bluuebunny/crossref_metadata_2025 huggingface dataset:
Principal component analysis for selection of optimal SNP‐sets that capture intragenic genetic variation
Authors: Horne Benjamin D. , Camp Nicola J.
Published: December 2003

Candidate gene association studies often utilize one single nucleotide polymorphism (SNP) for analysis, with an initial report typically not being replicated by subsequent studies. The failure to replicate may result from incomplete or poor identification of disease‐related variants or haplotypes, possibly due to naive SNP selection. A method for identification of linkage disequilibrium (LD) groups and selection of SNPs that capture sufficient intra‐genic genetic diversity is described. We assume all SNPs with minor allele frequency above a pre‐determined frequency have been identified. Principal component analysis (PCA) is applied to evaluate multivariate SNP correlations to infer groups of SNPs in LD (LD‐groups) and to establish an optimal set of group‐tagging SNPs (gtSNPs) that provide the most comprehensive coverage of intra‐genic diversity while minimizing the resources necessary to perform an informative association analysis. This PCA method differs from haplotype block (HB) and haplotype‐tagging SNP (htSNP) methods, in that an LD‐group of SNPs need not be a contiguous DNA fragment. Results of the PCA method compared well with existing htSNP methods while also providing advantages over those methods, including an indication of the optimal number of SNPs needed. Further, evaluation of the method over multiple replicates of simulated data indicated PCA to be a robust method for SNP selection. Our findings suggest that PCA may be a powerful tool for establishing an optimal SNP set that maximizes the amount of genetic variation captured for a candidate gene using a minimal number of SNPs. Genet Epidemiol 26:11–21, 2004. © 2003 Wiley‐Liss, Inc.
Power estimation of multiple SNP association test of case‐control study and application
Authors: Hao Ke , Xu Xin , Laird Nan , Wang Xiaobin , Xu Xiping
Published: December 2003

At the current stage, a large number of single nucleotide polymorphisms (SNPs) have been deployed in searching for genes underlying complex diseases. A powerful method is desirable for efficient analysis of SNP data. Recently, a novel method for multiple SNP association test using a combination of allelic association (AA) and Hardy‐Weinberg disequilibrium (HWD) has been proposed. However, the power of this test has not been systematically examined. In this study, we conducted a simulation study to further evaluate the statistical power of the new procedure, as well as of the influence of the HWD on its performance. The simulation examined the scenarios of multiple disease SNPs among a candidate pool, assuming different parameters including allele frequencies and risk ratios, dominant, additive, and recessive genetic models, and the existence of gene‐gene interactions and linkage disequilibrium (LD). We also evaluated the performance of this test in capturing real disease associated SNPs, when a significant global P value is detected. Our results suggest that this new procedure is more powerful than conventional single‐point analyses with correction of multiple testing. However, inclusion of HWD reduces the power under most circumstances. We applied the novel association test procedure to a case‐control study of preterm delivery (PTD), examining the effects of 96 candidate gene SNPs concurrently, and detected a global P value of 0.0250 by using Cochran‐Armitage χ2s as “starting” statistics in the procedure. In the following single point analysis, SNPs on IL1RN, IL1R2, ESR1, Factor 5, and OPRM1 genes were identified as possible risk factors in PTD. Genet Epidemiol 26:22–30, 2004. © 2003 Wiley‐Liss, Inc.
Tests for covariate‐associated heterogeneity in IBD allele sharing of affected relatives
Authors: Mirea Lucia , Briollais Laurent , Bull Shelley
Published: December 2003

Linkage studies that aim to map susceptibility genes for complex diseases commonly test for excess allele sharing among affected relatives. Conventional methods based on identical‐by‐descent IBD allele sharing do not allow for possible differences among families, such as arise in the case of locus heterogeneity, and thus have reduced ability to detect linkage in the presence of such heterogeneity. We investigated two approaches to test for heterogeneity in allele sharing, using a family‐level covariate that may be associated with different disease mechanisms leading to differences in allele sharing. Likelihood ratio tests for heterogeneity were formulated based on an extension of the linear and exponential likelihood models developed by Kong and Cox ([1997] Am. J. Hum. Genet. 61:1179–1188). Alternatively, we examined the asymptotic and permutation distributions of T‐tests for differences between mean allele‐sharing linkage scores from two covariate‐defined family subgroups, assuming exchangeability. The size and power of heterogeneity tests were evaluated for Sall and Spairs allele‐sharing scoring functions using data sets of families with affected sibling and cousin pairs, generated under a model of locus heterogeneity. In certain simulation scenarios, the likelihood ratio test statistics did not follow the expected asymptotic distributions. The type I error estimates for the T‐statistics conformed to nominal 5 and 1% levels in all scenarios considered, and corresponding power was comparable to that of the likelihood ratio tests. Application of these tests for heterogeneity detected significant differences in allele sharing between subgroups of families with inflammatory bowel disease. Genet Epidemiol 26:44–60, 2004. © 2003 Wiley‐Liss, Inc.
Family‐based tests for associating haplotypes with general phenotype data: Application to asthma genetics
Authors: Horvath Steve , Xu Xin , Lake Stephen L. , Silverman Edwin K. , Weiss Scott T. , Laird Nan M.
Published: December 2003

We provide a general purpose family‐based testing strategy for associating disease phenotypes with haplotypes when phase may be ambiguous and parental genotype data may be missing. These tests for linkage and association can be used in candidate gene studies with tightly linked markers. Our proposed weighted conditional approach extends the method described in Rabinowitz and Laird [Human Heredity 504:227–233, 2000] to multiple markers. It is attractive because it provides haplotype tests for family‐based studies that are efficient and robust to population admixture, phenotype distribution specification, and ascertainment based on phenotypes. It can handle missing parental genotypes and/or missing phase in both offspring and parents. It yields either haplotype‐specific (univariate) tests or multi‐haplotype (global) tests. This extension has been implemented in the freely available software haplotype FBAT. We used the haplotype FBAT program to test for associations between asthma phenotypes and single nucleotide polymorphisms (SNPs) in the beta‐2 adrenergic receptor gene. Whereas no single SNP showed significant association with asthma diagnosis or bronchodilator responsiveness (quantitative trait), a haplotype‐based global test found a highly significant association with asthma diagnosis (P value <0.00005) and the measure of bronchodilator responsiveness (P value =0.016). Genet Epidemiol 26:61–69, 2004. © 2003 Wiley‐Liss, Inc.
M&A lesson: Beware of empire builders
Authors: Gaughan Patrick A.
Published: December 2003

We must learn some lessons from the last wave of mergers, says the author of this article. Many of the largest deals were colossal
failures—because empire‐building CEOs were unrestrained by lazy boards of directors. © 2004 Wiley Periodicals,
Inc.
Uncle Sam watches nervously: Foreign investment in U.S. industries
Authors: Rosener James D. , Dorris Gregory C.
Published: December 2003

As the war on terrorism continues, foreign investment in U.S. industries has come under ever closer scrutiny. This has a big impact on M&A
with foreign partners or investors. The authors explain what you need to know to safely navigate this maze. © 2004 Wiley Periodicals,
Inc.
Near zero‐defect accounting with Six Sigma
Authors: Brewer Peter C. , Bagranoff Nancy A.
Published: December 2003

Many companies have used the Six Sigma methodology to improve manufacturing processes, but in recent years, companies have started using Six Sigma to
improve the finance function. This article provides an overview of Six Sigma, explains how two companies are using Six Sigma to streamline their
respective finance departments, and offers tips for companies interested in adopting Six Sigma for their finance departments. © 2004 Wiley
Periodicals, Inc.
Approaches to better management
Authors: Goldberg Stephen R. , Godwin Joseph H.
Published: December 2003

Bloxham, Eleanor. 2003. Economic Value Management (New York: John Wiley & Sons).

Stamitis, D. H. 2003. Six Sigma for Financial Professionals (New York: John Wiley & Sons).
The relationship of sociotropy and autonomy to posttraumatic cognitions and PTSD symptomatology in trauma survivors
Authors: Kolts Russell L. , Robinson April M. , Tracy Jessica J.
Published: December 2003

The current study examined relationships between sociotropic and autonomous personality styles and posttraumatic stress disorder (PTSD) symptomatology following trauma as well as specific posttraumatic cognitions that have been shown to characterize individuals with PTSD. Self‐report data were collected in a sample of 156 college students indicating a history of traumatic experience. Significant relationships were found between symptoms of PTSD and depression and measures of sociotropy, autonomy, and negative posttraumatic beliefs about self and world. Additionally, measures of autonomy and negative posttraumatic thoughts improved prediction of PTSD symptom level after controlling for depressive symptoms. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
A revised Spanish version of the Beck Depression Inventory: Psychometric properties with a Puerto Rican sample of college students
Authors: Bonilla Janet , Bernal Guillermo , Santos Axel , Santos Douglas
Published: December 2003

The Beck Depression Inventory (BDI) is a widely used self‐report measure for depression. This study has two objectives: (a) to revise, develop, and adapt a Spanish language BDI (BDI‐S) that takes the criteria for the diagnosis of major depression according to the DSM‐IV into consideration; and (b) to evaluate the psychometric properties (internal reliability and construct validity) of the revised version of the BDI (BDI‐S). A sample of 351 undergraduate students at the University of Puerto Rico participated in this study. The participants who agreed to participate in the study and signed the consent form completed self‐report measures related to depression (BDI‐S, CES‐D, and LCSd‐7), dysfunctional cognition (DAS‐A and IBT), stressful life events (LES), and social support (CAS). The coefficient of internal consistency obtained for the 22 BDI‐S items was .88. The correlation coefficients between the BDI‐S and instruments that measured other constructs (not depression) were lower than the correlation coefficients between instruments that measured the same constructs. Factor analysis
revealed that the factor loading for the BDI‐S was congruent with dimensions of depression reported in the literature. These results generally support the internal consistency and the construct validity of the BDI‐S. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Recommendations for applying tests of equivalence
Authors: Cribbie Robert A. , Gruman Jamie A. , Arpin‐Cribbie Chantal A.
Published: December 2003

Researchers in psychology reliably select traditional null hypothesis significance tests (e.g., Student's t test), regardless of whether the research hypothesis relates to whether the group means are equivalent or whether the group means are different. Tests of equivalence, which have been popular in biopharmaceutical studies for years, have recently been introduced and recommended to researchers in psychology for demonstrating the equivalence of two group means. However, very few recommendations exist for applying tests of equivalence. A Monte Carlo study was used to compare the test of equivalence proposed by Schuirmann with the traditional Student t test for deciding if two group means are equivalent. It was found that Schuirmann's test of equivalence is more effective than Student's t test at detecting population mean equivalence with large sample sizes; however, Schuirmann's test of equivalence performs poorly relative to Student's t test with small sample sizes and/or inflated variances. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Remembering the 1978 and 1990 task forces on self‐help therapies
Authors: Rosen Gerald M.
Published: December 2003

A special series on self‐administered therapies was edited by Forrest R. Scogin for the Journal of Clinical Psychology (Volume 59, Number 3). Articles in the edited series failed to mention two task forces on self‐help therapies that were sponsored by groups within the American Psychological Association in 1978 and 1990. Consideration of the work by these task forces provides an historical perspective for the issues and recommendations provided in Scogin's series. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
A national survey of trainee impairment in clinical, counseling, and school psychology doctoral programs and internships
Authors: Huprich Steven K. , Rudd M. David
Published: December 2003

The purpose of this study was to assess the frequency, type, and management of trainee impairment at a national level across doctoral programs in clinical, counseling, and school psychology and predoctoral internships. A total of 199 surveys were completed, returned, and usable. In general, doctoral programs reported a greater frequency of trainee impairment than internships. However, a greater percentage of internships had a policy and program in place for managing impairments than did doctoral programs. These findings are compared with past studies and reviews of this issue. In light of these findings, specific implications for training programs are discussed, with the recommendation that training programs address more attention to the assessment and management of such problems. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Comparative analysis of methods for determining bite force in the spiny dogfish Squalus acanthias
Authors: Huber Daniel Robert , Motta Philip Jay
Published: December 2003

Many studies have identified relationships between the forces generated by the cranial musculature during feeding and cranial design. Particularly important to understanding the diversity of cranial form amongst vertebrates is knowledge of the generated magnitudes of bite force because of its use as a measure of ecological performance. In order to determine an accurate morphological proxy for bite force in elasmobranchs, theoretical force generation by the quadratomandibularis muscle of the spiny dogfish Squalus acanthias was modeled using a variety of morphological techniques, and lever‐ratio analyses were used to determine resultant bite forces. These measures were compared to in vivo bite force measurements obtained with a pressure transducer during tetanic stimulation experiments of the quadratomandibularis. Although no differences were found between the theoretical and in vivo bite forces measured, modeling analyses indicate that the quadratomandibularis muscle should be divided into its constituent divisions and digital images of the cross‐sections of these divisions should be used to estimate cross‐sectional area when calculating theoretical force production. From all analyses the maximum bite force measured was 19.57 N. This relatively low magnitude of bite force is discussed with respect to the ecomorphology of the feeding mechanism of S. acanthias to demonstrate the interdependence of morphology, ecology, and behavior in organismal design. J. Exp. Zool. 301A:26–37, 2004. © 2004 Wiley‐Liss, Inc.
Quantitation of cytomegalovirus DNA in cerebrospinal fluid and serum specimens from AIDS patients using a novel highly sensitive nested competitive PCR and the cobas amplicor CMV monitor™
Authors: Tarragó David , Mateos María‐Luisa , Avellón Ana , Pérez‐Vázquez María‐Dolores , Tenorio Antonio
Published: December 2003

A novel nested quantitative‐competitive polymerase chain reaction (nQC‐PCR) assay was developed to quantify as few as ten copies per tube of human cytomegalovirus DNA with an overall dynamic range of 10–105 copies per tube. This nQC‐PCR assay is based on co‐amplification of a mimic DNA and it was evaluated with 26 cerebrospinal fluid (CSF) specimens and 44 serum specimens from 70 CMV‐infected AIDS patients, 35 of them were diagnosed of CMV retinitis. An excellent correlation was found between nQC‐PCR assay and the commercially available Cobas Amplicor CMV Monitor™ (CACM) assay (R = 0.9999; P < 0.001; n = 42). Moreover, 13 serum samples with CMV viral loads undetectable with the CACM were successfully quantified by nQC‐PCR. CMV viral load was significantly higher in patients with CMV retinitis (P = 0.003). The nQC‐PCR assay described below is a very sensitive test for accurate quantitative detection of CMV DNA in different clinical specimens that avoids the need for high‐cost instrumentation. J. Med. Virol. 72:249–256, 2004. © 2004 Wiley‐Liss, Inc.
Hepatitis B virus DNA in liver, serum, and peripheral blood mononuclear cells after the clearance of serum hepatitis B virus surface antigen
Authors: Murakami Yoshiki , Minami Masahito , Daimon Yukiko , Okanoue Takeshi
Published: December 2003

The integration of hepatitis B virus (HBV) DNA in the liver of chronic HBV carriers has been documented extensively. However, the status of the viral genome during acute infection has not been assessed conclusively. While HBV DNA sequences are detected often in serum, liver, and peripheral blood mononuclear cells (PBMCs) after the clearance of serum the hepatitis B virus surface antigen (HBsAg), the precise status of the viral genome, and in particular the possible persistence of integrated genomes in PBMCs, has not been established. A highly sensitive PCR‐derived assay (Alu–PCR) was employed to re‐examine liver and PBMC specimens obtained from patients with acute (n = 19) and chronic (n = 22) hepatitis in whom serum HBsAg was present (n = 12) (HBV‐related chronic active hepatitis) or absent with anti‐HCV (n = 10) (HCV‐related chronic active hepatitis). Viral integration was demonstrated in 3 out of 19 liver specimens from patients with acute hepatitis and 12 out of 12 specimens from patients with chronic hepatitis. Viral integration was also observed in 4 out of 7 PBMC samples from HBV‐related chronic active hepatitis patients and 2 out of 10 liver and PBMC samples from HCV‐related chronic active hepatitis patients. In one liver specimen from an acute hepatitis patient, HBV DNA was found integrated in the intronic sequence of the tumour necrosis factor (TNF)‐induced protein gene; viral integration into cellular sequences was also found in the PBMCs of four HBV‐related chronic active hepatitis and two HCV‐related chronic active hepatitis. The results demonstrate the early integration of HBV genome during acute viral infections and the persistence of the viral genome in an integrated form in PBMCs. J. Med. Virol. 72:203–214, 2004. © 2004 Wiley‐Liss, Inc.
Influence of antigenic drift on the intensity of influenza outbreaks: Upper respiratory tract infections of military conscripts in Finland
Authors: Pyhälä Reijo , Visakorpi Risto , Ikonen Niina , Kleemola Marjaana
Published: December 2003

A total of 102,600 upper respiratory infections (URI) were recorded among young military conscripts in the Finnish Defence Forces during the study period from October 1991 to March 1994. This period covered three outbreaks caused by H3N2‐subtype influenza A virus and one outbreak of influenza B. During the 1991/92 outbreak caused by A/Beijing/353/89‐like virus, the calculated influenza A incidence was 2,206/10,000 men. During the 1992/93 outbreak when influenza B was the predominant virus, a new drift variant of influenza A that belonged to the lineage of A/Beijing/32/92‐like and A/Shangdong/9/93‐like viruses circulated but the incidence of influenza A was not more than 1,044/10,000. A higher incidence, 2,810/10,000, was recorded during the 1993/94 outbreak, when the circulating virus was similar to the 1992/93 virus antigenically and with regard to haemagglutinin and neuraminidase (NA) gene sequences. Crossreactive haemagglutination‐inhibition antibodies induced in 1991/92 probably were sufficient to restrict the epidemic activity in 1992/93 but no longer in 1993/94. Furthermore, during the 1991/92 outbreak, some of the A/Beijing/353/89‐like viruses already had shared the NA sequence markers characteristic of the viruses in 1992/93 and 1993/94, which may also have strengthened protection in 1992/93. J. Med. Virol. 72:275–280, 2004. © 2004 Wiley‐Liss, Inc.
Genotyping of the JC virus in urine samples of healthy Korean individuals
Authors: Jeong Byung‐Hoon , Lee Kyung‐Hee , Choi Eun‐Kyoung , Kim Kyunghoon , Kim Yong‐Sun
Published: December 2003

A human polyomavirus, JC virus (JCV) is ubiquitous in humans and infects children asymptomatically. It persists in renal tissue and is excreted progeny in urine. DNAs from urine samples of 100 healthy Korean individuals were screened for the presence of JCV by polymerase chain reaction (PCR). Twenty of the samples were positive for JCV. JCV DNA was found in one individual (4%) in the 1–19‐year group, two individuals (9%) in the 20–39‐year group, ten individuals (38%) in the 40–59‐year group, seven individuals (28%) in the over 60‐year group. The prevalence of JC viral DNA was the highest in the 40–59‐year‐old Korean population. To investigate genotypes of JCV in Korea, the genotypes were determined by DNA sequence analysis of the regulatory region (333 bp) and the VT‐intergenic region (656 bp) of DNA from the 20 JCV isolates. We have identified three distinctive JCV strains in the regulatory region and ten distinctive JCV strains in the VT‐intergenic region of DNA from the 20 isolates. Based on restriction fragment length polymorphism (RFLP) analysis and phylogenetic analysis of the VT‐intergenic region of JCV, two distinct subtypes, CY and type 2A (MY), were found to be prevalent in this Korean population. CY and type 2A of JCV were identified in 13 individuals (65%) and four individuals (20%), respectively. Interestingly, type 1, which was distributed mostly in Europe, was found in 3 (15%) isolates from healthy Korean individuals. J. Med. Virol. 72:281–289, 2004. © 2004 Wiley‐Liss, Inc.
Surveillance of norovirus infection in a study of sporadic childhood gastroenteritis in South West England and South Wales, during one winter season (1999–2000)
Authors: Froggatt Pippa C. , Barry Vipond I. , Ashley Charles R. , Lambden Paul R. , Clarke Ian N. , Caul E. Owen
Published: December 2003

Reverse transcriptase polymerase chain reaction (RT‐PCR), electron microscopy (EM) and a genotype II specific antigen capture enzyme immunoassay (EIA), (Lordsdale strain) were used to establish the prevalence of Norwalk‐like viruses (NLV) among sporadic cases of childhood gastroenteritis in South West England over a winter season. Samples of 3,172 stools from cases of gastroenteritis in children aged under 7 years sent to the Bristol Public Health Laboratory over the 1999/2000 winter ‘season’ were tested prospectively by EM, EIA and RT‐PCR. The results from sporadic cases were compared with 1,360 samples from 285 outbreaks of gastroenteritis which were sent to the laboratory over the same period. In total NLV was established as the causal agent in 326 cases (10.3%) of sporadic gastroenteritis by one or more of the tests (EM 30 (0.9%), EIA 132 (4.2%) and RT‐PCR 276 (8.7%)). The presence of other enteric viruses was established using EM and rotavirus EIA. Rotaviruses were the most common cause of viral gastroenteritis with 684 cases (21.6%). Other viruses detected included, adenovirus 124 cases (3.9%), astrovirus 97 cases (3.1%) and calicivirus in 7 cases (0.2%). NLV was the second most common viral agent indicating a significant role in cases of sporadic childhood gastroenteritis. J. Med. Virol. 72:307–311, 2004. © 2004 Wiley‐Liss, Inc.
Detection and characterization of norovirus outbreaks in Germany: Application of a one‐tube RT‐PCR using a fluorogenic real‐time detection system
Authors: Höhne M. , Schreier E.
Published: December 2003

Outbreaks of gastroenteritis caused by Norovirus are an increasing public health problem worldwide. The virus is transmitted by contaminated food and by person‐to‐person. In Germany, a new health reporting system including Norovirus infections has been introduced in 2001. Norovirus outbreaks (73%) diagnosed in our lab occurred in the first half of the year. Phylogenetic analysis shows that 90% belonged to genogroup II (GGII) with the majority related to prototypes Lordsdale/93 and Tarragona/2001. To date, PCR is the most sensitive and specific method for the detection but several procedures are needed to evaluate the amplification product. To minimize the risk of product carryover, a fast and simple procedure with a minimal number of steps are required. A one‐tube RT‐PCR method is described using the real‐time TaqMan‐PCR system. Primer sets and probes for both genogroup I (GGI) and genogroup II (GGII) sequences were developed. The specificity and sensitivity of this method was evaluated on 70 Norovirus positive stool samples of 70 outbreaks in Germany and 34 European samples by comparing the detection rate to those of an in‐house RT‐nested PCR. Overall, 93% of the PCR positive samples have been detected by the TaqMan‐PCR including isolates of four different GGI and seven different GGII genotypes. Using plasmid standards for quantitation, virus loads between 102 and 1010 genomic equivalents/ml stool suspension were found. The advantages of the one‐step RT/TaqMan‐PCR system for detection and quantitation of Norovirus are the high throughput of clinical samples and a decrease of the risk of contamination. J. Med. Virol. 72:312–319, 2004. © 2004 Wiley‐Liss, Inc.
The effect of highly active antiretroviral therapy for HIV on the anti‐HCV specific humoral immune response
Authors: Herrero‐Martínez Esteban , Sabin Caroline A. , Lee Christine A. , Jones Ian M. , Pillay Deenan , Emery Vincent C.
Published: December 2003

The effect of highly active antiretroviral therapy (HAART) on HCV replication is controversial, with some studies reporting no effect and others increases, reductions and even clearances of HCV RNA after treatment. In this study, the effect of HAART was investigated on the titre of anti‐HCV specific antibodies and on the relationship between these antibodies and HCV RNA level in a cohort of 24 patients with inherited bleeding disorders. A significant inverse correlation between antibodies to both total HCV proteins and HCV RNA (R = −0.42, P = 0.05) and between antibodies to HCV envelope glycoproteins and HCV RNA (R = −0.54, P = 0.01) was observed pre‐HAART. The relationship disappeared or was obscured after therapy (R = 0.24, P = 0.30 and R = 0.16, P = 0.50, respectively). Thus, we show that HAART affects the HCV specific humoral immune responses without affecting the HCV RNA level. J. Med. Virol. 72:187–193, 2004. © 2004 Wiley‐Liss, Inc.
Molecular characterization of coxsackievirus B5 isolates
Authors: Rezig Dorra , Yahia Ahlem Ben , Abdallah Hager Ben , Bahri Olfa , Triki Hinda
Published: December 2003

Coxsackie B viruses of serotype 5 are associated frequently with sporadic cases of neurological diseases, epidemics of meningitis, and chronic diseases such as cardiomyopathy and diabetes. In this article, 15 strains of Coxsackievirus B5 isolated from patients with neurological disorders and healthy people were investigated by partial sequencing in the 5′ half of the VP1 region and compared to other published sequences of Coxsackievirus B5, in the same genomic region. All Coxsackievirus B5 sequences showed less than 25% nucleotide difference between each other and a minimum of 27.8% of divergence with prototype sequences from other Coxsackievirus B serotypes. Within the Coxsackievirus B5 group of sequences, four clusters were individualized and may correspond to four genotypes: one genotype with large geographical distribution, containing most recent strains that have circulated from 1984 to 2000, another genotype represented by the prototype Faulkner strain, isolated in the early 1950s, and two intermediate genotypes, comprising strains isolated from 1970 to 1999 and closely related to swine vesicular disease virus. This study confirms the ability of partial sequencing in VP1 to determine serotype and to genetically characterize Coxsackievirus B5 field isolates. It gives a first approach on the molecular epidemiology of these viruses, which have a particular importance in human health. J. Med. Virol. 72:268–274, 2004. © 2004 Wiley‐Liss, Inc.
The urban heat island in winter at Barrow, Alaska
Authors: Hinkel Kenneth M. , Nelson Frederick E. , Klene Anna E. , Bell Julianne H.
Published: December 2003

The village of Barrow, Alaska, is the northernmost settlement in the USA and the largest native community in the Arctic. The population has grown from about 300 residents in 1900 to more than 4600 in 2000. In recent decades, a general increase of mean annual and mean winter air temperature has been recorded near the centre of the village, and a concurrent trend of progressively earlier snowmelt in the village has been documented. Satellite observations and data from a nearby climate observatory indicate a corresponding but much weaker snowmelt trend in the surrounding regions of relatively undisturbed tundra. Because the region is underlain by ice‐rich permafrost, there is concern that early snowmelt will increase the thickness of the thawed layer in summer and threaten the structural stability of roads, buildings, and pipelines. Here, we demonstrate the existence of a strong urban heat island (UHI) during winter. Data loggers (54) were installed in the ∼150 km2 study area to monitor hourly air and soil temperature, and daily spatial averages were calculated using the six or seven warmest and coldest sites. During winter (December 2001–March 2002), the urban area averaged 2.2 °C warmer than the hinterland. The strength of the UHI increased as the wind velocity decreased, reaching an average value of 3.2 °C under calm (<2 m s−1) conditions and maximum single‐day magnitude of 6 °C. UHI magnitude generally increased with decreasing air temperature in winter, reflecting the input of anthropogenic heat to maintain interior building temperatures. On a daily basis, the UHI reached its peak intensity in the late evening and early morning. There was a strong positive relation between monthly UHI magnitude and natural gas production/use. Integrated over the period September–May, there was a 9% reduction in accumulated freezing degree days in the urban area. The evidence suggests that urbanization has contributed to early snowmelt in the village. Copyright © 2003 Royal Meteorological Society
A process‐based approach to knowledge‐flow analysis: a case study of a manufacturing firm
Authors: Kim Suyeon , Hwang Hyunseok , Suh Euiho
Published: December 2003

The manufacturing industry is usually operated on the basis of business processes, and most workers are familiar with their own processes. The process‐based approach can provide an efficient way to capture and navigate knowledge. In this study, we focus on knowledge that may be missed during knowledge transfer among workers. For this, we propose a method for analysing knowledge flow, which is passed among business processes.

As a means of developing a process‐based approach to analysing knowledge flow, a new categorization of knowledge is presented in three dimensions: scope, type, and usage level. Then we propose a process‐based knowledge management framework for analysing knowledge flow, which employs a two‐phase analysis: process analysis and knowledge‐flow analysis. We use process decomposition and process dependency analysis techniques for process analysis. A knowledge‐flow model, represented by a knowledge‐flow diagram, is proposed as a tool for representing knowledge. We formulate several semantics for knowledge‐flow modelling and suggest procedures for knowledge‐flow analysis. The proposed approach is verified and illustrated through a case study of the manufacturing process. Copyright © 2003 John Wiley & Sons, Ltd.
Complete assignment of the 1H, 13C, 15N and 19F NMR spectra of nine DL‐phenylalcoholamide anticonvulsants
Authors: Peralta‐Cruz Javier , Meza‐Toledo Sergio Enrique
Published: December 2003

The 1H, 13C, 15N and 19F NMR spectra of nine DL‐phenylalcoholamides bearing fluorine and chlorine as substituents of the phenyl ring are reported. All of them are active as anticonvulsants in pentylenetetrazole‐induced seizures. Copyright © 2003 John Wiley & Sons, Ltd.
Identifying residues in natural organic matter through spectral prediction and pattern matching of 2D NMR datasets
Authors: Simpson Andre J. , Lefebvre Brent , Moser Arvin , Williams Antony , Larin Nicolay , Kvasha Mikhail , Kingery William L. , Kelleher Brian
Published: December 2003

This paper describes procedures for the generation of 2D NMR databases containing spectra predicted from chemical structures. These databases allow flexible searching via chemical structure, substructure or similarity of structure as well as spectral features. In this paper we use the biopolymer lignin as an example. Lignin is an important and relatively recalcitrant structural biopolymer present in the majority of plant biomass. We demonstrate how an accurate 2D NMR database of ∼600 2D spectra of lignin fragments can be easily constructed, in ∼2 days, and then subsequently show how some of these fragments can be identified in soil extracts through the use of various search tools and pattern recognition techniques. We demonstrate that once identified in one sample, similar residues are easily determined in other soil extracts. In theory, such an approach can be used for the analysis of any organic mixtures. Copyright © 2003 John Wiley & Sons, Ltd.
Application of the TORO technique of 1H NMR to the structural analysis of cyclic peptide isomers having a slightly distorted symmetry from C2
Authors: Watanabe Eiji , Tamaki Makoto , Yamakura Fumiyuki , Akiyama Minoru
Published: December 2003

The extended TORO technique was applied to the structural analysis of endo‐D‐Tyr‐gramicidin S, cyclo(‐Val‐Orn‐Leu‐D‐Phe‐D‐Tyr‐Pro‐Val‐Orn‐Leu‐D‐Phe‐Pro‐), which has a slightly distorted symmetry from C2, by the insertion of D‐Tyr and equivalent α‐proton chemical shifts in the 1H NMR spectrum. All NMR signals of the two dominant isomers of this antibiotic with trans–trans prolines were determined by using the extended TORO technique with TOCSY and ROESY spectra. This technique is generally applicable for distinguishing overlapped signals of α‐ and amide protons from the main chains of peptides. Copyright © 2003 John Wiley & Sons, Ltd.
Non‐empirical calculations of NMR indirect carbon–carbon coupling constants. Part 6: Propellanes
Authors: Krivdin Leonid B.
Published: December 2003

A full set of carbon–carbon coupling constants have been calculated at the SOPPA level in the series of six most representative propellanes. Special attention was focused on spin–spin couplings involving both bridgehead carbons, and these data were rationalized in terms of the multipath coupling mechanism and hybridization effects. Many unknown couplings in the propellane frameworks were predicted with high reliability. Copyright © 2003 John Wiley & Sons, Ltd.
Fetal cystoscopy in the management of fetal obstructive uropathy: experience in a single European centre
Authors: Welsh Alec , Agarwal Sanjiv , Kumar Sailesh , Smith Richard P. , Fisk Nicholas M.
Published: December 2003

Objective

To audit diagnostic and therapeutic fetal cystoscopy for suspected posterior urethral valves (PUV).

Methods

In 13 fetuses, (14–28 weeks) the bladder was entered with a 1.3 mm embryo‐fetoscope and intravesical findings documented. In 10 fetuses, an attempt was made to treat the obstruction by saline hydro‐ablation (n = 4) and/or guide‐wire passage (n = 9). Renal function was assessed post‐natally at 10 to 34 months.

Results

The bladder wall was visualised in 12/13 cases and the bladder neck in 11; in 10 cases the upper urethra was entered, and the obstruction visualised in five. PUV were ‘seen’ in 4/9 confirmed cases, but also in one case of urethral atresia, while in two others the degree of resistance to guide‐wire passage suggested atresia or prune belly. Therapeutic attempts were technically successful, at least initially, in 6/10 cases. Of the five cases with confirmed PUV and normal fetal urinary electrolytes, two have acceptable renal function at follow‐up. Hydro‐ablation in one case resulted in resolution of sonographic signs of obstruction, and ablated valves were confirmed post‐natally.

Conclusions

Semi‐rigid fetal cystoscopy allows entry into the upper urethra in most obstructive uropathies, although bladder neck angulation precludes visualisation of the site of obstruction in the majority. Guide‐wire passage or hydro‐ablation may allow relatively atraumatic ablation of PUV in utero without the chronic bladder decompression associated with vesico‐amniotic shunting. However, current technical limitations need to be overcome, possibly by the use of flexible or angled fetoscopes, before the role of cystoscopic treatment can be formally evaluated. Copyright © 2003 John Wiley & Sons, Ltd.
Providing letters and audiotapes to supplement a prenatal diagnostic consultation: effects on later distress and recall
Authors: Cope C. D. , Lyons A. C. , Donovan V. , Rylance M. , Kilby M. D.
Published: December 2003

Objectives

Information provided at a mid‐trimester fetal scan aims to improve patients' knowledge and minimize anxiety. This randomized controlled trial conducted at the Fetal Medicine Centre at Birmingham Women's Hospital aimed to assess the relative value of providing

standard information: a consultation and computer‐generated ultrasound report (n = 29);

standard information plus a post scan written non‐technical letter (n = 29);

standard information plus audiotapes of the consultation (n = 29);

standard information plus both non‐technical letters and audiotapes (n = 30).

It also aimed at exploring whether severity of diagnosis (none; mild; moderate‐severe) interacted with the type of information provided to affect subsequent anxiety, depression and recall of information.

Participants

Women (n = 550) referred with suspected fetal anomalies (without a previous history of anomaly or known psychiatric illness) were sent information regarding this study. One hundred and seventeen women consented and were randomly assigned to one of four information groups. The groups were similar with regard to age, education and marital status.

Main outcome measures

State anxiety and depression were evaluated with the self‐report State‐Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) prior to consultation and two weeks post‐scan. A structured telephone interview assessed recall of information approximately two weeks later.

Results

Two weeks after the initial consultation, women who received an audiotaped recording of the consultation reported significantly less anxiety than the control group (mean STAI 41.44 [95% CI 35.63–47.26] versus 44.92 [39.32–50.52]; difference = 10.70 [3.56–17.83], p < 0.01). Women who received a non‐technical letter also reported less anxiety than the control group, an effect that approached significance (mean STAI 39.08 [95% CI 32.85–45.30]; difference = 6.48 [0.21–13.16], p = 0.058). There were no differences between the information groups on depression scores or recall of information. Women with a more severe abnormality reported higher anxiety and depression two weeks post‐consultation, and had greater free recall but less cued recall of information.

Conclusions

Provision of additional material (particularly an audiotape) following a prenatal scan appears to minimise anxiety compared with standard practice. Provision of audiotapes and non‐technical letters do not appear to affect patient recall. Copyright © 2003 John Wiley & Sons, Ltd.
Maternal midtrimester free β‐HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy‐induced hypertension or obstetric cholestasis
Authors: Räty R. , Anttila L. , Virtanen A. , Koskinen P. , Laitinen P. , Mörsky P. , Tiitinen A. , Martikainen H. , Ekblad U.
Published: December 2003

Objectives

The present study aims at finding out whether a connection exists between altered serum free β‐hCG and/or α‐fetoprotein (AFP) levels and the manifestation of specific pregnancy complications [i.e. gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis of pregnancy (ICP)].

Methods

We compared free β‐hCG and AFP multiples of median (MoM) values in singleton pregnancies. The study population consisted of 117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group consisted of 1148 singleton pregnancies without any pregnancy complications. All were spontaneously conceived.

Results

In the group with GDM, both the free β‐hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in controls (β‐hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No statistically significant differences in the marker levels were observed between the ICP pregnancies and the control group.

Conclusions

GDM has an impact on maternal midtrimester free β‐hCG and AFP levels and may change the DS screening result. Copyright © 2003 John Wiley & Sons, Ltd.
The ‘in‐plane’ view of the inter‐ventricular septum. A new approach to the characterization of ventricular septal defects in the fetus
Authors: Paladini Dario , Giovanna Russo Maria , Vassallo Michele , Tartaglione Antonio
Published: December 2003

Objectives

Objectives of this study are (1) to describe how to obtain the in‐plane view of the inter‐ventricular septum, (2) to assess its feasibility in a population of fetuses referred for fetal echocardiography, (3) to demonstrate its effectiveness in the characterization of VSD in the fetus.

Methods

The in‐plane view of the inter‐ventricular septum is conducted in a plane almost perpendicular to that of the long axis of the left ventricle, tilting the transducer towards the right ventricle, paying attention not to ‘enter’ the right ventricular chamber. Its feasibility has been assessed in 41 fetuses referred for fetal echocardiography, by recording the visualization/failure rates by fetal lie and acoustic window. The in‐plane view of the inter‐ventricular septum was then employed in healthy fetuses and diseased fetuses with VSDs.

Results

The success rates in obtaining the in‐plane view of the inter‐ventricular septum was dependent upon fetal lie; visualization rates were 100, 36 and 0% in case of posterior, lateral and anterior spine, respectively. When used in the anatomic characterization of VSDs, this view provided significant additional information.

Conclusions

The in‐plane view of the inter‐ventricular septum represents a new echocardiographic view that can be used to enhance the assessment of the inter‐ventricular septum of the fetal heart. Its use should be considered whenever the presence of a VSD is suspected during fetal echocardiography, and in these cases it often provides additional information. Copyright © 2003 John Wiley & Sons, Ltd.
Medically assisted reproduction and second‐trimester maternal serum marker screening for Down syndrome
Authors: Muller Françoise , Dreux Sophie , Lemeur Alain , Sault Corinne , Desgrès Jean , Bernard Marguerite‐Anne , Giorgetti Claude , Lemay Catherine , Mirallié Sophie , Beauchet Alain
Published: December 2003

Objectives

To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ß‐hCG, AFP and unconjugated estriol (uE3) used as markers for second‐trimester Down syndrome maternal serum screening.

Methods

Second‐trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ß‐hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at‐risk patients (≥1/250) were also compared.

Results

No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen‐positive rate for Down syndrome screening did not differ between the two groups.

Conclusion

Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies. Copyright © 2003 John Wiley & Sons, Ltd.
Free fetal DNA concentration in maternal plasma during normal labour at term
Authors: Ingargiola Ingrid , Vaerman Jean‐Luc , Debiève Frédéric , Palgen Gaëtane , Verellen‐Dumoulin Christine , Hubinont Corinne
Published: December 2003

Objective

Our aim was to investigate the effect of uterine contractions on free fetal DNA concentration in maternal plasma at term.

Study design

Nine pregnant women were admitted for elective induction of labour between 38 and 40 weeks of gestation. All patients carrying male fetuses and without history of pre‐term labour and membrane rupture were selected. Maternal venous blood samples were serially collected every hour during labour, one hour after delivery and 24 h after delivery. In order to amplify fetal and total free DNA, primers for SRY and GAPDH genes were respectively chosen. Real‐ time PCR analysis was performed with an GeneAmp® 5700 Sequence Detection System (Applied Biosystems Foster City, USA). Statistical significance was determined using the Wilcoxon test.

Result

Median concentration of fetal DNA in plasma before labour was 3081 copies/mL (Range 812–15 864 copies/mL). No significant difference between the number of copies per millilitre before any contractions and during labour was demonstrated.

One hour after delivery, significant decrease in the fetal DNA rate was observed with a median concentration of 293 copies/mL (Range 0–2037 copies/mL) (p‐value: 0.04).

This drop was more significant 24 h after delivery with a median concentration of 0 copies/mL (Range 0–95 copies/mL) (p‐value: 0.02).

Conclusions

During labour, no changes in free fetal DNA in maternal plasma were demonstrated. This suggests that labour does not have effect on free fetal DNA release in maternal circulation at term. Copyright © 2003 John Wiley & Sons, Ltd.
Rapid prenatal diagnosis of X‐linked chronic granulomatous disease using a denaturing high‐performance liquid chromatography (DHPLC) system
Authors: Chien Shu‐Chin , Lee Chien‐Nan , Hung Chia‐Cheng , Tsao Po‐Nien , Su Yi‐Ning , Hsieh Fon‐Jou
Published: December 2003

Objective

To describe a family on whom it was possible to perform a rapid prenatal diagnosis for chronic granulomatous disease (CGD) using a denaturing high‐performance liquid chromatography (DHPLC) system.

Methods

For a family whose first‐born, a boy, suffered from X‐linked chronic granulomatous disease, fetal DNA was obtained from an ongoing pregnancy by amniocentesis early in the second trimester. Denaturing high‐performance liquid chromatography and direct sequencing were used to attempt to detect the previously identified X‐linked chronic granulomatous disease mutation.

Results

Our studies predicted that the fetus in question was not likely to be affected by chronic granulomatous disease, which was demonstrated to be correct at birth.

Conclusions

Here, we introduce a molecular diagnostic tool (DHPLC) for an effective and exact prenatal diagnosis of normality for the second‐born child, as determined from amniocentesis during the second trimester. Copyright © 2003 John Wiley & Sons, Ltd.