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The inadequacy of current diagnostics for the detection of low worm burdens in humans means that schistosomiasis mansoni is more widespread than previously acknowledged. With the inception of mass drug treatment programmes aimed at disease elimination and the advent of human vaccine trials, the need for more sensitive diagnostics is evident. In this review, we evaluate the merits and limitations of the principal diagnostic methods, namely detection of eggs in faeces; anti-schistosome antibodies in serum; parasite-derived proteins and glycans in serum or urine; parasite DNA in blood, faeces or urine. Only in the baboon model, where actual worm burden is determined by portal perfusion, have faecal smear and circulating antigen methods been calibrated, and shown to have thresholds of detection of 10–19 worm pairs. There is scope for improvement in all the four methods of detection, e.g. the identification of single targets for host antibodies to improve the specificity of enzyme linked immunosorbent assay. Despite recent advances in the definition of the schistosome secretome, there have been no comprehensive biomarker investigations of parasite products in the urine of infected patients. Certainly, the admirable goal of eliminating schistosomiasis will not be achieved unless individuals with low worm burdens can be diagnosed.
A “giant” outburst of A 0535+262, a transient X-ray binary pulsar, was observed in 1994 February and March with the Burst and Transient Source Experiment (BATSE) onboard the Compton Gamma-Ray Observatory. During the outburst power spectra of the hard X-ray flux contained a QPO-like component with a FWHM of approximately 50% of its center frequency. Over the course of the outburst the center frequency rose smoothly from 35 mHz to 70 mHz and then fell to below 40 mHz. We compare this QPO frequency with the neutron star spin-up rate, and discuss the observed correlation in terms of the beat frequency and Keplerian frequency QPO models in conjunction with the Ghosh-Lamb accretion torque model.
This paper examines employment issues concerning deafened adults, especially those with cochlear implants. The analysis shows that deafened people have fewer educational qualifications and are less likely to be in paid employment when compared with people without a hearing disability. In consequence, they report lower income levels. Conversely, respondents with cochlear implants reported higher levels of employment and income. In addition to disability, social factors such as age and sex may contribute to a person's socio-economic status. As such, rehabilitation interventions need to consider the person's social as well as auditory needs.
The potential of various quantitative lateral flow (LF) based assays utilizing up-converting phosphor (UCP) reporters for the diagnosis of schistosomiasis is reviewed including recent developments. Active infections are demonstrated by screening for the presence of regurgitated worm antigens (genus specific polysaccharides), whereas anti-Schistosoma antibodies may indicate ongoing as well as past infections. The circulating anodic antigen (CAA) in serum or urine (and potentially also saliva) is identified as the marker that may allow detection of single-worm infections. Quantitation of antigen levels is a reliable method to study effects of drug administration, worm burden and anti-fecundity mechanisms. Moreover, the ratio of CAA and circulating cathodic antigen (CCA) is postulated to facilitate identification of either Schistosoma mansoni or Schistosoma haematobium infections. The UCP-LF assays allow simultaneous detection of multiple targets on a single strip, a valuable feature for antibody detection assays. Although antibody detection in endemic regions is not a useful tool to diagnose active infections, it gains potential when the ratio of different classes of antibody specific for the parasite/disease can be determined. The UCP-LF antibody assay format allows this type of multiplexing, including testing a linear array of up to 20 different targets. Multiple test spots would allow detection of specific antibodies, e.g. against different Schistosoma species or other pathogens as soil-transmitted helminths. Concluding, the different UCP-LF based assays for diagnosis of schistosomiasis provide a collection of tests with relatively low complexity and high sensitivity, covering the full range of diagnostics needed in control programmes for mapping, screening and monitoring.
Burkitt (BL) and lymphoblastic lymphomas (LBL) are highly aggressive diseases with distinct natural histories and clinical presentations. BL mostly occurs in the first two decades of life and accounts for 1–2% of all lymphomas. Three clinical variants are recognized: (1) endemic BL, which is primarily found in equatorial Africa; (2) sporadic BL, which presents worldwide but is the most common type in western countries; and (3) immunodeficiency-associated BL, which is associated with HIV infection. There are important clinical differences in these variants (Table 11.1), with endemic BL involving the jaw, orbit, and paraspinal regions in half of the cases as well as the mesentery and gonads, while sporadic BL mostly involves the distal ileum, cecum, and/or mesentery, and rarely the jaw. When bulky or disseminated disease is present, extranodal involvement of the ovaries, kidney, breasts, and/or CNS may be seen. Clinical presentation in a Berlin–Frankfurt–Munster Group (BFM) series of 152 pediatric patients included advanced stage (III/IV) disease in 38%, bone marrow involvement in 33%, and central nervous system (CNS) disease in 4%. Of the patients in this series, 27% presented as acute leukemia, referred to as the L3 subtype of acute lymphoblastic leukemia (ALL) within the French-American-British (FAB) classification, or B-ALL. BL infrequently presents in adults, but does occur with increased frequency in patients with HIV infection.
LBL is most commonly a malignancy of T-cell precursor cells, and, as such, it is identical to T-cell acute lymphoblastic leukemia (T-ALL).
The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not.
Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging.
The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%.
There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
The purpose of this paper is to examine firms’ adoption of corporate social responsibility activities and the efficacy of such activities in specific contexts and industries. This paper analyses the specific context of the Spanish construction and real-estate industry. By using a longitudinal multi-case approach, the study suggests links between market orientation and corporate social responsibility. The research also identifies two profiles of firms. The first group, which is proactive (e.g., market oriented), demonstrate altruistic concerns about consumers and corporate social responsibility; for the second, which is more reactive, their concerns about corporate social responsibility are more opportunistic and aimed at attracting additional customers or responding to competitive pressures.
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0–13 weeks and 0–39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
Since 2004 there has been a remarkable increment in our knowledge of the proteins and glycans that reside at, or are released from the surfaces of schistosomes in the mammalian host. Initial characterization of the soluble proteome permits distinctions to be made between the parasite secretome and its necrotome. The principal proteins secreted by the cercaria to gain access to the skin have been described as well as those released by migrating schistosomula. An inventory of transporters, enzymes and structural proteins has been shown to reside the tegument surface, but also immunoglobulins, complement factors and host CD44. The secreted membranocalyx that overlies the plasma membrane may contain a small number of proteins, not simply acting as physical barrier, but its lipid composition remains elusive. Analysis of worm vomitus has provided insights into blood feeding, increasing the number of known lysosomal hydrolases, and identifying a series of carrier proteins potentially involved in uptake of lipids and inorganic ions by the gut epithelium. The egg secretions that aid escape from the tissues include a mixture of MEG-2 and MEG-3 family variant proteins. The utility of identified proteins for the development of new diagnostics, and their potential as vaccines candidates is evaluated.
The U.S. Geological Survey (USGS) has been producing reference materials since the 1950s. Over 50 materials have been developed to cover bulk rock, sediment, and soils for the geological community. These materials are used globally in geochemistry, environmental, and analytical laboratories that perform bulk chemistry and/or microanalysis for instrument calibration and quality assurance testing. To answer the growing demand for higher spatial resolution and sensitivity, there is a need to create a new generation of microanalytical reference materials suitable for a variety of techniques, such as scanning electron microscopy/X-ray spectrometry (SEM/EDS), electron probe microanalysis (EPMA), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS). As such, the microanalytical reference material (MRM) needs to be stable under the beam, be homogeneous at scales of better than 10–25 micrometers for the major to ultra-trace element level, and contain all of the analytes (elements or isotopes) of interest. Previous development of basaltic glasses intended for LA-ICP-MS has resulted in a synthetic basaltic matrix series of glasses (USGS GS-series) and a natural basalt series of glasses (BCR-1G, BHVO-2G, and NKT-1G). These materials have been useful for the LA-ICP-MS community but were not originally intended for use by the electron or ion beam community. A material developed from start to finish with intended use in multiple microanalytical instruments would be useful for inter-laboratory and inter-instrument platform comparisons.
This article summarizes the experiments undertaken to produce a basalt glass reference material suitable for distribution as a multiple-technique round robin material. The goal of the analytical work presented here is to demonstrate that the elemental homogeneity of the new glass is acceptable for its use as a reference material. Because the round robin exercise is still underway, only nominal compositional ranges for each element are given in the article.
Transposons of the Mutator superfamily have been widely described in plants, but only recently have metazoan organisms been shown to harbour them. In this work we describe novel Mutator superfamily transposons from the genomes of the human parasites Schistosoma mansoni and S. japonicum, which we name Curupira-1 and Curupira-2. Curupira elements do not have Terminal Inverted Repeats (TIRs) at their extremities and generate Target Site Duplications (TSDs) of 9 base pairs. Curupira-2 transposons code for a conserved transposase and SWIM zinc finger domains, while Curupira-1 elements comprise these same domains plus a WRKY zinc finger. Alignment of transcript sequences from both elements back to the genomes indicates that they are subject to splicing to produce mature transcripts. Phylogenetic analyses indicate that these transposons represent a new lineage of metazoan Mutator-like elements with characteristics that are distinct from the recently described Phantom elements. Description of these novel schistosome transposons provides new insights in the evolution of transposable elements in schistosomes.
Scanning electron beam annealing techniques have been applied to the study of diffusion of implanted arsenic and boron difluoride. Electron beam anneals over the time range 0-180s (at Tmax), with peak temperatures in the range 1100-1200°C have been performed on uniformly implanted samples. Controlled slow cooling has been performed for some samples. Direct sample temperature measurements were made using a dual-colour pyrometer under control of a microcomputer, which provided data-logging and feedback control of temperature. The accurate temperature control achieved using this system is important for realistic diffusion modelling.
Measurement of the resulting chemical and electrical dopant profiles, using SIMS, RBS and spreading resistance methodshas shown the presence of non-equilibrium diffusion at short times . Channelling RBS studies used to investigate the activation and clustering behaviour of arsenic during the first stages of these very rapid anneals is reported.
Modelling of the arsenic diffusion occuring for a range of implant doses subjected to these anneals has been performed,applying avariety of models, including a dynamic clustering model. This dynamic clustering model, based upon an equilibrium cluster model and a measured de-clustering rate, has been shown previously to give good agreementwith experiment. Forthese experiments, a modified de-clustering coefficient was needed to model the diffusion occuring for a wider range of arsenic implants. A solution of the Poisson equation for the internal electric field has also been incorporated.
DLTS techniques have been used to study the defects remaining in diodes fabricated using these implagts andanneals. Trap densities of <5×1010cm−3 and leakages of <2×10−9 A.cm2 at −5V have been measured for the best devices, similar tothose observed for control furnace anneals.
Metastable Intermolecular Composite (MIC) materials are comprised of a mixture of oxidizer and fuel with particle sizes in the nanometer range. Characterizing their ignition and combustion is an ongoing effort at Los Alamos. In this paper we will present some recent studies at Los Alamos aimed at developing a better understanding of ignition and combustion of MIC materials. Ignition by impact has been studied using a laboratory gas gun using nano-aluminum (Al) and nano-tantalum (Ta) as the reducing agent and bismuth (III) oxide (Bi2O3) as the oxidant. As expected from the chemical potential, the Al containing composites gave higher peak pressures. It was found, for the Al/Bi2O3 system, that impact velocity under observed conditions plays no role in the pressure output until approximately 100 m/s, below which speed, impact energy is insufficient to ignite the reaction. This makes the experiment more useful in evaluating the reactive performance. Replacing the atmosphere on impact with an inert gas reduced both the amount of light produced and the realized peak pressure. The combustion of low-density MIC powders has also been studied. To better understand the reaction mechanisms of burning MIC materials, dynamic electrical conductivity measurements have been performed on a MIC material for the first time. Simultaneous optical measurements of the wave front position have shown that the reaction and conduction fronts are coincident within 160 μm.
Antimony is a useful n-type dopant for buried layers, due to its low rate of lateral diffusion in subsequent processing steps. To date, no solid planar diffusion source has been available. Reported here is the development of such a source.
The source is made by high temperature synthesis in a hot press. A mixture of antimony trioxide and silicon powders is placed in the press, and heated under pressure. The reaction
results in a solidified product. Wafers are sliced from this product to form the actual planar diffusion sources.
The sources are used in a two-step doping process: a predeposition followed by a drive-in. Oxygen is required in both steps, due to the chemistry involved. Typical properties of the doped silicon are: sheet resistance, 10 Ω/square, junction depth, 4–6 microns, and antimony surface concentration. 3–8 × 1019/cm3.