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Plant–microbe interactions play crucial roles in species invasions but are rarely investigated at the intraspecific level. Here, we study these interactions in three lineages of a globally distributed plant, Phragmites australis. We use field surveys and a common garden experiment to analyze bacterial communities in the rhizosphere of P. australis stands from native, introduced, and Gulf lineages to determine lineage-specific controls on rhizosphere bacteria. We show that within-lineage bacterial communities are similar, but are distinct among lineages, which is consistent with our results in a complementary common garden experiment. Introduced P. australis rhizosphere bacterial communities have lower abundances of pathways involved in antimicrobial biosynthesis and degradation, suggesting a lower exposure to enemy attack than native and Gulf lineages. However, lineage and not rhizosphere bacterial communities dictate individual plant growth in the common garden experiment. We conclude that lineage is crucial for determination of both rhizosphere bacterial communities and plant fitness., Environmental factors often outweigh host heritable factors in structuring host-associated microbiomes. Here, Bowen et al. show that host lineage is crucial for determination of rhizosphere bacterial communities in Phragmites australis, a globally distributed invasive plant.

Purpose To evaluate the safety and efficacy of intravitreal administration of a steroid and antibiotics during cataract surgery compared with the typical postoperative topical regimen in preventing postoperative inflammation, pain, cystoid macular edema (CME), and endophthalmitis. Setting Private practice, Sioux Falls, South Dakota, USA. Design Retrospective case series. Methods The study group included eyes that had an intravitreal injection of triamcinolone–moxifloxacin–vancomycin at the time of cataract surgery with concomitant trabecular microbypass stent insertion. The control eyes had the same procedure but were prescribed topical antibiotics, steroids, and nonsteroidal antiinflammatory drugs postoperatively. Data were recorded preoperatively and 1 day, 1 week, 1 month, and 3 months postoperatively. Primary outcomes included the number of glaucoma medications, intraocular pressure (IOP), and IOP spikes of at least 15 mm Hg from baseline. Results There were 234 eyes in the study group and 249 eyes in the control group. The mean reduction in glaucoma medications was 0.24 drops in the study group and 0.80 drops in the control group 3 months postoperatively, whereas the mean IOP reduction was 2.59 mm Hg in the study group and 3.63 mm Hg in the control group. Pressure spikes were detected at 54 (5.7%) of 936 postoperative visits in the study group and at 37 (3.7%) of 996 visits in the control group. There were no cases of severe inflammation, CME, infection, or retinal detachments. Conclusions Both groups had similar postoperative pressure reductions and incidence of IOP spikes. The results indicate that intravitreal injections of a steroid and antibiotics might be a safe option for glaucomatous eyes having cataract surgery with trabecular microbypass stent insertion.

The eye and body are constantly exposed to a constant ambient pressure known as atmospheric pressure. At sea level, atmospheric pressure is approximately 760 mmHg. As one enters the deep-sea environment, the pressure of the water is added to the atmospheric pressure. The increased ambient pressure provides a unique environment for the eye.

Introduction: Topical corticosteroids are commonly prescribed for children with atopic dermatitis. Although generally well tolerated, long term unsupervised use can lead to ocular damage, including glaucoma. Much of the current literature focuses on the periorbital use in older patients. We present a case of an adolescent who suffered glaucomatous damage secondary to long term topical steroid use on her extremities. Methods: This is a case report of a child with extensive work-up for glaucoma suspect. Results: A 7-year-old African American female was found to have glaucomatous damage after using 2.5% hydrocortisone cream on her arms, legs, and back of neck twice daily continuously for 2 years. There were no other mechanisms that could have produced a secondary glaucoma. Congenital anomalous disk is a remote possibility. Discussion: Steroid cream use for atopic dermatitis is relatively common. The side effect profile of topical corticosteroids has been well documented and includes glaucoma. These patients may not have any visual symptoms, and can present at an advanced stage, with irreversible vision loss. Children with atopic dermatitis are especially susceptible to the systemic effects of steroids because of the damaged epithelial layer and also the body surface area to volume, both of which increase the bioavailability of the medication. Conclusion: Because topical steroids are commonly used, especially in children, patients need to be aware of the potentially dangerous side effects, including vision loss from glaucoma.

Introduction: The phase 3 international, randomized, double-blind ROBUST clinical trial (NCT02285062) compared progression-free survival between patients with previously untreated ABC-type DLBCL treated with placebo plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) versus lenalidomide + R-CHOP (R2-CHOP) for 6 21-day cycles. HRQoL, as measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EuroQoL 5-dimension 3-level (EQ-5D-3L) patient-reported questionnaires, was evaluated as a secondary endpoint for the 2 treatment arms. Methods: For each treatment group, FACT-Lym and EQ-5D-3L scores were measured at baseline (BL), mid-, end-of-treatment (EOT), and post-treatment, in 12-week intervals from Week 34 onward. Patients were evaluated if they had completed BL and ≥ 1 post-BL calculable FACT-Lym subscale measurements. Non-inferiority (NI) of R2-CHOP versus placebo-R-CHOP was measured for 4 key FACT-Lym subscales: Physical Well-Being (PWB), Additional Concerns (AC), Functional Well-Being (FWB), and Trial Outcome Index (TOI). NI was assessed at EOT (typically 3-4 weeks after completing Cycle 6) and at post-treatment follow-up at Week 34 by analysis of covariance (ANCOVA). The NI margins were prespecified as 1 less than the higher published minimal important difference (MID) for each subscale. Since a range of MIDs have been published, a more conservative value was also used as a sensitivity analysis. Time to improvement (TTI), using published responder definitions, was also assessed for the FACT-Lym subscales. EQ-5D-3L scores were summarized descriptively. Results: Demographic and baseline disease characteristics were balanced across the 2 treatment arms (N = 285 per arm). The percentage of patients who completed the FACT-Lym out of the expected population remained > 85% at all time points with > 50 patients still on the study in each treatment arm up to Week 142. Completion rates and reasons for missing assessments were balanced across the 2 treatment arms. FACT-Lym subscale scores were generally higher after EOT, similar for both treatment groups, and mean changes from BL were close to or above MID (where defined), except for the Social/Family Well-Being subscale. Mean differences in FACT-Lym TOI between treatment arms are shown in Table 1. As positive treatment differences favor R2-CHOP and -10 was the predefined NI margin, NI was demonstrated for the FACT-Lym TOI subscale at both EOT and Week 34 assessments. Superiority of R2-CHOP was demonstrated at EOT as the confidence interval (CI) lies completely above 0 (P < 0.04); however, this difference was not clinically meaningful. Furthermore, NI was also demonstrated when using the sensitivity analysis margin of -4.5. ANCOVA models were also fitted for the other key subscales of PWB, AC and FWB (Table 2). NI was demonstrated for all NI margins at both time points for the PWB and AC subscales. The FACT-Lym FWB subscale demonstrated NI for both margins at EOT and Week 34 for the primary NI margin of -2 based on the MID minus 1, but did not demonstrate NI when an NI margin of -1, based on an alternative published MID, was used. The TTI curves and associated summary statistics were similar for the 2 treatment arms, with a median TTI for the FACT-Lym TOI of 21 weeks (95% CI 15-22) for patients treated with R2-CHOP and 18 weeks (95% CI 15-22) for patients treated with placebo-R-CHOP. Mean EQ-5D-3L visual analogue scale (VAS) and Utility Index (UK weights) change from baseline scores were higher in both treatment arms and the mean changes were above, or close to, the published MID (7 for VAS, 0.1 for Utility Index) at EOT assessments. Prespecified sensitivity and subgroup analyses supported the conclusions from the primary HRQoL analyses. Conclusions: The predefined NI levels were met for the 4 key FACT-Lym subscales. Similar results were observed across the other HRQoL assessments, sensitivity, and subgroup analyses. Adding lenalidomide to the R-CHOP regimen did not adversely affect the HRQoL of patients with DLBCL as measured by FACT-Lym and EQ-5D-3L. These data serve as a benchmark for future clinical trials combining next-generation immunomodulatory drugs with standard R-CHOP to improve clinical efficacy while maintaining HRQoL in patients with DLBCL. HRQoL analyses should become an integral part of future clinical trials of novel combination regimens in DLBCL. Disclosures Chiappella: Roche: Speakers Bureau; Teva: Speakers Bureau; Servier: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau; Celgene: Other: advisory board, Speakers Bureau. Cocks:Adelphi Values: Employment; Amgen: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy; Endomag Ltd.: Consultancy. Greenwood:Adelphi Values: Employment. Williams:Adelphi Values: Employment. Scott:Celgene: Consultancy; Roche/Genentech: Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Janssen: Consultancy, Research Funding. Yamamoto:SymBio: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria; Sanofi: Honoraria; Astra-Zeneca: Consultancy, Research Funding; Sumitomo Dainippon: Honoraria; Chugai: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Gilead Sciences: Research Funding; Solasia Pharma: Research Funding; Bayer: Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; ARIAD: Research Funding; Pfizer: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Kyowa Kirin: Honoraria; MSD: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Research Funding; Meiji Seika Pharma: Consultancy, Honoraria; HUYA/IQVIA Services Japan: Consultancy, Honoraria; Novartis: Honoraria, Research Funding; Incyte: Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Jurczak:Bayer: Research Funding; Takeda: Research Funding; Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Incyte: Research Funding; Celgene Corporation: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celtrion: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding. Özcan:Sanofi: Other: Travel support; Abdi Ibrahim: Other: Travel support; BMS: Other: Travel support; Takeda: Honoraria, Other: Travel support, Research Funding; Archigen: Research Funding; Roche: Other: Travel support, Research Funding; Bayer: Research Funding; Janssen: Other: Travel support, Research Funding; Celgene Corporation: Research Funding, Travel support; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Novartis: Research Funding; Jazz: Other: Travel support; Amgen: Honoraria, Other: Travel support. Belada:Roche: Consultancy; Gilead Sciences: Consultancy; Takeda: Consultancy. Margunato-Debay:Celgene Corporation: Employment, Equity Ownership. Czuczman:Celgene Corporation: Employment, Equity Ownership. Zhai:Celgene Corporation: Employment, Equity Ownership. Braverman:Celgene Corporation: Employment. Vitolo:Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Background: Human leukocyte antigen (HLA) genes on chromosome 6p21 encode the major histocompatibility complex (MHC). MHC molecules are expressed on all nucleated cells and are essential to the immune system's ability to distinguish healthy native cells from foreign or abnormal ones. Specialized antigen presenting cells display MHC molecules loaded with foreign peptides to initiate T cell responses. HLA sequencing variability is critical to function; studies have shown even single allelic changes can alter the ability of MHC molecules to recognize cognate T cell receptors. Given the role of MHC molecules in identifying cells as "self", associations between HLA sequence variation and autoimmunity is a research focus. Like other autoimmune disorders, association between ITP and HLA genes has been investigated. Prior studies are limited by outdated HLA typing methods, genetically homogenous study populations, and lack of validation studies. Preexisting exome data has historically not been used to provide accurate HLA sequencing information given the polymorphic, highly repetitive sequence in this region. This study applied a novel bioinformatics pipeline, xHLA, to an existing set of whole exome sequencing in a cohort of chronic pediatric ITP patients. xHLA, reported by Xie et al. in 2017, yields high-resolution, two field HLA typing for HLA-A, -B, -C, -DQB1, -DPB1, and -DRB1. A prior genetic analysis of chronic ITP patient whole exome data identified a missense variant in BTNL2, a gene which plays a role in peripheral regulatory T cell induction. This variant (rs143211074) is upregulated in chronic ITP versus healthy controls (minor allele frequency= 4.17% in ITP v. 0.54% in controls, p=1.43x10-4). Linkage of rs143211074 and HLA alleles was examined in this study. Methods: Whole exome sequencing data for a cohort of 272 chronic ITP patients was processed using the xHLA method. In order to eliminate sequencing variability related to ethnicity alone, initial analyses were focused on Caucasians only (n=170), using Eigenvectors for principle components analysis. The frequency of individual HLA alleles and HLA haplotypes for Caucasians from the National Marrow Donor Program (NMDP) Be The Match Registry® were compared to the ITP cohort. HLA haplotypes were inferred using the NMDP HaploStats program. A chi-squared test was utilized to compare nonparametric categorical data using GraphPad Prism version 8.0.1 for Windows, GraphPad Software, San Diego, California, USA, www.graphpad.com. A Bonferroni correction was applied and a p-value of Results: 12 HLA alleles had increased frequency in the chronic ITP cohort versus controls. (Table 1) The BTNL2 variant, rs143211074, was found in linkage disequilibrium with the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype. Of the 10 patients heterozygous for the variant allele, 80% had the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype. Both patients homozygous for rs143211074 were also homozygous for the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype. In the entire cohort, this haplotype was identified in 3.63% of ITP patients, and only in 1.27% of controls. Our group recently published that a positive direct antiglobulin test is associated with chronic ITP and need for second line treatments. Of the patients with the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype with DAT testing performed (n=9), 66% had a positive DAT test and 33% had a negative DAT result. Of those without the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype who had DAT testing, 17.2% had a positive DAT and 82.8% had a negative test (p=0.0026). Conclusions: HLA alleles are seen at increased frequency in a cohort of Caucasian chronic ITP patients. The HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype is linked to a variant previously identified in BTNL2. Coupled with prior data suggesting that a positive DAT result is associated with chronic disease and use of second line agents, this presence of the HLA-DRB1*04:02, HLA-DQB1*03:02 haplotype may also be linked to refractory disease. Confirmation of the accuracy of the xHLA method in a cohort of patients with both exome data and traditional HLA typing is underway. In the future, a separate cohort of chronic and acute ITP patients will undergo next generation sequencing and have similar HLA typing performed as an independent validation set. Table 1 Disclosures Despotovic: Novartis: Research Funding; Amgen: Research Funding; Dova: Honoraria.

The atomic scale interaction of solute with a migrating grain boundary has been studied using a binary phase field crystal (PFC) model. This model bridges between atomistic and continuum simulation techniques as it operates on diffusive timescales but at atomistic length scales. For this study, a two-dimensional channel containing two grains separated by a flat grain boundary has been constructed that allows for a channel length on the order of one micrometer. A new formalism has been developed to allow for the application of an external driving pressure for the growth of one grain. These simulations account for solute/grain boundary interactions, resulting in a solute drag effect on the grain boundary motion. The PFC simulations show good agreement with classical solute drag theory, though deviations due to the atomic scale nature of the interface exist.

Aim Histocompatibility testing is used to predict the risk of hyperacute and accelerated-acute transplant rejection. The presence of HLA-specific antibodies, as detected by single antigen bead testing (SAB), are used in organ allocation through the calculated panel reactive antibody (cPRA) and by assessing the presence of donor HLA-specific antibodies (DSA). The presence of DSA and cPRA are considered in the algorithm for assigning patients to immunosuppression protocols. However, the interpretation of low level antibodies in SAB and DSA testing is challenging. Our aim was to look at antibodies below our current threshold of 2000 MFI but above our analytical threshold of 1000 MFI to determine if there is residual risk related to these antibodies. Methods Patient antibody screens were evaluated with 2000 MFI and 1000 MFI cutoff values. 181 patients were assessed for pre-transplant patient risk category and donor compatibility by determining: the change in cPRA, number of identified HLA specific antibodies between the thresholds, the presence of DSA identified between thresholds and the predicted change in immunosuppression protocols. Living donor kidney transplants with an average of 2 years of follow-up were reviewed. 81 recipients were scored for the presence of DSA and examined for the development of de novo DSA (dnDSA) post-transplant. Biopsy data was also reviewed on 40 living donor kidney transplant recipients to determine the incidence of biopsy-proven rejection. Results The reduction in antibody threshold was associated with an average increase in cPRA of 15% for HLA-Class I and 18% for HLA-Class II which corresponded to detection of 10 additional HLA specificities. We determined that using the 1000 MFI threshold, 15% of patients would have been considered higher risk based on transplant center protocols and would have necessitated increased immunosuppression. Changes in risk category were weakly associated with higher rates of dnDSA post-transplant and biopsy-proven rejection. Conclusions In this study, the development of biopsy-proven rejection was not associated with pre-transplant DSA or post-transplant dnDSA that were between 1000 and 2000 MFI.

A new phase-field model of microstructural evolution is presented that includes the effects of elastic strain energy. The model’s thin interface behavior is investigated by mapping it onto a recent model developed by Echebarria et al. [Echebarria B, Folch R, Karma A, Plapp M. Phys Rev E 2004;70:061604]. Exploiting this thin interface analysis, the growth of solid-state dendrites are simulated with diffuse interfaces and the phase-field and mechanical equilibrium equations are solved in real space on an adaptive mesh. A morphological competition between surface energy anisotropy and elastic anisotropy is examined. Two dimensional simulations are reported that show that solid-state dendritic structures undergo a transition from a surface-dominated [Meiron DI. Phys Rev A 1986;33:2704] growth direction to an elastically driven [Steinbach I, Apel M. Phys D – Nonlinear Phenomena 2006;217:153] growth direction due to changes in the elastic anisotropy, the surface anisotropy and the supersaturation. Using the curvature and strain corrections to the equilibrium interfacial composition and linear stability theory for isotropic precipitates as calculated by Mullins and Sekerka, the dominant growth morphology is predicted.

The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

We review the use of phase field methods in solidification modeling, describing their fundamental connection to the physics of phase transformations. The inherent challenges associated with simulating phase field models across multiple length and time scales are discussed, as well as how these challenges have been addressed in recent years. Specifically, we discuss new asymptotic analysis methods that enable phase field equations to emulate the sharp interface limit even in the case of quite diffuse phase-field interfaces, an aspect that greatly reduces computation times. We then review recent dynamic adaptive mesh refinement algorithms that have enabled a dramatic increase in the scale of microstructures that can be simulated using phase-field models, at significantly reduced simulation times. Combined with new methods of asymptotic analysis, the adaptive mesh approach provides a truly multi-scale capability for simulating solidification microstructures from nanometers up to centimeters. Finally, we present recent results on 2D and 3D dendritic growth and dendritic spacing selection, which have been made using phase-field models solved with adaptive mesh refinement.

The metabolic fate of high doses of B a P is not fully established. To fill this important data need, a comprehensive metabolism, bioavailability, and toxicokinetic study has been undertaken to track the fate of B a P subsequent to single acute exposures. Doses of 100 mg/kg body weight, 0.1 mg/m 3 (equivalent to 19 mg/kg oral dose), and 4.5 w g/kg B a P were administered to 8-week-old male F-344 rats via oral, inhalation (nose only), and intravenous routes, respectively. Rats were sacrificed at 0, 0.5, 1, 2, 4, 6, 24, 48, and 72 hr postexposure. Blood, liver, lung, brain, reproductive tissues, urine, and feces samples were analyzed for parent B a P and metabolites by HPLC with fluorescence detection. Most of the administered B a P was metabolized 4, 6, and 72 hr postexposure for inhalation, intravenous, and oral routes, respectively. The following metabolites were detected: 4,5-dihydrodiol, 7,8-dihydrodiol, 9,10-dihydrodiol, 3,6-dione, 3-hydroxy, and 9-hydroxy B a P (organic fraction), glucuronides, sulfa...

Omental extragastrointestinal stromal tumors are rare neoplasms. We present a case of an elderly woman who was found to have a large solid and cystic pelvic mass of presumed ovarian origin with associated omental neovascularity. Histopathologic examination showed a mixed spindled and epithelioid tumor which was essentially negative for c-KIT and positive for smooth muscle markers by immunohistochemistry. A next generation sequencing panel was performed, analyzing the patient’s tumor for actionable mutations in 50 genes commonly associated with human cancers. Identification of a point mutation in PDGFRA enabled accurate diagnosis and provided an option for targeted therapy for this rare tumor.

Any alteration of the critical sequence of genes that are required to coordinate the differentiation of cells, the promotion of migration, dendritic arborization, synapse formation, and myelination in the developing nervous system would be expected to have deleterious consequences. The focus of this article is a molecular evaluation of the neurotoxicological effects that result subsequent to the transplacental exposure of fetal rats to desorbed benzo(a)pyrene (BaP) following maternal inhalation. A state-of-the-art, newly designed, fabricated, and tested model aerosol generation system was utilized in these studies. Timed-pregnant Sprague Dawley rats were exposed for 4 h on gestation day 15 of a 21-day gestation period to an acute dose of BaP:carbon black aerosol (100 microg/m(3)). Controls received carbon black only. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The aerosol exhibited a trimodal distribution with 95% cumulative mass less than 15.85 microm, 90% cumulative mass less than 10 microm, 67. 5% cumulative mass less than 2.5 microm and 66.2% cumulative mass less than 1.0 microm. Time-course bioavailability results indicated that greater than 95% of the parent compound is cleared from blood 240 min postexposure. An Sp1 transcription factor consensus sequence was examined by electrophoretic mobility shift analysis of nuclear extracts from various brain regions of resulting pups on postnatal days 3, 5, 7, 10, and 15. It revealed perturbations in the developmental expression profile of Sp1 abundance as a result of nose-only particulate aerosol exposure to the timed-pregnant dam. The data obtained on the temporal and spatial regulation of gene expression in the brain indicate that (1) Sp1 DNA-binding is developmentally regulated and expressed very highly in actively developing brain regions, and (2) a consequence of the transplacental deposition of desorbed BaP to the fetus is in utero neurotoxicity.

The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis.Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively.Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress.OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.

We present a new phase field crystal model for structural transformations in multi-component alloys. The formalism builds upon the two-point correlation kernel developed in Greenwood et al. for describing structural transformations in pure materials [Phys. Rev. Lett. 105, 045702 (2010)]. We introduce an effective twopoint correlation function for multi-component alloys that uses the local species concentrations to interpolate between different crystal structures. A simplified version of the model is derived for the particular case of threecomponent (ternary) alloys, and its equilibrium properties are demonstrated. Dynamical equations of motion for the density and multiple species concentration fields are derived, and the robustness of the model is illustrated with examples of complex microstructure evolution in dendritic solidification and solid-state precipitation., 14 pages, 5 figures

Background: Acute Myeloid Leukemia (AML) without favorable and particular unfavorable cytogenetic aberrations is classified as intermediate prognosis. Recurrent somatic genomic mutations through The Cancer Genome Atlas (TCGA) have provided valuable prognostic information in AML. There are very few studies that have incorporated the cytogenetics (Cy), Next Generation sequencing (NGS) and Overall Survival (OS) in AML. Moreover prognostic NGS studies have a limited collective context without a quantifiable stratification. For the purpose of prognostic risk stratification, we utilized the TCGA data by Ley et.al and developed a system of Integer Weights for the Genomic Mutation Score (IWGMS) obtained by targeted NGS at Houston Methodist Hospital. We then correlated the IWGMS with patients' outcomes in a retrospective manner. Methods: The patient data was queried from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse that integrates existing data with internal and external research databases and national registries. We queried for the diagnosis of AML and demographics, Cy, NGS and OS. We divided the patients into 3 groups according to their MRC cytogenetic risks- Favorable (FCy), Intermediate (ICy), Poor (PCy)). Mutations in 54 genes associated with myeloid disorders were tested in NGS by using the TruSight Myeloid Sequencing Panel (Illumina) (Table 1). Briefly, genomic DNA was extracted from sorted specimens using automated methods on the MagnaPure Compact instrument (Roche Diagnostics). Sequencing libraries were prepared using TruSight reagents and sequenced on a MiSeq instrument using a 2x300 bp paired end strategy. Read alignment and variant calling for minimum of 100x amplicon coverage was performed using VariantStudio Software (Illumina). The biologic significance of detected variants was determined using VarView5 (an in-house developed bioinformatics tool). Interpretations are reviewed in a consensus conference. For the data described herein, interpretations were limited to known nonsynonymous (single nucleotide polymorphsims and insertions or deletions) somatic mutations. Results: Of the 1200 AML patients reviewed, 100 patients meet the criteria for having the information on Cy and NGS. The mortality rate for FCy, ICy and PCy groups are 43%, 52%, and 51% respectively. IWGMS was designed by assigning a score for each genomic mutation between the range of negative 2 (-2) for good risk to positive 2 (+2) for each of 9 TCGA mutation categories (Transcription- Factor Fusion, Nucleophosmin (NPM1), Tumor Suppressor Genes, DNA-Methylation related genes, Signaling Genes, Chromatin Modifying Genes, Myeloid Transcription Factor Genes, Cohesion complex Genes and Spliceosome-complex genes). The total IWGMS for each patient was calculated by the sum of mutation scores in each 9 categories. The score greater than 3 was defined as high risk. By univariate analysis, in the ICy, high IWGMS was associated with significantly higher mortality rate than low IWGMS (80% vs 44%, p=0.045). In PCy, patients with high IWGMS and low IWGMS had similar mortality rate (50% vs 52%, p=0.910) (Table 1). Conclusions: We have developed an IWGMS system to stratify patients with ICy into high and low risk groups. Our result demonstrated the significance of high mutation score in this group of patients, which will impact the management. The identification of genomic alterations along with the scoring system has a great potential for developing rationally-targeted therapies and improving outcomes. Further analysis along with the treatment outcomes will be presented at the ASH meeting in San Diego. Disclosures Rice: Novartis Pharma: Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Other: Participation in registry studies; Apellis/Synergy: Other: Data Safety Monitoring Committee member; Ablynx: Other: Participation in multi-center research trial; Selexys: Other: Participation in multi-center research trial; Incyte: Other: Participation in multi-center research trial. Iyer:Genentech: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding; Incyte: Research Funding; Arog: Research Funding; Celgene: Research Funding.

We develop a phase field crystal model for structural transformations in two-component alloys. In particular, the interactions between components are described by direct correlation functions that are an extension of those introduced by Greenwood et al. [Phys. Rev. Lett. 105, 045702 (2010)] for pure materials. These correlation functions result in broad density modulations that can be treated with high numerical efficiency, hence enabling simulations of phase transformations between a wide range of crystal structures. A simplified binary alloy model is shown to describe the equilibrium properties of eutectic and peritectic binary alloys in two and three dimensions. The robustness and versatility of this method is demonstrated by applying the model to the growth of structurally similar and dissimilar eutectic lamella and to segregation to defects.

We introduce and characterize free-energy functionals for modeling of solids with different crystallographic symmetries within the phase-field-crystal methodology. The excess free energy responsible for the emergence of periodic phases is inspired by classical density-functional theory, but uses only a minimal description for the modes of the direct correlation function to preserve computational efficiency. We provide a detailed prescription for controlling the crystal structure and introduce parameters for changing temperature and surface energies, so that phase transformations between body-centered-cubic (bcc), face-centered-cubic (fcc), hexagonal-close-packed (hcp), and simple-cubic (sc) lattices can be studied. To illustrate the versatility of our free-energy functional, we compute the phase diagram for fcc-bcc-liquid coexistence in the temperature-density plane. We also demonstrate that our model can be extended to include hcp symmetry by dynamically simulating hcp-liquid coexistence from a seeded crystal nucleus. We further quantify the dependence of the elastic constants on the model control parameters in two and three dimensions, showing how the degree of elastic anisotropy can be tuned from the shape of the direct correlation functions.

The effectiveness of a content dependent learning strategy and a content independent learning strategy on the performance of a closed motor skill (underhand dart throw) and the transfer of these strategies to the performance of two related closed motor skills (an underhand jart throw and a ball toss) were examined in 50 female and 50 male older adults (range = 65-75 years). In addition, the effectiveness of the content independent strategy was compared to that of the content dependent strategy when the strategies were combined with verbal praise. Gender differences in task performance were also examined. All older adults' performances greatly benefitted from both cognitive learning strategies. Verbal praise combined with the cognitive learning strategies did not further improve subjects' performances, nor did performance differences exist between the experimental conditions. Based on these data practitioners should encourage older adults to use cognitive learning strategies when performing closed motor sk...

The phase field crystal (PFC) method has emerged as a promising technique for modeling materials with atomistic resolution on mesoscopic time scales. The approach is numerically much more efficient than classical density functional theory (CDFT), but its single mode free energy functional only leads to lattices with triangular (2D) or BCC (3D) symmetries. By returning to a closer approximation of the CDFT free energy functional, we develop a systematic construction of two-particle direct correlation functions that allow the study of a broad class of crystalline structures. This construction examines planar spacings, lattice symmetries, planar atomic densities and the atomic vibrational amplitude in the unit cell of the lattice and also provides control parameters for temperature and anisotropic surface energies. The power of this new approach is demonstrated by two examples of structural phase transformations., 4 pages, 4 figures

A formalism is presented for performing quantitative phase-field simulations of single-phase solidification in binary alloys with nonlinear solidus and liquidus curves. It is shown that, close to equilibrium, Gibbs free energy of an alloy phase can be approximated by the free energy function of a dilute ideal binary alloy, modified by effective temperature-dependent coefficients. This makes it possible to exploit a recent phase-field technique [A. Karma, Phys. Rev. Lett. 87, 115701 (2001)] to model the free-boundary kinetics of single-phase solidification in binary alloys having nonlinear phase coexistence curves. Simulations of isothermal and nonisothermal dendritic solidification in an isomorphous binary alloy are used to demonstrate convergence of tip speed and radius for different values of the phase-field interface thickness. The effect linear versus nonlinear phase boundaries on dendritic tip speed is examined.

We investigate the role of heterogeneous expression of IP3R and RyR in generating diverse elementary Ca2+ signals. It has been shown empirically (Wojcikiewicz and Luo in Mol. Pharmacol. 53(4):656-662, 1998; Newton et al. in J. Biol. Chem. 269(46):28613-28619, 1994; Smedt et al. in Biochem. J. 322(Pt. 2):575-583, 1997) that tissues express various proportions of IP3 and RyR isoforms and this expression is dynamically regulated (Parrington et al. in Dev. Biol. 203(2):451-461, 1998; Fissore et al. in Biol. Reprod. 60(1):49-57, 1999; Tovey et al. in J. Cell Sci. 114(Pt. 22):3979-3989, 2001). Although many previous theoretical studies have investigated the dynamics of localized calcium release sites (Swillens et al. in Proc. Natl. Acad. Sci. U.S.A. 96(24):13750-13755, 1999; Shuai and Jung in Proc. Natl. Acad. Sci. U.S.A. 100(2):506-510, 2003a; Shuai and Jung in Phys. Rev. E, Stat. Nonlinear Soft Matter Phys. 67(3 Pt. 1):031905, 2003b; Thul and Falcke in Biophys. J. 86(5):2660-2673, 2004; DeRemigio and Smith in Cell Calcium 38(2):73-86, 2005; Nguyen et al. in Bull. Math. Biol. 67(3):393-432, 2005), so far all such studies focused on release sites consisting of identical channel types. We have extended an existing mathematical model (Nguyen et al. in Bull. Math. Biol. 67(3):393-432, 2005) to release sites with two (or more) receptor types, each with its distinct channel kinetics. Mathematically, the release site is represented by a transition probability matrix for a collection of nonidentical stochastically gating channels coupled through a shared Ca2+ domain. We demonstrate that under certain conditions a previously defined mean-field approximation of the coupling strength does not accurately reproduce the release site dynamics. We develop a novel approximation and establish that its performance in these instances is superior. We use this mathematical framework to study the effect of heterogeneity in the Ca2+-regulation of two colocalized channel types on the release site dynamics. We consider release sites consisting of channels with both Ca2+-activation and inactivation ("four-state channels") and channels with Ca2+-activation only ("two-state channels") and show that for the appropriate parameter values, synchronous channel openings within a release site with any proportion of two-state to four-state channels are possible, however, the larger the proportion of two-state channels, the more sensitive the dynamics are to the exact spatial positioning of the channels and the distance between channels. Specifically, the clustering of even a small number of two-state channels interferes with puff/spark termination and increases puff durations or leads to a tonic response.

We implement an adaptive mesh algorithm for calculating the space and time dependence of the atomic density field during materials processing. Our numerical approach uses the systematic renormalization-group formulation of the phase field crystal model to provide the underlying equations for the complex amplitude of the atomic density field--a quantity that is spatially uniform except near topological defects, grain boundaries and other lattice imperfections. Our algorithm is a hybrid formulation of the amplitude equations, combining Cartesian and polar decompositions of the complex amplitude. We show that this approach leads to an acceleration by three orders of magnitude in model calculations of polycrystalline domain formation in two dimensions., 37 pages, 15 figures. Submitted to Phys. Rev. E

The U.S. Federal Courts Administrative Office of the U.S. Courts (AOUSC) was responsible for developing the Case Management/Electronic Case File system (legacy CM/ECF) originally implemented in 1996 to service the federal courts. The AOUSC is presently developing its 2nd generation service (NextGen). The IJCA carried an earlier narrative of CM/ECF’s evolution. This second IJCA article describes the approach taken to define and develop that 2nd generation CM/ECF system. This article reviews the methodology used for determining requirements; the new software tools and hardware technologies used; and the expanded functions and enhanced services being incorporated into the new product. Also included is an exploration of the various obstacles, problems, and organizational issues which occur when transitioning from a legacy system to one that is more modern and complex.

Time-dependent simulations of two-dimensional isothermal Ni-Cu dendrites are simulated using a phase-field model solved with a finite-difference adaptive mesh refinement technique. Dendrite tip velocity selection is examined and found to exhibit a transition between two markedly different regimes as undercooling is increased. At low undercooling, the dendrite tip growth rate is consistent with the kinetics of the classical Stefan problem, where the interface is assume to be in local equilibrium. At high undercooling, the growth velocity selected approaches a linear dependence on melt undercooling, consistent with the continuous growth kinetics of Aziz and with a one-dimensional steady-state phase-field asymptotic analysis of Ahmad [Phys. Rev. E 58, 3436 (1998)]. Our simulations are also consistent with other previously observed behaviors of dendritic growth as undercooling is increased. These include the transition of dendritic morphology to absolute stability and nonequilibrium solute partitioning. Our results show that phase-field models of solidification, which inherently contain a nonzero interface width, can be used to study the dynamics of complex solidification phenomena involving both equilibrium and nonequilibrium interface growth kinetics.

Sex steroids modify sexual behavior and autonomic function. The gradual decline in circulating levels is correlated with several diseases in humans and animals. However, little is known about age-related changes that occur in the availability of these steroids. In the current studies, we characterized age-related changes in (1) circulating levels of estradiol (females) or testosterone (males), (2) reproductive function (estrous cyclicity in females; erectile reflexes in males), and (3) blood pressure in a longitudinal study. In a separate study, we characterized the estrous cyclicity of sex steroids in female, and diurnal periodicity in male, Long-Evans rats. Young females exhibit regular estrous cycles, transition to irregular cycles at about 10 mo of age, then to cycles characterized by extended periods of estrous, and to persistent estrous. Despite the loss of cyclicity, circulating 17beta-estradiol in middle-aged females was maintained at levels similar to those in young females during diestrous. Males display an age-related decline in testosterone, circulating levels decrease by about 25% during the period from 8 to 16 mo of age. Also, during any 24 h period testosterone levels in young males vary from a peak of about 3.5 ng/mL (late light period) to a trough of 0.7 ng/mL (early dark period). In middle-aged males the rhythm amplitude is greatly blunted (1.4 to 0.7 ng/mL). Males exhibit age-related decrements in erectile reflexes. In females and males systolic blood pressure is relatively stable until 8 mo of age, but significantly increases during the next 5 mo of age. In males, the increase in arterial pressure is gradual from about 8 mo of age. Young females have lower blood pressures than age-matched males, but by 14 mo of age this sex-related advantage is lost. Thus, by middle age, male and female rats are exposed to less gonadal hormone/altered patterns of availability, exhibit decrements in reproductive function, and display an increase in systolic blood pressure.

We simulate dendritic growth in directional solidification in dilute binary alloys using a phase-field model solved with an adaptive-mesh refinement. The spacing of primary branches is examined for a range of thermal gradients and alloy compositions and is found to undergo a maximum as a function of pulling velocity, in agreement with experimental observations. We demonstrate that wavelength selection is unambiguously described by a non-trivial crossover scaling function from the emergence of cellular growth to the onset of dendritic fingers, a result validated using published experimental data., Comment: 4 pages, four figures, submitted to Physical Review Letters

OBJECTIVE: To examine the effects of creatine supplementation on the incidence of cramping and injury observed during 1 season of National Collegiate Athletic Association Division IA football training and competition. DESIGN AND SETTING: In an open-label manner, subjects who volunteered to take creatine ingested 0.3 g.kg(-1).d(-1) of creatine for 5 days followed by an average of 0.03 g.kg.(-1)d(-1) after workouts, practices, and games. Creatine intake was monitored and recorded by researchers throughout the course of the study. SUBJECTS: Thirty-eight of 72 athletes (53.0%) participating in the 1999 Division IA collegiate football season from the same university volunteered to take creatine in this study. Subjects trained, practiced, or played in environmental conditions ranging from 15 degrees C to 37 degrees C (mean = 27.26 degrees +/- 10.93 degrees C) and 46.0% to 91.0% relative humidity (mean = 54.17% +/- 9.71%). MEASUREMENTS: Injuries treated by the athletic training staff were recorded and categorized as cramping, heat illness or dehydration, muscle tightness, muscle strains, noncontact joint injuries, contact injuries, and illness. The number of missed practices due to injury and illness was also recorded. Data were analyzed using a 2 x 2 chi(2) test to examine the first reported incidences of cramping and injury for creatine users and nonusers. RESULTS: Creatine users had significantly less cramping (chi(2)(1) = 5.35 P =.021); heat illness or dehydration (chi(2)(1) = 4.09, P =.043); muscle tightness (chi(2)(1) = 5.39, P =.020); muscle strains (chi(2)(1) = 5.36, P =.021); and total injuries (chi(2)(1) = 17.80, P.001) than nonusers. There were no significant differences between groups regarding noncontact joint injuries (chi(2)(1)= 3.48, P =.062); contact injuries (chi(2)(1) = 0.00, P =.100); illness (chi(2)(1) = 6.82, P =.409); missed practices due to injury (chi(2)(1) = 1.43, P =.233); or players lost for the season (chi(2)(1) = 4.75, P =.491). CONCLUSIONS: The incidence of cramping or injury in Division IA football players was significantly lower or proportional for creatine users compared with nonusers.

Creatine has been reported to be an effective ergogenic aid for athletes. However, concerns have been raised regarding the long-term safety of creatine supplementation. This study examined the effects of long-term creatine supplementation on a 69-item panel of serum, whole blood, and urinary markers of clinical health status in athletes. Over a 21-month period, 98 Division IA college football players were administered in an open label manner creatine or non-creatine containing supplements following training sessions. Subjects who ingested creatine were administered 15.75 g/day of creatine monohydrate for 5 days and an average of 5 g/day thereafter in 5-10 g/day doses. Fasting blood and 24-h urine samples were collected at 0, 1, 1.5, 4, 6, 10, 12, 17, and 21 months of training. A comprehensive quantitative clinical chemistry panel was determined on serum and whole blood samples (metabolic markers, muscle and liver enzymes, electrolytes, lipid profiles, hematological markers, and lymphocytes). In addition, urine samples were quantitatively and qualitative analyzed to assess clinical status and renal function. At the end of the study, subjects were categorized into groups that did not take creatine (n = 44) and subjects who took creatine for 0-6 months (mean 4.4 +/- 1.8 months, n = 12), 7-12 months (mean 9.3 +/- 2.0 months, n = 25), and 12-21 months (mean 19.3 +/- 2.4 months, n = 17). Baseline and the subjects' final blood and urine samples were analyzed by MANOVA and 2 x 2 repeated measures ANOVA univariate tests. MANOVA revealed no significant differences (p = 0.51) among groups in the 54-item panel of quantitative blood and urine markers assessed. Univariate analysis revealed no clinically significant interactions among groups in markers of clinical status. In addition, no apparent differences were observed among groups in the 15-item panel of qualitative urine markers. Results indicate that long-term creatine supplementation (up to 21-months) does not appear to adversely effect markers of health status in athletes undergoing intense training in comparison to athletes who do not take creatine.

The purpose of this study was to examine the effects of creatine supplementation on the incidence of injury observed during 3-years of NCAA Division IA college football training and competition. In an open label manner, athletes participating in the 1998-2000 football seasons elected to take creatine or non-creatine containing supplements following workouts/practices. Subjects who decided to take creatine were administered 15.75 g of creatine for 5 days followed by ingesting an average of 5 g/day thereafter administered in 5-10 g doses. Creatine intake was monitored and recorded by research assistants throughout the study and ranged between 34-56% of players during the course of the study. Subjects practiced or played in environmental conditions ranging from 8-40 degrees C (mean 24.7 +/- 9 degrees C) and 19-98% relative humidity (49.3 +/- 17%). Injuries treated by the athletic training staff were recorded and categorized as cramping, heat/dehydration, muscle tightness, muscle strains/pulls, noncontact joint injuries, contact injuries, and illness. The number of missed practices due to injury/illness was also recorded. Data are presented as the total number of treated injuries for creatine users/total injuries observed and percentage occurrence rate of injuries for creatine users for all seasons. The incidence of cramping (37/96, 39%), heat/dehydration (8/28, 36%), muscle tightness (18/42, 43%), muscle pulls/strains (25/51, 49%), non-contact joint injuries (44/132, 33%), contact injuries (39/104, 44%), illness (12/27, 44%), number of missed practices due to injury (19/41, 46%), players lost for the season (3/8, 38%), and total injuries/missed practices (205/529, 39%) were generally lower or proportional to the creatine use rate among players. Creatine supplementation does not appear to increase the incidence of injury or cramping in Division IA college football players.

We simulate directional solidification using the phase field method solved with adaptive mesh refinement. We examine length scale selection for two cases. For small surface tension anisotropy directed at forty five degrees relative to the pulling direction, we observe a transition from a seaweed to dendrite morphology as the thermal gradient is lowered, consistent with recent experimental findings. We show that the morphology of crystal structures can be unambiguously characterized through the local interface velocity distribution. We derive semi-empirically a phase diagram for the transition from seaweed to dendrites as a function of thermal gradient and pulling speed. As surface tension anisotropy is increased and aligned with the pulling direction we observe cellular and dendritic arrays directed in the pulling direction. We characterize wavelength selection and obtain a new universal scaling of the wavelength that differs from previous theories.

The objective of this study was to evaluate the effect of subacute exposure to inhaled benzo(a)pyrene (BaP) on fetal survival and luteal maintenance using timed-pregnant Fisher 344 rats. Prior to assignment of pregnant rats to treatment and control groups, numbers of implantation sites were determined on gestation day (GD) 8 via midventral laparotomy. Subsequently, animals were assigned randomly to three treatment groups and two control groups. Treatment consisted of subacute exposure of rats via inhalation to BaP 25, 75, and 100 micro g/m(3), 4h daily for 10 days (GD-11-20). Control animals were either sham exposed to carbon black (CB) to control for inert BaP carrier or remained unexposed (UNC). Blood samples were collected on days 15 and 17 of gestation via sinus orbital veini-puncture for plasma. Number of pups per litter was determined postpartum and fetal survival rate was expressed as a percentage of the corresponding implantation sites. Radioimmunoassays were used to determine plasma progesterone, estrogen, and prolactin (indirect measurement of decidual luteotropin) concentrations. Fetal survival among BaP-treated rats declined in a dose-dependent manner (25 micro g/m(3), 78.3% per litter; 75 micro g/m(3), 38.0% per litter; 100 micro g/m(3), 33.8% per litter; P

Conjugated linoleic acids (CLA) are essential fatty acids that have been reported in animal studies to decrease catabolism, promote fat loss, increase bone density, enhance immunity, and serve as an antiatherogenic and anticarcinogenic agent. For this reason, CLA has been marketed as a supplement to promote weight loss and general health. CLA has also been heavily marketed to resistance-trained athletes as a supplement that may help lessen catabolism, decrease body fat, and promote greater gains in strength and muscle mass during training. Although basic research is promising, few studies have examined whether CLA supplementation during training enhances training adaptations and/or affects markers of health. This study evaluated whether CLA supplementation during resistance training affects body composition, strength, and/or general markers of catabolism and immunity. In a double-blind and randomized manner, 23 experienced, resistance-trained subjects were matched according to body mass and training volume and randomly assigned to supplement their diet with 9 g;pdd(-1) of an olive oil placebo or 6 g;pdd(-1) of CLA with 3 g;pdd(-1) of fatty acids for 28 days. Prior to and following supplementation, fasting blood samples, total body mass, and dual-energy X-ray absorptiometry (DEXA) determined body composition, and isotonic bench press and leg press 1 repetition maximums (1RMs) were determined. Results revealed that although some statistical trends were observed with moderate to large effect sizes, CLA supplementation did not significantly affect (p0.05) changes in total body mass, fat-free mass, fat mass, percent body fat, bone mass, strength, serum substrates, or general markers of catabolism and immunity during training. These findings indicate that CLA does not appear to possess significant ergogenic value for experienced resistance-trained athletes.

Bioavailability and toxicokinetic studies are essential in order to establish dose-response relationships of widely distributed environmental toxicants such as benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Fischer 344 rats were exposed for 4 h (via nose-only inhalation) to aerosol exposure concentrations of 0.1, 1.0, and 2.5 mg/m(3) of BaP absorbed onto carbon black particles using a state-of-the-art model aerosol generation system. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The average aerosol for the 3 exposure concentrations used in this study exhibited a trimodal distribution with 93% cumulative mass less than 15.85 microm, 89% cumulative mass less than 10 microm, 55.3% cumulative mass less than 2.5 microm, and 38% less than 1 microm. Fifty-five percent of the aerosol had a cumulative mass less than PM(2.5) and the mass median aerodynamic diameter (MMAD) -/+ geometric standard deviation (GSD) for this mode was 1.7 -/+ 0.085 microm. Plasma and lung samples were collected at 30, 60, 120, and 240 min postexposure. The concentrations of BaP parent compound and metabolites were determined by high-performance liquid chromatography. The toxicokinetic parameters were computed from the time course of plasma BaP concentration. The bioavailability of BaP increased as a function of exposure concentration, and toxicokinetic analysis indicates first-order pharmacokinetics for BaP. However, some toxicokinetic parameters such as clearance and volume of distribution remained constant throughout the duration of the postexposure period. BaP and its metabolite concentrations in plasma peaked at 1 h postexposure. At 240 min postexposure, only trace levels of BaP remained in the plasma. The BaP metabolites in the lung showed an identical trend where no parent compound was detected. Among the metabolites detected, BaP 4,5-, 7,8-, and 9,10-dihydrodiols, 3-OH-BaP, and 9-OH-BaP were predominant.

In many polycrystalline materials, second phase particles and solute atoms impose a drag pressure on the motion of grain boundaries. The drag effect occurs on a scale comparable to the particle diameter and interface thickness. However, to simulate grain growth with numerical efficiency one requires a model that captures the drag pressure on the interfaces but does not resolve the fine particles or solute segregation spike. In this paper, a multiphase-field model is proposed to simulate the evolution of microstructure under constant and velocity dependent drag pressures. The accuracy of the model is confirmed in comparison with analytical expressions for a shrinking circular grain. Application of the model is presented for grain growth in two dimensions under particle pinning. Measuring curvature of grain-boundary segments reveals that in the completely pinned structure, the average driving pressure is not equal to but lower than the pinning pressure. Considering this effect, the predicted limiting grain size is about three times larger than that assumed in conventional mean-field theories. Based on this observation, a correction factor is introduced for these mean-field models. The proposed phase-field formulation is also applied to simulate grain growth in the presence of solute drag. The grain growth kinetics follows a phenomenological relationship that can be described with a power law with a time exponent in the range 0.35–0.50. The deviation of the time exponent from 0.5, associated with ideal grain growth, and its correlation with the solute drag parameters is discussed.

We present a computational study of the morphology of adsorbed monolayers on quasicrystalline surfaces with five- and seven-fold symmetry. The phase field crystal model is employed to first simulate the growth of the quasicrystal surfaces and then to elastically couple a two-dimensional film to the substrate. We find several distinct pseudomorphic phases that depend on the position of adsorption sites as well as the strength of the monolayer/substrate interaction, and quantify them by computing local order parameters. In qualitative agreement with recent experiments using colloids in quasiperiodic light fields, we find that the formation of quasicrystalline order is greatly inhibited on seven-fold surfaces.

This paper describes Esso Australia's drive to further improve safety performance in its operations following a survey of 1330 employees and contractors to assess organisational culture, with a specific focus on safety. Organisational culture is widely recognised as a key element to support and sustain an effective safety culture, which in turn drives safety outcomes. The survey examined organisational, team interaction, individual and specific safety factors. Analysis of survey data and feedback obtained through focus groups involving 160 (12 %) survey respondents has identified key improvement opportunities in the areas of leadership, engagement and alignment across the organisation. A comprehensive action plan has been implemented to address the cultural elements that significantly influence safety performance. As a response to the survey Esso has developed the Fundamentals of Safety Leadership Program to engage the hearts and minds of its workplace leaders and to provide them with knowledge, skills and confidence to effectively establish and influence stronger safer behaviours amongst the workforce. This program was completed late in 2010 with over 400 workplace leaders (employees and contractors) having attended the training, and a subsequent phase has commenced in 2011 for the entire workforce including employees and contractors (∼ 1,800 people). Key elements include the development of personal leadership credos and personal safety leadership action plans. Beyond the initial program, there will be ongoing coaching and mentoring for the workplace leadership team. The Fundamentals of Safety Program will be repeated on a five year cycle and has been included in the leader training roadmap.