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PubMedDate not supplied

The two trace transfer problem re-examined.

The classical two trace transfer problem initially discussed by Evett is reconsidered [Evett IW. On Meaningful Questions: A Two-Trace Transfer Problem. Journal of the Forensic Science Society 1987; 27: 375-381]. In this problem we consider the situation where there are two stains of differing types at a crime scene. Evett considered the situation where both are known to be relevant to the offence. It was further assumed that there were exactly two offenders. Reanalysis of this problem suggests that the key consideration is the conditioning on there being exactly two offenders, not that there were two stains. The treatment here leads easily to a generalisation in which stains have differing relevance and there are k offenders.

Crime↗
PubMed2001

Cortical activation in reading assessed by region of interest-based analysis and statistical parametric mapping.

Reanalysis of our positron emission tomography study on the reading of Japanese Kanji (morphograms) and Kana (phonograms) with Statistical Parametric Mapping (SPM) Version 96 (Cogn. Brain Res. 9 (2000) 111) were described in comparison with our previous region of interest (ROI)-based analysis. Some areas were activated in one analysis but not in the other, which was due to the methodological differences. Furthermore, we conducted cognitive subtraction analysis between Kanji and Kana and between Kana words and nonwords and confirmed that Kana words activated the lateral occipital gyri more extensively than Kanji words.

Adolescent↗
PubMedDate not supplied

Impact of parental gonosomal mosaicism detected in peripheral blood on preimplantation embryos.

This study evaluated the chromosomal condition of embryos generated by patients with an altered karyotype due to gonosomal mosaicism and the clinical outcome after preimplantation genetic diagnosis (PGD) for aneuploidy. Thirty-six patients aged 34.6 +/- 3.6 years performed 54 treatment cycles and had 295 embryos diagnosed by fluorescence in-situ hybridization (FISH). Thirty-seven per cent of the embryos were chromosomally normal and generated 19 clinical pregnancies after replacement in 39 cycles. Only one pregnancy miscarried, yielding a take-home baby rate of 33.3%. Autosomal monosomy and trisomy contributed 36.1% of total abnormalities and gonosomal aneuploidy 5.9%, similar to the results detected in patients who undergo PGD for increased maternal age. Reanalysis was performed on 114 non-transferrable embryos: 41 were found to be mosaics, which were grouped in three different types, chaotic mosaics (56%), aneuploid mosaics (29%) and diploid/haploid/polyploid mosaics (15%). The incidence of aneuploid mosaics was higher than expected compared with PGD patients of the same age and resembled the condition observed in patients of advanced maternal age. These findings suggest that constitutional carriers of sex chromosome mosaicism are predisposed to autosomal mosaicism of embryos, possibly due to errors of cell division. There is an indication that this tendency is higher in female than male carriers.

Adult↗
PubMed2004

An overview of oocyte cryopreservation.

The ability to cryopreserve human oocytes and store them indefinitely would be beneficial for cancer patients at risk of becoming sterile after therapy, allow women to delay reproduction, and alleviate religious concerns associated with embryo storage. In 1986, Chen was the first to report a pregnancy originating from a frozen-thawed human oocyte. Although over 100 babies have been born from oocyte storage since then, pregnancy rates remain unacceptably low. Adapting embryo cryopreservation techniques to oocyte storage has had limited success and new reproducible methods are needed. Problem areas other than intracellular ice formation and osmotic effects need to be identified. A broad approach of critical analysis should be conducted regarding the entire cryopreservation process from pre-equilibration and cooling, to thawing and stepout. All established facets deserve reanalysis in order to assess which aspects can be optimized or changed so that cellular demise can be avoided and cellular viability enhanced. New methods, including the use of choline-based media and vitrification have proven useful in increasing survival and pregnancy rates in some clinics. Other methods yet untested, such as injection of complex carbohydrates into the oocyte, deserve further studies. Vitrification research has led to the formulation of new ideas and has demonstrated the flexibility of cells to survive cryopreservation. Although successful, vitrification protocols are potentially harmful and technically challenging, due to elevated cryoprotectant concentrations and rapid cooling rates. Bovine embryo vitrification methods have been used to store human oocytes and embryos, particularly blastocysts with some success. Vitrification solutions containing high molecular weight polymers have also proved beneficial by reducing solution toxicity. In general, further advances are needed to improve human oocyte storage before widespread routine clinical use.

Animals↗
PubMedDate not supplied

Paraspinal denervation and the spinal degenerative cascade.

BACKGROUND CONTEXT: The aging of the spine has been reported to follow a degenerative cascade described by Kirkaldy-Willis. This cascade does not take into account the paraspinal muscles. Substantial recent knowledge of the anatomy, physiology and pathophysiology of the paraspinal muscles suggests that they should play a role in the degenerative cascade. Pain relates to paraspinal denervation in a number of disorders. Using new needle electromyographic technique, MiniPM, we may be able to quantify the extent of paraspinal muscle denervation. PURPOSE: To explore the potential interactions between paraspinal muscle denervation and the degenerative cascade. STUDY DESIGN: Literature review, reanalysis of a blinded electromyographic study and case reports. PATIENT SAMPLE: A previously reported group of 35 asymptomatic paid volunteers, ages 18 to 58 years. Two elderly volunteers with moderate to severe spinal stenosis on magnetic resonance imaging (MRI), one significantly disabled, one asymptomatic. OUTCOME MEASURES: Blinded electromyographic testing, including MiniPM, a codified, quantified needle electromyography technique for the paraspinal muscles. In the two case reports, magnetic resonance imaging and 15-minute timed ambulation. METHODS: The 35 volunteers were tested by a blinded electromyographer using the MiniPM technique. The two older subjects underwent MRI, MiniPM and extensive electrodiagnostic evaluations, functional testing, complete history and physical examination. RESULTS: The patient with symptomatic stenosis had a MiniPM score of 6 on each side, and the asymptomatic volunteer had a score of 0. In the asymptomatic subject group, reproducible evidence for denervation was found in 20 subjects (57%), sparsely distributed, but more caudal than cranial (p<.0001). Based on conservative estimates of nerve regeneration rates, the population averaged a detected axonotemesis denervating event approximately once every 120 days. CONCLUSIONS: Paraspinal denervation may be proven to be a better marker than MRI findings for symptomatic spinal stenosis. Subtle paraspinal muscle denervation occurs frequently in asymptomatic persons. Whether a cause or an effect, paraspinal denervation might lead to hypermobility and thus progression along the degenerative cascade.

Adolescent↗
PubMed1992

The current status of Weinberg's differential rule.

A reanalysis of the data presented in a recent large twin study suggests that opposite-sexed (OS) pairs may be not as exhaustively tested as same-sexed (SS) pairs on genetic markers. This is contrary to an assumption I made in estimating that there are about 8 SS dizygotic pairs to every 7 OS pairs (thus impugning Weinberg's differential rule). If this assumption is false also in regard to the samples I discussed, then that estimate is unsound and Weinberg's rule is unscathed by empirical data. However, regardless of such considerations, there are strong theoretical reasons for questioning the status of Weinberg's rule. It is based on two assumptions, namely that p (the probability that a dizygotic twin zygote is male) is equal and independent for all dizygotic twin zygotes. Data are adduced here to suggest that both assumptions are false. The upshot is that, at present, without testing, we cannot know, of any given population, whether the rule holds or not. Otherwise, though Weinberg's rule may be useful (like Hellin's law) as a rule-of-thumb, it cannot be assumed as a basis for serious scientific argument.

Animals↗
PubMed1990

Persist or quit? Testing for a genetic contribution to smoking persistence.

We consider three alternative parametric models to describe genetic and environmental influences on smoking initiation and smoking persistence. Under the single liability dimension model, the same genetic and environmental influences which determine smoking initiation also influence smoking persistence. Under the independent liability dimensions model, independent initiation and persistence dimensions determine onset of smoking, and persistence in those who become smokers. The combined model also postulates separate initiation and persistence dimensions, but allows for the possibility that some smokers are so low on liability to smoke on the initiation dimension that they become ex-smokers for this reason. Reanalysis of London twin data published by Eaves and Eysenck support the single liability dimension model. We discuss the difficulty of reconciling this finding with the hypothesis that nicotine dependence is a major determinant of smoking persistence, but caution that sample sizes in the London twin study were small.

Diseases in Twins↗
PubMed2004

The effect of an imprecise map on interval mapping QTLs.

The statistical analysis of quantitative trait locus (QTL) experiments relies on the use of a linkage map of the markers genotyped. Such a map is, at best, a good estimate of the true map. Resources might be diverted into developing better marker maps or improved maps become available after the analysis, raising concerns over the original analysis. It is therefore important to understand the sensitivity of QTL analysis to map inaccuracy. We have used simulation methods to investigate the consequences of an incorrect map on the results of a QTL analysis using interval mapping. Backcross data sets were generated with a particular map and then analysed with both the correct map and incorrect maps. If the incorrect maps maintained the true linkage groups (i.e. no markers were incorrectly assigned to another linkage group), the accuracy of the map had little or no impact on the ability to detect QTLs, the true significance levels of the tests or the relative placement of QTLs. When a marker was incorrectly placed on another linkage group, there was a small increase in the level of the test. After adjusting for this increase, there was a decrease in power to detect a QTL near the misplaced marker. This decrease was of a similar magnitude to that found when using a single-marker analysis compared with interval mapping. These results mean that QTL analyses can proceed without the need for very accurate marker maps, and that estimated QTL positions can be translated onto updated maps without the need for reanalysis.

Chromosome Mapping↗
PubMed1990

The relationship between social vulnerability and the occurrence of severely threatening life events.

Research on the role of life events in the onset of depression has suggested that certain vulnerability factors can increase the risk of disorder in the face of a threatening event. The role of vulnerability factors to increase the likelihood of severe events occurring in the first place has remained largely unexplored. The vulnerability factor which has received the most attention is a lack of social support, particularly lack of a confiding relationship with a husband for women. A reanalysis of a number of published studies is undertaken; this shows that there is a positive relationship between lack of intimacy and the occurrence of adversity. The implications of this finding are briefly discussed, with emphasis on the need for a life-span developmental perspective in future life events research.

Humans↗
PubMed1983

Public opinion and the privatization of welfare: some theoretical implications.

The social policy of the Thatcher government is characterized by an abrupt shift in the direction of the private sector. To what extent does this reflect what people want? The Institute of Economic Affairs conclude from the only suitable national opinion survey that such a move is strongly supported. Our reanalysis of their data shows that this strand in public opinion can coexist with, and need not contradict, an equal public enthusiasm for state welfare. Such results have important implications for our understanding of social policy. We conclude, therefore, with a discussion of contrasting marxist and liberal accounts which seeks to show that the evidence of ambivalence in popular attitudes about the welfare state supports particular developments in theory.

Analysis of Variance↗
PubMed1989

Theoretical implications of complement structure acquisition in Korean.

The acquisition of complement phrasal constructions in Korean is examined in spontaneous speech data from two children, who were observed from one and a half to three years of age. In spite of typological differences between English and Korean, both syntactic and semantic characteristics are found to be shared by children acquiring complement constructions in the two languages. However, certain language-specific features of Korean complement structures make it possible to address theoretical points concerning the structure of infinitival complements which cannot be resolved with the acquisition data on English. The error pattern in the acquisition of certain 'subject-equi' verbs in Korean poses problems both for LFG and GB accounts of the constituent structure of infinitival complements and the acquisition of those constructions. On the basis of the Korean data, I propose that base-generated VP complements are acquired first, with semantically motivated reanalysis of previously acquired infinitival complement structures occurring at a later stage.

Child, Preschool↗
PubMed1991

On the acquisition of syntax in Tamil: a comment on Garman (1974).

Garman (1974), reporting on twenty Tamil children aged three to five, postulated a linguistic strategy and two prelinguistic strategies to explain the results of a question-picture choice task involving sentences with embedded and subordinate clauses. In a reanalysis of his data, we identify four processing strategies and show that some of Garman's findings are better explained not as the outcome of prelinguistic strategies but as an artefact of the experimental design. In fact the data provide evidence of a grammatical sensitivity which is consonant with a sensitivity--demonstrated in recent language--acquisition studies-to the branching direction of the language being acquired.

Child Language↗
PubMed1992

The relationship between infecting dose and severity of disease in reported outbreaks of Salmonella infections.

The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used. There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed.

Disease Outbreaks↗
PubMed2002

Collection, storage, and filtration of in vivo study samples using 96-well filter plates to facilitate automated sample preparation and LC/MS/MS analysis.

The benefits of high-throughput bioanalysis within the pharmaceutical industry are well established. One of the most significant bottlenecks in bioanalysis is transferring in vivo-generated study samples from their collection tubes during sample preparation and extraction. In most cases, the plasma samples must be stored frozen prior to analysis, and the freeze/thaw (F/T) process introduces thrombin clots that are capable of plugging pipets and automated liquid-transfer systems. A new approach to dealing with this problem involves the use of Ansys Captiva 96-well 20-microm polypropylene filter plates to collect, store frozen, and filter plasma samples prior to bioanalysis. The samples are collected from the test subjects, and the corresponding plasma samples are placed directly into the wells of the filter plate. Two Duoseal (patent pending) covers are used to seal the top and bottom of the plate, and the plate is stored at down to -70 degrees C. Prior to sample analysis, the seals are removed and the plate is placed in a 96-well SPE manifold. As the plasma thaws, it passes (by gravity or mild vacuum) through the polypropylene filter into a 96-well collection plate. A multichannel pipet or automated liquid-transfer system is used to transfer sample aliquots without fear of plugging. A significant advantage of this approach is that, unlike other methods, issues related to incomplete pipetting are virtually eliminated. The entire process is rapid since thawing and filtering take place simultaneously, and if a second F/T cycle is required for reanalysis, it is not necessary to refilter the samples (additional clotting was not observed after three F/T cycles). This technique was tested using monkey, rat, and dog plasma and sodium heparin and EDTA anticoagulants. To assess the possibility of nonspecific binding to the polypropylene filter, a variety of drug candidates from diverse drug classes were studied. Validation data generated for two Lilly compounds from distinct classes, before and after filtering, are presented in this paper as practical examples of this technique. While LC/MS/MS is the primary method of bioanalysis in our laboratory, the technique presented in this paper is applicable to other forms of detection as well.

Autoanalysis↗
PubMed2005

Combined top-down and bottom-up mass spectrometric approach to characterization of biomarkers for renal disease.

Here we describe a mass spectrometry (MS) approach for biomarker discovery and structural characterization, based on both top-down and bottom-up analyses. Capillary electrophoresis (CE) coupled to electrospray ionization (ESI) time-of-flight (TOF) MS serves to separate and mass-measure the thousands of polypeptides contained in human urine. Statistical analysis of the differences between healthy control samples and patients with focal-segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, IgA nephropathy, and diabetic nephropathy validates multiple biomarkers for the control and each of the diseases. To identify those biomarkers, we employ preparative CE, enabling direct infusion ESI MS analysis, followed by sample manipulation and reanalysis where necessary. We show how tandem Fourier transform ion cyclotron resonance (FT-ICR) MS identifies these sometimes large (>8 kDa) biomarkers. Critically, we maintain connectivity between the CE TOF MS data and the ICR data used for biomarker identification.

Amino Acid Sequence↗
PubMed1997

NIST/NCI Micronutrients Measurement Quality Assurance Program: measurement repeatabilities and reproducibilities for fat-soluble vitamin-related compounds in human sera.

The NIST/NCI Micronutrient Measurement Quality Assurance Program has conducted 33 interlaboratory comparison exercises for fat-soluble vitamin-related compounds in human sera over the past 12 years. Periodic reanalysis of lyophilized serum samples prepared from more than 70 different sera has enabled estimation of the short- and long-term measurement characteristics. Median- and interquartile-range-based statistics adequately estimate the distribution of results from laboratories that are in analytical control from total distributions that include a significant minority of outlier data. Short-term interlaboratory reproducibility standard deviations (SDs) are predictable functions of analyte concentration, with an asymptotic limit at low analyte concentration and a linear relationship at high concentrations. Long-term trends in the interlaboratory reproducibility can be estimated by standardizing the short-term SD at the observed analyte concentration to an expected SD at a given physiologically significant analyte concentration. The "average" laboratory's same-day analytical repeatability SD is about one-third of the estimated interlaboratory reproducibility; repeatability for longer periods between analyses is, on average, on better than the reproducibility. While a few exceptional laboratories have maintained excellent repeatability over the entire decade, long-term study measurements generated within a single laboratory are not generally more internally consistent than results from multiple laboratories. Enhanced and more consistently implemented intralaboratory quality control and quality assurance methods are required to further improve and maintain interlaboratory measurement comparability.

Humans↗
PubMed1998

Characterization of heparin oligosaccharide mixtures as ammonium salts using electrospray mass spectrometry.

Among glycosaminoglycans, polysulfated heparin chains provide the greatest challenge to characterization due to high polarity, structural diversity, and sulfate lability. The present report demonstrates how electrospray mass spectrometry (ESMS) can be used to derive compositional information from pure and mixed fractions of heparin tetra- to decasaccharide fragments prepared by controlled digestion of heparin with heparinase I. It also describes an improved procedure for fractionation of heparin oligosaccharides up to octadecasaccharides. Ammonium salts prove to be superior to sodium salts, particularly for analysis of mixed components. In the mass spectrum of a hexasaccharide fraction, the identification of six major mass peaks that represent the known hexasaccharide structures confirms that ESMS analysis of heparin oligosaccharide fragments gives a close representation of their constituent composition. In addition to the previously identified components, several unreported oligosaccharides were detected in the spectra of octa- and decasaccharide fractions. The ESMS identification of the three major species in a decasaccharide fraction was confirmed after HPLC subfractionation and reanalysis. ESMS detection sensitivity of low picomole amounts of oligosaccharides can be readily achieved.

Chemical Fractionation↗
PubMed1983

Water catalysis of peptide hydrogen isotope exchange.

The temperature dependence of the hydrogen-tritium and deuterium-hydrogen exchange reactions in poly(DL-alanine) has been reexamined. The results indicate a significant contribution to the observed exchange rates from the water-catalyzed reaction at pD values near pDmin. The activation enthalpy for water-catalyzed deuterium-hydrogen exchange in poly(DL-alanine) is found to be 21 kcal mol-1. As a result, the contribution to the observed exchange rate from the water-catalyzed reaction increases with increasing temperature which in turn leads to broad, shallow pD minima and the appearance of apparent reaction orders with respect to [D+] and [OD-] that are substantially less than first order over an extended range of pD values. The importance of water catalysis in protein hydrogen exchange is demonstrated by a reanalysis of data for the exchange of single protons in bovine pancreatic trypsin inhibitor [Hilton, B.D., & Woodward, C. K. (1979) Biochemistry 18, 5834; Richarz, R., Sehr, P., Wagner, G., & Wüthrich, K. (1979) J. Mol. Biol. 130, 19]. The pD dependence of these protons can be explained in terms of an increased contribution from water catalysis.

Calorimetry↗