Anemia screening in potential female blood donors: comparison of two different quantitative methods

Anemia screening before blood donation requires an accurate, quick, practical, and easy method with minimal discomfort for the donors. The aim of this study was to compare the accuracy of two quantitative methods of anemia screening: the HemoCue 201(+) (Aktiebolaget Leo Diagnostics) hemoglobin (Hb) and microhematocrit (micro-Hct) tests. Two blood samples of a single fingerstick were obtained from 969 unselected potential female donors to determine the Hb by HemoCue 201(+) and micro-Hct using HemataSTAT II (Separation Technology, Inc.), in alternating order. From each participant, a venous blood sample was drawn and run in an automatic hematology analyzer (ABX Pentra 60, ABX Diagnostics). Considering results of ABX Pentra 60 as true values, the sensitivity and specificity of HemoCue 201(+) and micro-Hct as screening methods were compared, using a venous Hb level of 12.0 g per dL as cutoff for anemia. The sensitivities of the HemoCue 201(+) and HemataSTAT II in detecting anemia were 56 percent (95% confidence interval [CI], 46.1%-65.5%) and 39.5 percent (95% CI, 30.2%-49.3%), respectively (p < 0.001). Analyzing only candidates with a venous Hb level lower than 11.0 g per dL, the deferral rate was 100 percent by HemoCue 201(+) and 77 percent by HemataSTAT II. The specificities of the methods were 93.5 and 93.2 percent, respectively. The HemoCue 201(+) showed greater discriminating power for detecting anemia in prospective blood donors than the micro-Hct method. Both presented equivalent deferral error rates of nonanemic potential donors. Compared to the micro-Hct, HemoCue 201(+) reduces the risk of anemic female donors giving blood, specially for those with lower Hb levels, without increasing the deferral of nonanemic potential donors.

Molecular orbital calculations of two-electron states for P-donor solid-state spin qubits

We theoretically study the Hilbert space structure of two neighboring P-donor electrons in silicon-based quantum computer architectures. To use electron spins as qubits, a crucial condition is the isolation of the electron spins from their environment, including the electronic orbital degrees of freedom. We provide detailed electronic structure calculations of both the single donor electron wave function and the two-electron pair wave function. We adopted a molecular orbital method for the two-electron problem, forming a basis with the calculated single donor electron orbitals. Our two-electron basis contains many singlet and triplet orbital excited states, in addition to the two simple ground state singlet and triplet orbitals usually used in the Heitler-London approximation to describe the two-electron donor pair wave function. We determined the excitation spectrum of the two-donor system, and study its dependence on strain, lattice position, and interdonor separation. This allows us to determine how isolated the ground state singlet and triplet orbitals are from the rest of the excited state Hilbert space. In addition to calculating the energy spectrum, we are also able to evaluate the exchange coupling between the two donor electrons, and the double occupancy probability that both electrons will reside on the same P donor. These two quantities are very important for logical operations in solid-state quantum computing devices, as a large exchange coupling achieves faster gating times, while the magnitude of the double occupancy probability can affect the error rate.

DISCORDANCE FOR RETINITIS PIGMENTOSA IN TWO MONOZYGOTIC TWIN PAIRS

Background: Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with progressive degeneration of the retina. The condition can be inherited as an autosomal dominant, autosomal recessive, and X-linked trait. Methods: We report on two female twin pairs. One twin of each pair is affected with RP, the other twin is unaffected, both clinically and functionally. Molecular analysis in both twins included zygosity determination, arrayed primer extension chip analysis for autosomal recessive and dominant RP, sequencing of the entire RPGR gene, and analysis of X-chromosome inactivation status. Results: Both unrelated twin pairs were genetically identical. Of the potential pathogenetic mechanisms, skewed X-inactivation was excluded on leukocytes. Autosomal recessive RP and autosomal dominant RP arrayed primer extension chip analysis result was completely normal, excluding known mutations in known genes as the cause of disease in the affected twins. Sequencing excluded mutations in RPGR. A postzygotic recessive or dominant genetic mutation of an RP gene is not impossible. A postfertilization error as a potential cause of uniparental isodisomy is unlikely albeit not entirely impossible. Conclusion: The authors report on the second and third unrelated identical twin pair discordant for RP. The exact cause of the condition and the explanation of the clinical discordance remain elusive. RETINA 31:1164-1169, 2011

Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type

Methylmalonic aciduria (MMA) and homocystinuria, cblC type (MIM 277400) is the most frequent inborn error of vitamin B-12. The recent identification of the disease gene, MMACHC, has permitted preliminary genotype-phenotype correlations. We studied 24 Italian and 17 Portuguese patients with cblC defect to illustrate the spectrum of mutations in a southern European population and discuss the impact that mutation identification has on routine diagnostic procedures. Since the metabolic defect raises the serum levels of homocysteine, we also tested if variants in MTHFR-playing a key role in homocysteine remethylation pathway-could act as genetic modifier in cblC defect. We found that the c.271 dupA (accounting for 55% of the MMA CH alleles in our cohort) followed by c.394C > T (16%) and c.331C > T (9%) were the most frequent mutations. In our study we also identified a novel mutation (c.544T > C). On the other hand, the MTHFR genotype did not appear to influence age at onset, the clinical phenotype and outcome of patients with cblC defect. This study shows that mutation screening for the most common MMACH mutations occurring in early-onset forms (c.271dupA and c.331C > T) seems to have a high diagnostic yield in a southern European population with cblC defect. Although the identification of the gene defect per se does not predict completely time and severity of disease appearance, our data corroborate the importance of a molecular testing to offer accurate prenatal diagnosis to couples at high risk of having affected children. (C) 2007 Elsevier Inc. All rights reserved.

Anthropometric measures in relation to Basal Cell Carcinoma: a longitudinal study

Background: The relationship between anthropometric indices and risk of basal cell carcinoma ( BCC) is largely unknown. We aimed to examine the association between anthropometric measures and development of BCC and to demonstrate whether adherence to World Health Organisation guidelines for body mass index, waist circumference, and waist/ hip ratio was associated with risk of BCC, independent of sun exposure. Methods: Study participants were participants in a community- based skin cancer prevention trial in Nambour, a town in southeast Queensland ( latitude 26 degrees S). In 1992, height, weight, and waist and hip circumferences were measured for all 1621 participants and weight was remeasured at the end of the trial in 1996. Prevalence proportion ratios were calculated using a log- binomial model to estimate the risk of BCC prior to or prevalent in 1992, while Poisson regression with robust error variances was used to estimate the relative risk of BCC during the follow- up period. Results: At baseline, 94 participants had a current BCC, and 202 had a history of BCC. During the 5- year follow- up period, 179 participants developed one or more new BCCs. We found no significant association between any of the anthropometric measures or indices and risk of BCC after controlling for potential confounding factors including sun exposure. There was a suggestion that short- term weight gain may increase the risk of developing BCC for women only. Conclusion: Adherence to World Health Organisation guidelines for body mass index, waist circumference and waist/ hip ratio is not significantly associated with occurrence of basal cell carcinomas of the skin.

Neurological manifestations and ATP7B mutations in Wilson`s disease

Wilson`s disease (WD) is a rare inborn metabolic error characterized by deficient biliary copper excretion secondary to ATP7B gene mutations. Neurological presentations are variable in respect to both pattern and age of onset; commonly a movement disorder presents in the second or third decade. The aim of this study was to ascertain genotype correlations with distinct neurological manifestations in 41 WD patients in a Brazilian center for WD. A total of 23 distinct mutations were detected, and the frameshift 3402de1C had the highest allelic frequency (31.7%). An association between 3402de1C and dysphagia was detected (p = 0.01) but the limited number of patients is insufficient to allow one to draw conclusions. Both clinical studies analyzing larger cohorts and basic research on ATP7B protein function could potentially shed more light on our understanding of WD. (c) 2007 Elsevier Ltd. All rights reserved.

Speech disorder in preschool children exposed to Cantonese and English

Speech disorder in monolingual Cantonese- or English-speaking children has been well described in the literature. There appear to be no reports, however, that describe speech-disordered children who have been exposed to both languages. Here we report on the error patterns of two preschool speech-disordered children who were learning two languages. Both children's first language was Cantonese, but they were also exposed to English through the media and child care. Their disorders were of unknown aetiology. The following questions were asked of the data: (a) Do bilingual children, suspected of having speech problems, make errors in Cantonese and English that reflect delay or disorder when compared with normative data on monolingual speech development in each language? (b) How does the children's speech differ from other bilingual children from the same language learning background? (c) Are the children's speech difficulties apparent in both languages? (d) Is the pattern of errors the same in both languages or do language-specific processes operate? The results bear on theories of acquisition, disorder and bilingualism; they also have clinical implications for speech-language pathologists whose caseloads include bilingual preschool children.

Characterisation of five missense mutations in the cystathionine beta-synthase gene from three patients with B-6-nonresponsive homocystinuria

Homocystinuria, due to a deficiency of the enzyme cystathionine beta-synthase (CBS), is an inborn error of sulphur-amino acid metabolism, This is an autosomal recessive disease which results in hyperhomocysteinaemia and a wide range of clinical features, including optic lens dislocation, mental retardation, skeletal abnormalities and premature thrombotic events, We report the identification of 5 missense mutations in the protein-coding region of the CBS gene from 3 patients with pyridoxine-nonresponsive homocystinuria. Reverse-transcription PCR was used to amplify CBS cDNA from each patient and the coding region was analysed by direct sequencing, The mutations detected included 3 novel (1058C --> T, 992C --> A and 1316G --> A) and 2 previously identified (430G --> A and 833C --> T) base alterations in the CBS cDNA, Each of these mutations predicts a single amino acid substitution in the CBS polypeptide, Appropriate cassettes of patient CBS cDNA, containing each of the above defined mutations, were used to replace the corresponding cassettes of normal CBS cDNA sequence within the bacterial expression vector pT7-7. These recombinant mutant and normal CBS constructs were expressed in Escherichia coli cells and the catalytic activities of the mutant proteins were compared with normal. All of the mutant proteins exhibited decreased catalytic activity in vitro, which confirmed the association between the individual mutation and CBS dysfunction in each patient.

Studies on the gelation of photocatalysed dicyanate ester resins

The gel point of a dicyanate ester resin (Arocy B-10 (4-4'-dicyanato-2,2'-diphenylpropane)) heated following irradiation in the presence of the catalyst tricarbonyl cyclopentadienyl manganese (CpMn(CO)(3)) was studied using differential scanning calorimetry (d.s.c.) and dynamic rheological techniques over the temperature range 110-140 degrees C. The gel times of another commercial cyanate ester (RTX366) were also studied using independent rheological techniques, and the results agreed within experimental error. Gel times decreased linearly with increasing catalyst level and with increasing temperature according to an Arrhenius relation with activation energy of 68 +/- 6 kJmol(-1). The gel conversion was calculated by correlation of the rheological gel data to d.s.c. data to be 0.57 +/- 0.02, and differences between techniques, and between theoretical predictions, are discussed. Evidence is produced that the photocatalysed polymerization results in a greater rate of cyclotrimerization, less intramolecular cyclization and a more rigid network than the uncatalysed or metal salt-catalysed high-temperature polymerization. (C) 1997 Elsevier Science Ltd.

Strategies for genetic model specification in the screening of genome-wide meta-analysis signals for further replication

Background Meta-analysis is increasingly being employed as a screening procedure in large-scale association studies to select promising variants for follow-up studies. However, standard methods for meta-analysis require the assumption of an underlying genetic model, which is typically unknown a priori. This drawback can introduce model misspecifications, causing power to be suboptimal, or the evaluation of multiple genetic models, which augments the number of false-positive associations, ultimately leading to waste of resources with fruitless replication studies. We used simulated meta-analyses of large genetic association studies to investigate naive strategies of genetic model specification to optimize screenings of genome-wide meta-analysis signals for further replication. Methods Different methods, meta-analytical models and strategies were compared in terms of power and type-I error. Simulations were carried out for a binary trait in a wide range of true genetic models, genome-wide thresholds, minor allele frequencies (MAFs), odds ratios and between-study heterogeneity (tau(2)). Results Among the investigated strategies, a simple Bonferroni-corrected approach that fits both multiplicative and recessive models was found to be optimal in most examined scenarios, reducing the likelihood of false discoveries and enhancing power in scenarios with small MAFs either in the presence or in absence of heterogeneity. Nonetheless, this strategy is sensitive to tau(2) whenever the susceptibility allele is common (MAF epsilon 30%), resulting in an increased number of false-positive associations compared with an analysis that considers only the multiplicative model. Conclusion Invoking a simple Bonferroni adjustment and testing for both multiplicative and recessive models is fast and an optimal strategy in large meta-analysis-based screenings. However, care must be taken when examined variants are common, where specification of a multiplicative model alone may be preferable.

Monte Carlo evidence on cointegration and causation

The small sample performance of Granger causality tests under different model dimensions, degree of cointegration, direction of causality, and system stability are presented. Two tests based on maximum likelihood estimation of error-correction models (LR and WALD) are compared to a Wald test based on multivariate least squares estimation of a modified VAR (MWALD). In large samples all test statistics perform well in terms of size and power. For smaller samples, the LR and WALD tests perform better than the MWALD test. Overall, the LR test outperforms the other two in terms of size and power in small samples.

Direct visualisation of B-1 inhomogeneity by flip angle dependency

Inhomogeneities in the spatial distribution of the excitatory Radio Frequency (RF) field, are still a dominant source of artifacts and loss of signal to noise ratio in MR imaging experiments, A number of strategies have been proposed to quantify this distribution, However, in this technical note we present a relatively simple MR imaging procedure which can be used to visualise RF inhomogeneities directly either by means of the magnitude or the phase of an image. To visualise the RF field distribution in both the inner and outer volumes of the coil, we have performed experiments in which the entire coil is submerged in a non-conducting fluid, To the best of our knowledge this strategy has not been used previously in order to evaluate coil performance, Finally, we demonstrate that the method is sensitive enough to reveal the effects of the sample properties on the effective RF wavelength of the transmitted field. (C) 1997 Elsevier Science Inc.

Correcting the effects of spontaneous emission on cold-trapped ions

We propose two quantum error-correction schemes which increase the maximum storage time for qubits in a system of cold-trapped ions, using a minimal number of ancillary qubits. Both schemes consider only the errors introduced by the decoherence due to spontaneous emission from the upper levels of the ions. Continuous monitoring of the ion fluorescence is used in conjunction with selective coherent feedback to eliminate these errors immediately following spontaneous emission events.

Acute intermittent porphyria: the in vitro expression of mutant hydroxymethylbilane synthase

Acute intermittent porphyria (AIP) is an inborn error of haem biosynthesis caused by a variety of mutations in the gene coding for hydroxymethylbilane synthase (HMB-S). The entire coding sequence of this gene, from each of three South African AIP patients, was therefore screened for mutations using chemical cleavage mismatch (CCM) analysis and any changes detected characterized by DNA sequencing. Three single base changes were identified; a G(77) to A in exon 3, a C-346 to T in exon 8 and a G(518) to A in exon 10. These missense mutations, previously reported to be present in other populations, are known to be responsible for the structurally deleterious amino acid replacements R26H, R116W and R173Q, respectively. The in vitro expression of the enzymes containing these mutations and the subsequent measurement of their specific activities revealed a reduction to approximately 4% of normal activity. (C) 1997 Academic Press Limited.

A stochastic frontier production function with flexible risk properties

This paper considers a stochastic frontier production function which has additive, heteroscedastic error structure. The model allows for negative or positive marginal production risks of inputs, as originally proposed by Just and Pope (1978). The technical efficiencies of individual firms in the sample are a function of the levels of the input variables in the stochastic frontier, in addition to the technical inefficiency effects. These are two features of the model which are not exhibited by the commonly used stochastic frontiers with multiplicative error structures, An empirical application is presented using cross-sectional data on Ethiopian peasant farmers. The null hypothesis of no technical inefficiencies of production among these farmers is accepted. Further, the flexible risk models do not fit the data on peasant farmers as well as the traditional stochastic frontier model with multiplicative error structure.