873 resultados para 13200-058


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The difluoromethyl-allo-threonyl hydroxamate-based compound LPC-058 is a potent inhibitor of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) in Gram-negative bacteria. A scalable synthesis of this compound is described. The key step in the synthetic sequence is a transition metal/base-catalyzed aldol reaction of methyl isocyanoacetate and difluoroacetone, giving rise to 4-(methoxycarbonyl)-5,5-disubstituted 2-oxazoline. A simple NMR-based determination of enantiomeric purity is also described.

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The South Carolina Department of Health and Human Services publishes Medicaid Bulletins to clarify existing policies or explain new policies of the Medicaid program.

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Three anaerobic ponds used to store and treat piggery wastes were fully covered with permeable materials manufactured from polypropylene geofabric, polyethylene shade cloth and supported straw. The covers were assessed in terms of efficacy in reducing odour emission rates over a 40-month period. Odour samples were collected from the surface of the covers, the surface of the exposed liquor and from the surface of an uncovered (control) pond at one of the piggeries. Relative to the emission rate of the exposed liquor at each pond, the polypropylene, shade cloth and straw covers reduced average emission rates by 76%, 69% and 66% respectively. At the piggery with an uncovered control pond, the polypropylene covers reduced average odour emission rates by 50% and 41% respectively. A plausible hypothesis, consistent with likely mechanisms for the odour reduction and the olfactometric method used to quantifying the efficacy of the covers, is offered.

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Protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD). The condition is characterised by chronic, systemic low-grade inflammation which affects nutritional status by a variety of mechanisms including reducing appetite and food intake and increasing muscle catabolism. PEW is linked with co-morbidities such as cardiovascular disease, and is associated with lower quality of life, increased hospitalisations and a 6-fold increase in risk of death1. Significant gender differences have been found in the severity and effects of several markers of PEW. There have been limited studies testing the ability of anti-inflammatory agents or nutritional interventions to reduce the effects of PEW in dialysis patients. This thesis makes a significant contribution to the understanding of PEW in dialysis patients. It advances understanding of measurement techniques for two of the key components, appetite and inflammation, and explores the effect of fish oil, an anti-inflammatory agent, on markers of PEW in dialysis patients. The first part of the thesis consists of two methodological studies conducted using baseline data. The first study aims to validate retrospective ratings of hunger, desire to eat and fullness on visual analog scales (VAS) (paper and pen and electronic) as a new method of measuring appetite in dialysis patients. The second methodological study aims to assess the ability of a variety of methods available in routine practice to detect the presence of inflammation. The second part of the thesis aims to explore the effect of 12 weeks supplementation with 2g per day of Eicosapentaenoic Acid (EPA), a longchain fatty acid found in fish oil, on markers of PEW. A combination of biomarkers and psychomarkers of appetite and inflammation are the main outcomes being explored, with nutritional status, dietary intake and quality of life included as secondary outcomes. A lead in phase of 3 months prior to baseline was used so that each person acts as their own historical control. The study also examines whether there are gender differences in response to the treatment. Being an exploratory study, an important part of the work is to test the feasibility of the intervention, thus the level of adherence and factors associated with adherence are also presented. The studies were conducted at the hemodialysis unit of the Wesley Hospital. Participants met the following criteria: adult, stage 5 CKD on hemodialysis for at least 3 months, not expected to receive a transplant or switch to another dialysis modality during the study, absence of intellectual impairment or mental illness impairing ability to follow instructions or complete the intervention. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and 12 weeks. Inflammation was measured using five biomarkers: c-reactive protein (CRP), interleukin-6 (IL6), intercellular adhesion molecule (sICAM-1), vascular cell adhesion molecule (sVCAM-1) and white cell count (WCC). Subjective appetite was measured using the first question from the Appetite and Dietary Assessment (ADAT) tool and VAS for measurements of hunger, desire to eat and fullness. A novel feature of the study was the assessment of the appetite peptides leptin, ghrelin and peptide YY as biomarkers of appetite. Nutritional status/inflammation was assessed using the Malnutrition-Inflammation Score (MIS) and the Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day records. Quality of life was measured using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™ v1.3 © RAND University), which combines the Short-Form 36 (SF36) with a kidney-disease specific module2. A smaller range of these variables was available for analysis during the control phase (CRP, ADAT, dietary intake and nutritional status). Statistical analysis was carried out using SPSS version 14 (SPSS Inc, Chicago IL, USA). Analysis of the first part of the thesis involved descriptive and bivariate statistics, as well as Bland-Altman plots to assess agreement between methods, and sensitivity analysis/ROC curves to test the ability of methods to predict the presence of inflammation. The unadjusted (paired ttests) and adjusted (linear mixed model) change over time is presented for the main outcome variables of inflammation and appetite. Results are shown for the whole group followed by analyses according to gender and adherence to treatment. Due to the exploratory nature of the study, trends and clinical significance were considered as important as statistical significance. Twenty-eight patients (mean age 61±17y, 50% male, dialysis vintage 19.5 (4- 101) months) underwent baseline assessment. Seven out of 28 patients (25%) reported sub-optimal appetite (self-reported as fair, poor or very poor) despite all being well nourished (100% SGA A). Using the VAS, ratings of hunger, but not desire to eat or fullness, were significantly (p<0.05) associated with a range of relevant clinical variables including age (r=-0.376), comorbidities (r=-0.380) nutritional status (PG-SGA score, r=-0.451), inflammatory markers (CRP r=-0.383; sICAM-1 r=-0.387) and seven domains of quality of life. Patients expressed a preference for the paper and pen method of administering VAS. None of the tools (appetite, MIS, PG-SGA, albumin or iron) showed an acceptable ability to detect patients who are inflamed. It is recommended that CRP should be tested more frequently as a matter of course rather than seeking alternative methods of measuring inflammation. 27 patients completed the 12 week intervention. 20 patients were considered adherent based on changes in % plasma EPA, which rose from 1.3 (0.94)% to 5.2 (1.1)%, p<0.001, in this group. The major barriers to adherence were forgetting to take the tablets as well as their size. At 12 weeks, inflammatory markers remained steady apart from the white cell count which decreased (7.6(2.5) vs 7.0(2.2) x109/L, p=0.058) and sVCAM-1 which increased (1685(654) vs 2249(925) ng/mL, p=0.001). Subjective appetite using VAS increased (51mm to 57mm, +12%) and there was a trend towards reduction in peptide YY (660(31) vs 600(30) pg/mL, p=0.078). There were some gender differences apparent, with the following adjusted change between baseline and week 12: CRP (males -3% vs females +17%, p=0.19), IL6 (males +17% vs females +48%, p=0.77), sICAM-1 (males -5% vs females +11%, p=0.07), sVCAM-1 (males +54% vs females +19%, p=0.08) and hunger ratings (males 20% vs females -5%, p=0.18). On balance, males experienced a maintainence or reduction in three inflammatory markers and an improvement in hunger ratings, and therefore appeared to have responded better to the intervention. Compared to those who didn’t adhere, adherent patients maintained weight (mean(SE) change: +0.5(1.6) vs - 0.8(1.2) kg, p=0.052) and fat-free mass (-0.1 (1.6) vs -1.8 (1.8) kg, p=0.045). There was no difference in change between the intervention and control phase for CRP, appetite, nutritional status or dietary intake. The thesis makes a significant contribution to the evidence base for understanding of PEW in dialysis patients. It has advanced knowledge of methods of assessing inflammation and appetite. Retrospective ratings of hunger on a VAS appear to be a valid method of assessing appetite although samples which include patients with very poor appetite are required to confirm this. Supplementation with fish oil appeared to improve subjective appetite and dampen the inflammatory response. The effectiveness of the intervention is influenced by gender and adherence. Males appear to be more responsive to the primary outcome variables than females, and the quality of response is improved with better adherence. These results provide evidence to support future interventions aimed at reducing the effects of PEW in dialysis patients.

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Aims: To describe a local data linkage project to match hospital data with the Australian Institute of Health and Welfare (AIHW) National Death Index (NDI) to assess longterm outcomes of intensive care unit patients. Methods: Data were obtained from hospital intensive care and cardiac surgery databases on all patients aged 18 years and over admitted to either of two intensive care units at a tertiary-referral hospital between 1 January 1994 and 31 December 2005. Date of death was obtained from the AIHW NDI by probabilistic software matching, in addition to manual checking through hospital databases and other sources. Survival was calculated from time of ICU admission, with a censoring date of 14 February 2007. Data for patients with multiple hospital admissions requiring intensive care were analysed only from the first admission. Summary and descriptive statistics were used for preliminary data analysis. Kaplan-Meier survival analysis was used to analyse factors determining long-term survival. Results: During the study period, 21 415 unique patients had 22 552 hospital admissions that included an ICU admission; 19 058 surgical procedures were performed with a total of 20 092 ICU admissions. There were 4936 deaths. Median follow-up was 6.2 years, totalling 134 203 patient years. The casemix was predominantly cardiac surgery (80%), followed by cardiac medical (6%), and other medical (4%). The unadjusted survival at 1, 5 and 10 years was 97%, 84% and 70%, respectively. The 1-year survival ranged from 97% for cardiac surgery to 36% for cardiac arrest. An APACHE II score was available for 16 877 patients. In those discharged alive from hospital, the 1, 5 and 10-year survival varied with discharge location. Conclusions: ICU-based linkage projects are feasible to determine long-term outcomes of ICU patients

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The ideal dermal matrix should be able to provide the right biological and physical environment to ensure homogenous cell and extracellular matrix (ECM) distribution, as well as the right size and morphology of the neo-tissue required. Four natural and synthetic 3D matrices were evaluated in vitro as dermal matrices, namely (1) equine collagen foam, TissuFleece®, (2) acellular dermal replacement, Alloderm®, (3) knitted poly(lactic-co-glycolic acid) (10:90)–poly(-caprolactone) (PLGA–PCL) mesh, (4) chitosan scaffold. Human dermal fibroblasts were cultured on the specimens over 3 weeks. Cell morphology, distribution and viability were assessed by electron microscopy, histology and confocal laser microscopy. Metabolic activity and DNA synthesis were analysed via MTS metabolic assay and [3H]-thymidine uptake, while ECM protein expression was determined by immunohistochemistry. TissuFleece®, Alloderm® and PLGA–PCL mesh supported cell attachment, proliferation and neo-tissue formation. However, TissuFleece® contracted to 10% of the original size while Alloderm® supported cell proliferation predominantly on the surface of the material. PLGA–PCL mesh promoted more homogenous cell distribution and tissue formation. Chitosan scaffolds did not support cell attachment and proliferation. These results demonstrated that physical characteristics including porosity and mechanical stability to withstand cell contraction forces are important in determining the success of a dermal matrix material.

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Background: A number of studies have examined the relationship between high ambient temperature and mortality. Recently, concern has arisen about whether this relationship is modified by socio-demographic factors. However, data for this type of study is relatively scarce in subtropical/tropical regions where people are well accustomed to warm temperatures. Objective: To investigate whether the relationship between daily mean temperature and daily all-cause mortality is modified by age, gender and socio-economic status (SES) in Brisbane, Australia. Methods: We obtained daily mean temperature and all-cause mortality data for Brisbane, Australia during 1996–2004. A generalised additive model was fitted to assess the percentage increase in all deaths with every one degree increment above the threshold temperature. Different age, gender and SES groups were included in the model as categorical variables and their modification effects were estimated separately. Results: A total of 53,316 non-external deaths were included during the study period. There was a clear increasing trend in the harmful effect of high temperature on mortality with age. The effect estimate among women was more than 20 times that among men. We did not find an SES effect on the percent increase associated with temperature. Conclusions: The effects of high temperature on all deaths were modified by age and gender but not by SES in Brisbane, Australia.

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The mineral tsumebite Pb2Cu(PO4)(SO4)(OH), a copper phosphate-sulfate hydroxide of the brackebuschite group has been characterised by Raman and infrared spectroscopy. The brackebuschite mineral group are a series of monoclinic arsenates, phosphates and vanadates of the general formula A2B(XO4)(OH,H2O), where A may be Ba, Ca, Pb, Sr, while B may be Al, Cu2+,Fe2+, Fe3+, Mn2+, Mn3+, Zn and XO4 may be AsO4, PO4, SO4,VO4. Bands are assigned to the stretching and bending modes of PO43- and HOPO3 units. Hydrogen bond distances are calculated based upon the position of the OH stretching vibrations and range from 2.759 Å to 3.205 Å. This range of hydrogen bonding contributes to the stability of the mineral.

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Some minerals are formed which show poorly defined X-ray diffraction patterns. Vibrational spectroscopy offers one of the few methods for the assessment of the structure of the oxyanions in such minerals. Among this group of minerals is mallestigite with formula Pb3Sb5+(SO4)(AsO4)(OH)6•3H2O. The objective of this research is to determine the molecular structure of the mineral mallestigite using vibrational spectroscopy. Raman and infrared bands are attributed to the AsO43- , SO42- and water stretching vibrations. Mallestigite is a mineral formed in ancient waste dumps such as occurs at Mallestiger, Carinthia, Austria and as such is a mineral of archaeological significance.

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A new accelerometer, the Kenz Lifecorder EX (LC; Suzuken Co. Ltd, Nagoya, Japan), offers promise as a feasible monitor alternative to the commonly used Actigraph (AG: Actigraph LLC, Fort Walton Beach, FL). Purpose: This study compared the LC and AG accelerometers and the Yamax SW-200 pedometer (DW) under free-living conditions with regard to children's steps taken and time in light-intensity physical activity (PA) and moderate to vigorous PA (MVPA). Methods: Participants (N = 31, age = 10.2 ± 0.4 yr) wore LC, AG, and DW monitors from arrival at school (7:45 a.m.) until they went to bed. Time in light and MVPA intensities were calculated using two separate intensity classifications for the LC (LC_4 and LC_5) and four classifications for the AG (AG_Treuth, AG_Puyau, AG_Trost, and AG_Freedson). Both accelerometers provided steps as outputs. DW steps were self-recorded. Repeated-measures ANOVA was used to assess overlapping monitor outputs. Results: There was no difference between DW and LC steps (Δ = 200 steps), but a nonsignificant trend was observed in the pairwise comparison between DW and AG steps (Δ = 1001 steps, P = 0.058). AG detected significantly greater steps than the LC (Δ = 801 steps, P = 0.001). Estimates of light-intensity activity minutes ranged from a low of 75.6 ± 18.4 min (LC_4) to a high of 309 ± 69.2 min (AG_Treuth). Estimates of MVPA minutes ranged from a low of 25.9 ± 9.4 min (LC_5) to a high of 112.2 ± 34.5 min (AG_Freedson). No significant differences in MVPA were seen between LC_5 and AG_Treuth (Δ = 4.9 min) or AG_Puyau (Δ = 1.7 min). Conclusion: The LC detected a comparable number of steps as the DW but significantly fewer steps than the AG in children. Current results indicate that the LC_5 and either AG_Treuth or AG_Puyau intensity derivations provide similar mean estimates of time in MVPA during-free living activity in 10-yr-old children.

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Traffic related emissions have been recognised as one of the main sources of air pollutants. In the research study discussed in this paper, variability of atmospheric total suspended particulate matter (TSP), polycyclic aromatic hydrocarbons (PAH) and heavy metal (HM) concentrations with traffic and land use characteristics during weekdays and weekends were investigated. Data required for the study were collected from a range of sampling sites to ensure a wide mix of traffic and land use characteristics. The analysis undertaken confirmed that zinc has the highest concentration in the atmospheric phase during weekends as well as weekdays. Although the use of leaded gasoline was discontinued a decade ago, lead was the second most commonly detected heavy metal. This is attributed to the association of previously generated lead with roadside soil and re-suspension to the atmosphere. Soil related particles are the primary source of TSP and manganese to the atmosphere. The analysis further revealed that traffic sources are dominant in gas phase PAHs compared to the other sources during weekdays. Land use related sources become important contributors to atmospheric PAHs during weekends when traffic sources are at their minimal levels.

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Aim: To determine the effects of an acute multi-nutrient supplement on physiological, performance and recovery responses to intermittent-sprint running and muscular damage during rugby union matches. Methods: Using a randomised, double-blind, cross-over design, twelve male rugby union players ingested either 75 g of a comprehensive multi-nutrient supplement (SUPP), [Musashi] or 1 g of a taste and carbohydrate matched placebo (PL) for 5 days pre-competition. Competitive rugby union game running performance was then measured using 1 Hz GPS data (SPI10, SPI elite, GPSports), in addition to associated blood draws, vertical jump assessments and ratings of perceived muscular soreness (MS) pre, immediately post and 24 h post-competition. Baseline (BL) GPS data was collected during six competition rounds preceding data collection. Results: No significant differences were observed between supplement conditions for all game running, vertical jump, and ratings of perceived muscular soreness. However, effect size analysis indicated SUPP ingestion increased 1st half very high intensity running (VHIR) mean speed (d = 0.93) and 2nd half relative distance (m/min) (d = 0.97). Further, moderate increases in 2nd half VHIR distance (d = 0.73), VHIR m/min (d = 0.70) and VHIR mean speed (d = 0.56) in SUPP condition were also apparent. Moreover, SUPP demonstrated significant increases in 2nd half dist m/min, total game dist m/min and total game HIR m/min compared with BL data (P < 0.05). Further, large ES increases in VHIR time (d = 0.88) and moderate increases in 2nd half HIR m/min (d = 0.65) and 2nd half VHIR m/min (d = 0.74) were observed between SUPP and BL. Post-game aspartate aminotransferase (AST) (d = 1.16) and creatine kinase (CK) (d = 0.97) measures demonstrated increased ES values with SUPP, while AST and CK values correlated with 2nd half VHIR distance (r = −0.71 and r = −0.76 respectively). Elevated c-reactive protein (CRP) was observed post-game in both conditions, however was significantly blunted with SUPP (P = 0.05). Additionally, pre-game (d = 0.98) and post-game (d = 0.96) increases in cortisol (CORT) were apparent with SUPP. No differences were apparent between conditions for pH, lactate, glucose, HCO3, vertical jump assessments and MS (P > 0.05). Conclusion: These findings suggest SUPP may assist in the maintenance of VHIR speeds and distances covered during rugby union games, possibly via the buffering qualities of SUPP ingredients (i.e. caffeine, creatine, bicarbonate). While the mechanisms for these findings are unclear, the similar pH between conditions despite additional VHIR during SUPP may support this conclusion. Finally, correlations between increased work completed at very high intensities and muscular degradation in SUPP conditions, may mask any anti-catabolic properties of supplementation.