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Research has shown that inhalation of pure oxygen is effective in aborting cluster headache. This article advances the hypothesis that cooling is the critical ingredient behind the effectiveness of oxygen inhalation, rather than the oxygen concentration. To test this hypothesis, eight cluster headache participants used a device that delivered cooled room air as a means to abort headache attacks. Additionally, six of the subjects administered pure oxygen so that comparisons could be made to the air-cooling device. The proportion of cases in which subjects attained effective relief from cluster headache pain by use of the air-cooling device was significantly higher than the proportion of cases in which subjects did not attain effective relief from headache pain. There was no significant difference between the proportion of headaches relieved by oxygen and the proportion of headaches relieved by the air-cooling device. This study raises questions about the mechanisms of action of oxygen inhalation for treating cluster headache, and indicates that future clinical investigations into the use of cold room air for treating cluster headache pain are warranted. [ABSTRACT FROM AUTHOR]

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two-stage initiation-promotion models and induces cell proliferation and development of enzyme-altered hepatic foci. It is believed that increased cell proliferation is a necessary step in carcinogenesis. Therefore, the analysis of the effect of TCDD on cell proliferation in rat liver may aid in the understanding of the mechanism of hepatocarcinogenesis induced by TCDD. The aim of this study was to investigate the time course and reversibility of cell proliferation in non-initiated and diethylnitrosamine-initiated female rats exposed biweekly to a daily averaged dose of 125 ng TCDD/kg/day for up to 60 weeks. In addition we evaluated the suitability of different dose metrics for the evaluation of TCDD-induced changes in cell proliferation and CYP1A1 enzyme induction. Cell proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into hepatocytes undergoing replicative DNA synthesis. Mean BrdU labeling indices in TCDD-treated animals were not increased over controls after 14 weeks exposure, but were increased 8- and 2-fold after 30 and 60 weeks' treatment respectively, despite similar liver levels of TCDD at all these times (23-30 p.p.b.). In comparison, CYP1A1 activity, as measured by ethoxyresorufin deethylase activity, was significantly induced at all times points analyzed. Sixteen weeks following cessation of TCDD treatment, labeling indices were still significantly elevated over controls, but after 30 weeks of withdrawal, labeling indices were no different from controls, indicating that TCDD-induced changes in cell proliferation were reversible. Dosimetric analysis indicated that rat liver tissue burden was suitable for prediction of CYP1A1 expression but not cell proliferation and that the area under the curve was unsuitable for prediction of both TCDD-induced changes in CYP1A1 expression and cell proliferation. [ABSTRACT FROM PUBLISHER]

Background: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children., Objective: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control., Methods: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3)., Results: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (r s 2 = 0.584)., Conclusion: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL., Trial Registration: ClinicalTrials.gov Identifier: NCT02809677., Competing Interests: Disclosures Dr Brown reports serving on an advisory board for Medscape/WebMD. The other authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: This study updates the American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention., Methods: This was a secondary analysis of a multicenter retrospective study including patients with high-grade renal trauma from seven level 1 trauma centers from 2013 to 2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed-effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST OIS., Results: Based on the 2018 OIS grading system, we included 549 patients with AAST grades III to V injuries and computed tomography scans (III, 52% [n = 284]; IV, 45% [n = 249]; and V, 3% [n = 16]). Among these patients, 89% experienced blunt injury (n = 491), and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded, and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from grade IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC, 0.805; revised AUC, 0.883; p = 0.001) and number of units of packed red blood cells transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention., Conclusion: A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system., Level of Evidence: Diagnostic Test/Criteria; Level III., (Copyright © 2024 American Association for the Surgery of Trauma.)

Lys ubiquitination is catalysed by E3 ubiquitin ligases and is central to the regulation of protein stability and cell signalling in normal and disease states. There are gaps in our understanding of E3 mechanisms, and here we use protein semisynthesis, chemical rescue, microscale thermophoresis and other biochemical approaches to dissect the role of catalytic base/acid function and conformational interconversion in HECT-domain E3 catalysis. We demonstrate that there is plasticity in the use of the terminal side chain or backbone carboxylate for proton transfer in HECT E3 ubiquitin ligase reactions, with yeast Rsp5 orthologues appearing to be possible evolutionary intermediates. We also show that the HECT-domain ubiquitin covalent intermediate appears to eject the E2 conjugating enzyme, promoting catalytic turnover. These findings provide key mechanistic insights into how protein ubiquitination occurs and provide a framework for understanding E3 functions and regulation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one-third of the human genome through a 'copy and paste' mechanism catalysed by its multifunctional enzyme, open reading frame 2 protein (ORF2p) 1 . ORF2p reverse transcriptase (RT) and endonuclease activities have been implicated in the pathophysiology of cancer 2,3 , autoimmunity 4,5 and ageing 6,7 , making ORF2p a potential therapeutic target. However, a lack of structural and mechanistic knowledge has hampered efforts to rationally exploit it. We report structures of the human ORF2p 'core' (residues 238-1061, including the RT domain) by X-ray crystallography and cryo-electron microscopy in several conformational states. Our analyses identified two previously undescribed folded domains, extensive contacts to RNA templates and associated adaptations that contribute to unique aspects of the L1 replication cycle. Computed integrative structural models of full-length ORF2p show a dynamic closed-ring conformation that appears to open during retrotransposition. We characterize ORF2p RT inhibition and reveal its underlying structural basis. Imaging and biochemistry show that non-canonical cytosolic ORF2p RT activity can produce RNA:DNA hybrids, activating innate immune signalling through cGAS/STING and resulting in interferon production 6-8 . In contrast to retroviral RTs, L1 RT is efficiently primed by short RNAs and hairpins, which probably explains cytosolic priming. Other biochemical activities including processivity, DNA-directed polymerization, non-templated base addition and template switching together allow us to propose a revised L1 insertion model. Finally, our evolutionary analysis demonstrates structural conservation between ORF2p and other RNA- and DNA-dependent polymerases. We therefore provide key mechanistic insights into L1 polymerization and insertion, shed light on the evolutionary history of L1 and enable rational drug development targeting L1., (© 2023. The Author(s).)

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring., Significance: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 μL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489., (©2023 The Authors; Published by the American Association for Cancer Research.)

Management of patients who are acutely intoxicated with methamphetamine (a member of the substituted amphetamine class of drugs) can be resource-intensive for most emergency departments. Clinical presentations of the methamphetamine sympathomimetic toxidrome range from mild agitation to rhabdomyolysis, acute kidney injury, seizures, and intracranial hemorrhage. High-quality evidence on how to best manage these patients is lacking, and most research focuses on symptomatic interventions to control patients' agitation and hemodynamics. This review analyzes the best available evidence on the diagnosis and management of emergency department patients with substituted amphetamine toxicity and offers best-practice recommendations on treatment and disposition.

Purpose: To investigate management trends for American Association for the Surgery of Trauma (AAST) grade V renal trauma with focus on non-operative management., Methods: We used prospectively collected data as part of the Multi-institutional Genito-Urinary Trauma Study (MiGUTS). We included patients with grade V renal trauma according to the AAST Injury Scoring Scale 2018 update. All cases submitted by participating centers with radiology images available were independently reviewed to confirm renal trauma grade. Management was classified as expectant, conservative (minimally invasive, endoscopic or percutaneous procedures), or operative (renal-related surgery)., Results: Eighty patients were included, 25 of whom had complete imaging and had independent confirmation of AAST grade V renal trauma. Median age was 35 years (Interquartile range (IQR) 25-50) and 23 (92%) had blunt trauma. Ten patients (40%) were managed operatively with nephrectomy. Conservative management was used in nine patients (36%) of which six received angioembolization and three had a stent or drainage tube placed. Expectant management was followed in six (24%) patients. Transfusion requirements were progressively higher with groups requiring more aggressive treatment, and injury characteristics differed significantly across management groups in terms of hematoma size and laceration size. Vascular contrast extravasation was more likely in operatively managed patients though a statistically significant association was not found., Conclusion: Successful use of nonoperative management for grade V injuries is used for a substantial subset of patients. Lower transfusion requirement and less severe injury radiologic phenotype appear to be important characteristics delineating this group., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Depression is common in caregivers of children with asthma and is associated with poor outcomes in their child. No prior studies have longitudinally examined caregiver depression remission as a predictor of improvement in child asthma control., Objective: This 2-site study examined whether the proportion of time a caregiver was in depression remission predicted subsequent child asthma control at exit., Method: Caregivers (n = 205) with current major depressive disorder and their children, ages 7 to 17, with persistent asthma were observed every 4 weeks for 52 weeks. Caregiver depressive symptoms were measured using the 17-item Hamilton Rating Scale for Depression (HRSD). Child asthma was assessed with the (Childhood) Asthma Control Test (cACT/ACT) and spirometry, and depression with the Children's Depression Inventory (CDI). Linear regression analyses were conducted with change in cACT/ACT, CDI, and forced expiratory volume in 1 second (FEV 1 )% predicted as outcomes and proportion of time the caregiver was in remission (HRSD score ≤ 7) as the predictor. Multilevel mediation analyses examined the role of child depressive symptoms and asthma controller medication adherence., Results: Children were, on average, 54.1% female and 11 years old. Caregiver proportion of time in HRSD-assessed remission of depression was a significant predictor of improvement in cACT/ACT, CDI, and FEV 1 % predicted. Child CDI score, but not medication adherence, mediated the relationship between caregiver HRSD scores and child asthma control scores., Conclusions: Improvement in caregiver depression positively influences child asthma outcomes partially through improvement in child depressive symptom severity. Caregiver depression screening and treatment might lead to improvement in child asthma outcomes., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Child asthma disparities are prevalent in socio-economically stressed single-parent families. Stress impacts childhood asthma mediated by immune and autonomic pathways, but specific family stress pathways are not well established. This study tests the hypothesis, derived from a version of the Biobehavioral Family Model, that single parent maternal depression impacts child asthma mediated by insecure attachment and child depression., Methods: In a cross-sectional study, children with asthma (age 7-17 years old) from a socio-economically disadvantaged population and their single parent mothers (N = 202) were assessed for depression and attachment security. Child asthma disease activity was assessed by symptom report and lung function tests. Structural equation modeling (SEM) was used to test a model in which caregiver depression impacts child asthma disease activity mediated by insecure attachment and child depression., Results: SEM results indicated that maternal depression statistically predicted child depression (β = 0.21, p < 0.01) and insecure mother-child attachment (β = 0.17, p < 0.05). In addition, insecure attachment statistically predicted child depression (β = 0.50, p < 0.001). Child depression mediated the adverse effects of maternal depression and insecure attachment on child asthma disease activity (β = 0.43, p < 0.01). There was no direct effect of insecure attachment on child asthma., Conclusion: In single-parent families, maternal depression may impact child asthma disease activity, mediated serially by insecure attachment and child depression. Longitudinal and/or intervention studies are needed to establish a causal effect. These findings suggest that caregiver depression and parent-child relationships may be important targets for family intervention. These interventions may help improve child asthma outcomes and reduce health disparities., (© 2022 The Authors. Family Process published by Wiley Periodicals LLC on behalf of Family Process Institute.)

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

The SARS-CoV-2 pandemic and vaccination campaign has illustrated the need for high throughput serological assays to quantitatively measure antibody levels. Here, we present a protocol for a high-throughput colorimetric ELISA assay to detect IgG antibodies against the SARS-CoV-2 spike protein. The assay robustly distinguishes positive from negative samples, while controlling for potential non-specific binding from serum samples. To further eliminate background contributions, we demonstrate a computational pipeline for fitting ELISA titration curves, that produces an extremely sensitive antibody signal metric for quantitative comparisons across samples and time., Competing Interests: Competing interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. While performing this research, no company had invested in the research, and no commercialization was intended., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)

Objective: To test the hypothesis that undergoing nephrectomy after high-grade renal trauma is associated with higher mortality rates., Methods: We gathered data from 21 Level-1 trauma centers through the Multi-institutional Genito-Urinary Trauma Study. Patients with high-grade renal trauma were included. We assessed the association between nephrectomy and mortality in all patients and in subgroups of patients after excluding those who died within 24 hours of hospital arrival and those with GCS≤8. We controlled for age, injury severity score (ISS), shock (systolic blood pressure <90 mmHg), and Glasgow Coma Scale (GCS)., Results: A total of 1181 high-grade renal trauma patients were included. Median age was 31 and trauma mechanism was blunt in 78%. Injuries were graded as III, IV, and V in 55%, 34%, and 11%, respectively. There were 96 (8%) mortalities and 129 (11%) nephrectomies. Mortality was higher in the nephrectomy group (21.7% vs 6.5%, P <.001). Those who died were older, had higher ISS, lower GCS, and higher rates of shock. After adjusting for patient and injury characteristics nephrectomy was still associated with higher risk of death (RR: 2.12, 95% CI: 1.26-2.55)., Conclusion: Nephrectomy was associated with higher mortality in the acute trauma setting even when controlling for shock, overall injury severity, and head injury. These results may have implications in decision making in acute trauma management for patients not in extremis from renal hemorrhage., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Elongin complex was originally identified as an RNA polymerase II (RNAPII) elongation factor and subsequently as the substrate recognition component of a Cullin-RING E3 ubiquitin ligase. More recent evidence indicates that the Elongin ubiquitin ligase assembles with the Cockayne syndrome B helicase (CSB) in response to DNA damage and can target stalled polymerases for ubiquitylation and removal from the genome. In this report, we present evidence that the CSB-Elongin ubiquitin ligase pathway has roles beyond the DNA damage response in the activation of RNAPII-mediated transcription. We observed that assembly of the CSB-Elongin ubiquitin ligase is induced not just by DNA damage, but also by a variety of signals that activate RNAPII-mediated transcription, including endoplasmic reticulum (ER) stress, amino acid starvation, retinoic acid, glucocorticoids, and doxycycline treatment of cells carrying several copies of a doxycycline-inducible reporter. Using glucocorticoid receptor (GR)-regulated genes as a model, we showed that glucocorticoid-induced transcription is accompanied by rapid recruitment of CSB and the Elongin ubiquitin ligase to target genes in a step that depends upon the presence of transcribing RNAPII on those genes. Consistent with the idea that the CSB-Elongin pathway plays a direct role in GR-regulated transcription, mouse cells lacking the Elongin subunit Elongin A exhibit delays in both RNAPII accumulation on and dismissal from target genes following glucocorticoid addition and withdrawal, respectively. Taken together, our findings bring to light a new role for the CSB-Elongin pathway in RNAPII-mediated transcription., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pediatric asthma is associated with increased health services utilization, missed school days, and diminished quality of life. Children with asthma also report more frequent depressive and anxiety symptoms than children without asthma, which may further worsen asthma outcomes., Objective: The current study investigated the relationship between depressive and anxiety symptoms and 4 asthma outcomes (asthma control, asthma severity, lung function, and asthma-related quality of life) in children (N = 205) with moderate to severe persistent asthma., Methods: The data were analyzed using a canonical correlation analysis, a multivariate framework that allows examination of all variables of interest in the same model., Results: We found a statistically significant relationship between symptoms of depression and anxiety and asthma outcomes (1 - Λ = .372; P < .001). A large effect size suggests that 37.2% of variance is shared between depression and anxiety symptoms and 4 asthma outcomes (particularly asthma control and asthma-related quality of life) in the overall sample. Among girls (vs. boys), asthma control (measured by the Asthma Control Test) emerged as a stronger contributor to asthma outcomes compared with boys., Conclusions: These results suggest that psychiatric symptoms, especially anxiety, are associated with poor asthma-related quality of life, and more negative perception of asthma control in girls compared with boys (with no observed sex difference in physiological lung function). Clinicians should consider incorporating questions about psychiatric symptoms as part of routine asthma management, and focus patient education on unique differences in which boys and girls perceive their asthma symptoms., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS., Methods: Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values., Results: The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%., Conclusions: The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS., Competing Interests: R.K. is a scholar supported in part by the National Institutes of Health grant K12 DK0083014 and K23DK118209 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The authors have declared they have no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach., Materials and Methods: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications., Results: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01)., Conclusions: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

Background: Overweight/obesity (OV/OB) and depression have each been separately associated with worsened childhood asthma severity and control. Pathways by which these factors may jointly affect childhood asthma have not been elucidated., Objective: To examine the interrelationship of OV/OB and depressive symptoms with childhood asthma and explore associated psychobiologic pathways. The present study investigated whether comorbid OV/OB and depressive symptoms are associated with impaired baseline lung function and increased airway resistance during emotional stress, and to assess whether such effects may be mediated by autonomic nervous system (ANS) dysregulation, specifically through predominance of vagal over sympathetic reactivity (vagal bias)., Methods: A total of 250 children with asthma, aged 7 to 17, were assessed for OV/OB using body mass index, depressive symptoms using the Children's Depression Inventory (CDI), and asthma severity using National Asthma Education and Prevention Program Expert Panel Report 3 criteria. Baseline pulmonary function (forced expiratory volume in 1 second [FEV 1 ]) was assessed. The film "E.T. the Extra-Terrestrial" was used in a laboratory paradigm to evoke emotional stress/arousal. Airway resistance (R int ) was measured before and after the film to determine changes in airway function. ANS reactivity was assessed by measuring parasympathetic/vagal and sympathetic reactivity throughout the film., Results: In OV/OB children with asthma, depressive symptoms predicted lower baseline FEV 1 (β = -0.67, standard error [SE] = 0.24, P = .008), CDI predicted vagal bias under emotion stress/arousal (β = 0.27, SE = 0.09, P = .009), and vagal bias predicted increased R int (β = 3.55, SE = 1.54, P = .023)., Conclusion: This study is the first to link OV/OB and depressive symptoms in their relationship to childhood asthma. In OV/OB children with asthma, depression may potentiate airway compromise, mediated by vagal bias. Use of antidepressant and anticholinergic therapies should be studied in this subgroup of patients., (Published by Elsevier Inc.)

Background: In 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions., Methods: Data on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared., Results: Of the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34)., Conclusion: About one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions., Level of Evidence: Prognostic and Epidemiological Study, level III.

While machine learning has been making enormous strides in many technical areas, it is still massively underused in transmission electron microscopy. To address this, a convolutional neural network model was developed for reliable classification of crystal structures from small numbers of electron images and diffraction patterns with no preferred orientation. Diffraction data containing 571,340 individual crystals divided among seven families, 32 genera, and 230 space groups were used to train the network. Despite the highly imbalanced dataset, the network narrows down the space groups to the top two with over 70% confidence in the worst case and up to 95% in the common cases. As examples, we benchmarked against alloys to two-dimensional materials to cross-validate our deep-learning model against high-resolution transmission electron images and diffraction patterns. We present this result both as a research tool and deep-learning application for diffraction analysis., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Irradiation of low enriched uranium-molybdenum fuel results in the production and agglomeration of fission gas bubbles that can potentially lead to fuel failure. Manual point volume fraction counting in accordance with ASTME562 standard has been historically used to conduct pore size distribution analysis. While effective, the manual methodology is not efficient and therefore not feasible for the characterization of several fuel plates in a timely manner. In this contribution, ImageJ and MATLAB software were investigated as suitable alternatives to manual counting. Validation and verification were performed to show that the results are reproducible. Image analysis revealed insignificant variation of fission gas pore morphology with fission density. In addition, the results from two different sample preparation techniques - vibratory polishing and focused ion beam milling were compared. Sample preparation has more than 1% influence on the results of pore size distribution analysis. Comprehensive comparison identified vibratory polishing as the preferred method for conducting fission gas pore size distribution analysis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

While numerous gait families have been defined and studied for legged systems traversing level ground (e.g. walking, running, bounding, etc), formal distinctions have yet to be developed for dynamic gaits in the vertical regime. Recognition and understanding of different gait families has clear implications to control strategy, efficiency, and stability. While several climbing robotic systems have been described as achieving 'running' behaviors on vertical surfaces, the question of whether distinct dynamic gaits exist and what differentiates these gaits has not been rigorously explored. In this paper, by applying definitions developed in the horizontal regime to simulation and experimental data, we show evidence of three distinct dynamic climbing gaits families and discuss the implications of these gaits on the development of more advanced climbing robots.

Objective: To review the literature regarding the effects of caregiver depression on childhood asthma and integrate the findings into a multilevel model of pathways by which these effects occur to further the understanding of the complex biopsychosocial nature of childhood asthma and the key role that is played by caregiver depression., Data Sources: PubMed was searched for articles published from 2007 to the present (10-year search), and Google Scholar was searched for articles published in 2017 and 2018 to identify the most recent publications., Study Selections: Studies selected were recent, empirical, or meta-analytic, conducted in humans, and had specific relevance to one or more of the identified pathways. Articles published before 2007 were included if deemed essential because they addressed key pathways, for which there were no more recent articles., Results: Review of the literature substantiates that caregiver depression plays a key role in the socioeconomic, familial, psychological, and biological cascade of effects on childhood asthma. Childhood asthma outcomes are affected indirectly by socioeconomic status and family stress mediated by caregiver depression, which affects disease management, and/or stress and depression in the child, which, in turn, affect asthma through alterations in immune modulation and autonomic regulation., Conclusion: Findings indicate that future research should concentrate on mediators and moderators to further clarify the complex interplay of these factors that affect childhood asthma. The findings also have substantial translational implications. Given that child stress and depression contribute to asthma disease activity and that treating caregiver depression improves child stress and depression, there is strong rationale for treating depressed caregivers of children with asthma as a component means of improving childhood asthma control., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: Weakened pelvic floor support is believed to be the main cause of various pelvic floor disorders. Modern theories of pelvic floor support stress on the structural and functional integrity of multiple structures and their interplay to maintain normal pelvic floor functions. Connective tissues provide passive pelvic floor support while pelvic floor muscles provide active support through voluntary contraction. Advanced modern medical technologies allow us to comprehensively and thoroughly evaluate the interaction of supporting structures and assess both active and passive support functions. The pathophysiology of various pelvic floor disorders associated with pelvic floor weakness is now under scrutiny from the combination of (1) morphological, (2) dynamic (through computational modeling), and (3) neurophysiological perspectives. This topical review aims to update newly emerged studies assessing pelvic floor support function among these three categories., Recent Findings: A literature search was performed with emphasis on (1) medical imaging studies that assess pelvic floor muscle architecture, (2) subject-specific computational modeling studies that address new topics such as modeling muscle contractions, and (3) pelvic floor neurophysiology studies that report novel devices or findings such as high-density surface electromyography techniques. We found that recent computational modeling studies are featured with more realistic soft tissue constitutive models (e.g., active muscle contraction) as well as an increasing interest in simulating surgical interventions (e.g., artificial sphincter). Diffusion tensor imaging provides a useful non-invasive tool to characterize pelvic floor muscles at the microstructural level, which can be potentially used to improve the accuracy of the simulation of muscle contraction. Studies using high-density surface electromyography anal and vaginal probes on large patient cohorts have been recently reported. Influences of vaginal delivery on the distribution of innervation zones of pelvic floor muscles are clarified, providing useful guidance for a better protection of women during delivery. We are now in a period of transition to advanced diagnostic and predictive pelvic floor medicine. Our findings highlight the application of diffusion tensor imaging, computational models with consideration of active pelvic floor muscle contraction, high-density surface electromyography, and their potential integration, as tools to push the boundary of our knowledge in pelvic floor support and better shape current clinical practice.

Background: Chikungunya virus (CHIKV) is transmitted via mosquito bite and potentially by aerosol, causing chikungunya fever and arthritic disease in humans. There are currently no licensed vaccines or antiviral therapeutics to protect against CHIKV infection in humans. Animal models recapitulating human disease, especially for transmission by aerosol, are needed for licensure of such medical countermeasures., Methods: Cynomolgus macaques (CMs) were challenged by intradermal (ID) inoculation or exposure to an aerosol containing CHIKV Ross strain at different target infectious doses (10 3 -10 7 plaque forming units (PFU)). The clinical and virologic courses of disease were monitored up to 14 days post-exposure., Results: ID infection of CMs led to overt clinical disease, detectable viremia, and increased blood markers of liver damage. Animals challenged by aerosol exhibited viremia and increased liver damage biomarkers with minimal observed clinical disease. All animals survived CHIKV challenge., Conclusions: We have described CHIKV infection in CMs following ID inoculation and, for the first time, infection by aerosol. Based on limited reported cases in the published literature, the aerosol model recapitulates the virologic findings of human infection via this route. The results of this study provide additional evidence for the potential use of CMs as a model for evaluating medical countermeasures against CHIKV.

As mobile robots become more commonly utilized in everyday applications, the tasks they are given will often require them to quickly traverse unprepared and varied environments. While traditional mobile platforms may falter under such conditions, animals utilize distinct locomotion modalities such as running, jumping, or climbing, to adroitly negotiate a wide variety of challenging and changing terrains. Due to limitations including available on-board power, legged robots have struggled to match the speed of these animals, even in a single mode of transport. In this paper we experimentally investigate the synergies and trade-offs in developing a dynamical legged robot capable of both running and climbing. We utilize bio-inspired 'templates' or reduced-order models of motion to identify how the dynamics change from running to climbing and seek to identify a minimal set of robotic adjustments necessary to switch locomotion modalities. This template-based design methodology is explained and the resultant robot behavior in each domain is characterized. We show that using a trotting gait, the platform demonstrates running speeds of up to 0.67 ms(-1) on level ground and climbing speeds of up to 0.43 ms(-1)on near-vertical surfaces (and up to 0.16 ms(-1) on vertical surfaces) while exhibiting dynamical behaviors comparable to that of the inspirational models.

Asthma is the most common chronic disease in children. Despite dramatic advances in pharmacological treatments, asthma remains a leading public health problem, especially in socially disadvantaged minority populations. Some experts believe that this health gap is due to the failure to address the impact of stress on the disease. Asthma is a complex disease that is influenced by multilevel factors, but the nature of these factors and their interrelations are not well understood. This paper aims to integrate social, psychological, and biological literatures on relations between family/parental stress and pediatric asthma, and to illustrate the utility of multilevel systemic models for guiding treatment and stimulating future research. We used electronic database searches and conducted an integrated analysis of selected epidemiological, longitudinal, and empirical studies. Evidence is substantial for the effects of family/parental stress on asthma mediated by both disease management and psychobiological stress pathways. However, integrative models containing specific pathways are scarce. We present two multilevel models, with supporting data, as potential prototypes for other such models. We conclude that these multilevel systems models may be of substantial heuristic value in organizing investigations of, and clinical approaches to, the complex social-biological aspects of family stress in pediatric asthma. However, additional systemic models are needed, and the models presented herein could serve as prototypes for model development., (© 2015 Family Process Institute.)

Animals have demonstrated the ability to move through, across and over some of the most daunting environments on earth. This versatility and adaptability stems from their capacity to alter their locomotion dynamics and employ disparate locomotion modalities to suit the terrain at hand. As with modalities such as running, flying and swimming, dynamic climbing is commonly employed by legged animals, allowing for rapid and robust locomotion on vertical and near-vertical substrates. While recent robotic platforms have proven effective at anchoring reduced-order, dynamic climbing models, its adoption as a common modality for multi-modal, legged platforms remains nascent. In this work, we explore several of the open questions related to the physical implementation of dynamic climbing, including investigation of substrate inclinations for which dynamic climbing is suited, mitigation of destabilizing out-of-plane dynamics and improvement of attachment reliability in the presence of dynamic effects. The results from these inquiries provide several mechanisms and approaches for increasing the reliability and versatility of dynamic climbing as a dynamic legged modality. With these and other developments into legged locomotion modalities, future multi-modal platforms will begin to approach the expertise of biological creatures at moving through a complex and challenging world.

Beginning in 2007, a program was established at the Idaho National Laboratory to update key capabilities enabling microstructural and micro-chemical characterization of highly irradiated and/or radiologically contaminated nuclear fuels and materials at scales that previously had not been achieved for these types of materials. Such materials typically cannot be contact handled and pose unique hazards to instrument operators, facilities, and associated personnel. Over the ensuing years, techniques have been developed and operational experience gained that has enabled significant advancement in the ability to characterize a variety of fuel types including metallic, ceramic, and coated particle fuels, obtaining insights into in-reactor degradation phenomena not achievable by any other means. The following article describes insights gained, challenges encountered, and provides examples of unique results obtained in adapting dual beam FIB technology to nuclear fuels characterization., (Published by Elsevier Ltd.)

The Legionella species have been identified as important waterborne pathogens in terms of disease morbidity and mortality. Microbial exposure assessment is a tool that can be utilized to assess the potential of Legionella species inhalation exposure from common water uses. The screening-level exposure assessment presented in this paper developed emission factors to model aerosolization, quantitatively assessed inhalation exposures of aerosolized Legionella species or Legionella species surrogates while evaluating two generalized levels of assumed water concentrations, and developed a relative ranking of six common in-home uses of water for potential Legionella species inhalation exposure. Considerable variability in the calculated exposure dose was identified between the six identified exposure pathways, with the doses differing by over five orders of magnitude in each of the evaluated exposure scenarios. The assessment of exposure pathways that have been epidemiologically associated with legionellosis transmission (ultrasonic and cool mist humidifiers) produced higher estimated inhalation exposure doses than pathways where epidemiological evidence of transmission has been less strong (faucet and shower) or absent (toilets and therapy pool). With consideration of the large uncertainties inherent in the exposure assessment process used, a relative ranking of exposure pathways from highest to lowest exposure doses was produced using culture-based measurement data and the assumption of constant water concentration across exposure pathways. In this ranking, the ultrasonic and cool mist humidifier exposure pathways were estimated to produce the highest exposure doses, followed by the shower and faucet exposure pathways, and then the toilet and therapy pool exposure pathways., (Published by Elsevier Ltd.)

Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC 50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, rapid quantitative pharmacodynamic imaging reliably estimates EC 50 from the simulated data, except when noise overwhelms the drug effect or when the effect occurs only at high doses. In preliminary fMRI studies of primate brain using a dopamine agonist, the observed noise level is modest compared with observed drug effects, and a quantitative EC 50 can be obtained from some regional time-signal curves. Taken together, these results suggest that research and clinical applications for rapid quantitative pharmacodynamic imaging are realistic.

In August 2010, the Minnesota Department of Agriculture and Minnesota Department of Health investigated an outbreak of six cases of Salmonella Newport infection occurring in northwestern Minnesota, which identified fresh blueberries as the cause. Initially, traditional traceback methods involving the review of invoices and bills of lading were used to attempt to identify the source of the outbreak. When these methods failed, novel traceback methods were used. Specifically, supplier-specific 12-digit Global Trade Item Numbers (GTINs) and shopper-card information were used to identify a single blueberry grower linked to cases, corroborating the results of a case-control study in which consuming fresh blueberries was statistically associated with illness (5 of 5 cases versus 8 of 19 controls, matched odds ratio [MOR] undefined, P = 0.02). Consuming fresh blueberries from retailer A was also statistically associated with illness (3 of 3 cases versus 3 of 18 controls, MOR undefined, P = 0.03). Based on initially incomplete evidence in this investigation, the invoices pointed to wholesaler A and grower A, based on first-in-first-out product rotation. However, when point-of-sale data were analyzed and linked to shopper-card information, a common GTIN was identified. This information led to an on-site record evaluation at retailer A, and the discovery of additional records at this location documented the supply chain from grower B to wholesaler C to retailer A, shifting the focus of the investigation from grower A to grower B. This investigation demonstrates the emerging concepts of Critical Tracking Events (CTEs) and Key Data Elements (KDE) related to food product tracing. The use of these shopper-cased data and the event data that were queried by investigators demonstrates the potential utility of consciously designed CTEs and KDEs at critical points in the supply chain to better facilitate product tracing.

Background: To characterize the patterns of presentation of adults with head injury to the Emergency Department., Methods: This is a cohort study that sought to collect injury and outcome variables with the goal of characterizing the very early natural history of traumatic brain injury in adults. This IRB-approved project was conducted in collaboration with our Institution's Center for Translational Science Institute. Data were entered in REDCap, a secure database. Statistical analyses were performed using JMP 10.0 pro for Windows., Results: The cohort consisted of 2,394 adults, with 40% being women and 79% Caucasian. The most common mechanism was fall (47%) followed by motor vehicle collision (MVC) (36%). Patients sustaining an MVC were significantly younger than those whose head injury was secondary to a fall (P < 0.0001). Ninety-one percent had CT imaging; hemorrhage was significantly more likely with worse severity as measured by the Glasgow Coma Score (chi-square, P < 0.0001). Forty-four percent were admitted to the hospital, with half requiring ICU admission. In-hospital death was observed in 5.4%, while neurosurgical intervention was required in 8%. For all outcomes, worse TBI severity per GCS was significantly associated with worse outcomes (logistic regression, P < 0.0001, adjusted for age)., Conclusion: These cohort data highlight the burden of TBI in the Emergency Department and provide important demographic trends for further research.

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 10(6) colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 10(2), 1 × 10(3), 1 × 10(4), and 1 × 10(5) CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 10(2), 1 × 10(3), and 1 × 10(4) CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days.

The Substance Abuse and Mental Health Services Administration has been instrumental in supporting the development and implementation of systems of care to provide services to children and youth with serious mental health conditions and their families. Since 1993, 173 grants have been awarded to communities in all 50 states, Puerto Rico, Guam, the District of Columbia, and 21 American Indian/Alaska Native communities. The system of care principles of creating comprehensive, individualized services, family-driven and youth-guided care and cultural and linguistic competence, supported by a well-trained and competent workforce, have been successful in transforming the field of children's mental health and facilitating the integration of child-serving systems. This approach has achieved positive outcomes at the child and family, practice and system levels, and numerous articles have been published using data collected from system of care communities, demonstrating the effectiveness of this framework. This article will describe lessons learned from implementing the system of care approach, and will discuss the importance of expanding and sustaining systems of care across the country.

Methyl methacrylate used in bone cements has drawbacks of toxicity, high exotherm, and considerable shrinkage. A new resin, based on silorane/oxirane chemistry, has been shown to have little toxicity, low exotherm, and low shrinkage. We hypothesized that silorane-based resins may also be useful as components of bone cements as well as other bone applications and began testing on bone cell function in vitro and in vivo. MLO-A5, late osteoblast cells, were exposed to polymerized silorane (SilMix) resin (and a standard polymerized bisGMA/TEGDMA methacrylate (BT) resin and compared to culture wells without resins as control. A significant cytotoxic effect was observed with the BT resin resulting in no cell growth, whereas in contrast, SilMix resin had no toxic effects on MLO-A5 cell proliferation, differentiation, nor mineralization. The cells cultured with SilMix produced increasing amounts of alkaline phosphatase (1.8-fold) compared to control cultures. Compared to control cultures, an actual enhancement of mineralization was observed in the silorane resin-containing cultures at days 10 and 11 as determined by von Kossa (1.8-2.0 fold increase) and Alizarin red staining (1.8-fold increase). A normal bone calcium/phosphate atomic ratio was observed by elemental analysis along with normal collagen formation. When used in vivo to stabilize osteotomies, no inflammatory response was observed, and the bone continued to heal. In conclusion, the silorane resin, SilMix, was shown to not only be non cytototoxic, but actually supported bone cell function. Therefore, this resin has significant potential for the development of a nontoxic bone cement or bone stabilizer., (Copyright © 2012 Wiley Periodicals, Inc.)

The Children's Mental Health Initiative (CMHI) is funded by the Center for Mental Health Services within the Substance Abuse and Mental Health Services Administration. CMHI assists communities in developing comprehensive, coordinated services for children with serious emotional disturbances and their families. Broadly speaking, these systems are designed to be child centered, youth guided, family driven, community based, and culturally competent. To assure implementation of the "youth-guided" core value in the national evaluation, an advisory group of youth coordinator/youth teams representing communities across the country was developed. This group chose the name YADA-Youth Advisors Driving Action. YADA has made a substantive contribution to national evaluation efforts by bringing the youth perspective and voice to its audience at the community and national levels. This article describes YADA's founding and development, as well as related implications for psychosocial nurses., (Copyright 2012, SLACK Incorporated.)

Traceback methods by state regulatory agencies were used to complement traditional epidemiological cluster investigation methods and confirmed hazelnuts (also referred to as filberts) as the vehicle in a multistate outbreak of Escherichia coli O157:H7 infections. Bulk in-shell hazelnut and mixed-nut purchase locations were identified during the initial epidemiological interviews. Based on purchase dates and case onset dates, regulators in Minnesota, Michigan, and Wisconsin traced product back through the supply chain. Six (86%) retail locations received the suspect hazelnut or mixed-nut shipments from a Minnesota distributor, with one retailer (14%) receiving products from a Wisconsin distributor. Both distributors received 100% of their bulk in-shell hazelnuts and mixed nuts from a distributor in California. The California distributor received 99% of their hazelnuts from a packing company in Oregon. The California distributor received the hazelnuts in 50-lb (22.7-kg) bags and either resold them without opening the bags or used the in-shell hazelnuts in the manufacture of their in-shell mixed nuts. Records at the packing company in Oregon were incomplete or lacked sufficient detail needed to identify a suspect farm or group of suspect farms. Laboratory samples collected from human cases and subsequently recalled product matched the outbreak pulsed-field gel electrophoresis subtype of E. coli O157:H7. Hazelnut harvesting practices create a plausible route of contamination from fecal matter from domestic ruminants or wild deer. This outbreak investigation demonstrates the use of product traceback data to rapidly test an epidemiological hypothesis.

We have synthesized a filler-reinforced silorane composite that has potential applications in orthopaedic surgery, such as for a bone stabilizer. The purpose of the present work was to develop a method for estimating four properties of this material; namely, maximum exotherm temperature, flexural strength, flexural modulus, and fracture toughness. The method involved the use of mixture design-of-experiments and regression analysis of results obtained using 23 formulations of the composite. We validated the estimation method by showing that, for each of four composite formulations that were not included in the method development, the value of each of the aforementioned properties was not significantly different from that obtained experimentally. Our estimation method has the potential for use in the development of a wide range of orthopaedic materials., (Copyright © 2011 Wiley Periodicals, Inc.)

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition., Competing Interests: The authors have declared that no competing interests exist.

This study tested a hypothesized model of the relationships among parental depressive symptoms, family process (interparental negativity and negative parenting behavior), child internalizing symptoms, and asthma disease activity. A total of 106 children with asthma, aged 7 to 17, participated with their fathers and mothers. Parental depressive symptoms were assessed by self-report. Interparental and parenting behaviors were observed and rated during family discussion tasks. Child internalizing symptoms were assessed by self-report and by clinician interview and rating. Asthma disease activity was assessed according to National Heart, Lung and Blood Institute guidelines. Results of structural equation modeling generally supported interparental negativity and negative parenting behavior as mediators linking parental depressive symptoms and child emotional and physical dysfunction. However, paternal and maternal depressive symptoms play their role through different pathways of negative family process. (PsycINFO Database Record (c) 2011 APA, all rights reserved).