bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the genome and structural proteins of hepatitis C virus resolved from infected human liver
Authors: Nielsen Søren U. , Bassendine Margaret F. , Burt Alastair D. , Bevitt Debra J. , Toms Geoffrey L.
Published: May 2004

In the absence of satisfactory cell culture systems for hepatitis C virus (HCV), virtually all that is known about the proteins of the virus has been learned by the study of recombinant proteins. Characterization of virus proteins from patients with HCV has been retarded by the low virus titre in blood and limited availability of infected tissue. Here, the authors have identified a primary infection in a liver transplanted into an immunodeficient patient with chronic HCV. The patient required re-transplant and the infected liver, removed 6 weeks after the initial transplant, had a very high titre of HCV, 5×109International Units (IU) per gram of liver. The density distribution of HCV in iodixanol gradients showed a peak at 1·04 g ml−1with 73 % of virus below 1·08 g ml−1. Full-length HCV RNA was detected by Northern blotting and the ratio between positive- and negative-strand HCV RNA was determined as 60. HCV was partially purified by precipitation with heparin/Mn2+and a single species of each of the three structural proteins, core, E1 and E2, was detected by Western blotting. The molecular mass of core was 20 kDa, which corresponds to the mature form from recombinant sources. The molecular mass of glycoprotein E1 was 31 kDa before and 21 kDa after deglycosylation with PNGase F or endoglycosidase H. Glycoprotein E2 was 62 kDa before and 36 kDa after deglycosylation, but E2-P7 was not detected. This was in contrast to recombinant sources of E2 which contain E2-P7.
Development of a homology model for clade A human immunodeficiency virus type 1 gp120 to localize temporal substitutions arising in recently infected women
Authors: Poss Mary , Holley David C. , Biek Roman , Cox Harold , Gerdes John
Published: May 2004

The virus population transmitted by a human immunodeficiency virus type 1 (HIV-1) infected individual undergoes restriction and subsequent diversification in the new host. However, in contrast to men, who have limited virus diversity at seroconversion, there is measurable diversity in viral envelope gene sequences in women infected with clade A HIV-1. In this study, virus sequence diversity in three unrelated, clade A infected women preceding and shortly after seroconversion was evaluated. It was demonstrated that there is measurable evolution of envelope gene sequences over this time interval. Furthermore, in each of the three individuals, amino acid substitutions arose at five or six positions in sequences derived at or shortly after seroconversion relative to sequences obtained from the seronegative sample. Presented here is a model of clade A gp120 to determine the location of substitutions that appeared as the virus population became established in three clade A HIV-1 infected women.
Adverse effects of short‐acting beta‐agonists: Potential impact when anti‐inflammatory therapy is inadequate
Authors: WRAIGHT Jonathan M. , SMITH Andrew D. , COWAN Jan O. , FLANNERY Erin M. , HERBISON G. Peter , TAYLOR D. Robin
Published: May 2004

Background:  Short‐acting beta‐agonists (SABAs) are associated with reduced lung function and increased bronchial hyper‐responsiveness. Earlier studies have failed to show that these changes are clinically important when SABAs are taken regularly in modest doses. However, some patients use SABAs to excess, especially with deteriorating asthma. Our aim was to establish whether adverse effects of SABAs are greater at higher than normal doses and after withdrawing inhaled corticosteroid (ICS) therapy.

Methodology:  This was a randomized controlled study. The treatments were salbutamol/ipratropium 100 µg/20 µg/puff or ipratropium 20 µg/puff, each 12 puffs daily. Phase 1 was of 2 weeks duration. During phase 2 ICS were withdrawn until loss of control (LOC) occurred.

Results:  During phase 1 the mean FEV1 fell by 9.3% with salbutamol (0.26 L; 95% C.I. 0.13, 0.39), but by only 1.6% with ipratropium (0.05 L; 95% C.I. −0.06, 0.16; P= 0.006). During phase 2 FEV1 fell by a further 18.9% with salbutamol (0.54 L; 95% C.I. 0.39, 0.69), but by only 10.5% (0.33 L; 95% C.I. 0.17, 0.49; P= 0.032) with ipratropium. Time to LOC was significantly shorter with salbutamol (8.9 days) compared to ipratropium (16.8 days; P= 0.03).

Conclusion:  Adverse changes in lung function with SABA appear to be greater with higher doses and increasing airway inflammation. This highlights the risks of excessive SABA use in patients who neglect ICS therapy and/or who rely on ‘relievers’.
Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells in a patient with acromegaly
Authors: FESSLER Michael B. , COOL Carlyne D. , MILLER York E. , SCHWARZ Marvin I. , BROWN Kevin K.
Published: May 2004

Abstract:  Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a rare disorder that most often presents clinically as obliterative bronchiolitis, but has also been associated with ectopic corticotropin syndrome. We describe a 49‐year‐old lifetime non‐smoking female with longstanding cough, progressive exertional dyspnoea, and fixed airflow limitation, who presented with acromegaly. Head magnetic resonance imaging revealed a pituitary microadenoma and open lung biopsy revealed a multifocal proliferation of neuroendocrine cells which were immunopositive for both corticotropin and growth hormone‐releasing hormone. To our knowledge, this is the first report of acromegaly associated with IDHPNC, and supports the possibility that IDHPNC may fall at one extreme of the spectrum of disorders encountered in multiple endocrine neoplasia type 1.
A case of idiopathic pulmonary alveolar proteinosis accompanied by T‐cell receptor gene rearrangement in bronchoalveolar lavage fluid cells
Authors: HOSOKAWA Takeshi , YAMAGUCHI Etsuro , SHIRAI Shinya , FUKE Satoshi , TAKAOKA Kazuo , KOJIMA Jun‐ichiro , NAKATA Koh , NISHIMURA Masaharu
Published: May 2004

Abstract:  We describe a case of a patient with idiopathic pulmonary alveolar proteinosis (PAP), who had an elevated serum level of antigranulocyte‐macrophage colony stimulating factor (anti‐GM‐CSF) antibody accompanied by T‐cell receptor gene rearrangements in BAL fluid cells. Histopathological examination of the lung excluded lymphoma but revealed PAP and silicosis. There was no detectable serum anti‐GM‐CSF antibody in 50 outpatients with advanced silicosis who did not have PAP, suggesting that anti‐GM‐CSF antibody is directly linked to PAP but not to silicosis. We speculate that monoclonal expansion of a T‐cell population may play a role in the production of anti‐GM‐CSF antibody and the development of PAP.
Predictive risk factors for chronic renal failure in primary high‐grade vesico‐ureteric reflux
Authors: Caione P. , Villa M. , Capozza N. , De Gennaro M. , Rizzoni G.
Published: May 2004

OBJECTIVE

To evaluate and define the risk factors predictive of chronic renal failure (CRF) in children with severe bilateral primary vesico‐ureteric reflux (VUR), observed within the first year of life and with a long follow‐up.

PATIENTS AND METHODS

The study comprised 50 patients presenting with grade 3–5 bilateral VUR diagnosed in the first year of life; 12 were suspected prenatally and confirmed shortly after birth, before any urinary tract infection (UTI). The mean (range) follow‐up was 6.3 (1–16) years. The variables considered within the first year of life were: gender, prenatal diagnosis with no UTI, number of febrile UTIs, serum creatinine and urea nitrogen levels, metabolic acidosis, proteinuria, 24‐h urine output, hypertension, bilateral renal length on ultrasonography and renal scarring on renal scintigraphy. CRF was defined as a creatinine clearance of <80 mL/min/1.73 m2 at the last follow‐up. The results were assessed using univariate and multivariate analyses (backward‐stepwise multiple regression) of the selected variables.

RESULTS

CRF was detected at the last follow‐up in 27 patients (54%), all boys, while renal function was normal in 23 (46%; seven girls). None of the 12 patients with prenatal diagnosis had UTI, but six had CRF. Febrile UTI was the presenting symptom in 38 (76%) patients and 17 (34%) of them had renal scarring. There was no significant difference between the prenatally detected VUR and febrile UTI group in the outcome as CRF. The univariate and multiple regression analysis showed that the first serum creatinine threshold of >6 mg/L before 1 year old was the most significant risk factor for CRF (P < 0.001; odds ratio 1.25).

CONCLUSIONS

Children with primary bilateral high‐grade VUR and a serum creatinine of > 6 mg/L in the first year of life have a significant risk of developing CRF in the long‐term. Prenatal diagnosis and postnatal febrile UTI do not modify the outcome for renal function.
A re‐assessment of the role of combined androgen blockade for advanced prostate cancer
Authors: Klotz L. , Schellhammer P. , Carroll K.
Published: May 2004

Combined androgen blockade is a controversial topic, which has arguments both for and against. It is revisited by the authors of this mini‐review, with a full discussion on the benefits and cautions with this approach. A wide range of other issues is also addressed in this section: bilateral testicular cancer, male‐factor infertility, and buccal mucosa urethroplasty. All of these are of interest to general urologists, as well as to those with a more specific area of interest.
Male‐factor infertility: do we really need urologists? A gynaecological view
Authors: Nicopoullos J.D.M. , Gilling‐Smith C. , Ramsay J.W.A
Published: May 2004

The Royal College of Obstetricians and Gynaecologists state that male factor infertility is responsible for up to 25% of all cases of infertility and may contribute in a further 25%. Where the role of the urologist ends and gynaecologist begins in these couples is a matter of debate. We therefore discuss the management of these couples and the need for a multidisciplinary approach.
Consensus statement on urethral trauma
Authors: Chapple C. , Barbagli G. , Jordan G. , Mundy A.R. , Rodrigues‐Netto N. , Pansadoro V. , McAninch J.W.
Published: May 2004

In this continuation of the section on genitourinary trauma, the authors describe the consensus on urethral injury. This is an in‐depth statement, describing all aspects of the condition, from anatomy to general recommendations.
Urodynamic findings before and after noninvasive management of bladder calculi
Authors: Millán‐Rodríguez F. , Errando‐Smet C. , Rousaud‐Barón F. , Izquierdo‐Latorre F. , Rousaud‐Barón A. , Villavicencio‐Mavrich H.
Published: May 2004

OBJECTIVES

To determine the most frequent urodynamic observations associated with bladder calculi, and to assess whether the presence of calculi alters these observations.

PATIENTS AND METHODS

Fifty patients with bladder stones were included in a prospective study in which two urodynamic tests were used, one at inclusion and another once the patient was stone‐ free after treatment by noninvasive methods (mainly extracorporeal shockwave lithotripsy).

RESULTS

The results from the urodynamic evaluation with the stone in the bladder were: bladder outlet obstruction in 51%, detrusor overactivity in 68%, detrusor under‐activity in 10%, and a normal study in 18%. There were no significant differences between the urodynamic study before or after treatment in maximum flow rate and postvoid residual volume, detrusor overactivity and detrusor pressure at maximum flow.

CONCLUSIONS

Conversely to what has been accepted for years, bladder calculi are not always associated with bladder outlet obstruction and the urodynamic results are not influenced by the presence of bladder stones during the urodynamic testing.
An open‐label, randomized, flexible‐dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction
Authors: Eardley I. , Wright P. , MacDonagh R. , Hole J. , Edwards A.
Published: May 2004

Two papers in this section deal with well‐known pharmacological agents used to treat male erectile dysfunction. In the first of these, authors from the UK compared the efficacy and safety of sildenafil and apomorphine in such patients. This open‐label crossover trial suggested that sildenafil was better than apomorphine, where the primary endpoint was the erectile function domain of the International Index of Erectile Function.

The second paper is an update on the efficacy and safety of tadalafil. It describes the results of its use in a large number of men with erectile dysfunction, compared to placebo. Once again, the erectile function domain was one of the primary endpoints. Tadalafil was an effective and well tolerated treatment for this condition.

OBJECTIVE

To compare the efficacy and safety of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED).

PATIENTS AND METHODS

In all, 139 men with ED who were naïve to treatment were entered into an open‐label crossover trial with two treatment periods, each of 8 weeks, separated by a 2‐week washout period. Men were randomized to receive either sildenafil then apomorphine or apomorphine then sildenafil, and were allowed to titrate the dose on both drugs. The primary endpoint was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and other endpoints included diary data, the other domains of the IIEF, overall assessment questions and the Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire.

RESULTS

The EF domain score after treatment was 25.2 for sildenafil and 15.9 for apomorphine. The treatment difference of the adjusted means was 9.3 points (95% confidence interval 7.6–11.1; P < 0.001). After sildenafil the successful intercourse rate was 75%, vs 35% for apomorphine (P < 0.001), and the EDITS scores were 82.5 for sildenafil and 46.8 for apomorphine (P < 0.001). Of the men, 96% expressed a preference for sildenafil as a treatment for their ED. The side‐effect profiles for both drugs were in keeping with published data.

CONCLUSION

By all measurable endpoints sildenafil was superior to apomorphine in this open‐label crossover study of men with ED who were naïve to therapy
The efficacy and safety of tadalafil: an update
Authors: Carson C.C. , Rajfer J. , Eardley I. , Carrier S. , Denne J.S. , Walker D.J. , Shen W. , Cordell W.H.
Published: May 2004

OBJECTIVE

To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase‐5 inhibitor, in the treatment of erectile dysfunction (ED).

PATIENTS AND METHODS

In all, 2102 men (mean age 56 years) with mild‐to‐severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed ‘on‐demand’ doses of 10 or 20 mg in 11 randomized, double‐blind, placebo‐controlled trials lasting 12 weeks. The three co‐primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of ‘yes’ responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ).

RESULTS

Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline (P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP‐Q3) was 58% and 68%, respectively, compared with 31% in the placebo group (P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo (P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia.

CONCLUSION

Tadalafil was an effective and well‐tolerated treatment for ED.
Risk behaviours and benign prostatic hyperplasia
Authors: Kang D. , Andriole G.L. , Van De Vooren R.C. , Crawford D. , Chia D. , Urban D.A. , Reding D. , Huang W.‐Y. , Hayes R.B.
Published: May 2004

In many men from the PLCO screening trial authors from the USA identified risk factors for BPH. Their findings are interesting; Asian Americans were at the lowest risk of clinical BPH, with alcohol and possibly cigarettes related to a lower risk for the condition.

Three further papers investigate various epidemiological aspects of LUTS. I think that it is important for we urologists to have a sound epidemiological knowledge of this subject, to answer the increasingly educated questions of our patients.

A further paper from Barcelona describes the results of a urodynamic study in patients with bladder calculi. The authors found that bladder stones are not necessarily associated with BOO, and that the results of urodynamic testing are not influenced by their presence.

OBJECTIVE

To identify risk factors for benign prostatic hyperplasia (BPH).

SUBJECTS AND METHODS

Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer.

RESULTS

Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5–0.9), physician‐diagnosed BPH (0.3, 0.2–0.5) and transurethral prostatectomy (TURP, 0.2, 0.1–0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7–0.9), BPH (0.7, 0.6–0.8) and TURP (0.6, 0.4–0.8) but dose–response patterns were weak.

CONCLUSION

Asian‐Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH.
The use of Raman spectroscopy to identify and characterize transitional cell carcinoma in vitro
Authors: Crow P. , Uff J.S. , Farmer J.A. , Wright M.P. , Stone N.
Published: May 2004

OBJECTIVE

To determine whether Raman spectroscopy can be used to differentiate between normal, inflammatory and malignant bladder pathologies in vitro, and secondly if it can used to grade and stage transitional cell carcinoma (TCC).

MATERIALS AND METHODS

In all, 1525 Raman spectra were measured from 75 bladder samples comprising normal bladder, cystitis, carcinoma in situ (CIS), TCC and adenocarcinoma. Multivariate analysis was applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to determine the histological diagnosis of each sample from its Raman spectrum.

RESULTS

The diagnostic algorithms could be used to accurately differentiate among the pathological groups, in particular, a three‐group algorithm differentiated among normal bladder, cystitis and TCC/CIS with sensitivities and specificities of > 90%. Algorithms could also accurately characterize TCC in terms of splitting them into low (G1/G2) or high (G3) grade and superficial (pTa) or invasive (pT1/pT2) stage.

CONCLUSION

Raman spectroscopy can be used to accurately identify and grade/stage TCC in vitro. The technique therefore shows promise for use as an objective method to assist the pathologist in assessing bladder pathologies. Raman spectroscopy also has potential to provide immediate pathological diagnoses during surgical procedures. Following the promising results of this in vitro study, in vivo cystoscopic studies are planned.
Coping with bladder exstrophy: diverse results from early attempts at functional urinary tract surgery
Authors: Baird A.D. , Sanders C. , Woolfenden A. , Gearhart J.P.
Published: May 2004

Authors from Liverpool address the issue of quality of life in exstrophy patients, and assess the long‐term results of surgery for this condition. Their study not only yields interesting results, but the reader is also made aware of the problems there can be in conducting such a study.

Risk factors for developing chronic renal failure in patients with high‐grade VUR are described by authors from Rome. All patients were diagnosed in the first year of life, and the mean (range) follow‐up was 6.3 (1–16) years. The findings were of interest, although the reader may not be very surprised to hear that they found bilateral high‐grade reflux and existing renal damage to be the main predictors of subsequent chronic renal failure.

OBJECTIVES

To report the long‐term surgical outcome in a group of patients with bladder exstrophy treated from 1960 to 1982, and to assess physical health, social integration and sexual function, as attempts at functional closure during the development of this surgery resulted in patients with differing surgical status of the genitourinary organs.

PATIENTS AND METHODS

A review of medical record archives revealed 36 patients; of these, seven had died, six were untraceable and six declined to participate, leaving 15 evaluable subjects (seven men and eight women, mean age at follow‐up, 35 years). Data were collected from medical records and direct interviews were conducted using a semi‐structured questionnaire, after obtaining informed consent. The Short Form‐36 (SF‐36) v2 Health Survey instrument was used to assess health and well‐being.

RESULTS

Three patients have retained the use of their bladder, and 11 had initial bladder closure but required (at a mean age of 3.1 years) various urinary diversions. Eight patients had a pelvic osteotomy. Of 27 functioning renal units, 25 are in reasonable to good condition. Six men and six women had genital reconstruction. Four men are capable of penetrative intercourse and ejaculate; six women manage penetrative intercourse and five have orgasms. All patients attended mainstream school and 13 achieved examination success. Nine patients took vocational training and 11 work full‐time. Five patients are married and five are in long‐term relationships. Two men have achieved three pregnancies and one women has had a child. The mean total SF‐36 score (maximum 3600) was 2763 in men and 2235 in women.

CONCLUSIONS

Surgery for bladder exstrophy has been developing for more than 40 years and the legacy of early attempts at functional closure is a population of adults who have a diversity of lower urinary tracts, good preservation of renal function overall and acceptable sexual function. They are usually robust, healthy and well‐adjusted individuals functioning well in society, often in full‐time employment and long‐term relationships. Adolescent follow‐up must be clearly focused, incorporating a multidisciplinary team approach to facilitate a seamless transition into adulthood.
Photon-Induced Kondo Satellites in a Single-Electron Transistor
Authors: Kogan Andrei , Amasha Sami , Kastner M. A.
Published: May 2004

We measure the differential conductance of a single-electron transistor (SET) irradiated with microwaves. The spin-entangled many-electron Kondo state produces a zero-bias peakin the dc differential conductance if the quantum dot in the SET contains an unpaired electron. When the photon energy
hf
is comparable to the energy width of the Kondo peak and to
e
(the charge on the electron) times the microwave voltage across the dot, satellites appear in the differential conductance shifted in voltage by ±
hf/e
from the zero-bias resonance. We also observe an overall suppression of the Kondo features with increasing microwave voltage.
High Pore Fluid Pressure May Cause Silent Slip in the Nankai Trough
Authors: Kodaira Shuichi , Iidaka Takashi , Kato Aitaro , Park Jin-Oh , Iwasaki Takaya , Kaneda Yoshiyuki
Published: May 2004

Silent-slip events have been detected at several subduction zones, but the cause of these events is unknown. Using seismic imaging, we detected a cause of the Tokai silent slip, which occurred at a presumed fault zone of a great earthquake. The seismic image that we obtained shows a zone of high pore fluid pressure in the subducted oceanic crust located down-dip of a subducted ridge. We propose that these structures effectivelyextend a region of conditionallystable slips and consequently generate the silent slip.
How the Human Animal Found Its Self
Authors: Woolfson Adrian
Published: May 2004

Flesh in the Age of Reason
The Modern Foundations of Body and Soul. by Roy Porter. Norton, New York, 2004. 592 pp. $29.95. ISBN 0-393-05075-0. Allen Lane (Penguin), London, 2003. £25. ISBN 0-713-99149-6.

In his last book, Porter reviews 18th-century arguments about the mind, body, and soul to explore the interplay among "the moral, the material, and the medical" in Enlightenment Britain.
Leukaemia/lymphoma cell microparticles in childhood mature B cell neoplasms
Authors: Savaşan S , Büyükavcı M , Buck S , Ravindranath Y
Published: May 2004

Aims:Because of the observation of an abundance of leukaemia/lymphoma cell microparticles in the bone marrow aspiration sample of a patient with Burkitt’s leukaemia at diagnosis, the occurrence of this phenomenon in leukaemia/lymphoma samples with available immune phenotyping data was investigated retrospectively.

Methods:Flow cytometric immune phenotyping and spontaneous apoptosis analysis of the bone marrow mononuclear cell preparation of the index case were performed. Microparticles isolated form the bone marrow sample were also studied for the presence of leukaemia/lymphoma cell microparticles. List mode analysis of 225 cases of acute leukaemia or lymphoma with previously performed immune phenotyping was also carried out.

Results:The presence of leukaemia/lymphoma cell microparticles could be detected by flow cytometry and they were found to be different from apoptotic bodies. Leukaemia/lymphoma cell microparticles were released in all cases of mature B cell neoplasms studied, although this phenomenon was rare in precursor B cell disorders and acute myeloid leukaemia.

Conclusions:The generation of leukaemia/lymphoma cell microparticles in mature B cell neoplasms appears to be a common phenomenon. The pathogenesis and clinical implications must be investigated.
Chlamydia trachomatisserovar E isolates from patients with different clinical manifestations have similar courses of infection in a murine model: host factors as major determinants ofC trachomatismediated pathogenesis
Authors: Lyons J M , Ito J I , Morré S A
Published: May 2004

Background:Some investigators have proposed an association between certainChlamydia trachomatisserovars and the clinical course of infection in humans. A recent study of over 1100 patients with culture confirmed and serotypedC trachomatisurogenital infection detected no such association.

Aims:To corroborate these results using a murine model of female genital tract infection.

Methods:Various parameters of infection were assessed in mice intravaginally infected with human genital isolates ofC trachomatisserovar E from four cases with either a clear symptomatic or asymptomatic clinical course in both the patient and their partner.

Results:No differences were seen among the strains in the incidence or duration of infection, polymorphonuclear granulocyte responses, or upper genital tract progression.

Conclusions:An investigation to determine the correlation between the clinical manifestations of different isolates ofC trachomatisserovar E in humans and certain parameters of microbial pathogenesis in a mouse model failed to reveal an association between the measured parameters and the tendency of serovar E to produce symptomatic versus asymptomatic infections in humans. These findings suggest that differences in the clinical course of infection in humans seen with these strains may be more related to host factors than to genetic variation among strains.
Identification of three novel RB1 mutations in Brazilian patients with retinoblastoma by “exon by exon” PCR mediated SSCP analysis
Authors: Braggio E , Bonvicino C R , Vargas F R , Ferman S , Eisenberg A L A , Seuánez H N
Published: May 2004

Aims:To carry out a retrospective study, screening for mutations of the entire coding region of RB1 and adjacent intronic regions in patients with retinoblastoma.

Methods:Mutation screening in DNA extracts of formalin fixed, paraffin wax embedded tissues of 28 patients using combined “exon by exon” polymerase chain reaction mediated single strand conformational polymorphism analysis, followed by DNA sequencing.

Results:Eleven mutations were found in 10 patients. Ten mutations consisted of single base substitutions; 10 were localised in exonic regions (eight nonsense, one missense, and one frameshift) and another one in the intron–exon splicing region. Three novel mutations were identified: a 2 bp insertion in exon 2 (g.5506–5507insAG, R73fsX77), a G to A transition affecting the last invariant nucleotide of intron 13 (g.76429G>A), and a T to C transition in exon 20 (g.156795T>C, L688P). In addition, eight C to T transitions, resulting in stop codons, were found in five different CGA codons (g.64348C>T, g.76430C>T, g.78238C>T, g.78250C>T, and g.150037C>T). Although specific mutation hotspots have not been identified in the literature, eight of the 11 mutations occurred in CGA codons and seven fell within the E1A binding domains (codons 393–572 and 646–772), whereas five were of both types—in CGA codons within E1A binding domains.

Conclusions:CGA codons and E1A binding domains are apparently more frequent mutational targets and should be initially screened in patients with retinoblastoma. Paraffin wax embedded samples proved to be valuable sources of DNA for retrospective studies, providing useful information for genetic counselling.
Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma
Authors: Esposito I , Menicagli M , Funel N , Bergmann F , Boggi U , Mosca F , Bevilacqua G , Campani D
Published: May 2004

Background:Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness.

Aims:To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance.

Methods:Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker.

Results:There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages.

Conclusions:Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.
SELECTING TEXTILE PRODUCTS BY MANUFACTURING COMPANIES UNDER UNCERTAINTY
Authors: BALLESTERO ENRIQUE
Published: May 2004

Textile manufacturing companies are interested in selecting the best fibers and fabrics from their marketing properties and production characteristics. Many firms often face scenarios where the relative significance of each fabric characteristic can be hardly measured, and then the managers' decisions on fabric choice are made under uncertainty. To help determine a ranking of products intended for selection, an uncertainty model for cautious managers is proposed. A case study is developed dealing with seven fabric properties (tensile strength, shrinkage, pilling, density, fastness to light, fabric weight, and flame retardance) and four production characteristics (market price of materials, period of delivery, density, and required manufacturing processes), the opportunity set consisting of 132 fabrics.
A JOINT EOQ MODEL FOR SUPPLIER AND RETAILER WITH DETERIORATING ITEMS
Authors: LIN CHINHO , LIN YIHSU
Published: May 2004

The paper studies the joint inventory model between supplier and retailer relying on mutual cooperation. Unlike other studies, the deteriorated rate and partial back-ordering are consistent with assumptions for dealing with more general cases. Since it is difficult to solve this problem directly, we derived the sufficient and necessary conditions in the planning horizon, and proposed a procedure to find the optimal solution. Numerical examples and sensitivity analyses are also provided to illustrate the solution procedure. The results reveal that the extensions of the model provide a wider and reasonable situation in practice, and that they also reduce the total cost.
A USE OF NONPARAMETRIC TESTS FOR DEA-DISCRIMINANT ANALYSIS: A METHODOLOGICAL COMPARISON
Authors: SUEYOSHI TOSHIYUKI , HWANG SHIUH-NAN
Published: May 2004

Discriminant Analysis (DA) is a statistical tool that can predict the group membership of a newly sampled observation. Sueyoshi (European Journal of Operational Research, 115 (1999) 564; 131 (2001) 324; 152 (2004) 45) and Sueyoshi and Kirihara (International Journal of Systems Science, 29 (1998) 1249) have recently proposed a new type of nonparametric DA approach that provides a set of weights of a linear discriminant function, consequently yielding an evaluation score for the determination of group membership. The nonparametric DA is referred to as "Data Envelopment Analysis-Discriminant Analysis (DEA-DA)," because it maintains its discriminant capabilities by incorporating the nonparametric feature of DEA into DA. In this study, a use of two statistical tests is proposed for DEA-DA and its discriminant capability is compared with DEA from a perspective of financial analysis.
APPROXIMATE EFFICIENCY FOR n-SET MULTIOBJECTIVE FRACTIONAL PROGRAMMING
Authors: KUMAR NARENDER , BUDHRAJA R. K. , MEHRA APARNA
Published: May 2004

In this paper, we introduce new concepts of ε-weak efficient solutions and ε-efficient solutions for a nonconvex multiobjective fractional programming problem involving n-set functions. Using an ε-parametric approach and a new theorem of alternative for nonconvex n-set functions, some necessary and sufficient conditions for ε-approximate solutions are derived
DIFFERENTIAL EVOLUTION FOR SOLVING MULTIOBJECTIVE OPTIMIZATION PROBLEMS
Authors: SARKER RUHUL , ABBASS HUSSEIN A.
Published: May 2004

The use of evolutionary strategies (ESs) to solve problems with multiple objectives [known as vector optimization problems (VOPs)] has attracted much attention recently. Being population-based approaches, ESs offer a means to find a set of Pareto-optimal solutions in a single run. Differential evolution (DE) is an ES that was developed to handle optimization problems over continuous domains. The objective of this paper is to introduce a novel Pareto-frontier differential evolution (PDE) algorithm to solve VOPs. The solutions provided by the proposed algorithm for two standard test problems, outperform the "strength Pareto evolutionary algorithm", one of the state-of-the-art evolutionary algorithm for solving VOPs.
FITTING A TABLE TO A PAGE USING NONLINEAR OPTIMIZATION
Authors: BEAUMONT NICHOLAS
Published: May 2004

It is sometimes difficult to fit a large table comprising several rows and columns onto a page. The usual tactic is to manually adjust column widths, abbreviate some text, and/or change some cells' font sizes until the table fits onto a page. We show that it is possible to express the problem of adjusting column widths so as to minimize the height of a table as an optimization problem with nonlinear constraints. Five test problems were routinely solved using a free software package. We stress that the solutions are approximate because the model imperfectly simulates how many lines of a cell of a table will be required to contain a segment of text, but they appear to provide good approximations in difficult cases. The scant literature is summarized; the formulation and solution techniques outlined; examples are described; and differences between theoretical and actual answers explained. It would be possible to incorporate the calculations in word processing and typesetting packages such as Word and TeX.
RADIATIVE CAPTURE OF POLARIZED NEUTRONS BY POLARIZED PROTONS
Authors: RAMACHANDRAN G. , DEEPAK P. N.
Published: May 2004

A model-independent irreducible tensor approach is presented for the np fusion reaction. Appropriate spin-observables are identified to determine empirically the initial spin singlet and triplet contributions to the differential cross-section, in view of the recent experimental interest in studying radiative capture of polarized neutrons by polarized protons.
ANCESTRAL MAXIMUM LIKELIHOOD OF EVOLUTIONARY TREES IS HARD
Authors: ADDARIO-BERRY LOUIGI , CHOR BENNY , HALLETT MIKE , LAGERGREN JENS , PANCONESI ALESSANDRO , WAREHAM TODD
Published: May 2004

Maximum likelihood (ML) (Neyman, 1971) is an increasingly popular optimality criterion for selecting evolutionary trees. Finding optimal ML trees appears to be a very hard computational task — in particular, algorithms and heuristics for ML take longer to run than algorithms and heuristics for maximum parsimony (MP). However, while MP has been known to be NP-complete for over 20 years, no such hardness result has been obtained so far for ML.

In this work we make a first step in this direction by proving that ancestral maximum likelihood (AML) is NP-complete. The input to this problem is a set of aligned sequences of equal length and the goal is to find a tree and an assignment of ancestral sequences for all of that tree's internal vertices such that the likelihood of generating both the ancestral and contemporary sequences is maximized. Our NP-hardness proof follows that for MP given in (Day, Johnson and Sankoff, 1986) in that we use the same reduction from VERTEX COVER; however, the proof of correctness for this reduction relative to AML is different and substantially more involved.
CLUSTERING OF AMINO ACIDS FOR PROTEIN SECONDARY STRUCTURE PREDICTION
Authors: ZHENG WEI-MOU
Published: May 2004

Simple hidden Markov models are proposed for predicting secondary structure of a protein from its amino acid sequence. Since the length of protein conformation segments varies in a narrow range, we ignore the duration effect of length distribution, and focus on inclusion of short range correlations of residues and of conformation states in the models. Conformation-independent and -dependent amino acid coarse-graining schemes are designed for the models by means of proper mutual information. We compare models of different level of complexity, and establish a practical model with a high prediction accuracy.
EFFICIENTLY FINDING REGULATORY ELEMENTS USING CORRELATION WITH GENE EXPRESSION
Authors: BANNAI HIDEO , INENAGA SHUNSUKE , SHINOHARA AYUMI , TAKEDA MASAYUKI , MIYANO SATORU
Published: May 2004

We present an efficient algorithm for detecting putative regulatory elements in the upstream DNA sequences of genes, using gene expression information obtained from microarray experiments. Based on a generalized suffix tree, our algorithm looks for motif patterns whose appearance in the upstream region is most correlated with the expression levels of the genes. We are able to find the optimal pattern, in time linear in the total length of the upstream sequences. We implement and apply our algorithm to publicly available microarray gene expression data, and show that our method is able to discover biologically significant motifs, including various motifs which have been reported previously using the same data set. We further discuss applications for which the efficiency of the method is essential, as well as possible extensions to our algorithm.
MULTIVARIATE ENTROPY DISTANCE METHOD FOR PROKARYOTIC GENE IDENTIFICATION
Authors: OUYANG ZHENGQING , ZHU HUAIQIU , WANG JIN , SHE ZHEN-SU
Published: May 2004

A new simple method is found for efficient and accurate identification of coding sequences in prokaryotic genome. The method employs a Shannon description of artificial language for DNA sequences. It consists in translating a DNA sequence into a pseudo-amino acid sequence with 20 fundamental words according to the universal genetic code. With an entropy-density profile (EDP), the method maps a sequence of finite length to a vector and then analyzes its position in the 20-dimensional phase space depending on its nature. It is found that the ratio of the relative distance to an averaged coding and non-coding EDP over a small number (up to one) of open reading frames (ORFs) can serve as a good coding potential. An iterative algorithm is designed for finding a set of "root" sequences using this coding potential. A multivariate entropy distance (MED) algorithm is then proposed for the identification of prokaryotic genes; it has a feature to combine the use of a coding potential and an EDP-based sequence similarity analysis. The current version of MED is unsupervised, parameter-free and simple to implement. It is demonstrated to be able to detect 95–99% genes with 10–30% of additional genes when tested against the RefSeq database of NCBI and to detect 97.5–99.8% of confirmed genes with known functions. It is also shown to be able to find a set of (functionally known) genes that are missed by other well-known gene finding algorithms. All measurements show that the MED algorithm reaches a similar performance level as the algorithms like GeneMark and Glimmer for prokaryotic gene prediction.
TECHNIQUES FOR OPTIMIZATION OF QUERIES ON INTEGRATED BIOLOGICAL RESOURCES
Authors: LACROIX ZOÉ , RASCHID LOUIQA , ECKMAN BARBARA A.
Published: May 2004

Today, scientific data are inevitably digitized, stored in a wide variety of formats, and are accessible over the Internet. Scientific discovery increasingly involves accessing multiple heterogeneous data sources, integrating the results of complex queries, and applying further analysis and visualization applications in order to collect datasets of interest. Building a scientific integration platform to support these critical tasks requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web, as well as data that are locally materialized in warehouses or generated by software. The lack of efficiency of existing approaches can significantly affect the process with lengthy delays while accessing critical resources or with the failure of the system to report any results. Some queries take so much time to be answered that their results are returned via email, making their integration with other results a tedious task. This paper presents several issues that need to be addressed to provide seamless and efficient integration of biomolecular data. Identified challenges include: capturing and representing various domain specific computational capabilities supported by a source including sequence or text search engines and traditional query processing; developing a methodology to acquire and represent semantic knowledge and metadata about source contents, overlap in source contents, and access costs; developing cost and semantics based decision support tools to select sources and capabilities, and to generate efficient query evaluation plans.
Climate Research and Reinsurance*
Authors: Murnane Richard J.
Published: May 2004

Extreme weather events produce some of the most deadly and costly natural disasters and are a major concern of the catastrophe reinsurance industry. For example, in 1992 Hurricane Andrew caused over $20 billion (in 2002 U.S. dollars) in insured losses, the largest loss on record due to a natural disaster. In addition, 26 of the top 30 insured losses were produced by extreme weather events, mainly landfalling hurricanes and typhoons and European windstorms. A better understanding of how extreme events vary with climate would benefit the reinsurance industry and society.

The Risk Prediction Initiative hosted a workshop on Weather Extremes and Atmospheric Oscillations that examined how extreme meteorological events of interest to the reinsurance industry are influenced by the quasi-biennial oscillation (QBO), the Arctic Oscillation (AO), and the Madden–Julian oscillation (MJO). Workshop participants concluded that the stratosphere is much more relevant to predictions that aid the reinsurance industry than is generally recognized and that there is mutual interest in fostering research on the relationship between the stratospheric circulation and extreme weather events.

A preliminary science–business research agenda, based on presentations and discussions during and after the workshop, highlights four areas of mutual interest to scientists and insurers. The research areas focus mainly on understanding how the QBO, AO, and MJO influence the frequency and intensity of extreme events, with particular emphasis on tropical cyclones and European windstorms. An awareness of how the catastrophe reinsurance industry operates provides insights into why specific research areas were chosen. For example, the reinsurance industry operates on the basis of annual contracts, most of which are renewed on 1 January. Thus, although skillful forecasts at any lead are of interest, skillful forecasts of extreme events are of greatest value when made in the final quarter of a calendar year.
Possibilities and Challenges for Academic Psychology
Authors: Meara Naomi M. , Day Jeanne D.
Published: May 2004

This article focuses on explicitly expanding contemporary definitions of the academic community and its disciplines, in particular academic psychology, to include virtue. The academy benefits from the civic trust; thus, it has moral obligations to serve the public with integrity and respect. This article places academic psychology in this larger context of the academy and uses the metaphor of the academic conversation for describing tensions between coherence and uncertainty indicative of academic life. Four major virtues of academic psychology that derive from its goals, practices, and distinguishing features are suggested: the self-regarding virtues of prudence and integrity and the other-regarding virtues of respectfulness and benevolence. Several challenges to achieving a virtuous academic psychology are presented. The ideas in this article are not meant to be definitive but rather are intended to provoke further conversation about these matters and their helpfulness in enhancing competent psychological research, instruction, practice, and policy making.
Another Look at the New York City School Voucher Experiment
Authors: Krueger Alan B. , Zhu Pei
Published: May 2004

This article reexamines data from the New York City school choice program, the largest and best-implemented private school scholarship experiment yet conducted. In the experiment, low-income public school students in kindergarten to Grade 4 were eligible to participate in a series of lotteries for a private school scholarship in May 1997. Data were collected from students and their parents at baseline and in the spring of each of the next 3 years. Students with missing baseline test scores, which encompasses all those who were initially in kindergarten and 11% of those initially in Grades 1 to 4, were excluded from previous analyses of achievement, even thoughthese students were tested in the follow-up years. In principle, random assignment would be expected to lead treatment status to be uncorrelated with all baseline characteristics. In addition, it was found that the effect of vouchers was sensitive to the particular way race/ethnicity was defined.