care (EC) or hospitalization after injury. Nearly half (46.4%) ever received a medication or injection, mostly analgesics (53.4%) and local anesthetics (23.8%), while 9.4% ever received surgery, most often for open wound (47.0%) or fracture (16.7%). ASD group children were less likely than DD group children to receive medication/injection (41.1% vs. 53.2%, adjusted odds ratio [aOR] = 0.60 [0.40, 0.90]); receipt of EC/hospitalization and surgery were comparable. Children with ASD more often had surgery than POP children (14.3% vs. 4.9%, aOR = 2.62 [1.31, 5.25]); receipt of EC/hospitalization and medication/injection were similar. Loss of consciousness was uncommon (ASD = 6.3%, DD = 5.3%, POP = 3.4%), as was long-term or significant behavior change (ASD = 5.4%, DD = 3.2%, POP = 3.2%); differences were not significant., Conclusions: Injured children with ASD received fewer medications/injections than children with non-ASD developmental delays/disorders and more surgical treatments than general population children. Injury management was otherwise similar between groups. Understanding whether these results reflect child or injury characteristics or provider perceptions about behaviors and pain thresholds of children with ASD, and how these may influence care, requires further study.

Background: ASD-related services can improve outcomes for children, but less is known about service outside of school settings during preschool age. We aimed to describe amount and category of community-based service use among 3-5-year-old children with ASD and examine differences by health insurance., Methods: We used cross-sectional data on 792 children with ASD diagnoses in the Study to Explore Early Development, a community-based study of neurodevelopment with enrollment between 2012-2016. Mothers reported current child service use and insurance status at study entry. We used log-Poisson and logistic regression to compare service use by insurance group., Results: Nearly 40% of children were not receiving community-based services at study entry. Children with public insurance had fewer total services than children with private or both insurances. After adjustment for sociodemographic confounders, insurance status was not associated with types of different categories of community-based services. However, children with public insurance alone were least likely to receive community-based behavioral therapy and most likely to receive psychotropic medication compared to other insurances., Conclusion: Many preschool-aged children do not receive community-based services, with receipt associated with insurance type. Increasing access and availability for evidence-based service, especially for beneficiaries of public insurance, may improve service use and outcomes.

In high-standing islands of the Western Pacific, typhoon-triggered landslides occasionally strip parts of the landscape of its vegetative cover and soil layer and export large amounts of biomass and soil organic carbon (OC) from land to the ocean. After such disturbances, new vegetation colonizes the landslide scars and OC starts to reaccumulate. In the subtropical mountains of Taiwan and in other parts of the world, bamboo ( Bambusoideae ) species may invade at a certain point in the succession of recovering landslide scars. Bamboo has a high potential for carbon sequestration because of its fast growth and dense rooting system. However, it is still largely unknown how these properties translate into soil OC re-accumulation rates after landslide disturbance. In this study, a chronosequence was established on four former landslide scars in the Central Mountain Range of Taiwan, ranging in age from 6 to 41 years post disturbance as determined by landslide mapping from remote sensing. The younger landslide scars were colonized by Miscanthus floridulus , while after approx. 15 to 20 years of succession, bamboo species ( Phyllostachys ) were dominating. Biomass and soil OC stocks were measured on the recovering landslide scars and compared to an undisturbed Cryptomeria japonica forest stand in the area. After initially slow re-vegetation, biomass carbon accumulated in Miscanthus stands with mean annual accretion rates of 2 ± 0.5 Mg C ha -1 yr -1 . Biomass carbon continued to increase after bamboo invasion and reached ~40% of that in the reference forest site after 41 years of landslide recovery. Soil OC accumulation rates were ~2.0 Mg C ha -1 yr -1 , 6 to 41 years post disturbance reaching ~64% of the level in the reference forest. Our results from this in-situ study suggest that recovering landslide scars are strong carbon sinks once an initial lag period of vegetation re-establishment is overcome.

Isolating the role(s) of microstructural pathological features in affecting diastolic filling is important in developing targeted treatments for heart diseases. We developed a microstructure-based constitutive model of the myocardium and implemented it in an efficient open-source finite element modeling framework to simulate passive inflation of the left ventricle (LV) in a representative 3D geometry based on experimentally measured muscle fiber architecture. The constitutive model was calibrated using previous tissue-level biaxial mechanical test data derived from the canine heart and validated with independent sets of measurements made at both the isolated constituent and organ level. Using the validated model, we investigated the load taken up by each tissue constituent and their effects on LV passive inflation. The model predicts that the LV compliance is sensitive to the collagen ultrastructure, specifically, the collagen fiber azimuthal angle with respect to the local muscle fiber direction and its waviness. The model also predicts that most of the load in the sub-epicardial and sub-endocardial regions is taken up, respectively, by the muscle fibers and collagen fiber network. This result suggests that normalizing LV passive stiffness by altering the collagen fiber network and myocyte stiffness is most effective when applied to the sub-endocardial and sub-epicardial regions, respectively. This finding may have implication for the development of new pharmaceutical treatments targeting individual cardiac tissue constituents to normalize LV filling function in heart diseases. STATEMENT OF SIGNIFICANCE: Current constitutive models describing the tissue mechanical behavior of the myocardium are largely phenomenological. While able to represent the bulk tissue mechanical behavior, these models cannot distinguish the contribution of the tissue constituents and their ultrastructure to heart function. Although microstructure-based constitutive models can be used to isolate the role of tissue ultrastructure, they have not been implemented in a computational framework that can accommodate realistic 3D organ geometry. The present study addresses these issues by developing and validating a microstructure-based computational modeling framework, which is used to investigate the role of tissue constituents and their ultrastructure in affecting heart function., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: While voiding cystourethrogram (VCUG) is a widely-accepted test, it is invasive and associated with radiation exposure. Most cases of primary vesicoureteral reflux (VUR) are low-grade and unlikely to be associated with acquired renal scarring. To select patients at greatest risk, in 2011 the American Academy of Pediatrics (AAP) published guidelines for evaluation of children ages 2 - 24 months with urinary tract infections (UTIs). Similarly, in 2010 the Society for Fetal Urology (SFU) published guidelines for patients with hydronephrosis. Herein a prospectively-collected database was queried through the Institute of Clinical Evaluative Sciences (ICES), exploring trends in VCUG ordering within the Ontario Health Insurance Program (OHIP), which guarantees universal access to care., Material and Methods: A dedicated ICES analyst extracted data on all patients younger than 18 years in Ontario, Canada, with billing codes for VCUG and ICD-9 codes for VUR, from 2004-2014. The baseline characteristics included patient age, gender, geographic region, specialty of ordering provider and previous diagnoses of UTI and/or antenatal hydronephrosis to determine the indication for ordering the test. Of these, patients were subsequently incurred OHIP procedure codes for endoscopic injection or ureteral reimplantation. Patients who had a VCUG in the setting of urethral trauma, posterior urethral valves, and neurogenic bladder were excluded., Results and Discussion: Trend analysis demonstrated that the total number of VCUGs ordered in the province has decreased over a decade (Figure 1), with a concurrent decrease in VUR diagnosis. On multivariate regression analysis, the decrease in VCUG ordering could not be explained by changes in population demographics or other baseline patient variables. Most VCUGs obtained per year were ordered by pediatricians or family physicians (mean 2,022+523.8), compared with urologists and nephrologists (mean 616+358.3). Interestingly, while the rate of VCUG requests decreased, the annual number of surgeries performed for VUR (endoscopic or open) did not show a significant reduction over time., Conclusions: We present a large population-based analysis in a universal access to care system, reporting a decreasing trend in the number of cystograms and differences by primary care versus specialist providers. While it is reassuring to see practice patterns favorably impacted by guidelines, it is also encouraging to note that the number of surgeries has remained stable. This suggests that patients at risk continue to be detected and offered surgical correction. These data confirm previous institution-based assessments and affirm changes in VCUG ordering independent of variables not relevant to the healthcare system, such as the insurance status., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

In this paper, we propose a novel continuum finite strain formulation of the equilibrium gap regularization for image registration. The equilibrium gap regularization essentially penalizes any deviation from the solution of a hyperelastic body in equilibrium with arbitrary loads prescribed at the boundary. It thus represents a regularization with strong mechanical basis, especially suited for cardiac image analysis. We describe the consistent linearization and discretization of the regularized image registration problem, in the framework of the finite elements method. The method is implemented using FEniCS & VTK, and distributed as a freely available python library. We show that the equilibrated warping method is effective and robust: regularization strength and image noise have minimal impact on motion tracking, especially when compared to strain-based regularization methods such as hyperelastic warping. We also show that equilibrated warping is able to extract main deformation features on both tagged and untagged cardiac magnetic resonance images., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: There is a paucity of data comparing urethral stents after hypospadias repair. The aim of this study is to compare Silastic tubing vs Koyle stents (Cook Medical), addressing outcomes related to stent-related complications, added visits to healthcare providers in the early postoperative period, and postoperative complications at clinic follow-up., Materials and Methods: Following an alternate week allocation, 150 patients were prospectively assigned to have Silastic tubes (n = 76) and Koyle stents (n = 74) after hypospadias repair. Exclusion criteria included fistula repairs, drainage via alternative catheter, or stentless repairs. Silastic tubes were secured with 5-0 Prolene and removed during a planned clinic visit. Koyle stents were secured with 7-0 PDS and left to fall out spontaneously. Questionnaires capturing postoperative outcomes were completed., Results and Discussion: Median age was 13 and 11 months in the Silastic and Koyle stent groups, respectively (P = 0.48). There was no statistically significant difference in hypospadias location. Blockage/kinking of stents occurred in 8% (n = 6) of the Silastic and 9% (n = 7) Koyle stent groups, P = 0.78. Although follow-up was short, there was no difference in fistula rate among the Silastic (21%, n = 14) versus Koyle stent group (17%, n = 11), P = 0.66. There was a twofold higher rate of emergency department (ED) visits in the Silastic (32%, n = 24) versus Koyle stent group (16%, n = 12), P = 0.03. Half of ED visits in the Silastic group were related to stents falling out before planned removal. The authors propose that Silastic stents falling out before the removal date may have led to increased parental anxiety and thus a visit to the ED. With improved parental education, the authors propose that many of these visits may have been preventable., Conclusions: There were no significant differences in stent-related complications or fistula rate between the Silastic and Koyle stent groups. Although there were a twofold higher number of visits to the ED in the Silastic stent group, the authors propose that this was due to parental education rather than the stent itself., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Ileocystoplasty is the standard technique used for bladder augmentation, and has been used widely for decades. However, it is known to be associated with complications such as stone formation, mucus production, metabolic acidosis, urinary tract infections, intestinal obstruction, and a long-term risk of bladder cancer. Seromuscular bladder augmentation (SMBA) is an alternative to the standard ileocystoplasty, and has been associated with a lower incidence of bladder stones. Few reports have been published on intermediate outcomes of SMBA. Herein, we report long-term outcomes of SMBA from a single institution compared with standard ileocystoplasty., Methods: After Institutional Review Board approval, a retrospective chart review of all patients who underwent bladder augmentation at our institution over a 14-year period was performed. The status of patients after SMBA (10 patients) was compared according to age, sex, and diagnosis with patients who underwent traditional ileocystoplasty (30 patients). Parameters such as demographic information, pre- and postoperative bladder capacity as assessed by urodynamic studies, urinary tract infections (UTIs), bladder calculi, incontinence, need for secondary surgical procedures, and spontaneous bladder perforation were compared in the two groups. All the patients were on a clean intermittent catheterization (CIC) regimen., Results: Over the study period, 10 patients underwent SMBA and 30 patients (according to age, sex, and diagnosis) underwent standard ileocystoplasty; the average age at surgery was 10.3 and 10 years respectively, with a mean follow up of 6.7 years in the SMBA group and 6 years in the ileocystoplasty group. There were no statistically significant differences in the rate of UTIs, urinary incontinence, subsequent surgery, or spontaneous bladder perforation. The mean bladder capacity increased significantly for both groups as assessed by pre- and postoperative urodynamic studies, although the difference in the rate of bladder calculi between the two groups (0 [0%] vs. 8 [27%], p = 0.06) did not reach statistical significance (Table)., Conclusions: SMBA is safe and efficacious and may result in a lower rate of stone formation than standard ileocystoscopy. SMBA should be considered as a viable alternative to standard ileocystoplasty., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies., Objective: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing., Methods: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate., Results: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics., Conclusions: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study examined associations between ASD diagnosis retention and non-ASD co-occurring conditions (CoCs) by child sex. The sample included 7077 males and 1487 females who had an ASD diagnosis documented in their school or health records in a population-based ASD surveillance system for 8-year-old children. ASD diagnosis retention status was determined when an initial ASD diagnosis was not later ruled out by a community professional. We found that ASD diagnosis remains fairly stable, with only 9% of children who had an initial documented ASD diagnosis later being ruled-out. Although most of the associations between the ASD diagnosis retention status and CoCs are similar in both sexes, the co-occurrence of developmental diagnoses (e.g., intellectual disability or sensory integration disorder) was predictive of ASD diagnostic changes in males, whereas the co-occurrence of specific developmental (e.g., personal/social delay) and neurological diagnosis (e.g., epilepsy) was associated with ASD diagnostic change in females. More ASD-related evaluations and less ASD-related impairment were associated with later ASD rule outs in both sexes. Our findings highlight that CoCs can complicate the diagnostic picture and lead to an increased likelihood of ambiguity in ASD diagnosis. Using sensitive and appropriate measures in clinical practice is necessary for differential diagnosis, particularly when there are co-occurring developmental conditions., Competing Interests: Conflicts of interest The sponsor for the data collection of the Autism and Developmental Disabilities Monitoring (ADDM) Network is the US Centers for Disease Control and Prevention (CDC). The sponsor had no involvement in (1) study design; (2) analysis, and interpretation of data; (3) the writing of the report; or (4) the decision to submit the paper for publication. The authors do not have any potential conflict of interest, real or perceived.

Introduction: Percutaneous nephrolithotomy (PCNL) has surpassed open stone surgery as the operation of choice for large and complex stone burdens (figure). Although the procedure was developed in adults, its principles have been extrapolated to children. There is a paucity of literature comparing outcomes of PCNL in adults and children for similar stone burdens., Objective: The purpose of this study was to evaluate outcomes following PCNL among children and adults with similar stone burdens., Patients and Methods: Data on patient characteristics and outcomes for 2196 consecutive patients undergoing PCNL at a single institution were collected prospectively from January 1992 to July 2013. Thirty-one pediatric patients undergoing 39 PCNLs were identified. Each pediatric PCNL was matched in a ratio of 1:4 to adult PCNLs by year of surgery and stone burden characteristics (staghorn, partial staghorn, number of stones). All PCNLs were performed by two fellowship-trained endourologists who operate on both adult and pediatric patients. Ultrasonic lithotripsy was used primarily. The primary outcome measure was stone-free rate (SFR) at hospital discharge. Secondary outcomes included the need for second-look nephroscopy, length of hospital stay, complication rate, and blood transfusion rate. The Student t test was used for continuous variables and the Fisher exact for categorical variables., Results: The median age for the pediatric group was 13.9 ± 4.30 years and for the adult group was 55.4 ± 15.1 years. Pediatric patients tended to present with metabolic stones, with no difference in rates of infection stones. No difference was found in SFR at time of hospital discharge (86.1% vs. 86.4%, p = 0.2). More pediatric patients required a second access tract than adult patients (15.4% vs. 4.52%, p = 0.02). There was no significant difference in the need for second-look nephroscopy, length of stay, or complication rates (overall and by Clavien classification subgroup) between both groups. The rates of blood transfusion were low in both groups (0% vs. 0.6%, p = 0.80)., Discussion: There was no difference in primary and secondary outcomes among children compared with adults undergoing PCNL in our study. The outcomes reported in this study were similar to published literature. A limitation of this study is the low number of pediatric patients. However, it is unique to have a single-center study that compares PCNL outcomes in both adult and pediatric patient and accounts for stone burden characteristics., Conclusions: Although principles of PCNL were developed in adults, this study affirms the safety and efficacy of PCNL in both pediatric and adult patients., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients., Methods and Results: Magnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV., Conclusions: These results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: The DSM-IV-TR specifies 12 behavioral features that can occur in hundreds of possible combinations to meet diagnostic criteria for autism spectrum disorder (ASD). This paper describes the frequency and variability with which the 12 behavioral features are documented in a population-based cohort of 8-year-old children under surveillance for ASD, and examines whether documentation of certain features, alone or in combination with other features, is associated with earlier age of community identification of ASD., Method: Statistical analysis of behavioral features documented for a population-based sample of 2,757 children, 8 years old, with ASD in 11 geographically-defined areas in the US participating in the Autism and Developmental Disabilities Monitoring Network in 2006., Results: The median age at ASD identification was inversely associated with the number of documented behavioral features, decreasing from 8.2 years for children with only seven behavioral features to 3.8 years for children with all 12. Documented impairments in nonverbal communication, pretend play, inflexible routines, and repetitive motor behaviors were associated with earlier identification, whereas impairments in peer relations, conversational ability, and idiosyncratic speech were associated with later identification., Conclusions: The age dependence of some of the behavioral features leading to an autism diagnosis, as well as the inverse association between age at identification and number of behavioral features documented, have implications for efforts to improve early identification. Progress in achieving early identification and provision of services for children with autism may be limited for those with fewer ASD behavioral features, as well as features likely to be detected at later ages., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Objective: General surgery (GS) and otolaryngology (OTO) do not require a minimum number of thyroidectomies to qualify for board certification. No standardized criteria exist for declaring competence in this procedure. A survey was created to assess GS and OTO resident perspectives on becoming competent in thyroid surgery., Design: A survey was electronically mailed to all GS and OTO residents assessing their competence in thyroid surgery., Setting: National survey of general surgery and otolaryngology residents., Participants: National general surgery and otolaryngology residents., Results: A convenience sample of 526 residents responded (246/280 = GS/OTO). The mean clinical year of training was 3.3 (3.1/3.5). Most residents (50%/41%) performed between 1 and 10 thyroid operations. Residents believed 13 and 25 (GS/OTO) thyroidectomies were required by their respective Boards. Both groups felt that 30 (27/33) thyroid operations were necessary to obtain competence (p < 0.01). The most important feature was operative volume with graduated responsibility, followed by guidance under an expert mentor. Analysis of residents PGY4 and greater showed no significant differences., Conclusions: While residents of both specialties generally agree on learning methods, the perception of readiness to perform thyroid surgery after training is variable. A disconnect is present between the number of cases required for Board certification, the number of cases residents believe are required, and the number of cases residents believe it takes to achieve competency., (Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation., Methods: Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated., Results: Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone., Conclusions: Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: : Cognitive dysfunction is common in patients with advanced, life-threatening illness and can be attributed to a variety of factors (e.g., advanced age, opiate medication). Such dysfunction likely affects decisional capacity, which is a crucial consideration as the end-of-life approaches and patients face multiple choices regarding treatment, family, and estate planning. This study examined the prevalence of cognitive impairment and its impact on decision-making abilities among hospice patients with neither a chart diagnosis of a cognitive disorder nor clinically apparent cognitive impairment (e.g., delirium, unresponsiveness)., Design: : A total of 110 participants receiving hospice services completed a 1-hour neuropsychological battery, a measure of decisional capacity, and accompanying interviews., Results: : In general, participants were mildly impaired on measures of verbal learning, verbal memory, and verbal fluency; 54% of the sample was classified as having significant, previously undetected cognitive impairment. These individuals performed significantly worse than the other participants on all neuropsychological and decisional capacity measures, with effect sizes ranging from medium to very large (0.43-2.70). A number of verbal abilities as well as global cognitive functioning significantly predicted decision-making capacity., Conclusion: : Despite an absence of documented or clinically obvious impairment, more than half of the sample had significant cognitive impairments. Assessment of cognition in hospice patients is warranted, including assessment of verbal abilities that may interfere with understanding or reasoning related to treatment decisions. Identification of patients at risk for impaired cognition and decision making may lead to effective interventions to improve decision making and honor the wishes of patients and families.

Background: The temporal progression in extent and severity of regional myofiber contractile dysfunction in normally perfused border zone (BZ) myocardium adjacent to a myocardial infarction (MI) has been shown to be an important pathophysiologic feature of the adverse remodeling process in large animal models. We sought, for the first time, to document the presence of impaired contractility of the myofibers in the human BZ myocardium., Methods: A 62-year-old man who experienced an MI in 1985 and had recently had complete revascularization was studied. Myofiber systolic contractile stress developed in the normally perfused BZ adjacent to the MI (T(max&#95;B)) and that developed in regions remote from the MI (T(max&#95;R)) were quantified using cardiac catheterization, magnetic resonance imaging, and mathematical modeling., Results: The resulting finite element model of the patient's beating left ventricle was able to simulate the reduced systolic strains measured using magnetic resonance imaging at matching left ventricular pressures and volumes. The T(max&#95;B) (73.1 kPa) was found to be greatly reduced relative to T(max&#95;R) (109.5 kPa). These results were found to be independent of assumptions relating to BZ myofiber orientation., Conclusions: The results of this study document the presence of impaired contractility of the myofibers in the BZ myocardium and support its role in the post-MI remodeling process in patients. To fully establish this important conclusion serial evaluations beginning at the time of the index MI will need to be performed in a cohort of patients. The current study supports the importance and demonstrates the feasibility of larger and longer-term studies., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: A 57% increase in the U.S. prevalence of autism spectrum disorders (ASD) for 8-year-old children born in 1994 versus 1998 was recently reported., Methods: To quantify the possible contributions of given risk/predictive factors on the recent ASD prevalence increase, we formulated a mathematical model based on the baseline risk factor prevalence (RFP), the proportionate change in RFP (cRFP), and the magnitude of the association between the risk factor and ASD [estimated relative risk (RR)]. We applied this model to several pregnancy-related factors (preterm, very preterm, low and very low birth weight, multiple birth, cesarean delivery, breech presentation, and assisted reproductive technology use). RFP and cRFP estimates for each factor were obtained from U.S. population-based surveillance datasets. Estimated RRs were obtained from a series of systematic literature reviews., Results: We estimate that each risk factor examined, alone or in various combinations, accounted for a very small proportion (<1%) of the ASD increase. Additionally, hypothetical scenarios indicate RFP, cRFP, and RR all need to be sizable for a risk factor to appreciably influence ASD prevalence., Conclusions: Thus, although various pregnancy factors have been found to be associated with ASDs, the contribution of many of these factors to the recently observed ASD increase is likely minimal., (Published by Elsevier Inc.)

Background: We sought to describe autism spectrum disorder (ASD) population characteristics and changes in identified prevalence across 3 time periods., Methods: Children with a potential ASD were identified through records abstraction at multiple sources with clinician review based on Diagnostic and Statistical Manual (DSM-IV-TR) criteria. Multisite, population-based data from the Autism and Developmental Disabilities Monitoring (ADDM) Network were analyzed from areas of Arizona (AZ), Georgia (GA), Maryland (MD), and South Carolina (SC). Participants were 8-year-old children (born in 1992, 1994, or 1996) in 2000, 2002, or 2004 (and children born in 1988 residing in metropolitan Atlanta in 1996) who had been evaluated for a variety of developmental concerns at education and/or health sources., Results: From 2000 to 2004, the identified prevalence of the ASDs per 1,000 8-year-old children showed significant increases of 38% in GA and 72% in MD and a nonsignificant increase of 26% in AZ. ASD prevalence was relatively stable in SC with a nonsignificant decrease of 17%. Males had a higher identified prevalence of ASD in all years. Increases among racial, ethnic, and cognitive functioning subgroups varied by site and surveillance year. More children were classified with an ASD by community professionals over time, except in AZ., Conclusions: There was a trend toward increase in identified ASD prevalence among 8-year-old children who met the surveillance case definition in 3 of the 4 study sites from 2000 to 2004. Some of the observed increases are due to improved ascertainment; however, a true increase in ASD symptoms cannot be ruled out. These data confirm that the prevalence of ASDs is undergoing significant change in some areas of the United States and that ASDs continue to be of urgent public health concern., (Published by Elsevier Inc.)

Background: Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad., Methods: We screened for triplet expansion in the TBP gene in Taiwanese Parkinson's disease (PD), Alzheimer's disease (AD) and atypical parkinsonism and investigated the functional implication of expanded alleles using lymphoblastoid cells as a model., Results: A total of 6 mildly expanded alleles (44-46) were identified in patients group. The frequency of the individuals carrying expanded alleles in PD (3/602 [0.5%]), AD (2/245 [0.8%]) and atypical parkinsonism (1/44 [2.3%]) is not significant as compared to that in the control subjects (0/644 [0.0%]). In lymphoblastoid cells, HSPA5, HSPA8 and HSPB1 expression levels in cells with expanded TBP were significantly lower than that of the control cells. Although not significantly, the levels of PARK7 protein isoforms 6.1 and 6.4 are notably increased in SCA17 lymphoblastoid cells. Treatment of TBH (tert-butyl hydroperoxide) significantly increases cell death in the cells with mildly expanded TBP., Conclusions: Our findings expand the spectrum of SCA17 phenotype and may contribute to our understanding of the disease., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: We investigated the prevalence and predictors of obstructive sleep apnea (OSA) in patients admitted to the hospital for acute myocardial infarction and whether OSA has any association with microvascular perfusion after primary percutaneous coronary intervention (PCI)., Methods: Recruited patients were scheduled to undergo an overnight sleep study between 2 and 5 days after primary PCI. An apnea-hypopnea index (AHI) of > or = 15 was considered diagnostic of OSA. Impaired microvascular perfusion after primary PCI was defined as an ST-segment resolution of < or = 70%, myocardial blush grade 0 or 1, or a corrected Thrombolysis in Myocardial Infarction (TIMI) [antegrade flow scale] frame count > 28., Results: Sleep study was performed in 120 patients and completed in 105 patients (study cohort, mean age 53 +/- 10 years, male 98%) with uncomplicated myocardial infarction. An AHI was > or = 15 in 69 patients (OSA-positive), giving a prevalence of 65.7%. Diabetes mellitus was found to be a significant risk factor for OSA (odds ratio, 2.86; 95% confidence interval, 1.06 to 8.24; p = 0.033). There were no differences between OSA-positive and OSA-negative groups with regard to the percentage of patients with < or = 70% ST-segment resolution (73% vs 64%, respectively; p = 0.411), myocardial blush grade 0 or 1 (39.1% vs 38.9%, respectively; p = 1.000), or corrected TIMI frame count > 28 (21.7% vs 25.0%, respectively; p = 0.807)., Conclusions: We found a high prevalence of previously undiagnosed OSA in patients admitted with acute myocardial infarction. Diabetes mellitus was independently associated with OSA. No evidence indicated that OSA is associated with impaired microvascular perfusion after primary PCI.

Objective: At what age are children with an autism spectrum disorder (ASD) identified by community providers? What factors influence the timing of when children are identified with ASDs? This study examined the timing of when children with ASDs are identified., Method: Data came from 13 sites participating in the Centers for Disease Control and Prevention's 2002 multisite ongoing autism surveillance program, the Autism and Developmental Disabilities Monitoring Network. Survival analysis was used to examine factors that influence the timing of community-based identification and diagnosis., Result: Data from health and education records reveal that the median age of identification was 5.7 years (SE 0.08 years). Parametric survival models revealed that several factors were associated with a younger age of identification: being male, having an IQ of 70 or lower, and having experienced developmental regression. Significant differences in the age of identification among the 13 sites were also discovered., Conclusions: The large gap between the age at which children can be identified and when they actually are identified suggests a critical need for further research, innovation, and improvement in this area of clinical practice.

Background: Expansion of the CAG repeat of the TATA-box binding protein (TBP) gene has been identified as the causative mutations in spinocerebellar ataxia 17 (SCA17). TBP is ubiquitously expressed in both central nervous system and peripheral tissues. The underlying molecular changes of SCA17 are rarely explored., Methods: To study the molecular mechanisms underlying SCA17, we generated stably induced isogenic 293 cells expressing normal TBP-Q(36) and expanded TBP-Q(61) and analyzed the expressed proteins using two-dimensional difference in gel electrophoresis (2D-DIGE), followed by mass spectrometry and immunoblotting., Results: Upon induction with doxycycline, the expanded TBP-Q(61) formed aggregates with significant increase in the cell population at subG1 phase and cleaved caspase-3. Proteomics study identified a total of 16 proteins with expression changes greater than 1.5 fold. Among the 16 proteins, PARK7, GLRX3, HNRNPA1, GINS1, ENO1, HNRPK and NPM1 are increased, and SERPINA5, HSPA5, VCL, KHSRP, HSPA8, HNRPH1, IMMT, VCP and HNRNPL are decreased in cells expressing TBP-Q(61) compared with those expressing TBP-Q(36). The altered expression of HSPA5, HSPA8 and PARK7 were further validated by 2D and Western immunoblot analyses., Conclusions: The results illustrate the utility of proteomics to identify alterations of proteins which underlie pathogenesis of SCA17, and may serve as potential therapeutic targets.

Autism is a neurodevelopmental disorder of prenatal onset that is behaviorally defined. There is increasing evidence for systemic and neuroimmune mechanisms in children with autism. Although genetic factors are important, atypical prenatal maternal immune responses may also be linked to the pathogenesis of autism. We tested serum reactivity in 11 mothers and their autistic children, maternal controls, and several groups of control children, to prenatal, postnatal, and adult rat brain proteins, by immunoblotting. Similar patterns of reactivity to prenatal (gestational day 18), but not postnatal (day 8) or adult rat brain proteins were identified in autistic children, their mothers, and children with other neurodevelopmental disorders, and differed from mothers of normal children, normal siblings of children with autism and normal child controls. Specific patterns of antibody reactivity were present in sera from the autism mothers, from 2 to 18 years after the birth of their affected children and were unrelated to birth order. Immunoblotting using specific antigens for myelin basic protein (MBP) and glial acidic fibrillary protein (GFAP) suggests that these proteins were not targets of the maternal antibodies. The identification of specific serum antibodies in mothers of children with autism that recognize prenatally expressed brain antigens suggests that these autoantibodies could cross the placenta and alter fetal brain development.

Purpose: Dupuytren's disease (DD) is characterized by fibroblastic proliferation of the palmar fascia, often leading to flexion contracture in the hand. Although there is a strong genetic component the genome-wide expression of novel genes is not known. The purpose of this study was to use DNA microarray technology to identify upregulated genes in DD., Methods: Human tissue samples were harvested from 3 patient sources: DD cord tissue (n = 20), normal-appearing adjacent control fascia (n = 15), and palmar fascia from patients having carpal tunnel release (n = 15). DNA microarray analysis was performed on amplified sample RNA. Novel genes were compared with known gene functions. A candidate gene of interest was studied further by using immunohistochemistry on DD tissue samples and controls., Results: Several novel genes not described previously in the study of DD were upregulated significantly, including MafB, collagen type V, alpha-2 (COL5A2), collagen type VIII, alpha-1 (COL8A1), contactin I (CNTN1), and leucine-rich repeat containing 17 (LRRC17). These upregulated genes were compared with their known gene-expression profiles in other tissues and their purported functions. MafB was found to be of particular interest because of its prominent role in tissue development and cellular differentiation. MafB immunohistochemistry showed positive staining in 50% of the DD specimens but complete absence of MafB in all control tissues (adjacent control fascia, carpal tunnel fascia). Co-localization experiments with MafB and alpha-smooth muscle actin showed staining properties in similar regions but these 2 proteins were not confined solely to the same cells., Conclusions: Microarray analysis of DD tissue has identified significant upregulated gene expression of MafB. MafB protein also is found in Dupuytren's cords but not in control fascia. Co-localization data suggest that the association of MafB with DD is not related exclusively to myofibroblast proliferation. Because of its role in fibroblastic transformation in other models MafB and its relationship to the pathogenesis of DD deserves further study.

Essential thrombocythemia (ET) is a heterogeneous disorder in which the clonality of hematopoiesis varies. The clinical significance of clonality status in ET remains to be determined. We used the human androgen receptor gene (HUMARA)-polymerase chain reaction assay to investigate X-chromosome inactivation patterns (XCIPs) and their value in predicting vascular complications in 89 female patients with ET. Fifty-four (68.4%) patients had a clonal pattern of XCIP, and 15 (19.0%) had a polyclonal pattern. The remaining 20 patients had either an ambiguous or a homozygous pattern of XCIP and were therefore excluded from further analysis. Patients with clonal XCIPs were older (P =.029) and were at greater risk for thrombosis (P =.007) than were those with polyclonal XCIPs. We did not find a correlation between the occurrence of hemorrhage and XCIP (P =.492). Advanced age was predictive of thrombosis and hemorrhage. Platelet count did not influence the risk for vascular complications. Hypertension was significantly correlated with thrombotic events (P =.002), whereas diabetes mellitus and hypercholesterolemia were of no predictive value. In a multivariate analysis, age was the significant predictor of thrombosis (P =.030); however, XCIPs (P =.083) and hypertension (P =.073) tended to predict thrombosis. Our results suggest that older patients who have clonal XCIPs or hypertension are at increased risk for thrombosis and should be monitored closely for this complication.

Objective: To examine whether the two-factor model of affect presented by Watson and colleagues is applicable to school children., Method: A child self-report scale of symptoms of depression and anxiety was administered to 624 school children in the third and sixth grades. Factor analyses were applied to extract factors of positive and negative affect. Reliabilities, correlations, and longitudinal analyses were performed to examine the developmental pathway of positive affect (PA) and negative affect (NA)., Results: In contrast to Watson's early findings, our results indicate that the PA and NA scales are significantly negatively correlated cross-sectionally as well as longitudinally. Moreover, our findings indicate that children with high NA and low PA in the third grade display a worse prognosis than children who have either high NA or low PA., Conclusions: A new affect model is needed for describing children's mood status. In addition, an important implication of these findings is that the occurrence of comorbid mood status in children confers a high risk for later emotional problems.

[11C]Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9-[11C]methoxy-10 -methoxy-1,2,3,4,6,7,- hexahydro-11bH-bezo[alpha]-quinolizine) ([11C]DTBZ) was synthesized by reacting the 9-hydroxy precursor in DMSO with gas-phase [11C]methyl iodide on a column of alumina impregnated with KOH. The reaction was instantaneous at room temperature. This column was then connected to the inlet of a short column containing basic alumina. Elution with cyclohexane removed radioactive contaminants. The radioactive product was then eluted with a few milliliters ether containing 1% ethanol. The [11C]DTBZ was obtained in isolated yields of > 200 mCi and specific activities > 1600 Ci/mmol.

The IS2 sequence encodes five open reading frames (ORF1 to ORF5) that are greater than 150 nucleotides each. Only one protein of 14 kDa was detected when the expression of IS2 genes was examined in minicells. This 14 kDa protein was referred to as InsA in this study and was determined to be encoded by ORF1. A sixfold decrease in IS2 transposition frequency was observed when insA was overexpressed. DNA footprinting results indicated that InsA binds to the sequence 5'-TAAATAA-3' located at IS2 nucleotide numbers 1286 to 1292. (The IS2 right terminal repeat spans nucleotides 1290 to 1331.) This InsA binding sequence is situated 4 bp upstream from the putative "-10" sequence of the insA promoter that overlaps the right terminal repeat of IS2. The presence of a promoter located in this region was demonstrated by the ability of a DNA fragment containing the right terminal repeat to drive the expression of a promoterless lacZ gene. The transcription of insA was determined to start at the A residue located at nucleotide number 1268. With the same insA promoter-lacZ fusion construct, overexpression of insA in the same cell was found to decrease the beta-galactosidase activity. The results of this study suggest that InsA affects IS2 transposition by regulating the transcription of IS2 genes.

Two children manifested EEG discharges which were triggered by blinking and/or eye closure in light and in darkness. The first case demonstrated single focal posterior discharges with eye blinks and repetitive focal posterior sharp wave discharges with eye closures. No photoparoxysmal responses were obtainable. Case 2 manifested generalized epileptic discharges triggered by eye closure which were sometimes associated with clinical seizures. In addition she showed photoconvulsive responses. Since the discharges triggered by eye blink and by eye closure occurred in both bright light and in darkness it is suggested that sensory afferents arising from contraction of the orbicularis oculi muscles may have been the epileptic trigger in Case 1 and could have contributed to the epileptic triggering mechanism in Case 2.