Global and age-related neuroanatomical abnormalities in a Pax6-deficient mouse model of aniridia suggests a role for Pax6 in adult structural neuroplasticity.

PAX6 encodes a highly conserved transcription factor necessary for normal development of the eyes and central nervous system. Heterozygous loss-of-function mutations in PAX6 cause the disorder aniridia in humans and the Small eye trait in mice. Aniridia is a congenital and progressive disorder known for ocular phenotypes; however, recently, consequences of PAX6 haploinsufficiency in the brains of aniridia patients have been identified. These findings span structural and functional abnormalities, including deficits in cognitive and sensory processing. Furthermore, some of these abnormalities are accelerated as aniridia patients age. Although some functional abnormalities may be explained by structural changes, variability of results remain, and the effects of PAX6 heterozygous loss-of-function mutations on neuroanatomy, particularly with regard to aging, have yet to be resolved. Our study used high-resolution magnetic resonance imaging (MRI) and histology to investigate structural consequences of such mutations in the adult brain of our aniridia mouse model, Small eye Neuherberg allele (Pax6SeyNeu/+), at two adult age groups. Using both MRI and histology enables a direct comparison with human studies, while providing higher resolution for detection of more subtle changes. We show volumetric changes in major brain regions of the the Pax6SeyNeu/+ mouse compared to wild-type including genotype- and age-related olfactory bulb differences, age-related cerebellum differences, and genotype-related eye differences. We also show alterations in thickness of major interhemispheric commissures, particularly those anteriorly located within the brain including the optic chiasm, corpus callosum, and anterior commissure. Together, these genotype and age related changes to brain volumes and structures suggest a global decrease in adult brain structural plasticity in our Pax6SeyNeu/+ mice.

Diel rhythm of volatile emissions of males and females of the peach fruit fly Bactrocera zonata.

Fruit flies in the genus Bactrocera are among the most destructive insect pests of fruits and vegetables throughout the world. A number of studies have identified volatiles from fruit flies, but few reports have demonstrated behavioral effects or sensitivities of fly antennae to these compounds. We applied a recently developed method of automated headspace analysis using SPME (Solid Phase Microextraction) fibers and GC-MS (gas chromatography mass spectrometry), termed SSGA, to reveal volatiles specific to each sex of B. zonata that are emitted in a diel periodicity. The volatiles released primarily at dusk were identified by GC-MS and chemical syntheses as several spiroacetals, pyrazines, and ethyl esters. Solvent extraction of male rectal glands or airborne collections from each sex, followed by GC-MS, showed that certain of the volatiles increase or decrease in quantity sex-specifically with age of the flies. Electroantennographic (EAG) analysis of dose-response indicates differences in sensitivities of male and female antenna to the various volatiles. Our study provides a comprehensive analysis of the volatile chemicals produced and released by B. zonata and their antennal responses. The possible pheromone and semiochemical roles of the various volatiles released by each sex and the difficulties of establishing behavioral functions are discussed.

Adding diffusion ordered NMR spectroscopy (DOSY) to the arsenal for characterizing paramagnetic complexes.

Herein we report the development of diffusion ordered NMR spectroscopy (DOSY) for its use to characterize metal complexes containing paramagnetic first row transition metal elements. This technique is capable of assessing the purity and speciation of paramagnetic complexes, and also provides a convenient method to provide qualitative and sometimes quantitative molecular weight data.

Monitoring and mass-trapping methodologies using pheromones: the lesser date moth Batrachedra amydraula.

The lesser date moth (LDM) Batrachedra amydraula is a significant pest of date palm fruits. Previously, detection and monitoring of the pest was inaccurate due to high costs of sampling with lifting machines. We report a practical system for detection and monitoring of LDM based on pheromone traps and relevant models. Dose-response experiments with LDM pheromone traps indicated a 1 mg lure is optimal for monitoring. Delta traps with adhesive covering their entire inner surface gave the highest captures while trap colour was unimportant. Sampling pheromone traps throughout the night indicated male flight began at 1:00-2:00 and reached a peak 2 h before sunrise. Monitoring traps exposed all year long in Israel revealed three generations with different abundance. Trapping transects in a date plantation indicated interference from a monitoring trap became minimal at distances >27 m away. Inter-trap distances closer than this may lower efficiency of monitoring and mass trapping in control programs. Our estimate of the circular effective attraction radius (EARc) of a 1 mg delta trap for LDM (3.43 m) shows this bait is among the most attractive compared with baits for other insects. We developed encounter-rate equations with the pheromone trap EARc to model the interplay between population levels, trap density and captures that are useful for detection of invasive LDM and its control by mass trapping. The integrated methodologies are applicable to many pest species.

The role of ligand redox non-innocence in ring-opening polymerization reactions catalysed by bis(imino)pyridine iron alkoxide complexes.

The reactivity of iron-based ring opening polymerization catalysts is compared when the catalyst is in three different oxidation states. Formally iron(i) monoalkoxide complexes 3a (p-methoxyphenoxide) and 3b (neopentoxide) supported by bis(imino)pyridine ligands were synthesized and investigated as catalysts for the ring opening polymerization and copolymerization of various monomers. For most monomers, 3a and 3b were superior catalysts compared to analogous, formally iron(ii) and iron(iii) complexes (1a/1b and 2a/2b, respectively) for the ring opening polymerization of various cyclic ester and cyclic carbonate monomers. Experimental and computational investigation into the electronic structures of 3a and 3b revealed that they are most accurately described as containing a high spin iron(ii) center that is antiferromagnetically coupled to a singly reduced bis(imino)pyridine ligand. This electronic structure leads to increased electron density near the metal center without modulating the apparent metal oxidation state, which results in superior catalytic performance for the more highly reduced 3a and 3b compared to the increasingly more oxidized complexes (i.e.1a/1b and 2a/2b, respectively) in ring opening polymerization reactions. These findings have significant ramifications for the emerging field of redox-switchable polymerization catalysis.

Dimension from covariance matrices.

We describe a method to estimate embedding dimension from a time series. This method includes an estimate of the probability that the dimension estimate is valid. Such validity estimates are not common in algorithms for calculating the properties of dynamical systems. The algorithm described here compares the eigenvalues of covariance matrices created from an embedded signal to the eigenvalues for a covariance matrix of a Gaussian random process with the same dimension and number of points. A statistical test gives the probability that the eigenvalues for the embedded signal did not come from the Gaussian random process.

Enabling Overall Water Splitting on Photocatalysts by CO-Covered Noble Metal Co-catalysts.

Photocatalytic overall water splitting requires co-catalysts that efficiently promote the generation of H2 but do not catalyze its reverse oxidation. We demonstrate that CO chemisorbed on metal co-catalysts (Rh, Pt, Pd) suppresses the back reaction while maintaining the rate of H2 evolution. On Rh/GaN:ZnO, the highest H2 production rates were obtained with 4-40 mbar of CO, the back reaction remaining suppressed below 7 mbar of O2. The O2 and H2 evolution rates compete with CO oxidation and the back reaction. The rates of all reactions increased with increasing photon absorption. However, due to different dependencies on the rate of charge carrier generation, the selectivities for O2 and H2 formation increased in comparison to CO oxidation and the back reaction with increasing photon flux and/or quantum efficiency. Under optimum conditions, the impact of CO to prevent the back reaction is identical to that of a Cr2O3 layer covering the active metal particle.

Grid-based partitioning for comparing attractors.

Stationary dynamical systems have invariant measures (or densities) that are characteristic of the particular dynamical system. We develop a method to characterize this density by partitioning the attractor into the smallest regions in phase space that contain information about the structure of the attractor. To accomplish this, we develop a statistic that tells us if we get more information about our data by dividing a set of data points into partitions rather than just lumping all the points together. We use this method to show that not only can we detect small changes in an attractor from a circuit experiment, but we can also distinguish between a large set of numerically generated chaotic attractors designed by Sprott. These comparisons are not limited to chaotic attractors-they should work for signals from any finite-dimensional dynamical system.

Identifying adults at risk of paracetamol toxicity in the acute dental setting: development of a clinical algorithm.

Paracetamol is widely used and effective for the management of dental pain in the UK. Acute dental pain is a recognised precipitant of unintentional paracetamol overdose and in a small but significant number of cases this results in hepatotoxicity. Patients' understanding of the risks of excess paracetamol ingestion remains poor and risk of over-medication before presentation is increased due to a variety of factors including dental anxiety and fragmented provision of dental emergency services. Early recognition of overdose is crucial to preventing significant hepatotoxicity and death. Dentists have a role to play in recognising unintentional overdose cases and directing patients timeously to appropriate medical care. Guidelines on the treatment of paracetamol toxicity are readily available but our data suggests some dental settings may present a weak link in the care pathway and overdose may not be readily recognised. We have developed an algorithm and training package targeted at dentists in the acute dental setting with the aim of improving recognition of paracetamol toxicity in adults and directing onward referral appropriately. This paper also revises the key pharmacokinetics and pharmacodynamics of paracetamol and is intended to raise awareness of issues of toxicity for dentists.

Directed differentiation of embryonic P19 cells and neural stem cells into neural lineage on conducting PEDOT-PEG and ITO glass substrates.

Differentiation of pluripotent and lineage restricted stem cells such as neural stem cells (NSCs) was studied on conducting substrates of various nature without perturbation of the genome with exogenous genetic material or chemical stimuli. Primary mouse adult neural stem cells (NSCs) and P19 pluripotent embryonal (P19 EC) carcinoma cells were used. Expression levels of neuronal markers ß-III-tubulin and neurofilament were evaluated by immunochemistry and flow cytometry. It was shown that the ability of the substrate to induce differentiation directly correlated with its conductivity. Conducting substrates (conducting oxides or doped π-conjugated organic polymers) with different morphology, structure, and conductivity mechanisms all promoted differentiation of NSC and P19 cells into neuronal lineage to a similar degree without use of additional factors such as poly-L-ornithine coating or retinoic acid, as verified by their morphology and upregulation of the neuronal markers but not astrocyte marker GFAP. However, substrates with low conductance below ca. 10(-4) S cm(-2) did not show this ability. Morphology of differentiating cells was visualized by atomic force microscopy. NSCs cells increased ß-III-tubulin expression by 95% and P19 cells by over 30%. Our results suggest that the substrate conductivity is a key factor governing the cell fate. Differentiation of P19 cells into neuronal lineage on conducting substrates was attributed to downregualtion of Akt signaling pathway and increase in expression of dual oxidase 1 (DUOX 1).

Acute cervico-facial infection in Scotland 2010: patterns of presentation, patient demographics and recording of systemic involvement.

Acute bacterial cervicofacial infection is a common problem that is most often secondary to dental infection. Most cases present as localised abscesses but some may be associated with serious morbidity including scarring, embarrassment of the airway, SIRS (systemic inflammatory response syndrome), and sepsis syndrome. Fourteen oral surgery or maxillofacial surgery units in Scotland took part in a clinical audit of acute infection during two four-week cycles (August and November) in 2010. Information regarding the patients, signs and symptoms, and management was recorded. Training material was distributed between cycles with information on SIRS, sepsis, and the prescription of antibiotics. Overall, 140 patients presented with acute infection. There was an equal sex distribution and ages ranged from 5 to 87 years. There was an association with deprivation and 36% of patients were from the lowest socioeconomic quintile. Most infections were dental (n=120, 86%), and patients presented with pain and swelling (n=120, 86% and n=134, 96%, respectively) Twenty-three patients (16%) met the criteria for SIRS. A further 23 (16%) had at least one positive SIRS marker with incomplete recording of the remaining markers. Twenty-six patients (19%) had no recorded SIRS markers. Cervicofacial infection can be associated with serious morbidity and mortality, which may be better managed if the systemic signs and symptoms of sepsis are recognised and recorded at presentation. This study showed that the recording of signs of sepsis was variable even with training. Further training of junior staff to recognise severe acute bacterial infection may improve management.

Potential of "lure and kill" in long-term pest management and eradication of invasive species.

"Lure and kill" technology has been used for several decades in pest management and eradication of invasive species. In lure and kill, the insect pest attracted by a semiochemical lure is not "entrapped" at the source of the attractant as in mass trapping, but instead the insect is subjected to a killing agent, which eliminates affected individuals from the population after a short period. In past decades, a growing scientific literature has been published on this concept. This article provides the first review on the potential of lure and kill in long-term pest management and eradication of invasive species. We present a summary of lure and kill, either when used as a stand-alone control method or in combination with other methods. We discuss its efficacy in comparison with other control methods. Several case studies in which lure and kill has been used with the aims of long-term pest management (e.g., pink bollworm, Egyptian cotton leafworm, codling moth, apple maggot, biting flies, and bark beetles) or the eradication of invasive species (e.g., tephritid fruit flies and boll weevils) are provided. Subsequently, we identify essential knowledge required for successful lure and kill programs that include lure competitiveness with natural odor source; lure density; lure formulation and release rate; pest population density and risk of immigration; and biology and ecology of the target species. The risks associated with lure and kill, especially when used in the eradication programs, are highlighted. We comment on the cost-effectiveness of this technology and its strengths and weaknesses, and list key reasons for success and failure. We conclude that lure and kill can be highly effective in controlling small, low-density, isolated populations, and thus it has the potential to add value to long-term pest management. In the eradication of invasive species, lure and kill offers a major advantage in effectiveness by its being inverse density dependent and it provides some improvements in efficacy over related control methods. However, the inclusion of insecticides or sterilants in lure and kill formulations presents a major obstacle to public acceptance.

Floral scent of Canada thistle and its potential as a generic insect attractant.

The flowers of Canada thistle, Cirsium arvense (L.), attract a wide range of insects, including pollinators and herbivorous species. This attraction is primarily mediated by floral odor, which offers potential for developing generic insect attractants based on odor. In this study, we have analyzed the chemical composition of the volatiles produced by Canada thistle flowers. Nineteen floral compounds were identified in the headspace, including phenylacetaldehyde (55%), methyl salicylate (14%), dimethyl salicylate (8%), pyranoid linalool oxide (4.5%), and benzaldehyde (3.5%). Other minor compounds include benzyl alcohol, methylbenzoate, linalool, phenylethyl alcohol, furanoid linalool oxide, p-anisaldehyde, 2,6-dimethyl-1,3,5,7-octatetraene, benzylacetate, benzyl tiglate, (E,E)-alpha-farnesene, benzyl benzoate, isopropyl myristate, and 2-phenylethyl ester benzoic acid. The relative attractiveness of various doses of the main floral volatile compound phenylacetaldehyde (i.e., 10, 100, 200, and 400 mg) was tested for insect attraction. Both the total catch and the biodiversity of insect species trapped increased as the loading of phenylacetaldehyde increased. Volatiles were chosen from the odors from the flowers of Canada thistle and formulated and tested in the field. An 11-component blend was the most attractive of several floral blends tested. These findings indicate that chemical components of flower odors of Canada thistle can serve as a generic insect attractant for monitoring of invasive pest species.

Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis.

Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.

Effect of wheat stem sawfly damage on yield and quality of selected Canadian spring wheat.

The wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), has reached outbreak status at most locations in the southern Canadian prairies. Solid-stemmed wheat, Triticum aestivum L., cultivars, which are less susceptible to damage, remain the primary management option. This article quantifies the effect of wheat stem sawfly damage on grain yield and quality at harvest and determines how cultivar selection affects harvest losses. Solid-stemmed cultivars were compared with hollow-stemmed cultivars and with blends of a 1:1 ratio of each. The hollow-stemmed cultivars with the exception of'McKenzie', which had intermediate levels of stem cutting, were all significantly more susceptible to stem cutting than solid-stemmed cultivars. Cultivar blends had lower damage but were still significantly higher than the solid-stemmed cultivars. The solid-stemmed 'AC Eatonia' and 'AC Abbey' had the lowest levels of stem cutting and ranked second and third overall for yield in 2001 and 2002. McKenzie ranked first, which reflects its yield potential in combination with its partial resistance to stem cutting. Lower cutting in AC Eatonia, AC Abbey, McKenzie, and the blend of AC Abbey/ McKenzie was significantly correlated with lower grain losses. Grain lost at harvest has major economic implications if sawfly pressure is moderate to high and susceptible cultivars predominate.

Potential of mass trapping for long-term pest management and eradication of invasive species.

Semiochemical-based pest management programs comprise three major approaches that are being used to provide environmentally friendly control methods of insect pests: mass trapping, "lure and kill," and mating disruption. In this article, we review the potential of mass trapping in long-term pest management as well as in the eradication of invasive species. We discuss similarities and differences between mass trapping and other two main approaches of semiochemical-based pest management programs. We highlight several study cases where mass trapping has been used either in long-term pest management [e.g., codling moth, Cydia pomonella (L.); pink bollworm, Pectinophora gossypiella (Saunders); bark beetles, palm weevils, corn rootworms (Diabrotica spp.); and fruit flies] or in eradication of invasive species [e.g., gypsy moth, Lymantria dispar (L.); and boll weevil, Anthonomus grandis grandis Boheman). We list the critical issues that affect the efficacy of mass trapping and compare these with previously published models developed to investigate mass trapping efficacy in pest control. We conclude that mass trapping has good potential to suppress or eradicate low-density, isolated pest populations; however, its full potential in pest management has not been adequately realized and therefore encourages further research and development of this technology.

Behavioral response of Lygus hesperus to conspecifics and headspace volatiles of alfalfa in a Y-tube olfactometer.

The western tarnished plant bug, Lygus hesperus Knight, feeds and develops on a variety of weeds in the spring, with later generations moving to alfalfa and cotton where severe damage to reproductive structures can occur. A synthetic attractant for monitoring or mass-trapping L. hesperus, or the identification of potential attractants for natural enemies, would be useful tools for integrated pest management programs. Studies investigated the response of naive and experienced fifth-instar and adult L. hesperus to odors associated with conspecifics and alfalfa, Medicago sativa L. Fifth-instar L. hesperus responded to all plant/insect combinations, whereas female L. hesperus only responded preferentially to vegetative and flowering alfalfa where conspecifics had fed for 24-72 hr, and to vegetative alfalfa where conspecifics were added approximately 30 min before the test began. Males were not attracted to headspace volatiles from any of the alfalfa treatments. Analysis of headspace volatiles showed that (E)-2-hexanal, (Z)-3-hexen-l-ol, alpha-pinene, (Z)-3-hexenyl acetate, (E)-2-hexenyl acetate, limonene, (Z)-ocimene, (E)-beta-ocimene, linalool, (3E)-4,8-dimethyl-1,3,7-nonatriene, and (E, E)-alpha-farnesene are emitted from both vegetative and flowering alfalfa. Indole and (3E, 7E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene were only detected in flowering alfalfa. Damage to alfalfa by L. hesperus increased emissions of (Z)-ocimene, (E)-beta-ocimene, (E)-beta-caryophyllene, and (E, E)-alpha-farnesene, while beta-pinene, myrcene, methyl salicylate, and (3E, 7E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene were only detected from damaged plants. Thus, individual or mixtures of these alfalfa volatiles may be useful as attractants for capturing nymphs and adult females of L. hesperus in the field.

Prediction of in vivo hepatic clearance from in vitro data using cryopreserved human hepatocytes.

1. Cryopreserved human hepatocytes were used to predict in vivo hepatic clearance (CL(hepatic)) from estimates of in vitro intrinsic clearance (CL' int). 2. (CL' int) was estimated for phenytoin, valproic acid, carbamazepine, theophylline, quinidine and procainamide after their addition to hepatocytes suspended either in human serum or in serum-free media. (CL' int)was estimated from in vitro concentration versus time data fitted to a monoexponential decay model. (CL' int) was estimated from concentrations measured at four time points and from just two-point measures, namely the initial concentration (C(0)) and the final concentration measurement (C(last)). 3. Predicted CL(hepatic) was within twofold of reported in vivo values of CL(hepatic) for all substrates. Moreover, predictions were not significantly different whether derived from hepatocytes suspended in serum or in serum-free medium. 4. Two-point estimates of (CL' int) were just as accurate in predicting CL(hepatic) as were multipoint estimates of (CL' int). 5. Although the data set was limited, the findings suggest that the measurement of the disappearance of xenobiotics from serum or serum-free media in which primary human hepatocytes have been suspended provides a physiologically relevant estimate of hepatic clearance that can be employed early in the drug development process to eliminate xenobiotics with unacceptable clearances.

Critical appraisal tools facilitate the work of the quality professional.

Quality management activities involve the application of scientific principles to performance improvement activities. With the plethora of available information, a systematic approach to evaluating the quality and usefulness of sources is necessary. One approach is critical appraisal, which is used to search for the best evidence or integrate evidence with clinical expertise. Two critical appraisal tools (CATs) are presented here, the first for any original clinical or health services research study and the second for research synthesis. The CAT scoring system and summaries of reviewed references facilitate understanding of the "state of the science" in the areas of interest.