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OBJECTIVE: To investigate the role of activated protein C (APC) in cartilage degradation. METHODS: Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNFalpha), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay. RESULTS: Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1alpha and TNFalpha stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1alpha-treated and TNFalpha-treated cartilage, but not in normal or in RetA-treated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity. CONCLUSION: APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis. [ABSTRACT FROM AUTHOR]

Background: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described., Methods: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial., Results: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks., Conclusion: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

Background: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development., Results: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred., Conclusion: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.

Vapor diffusion crystallizations are among the most versatile methods for growing X-ray quality crystals. While many experimental sections describe the successful use of various solvent combinations, the literature has been entirely lacking in quantitative data (rates, measures of solvent strength changes) that might allow more informed planning rather than simple trial-and-error approaches. We here report the diffusion-induced volume changes for 44 solvent combinations over the first 60 h under standardized conditions, plus six more combinations that exhibit little or no volume changes. Additionally, the inner and outer vial compositions at 24 h were determined, and the resulting changes in solvation parameters were quantified using Hansen solubility parameters. Some general preliminary effects of changes in volume ratios and scale are described. These results identify two dozen solvent combinations with larger changes in solvent parameters than the very commonly used diethyl ether/dichloromethane example. These results should allow a more informed approach to the execution of vapor diffusion crystallizations than has previously been possible.

Introduction: Written medicine information (WMI) is a collection of facts for a specific medication, and it helps facilitate patient understanding of medication therapy. The primary objective of this study was to assess consumer satisfaction with National Alliance on Mental Illness (NAMI) WMI. A secondary objective was to assess health care professional satisfaction., Methods: National Alliance on Mental Illness WMI and surveys were offered to consumers, health care professionals, and trainees at 3 treatment centers with psychiatric services. All adults who received medication counseling were eligible for inclusion. Survey responses were evaluated using descriptive statistics., Results: Most consumers (82.4%) and providers (74.5%) reported overall satisfaction with NAMI WMI. Consumers were least satisfied with information on how to manage unwanted effects, drug-drug interactions, and readability (9.5%, 14.9%, 41.9% dissatisfaction)., Discussion: Evaluation and feedback from consumers and health care professionals may influence decisions to refine NAMI WMI to meet consumer needs., Competing Interests: Disclosures: None for any author. The College of Psychiatric and Neurologic Pharmacists provided resources to facilitate communication among study group members including an Internet workspace and telephone conference lines. No grant funding was received for this project.

Objective: To investigate the role of the heparan sulfate (HS) proteoglycan perlecan (HSPG-2) in regulating fibroblast growth factor (FGF) activity, bone and joint growth, and the onset and progression of posttraumatic osteoarthritis (OA) in a mouse gene-knockout model., Methods: Maturational changes were evaluated histologically in the knees of 3-, 6-, and 12-week-old wild-type (WT) mice and Hspg2(Δ3-/Δ3-) mice (Hspg2 lacking domain 1 HS, generated by ablation of exon 3 of perlecan). Cartilage damage, subchondral bone sclerosis, osteophytosis, and synovial inflammation were scored at 4 and 8 weeks after surgical induction of OA in WT and Hspg2(Δ3-/Δ3-) mice. Changes in cartilage expression of FGF-2, FGF-18, HSPG-2, FGF receptor 1 (FGFR-1), and FGFR-3 were examined immunohistochemically. Femoral head cartilage from both mouse genotypes was cultured in the presence or absence of interleukin-1α (IL-1α), FGF-2, and FGF-18, and the content and release of glycosaminoglycan (GAG) and expression of messenger RNA (mRNA) for key matrix molecules, enzymes, and inhibitors were quantified., Results: No effect of perlecan HS ablation on growth plate or joint development was detected. After induction of OA, Hspg2(Δ3-/Δ3-) mice had significantly reduced cartilage erosion, osteophytosis, and synovitis. OA-induced loss of chondrocyte expression of FGF-2, FGF-18, and HSPG-2 occurred in both genotypes. Expression of FGFR-1 after OA induction was maintained in WT mice, while FGFR-3 loss after OA induction was significantly reduced in Hspg2(Δ3-/Δ3-) mice. There were no genotypic differences in GAG content or release between unstimulated control cartilage and IL-1α-stimulated cartilage. However, IL-1α-induced cartilage expression of Mmp3 mRNA was significantly reduced in Hspg2(Δ3-/Δ3-) mice. Cartilage GAG release in either the presence or absence of IL-1α was unaltered by FGF-2 in both genotypes. In cartilage cultures with FGF-18, IL-1α-stimulated GAG loss was significantly reduced only in Hspg2(Δ3-/Δ3-) mice, and this was associated with maintained expression of Fgfr3 mRNA and reduced expression of Mmp2/Mmp3 mRNA., Conclusion: Perlecan HS has significant roles in directing the development of posttraumatic OA, potentially via the alteration of FGF/HS/FGFR signaling. These data suggest that the chondroprotection conferred by perlecan HS ablation could be attributed, at least in part, to the preservation of FGFR-3 and increased FGF signaling., (© 2016, American College of Rheumatology.)

Since long term rodent carcinogenicity studies are used to test a very large number of potential tumor endpoints, finding a balance between the control of Type 1 and Type 2 error is challenging. As a result, these studies can suffer from very low power to detect effects of regulatory significance. In the present paper, a new design is proposed in order address this problem. This design is a simple modification of the existing standard designs and uses the same number of animals. Where it differs from the currently used designs is that it uses just three treatment groups rather than four, with the animals concentrated in the control and high dose groups, rather than being equally distributed among the groups. This new design is tested, in a pair of simulation studies over a range of scenarios, against two currently used designs, and against a maximally powerful two group design. It consistently performs at levels close to the optimal design, and except in the case of relatively modest effects and very rare tumors, is found to increase power by 10%-20% over the current designs while maintaining or reducing the Type 1 error rate., (Published by Elsevier Inc.)

Objective: To explore the involvement of protease-activated receptor 1 (PAR-1) and PAR-2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR-1 or PAR-2 in mice., Methods: OA was induced in the joints of wild-type (WT), PAR-1(+/+) , PAR-1(-/-) , and PAR-2(-/-) mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post-DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/activity were studied in cultures of mouse femoral head tissue with or without interleukin-1α (IL-1α). At 1 week post-DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription-polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry., Results: Deletion of PAR-2, but not that of PAR-1, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR-1 or PAR-2 ablation on IL-1α-induced cartilage degradation or chondrocyte metalloproteinase expression/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post-DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4+ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR-2(-/-) mice compared to PAR-1(-/-) and WT mice., Conclusion: Deletion of PAR-2, but not that of PAR-1, results in a significant decrease in DMM-induced cartilage damage. The chondroprotection in PAR-2(-/-) mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses., (Copyright © 2014 by the American College of Rheumatology.)

Objective: Levels of activated protein C (APC) are elevated in the synovial fluid of patients with osteoarthritis (OA), and increased APC levels are correlated with the levels of active matrix metalloproteinase 2 (MMP-2). This study sought to investigate whether APC is a relevant protein for activation of MMPs in the degradation of human OA cartilage, and to elucidate its mechanisms of action., Methods: Human articular cartilage was cultured with or without interleukin-1α (IL-1α), in the presence or absence of APC or protein C, and an MMP or serine proteinase inhibitor. Aggrecan and collagen release and chondrocyte gene expression levels were quantified. Aggrecanase and MMP cleavage of aggrecan was examined with neoepitope-specific antibodies, and MMP activity was measured using gelatin zymography and fluorogenic peptide assay., Results: In human OA cartilage, APC induced aggrecan and collagen release, whereas in non-OA cartilage, costimulation with IL-1α was required. Inhibition of MMP activity reduced APC-induced cartilage proteolysis, and MMP-induced aggrecanolysis was confirmed by Western blotting. In cultures with APC alone, the activity of MMPs 2, 9, and 13 was significantly increased in OA cartilage, although APC could not directly activate MMPs 2 or 9. Expression of MMP1, MMP2, MMP9, MMP13, TIMP1, and TIMP3 was not altered by APC in OA cartilage. Human OA chondrocytes expressed messenger RNA for protein C, endothelial protein C receptor, thrombomodulin, and protease-activated receptor 1, but these were unaltered or down-regulated by APC. The induction of MMP activation and cartilage degradation by APC was dependent on its serine protease activity., Conclusion: APC is a physiologically relevant activator of MMPs and cartilage breakdown in human OA. The effects of APC are dependent on its proteolytic activity and as-yet-undefined cell and/or cartilage matrix factors, and inhibition of this pathway may provide a novel therapeutic target to halt the progression of cartilage damage in OA., (Copyright © 2014 by the American College of Rheumatology.)

MEK inhibitors (MEKi) PD0325901 and AZD6244 (Selumetinib) are drugs currently under clinical investigation for cancer treatment, however the Ras-MAPK pathway is also an important mediator of normal bone cell differentiation and function. In this study we examined the effects of these compounds on endochondral processes using both in vitro and in vivo models. Treatment with PD0325901 or AZD6244 significantly increased Runx2 and Alkaline phosphate gene expression in calvarial osteoblasts and decreased TRAP+ cells in induced osteoclast cultures. To test the effects of these drugs on bone healing, C57/Bl6 mice underwent a closed tibial fracture and were treated with PD0325901 or AZD6244 at 10mg/kg/day. Animals were culled at day 10 and at day 21 post-fracture for analysis of the fracture callus and the femoral growth plate in the contralateral leg. MEKi treatment markedly increased cartilage volume in the soft callus at day 10 post-fracture (+60% PD0325901, +20% AZD6244) and continued treatment led to a delay in cartilage remodeling. At the growth plate, we observed an increase in the height of the hypertrophic zone relative to the proliferative zone of +78% in PD0325901 treated mice. Osteoclast surface was significantly decreased both at the terminal end of the growth plate and within the fracture calluses of MEKi treated animals. The mechanistic effects of MEKi on genes encoding cartilage matrix proteins and catabolic enzymes were examined in articular chondrocyte cultures. PD0325901 or AZD6244 led to increased matrix protein expression (Col2a1 and Acan) and decreased expression of catabolic factors (Mmp13 and Adamts-5). Taken together, these data support the hypothesis that MEKi treatment can impact chondrocyte hypertrophy, matrix resorption, and fracture healing. These compounds can also affect bone architecture by expanding the hypertrophic zone of the growth plate and reducing osteoclast surface systemically., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

The purpose of this study is to test a methodology for describing the articulation of vowels. High front vowels are a test case because some theories suggest that high front vowels have little cross-linguistic variation. Acoustic studies appear to show counterexamples to these predictions, but purely acoustic studies are difficult to interpret because of the many-to-one relation between articulation and acoustics. In this study, vocal tract dimensions, including constriction degree and position, are measured from cinéradiographic and x-ray data on high front vowels from three different languages (North American English, French, and Mandarin Chinese). Statistical comparisons find several significant articulatory differences between North American English /i/ and Mandarin Chinese and French /i/. In particular, differences in constriction degree were found, but not constriction position. Articulatory synthesis is used to model the acoustic consequences of some of the significant articulatory differences, finding that the articulatory differences may have the acoustic consequences of making the latter languages' /i/ perceptually sharper by shifting the frequencies of F(2) and F(3) upwards. In addition, the vowel /y/ has specific articulations that differ from those for /i/, including a wider tongue constriction, and substantially different acoustic sensitivity functions for F(2) and F(3).

Traditional models of mappings from midsagittal cross-distances to cross-sectional areas use only local cross-distance information. These are not the optimal models on which to base the construction of a mapping between the two domains. This can be understood because phonemic identity can affect the relation between local cross-distance and cross-sectional area. However, phonemic identity is not an appropriate independent variable for the control of an articulatory synthesizer. Two alternative approaches for constructing cross-distance to area mappings that can be used for articulatory synthesis are presented. One is a vowel height-sensitive model and the other is a non-parametric model called loess. These depend on global cross-distance information and generally perform better than the traditional models., (© 2012 Acoustical Society of America.)

Objectives: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation., Methods: SOST and other Wnt-β-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250 ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-β-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified., Results: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-β-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro., Conclusions: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage., (Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Platinum-group element (PGE) concentrations in sewage sludge and incinerator ash compared with average PGE concentrations in road dust show a common pattern, characterized by a negative Rh anomaly. This similarity, found at 9 UK incinerators, suggests that there is a universal characteristic PGE pattern produced by common processes of dispersal of Pt, Pd and Rh derived from automobile catalytic converters. Ninety-one sewage sludge and incinerator ash samples from the sewage treatment facilities in Sheffield, Birmingham and 7 other UK cities were analyzed for PGE. The highest concentrations are 602ppb Pt and 710ppb Pd with lower maximum concentrations of 65ppb Rh, 100ppb Ru, 33ppb Ir and 12ppb Os. Ash from incinerated sewage was found to have higher PGE concentrations compared to the original sludge and the PGE ratios are preserved during incineration. Rh is more mobilized and dispersed than the other PGE as it is transported from roads into the drainage system and into sewage. Pt/Pd ratios of 1.0 in road dust and 0.9 in sewage and incinerator ash suggest that Pd is more mobile than Pt during dispersal. PGE abundances in stored incinerator ash of varying ages appear to have been affected by the variation in use of Pt, Pd and Rh in catalytic converters due to variation in their market prices. Concentrations of Os, Ir and Ru in ashes are greater in Sheffield and London than all the other city sites and may be derived from point industrial sources.

The purpose of this study was to devise a consistent and robust method for defining vocal tract constrictions in high front vowels. A procedure was devised to find the length and position of the articulatory constriction in high front vowels that is not sensitive to local fluctuations in vocal tract shape and to the constriction-defining parameters. A method based on a visual examination of plots for constriction length and position as functions of the constriction-defining parameters was found to provide stable constriction definitions.

The Coisley Hill roundabout, a typical urban source for PGE in stream sediments, has anomalously high values of up to 408 ppb Pt, 444 ppb Pd and 113 ppb Rh in road dust, up to 416 ppb Pt and 278 ppb Pd in gulley sediment and up to 606 ppb Pt and 1050 ppb Pd in verge soil. For samples collected at the same time, the road dust values are much higher than in sediments in the Shire Brook stream, that drains the roundabout, with values of 3-64 ppb Pt, 4-57 ppb Pd and up to 7 ppb Rh. Downstream sediments from rivers Rother and Don have lower values of 2-35 ppb Pt, 2-14 ppb Pd and up to 3 ppb Rh. The Humber estuary values are low with 6-8 ppb Pt, 5-8 ppb Pd and 1-2 ppb Rh. Pt/Pd increases down catchment with Coisley Hill 0.8, Shire Brook 1.0, Trent and Don 1.5 and the Humber estuary 2.0. Pt/Rh and Pd/Rh also increase downstream. Precious metals are generally dispersed away from their vehicle catalytic source and Pd is dispersed more than Pt and Rh but Pt and Pd are re-concentrated in acid mine drainage in the Shire Brook, with concentrations varying with stream flow. Pt and Pd values are slightly elevated at the tidal limit and in mud deposited when the river is in spate. On Coisley Hill, values of 133 ppb Pt and 230 ppb Pd occur in dust from a new road surface (two weeks old when sampled). These are similar to those on much older road surfaces suggesting that Pt and Pd collect and disperse rapidly from roads. Au is low in road dust and higher values in conurbations suggest the presence of more Au sources in urban rather than in rural areas. Au values are not diluted downstream as much as PGE suggesting different processes of dispersion and sedimentation.

In a re-analysis of x rays of speakers producing Swedish vowels, midsagittal pharyngeal dimensions were predicted from anterior tongue positions using procedures based on estimated tongue pellet positions. Principal component analysis was used to reduce the number of pellet degrees of freedom from eight to three prior to applying linear regression from these three independent variables to dependent vocal tract midsagittal cross distances. Except for the regions around the laryngopharynx and uvula, the pharynx dimensions were predictable from linear regressions and were significant at the p<0.05 level. Numerical experiments show that it is crucial to reduce the number of independent variables in tests of statistical significance.

Platinum (Pt) and Palladium (Pd) concentrations have been analysed in 194 samples from within the city of Sheffield in the UK. The samples were taken from road dust, gully pots (also known as drains), soils, a motorway drainage pipe, rivers, lakes, sewage sludge, incinerator ash, incinerator ash in landfill, street cleansers and gully cleansers. The introduction of Pt- and Pd-bearing automobile catalysts, has been cited as the cause of a rise in the concentration of urban Pt and Pd accumulations. Geochemical analyses for the different sample types are used here to show how the Pt and Pd accumulate in different urban environments as they are transported from their catalytic source. Initially Pt and Pd collect in road dust and gully pots at values of up to 450 ppb although most analyses for both elements are around 100 ppb. The four roadside soils analysed, have a great range in values, the highest with a value of over 600 ppb Pt and 1000 ppb Pd. Then the fate of the Pt and Pd is either to be removed by gully flushers and road sweepers (which contain around half the concentration of that in road dust) or to be washed from the roads, through the gully pots, into either the river or urban drainage systems. Due to the addition of terrestrial sediments, river samples contain much reduced values of Pt and Pd, at approximately an order of magnitude lower than in road dust. Similarly, sewage sludge contains Pt and Pd values which are lower than road dust. However, the Pt and Pd analyses are much higher in incinerated sewage (with many samples over 150 ppb for both metals), probably due to the loss of the mass of other material during the incineration process. Weathered incinerator ash in landfill has lower values of Pt and Pd than fresh ash from the incinerator. Although the range in values of Pt and Pd is similar for road dust and gully pot sediments their modal values tell a different story. The mode for Pt is very similar for both road dust and gully pot sediments, at around 100 ppb, whereas there is a drop of 50 ppb in the mode for Pd in the gully pots (from 80 ppb to around 40 ppb). Given that gully pot sediment is derived from road dust, it is suggested that in gully pots, Pd is preferentially mobilized over Pt. Furthermore, a comparison of the modal values of Pt and Pd in river sediments suggests that this process continues into the natural drainage system of the city.

Purpose: This study evaluates bone regeneration of critical sized cranial vault defects in New Zealand white rabbits using four commercially available bone substitutes: OsteoSet (calcium sulphate pellets), DynaGraft Putty (demineralized bone matrix delivered in a poloxmer excipient), Norian CRS, and Bone Source (two commercially available calcium phosphate cements)., Materials and Methods: Critical sized defects 15 mm in diameter were created bilaterally in the parietal bones of 30 adult male New Zealand White rabbits. They were divided into three groups with ten animals in each. Bone healing was assessed clinically, radiographically, and histomorphometrically. Group 1 had calcium sulfate bioimplant on one side of the calvarium and an unfilled defect on the contralateral side. Group 2 had DBM putty on one side and Poloxamer gel on the contralateral side. Group 3, the Calcium phosphate cements (CPC), had Norian CRS on one side and Bone Source on the contralateral side. Five animals in each group were killed at 6 weeks and 12 weeks post operatively., Results: All unfilled defects healed with fibrous scar, as did the Plaster of Paris and the poloxamer gel defects. Defects reconstructed with the demineralized bone matrix putty healed with bone throughout the entire defect. This was obvious clinically and radiographically where the defects appeared completely filled with a dense radiopaque tissue. The six-week group displayed new bone formation (87.1%) surrounding the remaining allogeneic particles. Resorption was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. By 12 weeks, the demineralized bone putty bioimplant was almost completely replaced by new bone (95.5%). Both calcium phosphate cement groups (Norian CRS and Bone Source) had identical patterns of healing. They clinically were visible and firm and uniformly radiopaque with little evidence of new bone formation. Histologically the cement remained unresorbed with little new bone with in the defect at 12 weeks., Conclusions: The utilization of a demineralized bone matrix putty appeared to allow for complete closure of critical sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks.

One hundred and twenty-two AFLP markers were mapped using an IR64 x Azucena rice doubled-haploid (DH) population. The distribution of these mapped markers was monitored across a set of 48 diverse landraces of rice. Strong statistical associations were observed between 960 of the 7381 possible pairs of markers across the diverse material. These 960 strongly associated pairs of markers mapped to the same chromosomes in only 111 cases. The remaining 849 pairs were the result of association between markers found on different chromosomes. More than 21% of these genetically unlinked but strongly associated markers are not randomly distributed across the genome but instead occupy blocks of DNA on different rice chromosomes. Amongst associated blocks, there has clearly been maintenance of combinations of marker alleles across very diverse germplasm. Analyses have also revealed that markers are found in association with performance for each of four quantitative traits in both the diverse landrace material and a DH mapping population. It is proposed that the present data provide strong evidence for the co-adaptation of geographically distinct landraces and that this has resulted over time in the maintenance of 'adaptive gene complexes' involving agronomically important quantitative traits.

In this article an implementation of a vocal tract model and its validation are described. The model uses a transmission line model to calculate pole and zero frequencies for a vocal tract with a closed side-branch such as a sublingual cavity. In the validation study calculated pole and zero frequencies from the model are compared with frequencies estimated using elementary acoustic formulas for a variety of vocal tract configurations.

Rice genetic resources, comprising landrace varieties, modern and obsolete varieties, genetic stocks, breeding lines, and the wild rices, are the basis of world food security. The International Rice Genebank at the International Rice Research Institute in the Philippines conserves the largest and most diverse collection of rice germplasm. The facilities of the genebank ensure the long-term preservation of this important diversity. In field research, factors that affect long-term viability of rice seeds have been identified, leading to the introduction of modified practices for germplasm multiplication and regeneration. The value of conserved germplasm can be assessed in terms of useful traits for rice breeding and the economic impact that germplasm utilization has on rice production and productivity. The application of molecular markers is changing perspectives on germplasm management. International policies affecting access to and use of rice germplasm are discussed.

Electronic control of the G-valve and pressure breathing regulator is being implemented in some advanced life support systems used in aircrew protection. This technological improvement, however, has not reached its full potential in the research environment. A computer-controlled life support system interface providing programmable schedules for G-suit inflation and positive pressure breathing during +Gz (PBG) was developed. Output pressures from a G-valve and pressure breathing regulator (Carleton Technologies) were controlled by a Macintosh computer running LabVIEW software. Required pressures were determined as functions of single or multiple control inputs (i.e. +Gz level, a pressure signal, time, etc.). Subject safety was ensured via hardware limitations and status checks incorporated into the software. Experiments conducted at +1 Gz and at various +Gz levels evaluated the computer software-life support hardware interface. Open-loop algorithms allowed independent control of multiple regulators using simple (single input) and complex (multiple input with adaptive loop) control structures. The system provided accurate and reproducible G-suit and mask pressures. Time of inflation, peak pressure attained, and deflation rate were effectively controlled at all +Gz levels. The ability to alter the pressure schedules independent of +Gz or time allowed comprehensive control over all parameters necessary to conduct acceleration research involving advanced life support systems.

Edwardsiella tarda infections are uncommon and have often been reported in association with pet reptiles. The majority of these infections occur as gastrointestinal disorders in immunocompromised hosts. We believe this to be the first reported American case of tuboovarian abscess caused by this organism in an otherwise healthy woman whose only known exposure was to raw seafood. This patient had fever and lower abdominal pain caused by a severe Edwardsiella tarda pelvic abscess that required surgical drainage and intravenous antibiotics for complete recovery.

A set of accessions of Oryza sativa from the International Rice Research Institute (Philippines) that included known and suspected duplicates as well as closely related germplasm has been subjected to RAPD analysis. The number of primers, the number of polymorphic bands and the total number of bands were determined that will allow the accurate discrimination of these categories of accessions, including the identification of true and suspected duplicates. Two procedures have been described that could be employed on a more general basis for identifying duplicates in genetic resources collections, and further discussion on the values of such activities is presented.

As part of the development of a molecular toolkit for the study of diversity within large plant germplasm collections, RAPD technology has been applied to accessions of rice (Oryza sativa) obtained from the major world collection held at IRRI (the International Rice Research Institute) which supplies germplasm to breeders. Methods for the speedy extraction of DNA representative of a rice accession, its amplification by PCR to reveal reproducible products, and the analysis of the banding data using numerical techniques have been established. The biological meaningfulness of RAPD data has also been demonstrated by reference to previous work on classification and crossability.

This paper describes two electromagnetic midsagittal articulometer (EMMA) systems that were developed for transducing articulatory movements during speech production. Alternating magnetic fields are generated by transmitter coils that are mounted in an assembly that fits on the head of a speaker. The fields induce alternating voltages in a number of small transducer coils that are attached to articulators in the midline plane, inside and outside the vocal tract. The transducers are connected by fine lead wires to receiver electronics whose output voltages are processed to yield measures of transducer locations as a function of time. Measurement error can arise with this method, because as the articulators move and change shape, the transducers can undergo a varying amount of rotational misalignment with respect to the transmitter axes; both systems are designed to correct for transducer misalignment. For this purpose, one system uses two transmitters and biaxial transducers; the other uses three transmitters and single-axis transducers. The systems have been compared with one another in terms of their performance, human subjects compatibility, and ease of use. Both systems can produce useful midsagittal-plane data on articular movement, and each one has a specific set of advantages and limitations. (Two commercially available systems are also described briefly for comparison purposes). If appropriate experimental controls are used, the three-transmitter system is preferable for practical reasons.

The Endosperm Balance Number (EBN) hypothesis can explain to a considerable degree the crossability between tuber-bearing Solanum species. It has been shown to be genetically controlled and is dosage dependent. There is a good correlation between EBN and the postulated evolution and present taxonomy of potatoes. The primitive white stellate-flowered species from Mexico are 1EBN, and this condition is also found in species from South America with flowers of the same colour and shape. The evolution of a rotate corolla seems to be correlated with 2EBN. It is postulated that the 2EBN state arose as a reproductive isolating mechanism in South America. The taxonomic and evolutionary implications of the EBN hypothesis are discussed.

A factor-analytic model, PARAFAC, has been shown to yield highly significant and interpretable results when applied to the analysis of tongue shapes in particular languages. However, the forms of the solutions differ from language to language. A conceptual model that provides an account for cross-language variability in terms of coordinative structures that may vary in a language-specific manner is developed. This model rationalizes both the success of the PARAFAC procedure within languages and the poor cross-language replicability of PARAFAC solutions. We consider methods for quantitatively comparing the results of PARAFAC analyses of data from different languages using data from Icelandic and English as a test case. A cross-language factor solution that accounts for 90% of the variance in tongue position measurements is presented and interpreted in terms of the conceptual model.

The authors describe a pregnancy complicated by rhesus sensitization and the May-Hegglin anomaly. The principal objective in caring for the patient was prevention of maternal and fetal hemorrhage. Transfusion of type-specific platelets corrected the patient's abnormal bleeding time. Cesarean section resulted in delivery of a healthy, but thrombocytopenic, infant who subsequently was shown to have the May-Hegglin defect.