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The psychometric properties of the Adult Manifest Anxiety Scale-Elderly Version (AMAS-E) scores were evaluated in two studies. In Study 1, the temporal stability and construct validity of the AMAS-E test scores were examined in a group of 226 older adults, aged 60 years and older. Results indicated adequate to excellent temporal stability (2-week interval) for the AMAS-E test scores. Evidence supporting the construct validity of the AMAS-E scale scores as measures of various aspects of anxiety was found. In Study 2, the factor structure of the AMAS-E was examined across gender for a sample of 863 older adults, 555 women and 308 men, aged 60 to 100 years. Coefficient of congruence and salient variable similarity index values reported suggest that the pairs of matched factors of each of the four factors (i.e., Fear of Aging, Physiological Anxiety, Worry/Oversensitivity, and Lie) and the general anxiety (g[anx]) or Total Anxiety factor were invariant across gender. Implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

The present study examined differences across gender, ethnicity, and age with regard to the nature of participants' self-reported attitudes toward school and teachers, based on previous research suggesting that students' school- and teacher-related attitudes appear to have an influence on academic achievement. This study employed an archival approach using the standardization data (N = 10,140) from the Attitude to School and Attitude to Teachers scales of the Behavior Assessment System for Children Self-Report of Personality. Results of data analyses suggest that in general, males reported more negative attitudes toward both school and teachers; however, the effect sizes for the statistically significant gender differences were rather small. Age was not a significant main effect in any of the analyses for these two scales; there were no consistent patterns of more or less negative attitudes with increasing age for any of the gender or ethnic groups. Perhaps the most notable finding in the present study was a trend toward Hispanics reporting the most negative attitudes toward school while also reporting the most positive attitudes toward teachers. This finding suggests that there are factors other than teachers that contribute to Hispanics' negative perceptions of school; the exploration of these factors represents an important area for future research. [ABSTRACT FROM AUTHOR]

Background: Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes)., Methods: This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis., Results: Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants., Conclusion: Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health., Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.S, using electronic health record (EHR) data. Our cohort included those with a positive SARS-CoV-2 molecular, serology or antigen test, or with a COVID-19, multisystem inflammatory disease in children, or PASC diagnosis from February 29, 2020 to August 1, 2022. We identified children/youth with at least 2 codes associated with respiratory and neurologic PASC. We measured associations between sociodemographic and clinical characteristics and respiratory and neurologic PASC using odds ratios and 95% confidence intervals estimated from multivariable logistic regression models adjusted for other sociodemographic characteristics, social vulnerability index or area deprivation index, time period of cohort entry, presence and complexity of chronic respiratory (respectively, neurologic) condition and healthcare utilization., Findings: Among 771,725 children in the cohort, 203,365 (26.3%) had SARS-CoV-2 infection. Among children with documented infection, 3217 children had respiratory PASC and 2009 children/youth had neurologic PASC. In logistic regression models, children <5 years (Odds Ratio [OR] 1.78, 95% CI 1.62-1.97), and of Hispanic White descent (OR 1.19, 95% CI 1.05-1.35) had higher odds of having respiratory PASC. Children/youth living in regions with higher area deprivation indices (OR 1.25, 95% CI 1.10-1.420 for 60-79th percentile) and with chronic complex respiratory conditions (OR 3.28, 95% CI 2.91-3.70) also had higher odds of respiratory PASC. In contrast, older (OR 1.57, 95% CI 1.40-1.77 for those aged 12-17 years), non-Hispanic White individuals and those with chronic pre-existing neurologic conditions (OR 2.04, 95% CI 1.78-2.35) were more likely to have a neurologic PASC diagnosis., Interpretation: Racial and ethnic differences in healthcare utilization for neurologic and respiratory PASC may reflect social drivers of health and inequities in access to care., Funding: National Institutes of Health., Competing Interests: Dr. Kleinman is Board Member for Dartnet Institute, and owns stocks with Glaxo, Amgen, Regeneron and Sanofi. Dr. Oliveira is on the Board of Directors for Eastern Society of Pediatric Research (ESPR) Executive Committee for American Academy of Pediatrics–Section on Epidemiology, Public Health, and Evidence (AAP-SOEPHE) Associate Editor for Journal of Pediatric Infectious Diseases Society. All other authors have no conflicts of interest to disclose., (© 2025 The Authors. Published by Elsevier Ltd.)

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue., Competing Interests: Dr. Jhaveri is a consultant for AstraZeneca, Seqirus, Dynavax, receives an editorial stipend from Elsevier and Pediatric Infectious Diseases Society and royalties from Up To Date/Wolters Kluwer. Dr. Rao reports prior grant support from GSK and Biofire and is a consultant for Sequiris. Dr Bailey has received grants from Patient-Centered Outcomes Research Institute. Dr. Brill received support from Novartis and Regeneron Pharmaceuticals within the last year. Dr. Horne is a member of the advisory boards of Opsis Health and Lab Me Analytics, a consultant to Pfizer regarding risk scores (funds paid to Intermountain), and an inventor of risk scores licensed by Intermountain to Alluceo and CareCentra and is site PI of a COVID-19 grant from the Task Force for Global Health, site PI of grants from the Patient-Centered Outcomes Research Institute, a member of the advisory board of Opsis Health, and previously consulted for Pfizer regarding risk scores (funds paid to Intermountain). All other authors have no conflicts of interest to disclose.

Objectives: To provide a foundational methodology for differentiating comorbidity patterns in subphenotypes through investigation of a multi-site dementia patient dataset., Materials and Methods: Employing the National Clinical Cohort Collaborative Tenant Pilot (N3C Clinical) dataset, our approach integrates machine learning algorithms-logistic regression and eXtreme Gradient Boosting (XGBoost)-with a diagnostic hierarchical model for nuanced classification of dementia subtypes based on comorbidities and gender. The methodology is enhanced by multi-site EHR data, implementing a hybrid sampling strategy combining 65% Synthetic Minority Over-sampling Technique (SMOTE), 35% Random Under-Sampling (RUS), and Tomek Links for class imbalance. The hierarchical model further refines the analysis, allowing for layered understanding of disease patterns., Results: The study identified significant comorbidity patterns associated with diagnosis of Alzheimer's, Vascular, and Lewy Body dementia subtypes. The classification models achieved accuracies up to 69% for Alzheimer's/Vascular dementia and highlighted challenges in distinguishing Dementia with Lewy Bodies. The hierarchical model elucidates the complexity of diagnosing Dementia with Lewy Bodies and reveals the potential impact of regional clinical practices on dementia classification., Conclusion: Our methodology underscores the importance of leveraging multi-site datasets and tailored sampling techniques for dementia research. This framework holds promise for extending to other disease subtypes, offering a pathway to more nuanced and generalizable insights into dementia and its complex interplay with comorbid conditions., Discussion: This study underscores the critical role of multi-site data analyzes in understanding the relationship between comorbidities and disease subtypes. By utilizing diverse healthcare data, we emphasize the need to consider site-specific differences in clinical practices and patient demographics. Despite challenges like class imbalance and variability in EHR data, our findings highlight the essential contribution of multi-site data to developing accurate and generalizable models for disease classification., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m 2 , End Stage Kidney Disease diagnosis, dialysis, or transplant., Competing Interests: Dr. Jhaveri is a consultant for AstraZeneca, Seqirus, Dynavax, receives an editorial stipend from Elsevier and Pediatric Infectious Diseases Society and royalties from Up To Date/Wolters Kluwer. Dr. Ruby Patel is the Primary Investigator for FIONA study, no stipend or compensation being given. Dr. Modi reports research funding outside of this work from the National Institutes of Health, Centers for Disease Control, the Patient-Centered Outcomes Research Institute, Travere Therapeutics, and Boehringer Ingelheim. He is also the current director of the Kidney Research Network Data Coordinating Center. Dr. Harshman reports research funding outside of this work from the National Institutes of Health. Dr. Harshman reports research funding outside of this work from Bayer Pharmaceuticals. Dr. Verghese reports research funding outside of this work from the Department of Defense and Viracor Pharmaceuticals. Dr. Dixon reports consultancies with Novartis Pharmaceuticals, Alexion Astra Zeneca Rare Disease, Apellis Pharmaceuticals, and Arrowhead Pharmaceuticals.

Purpose: To understand nursing home workers' experience during the coronavirus disease 2019 (COVID-19) pandemic and investigate the prevalence of health-related quality of life, emotional distress, job satisfaction, and the impact of the pandemic., Method: The Healthcare Worker Exposure Response and Outcomes (HERO) Registry served as the data source for this descriptive cross-sectional analysis. Recruitment was conducted nationally. Eligible nursing home workers ( N = 1,409) enrolled in the study online, self-reported demographic and employment characteristics, and completed electronic surveys., Results: Nursing home workers reported overall good physical health, frequent depressive symptoms, burnout, and a high prevalence of feeling tired, stressed, having trouble sleeping, and feeling worried. Age and race were found to be positively associated with the impact of the pandemic., Conclusion: Findings demonstrate the difficulties and challenges nursing home workers faced during the COVID-19 pandemic. Future research needs to evaluate the relationships among nursing home workers' roles, mental health, depressive symptoms, and prevalence of burnout with a larger, more diverse sample. [ Research in Gerontological Nursing, 17 (3), 131-140.].

Care coordination is a crucial component of healthcare systems. However, little is known about data needs and uses in ambulatory care coordination practice. Therefore, the purpose of this study was to identify information gathered and used to support care coordination in ambulatory settings. Survey respondents (33) provided their demographics and practice patterns, including use of electronic health records, as well as data gathered and used. Most of the respondents were nurses, and they described varying practice settings and patterns. Although most described at least partial use of electronic health records, two respondents described paper documentation systems. More than 25% of respondents gathered and used most of the 72 data elements, with collection and use often occurring in multiple locations and contexts. This early study demonstrates significant heterogeneity in ambulatory care coordination data usage. Additional research is necessary to identify common data elements to support knowledge development in the context of a learning health system., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality., Methods: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period., Results: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures., Conclusions: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Anzalone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This article presents a discussion of the process of precision fermentation (PF), describing the history of the space, the expected 70% growth over the next 5 years, various applications of precision fermented products, and the markets available to be disrupted by the technology. A range of prokaryotic and eukaryotic host organisms used for PF are described, with the advantages, disadvantages and applications of each. The process of setting up PF and strain engineering is described, as well as various ways that computational analysis and design techniques can be employed to assist PF engineering. The article then describes the design and implementation of a machine learning method, machine learning predictions having amplified secretion (MaLPHAS) to predict strain engineerings, which optimise the secretion of a recombinant protein. This approach showed an in silico cross-validated R 2 accuracy on the training data of up to 46.6% and in an in vitro test on a Komagataella phaffii strain, identified one gene engineering out of five predicted, which was shown to double the secretion of a heterologous protein and outperform three of the best-known edits from the literature for improving secretion in K. phaffii ., Competing Interests: Christopher Reynolds is CEO, founder and majority shareholder of Eden Bio Ltd, as well as a shareholder in Better Dairy. Rachel Shaw and Evgenia Markova are employees of Eden Bio Ltd., (© 2022 The Authors. Engineering Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Group sizes in an animal study are calculated from estimates on variation, effect, power and significance level. Much of the variation in glucose related parameters of the diet-induced obese (DIO) mouse model is due to inter-individual variation in gut microbiota composition. In addition, standard tandem repeats (STRs) in the non-coding DNA shows that inbred mice are not always homogenic. C57BL/6NTac (B6NTac) mice from Taconic and C57BL/6NRj (B6NRj) mice from Janvier Labs were fed a high calorie diet and treated with liraglutide. The fecal microbiota was sequenced before high-calorie feeding (time 1) and after diet-induced obesity instantly before liraglutide treatment (time 2) and mice were divided into clusters on the basis of their microbiota. Although liraglutide in both sub-strains alleviated glucose intolerance and reduced body weight, in a one-way ANOVA a borderline reduction in glycosylated hemoglobin (HbA1c) could only be shown in B6NTac mice. However, if the microbiota clusters from time 1 or time 2 were incorporated in a two-way ANOVA, the HbA1c effect was significant in B6NTac mice in both analyses, while this did not change anything in B6NRj mice. In a one-way ANOVA the estimated group size needed for a significant HbA1c effect in B6NTac mice was 42, but in two-way ANOVAs based upon microbiota clusters of time 1 or time 2 it was reduced to 21 or 12, respectively. The lowering impact on glucose tolerance was also powered by incorporation of microbiota clusters of both times in both sub-strains. B6NRj had up to six, while B6NTac had maximum three alleles in some of their STRs. In B6NRj mice in 28.8% of the STRs the most prevalent allele had a gene frequency less than 90%, while this was only 6.6% in the B6NTac mice. However, incorporation of the STRs with the highest number of alleles or the most even distribution of frequencies in two-way ANOVAs only had little impact on the outcome of data evaluation. It is concluded that the inclusion of microbiota clusters in a two-way ANOVA in the evaluation of the glucose related effects of an intervention in the DIO mouse model might be an efficient tool for increasing power and reducing group sizes in mouse sub-strains, if these have a microbiota, which influences these parameters., (© 2022. The Author(s).)

Alternatives to conventional cancer treatments are highly sought after for high-risk malignancies that have a poor response to established treatment modalities. With research advancing rapidly in the past decade, neoantigen-based immunotherapeutic approaches represent an effective and highly tolerable therapeutic option. Neoantigens are tumor-specific antigens that are not expressed in normal cells and possess significant immunogenic potential. Several recent studies have described the conceptual framework and methodologies to generate neoantigen-based vaccines as well as the formulation of appropriate clinical trials to advance this approach for patient care. This review aims to describe some of the key studies in the recent literature in this rapidly evolving field and summarize the current advances in neoantigen identification and selection, vaccine generation and delivery, and the optimization of neoantigen-based therapeutic strategies, including the early data from pivotal clinical studies.

Comprehensive participatory planning and evaluation (CPPE), a model used in community engagement research, has not been applied to patient engagement in research. We describe our methodology and interim results using CPPE in a project focused on improving research engagement of rural and distant patients and stakeholders. Specifically, we describe our development of a causal map and the subsequent use of the map to guide patient and stakeholder-driven evaluation.

Conoley, Powers, and Gutkin (2020) have provided an assessment of the progress and lack thereof of school psychology as a profession toward school reformation, especially as related to their various earlier calls for changes in training and practice. Conoley and Gutkin especially (and I have been colleagues of both) have called for decades for an emphasis on working with teachers, other adults in the school system, and the school system itself to alter the delivery of education. In some earlier work, they have characterized this as adult school psychology. In many ways this is a reconceptualization of earlier mental health consultation models of school psychology practice that were not widely adopted for reasons Conoley et al. (2020) explain. School psychology has a long history of wanting to be seen and to practice differently from in a primary role of test and place, and indeed I would characterize the primary organizations that represent the profession (the National Association of Psychologists and the American Psychological Association's Division of School Psychology) as being in many ways antagonistic toward psychological testing. Yet, it is what most school psychologists are in fact hired to do as their primary role, and training in psychological testing and assessment is one of the key skills that sets us apart and distinguishes us from others in the schools. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Peroxisomes exist in nearly every cell, oxidizing fats, synthesizing lipids and maintaining redox balance. As the brain ages, multiple pathways are negatively affected, but it is currently unknown if peroxisomal proteins are affected by aging in the brain. While recent studies have investigated a PEX5 homolog in aging C. elegans models and found that it is reduced in aging, it is unclear if PEX5, a mammalian peroxisomal protein that plays a role in peroxisomal homeostasis and degradation, is affected in the aging brain. To answer this question, we first determined the amount of PEX5, in brain homogenates from young (3 months) and aged (26 through 32+ months of age) wild-type mice of both sexes. PEX5 protein was decreased in aged male brains, but this reduction was not significant in female brains. RNAScope and real-time qPCR analyses showed that Pex5 mRNA was also reduced in aged male brain cortices, but not in females. Immunohistochemistry assays of cortical neurons in young and aged male brains showed that the amount of neuronal PEX5 was reduced in aged male brains. Cortical neurons in aged female mice also had reduced PEX5 levels in comparison to younger female mice. In conclusion, total PEX5 levels and Pex5 gene expression both decrease with age in male brains, and neuronal PEX5 levels lower in an age-dependent manner in the cortices of animals of both sexes., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Previous reports on positive surgical margin (PSM) after robot-assisted partial nephrectomy (RAPN) have reached inconsistent conclusions as to the impact of a PSM on oncologic outcomes. We sought to determine the effect of PSM on long-term cancer recurrence and survival outcomes., Methods: We queried our renal oncology database for patients having undergone RAPN and compared recurrence-free survival (RFS) and overall survival (OS) between patients with PSM and negative surgical margin (NSM). Kaplan-Meier analysis was also performed for RFS and OS for PSM versus NSM., Results: Of the 432 patients who underwent RAPN we identified 29 (6.7%) patients with PSM and 403 (93.3%) patients with NSM. Median follow-up for the overall cohort was 45.1 months. Three of the 29 patients with PSM and fourteen of the 403 patients with NSM had disease recurrence (P=0.09). RFS at 24, 48, and 72 months was 95.8%, 90%, and 85.5% for patients with NSM and 96.6%, 86.6%, and 80.4% for patients with PSM, respectively (log-rank P value =0.382). OS at 24, 48, and 72 months was 98%, 93.1%, and 89.7% for patients with NSM and 96.3%, 91.2%, and 85.2% for patients with PSM, respectively (log-rank P value =0.584)., Conclusions: While PSM are relatively uncommon, their presence still serves as a potential risk factor for worse oncologic outcomes. In instances of PSM, immediate secondary intervention is most likely unnecessary and more attentive long-term clinical follow-up, especially in patients with high-risk features, may be more advisable., Competing Interests: Conflicts of Interest: The series “Robotic-assisted Urologic Surgery” was commissioned by the editorial office without any funding or sponsorship. AKH served as the unpaid Guest Editor of the series and serves as the unpaid editorial board member of Translational Andrology and Urology from May 2019 to Apr 2021. The other authors have no other conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Amyloid plaques in Alzheimer's disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aβ) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the Aβ burden prior to brain, highlighting gut-brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular Aβ deposition in the IEB occur before cerebral Aβ aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral Aβ pathology. Lastly, we report Aβ deposition in the intestinal autopsy from AD patients with confirmed cerebral Aβ pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota.

Objective: To determine the effect of positive surgical margins (PSMs) on oncologic outcomes following robot-assisted partial nephrectomy (RAPN) and to identify factors that increase the likelihood of adverse oncologic outcomes. Methods: A multi-institutional database of patients who underwent RAPN with complete follow-up data was used to compare recurrence-free survival (RFS) and overall survival (OS) between 42 (5.1%) patients with a PSM and 797 (94.9%) patients with a negative surgical margin. Analysis was performed with univariable and multivariable Cox proportional hazard regression models adjusting for confounding variables. A Kaplan-Meier method was used to evaluate the relationship between PSM and oncologic outcomes (RFS and OS), and the equality of the curves was assessed using a log-rank test. Results: The rate of PSM was 5.1%. RFS at 12, 24, and 36 months was 97.8%, 95.2%, and 92.9%. OS at 12, 24, and 36 months was 98.6%, 97.7%, and 93.3%. PSM was not associated with worse RFS in both univariable and multivariable analyses (hazard ratio [HR] = 1.43; 95% confidence interval [CI] = 0.37, 5.55; p  = 0.607). Factors associated with worse RFS include pT3a upstaging (HR = 4.97; 95% CI = 1.63, 15.12; p  = 0.005), a higher Charlson comorbidity index (HR = 1.68; 95% CI = 1.20, 2.34; p  = 0.002); and advanced clinical stage (cT1a vs cT1b, HR = 4.22; 95% CI = 1.84, 9.68; p  = 0.001 vs cT2a, HR = 14.09; 95% CI = 3.85, 51.53; p  < 0.001). PSM was not associated with worse OS in both univariable and multivariable analyses (HR = 0.87; 95% CI = 0.26, 2.94; p  = 0.821). Higher R.E.N.A.L. nephrometry score was found to be associated with worse OS (HR = 1.26; 95% CI = 1.01, 1.57; p  = 0.041). Conclusions: Given the absence of association between PSM and worse oncologic outcomes, patients with PSM following RAPN should be carefully monitored for recurrence rather than undergo immediate secondary intervention. As advanced clinical stage (cT1b, cT2a) and pathologic upstaging (pT3a) were independently associated with disease recurrence, their presence may warrant more attentive postoperative surveillance.

The adaptive immune response in jawed vertebrates is marked by the ability to diversify somatically specific immune receptor genes. Somatic recombination and hypermutation of gene segments are used to generate extensive repertoires of T and B cell receptors. In contrast, jawless vertebrates utilize a distinct diversification system based on copy choice to assemble their variable lymphocyte receptors. To date, very little evidence for somatic immune gene diversification has been reported in invertebrate species. Here we show that the SpTransformer ( SpTrf ; formerly Sp185/333 ) immune effector gene family members from individual coelomocytes from purple sea urchins undergo somatic diversification by means of gene deletions, duplications, and acquisitions of single nucleotide polymorphisms. While sperm cells from an individual sea urchin have identical SpTrf gene repertoires, single cells from two distinct coelomocyte subpopulations from the same sea urchin exhibit significant variation in the SpTrf gene repertoires. Moreover, the highly diverse gene sequences derived from single coelomocytes are all in-frame, suggesting that an unknown mechanism(s) driving these somatic changes involve stringent selection or correction processes for expression of productive SpTrf transcripts. Together, our findings infer somatic immune gene diversification strategy in an invertebrate.

Background: The location of coelomocyte proliferation in adult sea urchins is unknown and speculations since the early 1800s have been based on microanatomy and tracer uptake studies. In adult sea urchins ( Strongylocentrotus purpuratus ) with down-regulated immune systems, coelomocyte numbers increase in response to immune challenge, and whether some or all of these cells are newly proliferated is not known. The gene regulatory network that encodes transcription factors that control hematopoiesis in embryonic and larval sea urchins has not been investigated in adults. Hence, to identify the hematopoietic tissue in adult sea urchins, cell proliferation, expression of phagocyte specific genes, and expression of genes encoding transcription factors that function in the conserved regulatory network that controls hematopoiesis in embryonic and larval sea urchins were investigated for several tissues. Results: Cell proliferation was induced in adult sea urchins either by immune challenge through injection of heat-killed Vibrio diazotrophicus or by cell depletion through aspiration of coelomic fluid. In response to either of these stimuli, newly proliferated coelomocytes constitute only about 10% of the cells in the coelomic fluid. In tissues, newly proliferated cells and cells that express SpTransformer proteins (formerly Sp185/333) that are markers for phagocytes are present in the axial organ, gonad, pharynx, esophagus, and gut with no differences among tissues. The expression level of genes encoding transcription factors that regulate hematopoiesis show that both the axial organ and the pharynx have elevated expression compared to coelomocytes, esophagus, gut, and gonad. Similarly, an RNAseq dataset shows similar results for the axial organ and pharynx, but also suggests that the axial organ may be a site for removal and recycling of cells in the coelomic cavity. Conclusions: Results presented here are consistent with previous speculations that the axial organ may be a site of coelomocyte proliferation and that it may also be a center for cellular removal and recycling. A second site, the pharynx, may also have hematopoietic activity, a tissue that has been assumed to function only as part of the intestinal tract.

Background: The automation of modular cloning methodologies permits the assembly of many genetic designs. Utilising characterised biological parts aids in the design and redesign of genetic pathways. The characterisation information held on datasheets can be used to determine whether a biological part meets the design requirements. To manage the design of genetic pathways, researchers have turned to modelling-based computer aided design software tools., Result: An automated workflow has been developed for the design and build of heterologous metabolic pathways. In addition, to demonstrate the powers of electronic datasheets we have developed software which can transfer part information from a datasheet to the Design of Experiment software JMP. To this end we were able to use Design of Experiment software to rationally design and test randomised samples from the design space of a lycopene pathway in E. coli . This pathway was optimised by individually modulating the promoter strength, RBS strength, and gene order targets., Conclusion: The use of standardised and characterised biological parts will empower a design-oriented synthetic biology for the forward engineering of heterologous expression systems. A Design of Experiment approach streamlines the design-build-test cycle to achieve optimised solutions in biodesign. Developed automated workflows provide effective transfer of information between characterised information (in the form of datasheets) and DoE software., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

EzMol is a molecular visualization Web server in the form of a software wizard, located at http://www.sbg.bio.ic.ac.uk/ezmol/. It is designed for easy and rapid image manipulation and display of protein molecules, and is intended for users who need to quickly produce high-resolution images of protein molecules but do not have the time or inclination to use a software molecular visualization system. EzMol allows the upload of molecular structure files in PDB format to generate a Web page including a representation of the structure that the user can manipulate. EzMol provides intuitive options for chain display, adjusting the color/transparency of residues, side chains and protein surfaces, and for adding labels to residues. The final adjusted protein image can then be downloaded as a high-resolution image. There are a range of applications for rapid protein display, including the illustration of specific areas of a protein structure and the rapid prototyping of images., (Copyright © 2018. Published by Elsevier Ltd.)

This study illustrates the accuracy and efficiency of using an evidence-based assessment (EBA) strategy for diagnosis of attention-deficit/hyperactivity disorder (ADHD) by integrating the scale scores obtained on BASC-3 teacher and parent rating scales. The examined process used empirical diagnostic likelihood ratios (DLRs) derived from a sample of children with ADHD (N = 339) matched on demographic characteristics from the normative sample. The results show that behavioral scales of executive functioning and functional communication provided incremental utility in ADHD diagnosis. With a revised probability of .80 or higher as the diagnostic criterion, teachers, and parents positively diagnosed 70% and 94% of the ADHD cases respectively. The EBA approach was efficient, with four scales on average used to reach the proposed posterior probability for final diagnosis. Finally, teachers and parents demonstrated a high agreement with respect to the diagnosis results and scales used for the diagnosis.

Objective: To compare perioperative and functional outcomes of patients with cT1a or cT1b renal masses undergoing robotic partial nephrectomy (RPN) in a large multi-institutional study PATIENTS AND METHODS: The present retrospective Institutional Review Board-approved multi-institutional study utilised a prospectively maintained database to identify patients undergoing RPN by six surgeons for a solitary cT1a (n = 1 307) or cT1b (n = 377) renal mass from 2006 to 2016. Perioperative and renal function outcomes at discharge and at a median follow-up of 12.2 months were compared in univariable and multivariable regression analyses adjusting for surgeon performing the procedure and date of surgery., Results: In univariable analysis, cT1b masses were associated with longer operative time (190.0 vs 159.0 min, P < 0.001), longer warm ischaemia time (18.8 vs 15.0 min, P < 0.001), higher estimated blood loss (150.0 vs 100.0 mL, P < 0.001), more intraoperative complications (5.6% vs 2.4%, P = 0.034), and more surgical postoperative complications (10.1% vs 5.7%, P =0.002). Results were similar in multivariable analysis with additional findings including more overall postoperative complications (odds ratio 1.55, P = 0.015) and longer length of stay (P < 0.001) associated with cT1b masses. There were no differences in the risk of progression of chronic kidney disease stage at 12.2 months, positive surgical margins, or major postoperative complications., Conclusions: Although our study shows a longer operative time, longer warm ischemia time, and higher complication rate for patients undergoing RPN for cT1b renal masses, the magnitude of these differences is small. RPN should be considered for cT1b lesions when anatomical and spatial location allow for a feasible procedure., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity. Importantly, we report a cocrystal structure of one of our compounds (29c) bound to SIRT2. This reveals our series to induce the formation of a previously reported selectivity pocket but to bind in an inverted fashion to what might be intuitively expected. We believe these findings will contribute significantly to an understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, second generation inhibitors.

We challenge the intuitive belief that greater leader sensitivity is always associated with desirable outcomes for employees and organizations. Specifically, we argue that followers' idiosyncratic desires for, and perceptions of, leader sensitivity behaviors play a key role in how followers react to their leader's sensitivity. Moreover, these resulting affective experiences are likely to have important consequences for organizations, specifically as they relate to employee counterproductive work behavior (CWB). Drawing from supplies-values (S-V) fit theory and the stressor-emotion model of CWB, the current study focuses on the affective and behavioral consequences of fit between subordinates' ideal leader sensitivity behavior preferences and subordinates' perceptions of their actual leader's sensitivity behaviors. Polynomial regression analyses reveal that congruence between ideal and actual leader sensitivity influences employee negative affect and, consequently, engagement in counterproductive work behavior. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Pathological cardiac hypertrophy is characterized by subcellular remodeling of the ventricular myocyte with a reduction in the scaffolding protein caveolin-3 (Cav-3), altered Ca(2+) cycling, increased protein kinase C expression, and hyperactivation of calcineurin/nuclear factor of activated T cell (NFAT) signaling. However, the precise role of Cav-3 in the regulation of local Ca(2+) signaling in pathological cardiac hypertrophy is unclear. We used cardiac-specific Cav-3-overexpressing mice and in vivo and in vitro cardiac hypertrophy models to determine the essential requirement for Cav-3 expression in protection against pharmacologically and pressure overload-induced cardiac hypertrophy. Transverse aortic constriction and angiotensin-II (Ang-II) infusion in wild type (WT) mice resulted in cardiac hypertrophy characterized by significant reduction in fractional shortening, ejection fraction, and a reduced expression of Cav-3. In addition, association of PKCα and angiotensin-II receptor, type 1, with Cav-3 was disrupted in the hypertrophic ventricular myocytes. Whole cell patch clamp analysis demonstrated increased expression of T-type Ca(2+) current (ICa, T) in hypertrophic ventricular myocytes. In contrast, the Cav-3-overexpressing mice demonstrated protection from transverse aortic constriction or Ang-II-induced pathological hypertrophy with inhibition of ICa, T and intact Cav-3-associated macromolecular signaling complexes. siRNA-mediated knockdown of Cav-3 in the neonatal cardiomyocytes resulted in enhanced Ang-II stimulation of ICa, T mediated by PKCα, which caused nuclear translocation of NFAT. Overexpression of Cav-3 in neonatal myocytes prevented a PKCα-mediated increase in ICa, T and nuclear translocation of NFAT. In conclusion, we show that stable Cav-3 expression is essential for protecting the signaling mechanisms in pharmacologically and pressure overload-induced cardiac hypertrophy., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

The use of virtual screening has become increasingly central to the drug development pipeline, with ligand-based virtual screening used to screen databases of compounds to predict their bioactivity against a target. These databases can only represent a small fraction of chemical space, and this paper describes a method of exploring synthetic space by applying virtual reactions to promising compounds within a database, and generating focussed libraries of predicted derivatives. A ligand-based virtual screening tool Investigational Novel Drug Discovery by Example (INDDEx) is used as the basis for a system of virtual reactions. The use of virtual reactions is estimated to open up a potential space of 1.21×10 12 potential molecules. A de novo design algorithm known as Partial Logical-Rule Reactant Selection (PLoRRS) is introduced and incorporated into the INDDEx methodology. PLoRRS uses logical rules from the INDDEx model to select reactants for the de novo generation of potentially active products. The PLoRRS method is found to increase significantly the likelihood of retrieving molecules similar to known actives with a p -value of 0.016. Case studies demonstrate that the virtual reactions produce molecules highly similar to known actives, including known blockbuster drugs.

Sirtuins, NAD(+) -dependent histone deacetylases (HDACs), have recently emerged as potential therapeutic targets for the treatment of a variety of diseases. The discovery of potent and isoform-selective inhibitors of this enzyme family should provide chemical tools to help determine the roles of these targets and validate their therapeutic value. Herein, we report the discovery of a novel class of highly selective SIRT2 inhibitors, identified by pharmacophore screening. We report the identification and validation of 3-((2-methoxynaphthalen-1-yl)methyl)-7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one (ICL-SIRT078), a substrate-competitive SIRT2 inhibitor with a Ki value of 0.62 ± 0.15 μM and more than 50-fold selectivity against SIRT1, 3 and 5. Treatment of MCF-7 breast cancer cells with ICL-SIRT078 results in hyperacetylation of α-tubulin, an established SIRT2 biomarker, at doses comparable with the biochemical IC50 data, while suppressing MCF-7 proliferation at higher concentrations. In concordance with the recent reports that suggest SIRT2 inhibition is a potential strategy for the treatment of Parkinson's disease, we find that compound ICL-SIRT078 has a significant neuroprotective effect in a lactacystin-induced model of Parkinsonian neuronal cell death in the N27 cell line. These results encourage further investigation into the effects of ICL-SIRT078, or an optimised derivative thereof, as a candidate neuroprotective agent in in vivo models of Parkinson's disease., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Developmental differences between working and long-term associative memory were evaluated through a cross-sectional age difference study based on data from a memory battery's standardization sample. The scores of 856 children and adolescents ranging from 5 to 17 years of age were compared on memory subtests that assess verbal working and long-term memory. Data were examined using curve fitting and ANOVA procedures that evaluated age group and years of age differences. The major finding was that the developmental trajectories across age differed substantially between the two memory domains. The working memory trajectory was linear until age 11, whereas the long-term memory trajectory was curvilinear with an inflection point at age 8. Both trajectories plateaued after age 11. ANOVAs produced significant interactions between tests of working and associative memory with age, supporting the view that the age trajectories had differing courses. The results are discussed in terms of neurobiological implications for the two memory systems studied.

Violence directed against K-12 teachers is a serious problem that demands the immediate attention of researchers, providers of teacher pre-service and in-service training, school administrators, community leaders, and policymakers. Surprisingly, little research has been conducted on this growing problem despite the broad impact teacher victimization can have on schooling, recruitment, and retention of highly effective teachers and on student academic and behavioral outcomes. Psychologists should play a leadership role in mitigating school violence, including violence directed toward teachers. There is a need for psychologists to conduct research accurately assessing the types and scope of violence that teachers experience; to comprehensively evaluate the individual, classroom, school, community, institutional, and cultural contextual factors that might predict and/or explain types of teacher violence; and to examine the effectiveness and sustainability of classroom, school, and district-wide prevention and intervention strategies that target teacher violence in school systems. Collectively, the work of psychologists in this area could have a substantial impact on schooling, teacher experience and retention, and overall student performance., ((c) 2013 APA, all rights reserved.)

It is important to consider the prevalence of low scores when administering a battery of psychological tests. Understanding the prevalence of low scores is important for minimizing false-positive diagnoses of cognitive deficits in clinical practice. The purpose of this study was to expand the literature on base rates for use in children and adolescents. Participants were 408 healthy children and adolescents (M(age) = 13.1 years, SD = 3.7) and 139 children and adolescents (M(age) = 12.4 years, SD = 3.1) diagnosed with a medical, neurological, or learning condition. All participants were administered the Test of Verbal Conceptualization and Fluency (TVCF; Reynolds & Horton, 2006 ). The clinical sample performed significantly lower compared with the healthy control participants on three of the five TVCF scores. When all scores were considered simultaneously, 38% of healthy children obtained one or more scores below the 16th percentile and 15% had one or more scores in the 5th percentile or lower. By comparison, significantly higher proportions of children in the clinical sample had low scores below each of the five cutoffs (i.e., 63% had one or more test scores below the 16th percentile and 37% had one or more scores in the 5th percentile or lower). Our findings illustrate the importance of considering the prevalence of low TVCF scores in everyday clinical practice with children and adolescents.

Previous evaluation of the Comprehensive Trail-Making Test (CTMT) using a confirmatory factor analysis (CFA) revealed that for children, a two-factor model provided a better fit than did a one-factor model. The purpose of this study was to explore whether these findings suggested a developmental factor structure or if the two-factor structure also would be supported for adults. CFA was conducted using M-plus to examine the factor structure for adults in the standardization sample using all five trails tasks from the CTMT. The findings of the CFA indicated an excellent fit for the two-factor model. In contrast, the one-factor structure (i.e., use of a composite score) was not supported. Results were the same when younger (younger than 50 years of age) and older (50 years old or older) adults were considered separately. These data suggest that a single score may not be a valid representation of executive functioning. The results support a two-factor structure that represents attention/sequencing and set switching/inhibition.

The Investigational Novel Drug Discovery by Example (INDDEx) package has been developed to find active compounds by linking activity to chemical substructure and to guide the process of further drug development. INDDEx is a machine-learning technique, based on forming qualitative logical rules about substructural features of active molecules, weighting the rules to form a quantitative model, and then using the model to screen a molecular database. INDDEx is shown to be able to learn from multiple active compounds and to be useful for scaffold-hopping when performing virtual screening, giving high retrieval rates even when learning from a small number of compounds. Across the data sets tested, at 1% of the data, INDDEx was found to have average enrichment factors of 69.2, 82.7, and 90.4 when learning from 2, 4, and 8 active ligands, respectively. At 0.1% of the data, INDDEx had average enrichment factors of 492, 631, and 707 when learning from 2, 4, and 8 active ligands, respectively. Excluding all ligands with more than 0.5 Tanimoto Maximum Common Substructure, INDDEx had average enrichment factors at 1% of 52.3, 63.6, and 66.9 when learning from 2, 4, and 8 active ligands, respectively. The performance of INDDEx is compared with that of eHiTS LASSO, PharmaGist, and DOCK.

There is increasing concern for possible gender and ethnic differences on neuropsychological measures. The purpose of this study was to examine gender and ethnicity differences on the Comprehensive Trail-Making Test (CTMT) with a focus on individuals from 8 to 18 years of age. From the standardization sample, this included 251 boys and 306 girls with a mean age of 12.76 years (SD = 3.07 years) and who were predominantly White (81.51%). Only those participants who completed all five tasks that comprise the CTMT were considered; participants representing special groups were excluded. For ethnic group, no significant differences emerged; for gender, significant differences emerged; and no interaction effects for sex by ethnicity were found. Further, no differences based on ethnicity were found. Implications and possible explanations for this difference for practice and additional research are discussed.

Knowing the prevalence of low scores on a battery of executive-functioning tests supplements clinical interpretation and can reduce the likelihood of misdiagnosing deficits in executive functioning. The purpose of this study is to examine the base rates of low scores on the Test of Verbal Conceptualization and Fluency (TVCF; Reynolds & Horton, 2006 ) in healthy adults (n = 332; M (age) = 33.0 years, SD = 10.5, range = 20-59) and older adults (n = 138; M (age) = 74.9 years, SD = 7.8, range = 60-89) from the TVCF standardization sample. The TVCF consists of four tests of executive functioning (i.e., Category Fluency, Letter Naming, Classification, and Trails C) that provide five age-adjusted T-scores. The prevalence of low scores was examined in the total sample and was stratified by educational level. When the five T-scores were considered simultaneously, having one or more scores that were 1 standard deviation (SD) below the mean was found in 28% of healthy adults and 38% of older adults. Education-based differences were also present with more lenient cutoff scores (e.g., 1 SD) but not with more conservative cutoffs. Consistent with the existing literature on other test batteries, at least one low subtest score on the TVCF is common in healthy adults and older adults.

Pediatric traumatic brain injury (TBI) is associated with behavioral disturbances that can interfere with adjustment in the classroom. As such, standardized assessments of behavioral disturbances following TBI are useful in treatment planning and rehabilitation, although few studies have examined the sensitivity of standardized behavior assessments to behavioral abnormalities in this population. The present study compared the Behavior Assessment System for Children-Second Edition Teacher Rating Scale (BASC-2 TRS) profiles of 25 children who sustained TBI to those of 25 matched controls and to the BASC-2 standardization sample. Results indicated that teachers endorsed externalizing and school-related problems more severely and frequently than internalizing problems, with the greatest elevations on the Hyperactivity, Attention Problems, and Learning Problems subscales. In addition, BASC-2 scores appeared unrelated to IQ but were influenced by achievement functioning. Findings are consistent with previous studies of behavioral abnormalities in children with TBI and provide support for the usefulness of the BASC-2 TRS in evaluating behavioral disturbances in children that result from TBI.

Exploratory factor analyses (EFAs) of the Comprehensive Trail Making Test suggested a possible two-factor solution that might better reflect the differences in Trails 1-3 and Trails 4 and 5 as opposed to a single Composite Index for the total standardization sample. The purpose of this study was to conduct a confirmatory factor analysis (CFA) of the two-factor structure with a subset of the standardization sample ages 18 or younger that had completed all five-trail tasks. The sample included 251 boys and 306 girls, ages 8-18, with a mean age of 12.76 (SD = 3.07). Data were collected across 16 states with representation from all regions of the USA. Standardized scores on each of the trails (1-5) tasks were considered. The results of CFA using M-plus indicated a good fit for the two-factor model, χ(2)(4) = 18.686, p = .0009, root mean-square error of approximation = 0.081, comparative fit index = 0.986 and standardized root-mean-squared residual = 0.021. A one-factor model was not supported. As suggested by the EFA in the manual, Trails 1-3 and Trails 4 and 5, while related, appear to be different in subtle ways that may be most meaningful in conjunction with evaluation of children with neurodevelopmental differences. Implications and possible explanations for this difference are discussed.

Objective: The objectives of this study were to evaluate whether behaviors that differentiate children and adolescents with ADHD from those without are related to the primary diagnostic criteria (i.e., inattention and impulsivity-hyperactivity), symptoms of comorbid conditions, functional impairment, or a combination, and to determine whether behaviors that discriminate are consistent between the key developmental stages of childhood and adolescence., Method: Parents and teachers rated children and adolescents with a formal diagnosis of ADHD and those without any mental, physical, or emotional disorders on the multidimensional Behavior Assessment System for Children (2nd ed., BASC-2)., Results: Results indicated that behaviors that discriminate children and adolescents with ADHD from those without were associated with primary symptoms, symptoms of comorbid conditions, and indicators of functional impairment. Teachers rated atypicality as the strongest discriminator of children with ADHD from those without and learning problems as the strongest discriminator of adolescents. Parents rated hyperactivity as the strongest discriminator for children and attention problems for adolescents. Activities of daily living was the third strongest discriminator of adolescents as rated by parents., Conclusions: Findings supported the need for a multidimensional view of ADHD that adds emphasis to issues of functional impairment in routine, daily activities important to success in school and interpersonally. Findings showed that conceptualizing and assessing behaviors demonstrated by children and adolescents with ADHD as a whole instead of only equating a diagnosis of ADHD to hyperactivity, inattention, and impulsivity will establish a foundation for understanding, interpreting, and addressing students' academic and behavioral needs across the home and school.

Background: Implantable cardioverter-defibrillator (ICD) leads are traditionally placed in the right ventricular apex (RVA), in part because this is considered the preferred vector for minimizing defibrillation threshold (DFT). However, if adequate DFT safety margins are attainable, ICD leads placed in the right ventricular outflow tract (RVOT) might confer advantages if frequent ventricular pacing is anticipated., Objective: The purpose of this study was to compare RVA with RVOT transvenous ICD lead position on DFT., Methods: This was a prospective, randomized, crossover study of RVA versus RVOT DFT in 33 patients undergoing left pectoral ICD placement. A binary search algorithm was used to measure DFT, with initial lead position tested in randomized order. The relationship between RVOT position and DFT was assessed by evaluation of the distance between RVA and RVOT., Results: The study population had a mean age of 59 ± 12 years and ejection fraction of 33% ± 14%. Mean DFT in the RVA was 9.8 ± 7.3 J versus 10.8 ± 7.2 J in the RVOT (P = .53), with no correlation between RVOT location and DFT., Conclusion: The study found no evidence that ICD lead placement in the RVOT is associated with significantly higher DFT than lead placement in the RVA., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy has become part of the treatment strategy for advanced, symptomatic heart failure, but newly published trials show that more patients than previously realized may benefit from this therapy, including those with mild heart failure symptoms. The REVERSE and MADIT-CRT trials showed that cardiac resynchronization therapy reduces risk of hospitalization for heart failure and leads to beneficial reverse remodeling of the left ventricle in mild heart failure, especially in patients with prolonged QRS complexes. Ongoing studies aim to expand the indications for this therapy even further, including in patients with normal ejection fractions and a need for frequent ventricular pacing. The current body of evidence favors cardiac resynchronization therapy in patients with a depressed ejection fraction and prolonged QRS, even with minimal or no heart failure symptoms.

The maturational course of the development of executive functioning abilities is dependent on the functional capacity of the human brain. Unfortunately, there is a dearth of standardized functional assessments of executive functioning abilities for children. The present article describes neurodevelopment of executive functioning and several recent measures of executive functioning that have been developed to assess maturational periods of specific executive functions. Clinical implications of these results for traumatically brain-injured children are described.