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Purpose: This study aimed to stratify patients with locally advanced rectal cancer (LARC) based on their response to neoadjuvant chemoradiation therapy (nCRT) using DNA damage response (DDR)-related proteins measured in peripheral blood monocytes (PBMCs). We optimized and validated an innovative assay to quantify these proteins, providing a predictive framework for nCRT response., Experimental Design: We used PBMCs collected from LARC patients either before or after standard course of ∼5.5 weeks of nCRT, with patients categorized by neoadjuvant rectal (NAR) score. DDR was assessed by immunofluorescence (γH2AX S139 foci), and by Luminex multi-analyte platform (xMAP) assay providing semi-quantitative assessment of phosphorylated Chk1 S345 , Chk2 T68 , γH2AX S139 , p53 S15 and total ATR, MDM2, p21. Assay performance was evaluated using reference controls and banked PBMCs from healthy controls (n=50)., Results: PBMCs from poor responders (PoR; NAR >14; n=21) had significantly lower γH2AX S139 foci than complete responders (CR; NAR <1; n=21) (p<0.0001), with no significant differences between pre- and post-nCRT samples (p=0.4961). The xMAP assay performance assessment showed linear sample curves, precision with acceptable inter- and intra-assay coefficients of variability, and high reproducibility with ∼1% outliers in replicates. Clinical associations using the xMAP assay found levels of six proteins (ATR, MDM2, Chk1 S345 , Chk2 T68 , γH2AX S139 , p53 S15 ) significantly differentiating CRs from PoRs (p ≤ 1e-5). Univariate CART analysis determined thresholds that segregated PoRs from CRs with high precision (p<0.001)., Conclusion: We optimized an assay to assess DDR proteins in PBMCs and identified specific proteins, along with their threshold levels, that can accurately predict response to nCRT in patients with LARC., Translational Relevance: Although neoadjuvant chemoradiation therapy followed by surgery is the standard of care for patients with locally advanced rectal cancer (LARC), many patients do not benefit from this treatment and suffer from its side effects. The motivation for this study was to reliably identify patients with LARC who will or will not respond to treatment, thereby permitting more effective direction of therapy only to likely responders. In this report, we describe identification and optimization of a novel multianalyte assay for patients diagnosed with LARC. This assay uses a Luminex xMAP platform to detect DNA damage response (DDR) signaling proteins in peripheral blood monocytes of pre-treatment patients. This assay, detecting the DDR proteins, effectively segregates responders from non-responders (p ≤ 1e-5), supporting optimization of treatment efficacy and reduction of unnecessary toxicity, thus advancing personalized medicine in oncology.

Purpose: To study the role of prolonged prophylactic antibiotic therapy (PAT) in the prevention of Inter-costal drain (ICD) related infectious complications in patients with Blunt Trauma Chest (BTC)., Methods: Patients of age 15 years and above with BTC requiring ICD were included. Patients with penetrating chest injuries, associated injuries/illnesses requiring antibiotic administration, need for mechanical ventilation, known pulmonary disease or immuno-compromised status and need for open thoracotomy were excluded. 120 patients were randomized equally to two groups; no prolonged PAT group (Group A) and prolonged PAT group (group B). Both group patients received one shot of injectable antibiotic prior to ICD insertion. Primary outcome measure was comparison of ICD related infectious complications (pneumonia, empyema and SSI) and secondary outcome measures included the duration of ICD, Length of Hospital stay (LOS) and in-hospital mortality in both the groups., Results: Infectious complications (pneumonia, empyema and SSI) were seen in only one patient in antibiotic group, and none in no antibiotic group (p value = 0.500). Other complications such as post ICD pain scores, respiratory failure requiring ventilatory support, retained hemothorax or recurrent pneumothorax, did not show any statistical difference between both groups. Also, no significant difference was seen in both the groups in terms of mean duration of ICD (p value = 0.600) and LOS (p value = 0.259).m CONCLUSION: Overall prevalence of ICD related infectious complications are low in BTC patients. Definitive role of prolonged prophylactic antibiotics in reducing infectious complications and other associated co morbidities in BTC patients with ICDs could not be established., Trial Registry Details: Clinical Trial Registry, India (Trial registered at ctri.nic.in/clinical trials/login.php, number REF/2019/021704 dated 18/10/2019)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: The distinctive social nature of sport in its capacity to promote immigrants' adaptation to the new society has been regarded as a vehicle to cope with adverse mental health outcomes derived from acculturative stress (AS) and feelings of marginalization. However, the evidence on the relationship between sport participation (SP), AS, and mental health have been lacking and fragmented. Recognizing this challenge, we examined the mediating effect of AS on the relationship between SP and depressive symptoms (DS) among international college students in the USA., Methods: A total of 203 international college students in the USA were recruited via Prolific. The instrumentation included previously validated measures: SP (SLIM-18), AS (ASSIS), DS (CES-D-10), sense of coherence (SOC-13), and demographic characteristics., Results: Mediation analysis showed a significant association between (1) SP and DS (ß = -0.030, p < 0.05) and (2) AS and DS (ß = 0.053, p < 0.001), while (3) no significant indirect effect of AS was found [ß = -0.001, SE = 0.0003, 95% CI (-0.008, 0.004)]., Discussion: Even though several previous scholars have argued that SP is an effective tool to cope with AS among international students, the present study implies this may not be applied to all international students. Specifically, AS and DS among European participants were lower than those from non-European countries, including Asia. Future studies using meta-analysis could be beneficial to examine the external validity of the previous studies on the relationship between SP, acculturation, and mental health to address this potential heterogeneity on the level of AS based on their origin countries or continents. The current study provides meaningful implications for adopting the transformative marketing perspective, which is a marketing approach that pursues positive social outcomes by promoting positive behavior of the target population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yim, Kim, Du and James.)

Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca 2+ )-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience's ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.

Background: Bariatric surgery promotes weight loss and improves co-morbid conditions, with patients who are more physically active having better outcomes. However, levels of physical activity and sedentary behaviour often remain unchanged following surgery., Objectives: To identify interventions and components thereof that are able to facilitate changes in physical activity and sedentary behaviour., Eligibility: Physical activity and/or sedentary behaviour must have been measured, pre and post intervention, in patients who have undergone bariatric surgery., Study Appraisal and Synthesis Methods: Four databases were searched with key-words. Two researchers conducted paper screening, data extraction and risk-of-bias assessment., Results: Twelve studies were included; eleven were randomised. Two were delivered presurgery and ten postsurgery; five found positive effect. Moderate to vigorous physical activity increased in three studies, two of which also found a significant increase in step count. The fourth found a significant increase in strenuous activity and the fifth a significant increase in metabolic equivalent of task/day and reduced time spent watching television., Limitations: Meta-analysis could not be conducted due to heterogeneity of outcomes and the tools used., Conclusion and Implications of Key Findings: This review has identified interventions and components thereof that were able to provoke positive effect. However, intervention and control conditions were not always well described particularly in terms of behaviour change techniques and the rationale for their use., Systematic Review Registration Number: PROSPERO (CRD42019121372)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatitis C virus (HCV) infection rates are rising in the U.S. despite widely available tools to identify and effectively treat nearly all of these cases. This cross-sectional study aimed to use laboratory data to evaluate the prevalence of HCV diagnoses among active component U.S. military service members, describe the characteristics of those diagnosed with HCV, and evaluate the adherence of their care to current standards of practice. All service members in the active component U.S. military between 1 January and 31 December 2020 were included in the study population. The primary outcome was an HCV diagnosis at any time during military service, with secondary outcomes of HCV treatment and sustained virologic response (SVR). The initial case-finding algorithm used laboratory data to identify HCV patients seen in infectious disease and gastrointestinal disease clinics in military treatment facilities (MTFs) (direct care); this was supplemented with additional data to assess and correct for undercounting from cases occurring outside MTFs (purchased care). Thirty active component service members in 2020 had been diagnosed with HCV infection during their military service via direct care, or an estimate of 68 cases after correcting for additional cases from purchased care; this number represents only 12% of the expected number of infections based on previous studies. Of the 30 cases treated via direct care, 28 (93%) received HCV treatment, with 27 of those 28 (96%) achieving SVR. Changes to HCV screening policy for military accessions should be considered in order to effectively identify and treat asymptomatic HCV infections that would otherwise go undetected.

Background: Traumatic arterio-enteric fistula is predominantly seen after penetrating trauma with only 21 reported cases documented in the past 25 years. They may present in an acute or delayed manner with upper or lower gastrointestinal bleed. A detailed clinical examination with requisite imaging can help in detecting such injuries., Case Description: Case 1: A 20-year-old gentleman, presented with penetrating stab injury to the gluteal region with bleeding per rectum. Imaging revealed evidence of injury to the inferior rectal artery which was found to be communicating with the extraperitoneal portion of the rectum. He was managed with a combination of endovascular and open surgery with a successful outcome. Case 2: A 29-year-old gentleman, presented in a delayed manner 2 weeks after a gunshot wound to the gluteal region, which was managed operatively in another hospital. He developed a massive lower gastrointestinal bleed 2 weeks after presentation. Imaging revealed evidence of a pseudoaneurysm of the inferior gluteal artery which had a fistulous communication with the gastrointestinal tract leading to bleeding. It was managed by endovascular techniques successfully., Conclusion: Arterio-enteric fistulas following trauma are rare phenomena and they need a high index of suspicion for diagnosis. Once diagnosed, they can be managed based on their location and patient physiology by interventional techniques, surgery, or a combination of the two.

As Pennsylvania implements its managed long-term services and supports program, we explore how home- and community-based providers are preparing for and perceiving the transition through an online survey. We summarize responses and conduct chi-square analysis to measure differences between select provider groups. Despite high levels of uncertainty about program impact, over 84% of respondents plan to participate. We found that providers in the first implementation phase had more strategic and operational discussions with MCOs than the other two phases ( p < .03). As program rollout continues, we anticipate changes in MCO-provider conversation frequency and topics based upon implementation zone.

Acid-induced enamel demineralisation affects many individuals either by exposure to acidic diets, acidic gas pollution (dental erosion) or to dental plaque acids (dental caries). This study aimed to develop in situ X-ray and light imaging methods to determine progression of enamel demineralisation and the dynamic relationship between acid pH and mineral density. Hourly digital microradiograph time-lapse sequences showed the depth of enamel demineralisation in 500 µm thick sections progressed with time from the surface towards the dentine following a power-law function, which was 21% faster than the lateral demineralisation progression after exposure for 85 h to lactic acid (10%, pH 2.2). The minimum greyscale remaining (mineral content) within the induced enamel lesion followed an exponential decay, while the accumulated total greyscale loss with time was linear, which showed a constant anisotropic mineral release within the enamel architecture. This 85 h demineralisation method studied by polarised light microscopy time-lapse sequences showed that once the demineralisation front reached the enamel Hunter-Schreger bands, there was preferential demineralisation along those bands. Mineral density loss was linear with increasing pH acidity between pH 5.2 and pH 4.0 (with 0.4 pH increments) when incubated over a 3-week period exposed to 0.5% lactic acid. At pH 4.0, there was complete mineral loss in the centre of the demineralised area after the 3-week period and the linear function intercepted the x-axis at ~ pH 5.5, near the critical pH for hydroxyapatite (HAp). These observations showed how intrinsic enamel structure and pH affected the progression of demineralisation. STATEMENT OF SIGNIFICANCE: Hydroxyapatite crystallites (HAp) in human enamel dissolve when exposed to an acidic environment but little is known about how the intrinsic structures in enamel and pH influence the demineralisation kinetics. We have developed a time-lapse in situ microradiography method to quantify microscopic anisotropic mineral loss dynamics in response to an acid-only caries model. Correlation with polarised light microscopy time-lapse sequences showed that larger structures in enamel also influence demineralisation progression as demineralisation occurred preferentially along the Hunter-Schreger bands (decussating prismatic enamel). The pH-controlled enamel mineral release in a linear manner quantifying the relationship between HAp orientation and acid solubility. These findings should direct the development of improved anti-demineralisation/ remineralisation treatments to retain/ restore the natural intrinsic enamel structure., 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 © 2020. Published by Elsevier Ltd.)

Objective: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not., Background: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group., Methods: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing., Results: In all, 12 patients with "progressive" versus 12 with "nonprogressive" nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed., Conclusion: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

Background: Chronic inflammation caused by ulcerative colitis (UC) causes a pro-neoplastic drive in the inflamed colon, leading to a markedly greater risk of invasive malignancy compared to the general population. Despite surveillance protocols, 50% of cases proceed to cancer before neoplasia is detected. The Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C) trial is an observational multi-centre test accuracy study to ascertain the role of molecular markers in improving the detection of dysplasia. We aimed to validate previously identified biomarkers of neoplasia in a retrospective cohort and create predictive models for later validation in a prospective cohort., Methods: A retrospective analysis using bisulphite pyrosequencing of an 11 marker panel (SFRP1, SFRP2, SRP4, SRP5, WIF1, TUBB6, SOX7, APC1A, APC2, MINT1, RUNX3) in samples from 35 patients with cancer, 78 with dysplasia and 343 without neoplasia undergoing surveillance for UC associated neoplasia across 6 medical centres. Predictive models for UC associated cancer/dysplasia were created in the setting of neoplastic and non-neoplastic mucosa., Findings: For neoplastic mucosa a five marker panel (SFRP2, SFRP4, WIF1, APC1A, APC2) was accurate in detecting pre-cancerous and invasive neoplasia (AUC = 0.83; 95% CI: 0.79, 0.88), and dysplasia (AUC = 0.88; (0.84, 0.91). For non-neoplastic mucosa a four marker panel (APC1A, SFRP4, SFRP5, SOX7) had modest accuracy (AUC = 0.68; 95% CI: 0.62,0.73) in predicting associated bowel neoplasia through the methylation signature of distant non-neoplastic colonic mucosa., Interpretation: This multiplex methylation marker panel is accurate in the detection of ulcerative colitis associated dysplasia and neoplasia and is currently being validated in a prospective clinical trial., Funding: The ENDCAP-C study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) Programme (11/100/29)., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer., Patients and Methods: In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up., Results: Samples from 41 subjects were evaluated for PD-L1 expression; 23 (56%) were positive. Subjects with PD-L1-expressing versus PD-L1-negative tumors respectively had CRRs of 30.8 versus 12.1 recurrences/hPY (P=0.082), CMRs of 16.7 versus 12.0 deaths/hPY (P=0.47), and CERs of 39.2 versus 16.9 events/hPY (P=0.069)., Conclusions: PD-L1 positivity was associated with worse CRR and CER, and marginally worse CMR. The effect on progression-free and overall survival needs to be validated in a study with a larger sample size.

Executive Summary: Shifting healthcare market forces and regulation have exerted near-constant pressure on U.S. academic health centers (AHCs) attempting to successfully execute their traditional tripartite mission. A governance structure and organizational alignment that works well under one set of conditions is rarely optimal when conditions change. Thus, the degree and type of alignment of an AHC's clinical, educational, and faculty practice organizations have changed regularly within the sector, typically landing near one end or the other on a continuum from fully aligned with centralized governance to largely independent with separate governance. The authors examine the case of Georgia Regents University and Health System in this context. In step with industry trends, the institution's governance structure swung from fully aligned/centralized governance in the early 1990s to essentially separate and decentralized by 2000. In 2010, the Georgia Regents University organizations achieved rapid realignment by creating a governance structure of sufficient strength and flexibility to absorb and adjust to continuing external upheaval. The hospitals, clinics, and physician-faculty practice group were combined into one integrated health system, then aligned with the university to form the state's only public AHC under aligned, but distinct, corporate and management structures. The years since reorganization have seen significant growth in patient volumes and complexity, improved service quality, and enhanced faculty physician satisfaction, while also significantly increasing economic contributions from the health system to the academic mission. This case study offers observations and lessons learned that may be useful to other higher education institutions considering reorganization.

Background: Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA., Methods: DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free)., Results: Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity)., Conclusion: This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale-Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did not differ in number of interest areas, but the types of interests and intensity of those interests differed considerably. Using only the IS intensity score, 81% of individuals were correctly classified (NT or HF-ASD) in a logistic regression analysis. Among individuals with HF-ASD, Interests Scale scores were significantly related to Autism Diagnostic Observation Schedule, Behavior Rating Inventory of Executive Function, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale scores, but they were not related to Autism Diagnostic Interview-Revised scores, IQ, gender, age, or psychotropic medication use. The type and intensity, but not the number, of interests distinguish high-functioning individuals with ASD from NT individuals.

Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ), to be highly associated with the MES network. TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which correlated with CpG island hypermethylation of the TAZ promoter compared with MES GBMs. Silencing of TAZ in MES glioma stem cells (GSCs) decreased expression of MES markers, invasion, self-renewal, and tumor formation. Conversely, overexpression of TAZ in PN GSCs as well as murine neural stem cells (NSCs) induced MES marker expression and aberrant osteoblastic and chondrocytic differentiation in a TEAD-dependent fashion. Using chromatin immunoprecipitation (ChIP), we show that TAZ is directly recruited to a majority of MES gene promoters in a complex with TEAD2. The coexpression of TAZ, but not a mutated form of TAZ that lacks TEAD binding, with platelet-derived growth factor-B (PDGF-B) resulted in high-grade tumors with MES features in a murine model of glioma. Our studies uncover a direct role for TAZ and TEAD in driving the MES differentiation of malignant glioma., (© 2011 by Cold Spring Harbor Laboratory Press)

Objective: The objective was to determine if visual estimation of effort (VEE) during lifting tasks is accurate in classifying relative levels of exertion or distinguishing between incomplete lifts that may be potentially unsafe and incomplete lifts of "actors" feigning weakness., Participants: A convenience sample of 117 health professionals and lay subjects participated in the study., Methods: Four actors were videoed performing four complete dynamic lifts (sets of five repetitions) of varying levels of exertion (relative to subjects' physical maximum). Subjects viewed the videoed performances, presented in no apparent order, attempting to properly classify the lifting tasks. For the four levels of exertion, participants were to judge if the lifts were 25%, 50%, 75% and 100% of each actor's maximum lifting capacity and to distinguish between an incomplete (failed) lift of 110% of maximum and a feigned failure of a lift of 25% of maximum., Results: Accuracy for in classifying all lifting activities was marginally higher than chance. There were no differences in the accuracy of health professionals or lay subjects., Conclusion: The VEE does not accurately classify relative levels of exertion or distinguish between incomplete feigned effort lifts and lifts that are potentially too heavy to safely lift.

The goal was to investigate a potential causal pattern between the motives of sport spectators and team identification by using a cross-lagged panel design. Questionnaires were completed by 229 participants at the beginning and end of one NCAA (National Collegiate Athletic Association) college football season for 4 mo. in the USA. The questionnaire included three items for each motive (Social Interaction and Entertainment), three items measuring team identification, and demographic items. The relation of Entertainment at Time 1 to team identification at Time 2 was larger than the relation of team identification at Time 1 to Entertainment at Time 2. This suggests that the motivation of Entertainment may lead to the formation of team identification more than team identification leads to Entertainment. However, the motive of Social Interaction did not show the same pattern. As results of this study suggested some spectator sport motives might lead to identification with a team, the hypothesis that all motives would be the basis of team identification might not be correct.

Objective: To determine if passing or failing statistically-based validity criteria during a distraction-based hand strength assessment is related to test behavior during a lifting assessment., Participants: 200 consecutive clients presenting for an FCE., Methods: The two testing protocols, one involving a hand strength assessment, the other involving an assessment of lifting capacities, were administered to assess the variability between repeated measures., Results: Clients failing two or more statistically-based hand strength validity criteria had significantly more variability between repeated measures in the lifting assessment, p=0.001 and 0.014 for right and left unilateral lifts, respectively, and p<0.0005 for three different bilateral lifts., Conclusions: A pattern of performance related to the degree of variability in repeated measures protocols for these two distraction-based protocols is revealed. Passing or failing the hand strength assessment are each equally predictive of test outcome during the distraction-based lifting assessment. The failure of the validity criteria in these two distraction-based tests cannot be attributed to a history of surgery but, rather, is the result of abnormal test behavior.

Objective: To determine if isometric (static) strength accurately predicts dynamic lifting capacity., Participants: 107,755 male and 23,078 female prospective workers taking part in a post-offer employment test., Methods: Subjects were tested for strength three standard static lifts and attained physical maxima for four dynamic lifts., Results: The data confirms modest correlations between isometric and dynamic measures. However, the standard errors of estimate for all isometric-to-dynamic predictions make such predictions meaningless for the practical purpose for which they are most commonly used., Conclusions: The Static Leg Lift, Static Arm Lift and Static Back (Torso) Lift are not appropriate for making predictions relative to dynamic lifting capacity. Given the likely degree of error in such predictions, and in light of potential safety concerns as reported by previous investigators, employers, clinicians and risk managers now have substantial objective evidence to call such testing into question.

Objectives: 1. To determine if scores on pain questionnaires and overt behaviors during a functional capacity evaluation (FCE) were related to variability between repeated measures during a hand strength assessment. 2. To determine if failure of statistically-based validity criteria, as proposed by Schapmire, St. James and Townsend et al. [26] is likely to be due to pain., Participants: 200 consecutive clients presenting for an FCE., Methods: Subjects filled out pain questionnaires, were observed for various behaviors and were administered the distraction-based hand strength assessment., Results: Clients failing two or more of the statistically-based validity criteria had higher scores on most pain questionnaires, presented with a higher frequency of various pain behaviors (p < 0.05 and < 0.001, respectively), and had a lower rate of relevant surgeries (p < 0.001). There was no statistically significant difference in the number of failed validity criteria between this group of clients and for normal subjects feigning weakness in a controlled study (p> 0.05)., Conclusions: Pain does not reasonably explain the failure of the statistically-based validity criteria. The protocol is appropriate for use in a client population.

Recent estimates suggest that 31% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 24% of children with ASD exhibit subthreshold clinical ADHD symptoms. Presence of ADHD symptoms in the context of ASD could have a variety of effects on cognition, autistic traits, and adaptive/maladaptive behaviors including: exacerbating core ASD impairments; adding unique impairments specific to ADHD; producing new problems unreported in ASD or ADHD; having no clear impact; or producing some combination of these scenarios. Children with ASD and co-morbid ADHD symptoms (ASD+ADHD; n = 21), children with ASD without ADHD (ASD; n = 28), and a typically developing control group (n = 21) were included in the study; all groups were matched on age, gender-ratio, IQ, and socioeconomic status. Data were collected on verbal and spatial working memory, response inhibition, global executive control (EC), autistic traits, adaptive functioning, and maladaptive behavior problems. In this sample, the presence of ADHD symptoms in ASD exacerbated impairments in EC and adaptive behavior and resulted in higher autistic trait, and externalizing behavior ratings. ADHD symptoms were also associated with greater impairments on a lab measure of verbal working memory. These findings suggest that children with ASD+ADHD symptoms present with exacerbated impairments in some but not all domains of functioning relative to children with ASD, most notably in adaptive behavior and working memory. Therefore, ADHD may moderate the expression of components of the ASD cognitive and behavioral phenotype, but ASD+ADHD may not represent an etiologically distinct phenotype from ASD alone.

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.

We have previously shown that exposure to exogenous androgens causes female sticklebacks (Gasterosteus aculeatus) to produce the glue protein, spiggin, in their kidneys. This protein can be quantified by an enzyme-linked immunosorbent assay developed and validated at the Centre for Environment, Fisheries and Aquaculture Science. Here we report the development of an in vivo test for the detection of environmental antiandrogens. The system involves the simultaneous exposure of female sticklebacks to 17alpha-methyltestosterone (a model androgen) at 500 ng/L and suspected environmental antiandrogens over a period of 21 days. The spiggin content of the kidneys is then measured, and any antiandrogenic activity is evaluated by comparing the spiggin levels of female fish exposed to antiandrogens to those of female fish exposed solely to the model androgen. The assay detects the antiandrogenic activity of flutamide, vinclozolin (both used at 250 microg/L), linuron (at 150 microg/L), and fenitrothion (at 15 and 150 microg/L). These results provide the first evidence of in vivo antiandrogenic activity of both linuron and fenitrothion in teleosts. Although there are other suggested fish species that could be used for this purpose, the stickleback is the only widely available species in which it is now possible to study both estrogenic and antiandrogenic end points in the same individual. Furthermore, the species is endemic and ubiquitous in Europe, and it possesses many ecological traits that make it better suited than other potential species for field research into endocrine disruption.

Renal cell carcinoma (RCC) not uncommonly presents with metastases and causes diagnostic difficulty to the cytopathologist who is involved in the initial diagnostic workup of tumors with an unknown primary site. RCC marker (RCC Ma) recognizes a human proximal tubule antigen and was shown to have high specificity and relatively low sensitivity in preliminary studies on routinely processed tissue sections. We investigated the diagnostic usefulness of RCC Ma immunohistochemically in fine-needle aspiration (FNA) samples. A total of 34 FNA samples obtained from the following carcinomas were used: 7 RCCs, 5 metastatic RCCs, 4 hepatocellular carcinomas, 2 non-small cell carcinomas of the lung, 3 metastatic non-small cell carcinomas of the lung, 4 invasive ductal carcinomas of the breast, 2 pancreatic ductal adenocarcinomas, 4 metastatic transitional cell carcinomas of the urinary bladder, and 3 metastatic colon carcinomas. Routinely processed cell block sections of FNA specimens were stained with RCC Ma by using routine immunohistochemistry. Presence and distribution of staining were evaluated. Two of 7 (29%) primary and 2 of 5 (40%) metastatic RCCs showed immunoreactivity in less than 50% of carcinoma cells. Staining was focal, cytoplasmic, and granular. Scattered positive cells were present in two of the four hepatocellular carcinomas. All breast, lung, pancreas, colon, and transitional cell carcinomas were negative. RCC antibody has a low sensitivity (33%), most likely because of its focal staining pattern, and a high specificity (91%) in FNA specimens. Immunoreactivity in metastatic carcinoma of an unknown primary site, especially as part of a panel of antibodies, is useful in diagnostic cytopathology. RCC antibody has not been studied in hepatocellular carcinoma, and the significance of positivity observed in some of our cases is unclear.

The detection of feigned weakness in hand grip strength assessment is difficult. The authors review several proposed methods and their weaknesses. A comparison of unilateral testing and simultaneous bilateral testing with the Jamar dynamometer and the Baseline pinch gauge is demonstrated as a solution. An experiment involved 100 asymptomatic subjects who were tested twice, once under instructions to give a full effort and once under instructions to feign weakness. Seven statistical criteria of noncompliance were chosen. Defining noncompliance as failing two or more of the seven criteria, 99% of the instructed noncompliant subjects were correctly classified as noncompliant. No subjects were incorrectly classified as noncompliant during instructed compliant testing. Twelve subjects failed on a single criterion. On retesting, all but one were correctly classified. One subject in the instructed noncompliant group passed all criteria. Accuracy was 99.5%, including retesting of the 12 "gray-zone" subjects.

For years the Division of Radiation Protection (DRP) has participated in exercises, which are required by the Federal Emergency Management Agency (FEMA) to demonstrate our ability to deal with an accident at a nuclear power plant. These demonstrations are defined by objectives and are structured such that they offer little opportunity to practice for real-world radiological events in the exercise. Since real-world radiological incidents do occur throughout the year, this exercise was designed to be as realistic as possible. A scrap yard incident was chosen as the most probable type of event. The exercise was conducted on May 5 and 6, 1999.

The effect of high-pressure treatment (HPT) on the droplet-size distribution and small-deformation rheology of oil-in-water emulsions containing beta-lactoglobulin and a nonionic surfactant or sodium caseinate has been investigated at neutral pH. Addition of Tween 20 (polyoxyethylenesorbitan monolaurate) to a beta-lactoglobulin-stabilized emulsion results in competitive displacement of the adsorbed globular protein film and, following HPT, the formation of a less flocculated emulsion. The age of the beta-lactoglobulin-stabilized emulsion prior to addition of sodium caseinate influences the competitive adsorption behavior. The strengthening of the beta-lactoglobulin layer with time makes it more resistant to disruption by sodium caseinate. The level of pressure-induced flocculation of beta-lactoglobulin-coated oil droplets depends on the intensity of processing conditions and on the degree of interfacial displacement. In contrast, beta-lactoglobulin added after emulsification appears to show little evidence of competitive adsorption behavior at the caseinate oil-water interface. Changes in the rheological properties of these latter systems following HPT can be attributed to pressure-induced denaturation and gelation of beta-lactoglobulin in the continuous phase of the emulsion.

A cloned strain of Cydia pomonella granulovirus, CpGV-M1, was obtained using successive rounds of an in vivo limiting dilution method. A detailed physical map of the genome was constructed using 11 restriction enzymes. The region containing the granulin gene and an open reading frame immediately upstream of the granulin gene was sequenced. This region showed a high degree of homology to the equivalent region from Cryptophlebia leucotreta granulovirus with 98% amino acid identity for the granulins and 68% identity for the putative polypeptides encoded by the upstream ORFs. These latter polypeptides contained two zinc finger-like motifs and showed a low degree of homology to ME53 from Autographa californica nucleopolyhedrovirus (AcMNPV). Evidence is presented for a similar upstream ORF in Artogeia rapae GV also. Hybridization studies showed that the CpGV genome had a similar overall organization to the Artogeia rapae GV genome. Hybridization between CpGV and AcMNPV was limited to fragments spanning about 15% of each genome suggesting that very few genes are highly conserved between GVs and NPVs.

Antibodies specific to the dopamine D2 receptor have been raised in rabbits using synthetic peptides. The resulting antiserum was sensitive to picogram quantities of peptide as measured by enzyme-linked immunoassay and was shown to have a 33% cross-reactivity with partially purified D2 receptor protein. No detectable cross-reactivity with similarly prepared fungal membranes was observed. D2 receptor preparations from normal rat pituitary cells were used in Western blot analysis. Bands of M(r) = 95,000 and 34,000 were detected in these preparations with a third faint band at 120,000. These correspond to the pituitary D2 receptor.

The purpose of this study was to relate the two-hand (manual) and instrument tie techniques with the ultimate security of granny and square knots constructed in multifilament and monofilament nylon sutures. Instrument-tie technique constructed secure granny and square knots, which failed by breakage rather than slippage. Similarly, two-hand (manual) tie techniques constructed square knots, which achieved knot security, failing only by breakage. In contrast, knot security was not reliably achieved with granny knots constructed by the two-hand (manual) tie techniques, with the knots frequently failing by slippage.

Three experiments are detailed which indicate the usefulness of the frequency of double responses (DRs) as an indicant of response conflict, in addition to the usual RT measures. DRs are responses on which an initial (often partial) error response is made that is rapidly amended to a correct response. Such responses occur most frequently in stimulus conditions where response conflict is expected by theory to be present and is indicated by changes in RT. Partial activation of competing responses has been demonstrated before using physiological measures (Coles, Gratton, Bashore, C. W. Eriksen, & Donchin, 1985; C. W. Eriksen, Coles, Morris, & O'Hara, 1985) when both responses could physically be made at the same time. DRs seem to be an equivalent type of movement when the subject cannot physically make but one movement at a time. The usefulness of this index of response conflict lies in its ease of implementation.

As a test of a consolidation theory of reminiscence, 150 female college students practiced inverted-alphabet printing and the pursuit rotor for 5 min., rested for 20 min., and then practiced for 2 more min. During the rest period, some subjects rested while others performed reverse-cue rotary pursuit or mirror tracing. No reduction in reminiscence produced by tasks occurring during the rest period was found. While the failure to support a consolidation theory of reminiscence could not be explained, the possibility of sex differences in response to tasks occurring during the rest period was discussed.