bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumulative risk assessment for quantitative response data
Authors: Chen James J. , Chen Yi‐Ju , Teuschler Linda K. , Rice Glenn , Hamernik Karen , Protzel Alberto , Kodell Ralph L.
Published: May 2003

The Relative Potency Factor approach (RPF) is used to normalize and combine different toxic potencies among a group of chemicals selected for cumulative risk assessment. The RPF method assumes that the slopes of the dose–response functions are all equal; but this method depends on the choice of the index chemical, i.e. different index chemicals will give different predicted mean estimates. This article is part of an approach to explore and develop cumulative risk assessment strategies. As part of this approach this article proposes a procedure for cumulative risk assessment from exposure to multiple chemicals that have a common mechanism of toxicity. We propose two classification algorithms to cluster the chemicals into subclasses such that the chemicals in the same subclass have a common slope. The joint response is estimated by fitting the dose–response model of the mixture under dose addition. The proposed method will give the same predicted mean response regardless of the selection of the index chemical for the chemicals in the same subclass. The proposed method also allows one to estimate the joint response for chemicals having different slopes. An example data set of six hypothetical pesticide chemicals is used to illustrate the proposed procedure. Copyright © 2003 John Wiley & Sons, Ltd.
Bayesian uncertainty assessment in multicompartment deterministic simulation models for environmental risk assessment
Authors: Bates Samantha C. , Cullen Alison , Raftery Adrian E.
Published: May 2003

We use a special case of Bayesian melding to make inference from deterministic models while accounting for uncertainty in the inputs to the model. The method uses all available information, based on both data and expert knowledge, and extends current methods of ‘uncertainty analysis’ by updating models using available data. We extend the methodology for use with sequential multicompartment models. We present an application of these methods to deterministic models for concentration of polychlorinated biphenyl (PCB) in soil and vegetables. The results are posterior distributions of concentration in soil and vegetables which account for all available evidence and uncertainty. Model uncertainty is not considered. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of water quality using acceptance sampling by variables
Authors: Smith Eric P. , Zahran Alyaa , Mahmoud Mahmoud , Ye Keying
Published: May 2003

Under section 303(d) of the Clean Water Act, states must identify water segments where loads of pollutants are violating numeric water quality standards. Consequences of misidentification are quite important. A decision that water quality is impaired initiates the total maximum daily load or TMDL planning requirement. Falsely concluding that a water segment is impaired results in unnecessary TMDL planning and pollution control implementation costs. On the other hand, falsely concluding that a segment is not impaired may pose a risk to human health or to the services of the aquatic environment. Because of the consequences, a method is desired that minimizes or controls the error rates. The most commonly applied approach is to use the Environmental Protection Agency (EPA)'s raw score approach in which a stream segment is listed as impaired when greater than 10 per cent of the measurements of water quality conditions exceed a numeric criteria. An alternative to the EPA approach is the binomial test that the proportion exceeding the standard is 0.10 or less. This approach uses the number of samples exceeding the criteria as a test statistic along with the binomial distribution for evaluation and estimation of error rates. Both approaches treat measurements as binary; the values either exceed or do not exceed the standard. An alternative approach is to use the actual numerical values to evaluate standard. This method is referred to as variables acceptance sampling in quality control literature. The methods are compared on the basis of error rates.

If certain assumptions are met then the variables acceptance method is superior in the sense that the variables acceptance method requires smaller sample sizes to achieve the same error rates as the raw score method or the binomial method. Issues associated with potential problems with environmental measurements and adjustments for their effects are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Study of the space–time effects in the concentration of airborne pollutants in the Metropolitan Region of Rio de Janeiro
Authors: Paez Marina Silva , Gamerman Dani
Published: May 2003

In this article, we present an application of models with temporal and spatial components, from the Bayesian point of view, on data pollutants collected in 16 different monitoring sites located in the Metropolitan Area of Rio de Janeiro during 1999. All the models considered here assume conditionally independent observations, with a mean specified by the sum of random temporal and spatial components and a linear function of the maximum daily temperature and indicators of the day of the week. Our aim here is to analyze distinct specifications for the components, assuming different kinds of modeling that are not usually compared. The comparison is based on the posterior predictive loss function proposed by Gelfand and Ghosh (1998). The best specifications for the spatial component were the ones which considered a geostatistical approach to its correlation function. The best specification for the temporal component was the stationary autoregressive form. The pollutant concentrations were interpolated in a grid of points in the area of higher population density at a fixed period of time for the selected model. Copyright © 2003 John Wiley & Sons, Ltd.
On some aspects of data integration techniques with environmental applications
Authors: Sinha Bikas K. , Shah Kirti R.
Published: May 2003

Multiple Criteria Decision Making (MCDM) is a popular phrase used to describe situations where there is a need for integration of the results of different studies to make an overall judgement. Among the highest priorities towards socioeconiomic development around the world is the Environmental Protection Policy (EPP), and environmental assessment is a key to EPP. In the context of environmental studies, data integration techniques are very appealing and have wider applicability. It is well known that land, air and water are the three sources for determination of the extent of pollution of different regions. The purpose of MCDM is to rank the regions wrt all the sources taken together. For any individual source of pollution, it is trivial to rank the regions from best to worst. However, the problem of integration becomes non‐trivial in most cases since the regions do not lend themselves to the same pattern of ranking wrt different sources. In this article we examine critically the performance of two popular composite indices (CI) and suggest some alternatives. Copyright © 2003 John Wiley & Sons, Ltd.
Incorporation of ARMA models into flow forecasting by artificial neural networks
Authors: Cigizoglu H. K.
Published: May 2003

A frequently encountered problem during the application of artificial neural networks (ANNs) to various water resource problems is the limitation of the data sets required for the training stage of ANNs. This prevents ANNs from learning input and output data sets within different ranges, thus decreasing the prediction capability during the testing stage. In this article the well known ARMA models are used to generate synthetic series, and these series are incorporated into the training data sets of ANNs. The method is applied to the monthly mean river flow data of a station in the East Mediterranean region of Turkey. The forecasting accuracy of the future monthly flows carries significance because a water reservoir is planned for the downstream of this station. Because the available data record length is limited studies should be carried out to extend the training data set of ANNs. It is seen that the extension of input and output data sets in the training stage improves the accuracy of forecasting using ANNs. The introduction of periodicity components in the input layer also increases the forecasting accuracy of ANNs. Copyright © 2003 John Wiley & Sons, Ltd.
A study on the incidence of ABL gene deletion on derivative chromosome 9 in chronic myelogenous leukemia by interphase fluorescence in situ hybridization and its association with disease progression
Authors: Lee Dong Soon , Lee Yun‐Song , Yun Yeon‐sook , Kim Young‐Ree , Jeong Seok San , Lee Young Kyung , She Cha Ja , Yoon Sung Soo , Shin Hae Rim , Kim Yongsoo , Cho Han Ik
Published: May 2003

Fluorescence in situ hybridization for the BCR/ABL rearrangement in 138 bone marrow specimens from 59 Philadelphia+ (Ph+) chronic myelogenous leukemia (CML) patients, 35 Ph+ acute lymphoblastic leukemia (ALL) patients, and 57 Ph− ALL patients was used. Sixteen (27.1%) of the 59 CML patients had deletions of the residual ABL gene on the derivative chromosome 9. During the study period, 32 of the 59 CML patients progressed to blast crisis or accelerated phase. Of these, nine patients had residual ABL gene deletions on the derivative chromosomes 9 and 23 patients had no deletions. The mean duration from first diagnosis to blast crisis or accelerated phase for the nine patients with ABL deletions was 32.8 months, and for the 23 patients without ABL deletions, it was 62.4 months (P = 0.017). The overall survival time for the 16 patients with deletions was 32.8 months, and for the 43 patients without deletions, it was 60.1 months (P = 0.164). ABL deletions were not detected among the 35 ALL patients (17 with major BCR/ABL, 18 with minor BCR/ABL), and it appears that this deletion occurs rarely or not at all in Ph+ ALL patients, which is in contrast to the CML patients (27.1%). However, we detected two ALL cases with ABL deletion but without BCR/ABL rearrangement among 49 Ph− ALL and 66 Ph− AML patients. In conclusion, patients with ABL deletions progress to blast crisis or accelerated phase in a significantly shorter time than do those without such deletions. It is therefore suggested that the ABL deletion is an indicator of a poor prognosis in CML. © 2003 Wiley‐Liss, Inc.
Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification
Authors: Knutsen Turid , Pack Svetlana , Petropavlovskaja Maria , Padilla‐Nash Hesed , Knight Clement , Mickley Lyn A. , Ried Thomas , Elwood Patrick C. , Roberts Susan J.
Published: May 2003

Cytogenetic studies of patients with therapy‐induced acute myeloid leukemia (t‐AML) have demonstrated whole chromosome loss or q‐arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML‐1 and SAML‐2, from two patients who developed t‐AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML‐1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter→1p22::5q31→5qter), der(5)(5pter→5q22::1p22→1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML‐2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G‐banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t‐AML. © 2003 Wiley‐Liss, Inc.
Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping
Authors: Pavlovich Christian P. , Padilla‐Nash Hesed , Wangsa Danny , Nickerson Michael L. , Matrosova Vera , Linehan W. Marston , Ried Thomas , Phillips John L.
Published: May 2003

We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (±2.7) in the primary tumors and 19.3 (±4.6) in the cell lines. Both whole‐chromosome and chromosome‐segment imbalances were noted by CGH: consistent losses or gains included +5q23→ter (100%), −3p14→ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole‐chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations. © 2003 Wiley‐Liss, Inc.
Heterogeneous pattern of chromosomal breakpoints involving the MYC locus in multiple myeloma
Authors: Fabris Sonia , Storlazzi Clelia Tiziana , Baldini Luca , Nobili Lucia , Lombardi Luigia , Maiolo Anna Teresa , Rocchi Mariano , Neri Antonino
Published: May 2003

Chromosomal rearrangements of the MYC locus, which often involve the IG loci, are recurrent events in multiple myeloma (MM) and plasma cell leukemia (PCL). We used dual‐color fluorescence in situ hybridization (FISH) to characterize the breakpoint locations of chromosomal translocations/rearrangements involving the MYC locus at 8q24 found in a panel of 14 MM cell lines and 70 primary tumors (66 MM and 4 PCL). MYC locus alterations were observed in 21 cases: MYC/IG (mainly IGH@) fusions in 11 cell lines and three patients (2 MM and 1 PCL), and extra signals and/or abnormal MYC localizations in seven patients (5 MM and 2 PCL). Fourteen of these cases were investigated by FISH analyses by use of a panel of BAC clones covering about 6 Mb encompassing the MYC locus. The breakpoints were localized in a region 100–250 kb centromeric to MYC in four cases, a region 500–800 kb telomeric to the gene in four cases, and regions ≥ 2 Mb centromeric or telomeric to MYC in five cases. Two different breakpoints were detected in the KMS‐18 cell line, whereas the insertion of a MYC allele was found in a complex t(16;22) chromosomal translocation in the RPMI8226 cell line. Our data document a relatively high dispersion of 8q24 breakpoints in MM. © 2003 Wiley‐Liss, Inc.
Evidence for whole chromosome 6 loss and duplication of the remaining chromosome in acute lymphoblastic leukemia
Authors: McEvoy Christopher R.E. , Morley Alexander A. , Firgaira Frank A.
Published: May 2003

HLA class I molecules serve the essential immunological function of presenting antigen to CD8+ T lymphocytes. Tumor cells may present tumor‐specific antigen to T cells via these molecules, but many tumors show a loss or down‐regulation of HLA class I expression and this may serve as an immune escape mechanism. Using a microsatellite marker‐based method, we have searched for loss of heterozygosity (LOH) mutations at 3 genomic regions implicated in HLA class I expression in a cohort of 56 acute lymphoblastic leukemia (ALL) samples. The regions analyzed consisted of the HLA class I heavy chain genes located within the MHC genomic region on chromosome arm 6p, the HLA class I light chain (beta‐2‐microglobulin, B2M) gene on chromosome arm 15q, and the putative HLA modifier of methylation gene (MEMO1) located on chromosome arm 1q. Results revealed low frequencies of B2M (2/55) and MEMO1 (5/42) LOH but a high frequency of MHC LOH (19/56) that was usually associated with whole chromosome 6 loss (13/19). Cytogenetic data were available for 30 samples, including nine of those that exhibited apparent whole chromosome 6 loss. No cases of chromosome 6 monosomy were observed. We propose that whole chromosome 6 loss with reduplication of the remaining chromosome is common in ALL and that it is driven by the presence of tumor‐inhibiting factors on chromosome arm 6p (the HLA loci) along with previously localized tumor‐suppressor genes on chromosome arm 6q. © 2003 Wiley‐Liss, Inc.
High‐resolution analysis of acquired genomic imbalances in bone marrow samples from chronic myeloid leukemia patients by use of multiple short DNA probes
Authors: Reid Alistair G. , Tarpey Patrick S. , Nacheva Ellie P.
Published: May 2003

Chronic myeloid leukemia (CML) is a biphasic hematopoietic malignancy associated with a single cytogenetic aberration, the Philadelphia translocation t(9;22)(q34;q11), resulting in the BCR‐ABL1 fusion oncogene. Molecular heterogeneity was recently demonstrated in the form of extensive deletion of chromosomes 9 and 22 material from the der(9)t(9;22) in 15% of CML patients. The deletions were associated with a worse disease prognosis. Further genetic heterogeneity is seen during the terminal blast crisis stage of CML, in the form of additional non‐random chromosome abnormalities. These include most frequently an extra copy of the Ph chromosome, trisomy 8, and isochromosome 17q. We used the genetic heterogeneity of CML as a framework to explore a new technique for high‐throughput assessment of locus copy number in malignancy. Multiplex amplifiable probe hybridization (MAPH) relies on the ability of numerous short (100–300 bp) DNA probes to be recovered quantitatively by use of a common primer pair after hybridization to genomic DNA. Derivative chromosome 9 deletions were successfully mapped in a CML cell line (MC3) and nine patient bone marrow samples by simultaneous hybridization of 10 MAPH probes. All results were confirmed by fluorescence in situ hybridization. MAPH was found to be informative in the presence of up to 50% of normal cells, thus establishing the sensitivity of the technique in clonal tumor cell populations. MAPH was performed effectively on DNA samples extracted from fresh or methanol/acetic acid–fixed clonal cell populations. Amplifications of BCR‐ABL1 were also detected and quantified in four CML cell lines by use of MAPH probes specific for ABL1 exon 11 and BCR exon 1. Our results demonstrate that MAPH is a reproducible high‐throughput method suitable for the assessment of genomic imbalances of multiple loci in tumor DNA samples with heterogeneous cell populations at a resolution of 100–300 bp. © 2003 Wiley‐Liss, Inc.
Genome‐wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss
Authors: Simpson D. J. , Bicknell E. J. , Buch H. N. , Cutty S. J. , Clayton R. N. , Farrell W. E.
Published: May 2003

Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor‐suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome‐wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non‐functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre‐amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole‐genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non‐invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non‐functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non‐functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non‐invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non‐invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome‐wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype‐specific and were found at a higher frequency in invasive tumors than in their non‐invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype‐specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple “hotspots” throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic‐mediated gene‐silencing events. © 2003 Wiley‐Liss, Inc.
Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia
Authors: Steudel Christine , Wermke Martin , Schaich Markus , Schäkel Ulrike , Illmer Thomas , Ehninger Gerhard , Thiede Christian
Published: May 2003

Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well‐defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT‐PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease‐free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease‐free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor. © 2003 Wiley‐Liss, Inc.
Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2
Authors: Claes Kathleen , Poppe Bruce , Machackova Eva , Coene Ilse , Foretova Lenka , De Paepe Anne , Messiaen Ludwine
Published: May 2003

About 4% of all BRCA1 and BRCA2 alterations reported to the Breast Information Core database are splice site variants. Only a limited number of them have been studied at the RNA level. By BRCA1 and BRCA2 mutation analysis of breast/ovarian cancer families, we identified two novel and eight previously reported potential splice site mutations, never characterized at the cDNA level before. RT‐PCR was performed to determine whether these variants disrupted correct splicing. To ensure efficient detection of transcripts containing premature termination codons, a nonsense‐mediated mRNA decay inhibitor was added to the lymphoblastoid cell lines of the patients before RNA extraction. We found that BRCA1 IVS3+3A>C, 4304G>A (in the last codon of exon 12), and IVS19+2delT and BRCA2 IVS6+1G>A, IVS23−2A>G, and IVS24+1G>A lead to aberrant transcripts in lymphocytes. Therefore, they were considered to be true pathogenic mutations, predisposing carriers to cancers of the hereditary breast/ovarian cancer syndrome. BRCA2 IVS24−16T>C is a frequent polymorphism in linkage disequilibrium, with a polymorphic stop codon in exon 27, K3326X. BRCA1 IVS2−14C>T and BRCA2 IVS9−5insT and IVS25+9A>C represent rare variants, not disrupting normal splicing in blood lymphocytes. However, some of the alterations may act differently, qualitatively and/or quantitatively, in breast or ovarian tissues. The data provided in this paper allowed more accurate risk estimation of patients and relatives carrying the mutations described herein and have facilitated genetic counseling. Furthermore, our study is important for a better understanding of splicing mechanisms and revealed new patterns of alternative splicing in BRCA1 and BRCA2. © 2003 Wiley‐Liss, Inc.
SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia
Authors: Chen Chien‐Yuan , Tsay Woei , Tang Jih‐Luh , Shen Hwei‐Ling , Lin Shu‐Wha , Huang Sheng‐Yi , Yao Ming , Chen Yao‐Chang , Shen Ming‐Ching , Wang Chiu‐Hwa , Tien Hwei‐Fang
Published: May 2003

The proliferation and differentiation of hematopoietic precursor cells depend on various cytokines. The suppressor of cytokine signaling‐1 (SOCS1) down‐regulates Janus kinases/signal transducers and activators of transcription (JAK/STAT) pathway activity and inhibits the biological effects of cytokines. SOCS1 has been shown to have tumor‐suppressor activity, and methylation of this gene, resulting in transcriptional silencing, has been found in 65% of hepatocellular carcinoma and has been suggested to play an important role in the development of the cancer. The methylation status of the SOCS1 gene in acute myeloid leukemia (AML) has not been reported before. In this study, we analyzed SOCS1 methylation in 89 patients with newly diagnosed AML and correlated the result with immunophenotypes, cytogenetics, clinical features, and treatment outcome. SOCS1 methylation was found in the leukemic cells from 53 patients (60%). Thirteen (76%) of the 17 patients with t(15;17) had SOCS1 methylation, whereas this gene was methylated in only one (11%) of the nine patients with t(8;21). The frequencies of SOCS1 methylation among various cytogenetic subgroups differed significantly (P = 0.014). Other clinical and laboratory parameters and the disease‐free survival and overall survival were similar between patients with and without SOCS1 methylation. In conclusion, SOCS1 methylation occurs in more than half of AML cases, correlates with cytogenetic abnormalities, and may play an important role in the development of subsets of AML. © 2003 Wiley‐Liss, Inc.
Insertion of MLL sequences into chromosome band 5q31 results in an MLL‐AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemia
Authors: Deveney Ramona , Chervinsky David S. , Jani‐Sait Sheila N. , Grossi Mauro , Aplan Peter D.
Published: May 2003

MLL gene rearrangements leading to production of MLL fusion proteins are commonly detected in infant leukemia patients; the most common MLL fusion associated with infant leukemia is the MLL‐AF4 fusion. A single case of chromosomal rearrangement leading to production of an MLL fusion with AF5Q31, a gene structurally similar to AF4, has been detected recently in the malignant cells of an infant leukemia patient. We have identified a second case of MLL‐AF5Q31 fusion, arising from an insertion of MLL sequences into chromosome 5, also in an infant leukemia patient. Because MLL and AF5Q31 are transcribed in opposite orientations, a simple balanced chromosomal translocation cannot produce a fusion protein, and complex chromosomal rearrangements such as insertions and inversions are required to produce an MLL‐AF5Q31 fusion protein. This report demonstrates that chromosomal insertion of MLL sequences is a rare but recurrent abnormality associated with infant leukemia. © 2003 Wiley‐Liss, Inc.
Haploinsufficiency and reduced expression of genes localized to the 8p chromosomal region in human prostate tumors
Authors: Chaib Hassan , MacDonald James W. , Vessella Robert L. , Washburn Joseph G. , Quinn Janna E. , Odman Austin , Rubin Mark A. , Macoska Jill A.
Published: May 2003

Cytogenetic and molecular studies have suggested that deletion or rearrangement of sequences that map to the short arm of chromosome 8 may be permissive for tumorigenesis in several organ systems, and in human prostate tumors in particular. In this study, we hypothesized that genes deleted for one copy and localized to the 8p chromosomal region may be transcriptionally down‐regulated or ablated in affected human prostate tumor tissues. To test this hypothesis, we used cDNA microarray analysis to determine the transcriptional profiles for 259 transcribed sequences mapping to the 8p chromosomal region for seven human prostate tumor xenografts, completely characterized for numerical and structural alterations on chromosome 8, and five normal human prostate tissues. These experiments identified 33 genes differentially expressed between normal and malignant prostate tissues, the majority of which (28/33, 85%) were transcriptionally down‐regulated in malignant compared to normal human prostate tissues. These findings, that haploinsufficiency and transcriptional down‐regulation for genes mapping to 8p are largely coincident in human prostate tumors, should provide a powerful tool for the identification of tumor‐suppressor genes associated with human prostate cancer initiation and progression. © 2003 Wiley‐Liss, Inc.
Estimation of the determinants of household health care expenditures in Nepal with controls for endogenous illness and provider choice
Authors: Rous Jeffrey J. , Hotchkiss David R.
Published: May 2003

This paper uses the Nepal Living Standards Survey, a nationally representative sample of households from 1996, to investigate the determinants of household out‐of‐pocket health expenditures. The analysis uses a multi‐equation joint estimation to control for endogeneity of sickness and provider choice. The results of this analysis indicate several interesting findings. First, common unobserved factors were found to be statistically significant determinants of illness, choice of provider, and health expenditures, and may cause bias to parameter estimates if not controlled. Second, the income elasticity is estimated to be 1.10, with income having both a direct effect on health expenditure, and an indirect effect through likelihood of illness and the type of provider that is chosen. Third, housing and sanitary conditions were found to have a substantial effect on illness, and as a result, out‐of‐pocket health care expenditures. Fourth, despite the fact that urban, ill individuals who seek care are more likely to utilize care in more expensive settings, average health care expenditure among the urban sample was found to be substantially lower than among the rural sample, partly due to a lower likelihood of reporting illnesses and injuries and of using any type of health care provider. Copyright © 2002 John Wiley & Sons, Ltd.
The person trade‐off method and the transitivity principle: an example from preferences over age weighting
Authors: Dolan Paul , Tsuchiya Aki
Published: May 2003

The person trade‐off (PTO) is increasingly being used to elicit preferences in health. This paper explores the measurement properties of the PTO method in the context of a study about how members of the public prioritise between patients of different ages. In particular, it considers whether PTO responses satisfy the transitivity principle; that is, whether one PTO response can be inferred from two other PTO responses. The results suggest that very few responses to PTO questions satisfy cardinal transitivity condition. However, this study has produced results that suggest that cardinal transitivity will hold, on average, when respondents who fail to satisfy the ordinal transitivity condition have been excluded from the analysis. This suggests that future PTO studies should build in checks for ordinal transitivity. Copyright © 2002 John Wiley & Sons, Ltd.
The labour market for nursing: a review of the labour supply literature
Authors: Antonazzo Emanuela , Scott Anthony , Skatun Diane , Elliott Robert. F.
Published: May 2003

The need to ensure adequate numbers of motivated health professionals is at the forefront of the modernisation of the UK NHS. The aim of this paper is to assess current understanding of the labour supply behaviour of nurses, and to propose an agenda for further research. In particular, the paper reviews American and British economics literature that focuses on empirical econometric studies based on the classical static labour supply model.

American research could be classified into first generation, second generation and recent empirical evidence. Advances in methods mirror those in the general labour economics literature, and include the use of limited dependent variable models and the treatment of sample selection issues. However, there is considerable variation in results, which depends on the methods used, particularly on the effect of wages.

Only one study was found that used UK data, although other studies examined the determinants of turnover, quit rates and job satisfaction. The agenda for further empirical research includes the analysis of discontinuities in the labour supply function, the relative importance of pecuniary and non‐pecuniary job characteristics, and the application of dynamic and family labour supply models to nursing research. Such research is crucial to the development of evidence‐based policies. Copyright © 2002 John Wiley & Sons, Ltd.
A preliminary investigation of the effects of restrictions on Medicaid funding for abortions on female STD rates
Authors: Sen Bisakha
Published: May 2003

There is evidence in the economics literature that restrictions on Medicaid funding for abortion reduces the demand for abortion. The unresolved question is whether such restrictions also increase safe sex (that is, pregnancy avoidance) behavior among women. This study explores that issue using state‐level gonorrhea rates among women for 1975–1995. The rationale is that sexual behavior that leads to greater risk of accidental pregnancies is likely to be highly correlated with sexual behavior leading to greater risk of STD infection. Since gonorrhea has an incubation period of about a week, and is transmitted almost exclusively through sexual intercourse, a change in sexual behavior should soon be followed by a change in gonorrhea rates. The study used a partial adjustment model with lagged‐dependent variables estimated using Arellano‐Bond's GMM method. Results fail to find any statistically significant evidence that Medicaid funding restrictions are effective in reducing gonorrhea rates. This finding is robust to a variety of alternate specifications and tests. This suggests that restrictions on Medicaid funding for abortion fail to promote safe sex behavior among women. Copyright © 2002 John Wiley & Sons, Ltd.
Conjoint analysis. The cost variable: an Achilles' heel?
Authors: Slothuus Skjoldborg Ulla , Gyrd‐Hansen Dorte
Published: May 2003

This paper seeks to enlighten the readers on the potential complexities involved in including cost variables in conjoint analysis, with the aim of emphasising that interpretation of implicit WTP values should be tackled with caution. To illustrate the potential pitfalls, a large data set from a recent Danish study is applied. The data consists of 1991 interviews in which participants are required to perform three discrete choice tasks regarding choice of hospitals, and three choice tasks involving health‐care systems in general. Model comparisons are performed which test the effect of (1) the cost range applied and (2) the effect of including a dummy variable to represent the utility associated with payment per se. A wider cost range including higher payments is associated with lower parameter weights associated with the payment variable, and thus increased WTP values. Including a dummy variable to explain utility associated with payment per se has significant effects on the model incurring some of the other variables to become insignificant, and others to change sign. Results suggest that inclusion of a two‐dimensional structure to explain the relationship between cost and utility may avoid erroneous conclusions and give rise to significant changes in implicit WTP estimates. Copyright © 2002 John Wiley & Sons, Ltd.
The efficiency of health production: re‐estimating the WHO panel data using parametric and non‐parametric approaches to provide additional information
Authors: Hollingsworth Bruce , Wildman John
Published: May 2003

The World Health Report 2000 focuses on the performance of health‐care systems around the globe. The report uses efficiency measurement techniques to create a league table of health‐care systems, highlighting good and bad performers. Efficiency is measured using panel data methods. This paper suggests that the WHO's estimation procedure is too narrow and that contextual information is hidden by the use of one method. This paper uses and validates a range of parametric and non‐parametric empirical methods to measure efficiency using the WHO data. The rankings obtained are compared to the WHO league table and we demonstrate that there are trends and movements of interest within the league tables. We recommend that the WHO broaden its range of techniques in order to reveal this hidden information. Copyright © 2002 John Wiley & Sons, Ltd.
A note on the decomposition of the health concentration index
Authors: Clarke Philip M. , Gerdtham Ulf‐G , Connelly Luke B.
Published: May 2003

In recent work, the concentration index has been widely used as a measure of income‐related health inequality. The purpose of this note is to illustrate two different methods for decomposing the overall health concentration index using data collected from a Short Form (SF‐36) survey of the general Australian population conducted in 1995. For simplicity, we focus on the physical functioning scale of the SF‐36. Firstly we examine decomposition ‘by component’ by separating the concentration index for the physical functioning scale into the ten items on which it is based. The results show that the items contribute differently to the overall inequality measure, i.e. two of the items contributed 13% and 5%, respectively, to the overall measure. Second, to illustrate the ‘by subgroup’ method we decompose the concentration index by employment status. This involves separating the population into two groups: individuals currently in employment; and individuals not currently employed. We find that the inequality between these groups is about five times greater than the inequality within each group. These methods provide insights into the nature of inequality that can be used to inform policy design to reduce income related health inequalities. Copyright © 2002 John Wiley & Sons, Ltd.
Brain and behavior interface: Stress and the developing brain
Authors: Gunnar Megan R. , Cheatham Carol L.
Published: May 2003

Animal studies have shown that mother–infant interactions can have long‐term impacts on areas of the brain that regulate fearful behavior and the physiology of stress. Here, the research on human infants and children is reviewed with an eye to whether early experiences have similar effects in our species. Research shows that during the first year, sensitive and responsive caregiving becomes a powerful regulator of emotional behavior and neuroendocrine stress hormone activity in young children. Indeed, quality‐of‐care effects can be detected for children throughout the preschool years. Reviewed research suggests that temperament affects the likelihood that children will show increases in stress hormones as the quality of their care decreases. Finally, we review the literature on stress hormone activity in children who have been maltreated early in life, and explore the critical question of whether enhancing care later in development can reverse the effects on behavior and neurobiology of early adverse experiences. ©2003 Michigan Association for Infant Mental Health.
The development of psychopathology from infancy to adulthood: The mysterious unfolding of disturbance in time
Authors: Fonagy Peter
Published: May 2003

A model for the development of this mechanism is offered as well as evidence for it from five areas: (1) the nature of the association of early attachment and later cognitive functioning, (2) accumulating evidence for the association between secure attachment and the facility with which internal states are understood and represented, (3) the limited predictive value of early attachment classification, (4) the studies of the biological functions of attachment in other mammalian species, and (5) factor analytic studies of adult attachment scales that suggest the independence of attachment type and attachment quality. The author tentatively proposes that attachment in infancy has the primary evolutionary function of generating a mind capable of inferring and attributing causal motivational and epistemic mind states, and through these arriving at a representation of the self in terms of a set of stable and generalized intentional attributes thus ensuring social collaboration, whereas attachment in adulthood serves the evolutionary function of protecting the self representation from the impingements that social encounters inevitably create. Severe personality pathology arises when the psychological mechanism of attachment is distorted or dysfunctional and cannot fulfill its biological function of preserving the intactness of self representations. ©2003 Michigan Association for Infant Mental Health.
Parents and infants in changing cultural context: Immigration, trauma, and risk
Authors: Moro Marie Rose
Published: May 2003

“Entre les bibliothèques et les bébés en détresse, il y a un grand fossé” (S. Fraiberg). “Between library and at‐risk infants themselves lies a great gulf” (Fraiberg, 1999, p. 416). Whether they are African or Asian, children of immigrant families live in at‐risk situations where they may be exposed to serious trauma. Immigrant families often live in extreme conditions. Although research describes these conditions, the field of intervention remains weak. How many times have I heard that work among these families does not address treatment, but only basic needs, noting that the families are preoccupied with survival—where to find food, where to sleep, where to bury their dead. Yet, the psychological care of immigrant children and families has much to teach us. In this article I will describe work that attempts to bridge the gulf that Fraiberg referred to by sharing what I have learned regarding immigrant families with infants. ©2003 Michigan Association for Infant Mental Health.
Beyond the dyad: Parent–infant psychotherapy in a multicultural society—reflections from a South African perspective
Authors: Berg Astrid
Published: May 2003

Awareness of infant mental health has steadily been growing in South Africa. The University of Cape Town Parent–Infant Mental Health Service serves the under three population in two areas in Cape Town. The challenges that face professionals when working in a traditional community are numerous. Besides the problems that poverty bring, there are the differences in cultures that need to be understood and engaged with. Although South Africa is now in the phase of integrating its cultural diversity, professional training has been based on western models. These models place the emphasis on individual, personal relationships. The African worldview, however, includes a deep awareness of the importance of the collective community. The sense of person‐hood is rooted in this consciousness. For psychotherapy in South Africa to be relevant and appropriate, professionals working in this field have to be aware and genuinely respectful of differences between the various cultural groups. The complexity of two cultures meeting without sufficient awareness of difference is illustrated in the failed psychotherapy of a mother–infant dyad that resulted in attempted infanticide. This highlights the shortcomings of a psychotherapy based on dyadic attachment models only. ©2003 Michigan Association for Infant Mental Health.
Prebirth predictors of coparenting experiences in early infancy
Authors: Van Egeren Laurie A.
Published: May 2003

The aim of the current research was to identify prebirth predictors of coparenting experiences during the transition to parenthood. Questionnaires were used to assess 101 couples during the third trimester and one, three, and six months after the birth of the first child. Results of hierarchical linear modeling analyses indicated different predictors of coparenting level, linear change, and fluctuation for mothers and fathers. For mothers, coparenting experiences were associated with age, paternal education, concerns around child rearing, differences in child‐rearing philosophy, and reactance, whereas for fathers, coparenting experiences were related to occupation, maternal ego development, coparenting in the family of origin, and both parents' motivation to raise children. There were indications that mothers may drive the development of the coparenting relationship for both parents. ©2003 Michigan Association for Infant Mental Health.
Infant mental health as we enter the third millennium: Can we prevent aggression?
Authors: Gauthier Yvon
Published: May 2003

At the end of a murderous century, the author attempts to reflect on the origins of violence and finds that several authors working with murderers hear them talk about their childhood marked by abuse and violence. Research on early manifestations of violence shows that physical aggression present by age five is still the best predictor of physical aggression at adolescence, but also that it is present even before age five, and can be controlled early. Poverty is seen to be an important factor of aggression, particularly in association with family characteristics. Within attachment theory research, insecure attachment, specifically the disorganized‐disoriented (D) pattern, is closely tied up to aggressive behavior at ages five and seven. Development of self‐regulation and empathy in very young children is closely tied up to the empathic caregiving of the environment. Early intervention in disadvantaged areas is shown to lead to long‐term positive results in projects that were built on intensive family support and early education services mostly rendered in home visits. Recommendations are made for continuation of research and early intervention in its various forms, and for the importance of social policies that help all parents with infants and young children, but particularly parents from high‐risk populations. ©2003 Michigan Association for Infant Mental Health.