bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysthymia and chronic depression: Introduction, classification, risk factors, and course
Authors: Klein Daniel N. , Santiago Neil J.
Published: July 2003

Chronic forms of depression are more common and impairing than is generally recognized. This article introduces an In Session issue devoted to dysthymic disorder and chronic depression, and it reviews current knowledge about these disorders. First, we discuss nosological issues, followed by a summary of potential risk factors. Finally, the naturalistic course of chronic depression is described and implications for clinical practice are discussed. © 2003 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Treatment for chronic depression using Cognitive Behavioral Analysis System of Psychotherapy (CBASP)
Authors: McCullough James P.
Published: July 2003

The article presents an overview of the chronic depression construct in the Diagnostic and Statistical Manual of Mental Disorders (DSMs) since 1980, including developmental etiology and psychopathological patterns of the chronically depressed adult. Then the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), an empirically supported psychotherapy and the only therapy developed specifically to treat chronic depression, is described. CBASP addresses the idiosyncratic problems of the chronically depressed adult using Situational Analysis, the Interpersonal Discrimination Exercise, and Behavioral Skill Training/Rehearsal techniques. The first two techniques are illustrated using a verbatim case example. © 2003 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40
Authors: Knowles Wendy A. , Pipkin Pam , Andrews Nick , Vyse Andrew , Minor Philip , Brown David W.G. , Miller Elizabeth
Published: July 2003

Molecular studies suggest that the simian polyomavirus SV40 is present in the human population, possibly introduced in contaminated polio vaccine. However, no recent seroepidemiological data exist in England on SV40 or on the two human polyomaviruses, BKV and JCV. A comparative age seroprevalence study was undertaken on 2,435 residual sera from 1991 by haemagglutination inhibition (HI) for BKV and JCV, and virus neutralisation for SV40. The overall rates of seropositivity for BKV and JCV were 81% and 35%, respectively, and each was significantly related to age (P < 0.001). BKV seroprevalence reached 91% at 5–9 years of age, but JCV seroprevalence reached only 50% by age 60–69 years. There was a highly significant association between BKV antibody titre and age (P < 0.001), titres decreasing linearly at a rate of 8.7% per 10 years (95% CI = 7.4–10% drop). Significantly more males than females had antibody to JCV (P = 0.013). In individuals under 40 years of age there was a significant negative association between the presence of antibody to BKV and JCV (P < 0.001). By contrast, the antibody prevalence to SV40 remained at 1.3–5% throughout all age groups and titres were low. There was a significant positive association between the presence of antibody to SV40 and antibody to both BKV (P < 0.001) and JCV (P = 0.009), and also to the geometric mean titre (GMT) of BKV antibody (P = 0.011). The results indicate that BKV and JCV are transmitted by different routes. There is no serological evidence that SV40 entered the human population during the past 80 years, and the possibility of cross‐reaction with BKV or JCV antibody must be considered. J. Med. Virol. 71:115–123, 2003. © 2003 Wiley‐Liss, Inc.
HAV replication in acute hepatitis with typical and atypical clinical course
Authors: Sagnelli Evangelista , Coppola Nicola , Marrocco Cecilia , Onofrio Mirella , Scarano Ferdinando , Marotta Anna , Scolastico Carlo , Catuogno Antonio , Salzillo Angela , Sagnelli Caterina , Piccinino Felice , Filippini Pietro
Published: July 2003

The correlation between the length of viremia as detected by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and the clinical course of hepatitis A virus (HAV) infection was studied. Sixty‐six consecutive patients with acute hepatitis A who were admitted to hospital in two infectious disease units in southern Italy were enrolled: 57 had a self‐limited course of the disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma HAV RNA was sought by RT‐PCR, using primers made at 5′‐NTR of HAV, designed to amplify a 273‐bp fragment and detected by 2% agarose gel and by hybridization with a specific biotinylated probe. In four patients with prolonged acute hepatitis A, the plasma HAV RNA, which was positive on the day of admission to hospital, was found to be negative from day 62, 46, 84, and 105, respectively, after the onset of the symptoms. In patients with relapsing hepatitis, HAV viremia paralleled the clinical and biochemical course of disease. In all patients with a typical self‐limiting course, clearance of plasma HAV RNA was observed within 20 days of the onset of symptoms. In most patients, plasma HAV viremia became undetectable before the normalization of serum aminotransferases, underlining the importance of the immune reaction in the pathogenesis of acute hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 days of illness may predict a prolonged course of the disease, but relapsing hepatitis remains unpredictable on the basis of plasma HAV determination. J. Med. Virol. 71:1–6, 2003. © 2003 Wiley‐Liss, Inc.
Detection of human papillomavirus in urine and cervical swabs from patients with invasive cervical cancer
Authors: Stanczuk Grazyna A. , Kay Patti , Allan Bruce , Chirara Mike , Tswana Sam A. , Bergstrom Staffan , Sibanda Elopy N. , Williamson Anna‐Lise
Published: July 2003

Despite the high prevalence of both human papillomavirus (HPV) infections and cervical cancer among Zimbabwean women, the ability to test for HPV infection of the uterine cervix is limited by a lack of an easy sample collection method that does not require gynecological examination. The presence of HPVs in urine and cervical swab samples collected from 43 women who presented with invasive cervical cancer was investigated. HPV detection was done by means of degenerate primers in a nested polymerase chain reaction (PCR). Typing of HPVs was done using restriction fragment length polymorphism (RFLP) analysis. HPV was identified and typed in 98% (42/43) of cervical swabs and 72% (31/43) of paired urine samples. HPV type 16 was the most common (25/42, 59%), followed by types: 33 (13/42, 31%), 18 (6/42, 14%), and 31 (1/42, 2%). Type‐specific concordance between cervical and urine samples was high (22/28, 79%). Therefore, the HPV types identified in urine samples in most cases represent the same HPV type infecting the cervical epithelium. The results suggest that urine may be a practical sample for testing of HPV urogenital infection. Further research is required before the detection of HPV in urine can be applied in the routine cervical screening programs. J. Med. Virol. 71:110–114, 2003. © 2003 Wiley‐Liss, Inc.
Mutations within the hepatitis B virus genome among chronic hepatitis B patients with hepatocellular carcinoma
Authors: Bläckberg Jonas , Kidd‐Ljunggren Karin
Published: July 2003

Chronic hepatitis B infection is a major cause of hepatocellular cancer (HCC). The pathogenesis of the carcinogenesis is not fully understood. Viral proteins such as the X protein and the truncated middle S protein have been implicated to be transactivators. In order to investigate whether any mutations within relevant parts of the hepatitis B virus (HBV) genome could be associated with the development of HCC, the genomes of 16 HBV strains from chronic HBV carriers with HCC were studied. Serum samples were subjected to PCR and the HBV DNA sequenced subsequently. Genotypes A–D were represented. The sequence analysis showed that an especially high proportion, 50% (CI 95%, 25–75%), of the patients with HCC carried HBV mutants with deletions or insertions in the N‐terminal half of the pre‐S2 region or had a point mutation in the start codon of pre‐S2 compared with controls with chronic HBV infection, 21% (CI 95%, 3–39%). A high proportion (69%) also had mutations at position 1762 (A → T) and/or 1764 (G → A) in the core promoter region, but the proportion of core promoter mutations was no different from what was found in a control group of HBV carriers without HCC (68%). The pre‐S2 variants, which involve deletions of immunogenic regions, may have a survival advantage as they are mostly found in long‐standing HBV infection. There were no other mutations found frequently within the region coding for the X protein. J. Med. Virol. 71:18–23, 2003. © 2003 Wiley‐Liss, Inc.
Selectively primed adaptive driver RDA (SPAD‐RDA): An improved method for subtractive hybridization
Authors: Birkenmeyer Larry G. , Leary Thomas P. , Muerhoff A. Scott , Dawson George J. , Mushahwar Isa K. , Desai Suresh M.
Published: July 2003

A modification of the Representational Difference Analysis (RDA) method for subtractive hybridization, termed Selectively Primed Adaptive Driver (SPAD) RDA, is described. It differs from conventional RDA primarily in the manner by which initial driver (D) and tester (T) amplicon complexities are determined, and by optimizing the composition of D with respect to T for each round of subtraction. Total nucleic acid is extracted from serum or plasma and converted to double‐stranded DNA/cDNA. A polymerase chain reaction (PCR) primer containing a selective nucleotide(s) at its 3′‐end is used to generate amplicons of reduced complexity. Parallel subtractions are carried out, D vs. T (DT) for enrichment of tester‐unique sequences and D vs. D (Driver Control or DC) to generate an optimized driver for use in the subsequent round. Following each round, agarose gel electrophoresis is used to visually identify any DT‐unique bands through a side‐by‐side comparison of DT and DC subtraction products. In comparison to conventional RDA, SPAD‐RDA achieved greater enrichment of viral sequences from an HCV infected chimpanzee, resulting in isolation of 13.7% of the viral genome, and an overall enrichment for HCV sequences of 239‐fold. Virus fragments were also obtained from an HCV‐infected human sample subtracted against non‐paired human driver sequences. J. Med. Virol. 71:150–159, 2003. © 2003 Wiley‐Liss, Inc.
Evaluating the Performance of International Mutual Funds
Authors: Cumby Robert E. , Glen Jack D.
Published: July 2003

In this paper, the authors examine the performance of a sample of fifteen U.S.-based internationally diversified mutual funds between 1982 and 1988. Two performance measures are used, the Jensen measure and the positive period weighting measure proposed by Mark Grinblatt and Sheridan Titman. They find no evidence that the funds, either individually or as a whole, provide investors with performance that surpasses that of a broad, international equity index over this sample period. Journal of Finance, Vol. 45, No. 2 (June 1990), pp. 497-521. (Reprinted with permission of the Journal of Economic Literature.)
Tie-in arrangements of life insurance and savings
Authors: Venezia Itzhak
Published: July 2003

Cash-value insurance contracts can be viewed as tying life insurance with savings. The main purpose of this article is to provide an economic rationale for this widespread practice. It is assumed that there is an asymmetry of information between the insurers and insureds, where the latter know better their probability of death, and hence adverse selectin may cause a market failure. To overcome this problem, a multiperiod (for exposition purposes a three-period model is used) contract and a single-period contract are offered. The multiperiod contract specifies a savings element which may be received by the insured at his or her discretion.  If the insured lives at the end of the second period. It is shown that by the right choice of the savings element and the return on this element, the insurers can induce insureds to self-select. Insureds with lower probabilities of death will choose the multiperiod contract whereas insureds with higher mortality will choose successive single-period contracts. It is therefore shown that tie-in arrangements of savings and insurance may help the problem of adverse selection and hence an economic rationale is provided for their existence. (reprinted with permission).
Returns and Volatility of Low-Grade Bonds 1977-1989
Authors: Blume Marshall E. , Keim Donald B. , Patel Sandeep A.
Published: July 2003

This paper examines the risks and returns of long-term low-grade bonds for the period 1977-1989. We find: (1) low-grade bonds realized higher returns than higher-grade bonds and lower returns than common stocks, and low-grade bonds exhibited less volatility than higher-grade bonds due to their call features and high coupons; (2) there is no relation between the age of low-grade bonds and their realized returns; cyclical factors explain much of the observed relation between default rates and bond age; and (3) low-grade bonds behave like both bonds and stocks. Despite this complexity there is no evidence that low-grade bonds are systematically over- or under-priced. The Journal of Finance, Vol. XLVI, No. 1 (March 1991), pp. 49-74. (Reprinted with permission of The Journal of Finance.)
A population pharmacokinetic model for paclitaxel in the presence of a novel P‐gp modulator, Zosuquidar Trihydrochloride (LY335979)
Authors: Callies Sophie , De Alwis Dinesh P. , Harris Adrian , Vasey Paul , Beijnen Jos H. , Schellens Jan H. , Burgess Michael , Aarons Leon
Published: July 2003

Aims  To develop a population pharmacokinetic model for paclitaxel in the presence of a MDR modulator, zosuquidar 3HCl.

Methods  The population approach was used (implemented with NONMEM) to analyse paclitaxel pharmacokinetic data from 43 patients who received a 3‐h intravenous infusion of paclitaxel (175 mg m−2 or 225 mg m−2) alone in cycle 2 or concomitantly with the oral administration of zosuquidar 3HCl in cycle 1.

Results  The structural pharmacokinetic model for paclitaxel, accounting for the Cremophor ELTM impact, was a three‐compartment model with a nonlinear model for paclitaxel plasma clearance (CL), involving a linear decrease in this parameter during the infusion and a sigmoidal increase with time after the infusion. The final model described the effect of Zosuquidar 3HCl on paclitaxel CL by a categorical relationship. A 25% decrease in paclitaxel CL was observed, corresponding to an 1.3‐fold increase in paclitaxel AUC (from 14829 µg l−1 h to 19115 µg l−1 h following paclitaxel 175 mg m−2) when zosuquidar Cmax was greater than 350 µg l−1. This cut‐off concentration closely corresponded to the IC50 of a sigmoidal Emax relationship (328 µg l−1). A standard dose of 175 mg m−2 of paclitaxel could be safely combined with doses of zosuquidar 3HCl resulting in plasma concentrations known, from previous studies, to result in maximal P‐gp inhibition.

Conclusions  This analysis provides a model which accurately characterized the increase in paclitaxel exposure, which is most likely to be due to P‐gp inhibition in the bile canaliculi, in the presence of zosuquidar 3HCl (Cmax > 350 µg l−1) and is predictive of paclitaxel pharmacokinetics following a 3 h infusion. Hence the model could be useful in guiding therapy for paclitaxel alone and also for paclitaxel administered concomitantly with a P‐gp inhibitor, and in designing further clinical trials.
Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus
Authors: Ogutu Bernhards R. , Newton Charles R. J. C. , Muchohi Simon N. , Otieno Godfrey O. , Edwards Geoffrey , Watkins William M. , Kokwaro Gilbert O.
Published: July 2003

Aims  Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water‐soluble prodrug, fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and fosphenytoin sodium in children with severe falciparum malaria and status epilepticus.

Methods  Children received intravenous (i.v.) phenytoin as a 18 mg kg−1 loading dose infused over 20 min followed by a 2.5 mg kg−1 12 hourly maintenance dose infused over 5 min (n = 11), or i.v. fosphenytoin, administered at a rate of 50 mg min−1 phenytoin sodium equivalents (PE; n = 16), or intramuscular (i.m.) fosphenytoin as a 18 mg kg−1 loading dose followed by 2.5 mg kg−1 12 hourly of PE (n = 11). Concentrations of phenytoin in plasma and cerebrospinal fluid (CSF), frequency of seizures, cardiovascular effects (respiratory rate, blood pressure, trancutaneous oxygen tension and level of consciousness) and middle cerebral artery (MCA) blood flow velocity were monitored.

Results  After all routes of administration, a plasma unbound phenytoin concentration of more than 1 µg ml−1 was rapidly (within 5–20 min) attained. Mean (95% confidence interval) steady state free phenytoin concentrations were 2.1 (1.7, 2.4; i.v. phenytoin, n = 6), 1.5 (0.96, 2.1; i.v. fosphenytoin, n = 11) and 1.4 (0.5, 2.4; i.m. fosphenytoin, n = 6), and were not statistically different for the three routes of administration. Median times (range) to peak plasma phenytoin concentrations following the loading dose were 0.08 (0.08–0.17), 0.37 (0.33–0.67) and 0.38 (0.17–2.0) h for i.v. fosphenytoin, i.v. phenytoin and i.m. fosphenytoin, respectively.

CSF:  plasma phenytoin concentration ratio ranged from 0.12 to 0.53 (median = 0.28, n = 16). Status epilepticus was controlled in only 36% (4/11) following i.v. phenytoin, 44% (7/16), following i.v. fosphenytoin and 64% (7/11) following i.m. fosphenytoin administration, respectively. Cardiovascular parameters and MCA blood flow were not affected by phenytoin administration.

Conclusions  Phenytoin and fosphenytoin administration at the currently recommended doses achieve plasma unbound phenytoin concentrations within the therapeutic range with few cardiovascular effects. Administration of fosphenytoin i.v. or i.m. offers a practical and convenient alternative to i.v. phenytoin. However, the inadequate control of status epilepticus despite rapid achievement of therapeutic unbound phenytoin concentrations warrants further investigation.
Promoting psychosocial well‐being in unaccompanied asylum seeking young people in the United Kingdom
Authors: Kohli Ravi , Mather Rosie
Published: July 2003

Unaccompanied minors looking for asylum in industrialized nations come with a host of psychosocial needs associated with separation and settlement. They are also resourceful, and willing to make the best of themselves in their new environments. This paper reviews literature concerning vulnerability and resilience that has emerged from refugee related studies, and those from social work with children looked after by local authorities. In combining these two areas of enquiry, the paper tests the messages they contain in reference to the work of a young asylum seekers project run in the United Kingdom. It confirms the view that unaccompanied minors are children first and foremost, exhibiting understandable vulnerabilities associated with separation and trauma, as well as being carriers of capacities that can help them to recover and settle after arrival. In this paper, it is proposed that promoting psychosocial well‐being for unaccompanied minors involves entering the young people's inner and outer worlds with therapeutic care, to aid the processes of self‐recovery. It also involves finding ways to regenerate a lost sense of belonging and of being in charge of their lives. Examples from the project's work with the young people are used to illustrate the complexity of helping them find a sense of home within their new territories.
Effects of boron and calcium nutrition on the establishment of the Rhizobium leguminosarum–pea (Pisum sativum) symbiosis and nodule development under salt stress
Authors: EL‐HAMDAOUI A. , REDONDO‐NIETO M. , RIVILLA R. , BONILLA I. , BOLAÑOS L.
Published: July 2003

The effects of modifying boron (B) and calcium (Ca2+) concentrations on the establishment and development of rhizobial symbiosis in Pisum sativum plants grown under salt stress were investigated. Salinity almost completely inhibited the nodulation of pea plants by Rhizobium leguminosarum bv. viciae 3841. This effect was prevented by addition of Ca2+ during plant growth. The capacity of root exudates derived from salt‐treated plants to induce Rhizobium nod genes was not significantly decreased. However, bacterial adsorption to roots was highly inhibited in plants grown with 75 mM NaCl. Moreover, R. leguminosarum 3841 did not grow in minimal media containing such salt concentration. High Ca2+ levels enhanced both rhizobial growth and adsorption to roots, and increased nodule number in the presence of high salt. Nevertheless, the nodules developed were not functional unless the B concentration was also increased. Because B has a strong effect on infection and cell invasion, these processes were investigated by fluorescence microscopy in pea nodules harbouring a R. leguminosarum strain that expresses green fluorescent protein. Salt‐stressed plants had empty nodules and only those treated with high B and high Ca2+ developed infection threads and exhibited enhanced cell and tissue invasion by Rhizobium. Overall, the results indicate that Ca2+ promotes nodulation and B nodule development leading to an increase of salt tolerance of nodulated legumes.
Modification of the intracellular sugar content alters the incidence of freeze‐induced membrane lesions of protoplasts isolated from Arabidopsis thaliana leaves
Authors: UEMURA M. , STEPONKUS P. L.
Published: July 2003

Sugar content and freezing tolerance of protoplasts of Arabidopsis thaliana leaves were manipulated by incubating seedlings in a sucrose solution before protoplast isolation. Incubation in a 400 mM sucrose solution at 2 °C in the dark increased their freezing tolerance equivalent to that achieved after a conventional cold acclimation at 2 °C. The increased freezing tolerance was due to a decrease in the incidence of freeze‐induced lesions: expansion‐induced lysis (EIL) between −2 and −4 °C and loss of osmotic responsiveness (LOR) between −5 and −12 °C. The concentration of sucrose in the incubation medium required to minimize the incidence of the lesions was substantially different: 10–35 mM for EIL and 30–400 mM for LOR. Incubation in the sucrose solution at 23 °C decreased LOR only at −5 and −6 °C but less than that incubated at 2 °C, and there was no effect on EIL. Incubation in sorbitol solutions at 2 °C also decreased LOR at −5 and −6 °C but much less than in the sucrose solution. These results suggest that low concentrations of sucrose act as a metabolic substrate for the low‐temperature‐induced alterations required for the amelioration of EIL and, at higher concentrations, sucrose has a direct cryoprotective effect to minimize LOR.
An Arabidopsis porB porC double mutant lacking light‐dependent NADPH:protochlorophyllide oxidoreductases B and C is highly chlorophyll‐deficient and developmentally arrested
Authors: Frick Geneviève , Su Qingxiang , Apel Klaus , Armstrong Gregory A.
Published: July 2003

A key reaction in the biosynthesis of chlorophylls (Chls) a and b from cyanobacteria through higher plants is the strictly light‐dependent reduction of protochlorophyllide (Pchlide) a to chlorophyllide (Chlide) a. Angiosperms, unlike other photosynthetic organisms, rely exclusively upon this mechanism to reduce Pchlide and hence require light to green. In Arabidopsis, light‐dependent Pchlide reduction is mediated by three structurally related but differentially regulated NADPH:Pchlide oxidoreductases, denoted as PORA, PORB, and PORC. The PORA and PORB genes, but not PORC, are strongly expressed early in seedling development. In contrast, expression of PORB and PORC, but not PORA, is observed in older seedlings and adult plants. We have tested the hypothesis that PORB and PORC govern light‐dependent Chl biosynthesis throughout most of the plant development by identifying porB and porC mutants of Arabidopsis, the first higher plant por mutants characterized. The porB‐1 and porC‐1 mutants lack the respective POR transcripts and specific POR isoforms because of the interruption of the corresponding genes by a derivative of the maize Dissociation (Ds) transposable element. Single por mutants, grown photoperiodically, display no obvious phenotypes at the whole plant or chloroplast ultrastructural levels, although the porB‐1 mutant has less extensive etioplast inner membranes. However, a light‐grown porB‐1 porC‐1 double mutant develops a seedling‐lethal xantha phenotype at the cotyledon stage, contains only small amounts of Chl a, and possesses chloroplasts with mostly unstacked thylakoid membranes. PORB and PORC thus seem to play redundant roles in maintaining light‐dependent Chl biosynthesis in green plants, and are together essential for growth and development.
Multiple ileal ulcers and an ileal Dieulafoy's lesion induced by loxoprofen sodium
Authors: SUZUKI GAKU , OOISHI MASAE , KATO TAKASHI , KUNIEDA YASUYUKI , ISHIZAKI TADAHUMI , NAKAYAMA MASATO , NAKAJIMA NOBUHISA , YONEYAMA SHIGETO , TAKAGI TOMOTAKA , KATO MOTOTSUGU , ASAKA MASAHIRO
Published: July 2003

Loxoprofen sodium is one of the non‐steroidal anti‐inflammatory drugs (NSAIDs) that is a prodrug. Several adverse effects of the drug have been described, but ileal ulcer has not been reported so far. We experienced an 87‐year‐old male patient with disk herniation complicated with loxoprofen sodium‐induced multiple ileal ulcers and an ileal Dieulafoy's lesion that caused massive intestinal bleeding. The patient was saved by wedge resection of the Dieulafoy's lesion and discontinuance of the NSAID. 99mTc‐red blood cell scintigraphy and intraoperative enteroscopy of the small bowel were useful in the diagnosis. This is the first case of multiple ileal ulcers with an ileal Dieulafoy's lesion induced by loxoprofen sodium.
Beneficial effects of oats in the gluten-free diet of adults with special reference to nutrient status, symptoms and subjective experiences
Authors: Størsrud Stine , Hulthén Lena R. , Lenner Ragnhild A.
Published: July 2003

In several studies oats have been reported to be tolerated by coeliac patients. The aim of the present study was to investigate the nutritional and symptomatic effects of including oats in the gluten-free diet, as well as the patients' subjective experiences. Twenty adult coeliac patients included large amounts of oats in their diet. Food intake, gastrointestinal symptoms, blood samples and body weight were examined and compared with examination at baseline. Diet compliance was checked monthly. The results are based on fifteen patients eating oats for 2 years plus three with only 6-months consumption. The median daily intake of oats was 93 (range 27–137) g/d, and the compliance was good. The mean intakes of Fe and dietary fibre increased (P<0·001) with the oat diet, as well as the intakes of thiamin and Zn (P<0·02). The bioavailability of Fe tended to decrease; this seems not to have influenced the Fe status. Temporary increased flatulence was experienced the first few weeks, as well as improved bowel function with oats in the diet. All patients who carried out the whole study period wanted to continue eating oats after the study, as they found that addition of oats in the gluten-free diet gave more variation, better taste and satiety. Oats improved the nutritional value of the gluten-free diet, had no negative effects on nutritional status and were appreciated by the subjects. Including oats can help coeliac patients following a strict gluten-free diet.
Triiodothyronine administration reverses vitamin A deficiency-related hypo-expression of retinoic acid and triiodothyronine nuclear receptors and of neurogranin in rat brain
Authors: Husson Marianne , Enderlin Valérie , Alfos Serge , Féart Catherine , Higueret Paul , Pallet Véronique
Published: July 2003

Recent studies have revealed that retinoids play an important role in the adult central nervous system and cognitive functions. Previous investigations in mice have shown that vitamin A deficiency (VAD) generates a hypo-expression of retinoic acid (RA, the active metabolite of vitamin A) receptors and of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) and a concomitant selective behavioural impairment. Knowing that RC3 is both a triiodothyronine (T3) and a RA target gene, and in consideration of the relationships between the signalling pathways of retinoids and thyroid hormones, the involvement of T3on RA signalling functionality in VAD was investigated. Thus, the effects of vitamin A depletion and subsequent administration with RA and/or T3on the expression of RA nuclear receptors (RAR, RXR), T3nuclear receptor (TR) and on RC3 in the brain were examined. Rats fed a vitamin A-deficient diet for 10 weeks exhibited a decreased expression of RAR, RXR and TR mRNA and of RC3 mRNA and proteins. RA administration to these vitamin A-deficient rats reversed only the RA hypo-signalling in the brain. Interestingly, T3is able to restore its own brain signalling simultaneously with that of vitamin A and the hypo-expression of RC3. These results obtained in vivo revealed that one of the consequences of VAD is a dysfunction in the thyroid signalling pathway in the brain. This seems of crucial importance since the down regulation of RC3 observed in the depleted rats was corrected only by T3.
Plants and plant extracts for improving animal productivity
Authors: Greathead Henry
Published: July 2003

Plant secondary metabolites are a natural resource that is largely unexploited in ‘conventional’ animal production systems. They have in the past been generally considered as a source of anti-nutritional factors, and not as a source of exploitable performance-enhancing compounds. Recent and continuing changes to legislation controlling the use of animal feed additives have stimulated interest in bioactive secondary metabolites as alternative performance enhancers. They are broadly compatible with current thinking on the future of agriculture and food in Europe, and with consumer opinion. Interest has been largely on their manipulative role in the digestive and absorptive processes of the hindgut. The present paper will review the use of plants and their extracts to manipulate the rumen microbial ecosystem to improve the efficiency of rumen metabolism. The bioavailability of secondary metabolites and their actions on peripheral metabolism will be considered with a view to improving animal performance. The challenge of delivering plants and their extracts to animals outdoors in a controlled manner will be discussed. Much of what is known about the beneficial roles of plant secondary metabolites on animal performance is circumstantial and is based on tenuous data. In order to more fully exploit their bioactive properties for the benefit of animal performance, modes of action need to be understood. Uptake will be dependent on proven efficacy and consumer acceptance of assurances relating to safety, welfare and the environment.
Conjugated linoleic acid and its effects on animal products and health in single-stomached animals
Authors: Azain Michael J.
Published: July 2003

Conjugated linoleic acids (CLA) have been shown to have anti-carcinogenic, anti-obesity, anti-atherogenic and immunomodulatory functions. The basis for these effects has not been fully explained, but probably involves effects of CLA on eicosanoid metabolism, cytokine production and\or gene expression. The predominant isomer (85–90%) in the natural sources of CLA has thecis-9, trans-11 configuration. As interest in CLA grew and synthetic forms became available, the number of studies examining the effects of dietary CLA in rodents, human subjects and livestock has increased greatly. In the late 1990 s the observation that CLA had anti-obesity effects was reported. Subsequently, it was determined that this effect in mice could be attributed to thetrans-10, cw-12 isomer that, along with thecis-9,trans-11 isomer, predominates in the synthetic forms of CLA. The santi-obesity response varies in magnitude depending on species, and has not been consistent in non-rodents. In general, the response is greatest in mice and less or absent in other species. The basis for this lack of consistency is not clear and is unlikely to be accounted for by differences in the source of CLA. In the pig variation in body fat of animals may account for differences in responsiveness. There is no direct evidence of an anti-carcinogenic effect of CLA in human subjects or livestock. Indirect evidence fromin vitrostudies with cell lines, as well as epidemiological studies, suggest that CLA may be relevant as a natural anti-carcinogen. The immunomodulatory effects of CLA may have application in livestock production as an alternative to the use of feed antibiotics, or as a means of improving the response to vaccination and conferring disease resistance. The recent literature on the effects of CLA, with emphasis on its anti-obesity effects, is reviewed.
The co-evolution of people, plants, and parasites: biological and cultural adaptations to malaria
Authors: Etkin Nina L.
Published: July 2003

The urgency generated by drug-resistant strains of malaria has accelerated anti-malarial drug research over the last two decades. While synthetic pharmaceutical agents continue to dominate research, attention increasingly has been directed to natural products. The present paper explores the larger context in which plant use occurs and considers how the selection of medicinal plants has evolved over millennia as part of the larger human effort to mediate illness. First attention is directed to indigenous medicinal plants whose anti-malarial activity is based on an oxidant mode of action, by which intracellular constituents lose electrons (become more electropositive). Next, parallels are drawn between these plant substances and a suite of malaria-protective genetic traits: glucose-6-phosphate dehydrogenase deficiency; haemoglobins S, C and E; α- and β-thalassemias. These erythrocyte anomalies are classic examples of Darwinian evolution, occurring in high frequency in populations who have experienced considerable selective pressure from malaria. Characterized by discrete loci and pathophysiologies, they are united through the phenomenon of increased erythrocyte oxidation. In this model, then, oxidant anti-malarial plants are culturally constructed analogues, and molecular mimics, of these genetic adaptations. To further reinforce the scheme, it is noted that the anti-malarial action of pharmaceutical agents such as chloroquine and mefloquine duplicates both the genetic anomalies and the folk therapeutic models based in oxidant plants. This discussion coheres around a theoretical foundation that relates plant secondary metabolites (oxidants) to plasmodial biochemistry and human biological and cultural adaptations to malaria. Co-evolution provides a theoretical link that illuminates how medical cultures manage the relationships among humans, plants, herbivores and their respective pathogens.
Micronutrient supplementation: when is best and why?
Authors: L'abbé Mary R. , Cockell Kevin A. , Lee Nora S.
Published: July 2003

For many nutrients, a systematic determination of the effects of high intakes over extended periods of time has not been conducted. Governments and scientific bodies have just begun to establish the methodology for, and to conduct, nutrient risk assessments for setting ‘tolerable upper levels of intake’ (UL) for nutrients. Nutrient risk assessment provides the framework for using available information to evaluate the safety of nutrients when added to foods or when consumed as supplements, in order to minimize the risks from over-consumption. When intakes are inadequate, food fortification may be the appropriate choice for some nutrients, while in other situations, when requirements are markedly higher for some population subgroups than for the general population, supplements may be the most appropriate intervention. The present paper will present some examples of how to use the UL along with food consumption data to assess the appropriateness of food fortificationv. supplementation strategies and to assess their impact on nutrient intakes of the population. The important steps to be followed when evaluating which approach is best are: (a) establishing need, i.e. assessing the gap between current and desired intakes; (b) assessing safety, i.e. consider the margin of safety between requirement and UL as well as the severity and reversibility of the adverse effect that was used to establish the UL; (c) estimating exposure through statistical modelling, in which population-based estimates of intakes before and after the intervention are compared; (d) monitoring the impact of the intervention to ensure that the desired benefits are achieved and that excessive intakes are minimized. This approach can optimize the public health benefits of food fortification or supplement use while minimizing the risks due to excessive intakes.
From here to there: a proposed mechanism for transforming journals from closed to open access
Authors: Prosser David C.
Published: July 2003

A major barrier to the greater take‐up of an open access model for journal publishing has been the concern of many journal owners that they will not easily be able to migrate from the current subscription‐based model to open access. This paper presents a potential migration path which should significantly reduce the financial risk to journal owners, while allowing them to offer open access to their authors.
Cooperation and Community Empowerment in Myanmar in the context of Myanmar Agenda 21
Authors: James Helen
Published: July 2003

Since embracing the market economy in 1988 Myanmar has attempted to involve its civil society organisations, particularly in the health, education and welfare sectors. Both domestic and international non‐government organisations play a key role in service delivery, poverty alleviation and capacity building in these areas. Civil society is regarded as a partner in Myanmar's nation‐building processes. As Myanmar emerges from its decades of isolation (1962–88) and seeks to find its place amongst the family of nations, it set out, in Myanmar Agenda 21 (1997), a policy framework for sustainable development consistent with the identified principles of good governance based on cooperation and participative practices. This paper discusses how far this framework has been implemented; the obstacles to continued evolution of the socio‐political structures; and whether civil society, domestic and international, can foster the ‘coming out’ process in a way consistent with Myanmar's concept of nation building and holistic security.
Population, Unemployment and Economic Growth Cycles: A Further Explanatory Perspective
Authors: Fanati Luciano , Manfredi Piero
Published: July 2003

In this paper we investigate the dynamic interaction between economic growth, unemployment, income distribution and population growth. The reference framework combines rational behaviour of agents with endogenous fertility and unemployment, while profits are the determinant of the accumulation of firms. In particular the supply of labour is determined by the micro‐founded fertility choices of individuals. We first demonstrate, consistently with the empirical evidence, the existence of a positive income growth trend with sustained oscillations, therefore providing an alternative explanation of the relation between growth and cycle. Moreover interesting results are given on the relation between unemployment and growth. So far the literature has traditionally shown a negative relation between unemployment and growth (with the exception of the positive relation arising in a Schumpeter ‘creative’ disruption context). In contrast, we find a twofold effect of unemployment (via its effects on population) on economic growth: this can be both positive or negative depending on the relative level of the cost of childrearing of employed and unemployed persons, and on the level of unemployment benefits. This allows us to argue that an increase in unemployment benefit—as has occurred in recent years in many countries such as France and Spain—could lead to wide demo‐economic fluctuations and to a positive effect of unemployment on economic growth.
The National Minimum Wage and Hours of Work: Implications for Low Paid Women*
Authors: Connolly Sara , Gregory Mary
Published: July 2003

The largest group of beneficiaries from the introduction of the National Minimum Wage in the UK were women working part‐time. A potential threat to these wage gains is a reduction in the working hours available, with part‐time (flexible) jobs particularly vulnerable. This paper reports a range of difference‐in‐difference estimates using individual‐level data from the New Earnings Survey and the British Household Panel Survey. No significant changes in hours worked by either full‐ or part‐time women are found 1, 2 and 3 years after the NMW, and no change in the probabilities of remaining in full‐ or part‐time work or transiting between the two.
Using the BHPS Wave 9 Additional Questions to Evaluate the Impact of the National Minimum Wage*
Authors: Stewart Mark B. , Swaffield Joanna K.
Published: July 2003

This paper presents evidence on the impact of the introduction of the National Minimum Wage using specially designed questions added to wave 9 of the British Household Panel Survey. New direct information on the basic hourly wage rate of hourly paid employees demonstrates the almost complete truncation and ‘spike’ at £3.60. The paper presents an analysis of the causes of the differences between hourly wage constructions, and of who has benefited from the introduction of the minimum wage and by how much, and a brief summary of the findings from the other minimum wage questions added to wave 9.
Expression of a 28-Kilodalton Glutathione
S
-Transferase Antigen of
Schistosoma mansoni
on the Surface of Filamentous Phages and Evaluation of Its Vaccine Potential
Authors: Rao Kakuturu V. N. , He Yi-Xun , Kalyanasundaram Ramaswamy
Published: July 2003

A cloning and expression system that allows display of proteins on the surface of filamentous phages was exploited to display a 28-kDa glutathione
S
-transferase (Sm28GST) antigen of the human parasite
Schistosoma mansoni
. The phage-displayed Sm28GST (pdGST) was immunoreactive and was recognized by immune sera, suggesting that the Sm28GST protein displayed on the surface of phages potentially maintains native conformation. Subsequent immunization studies showed that mice can develop high titers of antibodies against pdGST and do not require any additional adjuvant for immunization. Isotype analysis suggested that the pdGST immunization predominantly induced immunoglobulin G2b (IgG2b), IgG3, and IgM anti-GST antibodies in mice. Furthermore, the pdGST immunization was found to confer about 30% protection after a challenge infection with 100 cercariae of
S. mansoni
in BALB/c mice. These findings suggest that phage display is a simple, efficient, and promising tool to express candidate vaccine antigens for immunization against infectious agents.
C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease
Authors: Jobe Dean A. , Lovrich Steven D. , Schell Ronald F. , Callister Steven M.
Published: July 2003

Borreliacidal antibodies specific for outer surface protein C (OspC) are induced shortly after infection withBorrelia burgdorferi. In this study, we identified the region of OspC recognized by immunoglobulin M (IgM) and IgG borreliacidal antibodies. Sera from patients with early Lyme disease were screened for borreliacidal activity specific forB. burgdorferi50772 and OspC antibodies. Seven sera that contained similarly high titers of each response were then chosen randomly and adsorbed with OspC or a truncated OspC (OspC-Dra) containing the 50 amino acids nearest the carboxy terminus. Adsorption with OspC or OspC-Dra completely eliminated the borreliacidal activity in six (86%) of seven sera and significantly decreased the activity in the remaining serum (titer of 10,240 to 1,280). Moreover, OspC antibodies were no longer detected by OspC enzyme-linked immunosorbent assay or in a Western blot that contained native OspC. The findings confirmed that sera from patients with early Lyme disease contain high concentrations of IgM or IgG borreliacidal antibodies that bind a conserved region of OspC.
Analytical Performance of a Highly Sensitive C-Reactive Protein-Based Immunoassay and the Effects of Laboratory Variables on Levels of Protein in Blood
Authors: Aziz Najib , Fahey John L. , Detels Roger , Butch Anthony W.
Published: July 2003

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 μg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4
o
C for short periods of time or at −70
o
C for longer periods and tested within the same run to minimize interassay variability.
Cement Manufacture and the Environment Part II: Environmental Challenges and Opportunities
Authors: van Oss Hendrik G. , Padovani Amy C.
Published: July 2003

Construction materials account for a significant proportion of nonfuel materials flows throughout the industrialized world. Hydraulic (chiefly portland) cement, the binding agent in concrete and most mortars, is an important construction material. Portland cement is made primarily from finely ground clinker, a manufactured intermediate product that is composed predominantly of hydraulically active calcium silicate minerals formed through high‐temperature burning of limestone and other materials in a kiln. This process typically requires approximately 3 to 6 million Btu (3.2 to 6.3 GJ) of energy and 1.7 tons of raw materials (chiefly limestone) per ton (t) of clinker produced and is accompanied by significant emissions of, in particular, carbon dioxide (CO2), but also nitrogen oxides, sulfur oxides, and particulates. The overall level of CO2output, about 1 ton/ton clinker, is almost equally contributed by the calcination of limestone and the combustion of fuels and makes the cement industry one of the top two manufacturing industry sources of this greenhouse gas. The enormous demand for cement and the large energy and raw material requirements of its manufacture allow the cement industry to consume a wide variety of waste raw materials and fuels and provide the industry with significant opportunities to symbiotically utilize large quantities of by‐products of other industries.

This article, the second in a two‐part series, summarizes some of the environmental challenges and opportunities facing the cement manufacturing industry. In the companion article, the chemistry, technology, raw materials, and energy requirements of cement manufacture were summarized. Because of the size and scope of the U.S. cement industry, the article relies primarily on data and practices from the United States.