Showing papers by "University of Leicester published in 2004"

The Swift Gamma-Ray Burst Mission

Abstract: The Swift mission, scheduled for launch in 2004, is a multiwavelength observatory for gamma-ray burst (GRB) astronomy. It is a first-of-its-kind autonomous rapid-slewing satellite for transient astronomy and pioneers the way for future rapid-reaction and multiwavelength missions. It will be far more powerful than any previous GRB mission, observing more than 100 bursts yr � 1 and performing detailed X-ray and UV/optical afterglow observations spanning timescales from 1 minute to several days after the burst. The objectives are to (1) determine the origin of GRBs, (2) classify GRBs and search for new types, (3) study the interaction of the ultrarelativistic outflows of GRBs with their surrounding medium, and (4) use GRBs to study the early universe out to z >10. The mission is being developed by a NASA-led international collaboration. It will carry three instruments: a newgeneration wide-field gamma-ray (15‐150 keV) detector that will detect bursts, calculate 1 0 ‐4 0 positions, and trigger autonomous spacecraft slews; a narrow-field X-ray telescope that will give 5 00 positions and perform spectroscopy in the 0.2‐10 keV band; and a narrow-field UV/optical telescope that will operate in the 170‐ 600 nm band and provide 0B3 positions and optical finding charts. Redshift determinations will be made for most bursts. In addition to the primary GRB science, the mission will perform a hard X-ray survey to a sensitivity of � 1m crab (� 2;10 � 11 ergs cm � 2 s � 1 in the 15‐150 keV band), more than an order of magnitude better than HEAO 1 A-4. A flexible data and operations system will allow rapid follow-up observations of all types of

Deep Eutectic Solvents Formed between Choline Chloride and Carboxylic Acids: Versatile Alternatives to Ionic Liquids

Abstract: Deep Eutectic Solvents (DES) can be formed between a variety of quaternary ammonium salts and carboxylic acids. The physical properties are significantly affected by the structure of the carboxylic acid but the phase behavior of the mixtures can be simply modeled by taking account of the mole fraction of carboxylic acid in the mixture. The physical properties such as viscosity, conductivity, and surface tension of these DES are similar to ambient temperature ionic liquids and insight into the cause of these properties is gained using hole-theory. It is shown that the conductivity and viscosity of these liquids is controlled by ion mobility and the availability of voids of suitable dimensions, and this is consistent with the fluidity of other ionic liquids and molten salts. The DES are also shown to be good solvents for metal oxides, which could have potential application for metal extraction.

Prevalence of mental disorders in Europe: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project

Abstract: Objective: To describe the 12-month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries. Method: A representative random sample of non-institutionalized inhabitants from Belgium, France, Germany, Italy, the Netherlands and Spain aged 18 or older (n = 21425) were interviewed between January 2001 and August 2003. DSM-IV disorders were assessed by lay interviewers using a revised version of the Composite International Diagnostic Interview (WMH-CIDI). Results: Fourteen per cent reported a lifetime history of any mood disorder, 13.6% any anxiety disorder and 5.2% a lifetime history of any alcohol disorder. More than 6% reported any anxiety disorder, 4.2% any mood disorder, and 1.0% any alcohol disorder in the last year. Major depression and specific phobia were the most common single mental disorders. Women were twice as likely to suffer 12-month mood and anxiety disorders as men, while men were more likely to suffer alcohol abuse disorders. Conclusion: ESEMeD is the first study to highlight the magnitude of mental disorders in the six European countries studied. Mental disorders were frequent, more common in female, unemployed, disabled persons, or persons who were never married or previously married. Younger persons were also more likely to have mental disorders, indicating an early age of onset for mood, anxiety and alcohol disorders.

What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data

Abstract: Objectives: To compare the performance of different meta-analysis methods for pooling odds ratios when applied to sparse event data with emphasis on the use of continuity corrections. Background: Meta-analysis of side effects from RCTs or risk factors for rare diseases in epidemiological studies frequently requires the synthesis of data with sparse event rates. Combining such data can be problematic when zero events exist in one or both arms of a study as continuity corrections are often needed, but, these can influence results and conclusions. Methods: A simulation study was undertaken comparing several meta-analysis methods for combining odds ratios (using various classical and Bayesian methods of estimation) on sparse event data. Where required, the routine use of a constant and two alternative continuity corrections; one based on a function of the reciprocal of the opposite group arm size; and the other an empirical estimate of the pooled effect size from the remaining studies in the meta-analysis, were also compared. A number of meta-analysis scenarios were simulated and replicated 1000 times, varying the ratio of the study arm sizes. Results: Mantel–Haenszel summary estimates using the alternative continuity correction factors gave the least biased results for all group size imbalances. Logistic regression was virtually unbiased for all scenarios and gave good coverage properties. The Peto method provided unbiased results for balanced treatment groups but bias increased with the ratio of the study arm sizes. The Bayesian fixed effect model provided good coverage for all group size imbalances. The two alternative continuity corrections outperformed the constant correction factor in nearly all situations. The inverse variance method performed consistently badly, irrespective of the continuity correction used. Conclusions: Many routinely used summary methods provide widely ranging estimates when applied to sparse data with high imbalance between the size of the studies' arms. A sensitivity analysis using several methods and continuity correction factors is advocated for routine practice. Copyright 2004 John Wiley & Sons, Ltd.

Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV

Abstract: Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV

Phase I Clinical Trial of Oral Curcumin: Biomarkers of Systemic Activity and Compliance

Abstract: Curcumin, a polyphenolic antioxidant derived from a dietary spice, exhibits anticancer activity in rodents and in humans. Its efficacy appears to be related to induction of glutathione S-transferase enzymes, inhibition of prostaglandin E2 (PGE2) production, or suppression of oxidative DNA adduct (M1G) formation. We designed a dose-escalation study to explore the pharmacology of curcumin in humans. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies consumed capsules compatible with curcumin doses between 0.45 and 3.6 g daily for up to 4 months. Levels of curcumin and its metabolites in plasma, urine, and feces were analyzed by highpressure liquid chromatography and mass spectrometry. Three biomarkers of the potential activity of curcumin were translated from preclinical models and measured in patient blood leukocytes: glutathione S-transferase activity, levels of M1G, and PGE2 production induced ex vivo. Dose-limiting toxicity was not observed. Curcumin and its glucuronide and sulfate metabolites were detected in plasma in the 10 nmol/L range and in urine. A daily dose of 3.6 g curcumin engendered 62% and 57% decreases in inducible PGE2 production in blood samples taken 1 hour after dose on days 1 and 29, respectively, of treatment compared with levels observed immediately predose (P < 0.05). A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the prevention or treatment of cancers outside the gastrointestinal tract. PGE2 production in blood and target tissue may indicate biological activity. Levels of curcumin and its metabolites in the urine can be used to assess general compliance.

The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke

Abstract: We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall.

The Impact Of Training Of University Teachers on their Teaching Skills, their Approach to Teaching and the Approach to Learning of their Students

Abstract: This article reports a study on the effectiveness of university teachers’ training involving 22 universities in 8 countries. A training group of teachers and their students were studied at the start of their training and one year later. A control group of new teachers received no training and both they and their students were studied in the same way. Evidence is reported of changes over time relating to three measures: (i) student ratings of their teachers using six scales from the Student Evaluation of Educational Quality questionnaire (SEEQ) and the ‘Good Teaching’ scale of the Module Experience Questionnaire (MEQ); (ii) the extent to which teachers described themselves as teacher-focused and student-focused in their approach to teaching, using two scales from the Approaches to Teaching Inventory (ATI); and (iii) the extent to which these teachers’ students take a surface approach and a deep approach to learning, using two scales from the MEQ. The article reports evidence of a range of positive changes ...

British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary

Abstract: Much new evidence has emerged on the importance of blood pressure as a risk factor for cardiovascular disease; the importance of lifestyle measures for the prevention and treatment of hypertension; the efficacy and safety of different drug classes; management of hypertension in groups at higher risk, including people with diabetes; the importance of assessing the total risk of cardiovascular disease; and additional benefits associated with the use of statins. Concern remains that national surveys continue to show substantial underdiagnosis, undertreatment, and poor rates of blood pressure control in the United Kingdom.1 A key reason for this is the predominant use of monotherapy by most doctors.1 To improve this suboptimal treatment, the British Hypertension Society recommends a treatment algorithm based on the AB/CD rule.2 Treatment of blood pressure alone will leave many hypertensive patients at unacceptably high risk of cardiovascular complications and death. This guideline reinforces the view that doctors should not focus solely on blood pressure but must also formally assess total risk of cardiovascular disease and use multifactorial interventions, including statins and aspirin, to reduce it. Most management of blood pressure and risk of cardiovascular disease will take place in primary care, and these guidelines are intended for general practitioners, practice nurses, and generalists in hospital practice. Detailed advice on implementation and the implications of the national service frameworks and the general medical services contract are contained in the full document (http://www.bhsoc.org/).3 These guidelines have been prepared by the guidelines working party of the British Hypertension Society on behalf of the society. The working party reviewed new data that have become available since the previous guidelines were published4 and amended the recommendations accordingly. Drafts of the full document were improved by consultation with …

Transcriptome analysis of haploid male gametophyte development in Arabidopsis

Abstract: Background: The haploid male gametophyte generation of flowering plants consists of two- or three-celled pollen grains. This functional specialization is thought to be a key factor in the evolutionary success of flowering plants. Moreover, pollen ontogeny is also an attractive model in which to dissect cellular networks that control cell growth, asymmetric cell division and cellular differentiation. Our objective, and an essential step towards the detailed understanding of these processes, was to comprehensively define the male haploid transcriptome throughout development. Results: We have developed staged spore isolation procedures for Arabidopsis and used Affymetrix ATH1 genome arrays to identify a total of 13,977 male gametophyte-expressed mRNAs, 9.7% of which were male-gametophyte-specific. The transition from bicellular to tricellular pollen was accompanied by a decline in the number of diverse mRNA species and an increase in the proportion of male gametophyte-specific transcripts. Expression profiles of regulatory proteins and distinct clusters of coexpressed genes were identified that could correspond to components of gametophytic regulatory networks. Moreover, integration of transcriptome and experimental data revealed the early synthesis of translation factors and their requirement to support pollen tube growth. Conclusions: The progression from proliferating microspores to terminally differentiated pollen is characterized by large-scale repression of early program genes and the activation of a unique late gene-expression program in maturing pollen. These data provide a quantum increase in knowledge concerning gametophytic transcription and lay the foundations for new genomic-led studies of the regulatory networks and cellular functions that operate to specify male gametophyte development.

Does Exporting Increase Productivity? A Microeconometric Analysis of Matched Firms

Abstract: Exporting involves sunk costs, so some firms export whilst others do not. This proposition derives from a number of models of firm behavior and has been exposed to microeconometric analysis. Evidence from the latter suggests that exporting firms are generally more productive than nonexporters. They self-select, in that they are more productive before they enter export markets, but the evidence suggests that entry does not make them any more productive. This paper investigates exporting and firm performance for a large panel of UK manufacturing firms, applying matching techniques. The authors find that exporters are more productive and they do self-select. In contrast to other evidence, however, exporting further increases firm productivity.

The problem of appraising qualitative research

Abstract: Qualitative research can make a valuable contribution to the study of quality and safety in health care. Sound ways of appraising qualitative research are needed, but currently there are many different proposals with few signs of an emerging consensus. One problem has been the tendency to treat qualitative research as a unified field. We distinguish universal features of quality from those specific to methodology and offer a set of minimally prescriptive prompts to assist with the assessment of generic features of qualitative research. In using these, account will need to be taken of the particular method of data collection and methodological approach being used. There may be a need for appraisal criteria suited to the different methods of qualitative data collection and to different methodological approaches. These more specific criteria would help to distinguish fatal flaws from more minor errors in the design, conduct, and reporting of qualitative research. There will be difficulties in doing this because some aspects of qualitative research, particularly those relating to quality of insight and interpretation, will remain difficult to appraise and will rely largely on subjective judgement.

Disability and quality of life impact of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project.

Abstract: Objective: This manuscript examines the impact of mental health state and specific mental and physical disorders on work role disability and quality of life in six European countries. Method: The ESEMeD study was conducted in: Belgium, France, Germany, Italy, the Netherlands and Spain. Individuals aged 18 years and over who were not institutionalized were eligible for an in-home computer-assisted interview. Common mental disorders, work loss days (WLD) in the past month and quality of life (QoL) were assessed, using the WMH-2000 version of the CIDI, the WHODAS-II, and the mental and physical component scores (MCS, PCS) of the 12-item short form, respectively. The presence of five chronic physical disorders: arthritis, heart disease, lung disease, diabetes and neurological disease was also assessed. Multivariate regression techniques were used to identify the independent association of mental and physical disorders while controlling for gender, age and Country. Results: In each country, WLD and loss of QoL increased with the number of disorders. Most mental disorders had approximately 1.0 SD-unit lower mean MCS and lost three to four times more work days, compared with people without any 12-month mental disorder. The 10 disorders with the highest independent impact on WLD were: neurological disease, panic disorder, PTSD, major depressive episode, dysthymia, specific phobia, social phobia, arthritis, agoraphobia and heart disease. The impact of mental vs. physical disorders on QoL was specific, with mental disorders impacting more on MCS and physical disorders more on PCS. Compared to physical disorders, mental disorders had generally stronger 'cross-domain' effects. Conclusion: The results suggest that mental disorders are important determinants of work role disability and quality of life, often outnumbering the impact of common chronic physical disorders.

Calpain-mediated proteolysis of talin regulates adhesion dynamics

Abstract: Dynamic regulation of adhesion complexes is required for cell migration and has therefore emerged as a key issue in the study of cell motility. Recent progress has been made in defining some of the molecular mechanisms by which adhesion disassembly is regulated, including the contributions of adhesion adaptor proteins and tyrosine kinases. However, little is known about the potential contribution of proteolytic mechanisms to the regulation of adhesion complex dynamics. Here, we show that proteolysis of talin by the intracellular calcium-dependent protease calpain is critical for focal adhesion disassembly. We have generated a single point mutation in talin that renders it resistant to proteolysis by calpain. Quantification of adhesion assembly and disassembly rates demonstrates that calpain-mediated talin proteolysis is a rate-limiting step during adhesion turnover. Furthermore, we demonstrate that disassembly of other adhesion components, including paxillin, vinculin and zyxin, is also dependent on the ability of calpain to cleave talin, suggesting a general role for talin proteolysis in regulating adhesion turnover. Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated.

Encoded evidence: DNA in forensic analysis

Abstract: Sherlock Holmes said "it has long been an axiom of mine that the little things are infinitely the most important", but never imagined that such a little thing, the DNA molecule, could become perhaps the most powerful single tool in the multifaceted fight against crime. Twenty years after the development of DNA fingerprinting, forensic DNA analysis is key to the conviction or exoneration of suspects and the identification of victims of crimes, accidents and disasters, driving the development of innovative methods in molecular genetics, statistics and the use of massive intelligence databases.

The Cassini Magnetic Field Investigation

Abstract: The dual technique magnetometer system onboard the Cassini orbiter is described. This instrument consists of vector helium and fluxgate magnetometers with the capability to operate the helium device in a scalar mode. This special mode is used near the planet in order to determine with very high accuracy the interior field of the planet. The orbital mission will lead to a detailed understanding of the Saturn/Titan system including measurements of the planetary magnetosphere, and the interactions of Saturn with the solar wind, of Titan with its environments, and of the icy satellites within the magnetosphere.

Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity.

Abstract: Background Adverse early circumstances may be more common in people who later develop psychotic disorders. Aims To use data from the second British National Survey of Psychiatric Morbidity to examine associations between psychotic disorders and a number of early victimisation experiences. Method Psychiatric disorders were identified through structured assessment of adults resident in private households in Britain ( n =8580). Respondents were asked whether they had experienced selected events displayed on cards. Results Compared with respondents with other psychiatric disorders or with none, the prevalence of every experience bar one was significantly elevated in those with definite or probable psychosis. The largest odds ratio was for sexual abuse. Controlling for depressed mood somewhat reduced the odds ratios for the individual experiences. Conclusions In people with psychosis, there is a marked excess of victimising experiences, many of which will have occurred during childhood. This is suggestive of a social contribution to aetiology.

The HIPASS catalogue - I. Data presentation

Abstract: The H I Parkes All-Sky Survey (HIPASS) catalogue forms the largest uniform catalogue of H I sources compiled to date, with 4315 sources identified purely by their H I content. The catalogue data comprise the southern region δ< + 2 ◦ of HIPASS, the first blind H I survey to cover the entire southern sky. The rms noise for this survey is 13 mJy beam −1 and the velocity range is −1280 to 12 700 km s −1 . Data search, verification and parametrization methods are discussed along with a description of measured quantities. Full catalogue data are made available to the astronomical community including positions, velocities, velocity widths, integrated fluxes and peak flux densities. Also available are on-sky moment maps, position‐velocity moment maps and spectra of catalogue sources. A number of local large-scale features are observed in the space distribution of sources, including the super-Galactic plane and the Local Void. Notably, large-scale structure is seen at low Galactic latitudes, a region normally obscured at optical wavelengths.

The 1000 Brightest HIPASS Galaxies: H I Properties

Abstract: We present the HIPASS Bright Galaxy Catalog (BGC), which contains the 1000 H I brightest galaxies in the southern sky as obtained from the H i Parkes All-Sky Survey ( HIPASS). The selection of the brightest sources is based on their H I peak flux density (S-peak greater than or similar to116 mJy) as measured from the spatially integrated HIPASS spectrum. The derived H I masses range from similar to10(7) to 4 x 10(10) M-.. While the BGC ( z 10degrees. Therefore, the BGC yields no evidence for a population of free-floating'' intergalactic H I clouds without associated optical counterparts. HIPASS provides a clear view of the local large-scale structure. The dominant features in the sky distribution of the BGC are the Supergalactic Plane and the Local Void. In addition, one can clearly see the Centaurus Wall, which connects via the Hydra and Antlia Clusters to the Puppis Filament. Some previously hardly noticable galaxy groups stand out quite distinctly in the H I sky distribution. Several new structures, including some not behind the Milky Way, are seen for the first time.

Use of mental health services in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project

Abstract: The ESEMeD ⁄ MHEDEA 2000 investigators. Use of mental health services in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand 2004: 109 (Suppl. 420): 47–54. a Blackwell Munksgaard 2004. Objective: Comprehensive information about access and patterns of use of mental health services in Europe is lacking. We present the first results of the use of health services for mental disorders in six European countries as part of the ESEMeD project. Method: The study was conducted in: Belgium, France, Germany, Italy, the Netherlands and Spain. Individuals aged 18 years and over who were not institutionalized were eligible for an computer-assisted interview done at home. The 21 425 participants were asked to report how frequently they consulted formal health services due to their emotions or mental health, the type of professional they consulted and the treatment they received as a result of their consultation in the previous year. Results: An average of 6.4% of the total sample had consulted formal health services in the previous 12months. Of the participants with a 12-month mental disorder, 25.7% had consulted a formal health service during that period. This proportion was higher for individuals with a mood disorder (36.5%, 95% CI 32.5–40.5) than for those with anxiety disorders (26.1%, 95% CI 23.1–29.1). Among individuals with a 12-month mental disorder who had contacted the health services 12months previously, approximately two-thirds had contacted a mental health professional. Among those with a 12-month mental disorder consulting formal health services, 21.2% received no treatment. Conclusion: The ESEMeD results suggest that the use of health services is limited among individuals with mental disorders in the European countries studied. The factors associated with this limited access and their implications deserve further research. The ESEMeD ⁄ MHEDEA 2000

Uses of Music in Everyday Life

Abstract: The value of music in people9s everyday lives depends on the uses they make of it and the degree to which they engage with it, which are in turn dependent on the contexts in which they hear it. Very few studies have investigated people9s experiences of music in naturalistic, everyday circumstances, and this exploratory study provides some initial normative data on who people listen with, what they listen to (and what their emotional responses to this music are), when they listen, where they listen, and why they listen. A total of 346 people who owned a mobile phone were sent one text message per day for 14 days. On receiving this message, participants were required to complete a questionnaire about any music they could hear, or had heard since their previous message. Responses indicated a high compliance rate; a high incidence of exposure to music; that the greatest number of musical episodes occurred while participants were on their own; that pop music was heard most frequently; that liking for the music varied depending on who the participant was with, where they were, and whether they had chosen to be able to hear music; that music was usually experienced during the course of some activity other than deliberate music listening; that exposure to music occurred most frequently in the evening, particularly between 10 pm and 11 pm, and on weekends; that music was heard most frequently at home, with only a small number of incidences occurring in public places; that the importance of several functions of music varied according to temporal factors, the place where the music was heard, and the person or people the participant was with. Further research should include participants from a greater range of sociodemographic backgrounds and should develop context-specific theoretical explanations of the different ways in which people use music as a resource.

Life at low water activity.

Abstract: Two major types of environment provide habitats for the most xerophilic organisms known: foods preserved by some form of dehydration or enhanced sugar levels, and hypersaline sites where water availability is limited by a high concentration of salts (usually NaCl). These environments are essentially microbial habitats, with high-sugar foods being dominated by xerophilic (sometimes called osmophilic) filamentous fungi and yeasts, some of which are capable of growth at a water activity (a(w)) of 0.61, the lowest a(w) value for growth recorded to date. By contrast, high-salt environments are almost exclusively populated by prokaryotes, notably the haloarchaea, capable of growing in saturated NaCl (a(w) 0.75). Different strategies are employed for combating the osmotic stress imposed by high levels of solutes in the environment. Eukaryotes and most prokaryotes synthesize or accumulate organic so-called 'compatible solutes' (osmolytes) that have counterbalancing osmotic potential. A restricted range of bacteria and the haloarchaea counterbalance osmotic stress imposed by NaCl by accumulating equivalent amounts of KCl. Haloarchaea become entrapped and survive for long periods inside halite (NaCl) crystals. They are also found in ancient subterranean halite (NaCl) deposits, leading to speculation about survival over geological time periods.

Palaeozoic accretionary and convergent tectonics of the southern Altaids: implications for the growth of Central Asia

Abstract: The southern Altaids present a unidirectional section from Mongolia to China through an accretionary orogen that youngs progressively from Neoproterozoic in the north to Permian in the south. The orogen formed by forearc accretion of island arcs, accretionary wedges, ophiolites and Precambrian microcontinents. This regularity was upset by early growth within the ocean of arcs that later collided at the accreting continental margin, by imbrication of old ophiolites with young arcs, and by Himalayan-style thrust–nappe tectonics when an arc collided into a microcontinent. Lateral growth of the Southern Altaids represents a massive addition of juvenile material to the Palaeozoic crust.

Internal charge behaviour of nanocomposites

Abstract: The incorporation of 23 nm titanium dioxide nanoparticles into an epoxy matrix to form a nanocomposite structure is described. It is shown that the use of nanometric particles results in a substantial change in the behaviour of the composite, which can be traced to the mitigation of internal charge when a comparison is made with conventional TiO2 fillers. A variety of diagnostic techniques (including dielectric spectroscopy, electroluminescence, thermally stimulated current, photoluminescence) have been used to augment pulsed electro-acoustic space charge measurement to provide a basis for understanding the underlying physics of the phenomenon. It would appear that, when the size of the inclusions becomes small enough, they act co-operatively with the host structure and cease to exhibit interfacial properties leading to Maxwell-Wagner polarization. It is postulated that the particles are surrounded by high charge concentrations in the Gouy-Chapman-Stern layer. Since nanoparticles have very high specific areas, these regions allow limited charge percolation through nano-filled dielectrics. The practical consequences of this have also been explored in terms of the electric strength exhibited. It would appear that there was a window in which real advantages accrue from the nano-formulated material. An optimum loading of about 10% (by weight) is indicated.

Simulating Hamiltonian Dynamics

Abstract: Geometric integrators are time-stepping methods, designed such that they exactly satisfy conservation laws, symmetries or symplectic properties of a system of differential equations. In this book the authors outline the principles of geometric integration and demonstrate how they can be applied to provide efficient numerical methods for simulating conservative models. Beginning from basic principles and continuing with discussions regarding the advantageous properties of such schemes, the book introduces methods for the N-body problem, systems with holonomic constraints, and rigid bodies. More advanced topics treated include high-order and variable stepsize methods, schemes for treating problems involving multiple time-scales, and applications to molecular dynamics and partial differential equations. The emphasis is on providing a unified theoretical framework as well as a practical guide for users. The inclusion of examples, background material and exercises enhance the usefulness of the book for self-instruction or as a text for a graduate course on the subject.

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration.

Abstract: Studies in vitro and in animal models of colorectal and hepatocellular cancers suggest that curcumin is an effective chemopreventive agent. In this pilot trial, we investigated whether oral administration of curcumin results in concentrations of the agent in normal and malignant human liver tissue, which are sufficient to elicit pharmacological activity. In total, 12 patients with hepatic metastases from colorectal cancer received 450-3600 mg of curcumin daily, for 1 week prior to surgery. Levels of curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue. Curcumin was poorly available, following oral administration, with low nanomolar levels of the parent compound and its glucuronide and sulphate conjugates found in the peripheral or portal circulation. While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected. In patients who had received curcumin, levels of malondialdehyde-DNA (M(1)G) adduct, which reflect oxidative DNA changes, were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples. The results suggest that doses of curcumin required to furnish hepatic levels sufficient to exert pharmacological activity are probably not feasible in humans.

Recent Developments in Low-Level Lead Exposure and Intellectual Impairment in Children

Abstract: In the last decade children's blood lead levels have fallen significantly in a number of countries, and current mean levels in developed countries are in the region of 3 Mu g/dL. Despite this reduction, childhood lead poisoning continues to be a major public health problem for certain at-risk groups of children, and concerns remain over the effects of lead on intellectual development in infants and children. The evidence for lowered cognitive ability in children exposed to lead has come largely from prospective epidemiologic studies. The current World Health Organization/Centers for Disease Control and Prevention blood level of concern reflects this and stands at 10 Mu g/dL. However, a recent study on a cohort of children whose lifetime peak blood levels were consistently less than 10 Mu g/dL has extended the association of blood lead and intellectual impairment to lower levels of lead exposure and suggests there is no safety margin at existing exposures. Because of the importance of this finding, we reviewed this study in detail along with other recent developments in the field of low-level lead exposure and children's cognitive development. We conclude that these findings are important scientifically, and efforts should continue to reduce childhood exposure. However, from a public health perspective, exposure to lead should be seen within the many other risk factors impacting on normal childhood development, in particular the influence of the learning environment itself. Current lead exposure accounts for a very small amount of variance in cognitive ability (1-4%), whereas social and parenting factors account for 40% or more.

Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice.

Abstract: The serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding to inhibitor of apoptosis proteins (IAPs) via its amino-terminal Reaper-related motif, thus inducing caspase activity, and also in mediating caspase-independent death through its own protease activity. We report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary suffer loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that leads to death of the mice around 30 days after birth. The phenotype of these mice suggests that it is the protease function of this protein and not its IAP binding motif that is critical. This conclusion is reinforced by the finding that simultaneous deletion of the other major IAP binding protein, Smac/DIABLO, does not obviously alter the phenotype of HtrA2/Omi knockout mice or cells derived from them. Mammalian HtrA2/Omi is therefore likely to function in vivo in a manner similar to that of its bacterial homologues DegS and DegP, which are involved in protection against cell stress, and not like the proapoptotic Reaper family proteins in Drosophila melanogaster.

A dwarf galaxy remnant in Canis Major: the fossil of an in-plane accretion on to the Milky Way

Abstract: We present an analysis of the asymmetries in the population of Galactic M-giant stars present in the 2MASS All Sky catalogue. Several large-scale asymmetries are detected, the most significant of which is a strong elliptical-shaped stellar over-density, close to the Galactic plane at (l = 240 ◦ , b = 8 ◦ ), in the constellation of Canis Major. A small grouping of globular clusters (NGC 1851, NGC 1904, NGC 2298, and NGC 2808), coincident in position and radial velocity, surround this structure, as do a number of open clusters. The population of M-giant stars in this over-density is similar in number to that in the core of the Sagittarius dwarf galaxy. We argue that this object is the likely dwarf galaxy progenitor of the ring-like structure that has recently been found at the edge of the Galactic disk. A numerical study of the tidal disruption of an accreted dwarf galaxy is presented. The simulated debris fits well the extant position, distance and velocity information on the “Galactic Ring”, as well as that of the M-giant overdensities, suggesting that all these structures are the consequence of a single accretion event. The disrupted dwarf galaxy stream orbits close to the Galactic Plane, with a pericentre at approximately the Solar circle, an orbital eccentricity similar to that of stars in the Galactic thick disk, as well as a vertical scale height similar to that of the thick disk. This finding strongly suggests that the Canis Major dwarf galaxy is a building block of the Galactic thick disk, that the thick disk is continually growing, even up to the present time, and that thick disk globular clusters were accreted onto the Milky Way from dwarf galaxies in co-planar orbits.