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Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a "culture of safety." The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de-identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self-reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety-related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.

Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure.Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death.A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

Background Evolutionary origins of derived morphologies ultimately stem from changes in protein structure, gene regulation, and gene content. A well-assembled, annotated reference genome is a central resource for pursuing these molecular phenomena underlying phenotypic evolution. We explored the genome of the Gulf pipefish (Syngnathus scovelli), which belongs to family Syngnathidae (pipefishes, seahorses, and seadragons). These fishes have dramatically derived bodies and a remarkable novelty among vertebrates, the male brood pouch. Results We produce a reference genome, condensed into chromosomes, for the Gulf pipefish. Gene losses and other changes have occurred in pipefish hox and dlx clusters and in the tbx and pitx gene families, candidate mechanisms for the evolution of syngnathid traits, including an elongated axis and the loss of ribs, pelvic fins, and teeth. We measure gene expression changes in pregnant versus non-pregnant brood pouch tissue and characterize the genomic organization of duplicated metalloprotease genes (patristacins) recruited into the function of this novel structure. Phylogenetic inference using ultraconserved sequences provides an alternative hypothesis for the relationship between orders Syngnathiformes and Scombriformes. Comparisons of chromosome structure among percomorphs show that chromosome number in a pipefish ancestor became reduced via chromosomal fusions. Conclusions The collected findings from this first syngnathid reference genome open a window into the genomic underpinnings of highly derived morphologies, demonstrating that de novo production of high quality and useful reference genomes is within reach of even small research groups. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1126-6) contains supplementary material, which is available to authorized users.

Aims To determine the efficacy and patient perception of various transfer procedures from paediatric to adult diabetes services. Methods Comparison between four districts in the Oxford Region employing different transfer methods, by retrospective study of case records and interviews of patients recently transferred from paediatric diabetes clinics. The main outcome measures were age at transfer, clinic attendance rates, HbA1c measurements and questionnaire responses. Results Two hundred and twenty-nine subjects (57% males) > 18 years old in 1998 and diagnosed with Type 1 diabetes

An etched long-period grating was used as a refractive index sensor for vapours of four volatile organic compounds, i.e. m-xylene, cyclohexane, trichloroethylene and commercial gasoline. The sensitivity to the vapours was further increased by solid-phase microextraction into a coating made of polydimethylsiloxane (PDMS)/polymethyl-octylsiloxane (PMOS) co-polymer. By further amplification of the optical loss in an optical cavity made of two identical fiber-Bragg gratings and interrogation by phase-shift cavity ring-down spectroscopy we could detect and distinguish xylene (detection limit: 134 ppm) from trichloroethylene (3300 ppm), cyclohexane (1850 ppm) and gasoline (10,500 ppm).

The contour lithography method [1] is used to improve the fabrication yield of previously demonstrated [2] microfluidic Fabry-Perot (FP) refractive index (RI) sensors. The sensors are then coated with polydimethylsiloxane (PDMS) based polymers to detect vapor analytes by solid-phase microextraction (SPME). Preliminary characterization of devices coated with two different polymers and exposed to xylenes vapors yields a maximum sensitivity of 0.015 nm/ppm and a detection limit below 120 ppm.

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1-81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log(10) copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.

The texture, or topography, interior of shells from native and exotic mollusks are measured and compared to determine if they can be discriminated. Area-scale fractal analysis is used to calculate relative areas as a function of scale, and the relative areas are used to evaluate the measurements. Measurements from a scanning laser profiler and from confocal and interferometric microscopes are compared, as are measurements of an original and a replica. The relative areas indicate clear differences between the measurement instruments. The largest relative areas are calculated from the confocal measurements. The trueness of the measurements has not been determined. However, the relative areas calculated from the confocal measurements are capable of discriminating the native clam from the exotic mussels with a confidence of greater than 99% at scales below 10 µm2. SCANNING 32: 250–255, 2010. © 2010 Wiley Periodicals, Inc.

Herpes simplex encephalitis was diagnosed by immunofluorescence and histology of a brain biopsy on the 19th day of life in a neonate in whom symptoms had begun at 12 days. Treatment with steroid, diuretic and cytosine arabinoside was begun and initially there was dramatic improvement in the symptoms. This improvement was not sustained, however, and the infant developed evidence of severe brain-damage. Disseminated herpes simplex virus infection is discussed and available therapy for this severe disease is outlined.

Many tons of electric furnace flue dust accumulated in an industrial area in Tifton, Georgia. Vehicles transporting the flue dust, classified as K061 hazardous waste because it contained lead and cadmium, initially dumped the material in a warehouse. Once the warehouse was full, the flue dust was dumped in uncovered piles. Run-off from the piles and wind-driven particles had the opportunity to contaminate nearby industries, residential buildings, and neighborhood soils over a period of many years. Scanning electron microscopy-energy dispersive x-ray spectrometry (SEM-EDS) was used to compare the morphology and chemical composition of fly ash dust from the suspect pile with samples collected from the surrounding buildings and soil. Adhesive samplers were used to collect dust that had accumulated in buildings surrounding the fly ash dump site. Suspect dust particles were analyzed by SEM-EDS and compared with known dust particles from the fly ash pile. Soil samples were dried, sieved, and the “fines” analyzed by SEM-EDS for comparison with samples from the fly ash pile. Fly ash particles similar in morphology and chemical composition to the fly ash in the suspect pile were identified in most of the buildings sampled surrounding the fly ash dump site and in all of the soil samples analyzed surrounding the dumpsite. This case study illustrates the usefulness of applying morphology and chemistry information acquired by SEM-EDS for pollution particle source determination.

An efficient method for the enantioselective 1,4-conjugate addition of amines to α,β-unsaturated esters containing an inexpensive chiral auxiliary, such as (S)-2-methyl-1-butanol and fenchyl alcohol, in solvent-free conditions mediated by solid lithium perchlorate is reported. Over 12 examples of the products are generated in excellent yields, accompanied by moderate enantioselectivity. The concentrated solution of LiClO4 in a diethyl ether system works well for the enantioselective 1,4-addition of organolithium compounds to α,β-unsaturated amides without any side reactions.

A survey was undertaken on the current assessment and refurbishment practices of North American utilities regarding substation grounding systems. The information was gathered using standard survey techniques where all interested parties were requested to fill out a short written survey and return it with the understanding that their responses would be kept anonymous. Survey results show that almost all utilities evaluate the integrity of their ground grids at some point, and have maintenance or engineering standards for determining the integrity. Test equipment is frequently used to evaluate integrity, and ground grids not meeting these standards are commonly upgraded. The results also show that most use high resistivity surfacing material, yet very few test the resistivity of the material at the time it is installed. This paper provides guidance on the recommended best practices based on these survey results, which can be used for benchmarking purposes. It also includes a short discussion on the importance of maintaining the substation grounding system.

A study of the hydrolysis of formamide is reported with the aims of isolating the water reaction for hydrolysis from the acid and base hydrolysis terms and determining the solvent deuterium kinetic isotope effect (dkie) on base-catalyzed hydrolysis. Respective activation parameters (ΔH‡and ΔS‡) of (17.0 ± 0.4) kcal mol–1and (–18.8 ± 1.3) cal mol–1K–1for the acid reaction and (17.9 ± 0.2) kcal mol–1and (–11.1 ± 0.5) cal mol–1K–1for the base reaction were determined from Eyring plots of the second-order rate constants over the range of 27–120°C. Kinetic studies at the minima of the pH/rate profiles in the pH range from 5.6 to 6.2 in MES buffers at 56°C, and in the pH range of 4.25–6.87 in acetate and phosphate buffers at 120°C are reported. At 56°C the available data fit the expression k56obs= 0.00303[H3O+] + 0.032[HO–] + (3.6 ± 0.1) × 10–9, while at 120°C the data fit k120obs= (0.15 ± 0.02)[H3O+] + (3.20 ± 0.24)[HO–] + (1.09 ± 0.29) × 10–6. Preliminary experimental estimates of Ea(ln A) of 22.5 kcal mol–1(15.03) for the water rate constant (kw) are calculated from an Arrhenius plot of the 56 and 120°C data giving an estimated kwof 1.1 × 10–10s–1(t1/2= 199 years) at 25°C. Solvent dkie values of kOH/kOD= 1.15 and 0.77 ± 0.06 were determined at [OL–] = 0.075 and 1.47 M, respectively. The inverse value is determined under conditions where the the first step of the reaction dominates and is analyzed in terms of a rate-limiting attack of OL–.Key words: formamide, activation parameters, water reaction, acid and base hydrolysis, solvent kinetic isotope effect.

Movement of radio-tagged riverine brown trout Salmo trutta, white sucker Catostomus commersoni and common carp Cyprinus carpio in the Grand River, Ontario, was minimal during the winter except during periods of high water discharge or the break-up of river ice. Ice break-up and flooding occur when southern air masses penetrate northwards in winter and as air temperatures increase in spring. Both white suckers and common carp moved the longest distances, generally in a downstream direction, during flooding and ice break-up. Brown trout moved less during these times. All three species had positive relationships between distance moved and water discharge. During periods of high water discharge and ice break-up, white suckers and common carp used backwater habitats more and main channel habitats less than during periods of low water discharge. During high flows, brown trout tended to use runs more and pools less. The break-up of river ice and accompanying flooding resulted in several fish being stranded on the floodplain. Backwater habitats appear to be important areas of refuge for riverine fishes during periods of flooding and ice break-up.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen involved in normal and abnormal angiogenesis. VEGF mRNA and protein are abundant in distal epithelium of midtrimester human fetal lung. In the present study, we identified immunoreactivity for KDR, a major VEGF-specific receptor, in distal lung epithelial cells of human fetal lung tissue, suggesting a possible autocrine or paracrine regulatory role for VEGF in pulmonary epithelial cell growth and differentiation. Addition of exogenous VEGF to human fetal lung explants resulted in increased epithelium volume density and lumen volume density in the tissues, both morphometric parameters of tissue differentiation. Cellular proliferation demonstrated by bromodeoxyuridine uptake was prominent in distal airway epithelial cells and increased in the VEGF-treated explants. VEGF-treated explants also demonstrated increased surfactant protein (SP) A mRNA, SP-C mRNA, and SP-A protein levels compared with controls. However, SP-B mRNA levels were unaffected by VEGF treatment. [3H]choline incorporation into total phosphatidylcholine was increased by VEGF treatment, but incorporation into disaturated phosphatidylcholine was not affected by exogenous VEGF. Based on these observations, we conclude that VEGF may be an important autocrine growth factor for distal airway epithelial cells in the developing human lung.

The interaction of La(3+) with diphenyl phosphate, methyl p-nitrophenyl phosphate, and bis(p-nitrophenyl) phosphate (4, 5, and 3) and the ensuing catalysis of methanolysis has been studied in methanol under completely homogeneous conditions of known pH. (31)P NMR shows that phosphates 3 and 4 are each associated with La(3+) as a rapidly interconverting mixture of complexes having 2:1, 1:1 (or 2:2), and 1:2 stoichiometry. At [La(3+)]2 x 10(-4) M, the kinetically dominant species in the pH regions of interest are phosphate-bound La(3+) dimers having 2-5 associated methoxides. Potentiometric titration reveals that 4 mM La(3+) alone in MeOH exhibits two apparent pK(a)s at 7.86 and 10.44 consuming 1 and 1.5 CH(3)O(-) per metal, the suggested structures being La(3+) dimers with first two and then five associated methoxides. In the presence of 0.5 equiv of 4 the potentiometric titration reveals strong complexation of 4 to La(3+) and a profile with apparent pK(a)s at 7.8 and 11.1 consuming 1 and 1.5 CH(3)O(-) per metal corresponding to phosphate-bridged La(3+) dimers with first two and then five associated methoxides. Methanolysis of 3-5 is strongly accelerated by La(3+). At pH 8.9 or 11.1, respectively, as little as 5 x 10(-4) M La(OTf)(3) accelerates the methanolysis of 3 or 4 by 10(10)-fold relative to the background reaction. Detailed kinetic studies of the methanolysis of 5 at varying [La(3+)] and pH indicate that both La(3+) monomers and dimers with associated methoxides are reactive species. The rate constants for La(3+) monomer and dimer catalysis of the methanolysis of 5 are dependent on pH, the slopes of the log plots being 0.35 and 0.5, respectively. A scheme is proposed to account for the non-first-order dependence on [CH(3)O(-)] wherein the La(3+)(CH(3)O(-))(x) + 5--La(3+)(CH(3)O(-))(x):5 and (La(3+))(2)(CH(3)O(-))(y) + 5--5:(La(3+))(2)(CH(3)O(-))(y) equilibria are driven to the left with increasing numbers of associated methoxides and that attack on these complexes, whether by external or metal-associated methoxide, is slower due to the reduced net positive charge on the complex.

In February 2000 the Swan-Canning estuary in Western Australia experienced a record bloom of the toxic cyanobacteria Microcystis aeruginosa. At its height, concentrations of M. aeruginosa reached integrated water column cell counts of 15,000/ml and formed bright green scums in sheltered bays, where counts of 130 million cells/ml were recorded. Due to public health concerns parts of the river were closed from 10 to 22 February 2000. Two unseasonably large summer rain events in early and late January 2000 created conditions for the bloom. Freshwater runoff, estimated at 270 GL, was enough to fill the Swan-Canning estuary five times over and brought with it high levels of nutrients, mainly nitrogen (>2.0mg/L TN) and phosphorus (>0.15mg/L TP). A number of methods to reduce bloom accumulations were tried, including an attempt to increase the salinity of the surface water above the critical 10 ppt level for Microcystis; using a bentonite clay and poly-aluminium chloride mixture to flocculate and sink the algae; and sucking up scums using oil spill equipment. Over 900 tonnes of M. aeruginosa were removed and safely disposed using sewage treatment facilities. The bloom collapsed when the freshwater flush subsided and seawater intrusion from the Indian Ocean re-established itself, raising the salinities above the tolerance of Microcystis.

Formation of a hanging dam, a large, thick sub-surface accumulation of frazil ice that blocked river flow, altered physical environmental conditions dramatically and common carp Cyprinus carpio, and brown trout Salmo trutta, evacuated the pool in which the dam developed. A mean of 80·1% of the pool volume was filled with frazil ice. Mean and bottom water velocities in the pool increased from 6 to 27 cm s−1 and from 4 to 21 cm s−1, respectively, when the hanging dam formed, and water depth decreased from a mean of 2·25 to 0·45 m. Activity levels of fish leaving the pool varied. Two carp had higher swimming activities when in the over wintering pool, compared to the period when they were out of it, and a third showed opposite results.

The hydrolysis of p-nitrophenyldiphenyl phosphate (PNPDPP, 7) catalyzed by N-dodecylaminoethanol (6a), N-tetradecylaminoethanol (6b), N-methyl-N-tetradecylaminoethanol (6c), and N-hexadecylaminoethanol (6d) was investigated at 25°C at various pH values in aqueous media containing additives. Added ethanol or dimethoxyethane produces very little activity of 6a, b, c toward 7. The highest activities of 6a, b were found at pH 8.0 and 8.5 in solvents containing 20% glycerol or ethylene glycol. Under no conditions was N-hexadecylaminoethanol (6d) found to be active. The kinetics of the reaction of 6b with 7 were also investigated in a medium containing various amounts of glycerol, polyethylene glycol 400 (PEG 400), and water at pH 7.6-8.5. The best catalytic system comprised 3 mM 6b in 20% aqueous ethylene glycol, pH 8.5, which accelerated the hydrolysis of 7 by 1700-fold over the blank rate. Kinetic experiments conducted using [7]/[6b] = 1 and 2 demonstrate that 6b exhibits true turnover catalysis. A mechanism for the catalyzed reaction is proposed.Key words: ß-aminoethanols, hydrolysis, p-nitrophenyldiphenyl phosphate, micelles, polyhydroxy alcohols.

The kinetics of methanolysis of acetyl imidazole (1) and acetyl pyrazole (2) have been investigated under anhydrous conditions in the presence of Zn(ClO4)2, Co(ClO4)2, and HClO4 at 25°C. In all cases, the plots of the pseudo-first-order rate constant for methanolysis (kobs) vs. [metal ion] or [HClO4] show saturation behavior indicative of equilibrium binding of the M2+ or H+ to the amide. Relative to the spontaneous methanolysis rate constant (ko), the catalytic rate constant obtained at saturation, kcat, is larger for metal-ion catalysis than for H+ catalysis. The (kcatH+/ko) ratio is 10.7 and 1.25 for 1 and 2, respectively, while the (kcatM2+/ko) for these divalent metals varies from 150-fold for 1 to between 700 and 5700-fold for 2. By contrast, in water, proton is far more effective at promoting the hydrolysis of 1 than are metals, the aqueous (kcatH+/ko) ratio being 560, while the (kcatZn2+ /ko) and (kcatNi2+/ko) ratios are 15 and 3.2, respectively.Key words: methanolysis, kinetics, metal-ion catalysis, acetyl imidazole, acetyl pyrazole.

Fishes inhabiting streams and rivers in the interior of North America experience a continental climate. Water temperatures reach 0 °C in winter and are high in summer. There is a marked seasonal cycle in discharge. These circumstances make groundwater a crucial component of river habitats. Groundwater can influence the distribution, reproductive success, biomass and productivity, behaviour and movements of fishes, and is especially important in winter and summer. Winter flows are minimal and are affected by ice. In winter, the importance of groundwater increases northwards. Groundwater provides overwintering habitat free of subsurface ice and fish may migrate long distances to take advantage of it. The melt season can account for up to half the annual discharge. In summer, groundwater is important for maintaining discharge and moderating stream temperatures. During critically hot weather, groundwater refugia protect species exposed to temperatures approaching their thermal limits. Since groundwater exerts such an important influence on river habitats, its quality, quantity and sustainability should be considered before development proposals are approved which could alter it. Examples of the role of groundwater in the ecology of some species show how localised and critical habitats influenced by groundwater can be, and, in consequence, how necessary it is to protect them. Protection is complicated because groundwater distribution pathways are often unknown and recharge areas may be remote from discharges. Scale becomes important in identifying potential risks to critical stream habitats from all types of landscape modification and water abstraction. Groundwater temperatures reflect mean annual air temperatures and are likely to change as global climates respond to increases in the greenhouse gases in the atmosphere. This could profoundly change critical fish habitats, particularly those at the margins of species distributions or those that are already overcrowded. Such considerations emphasise the importance of developing proper strategies for the conservation of groundwater. Copyright © 1999 John Wiley & Sons, Ltd.

The deuterium kinetic isotope effect (dkie) for the electrophilic bromination of ethylene-h4 and ethylene-d4 in methanol and dichloroethane (DCE) at 25 °C has been determined using mass spectrometr...

The electrophilic addition of Br2 to specifically deuterated cyclohexenes (1−5) was studied methanol (MeOH) by stopped-flow kinetics in order to determine a deuterium kinetic isotope effect (DKIE) ...

Two neutral cyclodextrins (CDs), hydroxypropyl-beta-CD (HP beta OD) and methyl-beta-CD (M beta CD), and two negatively charged forms, carboxymethyl-beta-CD (CM beta CD) and sulfobutylether-beta-CD (SB beta CD), were used to demonstrate the principle of separation of hydrophobic and non-charged polynuclear aromatic hydrocarbons (PAHs) by capillary electrophoresis (CE) based on differential partitioning of analytes between the CDs. The estimation of the partition coefficient (Ki) confirmed that the PAH components which partitioned most to the negative cyclodextrin (i.e. with the highest Ki) exhibited the longest migration time. The Ki values obtained for the CM beta CD-HP beta CD system are all below 1, indicating that the PAHs prefer to remain in the neutral HP beta CD. The Ki values for the SB beta CD-M beta CD buffer are all greater than 1, and cover a wider range, indicating preference of the PAHs for the anionic derivative. Methods were applied for separation of a PAH mixture containing various important PAHs on the US Environmental Protection Agency priority list. This novel procedure provided much better separation of PAH isomers, including benzo[a]pyrene and benzo[e]pyrene, than has been reported previously using CE. The system was applied to the sensitive determination of nanomolar levels of PAHs in contaminated soil.

The kinetics and products of addition of Br2 in MeOH to anti-sesquinorbornene (1) have been studied at 25 °C in the presence of varying [LiBr]. The products consist of ∼10% cis dibromide and 90% cis methoxy bromide, the amounts of these being independent of the [Br-]. The kinetics reveal that the reaction proceeds via the addition of Br2, and that Br3- is not a brominating agent for this olefin. Acetic acid is shown to add rapidly to the double bond of 1 in a spontaneous reaction and via an acid-catalyzed process in the presence of HClO4. For the spontaneous reaction a solvent deuterium kinetic isotope effect (DKIE) of 3.3 is observed. Proton inventory plots of kobs vs atom fraction of deuterium in the medium indicate that the DKIE arises from a transition state for addition involving two or more protons undergoing changes in bonding. The HClO4-catalyzed addition exhibits a large DKIE of 5.4 and is attributable to a simultaneous attack of HClO4 or ClO4- H2OAc+ and HOAc on the double bond. LiClO4 also cata...

The kinetics of the transfer of X+ from the bromonium and iodonium ions of adamantylideneadamantane (1-Br+ and 1-I+) to some 1,ω-alkenols and alkenoic acids in ClCH2CH2Cl at 25 °C was investigated. In all cases, the expected products of halocyclization were observed. For the iodonium ion transfer the reaction kinetics are second order overall, first order in both 1-I+ and acceptor olefin. Transfer of the bromonium ion from 1-Br+ to these acceptor olefins exhibits different kinetic characteristics. In most cases, the rate of the Br+ transfer is subject to strong retardation in the presence of added parent olefin (AdAd), suggestive of a common species rate depression. In some cases, such as 4-penten-1-ol (2b) and 4-pentenoic acid (4b), the reaction can be completely suppressed at high [AdAd]. In other cases, such as 3-buten-1-ol (2a), 5-hexen-1-ol (2c), cyclohexene, 4-(hydroxymethyl)cyclohexene (3), and 5-endo-carboxynorbornene (5), added AdAd does not suppress the reaction completely. In the cases of the 1...

Initial results are presented for a novel experimental arrangement which allows the successful study of laser-desorbed neutral species under matrix isolation conditions. In the current work, a pulsed carbon dioxide laser (10.6 μm) is employed for laser desorption. With the combination of a previously described cryogenic trapping technique with coaxial matrix isolation gas (xenon or argon) introduction, laser-desorbed neutrals have been matrix isolated and their Fourier transform infrared spectra recorded. Two different cinnamic acid derivatives ( p-coumaric acid and sinapinic acid) typically employed for matrix-assisted laser ionization (MALDI) mass spectrometry were utilized to demonstrate this new technique. Experimental conditions were determined for optimal matrix isolation of the laser-desorbed species. Two different desorption geometries were examined with respect to their effectiveness for matrix isolation of desorbed neutrals. A covalent dimer of p-coumaric acid produced in an external UV photoreactor and thought to be a possible photoreaction product in UV MALDI was studied by this technique. Thermal degradation of this dimer is shown to occur above threshold irradiance for laser desorption.

Inclusion complexes of 1,1'-dimethylferrocene (DMFe) with alpha-, 2-hydroxypropyl-beta- or gamma-cyclodextrins were formed in aqueous systems. For the first time, the interacting DMFe-cyclodextrin systems have been characterized using cyclic voltammetry which enabled the estimation of the complexation order, the formation constant and the diffusivity. Cyclic voltammetry was performed at a stationary electrode, yielding complexation ratios of 1:2 for DMFe with alpha-cyclodextrin and 1:1 with the other two cyclodextrins, as expected from the known cavity dimensions for the cyclodextrins. Formation constants of 4.4 x 10(4) M-2, 1.2 x 10(3) M-1 and 2.9 x 10(2) M-1 were then determined for the complexes between DMFe and the alpha-, beta- and gamma-cyclodextrins, respectively, in relative agreement with the literature. The maximum complexation efficiency, diffusivity and solubility were observed for the DMFe:2-hydroxypropyl-beta-cyclodextrin inclusion complex, which, combined with cost factors, resulted in the selection of this form for bioelectrocatalysis studies. The efficiency of the complex as a mediator for the glucose:glucose oxidase system was determined by measuring the rate constant (ks) for reaction of the oxidized DMFe with the reduced enzyme. The ks value decreased from 3.4 x 10(4) M-1 s-1 to 1.9 x 10(4) M-1 s-1 with an increase in 2-hydroxypropyl-beta-cyclodextrin concentration from 4 mM to 10 mM. In this range, the ks value is similar to that of free ferrocene, implying a high efficiency of the DMFe:2-hydroxypropyl-beta-cyclodextrin inclusion complex.

The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard-of-care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing terms and definitions must be updated, standardized and/or redefined for easier interpretation of data and effective communication among clinicians. A panel of experts in HCV infection treatment met on 3 December 2009. Goals of the panel were to evaluate terms and definitions used traditionally in treatment with peginterferon and ribavirin, to refine and clarify definitions of existing terms that have varying meanings and to propose new terms and definitions appropriate for novel treatment paradigms emerging with development of new agents. A number of recommendations were accepted unanimously by the panel. Adoption of these terms would improve communication among investigators, enhance comparability among clinical trials, facilitate development of therapeutic guidelines and provide a standardized terminology for use in clinical practice.

The recent European Directive (2006/7/CE) required member states to improve bathing water quality by reducing the sanitary risk for users. To be in agreement with the 2006 Directive expectations, actions need to be implemented to prevent, reduce or eliminate faecal pollution sources. In Europe, the culture-based reference methods used to evaluate bathing water quality (i.e. the ISO 9308-3 and ISO 7899-1 methods, which require 2 days analysis) do not allow active management of bathing areas as recommended by the 2006 Council Directive. Therefore, rapid methods for efficient Escherichia coli (E. coli) enumeration in recreational waters are needed. Anticipating this approach, we developed and used, since 2006, the rapid method Coliplage® based on the detection of the specific E. coli β-D-Glucuronidase activity for active management of bathing water, as a complement to the official analyses. Nevertheless, for some identified bathing water types, discrepancies were observed between the reference method (ISO 9308-3) and the Coliplage® method. Thus, other technologies or tools proposed for water monitoring were evaluated with the objective of answering the question, “Which method for what application?” Four alternative methods, including one method based on direct enzymatic detection (i.e. Coliplage®), one molecular method based on the real-time quantification of E. coli by PCR and two automated culture-based methods (coupled with signal detection by impedance measurement and enzyme activity measurement) were compared in the study. We evaluated the effectiveness and relevance of each of them (in terms of specificity, sensitivity, analysis time, viability, cost, ease of implementation), to determine their applicability for the bathing sites studied, according to the 2006 European Council Directive. In conclusion, enzymatic based methods (without culture) such as Coliplage® appear to be the most appropriate method to detect E. coli contamination in less than one hour and to provide an active management tool for faecal pollution.

The transfer of Br+ from the bromonium ion of adamantylideneadamantane (1-Br+/CF3SO3−) to the reactive alkenes cyclohexene, ω-alken-1-ols, 3a–c, and 4-pentenoic acid, 4, in 1,2-dichloroethane at 25 °C has been investigated. 1H NMR analysis of the reactions of equimolar 1-Br+/CF3SO3− and olefin indicates the products to be the expected cyclic ones in the cases of 3a–c and 4, and trans-2-bromocyclohexyltrifluoromethane sulfonate in the case of cyclohexene, along with adamantylideneadamantane (Ad=Ad). Detailed kinetic analysis shows that the reaction rates are suppressed by the addition of free Ad=Ad, suggestive of a common species rate depression. In the case of certain of the cyclization reactions such as that of 4-penten-1-ol, 3a, the cyclization reaction is bimolecular in acceptor olefin. A primary deuterium kinetic isotope effect of 2.0 on the cyclization of 3a-OH relative to 3a-OD exists. The role of the second molecule appears to be that of a general base in assisting the cyclization of an intermediate ω-hydroxy cyclic bromonium ion. A general mechanistic scheme for Br+ transfer from 1-Br+ to the reactive alkenes is proposed.

An instrument is described which measures fluorescence intensity and lifetime properties using a single optical fiber for the development of fiber optic chemical sensors. The instrument utilizes a fast-pulse nitrogen laser for excitation and a digital storage oscilloscope to provide time-resolved fluorescence decay curves. The time-resolved measurements permitted the separation of most of the scattered excitation radiation from the sample signal and allowed for analysis of samples exposed to ordinary room lighting. A method for determination of lifetimes from the time-resolved decays was developed based on the time-correlated single-photon counting method. The new method used reference fluorophore solutions to determine the instrument response function, including the influence of the optical fiber, and multiple decays were averaged to improve signal-to-noise and to provide statistical weighting for the analysis. The accuracy of the lifetime analysis was demonstrated by comparison of results for Stern-Volmer quenching of quinine sulfate by chloride ion (slope = 0.115 ± 0.001, int. = 1.04 ± 0.04, r2 = 0.9992) with a literature study on the same system (slope = 0.118 ± 0.002, int. = 1.06 ± 0.05, r2 = 0.9986). Measurement of the lifetime of pyrene in ethanol gave 17.8 ± 0.9 ns, while the value for coumarin was 3.82 ± 0.45 ns. When mixed together, two lifetimes with values of 17.43 ± 0.73 and 3.68 ± 1.30 ns were determined.

A substrate recycling assay for phenolic compounds was developed using tyrosinase, a copper-containing enzyme, in excess NADH. The reaction of various phenols with the enzyme produced an o-quinone, which was then detected by recycling between reactions with the enzyme and NADH. The recycling of quinones by excess NADH to their original reduced forms prevented the problems of subsequent quinone polymerization and product inactivation which occur in nonrecycling assays. Absorbance measurements of the NADH consumption rate enhanced the assay sensitivity for catechol 100-fold compared to nonrecycling o-quinone detection, giving a detection limit of 240 nM. Fluorescence NADH monitoring permitted a 10-fold improvement over absorbance, with a detection limit of 23 nM. The recycling reaction was selective for o-quinones, and no interference was noted for p-quinones or quinoneimines. The two-step oxidation of phenols was observed as an initial lag phase (ca. 10 min), requiring a higher enzyme concentration to achieve the same sensitivity as that for catechol. The procedure was most useful for assaying catechol, 4-chlorocatechol, phenol, p-cresol, and 4-chlorophenol and may provide selective detection of these components in mixtures. Several other derivatives of catechols, including amine derivatives, were also detected, with relative sensitivity being related to substrate activity of the enzyme.

The hydrolyses of phthalide (2a) and thiophthalide (3) have been stu- died in highly alkaline media, T=25 o C, μ=3 (HCl). For both esters, an upward curvature in the plot of k hyd vs [OH - ] is observed, sugges- tive of the onset of a second order in [OH - ] process in the hydrolysis. Carbonyl 18 O-exchange studies indicated that no 18 O is lost from the ester recovered from the hydrolysis media at times up to 3t 1/2 hydrolysis. Solvent kinetic isotope (skie) studies indicate that for 3, (k hyd ) H2O/D2O is inverse throughout the entire range of [OL - ]

1, 1'-dimethylferricinium (DMF+), a deep blue, and stable mediator, was prepared from a water-soluble 1, 1'-dimethylferrocene(DMF):2-hydroxypropyl- beta-cyclodextrin complex via enzymatic oxidation using immobilised bilirubin oxidase. This mediator was superior to other soluble ferrocenes, notably carboxyferrocene, in terms of both solubility (110 mM vs 0.5 mM) and oxidation potential (150 mV vs 300 mV against Ag/AgCl). Although the cyclic voltammogram of DMF+ was electrochemically equivalent to DMF, the use of the former resulted in a significantly lower background current (< 10 nA vs 30 nA). Because of its higher solubility, concentrated stock solutions of DMF+ can be prepared and supplied to the electrode. This is of particular importance when the signal is severely limited by the rate at which the working electrode can oxidase DMF to DMF+. A linear response of current versus units of glucose oxidase (GOD) was obtained up to 0.5 unit/ml. The detection limit was estimated to be 0.03 unit/ml and the response time was 2.5 min or less. The amperometric system was used successfully to follow the GOD activity during the growth of Aspergillus niger a well-known GOD producer. The results obtained correlated well with a standard absorbance-based assay using dichlorophenol-indophenol (DCPIP). The KM of GOD for the glucose in the lysate was measured as 38 mM. A reduced response and higher KM (48 mM) of the cell homogenate, compared to the lysate, illustrated the requirement for the DMF+ and glucose to diffuse across the cell membrane to interact with GOD in whole cells.

Hepatic encephalopathy (HE) is a brain disorder that often results from cirrhosis due to viral hepatitis, metabolic and alcohol-related liver disease, and is characterised by cognitive, psychiatric and motor impairments. Recurrent bouts of overt HE negatively impact daily functioning and quality of life.To evaluate the effect of rifaximin on health-related quality of life (HRQL) in cirrhotic patients with HE.Patients with cirrhosis in remission from HE (Conn score = 0 or 1) and a documented history of recurrent HE episodes (≥2 within 6 months of screening) were randomised to rifaximin 550 mg twice daily (N = 101) or placebo (N = 118) for 6 months. Concomitant lactulose was permitted during the study. The Chronic Liver Disease Questionnaire (CLDQ) was administered every 4 weeks, and time for occurrence of HE breakthrough was recorded. A longitudinal analysis using time-weighted averages of the CLDQ scores normalised by days on study therapy was used to evaluate the effect of treatment on HRQL, and between HE outcomes (HE recurrence, yes/no) irrespective of treatment.The time-weighted averages of the overall CLDQ score and each domain score were significantly higher in the rifaximin group vs. placebo (P-values ranged from 0.0087 to 0.0436); and were significantly lower in patients who experienced HE breakthrough compared to those who remained in remission (P-values were0.0001).Rifaximin significantly improved HRQL in patients with cirrhosis and recurrent hepatic encephalopathy. A lower HRQL may predict recurrence of hepatic encephalopathy.

The trans-2-bromotriflate of cycloherane (4) has been solvolyzed at ambient temperatures in HOAc and MeOH containing varying [Br - ] and in the presence of 0.5 M of a scavenger olefin, cyclopentene. The kinetics of solvolysis of 4 have been determined by observing the rate of change in color of an acid/base indicator that instantly responds to the production of HOTf or HBr. The kinetics show that the rate of solvolysis of 4 at constant ionic strength is independent of [Br - ]. The products of solvolysis of 4 under the various conditions have been determined by quantitative GLPC analysis. In the presence of Br - , the products consisted of the trans 1,2-dibromides and bromosolvates of cyclohexane and cyclopentane

The kinetics of bromine addition to various deuterated isotopomers of cyclohexene, namely the parent (3a), 3,3,6,6-tetradeuteriocyclohexene (3b), and cyclohexene-d 10 (3c), have been determined in HOAc (T=25 o C) as a function of added [Br - ], and the products were determined. The observed kinetic isotope effect for bromination of 3a/3b is k H /k D ≃1.0 with no added salt and indicates that deuteration of the allylic positions does not influence the kinetics

Maximum-likelihood restoration (MLR) data processing is applied to matrix-assisted laser desorption time-of-flight mass spectra of several peptide/protein samples. It is shown that this technique can enhance mass resolution for peptides (porcine insulin; MW = 5777.58 Da) sufficiently to assist in the identification of various matrix adduct ion species formed in the laser desorption process. For higher-molecular-weight proteins, mass resolution enhancement is such that peak overlap contributions from partially resolved matrix adduct ion species can be minimized. Mass accuracies are improved by approximately a factor of six for a sample of a bacterial protease (Subtilisin Carlsberg; Subtilopeptidase A) from Bacillus licheniformis (MW = 27,288.4 Da). The MLR technique also supports the contention that the mass resolution degradation observed with increasing analyte mass is at least partially due to ion signal tailing, presumably caused by secondary ion species being produced in the detection process. This factor is also postulated as being at least partially responsible for the lack of success at resolution enhancement for higher mass analytes (bovine serum albumin; MW = 66,430.3 Da) where the multiple matrix adduct ion species produced can no longer be resolved from the protonated molecular ion species, thus limiting experimental mass measurement accuracies.

The texture, or topography, interior of shells from native and exotic mollusks are measured and compared to determine if they can be discriminated. Area-scale fractal analysis is used to calculate relative areas as a function of scale, and the relative areas are used to evaluate the measurements. Measurements from a scanning laser profiler and from confocal and interferometric microscopes are compared, as are measurements of an original and a replica. The relative areas indicate clear differences between the measurement instruments. The largest relative areas are calculated from the confocal measurements. The trueness of the measurements has not been determined. However, the relative areas calculated from the confocal measurements are capable of discriminating the native clam from the exotic mussels with a confidence of greater than 99% at scales below 10 µm².