bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple framework for analysing bull and bear markets
Authors: Pagan Adrian R. , Sossounov Kirill A.
Published: February 2003

Bull and bear markets are a common way of describing cycles in equity prices. To fully describe such cycles one would need to know the data generating process (DGP) for equity prices. We begin with a definition of bull and bear markets and use an algorithm based on it to sort a given time series of equity prices into periods that can be designated as bull and bear markets. The rule to do this is then studied analytically and it is shown that bull and bear market characteristics depend upon the DGP for capital gains. By simulation methods we examine a number of DGPs that are known to fit the data quite well—random walks, GARCH models, and models with duration dependence. We find that a pure random walk provides as good an explanation of bull and bear markets as the more complex statistical models. In the final section of the paper we look at some asset pricing models that appear in the literature from the viewpoint of their success in producing bull and bear markets which resemble those in the data. Copyright © 2002 John Wiley & Sons, Ltd.
Evidence on agglomeration economies, diseconomies, and growth
Authors: Wheeler Christopher H.
Published: February 2003

Conventional urban economic analysis suggests that a local economy's size is closely related to a number of features, including levels of human capital and the availability of specialized inputs, which are likely to influence positively the rate at which it accumulates further economic activity. At the same time, urban theory also suggests that once cities reach a certain level of size, these agglomeration benefits begin to peter out, while diseconomies rise rapidly. Consequently, we should see an ‘inverted U‐shaped’ pattern of growth with respect to economic size—rates of growth first rise, then fall as size increases. This paper shows that, while such a pattern is largely absent from recent data on growth in metropolitan area population and employment, it emerges strikingly in county‐level data. Copyright © 2002 John Wiley & Sons, Ltd.
A structural model of aggregate US job flows: another look
Authors: Schmidt‐Dengler Philipp
Published: February 2003

A recent article (Collard et al., 2002) published in this journal presented a structural model of aggregate job flows. Unrestricted estimation of the model yields parameter estimates that would imply an unemployment rate of 99%. Instead of solving this problem by fixing one of the parameters, as originally attempted by the authors, I add moments regarding the employment rate. The new results call for a re‐evaluation of the model. Copyright © 2003 John Wiley & Sons, Ltd.
Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay
Authors: Talbot J. A. , Spencer K. , Abushoufa R. A.
Published: February 2003

Aim

To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome.

Methods

In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free β‐hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population.

Results

Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free β‐hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free β‐hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237).

When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free β‐hCG was used and some 7% lower than when total hCG was used.

Conclusion

Maternal serum GlyhCG, as measured by the sialic acid–binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester. Copyright © 2002 John Wiley & Sons, Ltd.
Assessment of the thymus at echocardiography in fetuses at risk for 22q11.2 deletion
Authors: Barrea Catherine , Yoo Shi‐Joon , Chitayat David , Valsangiacomo Emanuela , Winsor Elizabeth , Smallhorn Jeffrey F. , Hornberger Lisa K.
Published: February 2003

Objectives

An absent or hypoplastic thymus is common in patients with 22q11.2 deletion (del22q11.2). We sought to determine whether fetal echocardiography could identify absence of the thymus as a diagnostic tool in pregnancies at risk for fetal del22q11.2.

Methods

We evaluated the fetal thymus in 16 consecutive pregnancies at risk for fetal del22q11. Fourteen of the fetuses had a conotruncal cardiac lesion, one had a twin with a conotruncal lesion, and in one the mother had a diagnosis of del22q11.2. The fetal thymus assessment was performed by an individual who was not aware of the del22q11.2 status of the fetus.

Results

By 2D imaging, the thymus was identified in the anterosuperior mediastinum as a subtle hypoechogenic area. In nine cases, the thymus was demonstrated prenatally and none had del22q11.2. However, in one case the thymus was only seen on follow‐up fetal echocardiography. In six cases, the thymus could not be identified and all six had del22q11.2. In one additional case, analyzed retrospectively, the thymus could not be assessed. The status of the thymus was confirmed on postnatal echocardiography or autopsy in 11 of the 15 cases assessed prenatally.

Conclusions

Our study suggests that fetal echocardiography can assess the thymus in most cases at risk for del22q11.2. This information may be useful in counseling women/couples who decline amniocentesis or who are awaiting amniocentesis results. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal management of mosaic tetrasomy 5p
Authors: Reddy Kavita S , Huang Bing
Published: February 2003

An Erratum has been published for this article in Prenatal Diagnosis 2003; 23 (6): 521.

No Abstract.
HLA‐G positive trophoblastic cells in transcervical samples and their isolation and analysis by laser microdissection and QF‐PCR
Authors: Bulmer Judith N. , Cioni Riccardo , Bussani Cecilia , Cirigliano Vincenzo , Sole Francesc , Costa Carlota , Garcia Pilar , Adinolfi Matteo
Published: February 2003

Objective

To assess the frequency of cytotrophoblastic cells in endocervical samples collected by lavage at early stages of gestation using a specific anti‐HLA‐G McAb (G233). From a set of four selected samples, cells identified by immunostaining were collected by laser microdissection and then tested by quantitative fluorescent polymerase chain reaction (QF‐PCR) for the presence of paternally derived DNA markers, in order to establish their fetal origin.

Methods

Syncytial fragments and cytotrophoblastic cells from 23 transcervical samples were identified by immunostaining with McAb G233 reacting against HLA‐G antigen and with antibodies against cytokeratin. Slides from the same samples were also tested by fluorescent in situ hybridization (FISH), while selected samples were analysed by QF‐PCR.

Slides from four samples retrieved from mothers with male fetuses were immunolabelled and then cytotrophoblastic cells, syncytial fragments and maternal epithelial cells were collected by laser microdissection and tested by QF‐PCR.

Results

All endocervical samples retrieved from mothers with male fetuses were found to contain some cells with chromosome Y–specific signals when tested by FISH. Using McAb anti‐ HLA‐G, cytotrophoblastic cellular elements were detected in about 50% of the samples.

From four samples, cellular elements identified by immunostaining as cytotrophoblast or syncytial fragments were collected by laser microdissection and shown to be of fetal origin when tested by QF‐PCR for the presence of fetal DNA markers.

Conclusions

These results confirm that, during an early phase of gestation, fetal cells are released in the lower uterine cavity and that they can be isolated and analysed for prenatal diagnosis of single gene defects and aneuploidies. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal diagnosis of mosaic ring chromosome 22 associated with cardiovascular abnormalities and intrauterine growth restriction
Authors: Chen Chih‐Ping , Chern Schu‐Rern , Chang Tung‐Yao , Lee Chen‐Chi , Chen Li‐Feng , Tzen Chin‐Yuan , Wang Wayseen , Lin Chen‐Ju , Yang Brian P. T. , Yang Lawrence S. T.
Published: February 2003

Objectives

To present the prenatal diagnosis and perinatal findings of mosaic ring chromosome 22.

Case

Amniocentesis was performed at 18 gestational weeks because of an advanced maternal age. Cytogenetic analysis of the cultured amniotic fluid cells revealed mosaicism for ring chromosome 22, 45,XX,‐22[6]/46,XX,r(22)(p13q13.31)[15]. Abnormal fetal sonographic findings included small for gestational age, a ventricular septal defect, and truncus arteriosus. The pregnancy was terminated. Additional phenotypic findings included hypertelorism, epicanthal folds, and abnormal ears. Cytogenetic analysis of the cord blood lymphocytes revealed a complex mosaic karyotype, 45,XX,‐22[7]/46,XX,r(22)(p13q13.31)[82]/46,XX,idic r(22)(p13q13.31;p13q13.31)[11]. Cytogenetic analysis of the hepatocytes also revealed mosaic r(22) with mosaicism for idic r(22) and monosomy 22. The deletion of distal 22q and the duplication of 22q11.2 on idic r(22), and the distal 22q deletion on r(22) were demonstrated by fluorescent in situ hybridization (FISH) analysis using 22q terminal probes at 22q13 and a DiGeorge syndrome critical region probe at 22q11.2. The breakpoint on distal 22q13 and the extent of the duplication of 22q on idic r(22) was determined by examining polymorphic markers specific for chromosome 22 using quantitative fluorescent polymerase chain reaction assays. The chromosomal aberration was of maternal origin.

Conclusion

Molecular and FISH studies allow a better delineation of some prenatally detected aneuploidy syndromes and help elucidate the genetic pathogenesis. Fetuses having mosaic r(22) with a low level mosaicism for r(22) duplication/deletion may present cardiovascular abnormalities and intrauterine growth restriction on prenatal ultrasound. Copyright © 2002 John Wiley & Sons, Ltd.
The clinical application of spectral karyotyping (SKY™) in the analysis of prenatally diagnosed extra structurally abnormal chromosomes (ESACs)
Authors: Yaron Yuval , Carmon Erez , Goldstein Myriam , Voskoboinik Nadia , Ochshorn Yifat , Gelman‐Kohan Zully , Orr‐Urtreger Avi
Published: February 2003

Objective

The prenatal detection of de novo extra structurally abnormal chromosomes (ESACs) presents a challenge because the associated risk for congenital anomaly ranges from 100% to practically none, depending on the chromosomal origin. Despite the use of standard cytogenetic techniques and even fluorescence in situ hybridization (FISH), the origin of some ESACs often remains elusive. Spectral karyotyping (SKY™) is a molecular cytogenetic technique based on the simultaneous analysis of all chromosomes using a unique probe mix that allows the rapid identification of all chromosomes in 24 colors. The purpose of this study was to evaluate the use of SKY in the characterization of prenatally diagnosed de novo ESACs.

Methods

This series includes five cases of de novo ESACs detected prenatally in routine amniocentesis samples performed for advanced maternal age. Cases of inherited ESACs or ESACs defined by standard cytogenetic techniques were excluded.

Results

SKY analysis yielded valuable information, particularly in cases of nonsatellited ESACs: a der(18) and a ring(Y). In a case of a unisatellited der(15), SKY corroborated data obtained by standard cytogenetic techniques and FISH. Finally, in two cases of small bisatellited chromosomes, SKY was noncontributory.

Conclusions

While SKY may be a valuable tool in some cases, especially nonsatellited and ring ESACs, it does have limitations and should be used judiciously in conjunction with other cytogenetic techniques. Copyright © 2003 John Wiley & Sons, Ltd.
The variables affecting nuchal skin‐fold thickness in mid‐trimester
Authors: Lee P. R. , Won H. S. , Chung J. Y. , Shin H. J. , Kim A.
Published: February 2003

Objectives

To find out variables that have an effect on the measured values of nuchal skin‐fold thickness (NT) and to formulate a regression equation on the basis of those variables.

Methods

The data on gestational age (GA), cephalic index (CI), presentation (Pr, vertex or breech), and the presence or absence of nuchal cord (NC) were collected prospectively on 548 normal singleton fetuses between 16 and 24 weeks gestation, and independent correlation of those variables with NT was calculated by multiple regression analysis and a regression equation was produced.

Results

GA had positive correlation and CI had negative correlation with NT. The nuchal skin‐fold was thicker among fetuses with breech presentation rather than those with vertex presentation and increased in the presence of nuchal cord. We calculated the expected NT through these observations: for fetuses presenting vertex, NT = 5.608 + 0.243GA − 0.066CI + NC* and for breech, NT = 2.803 + 0.392GA − 0.066CI + NC*.

Conclusions

This is the first report, which takes GA, CI, Pr, and NC for correlation factors with NT as a whole. These equations and further studies on determining the cutoff values of the nuchal skin‐fold thickness may improve the sensitivity and specificity for the detection of Down syndrome and enable to minimize unnecessary invasive procedures such as amniocentesis or cordocentesis. Copyright © 2003 John Wiley & Sons, Ltd.
Refill compliance in type 2 diabetes mellitus: a predictor of switching to insulin therapy?
Authors: Spoelstra José A. , Stolk Ronald P. , Heerdink Eibert R. , Klungel Olaf H. , Erkens Joëlle A. , Leufkens Hubert G. M. , Grobbee Diederick E.
Published: February 2003

Objective

To assess whether switching to insulin therapy in patients with type 2 diabetes mellitus is associated with medication refill compliance of oral hypoglycemic agents.

Research Design and Methods

The PHARMO Record Linkage System was used as data source for this study. Patients with newly treated type 2 diabetes mellitus were defined as subjects in whom oral hypoglycemic therapy was initiated between 1991 and 1998. We performed a matched case‐control study in this cohort. Cases were patients who switched to insulin therapy. Date of switching in the case was defined as the index date. Controls were subjects still on oral therapy on the index date, matched on duration of diabetes and calendar time. We measured the medication refill compliance in the year starting 18 months before the index date and calculated various compliance indices.

Results

In total, 411 cases and 411 matched controls were identified. Cases suffered more often from more severe comorbidity and used a higher number of oral hypoglycemic agents and concomitant non‐diabetic drugs. The overall compliance rate did not differ significantly between cases and controls, the adjusted odds ratio (OR) was 1.3 (CI 95% 0.6–2.8). After performing multivariate logistic regression modeling, age at onset of diabetes, gender, comedication, combination therapy, and daily dosage frequency, were independently related to switching.

Conclusions

We were unable to confirm the hypothesis that noncompliance with treatment is more prevalent in patients with secondary failure. Other variables, like comorbidity and disease‐related factors seem to play a more important role in switching to insulin therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Prescriptions of systemic antibiotics for children in Germany aged between 0 and 6 years
Authors: Schindler Christoph , Krappweis Jutta , Morgenstern Ingolf , Kirch Wilhelm
Published: February 2003

Limited information is available about systemic antibiotic use among children in Germany. We therefore assessed prescription patterns by office‐based physicians to analyse antibiotic consumption in early childhood. A total of 331 children < 6 years were eligible for inclusion. The number of antibiotic prescriptions, consumed daily doses, number of treatment courses, types of antibiotics and diagnoses for prescribing were determined. The prevalence of systemic antibiotic treatment was 42.9%. Antibiotic consumption was highest between 2 and 3 years of age (55.8%). The percentage of children receiving one, two or three courses of antibiotic treatment was 49.3, 28.2 and 16.2%, respectively. Acute otitis media (32.2%), upper respiratory tract infections (18.9%), tonsillitis (15.9%) and acute bronchitis (15.4%) were principal indications for treatment. Macrolides were most frequently prescribed (48.1%), followed by penicillin V (21.3%), broad‐spectrum penicillins (14.3%), sulfonamides (10.5%) and cephalosporins (5.8%). Antibiotics not recommended for particular indication were selected in 5–43% of cases. The considerable prescription of systemic antibiotics to children in many European countries is also the case in Germany. A noteworthy trend emerged for suboptimal prescribing with second‐line antibiotics. As such treatment may be associated with the development of bacterial resistance, improved guidelines for antibiotic treatment should be drawn up and enforced. Copyright © 2002 John Wiley & Sons, Ltd.
Current Awareness: Pharmacoepidemiology and Drug Safety
Authors:   John Wiley & Sons, Ltd.
Published: February 2003

In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.
Improving the quality of adverse drug reaction reporting by 4th‐year medical students
Authors: Rosebraugh Curtis J. , Tsong Yi , Zhou Feng , Chen Min , Corken Mackey Ann , Flowers Charlene , Toyer Denise , Flockhart David A. , Honig Peter K.
Published: February 2003

Purpose

Evaluate whether a 15‐minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms.

Methods

Seventy‐eight 4th‐year medical students were randomized to intervention ‘Group‐A’ or non‐intervention ‘Group‐B’ on the first day of a required five‐day clinical pharmacology rotation. Group‐A participants attended a 15‐minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group‐B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA.

Results

Seventy‐eight MedWatch forms were evaluated (Group‐A=40, Group‐B = 38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non‐intervention group (p < 0.004).

Conclusions

As little as a 15‐minute intervention can significantly improve the quality of adverse drug reaction reporting by 4th‐year medical students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students. Copyright © 2003 John Wiley & Sons, Ltd.
For the good of the patient: risks and benefits of medicines
Authors: Breckenridge Alasdair
Published: February 2003

The basis of regulation of medicines is an assessment of risk and benefit. As the process of drug development has evolved with the advances in scientific knowledge, new and more precise methods of measuring drug efficacy have been created. Pharmacovigilance must also change with as much emphasis being placed on demonstrating the safety of a medicine as on preventing harm. Communication of these issues to interested parties remains problematical with room for considerable improvement. Copyright © 2003 John Wiley & Sons, Ltd.
The use of anti‐asthmatic medications among pediatric patients in Taiwan
Authors: Chen Chi‐Yu , Chiu Hui‐Fen , Yeh Ming‐Kung , Chang Chih‐Ching , Yang Chun‐Yuh
Published: February 2003

Purpose

To describe the use of anti‐asthma drugs in Taiwanese pediatric patients.

Methods

Using the data from the database of Bureau of National Health Insurance, we analyze the patterns and extent of medication use among asthma patients less than 18 years old. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) Classification system.

Results

Data on a total of 290 467 children were included in the study. Overall, patients were treated more frequently with oral medications. 69.43 and 40.24% of patients were using oral β‐agonists (OBAs) and methylxanthines respectively. Monotherapy with OBAs was the most popular regimen, accounting for 13.70% of the total prescriptions studied. Only 6.70% of patients were taking inhaled corticosteroids (ICSs). During the studied period, users of ICSs were using an average of 1.65 canisters.

Conclusions

The current practices of asthma management in Taiwan fall short of the goals stated in international guidelines. Anti‐inflammatory agents were being underused in Taiwanese pediatric patients. Copyright © 2003 John Wiley & Sons, Ltd.
Drug‐induced renal function impairment: a population‐based survey
Authors: Monster Taco B. M. , de Jong Paul E. , de Jong‐van den Berg Lolkje T. W. ,   for the PREVEND Study Group
Published: February 2003

Purpose

The knowledge that drugs can affect renal function is mainly based on experimental studies or case reports. Thus, it has only been investigated in selected populations. Here we describe drug groups associated with altered renal function in the general population.

Methods

To study this, we used baseline data of 8592 subjects of a population‐based cohort. Hyper‐ and hypofiltration were defined as a filtration above or below the 90% confidence interval of age‐and‐sex‐corrected creatinine clearance. Drug use was measured in the year preceding the kidney function measurement.

Results

The prevalence of hyperfiltration (4.6% in the general population) was higher among subjects using anti‐diabetics (11.7%), dermatological corticosteroids (5.9%) and sex hormones (5.8%), but lower in subjects using anti‐thrombotics (2.4%) and diuretics (2.1%). Hypofiltration (4.3% in the general population) was seen more often in users of beta blockers (6.2%), ACE inhibitors (7.1%), statins (7.2%), anti‐thrombitics (6.8%), trimethoprim (7.9%), vaccines (9.4%), NSAIDs (5.2%), anti‐ulcer agents (6.3%), laxatives (7.7%) and eyedrops (6.7%).

Conclusions

Several drug groups found in this overview were to be expected, since patients with kidney diseases often use them (e.g. cardiovascular drugs). Several other drug groups were somewhat unexpected and deserve further attention. Copyright © 2003 John Wiley & Sons, Ltd.
M. Bäckström, T. Mjörndal and R. Dahlqvist, ‘Spontaneous reporting of adverse drug reactions by nurses’. Pharmacoepidemiology and Drug Safety11(8): 647–650
Authors: Bäckström M. , Mjörndal T. , Dahlqvist R.
Published: February 2003

The original article to which this Erratum refers was published in Pharmacoepidemiology and Drug Safety 11(8): 647–650.
1H and 13C NMR conformational study of 2‐(benzotriazol‐1‐yl)‐substituted tetrahydrofurans
Authors: Katritzky Alan R. , Akhmedov Novruz G. , Ghiviriga Ion , Denisko Olga V. , Steel Peter J.
Published: February 2003

Assignments of the proton and carbon NMR signals for 2‐(benzotriazol‐1‐yl)tetrahydrofurans 1–6 are based on 1H–1H COSY, NOESY, 1H–13C heteronuclear HETCOR, 1H–13C heteronuclear long‐range HETCOR‐LR and nuclear Overhauser enhancement experiments, and supported by selective spin decoupling experiments. The electronic and steric effects of the 2‐benzotriazolyl substituent on the 1H and 13C NMR chemical shifts are evaluated and discussed. Conformational isomers cis and trans are distinguished by the magnitude of the J(H−2,H−3) coupling constant, by one‐bond 1J(C−2, H−2) coupling constants and by 13C chemical shifts of the C‐2 anomeric carbon. The benzotriazol‐1‐yl group prefers the pseudo‐axial orientation in each of 1–6. The stereochemistry and conformation of 6 are rigorously demonstrated by an x‐ray structure. Copyright © 2003 John Wiley & Sons, Ltd.
Cyclopropylbenzene ring opening by chlorine atom: radicals or radical ions?
Authors: Trukhin Aleksei V. , Eliseenkov Evgeny V. , Dneprovskii Aleksei S.
Published: February 2003

Cyclopropylbenzene radical chlorination leads to hydrogen atom abstraction and to ring opening. The contribution of the last process is increased in the presence of acids and in polar solvents. It is suggested that the ring opening process proceeds via radical cation formation by single electron transfer from cyclopropylbenzene to the chlorine atom in the first stage of reaction. Copyright © 2003 John Wiley & Sons, Ltd.
Theoretical study of the gas‐phase decomposition of neutral α‐amino acid ethyl esters. Part 2—Elimination of ethyl picolinate and ethyl 1‐methylpipecolinate
Authors: Notario Rafael , Quijano Jairo , León Luis A. , Sánchez Claudia , Quijano J. Camilo , Alarcón Gustavo , Chamorro Eduardo , Chuchani Gabriel
Published: February 2003

Theoretical studies of the thermolysis in the gas phase of two α‐amino acid ethyl esters, ethyl picolinate and ethyl 1‐methylpipecolinate, were carried out using ab initio theoretical methods, at the MP2/6–31G(d) and MP2/6–311+G(2d,p) levels of theory. The reactions studied have two steps: the first corresponds to the formation of a neutral amino acid intermediate via a six‐membered cyclic transition state, and the second is the rapid decarboxylation of this intermediate via a five‐membered cyclic transition state. The progress of the first step of the reactions was followed by means of the Wiberg bond indices. The results indicate that the transition states have an intermediate character between reactants and products, and the calculated synchronicities show that the reactions are concerted and slightly asynchronous. The bond‐breaking processes are more advanced than the bond‐forming processes, indicating a bond deficiency in the transition states. The kinetic parameters calculated for both reactions agree very well with the available experimental results. Copyright © 2003 John Wiley & Sons, Ltd.
Theory and example of a small‐molecule motor
Authors: Mock William L. , Ochwat Krzysztof J.
Published: February 2003

Conceptual principles for operation of a molecular motor stipulate that such a species must consist of an energy‐consuming catalyst that exhibits within its mechanism temporal overlap of successive catalytic cycles, so as to induce irreversible intramolecular motion during operation. The exothermic hydration reaction of MeCOCHCNCMe3 brought about by catalyst HO2CCH2OCMe(CO2H)2 qualifies as such a process, in the form of serial conversion between canonical carboxylic anhydride structures within the catalyst. The steady‐state kinetic behavior and inactivation by methanol demonstrate the operation of an appropriate repetitive catalytic loop in this case. Copyright © 2003 John Wiley & Sons, Ltd.
A new blue light‐emitting oligofluorene glass: synthesis, characterization and photophysical properties
Authors: Belfield Kevin D. , Bondar Mykhailo V. , Morales Alma R. , Yavuz Ozlem , Przhonska Olga V.
Published: February 2003

The synthesis, electrochemical, thermal and spectroscopic properties of the oligoaminofluorene derivative 9,9‐didecyl‐N,N‐bis(9,9‐didecyl‐7‐N,N‐diphenylaminofluoren‐2‐yl)‐N,N‐diphenylfluorene‐2,7‐diamine (4), an organic glass, were investigated in solvents of differing polarity at room and 77 K temperature, including quantum yield and lifetime. The oligomer exhibited a glass transition near room temperature and was thermally stable to ca 400 °C. Intramolecular interactions between the fluorenyl chromophores were investigated. The relatively complex nature of the emission band of 4 was characterized by reduced anisotropy and two components in its fluorescence decay at room temperature. Emission spectra of 4 at 77 K exhibited a single component in its fluorescence decay and a dependence on the excitation wavelength at the red edge of the absorption band. A spectroscopic model of 4 is proposed to explain the observed spectral behavior of this potentially important electroluminescent material. Copyright © 2003 John Wiley & Sons, Ltd.
Correlation analysis between equilibria for addition of semicarbazide and hydroxylamine to several carbonyl compounds and their equilibria for addition of water
Authors: Malpica A. , Calzadilla M.
Published: February 2003

Equilibrium constants for semicarbazide and hydroxylamine addition to several carbonyl compounds are reported and compared with those for addition of water. The results are correlated by the linear free relationship log Kadd = Sw + B, where w is a measure of the reactivity of a given compound to water addition, S is a measure of the sensitivity of the examined reactions compared with the model of hydration equilibrium constants and B is a constant for a given reaction series. Copyright © 2003 John Wiley & Sons, Ltd.
Diversity of Neuromuscular Pathology in Lethal Multiple Pterygium Syndrome
Authors: Cox Phillip M. , Brueton Louise A. , Bjelogrlic Predrag , Pomroy Penelope , Sewry Caroline A.
Published: February 2003

Lethal multiple pterygium syndrome (LMPS) is an uncommon fetal-onset disorder of unknown etiology. The pathogenesis of LMPS has been suggested to be early-onset fetal akinesia, fragile collagen, or generalized edema. Information on the neuromuscular pathology of LMPS in the literature is generally scanty. We present the findings from a review of 14 fetuses with features of LMPS from the archives of the Hammersmith Hospital Perinatal Pathology Department. Autopsy reports, photographs, fetograms, and histological sections were examined, and additional special stains and immunostaining were performed on muscle sections. In five cases, there was evidence of autosomal recessive inheritance. One case was later shown to be due to glycogen storage disease type IV. The skeletal muscle bulk was reduced in all fetuses and the remaining muscle showed a range of histological appearances including vacuolar degeneration, dystrophy, a generalized or patchy myotubular appearance, and generalized hypotrophy. In one, the histological appearance was essentially normal. Two cases had abnormalities in the brain. Large motor neurons were present in the anterior spinal horns of all fetuses in whom the spinal cord could be examined. There was no evidence of cartilaginous joint fusion. We conclude that LMPS is the phenotype resulting from fetal akinesia commencing in the first or early second trimester. In the majority of cases, the precise underlying cause will not be identified, however, occasionally a metabolic or neurodevelopmental disorder or a specific primary myopathy may be demonstrated, providing adequate autopsy investigations are undertaken.
Real-time Polymerase Chain Reaction as an Aid for the Detection of SYT-SSX1 and SYT-SSX2 Transcripts in Fresh and Archival Pediatric Synovial Sarcoma Specimens: Report of 25 Cases from St. Jude Children's Research Hospital
Authors: Hill D. Ashley , Riedley Shannon E. , Patel Anami R. , Shurtleff Sheila A. , Hyer Jennifer , Cain Alvida M. , Billups Catherine A. , Downing James R. , Pappo Alberto S.
Published: February 2003

Synovial sarcoma is the most common nonrhabdomyosarcomatous soft tissue sarcoma in children and adolescents and is characterized by a reciprocal t(X;18)(p11;q11) which results in the fusion of the SYT gene on chromosome 18q11 to either of two closely related genes, SSX1 (Xp11.23) or SSX2 (Xp11.21). Detection of this translocation or its resultant gene fusion by molecular methods is helpful in the pathologic diagnosis of synovial sarcoma, especially in poorly differentiated tumors. This study was designed to evaluate the utility of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect and distinguish SYT-SSX1 and SYT-SSX2 fusions in fresh and archival specimens of synovial sarcoma in pediatric patients seen at St. Jude Children's Research Hospital. In addition, the clinico-pathologic features of the tumors with SYT-SSX1 vs. SYT-SSX2 fusions were compared. The 25 patients studied had a median age of 13 years 9 months (range 5 to 19 years). Estimates of survival and event-free survival at 5 years were 78.7 ± 10.5% and 56.2 ± 13.2%, respectively. Seventeen (68%) tumors were monophasic, eight (32%) were biphasic. Seven tumors contained poorly differentiated areas. Positive results for either SYT-SSX1 or SYT-SSX2 were obtained in 21/25 (84%) cases. Three cases did not have a detectable gene fusion and one had no amplifiable RNA. SYT-SSX1 transcripts were found in 18/24 (75%) of the tumors while SYT-SSX2 transcripts were identified in 3/24 (12.5%). All of the poorly differentiated tumors and seven out of eight tumors from patients who developed lung metastases had an SYT-SSX1 fusion transcript. Real-time PCR is useful in detecting and distinguishing SYT-SSX1 from SYT-SSX2 gene fusions in synovial sarcoma. Valuable aspects of this methodology are the applicability to both frozen and formalin-fixed samples, decreased labor costs, and the rapidity of results. In addition, distinguishing SYT-SSX1 from SYT-SSX2 fusions with these methods allow for prospective collection of information that may clarify issues of prognostic relevance.
Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts
Authors: Hsueh Wei , Caplan Michael S. , Qu Xiao-Wu , Tan Xiao-Di , De Plaen Isabelle G. , Gonzalez-Crussi F.
Published: February 2003

Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-α (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.
Double Charges in Case of Posting of Employees: The Guiot Judgment and its Effects on the Construction Sector
Authors: Houwerzijl Mijke , Pennings Frans
Published: February 2003

A company which performs services by employing its workers in another Member State may be confronted with the obligation to pay contributions to social funds in both the country of establishment and the country of employment. It follows that in some cases there is a tension between on the one hand, the law concerning the freedom to provide services and, on the other hand, national labour law and social security law. In other cases there is a tension between the law on providing services and the EU law concerning the free movement of workers. This article is concerned with these tensions and outlines the case law of the Court of Justice in this field. In the Guiot Judgment, the Court considered an obligation to contribute to funds in both countries in some circumstances to be an infringement on the free movement of services. A consequence of this Judgment is that the employee may lose his entitlement to an advantage to which he would have been entitled under the law on the free movement of workers even if it is more attractive than the corresponding advantage in the country of establishment. We describe the problems in this area and the solution realized by employers' and employees' organisations in Belgium and the Netherlands by making a bilateral agreement.
Pension Systems and Reforms – Britain, Hungary, Italy, Poland and Sweden
Authors: Augusztinovics Maria
Published: February 2003

This paper provides a brief summary of the main findings of a crosscountry comparative project, completed in 1996 by an international research team. The comparison is rather unique in that it includes three established capitalist societies and two transition economies – two distinct groups of countries with different demographic and economic characteristics. The apparent dichotomy, however, is less clear in respect of pension issues: on the one hand, pension systems and reforms are specific to individual countries; on the other, there are common features and problems which cut across the systemic barrier. One of the major conclusions is that attempting to separate social assistance from social insurance is a more substantial issue for pension reforms than the simplistic choice between ‘public, pay-as-you-go’ and ‘private, funded’ schemes.
Beyond Social Security: The Economic Value of Giving Money to Unemployed People
Authors: Clasen Jochen
Published: February 2003

Within a traditional social security perspective, the quality of national income maintenance schemes tends to be assessed and compared as far as the degree of income protection is concerned. The respective embeddedness of transfer programmes within national political economies has received much less attention. By contrasting unemployment insurance systems in three European countries, this article discusses both sets of cross-national differences with an emphasis on identifying country-specific roles of benefit programmes, over and above the provision of transfers for those out of work; that is as substituting employment regulation and contributing to labour mobility and maintaining collaborative industrial relations in Denmark; as reinforcing work incentives and allowing wages to fall, particularly for younger workers in Britain; and acting as an instrument for workforce restructuring by circumventing labour law regulation in Germany. These functions are rarely addressed in cross-national comparisons of income maintenance systems but are crucial for a fuller understanding of the role of social security in modern capitalism.
Implementing Social Security in a Market System – An Analysis of the Purchaser Provider Relationship in the Provision of Reintegration Services
Authors: Bergsma Esther , Mullenders Pé
Published: February 2003

In the Netherlands, a market system is being introduced in the implementation of social security. One of the crucial assumptions of a market system is that a purchaser buys services from a provider, and will be able to stimulate a good price/quality ratio. On the basis of a specific case, the provision of reintegration services for the partially disabled, we analyse this purchaser-provider relationship. First, we analyse decisions taken in the provision of reintegration services. Then we analyse various aspects of the purchaser-provider relationship in terms of the concepts used by Bartlett and LeGrand. They identified conditions which have to be satisfied for a market to be able to achieve its aims. Considering some inherent imperfections of the purchaser-provider relationship, we argue that the quality of social security services will not be guaranteed automatically. We therefore recommend independent supervision of the quality of social security implementation.
Interaction of the verotoxin 1B subunit with soluble aminodeoxy analogues of globotriaosyl ceramides
Authors: MYLVAGANAM Murugesapillai , HANSEN Henrik C. , BINNINGTON Beth , MAGNUSSON Göran , NYHOLM Per-Georg , LINGWOOD Clifford A.
Published: February 2003

Specific hydroxy groups of the terminal disaccharide unit of globotriaosyl ceramide (Gb3Cer) were identified from binding studies with deoxyGb3Cer and verotoxins (VTs) [Nyholm, Magnusson, Zheng, Norel, Binnington-Boyd and Lingwood (1996) Chem. Biol. 3, 263—275]. Four such hydroxy groups (2′′, 4′′, 6′′ and 6′) were each substituted with an amino group and the corresponding deoxyamino globotrioses were conjugated to a ceramide-like aglycone which contained an adamantyl group instead of an acyl chain. Such aglycone modification significantly enhanced the water-solubility of the glycoconjugates [Mylvaganam and Lingwood (1999) Biochem. Biophys. Res. Commun. 257, 391—394]. The inhibitory potential of these soluble aminodeoxy conjugates on the binding of VT1 to Gb3Cer immobilized on an ELISA plate was evaluated. Only the 2′′ and the 6′ deoxyamino conjugates were effective inhibitors (IC50 10μM); the 4′′ and 6′′ conjugates were ineffective up to 10mM. To evaluate the importance of incorporating a rigid adamantyl hydrocarbon group into the ceramide aglycone, globotriaose was conjugated to a t-butylacetamido or an adamantaneacetamido aglycone. By similar ELISAs, only the adamantaneacetamido conjugate inhibited the binding of VT1 to Gb3Cer. When deoxyamino conjugates were adsorbed to silica on TLC plates, only the 2′′ and 6′′ conjugates bound VT1 and VT2. By a similar TLC assay, acetamido derivatives of 2′′ and 6′ deoxyamino conjugates showed less binding to VT1 and VT2. Neither the crystallographically determined structure of the VT1—globotriaose complex nor modelling studies fully explain the binding patterns shown by these deoxyamino glycoconjugates. Enhanced solvation of the ammonium group of the deoxyamino conjugate could enforce greater constraints in the binding interactions.
Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells
Authors: DUNCAN Roger F. , PETERSON Hazel , HAGEDORN Curt H. , SEVANIAN Alex
Published: February 2003

Dysregulated cell growth can be caused by increased activity of protein synthesis eukaryotic initiation factor (eIF) 4E. Dysregulated cell growth is also characteristic of atherosclerosis. It is postulated that exposure of vascular cells, such as endothelial cells, smooth muscle cells and monocytes/macrophages, to oxidants, such as oxidized low-density lipoprotein (oxLDL), leads to the elaboration of growth factors and cytokines, which in turn results in smooth muscle cell hyperproliferation. To investigate whether activation of eIF4E might play a role in this hyperproliferative response, vascular cells were treated with oxLDL, oxidized lipid components of oxLDL and several model oxidants, including H2O2 and dimethyl naphthoquinone. Exposure to each of these compounds led to a dose- and time-dependent increase in eIF4E phosphorylation in all three types of vascular cells, correlated with a modest increase in overall translation rate. No changes in eIF4EBP, eIF2 or eIF4B modification state were observed. Increased eIF4E phosphorylation was paralleled by increased presence of eIF4E in high-molecular-mass protein complexes characteristic of its most active form. Anti-oxidants at concentrations typically employed to block oxidant-induced cell signalling likewise promoted eIF4E phosphorylation. The results of this study indicate that increased eIF4E activity may contribute to the pathophysiological events in early atherogenesis by increasing the expression of translationally inefficient mRNAs encoding growth-promoting proteins.
Extensive temporally regulated reorganization of the lipid raft proteome following T-cell antigen receptor triggering
Authors: BINI Luca , PACINI Sonia , LIBERATORI Sabrina , VALENSIN Silvia , PELLEGRINI Michela , RAGGIASCHI Roberto , PALLINI Vitaliano , BALDARI Cosima T.
Published: February 2003

Signalling by immunoreceptors is orchestrated at specific plasma membrane microdomains, referred to as lipid rafts. Here we present a proteomics approach to the temporal analysis of protein association with lipid rafts following T-cell antigen receptor (TCR) triggering. We show that TCR engagement promotes the temporally regulated recruitment of proteins participating in the TCR signalling cascade to lipid rafts. Furthermore, TCR triggering results in profound modifications in the composition of lipid rafts involving a number of proteins associated either directly or indirectly with both plasma and intracellular membranes. Raft-associated proteins can be clustered according to their temporal profile of raft association. The data identify lipid rafts as highly dynamic structures and reveal a dramatic impact of surface TCR triggering not only on components of the TCR signalling machinery but also on proteins implicated in a number of diverse cellular processes.