bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful treatment of chemo‐refractory pulmonary metastases of renal pelvic cancer by second‐line chemotherapy including gemcitabine followed by salvage surgery
Authors: TADOKORO MANABU , YONESE JUNJI , TSUKAMOTO TETSURO , OKUBO YUHEI , HANADA EIKI , SATOH YUKITOSHI , NAKAGAWA KEN , ISHIKAWA YUICHI , FUKUI IWAO
Published: February 2005

Abstract  A 51‐year‐old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M‐VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.
Nutritional hypogonadotropic hypogonadism presented with decreased ejaculatory volume
Authors: UDAGAWA KOICH , NOMURA SAKAE
Published: February 2005

Abstract  A 19‐year‐old male college student presented with decreased ejaculatory volume. Endocrinological examinations demonstrated a hypogonadotropic hypogonadism (HH) caused by a gonadotropin‐releasing hormone deficiency from the hypothalamus. Cranial magnetic resonance imaging did not demonstrate any abnormalities. The possible causative factor of this adult‐onset HH was excessive weight‐loss (−26% in 1 year) due to inadequate food intake and an irregular lifestyle. Semen analyses and serum gonadotropin and testosterone values gradually improved as the patient became accustomed to his new life and regained weight.
Placement of a urethral catheter into the ureter: An unexpected complication after retropubic suspension
Authors: HARA NOBORU , KOIKE HIROSHI , BILIM VLADIMIR , TAKAHASHI KOTA
Published: February 2005

Abstract  We describe an unusual complication caused by urethral catheterization which, to our knowledge, has not yet been reported. A 16 Fr urethral balloon catheter was unintentionally placed into the left ureter through the ureteral orifice in a 51‐year‐old woman following retropubic suspension surgery for stress urinary incontinence. After retrograde urography from the urethral catheter and removal of the catheter, reoperation was performed and a double pig‐tail ureteral stent was placed in the left ureter with subsequent proper replacement of a urethral catheter. The patient had uneventful postoperative recovery. Although the presented accident was an unexpected complication which might be associated with anatomical changes resulting from colposuspension, we should have confirmed the catheter position intraoperatively.
Impact of hormonal therapy prior to radical prostatectomy on the recovery of quality of life
Authors: NAMIKI SHUNICHI , SAITO SEIICHI , TOCHIGI TATSUO , KUWAHARA MASAAKI , IORITANI NAOMASA , YOSHIMURA KOJI , TERAI AKITO , KOINUMA NOBUO , ARAI YOICHI
Published: February 2005

Background: We investigated the changes in health‐related quality of life (HRQOL) in patients who underwent prostatectomy (RP) with or without neoadjuvant hormonal therapy (NHT).

Methods: A total of 72 patients undergoing direct RP (DRP group) and 26 patients receiving neoadjuvant hormonal therapy (NHT group) were enrolled in the present study. The baseline interview was conducted before RP (not initiation of therapy). Follow‐up interviews were conducted in person at scheduled study visits of 3, 6, and 12 months after surgery. We measured general and disease specific HRQOL with the Medical Outcomes Study 36‐Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively.

Results: At baseline, the NHT group scored statistically lower for not only sexual function (P < 0.001), but also the general HRQOL, such as role limitations due to physical problems (P = 0.007), social function (P = 0.045) and mental health (P = 0.034), than the DRP group. The NHT group reported lower scores in social function and mental health at 3 months (P = 0.040 and 0.006, respectively). Patients who received NHT for more than 3 months continued to show significantly lower scores for some HRQOL domains 12 months later.

Conclusion: Neoadjuvant hormonal therapy may decrease not only sexual function, but also general HRQOL before surgery. The recovery of HRQOL appeared to be further prolonged in patients who received long‐term NHT.
Efficacy and safety of laparoscopic surgery for pheochromocytoma
Authors: NAYA YUKIO , ICHIKAWA TOMOHIKO , SUZUKI HIROYOSHI , KOMIYA AKIRA , NAGATA MAKI , UEDA TAKESHI , YAMAGUCHI KUNIO , ITO HARUO
Published: February 2005

Objective: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome is well established. We report on our experiences with laparoscopic adrenalectomy for pheochromocytoma, and assess the efficacy and safety of the laparoscopic approach.

Methods: Between April 1998 and April 2003, a total of 23 patients underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of these patients with those of 106 patients with adrenal tumors due to other pathologies who underwent laparoscopic adrenalectomy during the same period.

Results: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative time nor mean estimated blood loss was greater for patients with pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180 mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the follow‐up period, there were no mortalities or recurrences of endocrinopathy.

Conclusions: Laparoscopic adrenalectomy for pheochromocytoma is a safe and minimally invasive procedure.
Preoperative prediction of final pathological features is not improved by the free‐to‐total prostate‐specific antigen ratio in Japanese men with clinically localized prostate cancer
Authors: MIYAKE HIDEAKI , SAKAI IORI , HARADA KEN‐ICHI , HARA ISAO , ETO HIROSHI
Published: February 2005

Background: The objective of the present study was to determine whether the percentage of free/total prostate‐specific antigen (f/tPSA) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can preoperatively predict organ‐confined versus extraprostatic disease.

Methods: Serum levels of fPSA and tPSA were measured in 97 patients with clinically organ‐confined disease before they underwent radical prostatectomy. The relationships of tPSA, f/tPSA and the pathological stage of the prostatectomy specimens were analyzed. Furthermore, the ability of f/tPSA to predict the pathological features was compared with those of tPSA and systematic biopsy findings.

Results: Organ‐confined and extraprostatic extension diseases were present in 51 and 46 men, respectively. tPSA in patients with extraprostatic diseases was significantly higher than that in those with organ‐confined diseases; however, there was no significant difference in f/tPSA between these two groups. There was also a significant difference in tPSA levels at each pathological stage, while f/tPSA did not parallel the pathological stage. Furthermore, there was no additional information concerning the extent of prostate cancer obtained when f/tPSA was combined with tPSA or with the percent of positive biopsy cores, which is the most significant predictor of the extent of prostate cancer among factors associated with systematic biopsy.

Conclusion: f/tPSA could not predict the final pathological features in patients with clinically localized prostate cancer before radical prostatectomy. Moreover, the predictive value provided by tPSA or systematic biopsy findings was not improved by combined analysis with f/tPSA.
A UNIFIED FRAMEWORK FOR MODELLING WILDLIFE POPULATION DYNAMICS†
Authors: Thomas Len , Buckland Stephen T. , Newman Ken B. , Harwood John
Published: February 2005

This paper proposes a unified framework for defining and fitting stochastic, discrete‐time, discrete‐stage population dynamics models. The biological system is described by a state‐space model, where the true but unknown state of the population is modelled by a state process, and this is linked to survey data by an observation process. All sources of uncertainty in the inputs, including uncertainty about model specification, are readily incorporated. The paper shows how the state process can be represented as a generalization of the standard Leslie or Lefkovitch matrix. By dividing the state process into subprocesses, complex models can be constructed from manageable building blocks. The paper illustrates the approach with a model of the British grey seal metapopulation, using sequential importance sampling with kernel smoothing to fit the model.
CONSTRUCTION OF RESOLVABLE ROW‐COLUMN DESIGNS BASED ON CONTRACTIONS
Authors: Wright C.L. , John J.A. , Whitaker D. , WiLLiAMS E.R.
Published: February 2005

This paper defines the contraction of a resolvable row‐column design for more than two replicates. It shows that the (M,S)‐optimality criterion for the row‐column designs can be expressed simply in terms of the elements of the row and column incidence matrices of the contraction. This allows the development of a very fast algorithm to construct optimal or near‐optimal resolvable row‐column designs. The performance of such an algorithm is compared with an existing algorithm.
BARBARIAN PIRACY AND THE SAXON SHORE: A REAPPRAISAL
Authors: PEARSON A.F.
Published: February 2005

Summary.  The tradition of Saxon and other Continental piracy is one of the longest standing tenets of Romano‐British studies. It may also be one of its greatest myths, which owes more to its considerable antiquarian pedigree than to any firm basis in fact. This paper reassesses Roman military strategy around the British coast, and suggests that the ‘Saxon Shore Forts’ and other coastal installations played a more significant economic and logistical role than is often appreciated. Moreover, the idea that each monument fulfilled a single, dedicated function is argued to be too simplistic: instead it is proposed that individual forts served in various capacities during their operational lifetime, and quite possibly not those for which they were originally conceived.
THE GRANITE COLUMN IN MODON: HOW TO MAKE A STONE SAY WHAT YOU WANT IT TO SAY!
Authors: FOUTAKIS PATRICE
Published: February 2005

Summary.  The 3 km long ramparts of the castle of Modon survive remarkably unscathed despite the attacks of Man and Nature over the centuries. The most interesting monument which remains, a column of red granite, crowned with a capital and a stone slab, has escaped the looters of antiquities who often passed by Modon. It has also escaped the scholars who have failed to give a reliable interpretation of the monument. This paper seeks to deal with this question and to set the monument in its proper historical context.
The role of the extrinsic thoracic limb muscles in equine locomotion
Authors: Payne R. C. , Veenman P. , Wilson A. M.
Published: February 2005

Muscles have two major roles in locomotion: to generate force and to absorb/generate power (do work). Economical force generation is achieved by short‐fibred pennate muscle while the maximum power output of a muscle is architecture independent. In this study we tested the hypothesis that there is an anatomical and structural separation between the force‐generating anti‐gravity muscles and the propulsive (limb/trunk moving) muscles of the equine forelimb. Muscle mass and fascicle length measurements were made on the thoracic limb extrinsic muscles of six fresh horse cadavers. Physiological cross‐sectional area and maximum isometric force were then estimated. Maximum power was estimated from muscle volume and published contraction velocity data. The majority of extrinsic forelimb muscles were large with long fascicles arranged in parallel to the long axis of the muscle. Muscles arranged in this way are optimised for doing work. The architecture of serratus ventralis thoracis (SVT) was unique. It had short (48 ± 17 mm) fascicles, arranged at about 45° to the long axis of the muscle, which would suggest a force‐generating, anti‐gravity role. The muscle belly of SVT was sandwiched between two broad, thick sheets of aponeurosis. Hence, SVT could make a significant contribution to the overall elastic properties of the thoracic limb.
Pregnancy outcomes in women of very advanced maternal age
Authors: CALLAWAY Leonie K. , LUST Karin , MCINTYRE H. David
Published: February 2005

Objective:  To assess outcomes for pregnancies progressing beyond 20 weeks’ gestation in women of very advanced maternal age.

Design:  Retrospective cohort study.

Setting:  Two tertiary level obstetric hospitals.

Population:  Women aged 45 years or more at the time of delivery over a 10‐year period from 1 January 1992 to 31 December 2001.

Methods:  Information regarding maternal, pregnancy and neonatal outcomes was obtained from the medical records. For comparison, routinely collected data from the obstetric database was obtained for women aged 20–29 years.

Results:  Seventy‐seven pregnancies in 76 women aged 45 years and over were registered in the 10‐year period. There were 74 liveborn singletons, two sets of liveborn twins and one set of twins stillborn at 20 weeks’ gestation. Sixteen women were primiparous. Eighty‐four percent of pregnancies were conceived naturally and 53% underwent prenatal chromosomal determination; 53% of women had no pre‐existing medical problems, 13% had hypertensive disorders of pregnancy and 8% of women developed gestational diabetes. There were 10 preterm and six post dates deliveries. The Caesarean section rate was 49%, compared to 23% in the 20–29 years age group (P < 0.001). Ten percent of neonates were small for gestational age, and 8% were large for gestational age. Seventeen percent required admission to the special care nursery and 6% had congenital abnormalities.

Conclusions:  Maternal and neonatal outcomes in this series were generally good. There was a significantly increased rate of Caesarean section. Overall, this study is reassuring for women aged 45 and over who have good general health and a chromosomally normal fetus.
Incidence of polycystic ovaries and polycystic ovary syndrome amongst women in Melbourne, Australia
Authors: LOWE Philip , KOVACS Gab , HOWLETT Donna
Published: February 2005

Background:  The incidence of polycystic ovaries (PCO) in the Australian population is unknown.

Aims:  To determine the incidence of PCO in a random population of Melbourne women.

Methods:  A retrospective survey of the transvaginal ultrasound of female partners of sterile males was undertaken.

Results:  Twenty‐three percent of subjects had polycystic ovaries on ultrasound criteria, 17% bilateral and 6% unilateral.

Conclusions:  The incidence of PCO in Australian women is similar to that of other Caucasian populations.
Comparison of transvaginal sonography, saline infusion sonography and hysteroscopy in the evaluation of uterine cavity pathologies
Authors: CEPNI Ismail , OCAL Pelin , ERKAN Sanli , SARICALI Funda Salihoglu , AKBAS Hande , DEMIRKIRAN Fuat , IDIL Mehmet , BESE Tugan
Published: February 2005

Aims:  To determine whether performing transvaginal sonography (TVS) and saline infusion sonography (SIS) before hysteroscopy could reduce the number of diagnostic hysteroscopies performed for the evaluation of uterine cavity abnormalities.

Methods:  Two hundred and twenty three women with suspected uterine cavity abnormalities were prospectively evaluated by TVS, SIS and hysteroscopy, and had histological evaluation of the endometrium with hysteroscopic biopsy or dilatation and curettage (D&C). One hundred and sixty five patients (74%) were premenopausal and 58 patients (26%) were postmenopausal.

Results:  The positive predictive value (PPV) for endometrial polyps was 69% for TVS, 78% for SIS and 81% for hysteroscopy in premenopausal patients. In the postmenopausal group, TVS and SIS could detect only 24% of endometrial polyps, whereas 70% were diagnosed by hysteroscopy. The PPV for submucous fibroids was 47% for TVS, 81% for SIS and 77% for hysteroscopy in the premenopausal group.

Conclusions:  In premenopausal patients, SIS and hysteroscopy are equally accurate in the diagnosis of endometrial polyps and submucous fibroids. Hysteroscopy is the most accurate test for polypoid lesions in the postmenopausal group. Performing TVS, SIS and D&C could reduce the number of diagnostic hysteroscopies performed for the evaluation of uterine cavity abnormalities by 71.5% in premenopausal patients. However, this rate decreases to 40% in the postmenopausal group.
Role of internal anal sphincter damage in the causation of idiopathic faecal incontinence: A prospective study
Authors: PETROS Peter , ANDERSON Jim
Published: February 2005

This prospective study aimed to examine the relationship between internal anal sphincter (IAS) damage and ‘idiopathic’ faecal incontinence (FI) in 50 consecutive patients, using endoanal ultrasound examination. The external anal sphincter (EAS) was intact on direct and ultrasonic assessment in all patients. IAS damage was defined as complete rupture or attenuation, less than 2 mm thickness in some part of the sphincter. Complete rupture was found in one patient and damage in a further 17 (total 36%). All three nulliparous patients had normal IAS and EAS. IAS damage was only minimally associated with ‘idiopathic’ FI, suggesting IAS per se is unlikely to be a direct cause of FI in the ‘idiopathic’ group of FI patients. Its role might be analogous to the periurethral striated horse‐shoe shape muscle in the urethra, which is thought to act as a mucosal sealant.
Demographic variables routinely collected at colposcopic examination do not predict who will default from conservative management of cervical intraepithelial neoplasia I
Authors: QUINLIVAN Julie A. , PETERSEN Rodney W. , GANI Linsey , TAN Jeffrey
Published: February 2005

Objective:  As a result of the low incidence of progression from low grade epithelial abnormalities to cervical intraepithelial neoplasia (CIN) 3 or cervical cancer, a conservative approach to management is supported, especially in young women. Loss to follow‐up is a recognised problem with a conservative approach however, with women defaulting known to experience higher rates of cancer.

Aim:  To determine if any routinely collected demographic variables could predict which Australian women would subsequently default from care having initially elected to have conservative management of CIN 1 lesions.

Methods:  Prospectively collected data was audited on 279 women with a colposcopically directed biopsy diagnosis of CIN 1, confirmed on external review, who were enroled by their own choice into a conservative management program and monitored until a definitive lesion outcome was determined. Women who defaulted from follow‐up and were lost to care providers despite follow‐up appointments and reminder letters were compared to women who completed follow‐up with either lesion resolution or progression requiring treatment, to establish if there were any demographic variables to predict default from care.

Results:  Fifty‐two (18.5%) women subsequently defaulted from follow‐up. There were no significant differences in age, parity, proportion of women who were pregnant at diagnosis, smoking status, immunosuppressed or had a ‘human papillomavirus (HPV) effect’ reported on Pap‐smear or colposcopic examination.

Conclusion:  We cannot easily identify a subgroup of women who are more likely to default from follow‐up of CIN 1 using routinely collected demographic data. Default from follow‐up is a major risk with conservative approaches and further research to reduce default rates are required.
Suburethral slingplasty evaluation study in North Queensland, Australia: The SUSPEND trial
Authors: LIM Yik Nyok , MULLER Reinhold , CORSTIAANS Audrey , DIETZ Hans P. , BARRY Christopher , RANE Ajay
Published: February 2005

Objective:  To compare the safety and efficacy of three types of suburethral slings for the treatment of urodynamic stress incontinence.

Methods:  Following ethics approval, 195 (3 × 65) patients with urodynamic stress incontinence were randomly assigned to undergo suburethral slingplasty with the Tension‐free Vaginal Tape (TVT; Gynecare, Ethicon, Somerville, NJ, USA), Intravaginal Sling (IVS; Tyco Healthcare, Mansfield, MA, USA), or Suprapubic Arc Sling (SPARC; American Medical Systems, Minnetonka, MN, USA). The patients were blinded to the type of sling implanted.

Main outcome measures were:  (1) operative and short‐term complications; (2) pre‐ and postoperative symptomatology; and (3) pre‐ and postoperative urodynamic findings.

Results:  There was a statistically significant increased rate of sling protrusion (13.1% vs. 3.3% and 1.7%; P = 0.04) in the SPARC group when compared to TVT and IVS. Otherwise, there were no significant differences between the groups with respect to the incidences of other operative complications, patients’ main subjective outcomes, satisfaction rates, or postoperative urodynamic findings. The overall objective stress incontinence cure rates were 87.9%, 81.5% and 72.4% for the TVT, IVS, SPARC groups respectively (P = 0.11).

Conclusions:  All three slings appear quite successful for the treatment of stress incontinence. The SPARC tapes showed more sling protrusion complications and a trend towards lower objective cure rates; probably as a result of the insertion method used in this study which favoured a loose SPARC sling placement. The authors recommend that the SPARC slings be left tighter than TVT, or for the cough test to be carried out.
African‐American and White Caregivers of Older Adults with Dementia: Differences in Depressive Symptomatology and Psychotropic Drug Use
Authors: Sleath Betsy , Thorpe Joshua , Landerman Lawrence R. , Doyle Marti , Clipp Elizabeth
Published: February 2005

Objectives: To examine relationships between race and psychotropic drug use (antidepressant, antianxiety, sedative/hypnotic agents) in informal caregivers with symptoms of depression who provide care for elderly relatives with progressive dementia. Whether racial differences in medication use relate to racial differences on predisposing, enabling, and need factors associated with use of these agents was also examined.

Design: National survey.

Setting: Community‐based population of informal caregivers of elderly male U.S. veterans with dementia living throughout the 48 contiguous states and Puerto Rico.

Participants: Two thousand thirty‐two African‐American and white female caregivers of elderly male veterans diagnosed with probable Alzheimer's disease or vascular dementia.

Measurements: Depressive symptoms were measured using a modified version of the Center for Epidemiological Studies Depression Scale. Antidepressant, antianxiety, and sedative/hypnotic agents were indexed using the Veterans Affairs medication classification system.

Results: Of caregivers with depressive symptoms, 19% used antidepressants, 23% antianxiety agents, and 2% sedative/hypnotics. African‐American caregivers with depressive symptoms were significantly less likely than whites with depressive symptoms to be using antidepressants and antianxiety medications. Caregivers who reported higher levels of social support and more physician visits during the previous 6 months were significantly more likely than others to be taking antidepressants.

Conclusion: This study found that 81% of caregivers with depressive symptoms were not taking antidepressant medication and that African‐American caregivers were less likely than whites to be taking antidepressants. Results suggest that routine screening for depression in dementia caregivers may identify unmet needs for antidepressant therapy. Particular care should be taken to ensure that African‐American caregivers are made aware of the potential benefits of such therapy.
Consequences of Preventing Delirium in Hospitalized Older Adults on Nursing Home Costs
Authors: Leslie Douglas L. , Zhang Ying , Bogardus Sidney T. , Holford Theodore R. , Leo‐Summers Linda S. , Inouye Sharon K.
Published: February 2005

Objectives: To determine whether costs of long‐term nursing home (NH) care for patients who received a multicomponent targeted intervention (MTI) to prevent delirium while hospitalized were less than for those who did not receive the intervention.

Design: Longitudinal follow‐up from a randomized trial.

Setting: Posthospital discharge settings: community‐based care and NHs.

Participants: Eight hundred one hospitalized patients aged 70 and older.

Measurements: Patients were followed for 1 year after discharge, and measures of NH service use and costs were constructed. Total long‐term NH costs were estimated using a two‐part regression model and compared across intervention and control groups.

Results: Of the 400 patients in the intervention group and 401 patients in the matched control group, 153 (38%) and 148 (37%), respectively, were admitted to a NH during the year, and 54 (13%) and 51 (13%), respectively, were long‐term NH patients. The MTI had no effect on the likelihood of receiving long‐term NH care, but of patients receiving long‐term NH care, those in the MTI group had significantly lower total costs, shorter length of stay and lower cost per survival day. Adjusted total costs were $50,881 per long‐term NH patient in the MTI group and $60,327 in the control group, a savings of 15.7% (P=.01).

Conclusion: Active methods to prevent delirium are associated with a 15.7% decrease in long‐term NH costs. Shorter length of stay of patients receiving long‐term NH services was the primary source of these savings.
Disparities in Antidepressant Treatment in Medicaid Elderly Diagnosed with Depression
Authors: Strothers Harry S. , Rust George , Minor Patrick , Fresh Edith , Druss Benjamin , Satcher David
Published: February 2005

Objectives: To determine whether there were racial or ethnic disparities in the use of antidepressants in low‐income elderly patients insured by Medicaid.

Design: Examination of 1998 Medicaid claims data.

Setting: Centers for Medicare and Medicaid Services Medicaid claims data for five U.S. states.

Participants: All Medicaid recipients aged 65 to 84 with a diagnosis of depression.

Measurements: Treatment versus no treatment; in those treated, treatment with drugs was classified as old‐ or new‐generation antidepressants.

Results: In 1998, 7,339 unique individuals aged 65 to 84 had at least one outpatient encounter with depression as the primary diagnosis. Nearly one in four (24.2%) received no antidepressant drug therapy, and 22% received neither psychotherapy nor an antidepressant. African‐American individuals were substantially more likely to be untreated (37.1%) than Hispanic (23.6%), white (22.4%), or Asian (13.8%) individuals. In logistic regression models adjusting for sex, state, long‐term care status, and age group, African Americans with a primary diagnosis of depression were almost twice as likely as whites not to receive an antidepressant within the study period (odds ratio=1.91, 95% confidence interval=1.62–2.24). Patients in long‐term care facilities and those aged 65 to 74 were less likely to receive treatment.

Conclusion: Substantial numbers of elderly Medicaid enrollees with a primary diagnosis of depression did not receive antidepressants or behavioral therapy. This gap in care disproportionately affected African‐American patients.
A Question of Identity
Authors: Balding David
Published: February 2005

The weight to be attached to DNA profile evidence was the centre of a huge scientific controversy in the early-mid-1990s, with scientists, including statistical scientists, criticising each other over both science and conduct in the editorials of prestigious journals, on television and radio, and in newspapers. Today, only the occasional shot rings out on the DNA evidence front. David Balding looks back and reflects on the causes of the dispute, its evolution and resolution, and the role in it of statistics and statisticians.
Appealing Statistics
Authors: Donnelly Peter
Published: February 2005

In the case of Regina versus Adams [1996], DNA evidence seemed to suggest that there was a 1 in 200 million chance that an innocent person would match the DNA found at the crime scene. Peter Donnelly explains how he subsequently became involved in the case and found himself trying to explain Bayes's Theorem to judge and jury.
THE UTILITY OF LACTATE AND ROSEMARY IN BEEF ENHANCEMENT SOLUTIONS: EFFECTS ON LONGISSIMUS COLOR CHANGES DURING DISPLAY
Authors: MANCINI R.A. , HUNT M.C. , HACHMEISTER K.A. , SEYFERT M.A. , KROPF D.H. , JOHNSON D.E. , CUSICK S. , MORROW C.
Published: February 2005

This study evaluated the utility of lactate and rosemary in beef enhancement solutions for improving strip loin steak color stability during display in modified atmosphere packages (80% O

2

/20% CO

2

). Beef longissimus muscles were injected (6%) with enhancement solutions containing water, salt, phosphate, and either rosemary, lactate, or a combination of rosemary and lactate. Steaks packaged in high oxygen were stored for 5 days prior to display. Throughout a 7‐day display, loins treated with rosemary were lighter red (P < 0.05) than loins treated with lactate or lactate plus rosemary, which were similar. However, lactate resulted in a dark‐red color rather than a brown metmyoglobin‐like discoloration. Even though steaks from rosemary‐enhanced loins were more red (P < 0.05) on day 0 of display than loins enhanced with lactate or lactate and rosemary, this bright‐red initial color did not continue throughout display, whereas the lactate‐enhanced products were darker but had a more stable red color.
How Long Is the Day on Saturn?
Authors: Sánchez-Lavega Agustín
Published: February 2005

Determining a planet's rotation period can be difficult if the planet lacks a solid surface. However, for planets with an internal magnetic field, emissions at radio wavelengths are modulated by the planet's rotation rate. The latest results from the Cassini spacecraft seem to indicate that Saturn's rotation rate has slowed down by 6 minutes since the Voyager 1 and 2 spacecraft flew by the planet in 1980 and 1981, but it is unclear whether a slowdown has in fact occurred. Future data collected by Cassini may be able to resolve the question.
Cassini Imaging Science: Initial Results on Saturn's Atmosphere
Authors: Porco C. C. , Baker E. , Barbara J. , Beurle K. , Brahic A. , Burns J. A. , Charnoz S. , Cooper N. , Dawson D. D. , Del Genio A. D. , Denk T. , Dones L. , Dyudina U. , Evans M. W. , Giese B. , Grazier K. , Helfenstein P. , Ingersoll A. P. , Jacobson R. A. , Johnson T. V. , McEwen A. , Murray C. D. , Neukum G. , Owen W. M. , Perry J. , Roatsch T. , Spitale J. , Squyres S. , Thomas P. , Tiscareno M. , Turtle E. , Vasavada A. R. , Veverka J. , Wagner R. , West R.
Published: February 2005

The Cassini Imaging Science Subsystem (ISS) began observing Saturn in early February 2004. From analysis of cloud motions through early October 2004, we report vertical wind shear in Saturn's equatorial jet and a maximum wind speed of â¼375 meters per second, a value that differs from both Hubble Space Telescope and Voyager values. We also report a particularly active narrow southern mid-latitude region in which dark ovals are observed both to merge with each other and to arise from the eruptions of large, bright storms. Bright storm eruptions are correlated with Saturn's electrostatic discharges, which are thought to originate from lightning.
A Piece of a Neuroscientist's Mind
Authors: Nelson Charles A. , Gottesman Irving I.
Published: February 2005

The Great Brain Debate
Nature or Nurture?.
By John E. Dowling
. Joseph Henry Press, Washington, DC, 2004. 197 pp. $24.95, C$32.95. ISBN 0-309-09223-X. Science Essentials. ()

In a short book-the first in a series in which National Academy of Science members will describe their science and research for general audiences-the author offers a concise primer on the brain and its development.
Vibrio parahaemolyticus
Disruption of Epithelial Cell Tight Junctions Occurs Independently of Toxin Production
Authors: Lynch Tarah , Livingstone Scott , Buenaventura Enrico , Lutter Erika , Fedwick Jason , Buret Andre G. , Graham David , DeVinney Rebekah
Published: February 2005

Vibrio parahaemolyticus
is a leading cause of seafood-borne gastroenteritis worldwide. Virulence is commonly associated with the production of two toxins, thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH). Although the majority of clinical isolates produce TDH and/or TRH, clinical samples lacking toxin genes have been identified. In the present study, we investigated the effects of
V. parahaemolyticus
on transepithelial resistance (TER) and paracellular permeability in Caco-2 cultured epithelial cells. We found that
V. parahaemolyticus
profoundly disrupts epithelial barrier function in Caco-2 cells and that this disruption occurs independently of toxin production. Clinical isolates with different toxin genotypes all led to a significant decrease in TER, which was accompanied by an increased flux of fluorescent dextran across the Caco-2 monolayer, and profound disruption of actin and the tight junction-associated proteins zonula occludin protein 1 and occludin. Purified TDH, even at concentrations eightfold higher than those produced by the bacteria, had no effect on either TER or paracellular permeability. We used lactate dehydrogenase release as a measure of cytotoxicity and found that this parameter did not correlate with the ability to disrupt tight junctions. As the effect on barrier function occurs independently of toxin production, we used PCR to determine the toxin genotypes of
V. parahaemolyticus
isolates obtained from both clinical and environmental sources, and we found that 5.6% of the clinical isolates were toxin negative. These data strongly indicate that the effect on tight junctions is not due to TDH and suggest that there are other virulence factors.
Sialic Acid Metabolism and Systemic Pasteurellosis
Authors: Steenbergen Susan M. , Lichtensteiger Carol A. , Caughlan Ruth , Garfinkle Jackie , Fuller Troy E. , Vimr Eric R.
Published: February 2005

Pasteurella multocida
subsp.
multocida
is a commensal and opportunistic pathogen of food animals, wildlife, and pets and a zoonotic cause of human infection arising from contacts with these animals. Here, an investigation of multiple serotype A strains demonstrated the occurrence of membrane sialyltransferase. Although
P. multocida
lacks the genes for the two earliest steps in de novo sialic acid synthesis, adding sialic acid to the growth medium resulted in uptake, activation, and subsequent transfer of sialic acid to a membrane acceptor resembling lipooligosaccharide. Two candidate-activating enzymes with homology to
Escherichia coli
cytidine 5′-monophospho-
N
-acetylneuraminate synthetase were overproduced as histidine-tagged polypeptides. The synthetase encoded by pm0187 was at least 37 times more active than the pm1710 gene product, suggesting pm0187 encodes the primary sialic acid cytidylyltransferase in
P. multocida
. A sialate aldolase (pm1715) mutant unable to initiate dissimilation of internalized sialic acid was not attenuated in the CD-1 mouse model of systemic pasteurellosis, indicating that the nutritional function of sialate catabolism is not required for systemic disease. In contrast, the attenuation of a sialate uptake-deficient mutant supports the essential role in pathogenesis of a sialylation mechanism that is dependent on an environmental (host) supply of sialic acid. The combined results provide the first direct evidence of sialylation by a precursor scavenging mechanism in pasteurellae and of a potential tripartite ATP-independent periplasmic sialate transporter in any species.
Efficacy of Vaccination of Calves against Hemorrhagic Septicemia with a Live
aroA
Derivative of
Pasteurella multocida
B:2 by Two Different Routes of Administration
Authors: Hodgson J. Christopher , Finucane Anna , Dagleish Mark P. , Ataei Saeed , Parton Roger , Coote John G.
Published: February 2005

Two groups of four calves each were immunized either intramuscularly (i.m. vaccinated) or intranasally (i.n. vaccinated) at 2 and 6 weeks of age with ca. 10
9
CFU of a derivative of
P. multocida
serotype B:2 strain 85020 containing a deletion in the
aroA
gene (strain JRMT12). Both groups of calves and three unvaccinated control calves were challenged subcutaneously at 8 weeks of age with ca. 10
7
CFU of the wild-type 85020 strain. The first and second vaccinations caused a significant pyrexia and increase in the mean demeanor score (
P
< 0.05) in i.m. but not i.n. vaccinated calves. Serum agglutinating activity against whole cells of
P. multocida
strain 85020 and immunoglobulin G antibody concentrations increased after the second vaccination in i.m. but not in i.n. vaccinated animals, and this difference was statistically significant (
P
< 0.05). Concentrations of serum amyloid A (SAA) increased significantly 3 h after both the primary (
P
< 0.05) and booster (
P
< 0.001) i.m. vaccinations, but not in i.n. vaccinated calves. All four i.m. vaccinated calves were solidly immune to challenge with wild-type
P. multocida
B:2. However, the mean rectal temperatures, demeanor scores, and serum SAA concentrations of i.n. vaccinated and control calves increased significantly (
P
< 0.01). Three i.n. vaccinated and two control calves were killed for humane reasons within 14 h postchallenge, and postmortem examination revealed pathological lesions consistent with hemorrhagic septicemia. These data showed that the
aroA
mutant strain, given i.m. as two doses 4 weeks apart, acted as an effective live-attenuated vaccine strain to protect calves against challenge with the virulent parent strain.
Helicobacter pyloriInduces Interleukin-8 Secretion by Toll-Like Receptor 2- and Toll-Like Receptor 5-Dependent and -Independent Pathways
Authors: Torok Anastasia M. , Bouton Amy H. , Goldberg Joanna B.
Published: February 2005

Helicobacter pyloriis an important human pathogen that causes gastritis and is strongly associated with gastric ulcers, gastric adenocarcinomas, and mucosa-associated lymphoid tissue lymphomas. In response toH. pylori, interleukin-8 (IL-8) is secreted from host cells to attract components of the innate and adaptive immune systems to the site of infection. Toll-like receptor 2 (TLR2) and TLR5 have been shown to recognizeH. pyloriand to initiate signaling pathways that result in enhanced activation of NF-κB. Here, we evaluated the contribution of mitogen-activated protein kinase signaling pathways to TLR2-dependent and TLR5-dependent secretion of IL-8. Secretion of IL-8 fromH. pylori-infected HEK293 cells was augmented by the expression of TLR2 or TLR5. WhileH. pyloriinfection resulted in the activation of ERK, JNK, and p38, the enhanced IL-8 secretion from TLR2- and TLR5-expressing cells coincided with increased p38 activation and phosphorylation of the transcription factor ATF2. When p38 activity was inhibited in TLR2- or TLR5-expressing cells,H. pylori-dependent IL-8 secretion returned to the level observed in infected parental HEK293 cells that did not express TLR2 or TLR5; inhibition of p38 had no effect on IL-8 secretion from infected parental HEK cells. In contrast, inhibition of JNK and/or ERK resulted in substantially less IL-8 secretion from infected cells, independent of TLR2 or TLR5 expression. Based on these data, we propose thatH. pyloriinduces IL-8 secretion through a dual mechanism that includes a TLR2/5-independent component involving the activities of JNK and ERK and a TLR2/5-dependent component that requires p38 activity.
Antibody against V Antigen Prevents Yop-Dependent Growth ofYersinia pestis
Authors: Philipovskiy Alexander V. , Cowan Clarissa , Wulff-Strobel Christine R. , Burnett Sandra H. , Kerschen Edward J. , Cohen Donald A. , Kaplan Alan M. , Straley Susan C.
Published: February 2005

The V antigen (LcrV) of the plague bacteriumYersinia pestisis a potent protective antigen that is under development as a vaccine component for humans. LcrV is multifunctional. On the bacterial surface it mediates delivery of a set of toxins called Yops into host cells, and as a released protein it can cause production of the immunosuppressive cytokine interleukin-10 (IL-10) and can inhibit chemotaxis of polymorphonuclear neutrophils. It is not known how these mechanisms of LcrV operate, what their relative importance is, when they function during plague, and which are critical to protection by antibody. This study investigated several of these issues. C57BL/6 mice, mice unable to express IL-10, or mice with the macrophage lineage eliminated were treated with a protective anti-LcrV antibody or a nonprotective antibody against YopM and infected intravenously byY. pestisKIM5 or a strain that lacked the genes encoding all six effector Yops. Viable bacterial numbers were determined at various times. The data indicated that Yops were necessary forYersiniagrowth after the bacteria had seeded liver and spleen. Anti-LcrV antibody prevented this growth, even in IL-10−/−mice, demonstrating that one protective mechanism for anti-LcrV antibody is independent of IL-10. Anti-LcrV antibody had no effect on persistence in organs ofY. pestislacking effector Yops, even though the yersiniae could strongly express LcrV, suggesting that Yops are necessary for building sufficient bacterial numbers to produce enough LcrV for its immunosuppressive effects. In vitro assays showed that anti-LcrV antibody could partially block delivery of Yops and downstream effects of Yops in infected macrophage-like J774A.1 cells. However, cells of the macrophage lineage were found to be dispensable for protection by anti-LcrV antibody in spleen, although they contributed to protection in liver. Taken together, the data support the hypothesis that one protective effect of the antibody is to block delivery of Yops to host cells and prevent early bacterial growth. The findings also identified the macrophage lineage as one host cell type that mediates protection.
Characterization of a Novel Leucine-Rich Repeat Protein Antigen from Group B Streptococci That Elicits Protective Immunity
Authors: Seepersaud Ravin , Hanniffy Sean B. , Mayne Peter , Sizer Phil , Le Page Richard , Wells Jerry M.
Published: February 2005

Group B streptococci (GBS) usually behave as commensal organisms that asymptomatically colonize the gastrointestinal and urogenital tracts of adults. However, GBS are also pathogens and the leading bacterial cause of life-threatening invasive disease in neonates. While the events leading to transmission and disease in neonates remain unclear, GBS carriage and level of colonization in the mother have been shown to be significant risk factors associated with invasive infection. Surface antigens represent ideal vaccine targets for eliciting antibodies that can act as opsonins and/or inhibit colonization and invasion. Using a genetic screen for exported proteins in GBS, we identified a gene, designatedlrrG, that encodes a novel LPXTG anchored surface antigen containing leucine-rich repeat (LRR) motifs found in bacterial invasins and other members of the LRR protein family. Southern blotting showed thatlrrGwas present in all GBS strains tested, representing the nine serotypes, and revealed the presence of anlrrGhomologue inStreptococcus pyogenes. Recombinant LrrG protein was shown in vitro to adhere to epithelial cells in a dose-dependent manner, suggesting that it may function as an adhesion factor in GBS. More importantly, immunization with recombinant LrrG elicited a strong immunoglobulin G response in CBA/ca mice and protected against lethal challenge with virulent GBS. The data presented in this report suggest that this conserved protein is a highly promising candidate antigen for use in a GBS vaccine.
Salmonella entericaSerovar Typhimurium Infection of Dendritic Cells Leads to Functionally Increased Expression of the Macrophage-Derived Chemokine
Authors: Fu Guo , Wijburg Odilia L. C. , Cameron Paul U. , Price Jason D. , Strugnell Richard A
Published: February 2005

Gene expression in murine dendritic cells (DCs) infected with green fluorescent protein-expressingSalmonella entericaserovar Typhimurium BRD509 was studied by mRNA differential display. Infected DCs were sorted from uninfected cells by flow cytometry. The mRNA expression patterns of infected and uninfected cells revealed a number of differentially expressed transcripts, which included the macrophage-derived chemokine (MDC). Up-regulation ofMDCtranscription in infected DCs was confirmed by Northern blotting, and the kinetics ofMDCexpression was examined by real-time reverse transcription-PCR, with which 31- and 150-fold increases were detected at 2 and 6 h postinfection, respectively. The increased release by DCs of MDC into culture media was detected by an enzyme-linked immunosorbent assay. The biological activity of MDC was investigated in in vitro and in vivo assays. In vitro, supernatants fromS. entericaserovar Typhimurium-infected DCs were chemoattractive to T cells, and neutralization of MDC in these supernatants inhibited T-cell migration. Passive transfer of anti-MDC antibody to mice infected with BRD509 revealed that neither growth of the bacterium nor resistance of the mice to reinfection was affected and that in vivo inhibition of MDC did not affect T-cell responses, as measured by the gamma interferon ELISPOT method 3 days after challenge infection.
Use of Green Fluorescent Protein and Reverse Transcription-PCR To Monitor
Candida albicans
Agglutinin-Like Sequence Gene Expression in a Murine Model of Disseminated Candidiasis
Authors: Green Clayton B. , Zhao Xiaomin , Hoyer Lois L.
Published: February 2005

Candida albicans
P
ALS
-green fluorescent protein (GFP) reporter strains were inoculated into mice in a disseminated candidiasis model, and GFP production was monitored by immunohistochemistry and reverse transcription-PCR (RT-PCR). GFP production from the
ALS1
and
ALS3
promoters was detected immunohistochemically.
ALS1
,
ALS2
,
ALS3
,
ALS4
, and
ALS9
transcription was detected by RT-PCR, further identifying ALS genes expressed in this model.
Production of a Proteolytically Active Protein, Chlamydial Protease/Proteasome-Like Activity Factor, by Five Different
Chlamydia
Species
Authors: Dong Feng , Zhong Youmin , Arulanandam Bernard , Zhong Guangming
Published: February 2005

We have previously identified a chlamydial protein, chlamydial protease/proteasome-like activity factor (CPAF), for degrading host transcription factors in cells infected with the human chlamydial species
Chlamydia trachomatis
or
Chlamydia pneumoniae
. We now report that functional CPAF was also produced during infection with the species
Chlamydia muridarum
,
Chlamydia psittaci
, and
Chlamydia caviae
, which primarily infect nonhuman hosts.
Glutathione and Nitrosoglutathione in Macrophage Defense againstMycobacterium tuberculosis
Authors: Venketaraman Vishwanath , Dayaram Yaswant K. , Talaue Meliza T. , Connell Nancy D.
Published: February 2005

We demonstrate thatMycobacterium tuberculosisgrown in vitro is sensitive to glutathione and its derivativeS-nitrosoglutathione. Furthermore, our infection studies with J774.1 macrophages indicate that glutathione is essential for the control of the intracellular growth ofM. tuberculosis. This study indicates the important role of glutathione in the control of macrophages byM. tuberculosis.
Genetic Vaccination against Murine Cysticercosis by Using a Plasmid Vector CarryingTaenia soliumParamyosin
Authors: Solís Carlos F. , Ostoa-Saloma Pedro , Lugo-Martínez Verónica H. , Johnston Stephen Albert , Laclette Juan Pedro
Published: February 2005

A plasmid vector carrying the immunoprotective amino-terminal fragment ofTaenia soliumparamyosin (VW2-1) was designed for genetic vaccination studies. Mice that were genetically immunized with VW2-1 and challenged by intraperitoneal inoculation ofTaenia crassicepscysticerci showed 43 to 48% reductions in the parasite burden, values which were similar to values obtained previously when the recombinant protein was used.