Frontal waves and transmissions for temporal laminates and imperfect chiral interfaces.

The analysis of wave patterns in a structure which possesses periodicity in the spatial and temporal dimensions is presented. The topic of imperfect chiral interfaces is also considered. Although causality is fundamental for physical processes, natural wave phenomena can be observed when a wave is split at a temporal interface. A wave split at a spatial interface is a more common occurrence; however, when the coefficients of the governing equations are time-dependent, the temporal interface becomes important. Here, the associated frontal waves are studied, and regimes are analysed where the growth of the solution in time is found. Imperfect interfaces, across which the displacements are discontinuous, are also considered in the vector case of chiral elastic systems. Analytical study and asymptotic approximations are supplied with illustrative numerical examples. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.

A structure activity relationship for ring closure reactions in unsaturated alkylperoxy radicals.

Terpenoids are an important class of multi-unsaturated volatile organic compounds emitted to the atmosphere. During their oxidation in the troposphere, unsaturated peroxy radicals are formed, which may undergo ring closure reactions by an addition of the radical oxygen atom on either of the carbons in the C[double bond, length as m-dash]C double bond. This study describes a quantum chemical and theoretical kinetic study of the rate of ring closure, finding that the reactions are comparatively fast with rates often exceeding 1 s-1 at room temperature, making these reactions competitive in low-NOx environments and allowing for continued autoxidation by ring closure. A structure-activity relationship (SAR) is presented for 5- to 8-membered ring closure in unsaturated RO2 radicals with aliphatic substituents, with some analysis of the impact of oxygenated substituents. H-migration in the cycloperoxide peroxy radicals formed after the ring closure was found to be comparatively slow for unsubstituted RO2 radicals. In the related cycloperoxide alkoxy radicals, migration of H-atoms implanted on the ring was similarly found to be slower than for non-cyclic alkoxy radicals and is typically not competitive against decomposition reactions that lead to cycloperoxide ring breaking. Ring closure reactions may constitute an important reaction channel in the atmospheric oxidation of terpenoids and could promote continued autoxidation, though the impact is likely to be strongly dependent on the specific molecular backbone.

Lipidomic and transcriptomic analyses of Chlamydomonas reinhardtii under heat stress unveil a direct route for the conversion of membrane lipids into storage lipids.

Studying how photosynthetic cells modify membrane lipids in response to heat stress is important to understand how plants and microalgae adapt to daily fluctuations in temperature and to investigate new lipid pathways. Here, we investigate changes occurring in lipid molecular species and lipid metabolism genes during early response to heat stress in the model photosynthetic microorganism Chlamydomonas reinhardtii. Lipid molecular species analyses revealed that, after 60 min at 42 °C, a strong decrease in specific polyunsaturated membrane lipids was observed together with an increase in polyunsaturated triacylglycerols (TAGs) and diacylglycerols (DAGs). The fact that decrease in the major chloroplastic monogalactosyldiacylglycerol sn1-18:3/sn2-16:4 was mirrored by an accumulation of DAG sn1-18:3/sn2-16:4 and TAG sn1-18:3/sn2-16:4/sn3-18:3 indicated that newly accumulated TAGs were formed via direct conversion of monogalactosyldiacylglycerols to DAGs then TAGs. Lipidomic analyses showed that the third fatty acid of a TAG likely originated from a phosphatidylethanolamine or a diacylglyceryl-O-4'-(N,N,N,-trimethyl)-homoserine betaine lipid species. Candidate genes for this TAG synthesis pathway were provided through comparative transcriptomic analysis and included a phospholipase A2 homolog and the DAG acyltransferase DGTT1. This study gives insights into the molecular events underlying changes in membrane lipids during heat stress and reveals an alternative route for TAG synthesis.

Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients.

Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases.

2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam.

Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (⩾3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)--the toxic equivalents (TEQ) levels⩾17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).

Enhanced payload of lipid nanocarriers using supersaturated solution prepared by solvent-mediated method.

With the aim to effectively enhance the payload for nanocarriers, supersaturated deltamethrin (SSD) solution was prepared using the solvent-mediated method to produce lipid nanocarriers by a combination method of homogenization and sonication. In this study, deltamethrin was used as an active ingredient, corn oil was used as a lipid medium, soybean lecithin and Tween-80 were used as surfactants. At 25°C, the solubility of deltamethrin in SSD solution prepared by solvent-mediated method was 3.4 times and 1.5 times higher than that in saturated deltamethrin (SD) solution and that in SSD solution prepared by thermal-mediated method, respectively. Therefore, compared to the use of SD solution for the production of nanocarriers, the use of SSD solution significantly enhanced the payload, while keeping the encapsulation efficiency high. Particularly, nanocarriers produced from SSD solution prepared by solvent-mediated method had the higher payload of 2.1 times and 4.4 times compared with preparations using SSD solution prepared by thermal-mediated method and SD solution, respectively.

Visual acuity in the short-tailed opossum (Monodelphis domestica).

Monodelphis domestica (short-tailed opossum) is an emerging animal model for studies of neural development due to the extremely immature state of the nervous system at birth and its subsequent rapid growth to adulthood. Yet little is known about its normal sensory discrimination abilities. In the present investigation, visual acuity was determined in this species using the optokinetic test (OPT), which relies on involuntary head tracking of a moving stimulus and can be easily elicited using a rotating visual stimulus of varying spatial frequencies. Using this methodology, we determined that the acuity of Monodelphis is 0.58 cycles per degree (cpd), which is similar to the acuity of rats using the same methodology, and higher than in mice. However, acuity in the short-tailed opossum is lower than in other marsupials. This is in part due to the methodology used to determine acuity, but may also be due to differences in diel patterns, lifestyle and phylogeny. We demonstrate that for the short-tailed opossum, the OPT is a rapid and reliable method of determining a baseline acuity and can be used to study enhanced acuities due to cortical plasticity.

Implementation of sepsis management guideline in a community-based teaching hospital - can education be potentially beneficial for septic patients?

OBJECTIVE: To assess clinical outcomes associated with the implementation of the sepsis management guideline in a community-based hospital. In addition, evaluate the utility and effectiveness of a Sepsis Education Program. RESEARCH DESIGN AND METHODS: This is an observational cohort study of patients presenting to the Emergency Department at a community-based teaching centre meeting severe sepsis or septic shock criteria. A quality improvement programme consisting of a comprehensive Sepsis Education Program based on recommendations from the Surviving Sepsis Campaign was implemented and evaluated. Patients were identify by the admission diagnosis and were evaluated over two time periods (7/2003-6/2004 and 7/2005-6/2006) and to show clinical outcomes before and after implementation of the sepsis guideline/quality improvement programme. RESULTS: A total of 96 patients with severe sepsis (34 control group and 62 SSC group) were included. Both groups had similar intensive care unit (ICU)-length of stay (3 vs. 3 days, p = 0.647). Patients who required mechanical ventilation (MV) had similar MV time (4 vs. 3.5 days p = 0.349). A greater percentage of survival was found in the SSC group [45% vs. 73% (p = 0.006)]. Patient received similar care with regards to appropriate early antibiotics (85% vs. 90%, p 0.459). The main difference between the two group was the early fluid resuscitation (2 l vs. 3 l, p = 0.006) over the first 3 h and a difference remained significant at 6 h (4.2 l vs. 6.3 l, p = 0.013). CONCLUSIONS: In a community based teaching hospital, implementing the surviving sepsis campaign guideline through an education programme was feasible and resulted in early therapy with aggressive fluid administration and appropriate antibiotics. The Sepsis Education Program resulted in early therapeutic interventions and contributed to the survival benefits.

Enhanced payload and photo-protection for pesticides using nanostructured lipid carriers with corn oil as liquid lipid.

With the aim to establish a novel nanocarrier system with higher payload and higher photo-protection for deltamethrin (active ingredient) compared to solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) were prepared by combining hot homogenization and sonication with different ratios of corn oil (liquid lipid) and beeswax (solid lipid). Compared to SLN, the incorporation of corn oil gave a higher payload, slower release rate and higher photo-protection for deltamethrin. Particularly, compared to beeswax solid lipid nanoparticles (BSLN), NLC gave a higher payload (approximately 1.79 times) with a high encapsulation efficiency (83.6%), higher photo-protection in direct photolysis (1.8 times) after 12 h exposure of ultraviolet light (UV) and in indirect photolysis (1.37 times) after 2 h exposure of UV in 2% (v/v) acetone solution used as a photosensitizer. This study demonstrated that novel nanocarrier possesses a wide range of applicability in protecting photo-labile compounds for the crop, food and pharmaceutical industries.

How to manage medications in the setting of liver disease with the application of six questions.

OBJECTIVE: Reviewing the current literature to guide clinicians managing medications in the setting of liver disease. LITERATURE SOURCES: Using the terms liver disease, medication management, and therapeutic monitoring, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966-April 2009). Reference citations were reviewed as an additional resource. Published English-language literatures, articles and trials were reviewed. Emphasis was placed on prospective, randomised, double-blind, placebo-controlled clinical trials. QUESTION SYNTHESIS: An informed decision on how to manage medications in the setting of liver disease should account for changes that transpire in a medication's first-pass metabolism, protein binding, volume of distribution, clearance and pharmacodynamic interactions. To incorporate these issues within one's thought process, clinicians can utilise the following six questions to evaluate a medication use: (i) Is the patient experiencing acute or chronic liver failure? (ii) Does the drug have high hepatic first-pass metabolism? (iii) Is the medication highly protein-bound? (iv) Is there a change in the volume of distribution for the medication? (v) Is the clearance of the medication significantly altered? and (vi) Is there a pharmacodynamic interaction with the medication? CONCLUSIONS: The introduction and use of six clinically relevant questions in the setting of liver disease can serve as a guide to clinicians who manage patients with liver disease.

Nesiritide utilization evaluation in a university teaching hospital.

BACKGROUND AND OBJECTIVES: Nesiritide is a new vasodilator approved for decompensated heart failure (DHF). Compared with nitroglycerin, nesiritide improves haemodynamics and symptoms in the first 3 h of therapy. However, nesiritide is more expensive than nitroglycerin (US$380-1500 daily vs. US$2-5 daily). Since its approval in the US in late 2001, nesiritide use has increased dramatically in our institution. Nesiritide has become a focus of our multidisciplinary drug utilization initiative, aimed at performing a nesiritide utilization evaluation (NUE) and developing a nesiritide usage guideline. METHODS: Medical records of patients who received nesiritide from 1 October 2003 to 31 March 2004 were reviewed. Nesiritide utilization pattern was presented to the initiative group for guideline development. RESULTS: A total of 162 records were reviewed. A 22.6% of inappropriate usage was reported. The most significant inappropriate usage was in patients who received the agent for precardiac valvular surgery optimization, followed by those for diuresis in non-cardiac-related fluid overload states. The median duration of nesiritide therapy was 6 days (range 1-94). The median length of stay (LOS) in our institution was 14 days (National statistics DHF LOS: 5.3 days). Eliminating inappropriate nesiritide usage can lead to a potential of US$141 886 savings per year. CONCLUSION: Based on the results, a 48-h nesiritide restriction policy was implemented. Usage beyond 48 h requires Heart Failure Service approval. Future NUE will evaluate the effectiveness of this policy. The overall management of DHF also needs to be evaluated to improve efficiency of care.

Quenching of the magnetic moment of a transition metal dopant in silver clusters.

Single magnetic atoms embedded in a nonmagnetic host exhibit the Kondo effect in the bulk limit, while in very small molecules the magnetic atom is hardly affected by the matrix. In a combined theoretical (density functional theory) and experimental (photofragmentation and mass spectrometry) study we consider the intermediate case of nanometer sized transition-metal-doped silver clusters. In particular, we provide experimental evidence for enhanced stability of the cobalt-doped silver cluster Ag10Co+ and show theoretically that it has a symmetric endohedral geometry with a closed 18-electron singlet electronic shell structure. This implies that the magnetic moment on the cobalt atom is quenched.

Sulfide-mediated dehydrative glycosylation.

The development of a new method for glycosylation with 1-hydroxy glycosyl donors employing dialkyl sulfonium reagents is described. The process employs the reagent combination of a dialkyl sulfide and triflic anhydride to effect anomeric bond constructions. This controlled dehydrative coupling of various C(1)-hemiacetal glycosyl donors and nucleophilic acceptors proceeds by way of a sulfide-to-sulfoxide oxidation process in which triflic anhydride serves as the oxidant.

Age at first marriage in Viet Nam: patterns and determinants.

"Using data from the 1991 Viet Nam Life History Survey, this article examines the patterns and determinants of age at first marriage. It shows that socio-economic and political changes during the last few decades are associated with a shift to older ages of first marriage. It identifies regional variations and discusses the significant impact of warfare on the country's age patterns of marriage. It concludes by bringing out the implications of the study for policy purposes." The full text is of this article is available electronically through www.undp.org/popin.

Design and application of a low-temperature Peltier-cooling microscope stage.

A light microscopy system has been designed for freezing and lyophilization studies of protein pharmaceuticals. The system consists of a cascade of four Peltier thermoelectric modules in the lyophilization cell to freeze samples to -60 degrees C, controllers to regulate temperature and pressure conditions, and a video camera to record the events under study. Specific demonstration of the system was conducted using recombinant CD4-IgG and human growth hormone (hGH) as model proteins. Observations of recrystallization during warming of frozen CD4-IgG solution and lyophilization of hGH solution are discussed. These examples demonstrate that the system is a useful tool for the fundamental understanding of freezing and lyophilization of protein pharmaceuticals.

Surface denaturation at solid-void interface--a possible pathway by which opalescent particulates form during the storage of lyophilized tissue-type plasminogen activator at high temperatures.

During protein lyophilization, it is common practice to complete the freezing step as fast as possible in order to avoid protein denaturation, as well as to obtain a final product of uniform quality. We report a contradictory observation made during lyophilization of recombinant tissue-type plasminogen activator (t-PA) formulated in arginine. Fast cooling during lyophilization resulted in a lyophilized product that yielded more opalescent particulates upon long term storage at 50 degrees C, under a 150 mTorr nitrogen seal gas environment. Fast cooling also resulted in a lyophilized cake with a large internal surface area. Studies on lyophilized products containing 1% (w/w) residual moisture and varying cake surface areas (0.22-1.78 m2/gm) revealed that all lyophilized cakes were in an amorphous state with similar glass transition temperatures (103-105 degrees C). However, during storage the rate of opalescent particulate formation in the lyophilized product (as determined by UV optical density measurement in the 360 to 340 nm range for the reconstituted solution) was proportional to the cake surface area. We suggest that this is a surface-related phenomenon in which the protein at the solid-void interface of the lyophilized cake denatures during storage at elevated temperatures. Irreversible denaturation at the ice-liquid interface during freezing in lyophilization is unlikely to occur, since repeated freezing/thawing did not show any adverse effect on the protein. Infrared spectroscopic analysis could not determine whether protein, upon lyophilization, at the solid-void interface would still be in a native form.

Determining the optimum residual moisture in lyophilized protein pharmaceuticals.

A general concern in the lyophilization of protein pharmaceuticals is how dry a product should be in order to maintain its stability during storage. This paper presents our exploratory studies on determining if there is an optimal residual moisture content for lyophilized recombinant protein products. The proteins used in this study were methionyl human growth hormone (met-hGH) and tissue type plasminogen activator (tPA). The amount of water adsorbed on each protein can be determined and approximated as a monolayer by the Brunauer-Emmett-Teller method. The result was in good agreement with the theoretical value calculated from the total number of strong polar groups in the molecule without regard to the conformation of the protein. This approach suggests that each protein may have a minimum moisture content that is necessary to shield the polar groups, and that over-drying will lead to exposure of these groups. The effect of residual moisture content on the stability of tPA in lyophilized excipient-free powder was studied. Samples that were dried to a water content below the calculated monolayer exhibited opalescence upon reconstitution, while those that were dried to either monolayer or multilayer water content tended to show a greater loss in biological stability upon storage under temperature stress conditions. The results of our studies reveal that the generally accepted concept "the drier the better" may not be appropriate for tPA. An optimum residual moisture content is required to balance the physical stability and the biological stability. These observations may apply to other protein products as well.