bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of dose titration with darifenacin, an M3‐selective receptor antagonist
Authors: Steers William , Corcos Jacques , Foote Jenelle , Kralidis Georg
Published: February 2005

OBJECTIVES

To evaluate the efficacy, tolerability and safety of a flexible‐dosing strategy with darifenacin, an M3‐selective receptor antagonist, in patients with symptoms of overactive bladder (OAB).

PATIENTS AND METHODS

In this multicentre double‐blind 12‐week study, 395 patients (aged 22–89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once‐daily treatment with darifenacin controlled‐release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo‐increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse‐event reports.

RESULTS

The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at − 8.2 (−62.9%) and − 6.0 (−48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P= 0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for ‘sensitive’ patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment‐related adverse events were mild‐to‐moderate dry mouth and constipation, which led to discontinuation in < 3.0% of darifenacin‐treated patients and <1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo.

CONCLUSIONS

Darifenacin appears to be an effective, well‐tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs.
Validation of the Urgency Perception Scale
Authors: Cardozo Linda , Coyne Karin S. , Versi Eboo
Published: February 2005

OBJECTIVE

To ascertain the validity and responsiveness of the Urgency Perception Scale (UPS) as an indicator of perceived urinary urgency.

PATIENTS AND METHODS

The UPS was developed to assess perceived urinary urgency in clinical studies evaluating the efficacy of the antimuscarinic drug, tolterodine, for treating the overactive bladder (OAB) syndrome. Secondary analyses of clinical and patient assessment data from three clinical studies of tolterodine were conducted to evaluate the UPS. Construct validity was assessed by correlations between the UPS and patient voiding diary variables and other patient assessments, including: perception of bladder condition; perception of treatment benefit; the Medical Outcomes Study Short‐Form 36 health survey; the King's Health Questionnaire; the OAB Questionnaire; and the Overall Treatment Effect scale.

RESULTS

The UPS correlated well with the patients’ perception of bladder condition (correlation coefficients − 0.29 to − 0.46; all P < 0.001) and with the voiding diary variables, especially incontinence episodes (−0.30 to − 0.41) and pad usage (−0.25 to − 0.38; all P < 0.001). An improvement in UPS score at the end of treatment was consistently reflected by significant improvements among all voiding variables.

CONCLUSION

Urinary urgency is a central symptom of OAB and is particularly bothersome because of its unpredictability and consequent impact on daily life. The UPS is a valid scale by which urinary urgency can be assessed subjectively, and provides a useful tool for research into urinary urgency.
Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction
Authors: Van Moorselaar R. Jeroen A. , Hartung Rudolf , Emberton Mark , Harving Niels , Matzkin Haim , Elhilali Mostafa , Alcaraz Antonio , Vallancien Guy ,   ALF‐ONE Study Group
Published: February 2005

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVE

To assess the effect on sexual function of alfuzosin 10 mg once daily, a uroselective α1‐blocker, in men with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction.

PATIENTS AND METHODS

In all, 3076 men (mean age 65.9 years) were treated for 1 year with alfuzosin 10 mg in ‘real life’ practice. They were asked to complete the International Prostatic Symptom Score (IPSS), its appended eighth question (bother score) and the Danish Prostatic Symptom Score questionnaire for sexual dysfunction (DAN‐PSSsex). The results were analysed at the endpoint in the intent‐to‐treat population.

RESULTS

At baseline, 2434 (79.1%) men were sexually active and answered correctly at least one item of the DAN‐PSSsex. Sexual dysfunction was highly prevalent (reduced stiffness of erection, 65.3%; reduced volume of ejaculate, 63.2%; pain/discomfort on ejaculation, 20.2%), and was strongly related to the severity of LUTS and impairment of quality of life. At the endpoint, alfuzosin significantly improved the total IPSS (−6.1, − 32%) and bother score (−1.4, − 33.2%, both P < 0.001) over baseline. In those men with sexual dysfunction there were significant improvements in weighted scores related to reduced rigidity of erection (−0.5), reduced amount of ejaculate (−0.4) and pain/discomfort on ejaculation (−1.2, all P < 0.001) over baseline. The perceived improvements were more marked in men with severe LUTS or a severe bother score at baseline.

CONCLUSIONS

Sexual dysfunction is highly prevalent in men with LUTS and related to the baseline IPSS and bother score. Alfuzosin 10 mg once daily for 1 year is effective in improving LUTS and quality of life, and is well tolerated. It may even improve sexual function in those men with concomitant erectile and/or ejaculatory dysfunction.
The role of indirect radionuclide cystography during the acute phase of pyelonephritis in young women
Authors: Pinthus Jehonathan H. , Oksman Yakov , Leibovitch Ilan , Goshen Elinor , Dotan Zohar A. , Schwartz Arnon , Ramon Jacob , Zwas S. Tzila , Mor Yoram
Published: February 2005

Authors from Israel have investigated the use of dynamic renal scans in young female patients with acute pyelonephritis, combined with indirect radionuclide cystography. They found that using these techniques may avoid up to half of the delayed voiding cysto‐urethrograms, preventing the related inconvenience and cost.

OBJECTIVE

To review our experience using dynamic 99mTc‐diethylenetriamine penta‐acetic acid renal scintigraphy combined with indirect radionuclide cystography (IRC) in the acute phase of pyelonephritis, as a possible alternative to the conventional imaging, as investigating acute pyelonephritis usually includes imaging the upper urinary tract during the acute phase, to exclude obstruction, and delayed voiding cysto‐urethrography (VCUG) when underlying vesico‐ureteric reflux (VUR) is suspected.

PATIENTS AND METHODS

Between 1997 and 1999, 47 young women (median age 22 years, range 18–37) were hospitalized for acute pyelonephritis. The combined study was used during the acute phase of the disease, usually within 24 h of hospitalization. The principle of IRC is based on the reappearance of radioactivity in the ureters or kidneys after previously detecting renal clearance of an intravenously injected radioisotope. The increase in radioactivity over the ureters or kidneys indicates VUR. The subsequent follow‐up included VCUG, after recovery and at least 6 weeks after discharge.

RESULTS

Overall, 47 patients had early IRC studies; obstruction of the urinary tract during the acute phase of the disease was excluded in all. In 13 (28%) of the patients early IRC studies showed VUR involving 21 upper tract units. The renal parenchymal scan was impaired in 17 (36%) patients, and six of these 17 also had detectable concomitant reflux on IRC. Overall, 24 IRC studies (51%) were considered positive, showing VUR, renal parenchymal pathology or both; 23 (49%) were normal. Follow‐up VCUG was used in 32 patients (68%); only three (9%) detected VUR. All of the patients with VUR on follow‐up VCUG had also had an abnormal early IRC study, showing either reflux (two) or findings suggestive of pathological renal parenchyma (one).

CONCLUSIONS

In addition to the well‐established role of renal scintigraphy in excluding obstruction of the collecting system, early IRC is characterized by high sensitivity and accurate negative predictive value for detecting VUR. It can therefore be used to screen adults presenting with acute pyelonephritis for the presence of VUR. Patients with an abnormal IRC require follow‐up VCUG after complete recovery, while those with a negative study may be managed expectantly, with no further radiological evaluation. This proposed strategy may avoid up to half of the delayed VCUG studies, preclude the related inconvenience, and substantially reduce the costs.
Buccal mucosal urethroplasty: a versatile technique for all urethral segments
Authors: Dubey Deepak , Kumar Anant , Mandhani Anil , Srivastava Aneesh , Kapoor Rakesh , Bhandari Mahendra
Published: February 2005

Authors from India describe their experience in a series of patients with bulbar urethral strictures in whom they used a buccal mucosal graft. They found this to be the most versatile substitute.

OBJECTIVE

To present our experience with buccal mucosa urethroplasty for substitution of all segments of the anterior urethra, as the buccal mucosal graft (BMG) has emerged as the tissue of choice for single‐stage reconstruction of bulbar urethral strictures, but its use for reconstructing meatal, pendulous and pan‐urethral strictures has not been widely reported.

PATIENTS AND METHODS

Between January 1998 and October 2003, 92 patients had a BMG substitution urethroplasty at our institution; 75 had a single‐stage dorsal onlay BMG urethroplasty (bulbar 41, pendulous 16 and pan‐urethral 18; six combined penile skin flap and BMG) and 17 (pendulous five, pan‐urethral 10, bulbar two) a two‐stage urethroplasty. Recurrence rates, complications and cosmetic outcomes were analysed retrospectively.

RESULTS

Over a median (range) follow‐up of 34 (8–72) months, 66 (88%) patients with a one‐stage reconstruction (14/16 pendulous; 37/41, 90%, bulbar; 15/16 pan‐urethral) remained stricture‐free. The mean (range) time to recurrence was 9.4 (3–17) months. Of the nine recurrent strictures, six were managed by one‐stage optical urethrotomy and three required a repeat urethroplasty. In patients who had a staged procedure, after a mean follow‐up of 24.2 (9–56) months, one had complete graft loss, requiring re‐grafting, five required stomal revision after stage 1, and only two (12%) developed a recurrent stricture after the two‐stage urethroplasty.

CONCLUSION

A one‐stage dorsal onlay BMG urethroplasty provides excellent results for strictures involving any segment of the anterior urethra. The BMG appears to be the most versatile urethral substitute, as it can be successfully used for both one‐ and two‐stage reconstruction of the entire anterior urethra.
Proliferating‐cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki‐67
Authors: Taftachi Reza , Ayhan Ayse , Ekici Sinan , Ergen Ali , Ozen Haluk
Published: February 2005

OBJECTIVE

To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki‐67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour.

PATIENTS AND METHODS

Two groups of patients with prostate cancer, i.e. ‘metastatic’ (M, 22) who had pT3b‐4aN0M0 and pTanyN1M0, and ‘nonmetastatic’ (NM, 18), who had ≤pT3aN0M0 disease, were selected from a well‐examined and mapped group of 114 treated by radical prostatectomy. Patients in the NM group were selected by the criteria of having a Gleason score of ≤ 7. To assess proliferation, 1000 cells were counted at × 400 magnification by two observers and the percentage of tumour cells positively stained with Ki‐67 and PCNA defined as the Ki‐67 and PCNA labelling index (LI), respectively. The two LI were compared in the NM and M groups, and the correlation of the LIs with pathological stage, progression and prostate‐specific antigen (PSA)‐free survival evaluated. Prognostic values of the LI were analysed using multivariate analysis.

RESULTS

The mean (range) follow‐up was 33 (4–78) months. The mean LIs were higher in the M than the NM group for both PCNA and Ki‐67 (P = 0.02 and 0.019, respectively). Both LIs were markedly different between the groups when stratified by progression, with both significantly higher in men with progression in the NM group. Both LIs had a significant association with Gleason score, pathological stage, progression and PSA‐free survival. In multivariate analysis the PCNA LI, surgical margin status and pathological stage were independent factors for progression.

CONCLUSION

Tumour cell proliferation as assessed by Ki‐67 or PCNA correlate significantly with progression. The PCNA LI was an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria.
A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma
Authors: Ioachim Elli , Michael Michalis , Stavropoulos Nicolaos E. , Kitsiou Evangelia , Salmas Marios , Malamou‐Mitsi Vasiliki
Published: February 2005

OBJECTIVE

To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression.

MATERIALS AND METHODS

Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27–89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki‐67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon.

RESULTS

Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour‐free interval than those with high levels of tenascin.

CONCLUSION

Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.
Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy
Authors: Carver Brett S. , Kattan Michael W. , Scardino Peter T. , Eastham James A.
Published: February 2005

The controversial topic of the effect of finasteride therapy on Gleason grade, raised by the Prostate Cancer Prevention Trial, is discussed by authors from New York. They assessed a series of patients who had been treated with finasteride, and who subsequently had a radical prostatectomy, to see if this pharmaceutical agent prevented accurate Gleason grade assignment and prediction of biochemical recurrence. They found that Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy.

Authors from Amsterdam assessed the accuracy of ultrasonography‐guided fine‐needle aspiration cytology as a method of detecting occult lymph node metastases in patients with penile cancer, and found that it can be used as an initial investigation in such patients, with helpful clinical outcomes.

OBJECTIVE

To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence.

PATIENTS AND METHODS

Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for ≥ 6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate‐specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5‐year freedom from recurrence using the Kaplan‐Meier method.

RESULTS

The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5‐year actuarial freedom from recurrence was 86%.

CONCLUSION

Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5‐year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer.
Interest Rate Pass-Through: Empirical Results for the Euro Area
Authors: Bondt Gabe J. de
Published: February 2005

This paper empirically examines the interest rate pass-through at the euro area level. The focus is on the pass-through of official interest rates, approximated by the overnight interest rate, to longer-term market interest rates, which, in turn, are a proxy for the marginal costs for banks to attract deposits or grant loans, and therefore passed through to retail bank interest rates. Empirical results, on the basis of a (vector) error-correction and vector autoregressive model, suggest that the pass-through of official interest to market interest rates is complete for money market interest rates up to three months, but not for market interest rates with longer maturities. Furthermore, the immediate pass-through of changes in market interest rates to bank deposit and lending rates is found to be at most 50%, whereas the final pass-through is typically found to be close to 100%, in particular for lending rates. Empirical results for a sub-sample starting in January 1999 show qualitatively similar findings and are supportive of a quicker interest rate pass-through since the introduction of the euro. It is shown that the difference between the adjustment speed of bank deposit and lending rates (typically around one versus three months since the common monetary policy) can to a large extent significantly be explained by credit risk considerations.
Informality and Circumscription: The Blair Style of Government in War and Peace
Authors: HENNESSY PETER
Published: February 2005

In the latest of his periodic 'overflights' of the Blair style of government since 1997, Peter Hennessy examines the significance of the 2004 Butler Report (on intelligence and weapons of mass destruction prior to the Iraq War) for Tony Blair both as war premier and also as an indicator of his governing practices in general. He concludes that the Cabinet's overall performance on the road to war was seriously inadequate, and is especially critical of its failure to test out fully the Attorney General's opinion in the legality of the war.
Britain and Europe: An Unforgettable Past and an Unavoidable Future
Authors: STEPHENS PHILIP
Published: February 2005

The title of this article is taken from the opening lines of Hugo Young's brilliant history of Britain's relationship with Europe, This Blessed Plot. That book begins with a sentence that says it all: 'This is the story of 50 years in which Britain struggled to reconcile the past she could not forget with the future she could not avoid.' Those words were written in the spring of 1998. Despite the early promise of Tony Blair's European policy, little has changed since. For France and Germany, the institutions of Europe represent a uniquely successful attempt to exorcise the past. For its part, Britain lives in the shadow of its history.

The struggle to reconcile national identity with strategic interests is as acute as it has ever been. For all that Mr Blair's government has done something in recent years to make Britain's case in Europe, it has failed to make Europe's case in Britain.
Islands of the Mind: New Labour's Defensive Engagement with the European Union
Authors: BAKER DAVID
Published: February 2005

This article reviews the cumulative development of New Labour's attitude and strategy towards the EU since the late 1980s and argues that the first two New Labour governments' approach to the EU represented a distinct retreat from the 'constructive engagement' and social democratic philosophy of Tony Blair's early modernising phase, moving steadily to occupy a much more traditional British position of 'defensive engagement', mixing national preferences with Atlanticism, and resisting further political integration in favour of traditional 'intergovernmentalism'. It is further argued that New Labour's prioritisation and preferencing of a UK institutional and political economy based upon economic liberalisation, the preservation of key aspects of national sovereignty, and maintaining Atlanticism as the bedrock of Europe's external foreign and defence policies have left Britain almost as far from the true 'heart of Europe' as when Blair inherited office from John Major in 1997.
Will the Government Catch the Wind?
Authors: TOKE DAVID
Published: February 2005

The government's Renewable Obligation system aims to supply 10 per cent of UK electricity from renewable sources by 2010. Although the headlines suggest that planning controversies hamper these objectives, by the summer of 2004 enough capacity had been given planning consent to supply 4 per cent of UK electricity from new renewable energy sources. Enough renewable capacity to supply 7 per cent of UK electricity from renewables will probably be operational by 2010. The bulk of this is coming from onshore wind power, especially based in Scotland, and also offshore wind power. The offshore schemes are more expensive and need additional support outside the Renewable Obligation. The Conservatives have promised to bring in planning curbs for onshore wind power. There is pressure for more nuclear power, but this is likely to be impossible to finance without a very large subsidy from the Department of Trade and Industry.
Why Are Houses More Affordable in France?
Authors: BALL JANE
Published: February 2005

It is not surprising that houses are more affordable in France than in Britain. Even the Barker Report proposes taxing builders, and the UK's record should be a source of shame. France has constructed roughly 150‐200 per cent more housing than the United Kingdom for the last 40 years, incentivising construction by fiscal measures and by the institutional environment, including favouring social housing. Spain has substantial recent construction which on its own may not produce affordability, with little social housing. Construction aids can be of relatively low cost and produce affordable homes, but this can reduce the funds available to assist the very poor.
Sweetening the US Legislature: The Remarkable Success of the Sugar Lobby
Authors: ALVAREZ JOSÉ
Published: February 2005

The US sweetener industry comprises the production and processing of sugarcane, sugar beet and corn and, more recently, non‐caloric products. The industry has always been protected by federal legislation. Such legislation has had positive and negative impacts on domestic sugar prices, which have remained relatively stable but well above the world price. José Alvarez discusses three factors behind that protective status: the industry's economic importance, the large representation of sweetener‐producing states in the US Congress, and a powerful and successful lobby. Under current conditions, no change in the status quo should be expected. The major potential contingency on the horizon could be an agreement reached at the World Trade Organization eliminating existing levels of worldwide protection. Free trade negotiations have added new pressures to the US support programme. Time will tell whether or not the domestic success of the US sweetener industry can be duplicated in the international arena.
The Hunting of the Snark: Reflections on a Half Century of Crime
Authors: CROFT JOHN
Published: February 2005

John Croft is a former head of the UK's Home Office Research and Planning Unit, so is able to draw on extensive experience to offer this reflective examination of half a century of involvement in the criminal justice system. He surveys the shifting patterns of research, popular attitudes and social emphasis, relates them to the changing political context, and asks a number of telling questions — including 'What works?' The author concludes that not much does work, and that government has had little influence on fluctuations in the crime rate since the Second World War. He recommends periodic reviews of research across the whole criminal justice system, perhaps on a ten‐year cycle; more comparative research, which would help to illuminate problems and perhaps suggest solutions; a closer look at the interaction between social and criminal policies; and a re‐examination of risk assessment, particularly in its implications for penology.
Reordering Honours: Perspectives and Possibilities
Authors: CANNADINE DAVID
Published: February 2005

The UK's honour system is a strange mixture of ancient tradition and Victorian invention, and is drifting into obsolescence. Many of its honours recall a vanished imperial past, or maintain increasingly unacceptable demarcations between classes of recipients. However, the high rate of acceptance of honours and the almost universal existence of similar systems throughout the world suggests that people do still value an honours system. But what form should it take? In 2004 two separate reports looked at most elements of the system and produced recommendations, though their impacts were lost in the shadow of the far more dramatic Butler Report. David Cannadine assesses both honours reports and their prospects for adoption at a time when the policy‐makers and government are preoccupied with other issues. He concludes that the time is right for change — in spite of the inevitable opposition from some quarters — given that both Whitehall and Westminster agree that change is necessary.
Setting Standards for Children
Authors: ROBERTS HELEN
Published: February 2005

In September 2004, the publication of a National Service Framework (NSF) for children set standards for what children and their families, young people, and expectant mothers can expect from the National Health Service. This article describes some of what the NSF includes, and why it is important.
Enduring Continuity and Endless Change in the British Civil Service
Authors: DAVIS JON
Published: February 2005

The British Civil Service has often been criticised. The most recent censure was from Ed Straw. In 'The dead generalist', an article for the think tank Demos, he attacked the Civil Service for its unchanging nature and its corresponding failure to meet the challenges of the twenty‐first century. Jon Davis's article demonstrates that change is a constant for officialdom, that Mr Straw has some of his facts wrong, and that very similar criticism was made nearly half a century ago, though all the while agreeing that all is not well (and possibly can never be perfect) in Whitehall.
Patterns and Personality Correlates of Implicit and Explicit Attitudes Toward Christians and Muslims
Authors: ROWATT WADE C. , FRANKLIN LEWIS M. , COTTON MARLA
Published: February 2005

We explored implicit and explicit attitudes toward Muslims and Christians within a predominantly Christian sample in the United States. Implicit attitudes were assessed with the Implicit Association Test (IAT), a computer program that recorded reaction times as participants categorized names (of Christians and Muslims) and adjectives (pleasant or unpleasant). Participants also completed self‐report measures of attitudes toward Christians and Muslims, and some personality constructs known to correlate with ethnocentrism (i.e., right‐wing authoritarianism, social dominance orientation, impression management, religious fundamentalism, intrinsic‐extrinsic‐quest religious orientations). Consistent with social identity theory, participants' self‐reported attitudes toward Christians were more positive than their self‐reported attitudes toward Muslims. Participants also displayed moderate implicit preference for Christians relative to Muslims. This IAT effect could also be interpreted as implicit prejudice toward Muslims relative to Christians. A slight positive correlation between implicit and explicit attitudes was found. As self‐reported anti‐Arab racism, social dominance orientation, right‐wing authoritarianism, and religious fundamentalism increased, self‐reported attitudes toward Muslims became more negative. The same personality variables were associated with more positive attitudes toward Christians relative to Muslims on the self‐report level, but not the implicit level.
MCTD – Mixed Connective Tissue Disease
Authors: Haustein Uwe‐Frithjof
Published: February 2005

Die Mixed connective tissue disease (MCTD) zeichnet sich als eine Krankheitsentität mit Überlappungssymptomen des Lupus erythematodes (LE), der systemischen Sklerodermie (SSc), Dermatomyositis/Polymyositis (DM/PM) sowie der Rheumatoid‐Arthritis (RA) aus. Als diagnostische Kriterien gelten der serologische Nachweis von hohen Antikörpertitern gegen U1RNP und das Vorkommen von mindestens 3 der 5 folgenden klinischen Symptome: Ödem der Hände, Synovitis, Myositis, Raynaud‐Phänomen und Akrosklerose. Pathogenetisch werden neben genetischen auch infektiöse (virale) Aspekte diskutiert. Die Anerkennung der MCTD als eigene Krankheitsentität ist nicht unumstritten, Bezeichnungen wie „undifferenzierte Bindegewebserkrankung” oder „Überlappungssyndrome” helfen nicht weiter. Jeweils ein Viertel bzw. ein Drittel der MCTD‐Patienten gehen im Krankheitsverlauf in einen LE bzw. in eine SSc über. Therapeutisch werden Glukokortikoide in Kombination mit Immunsuppressiva sowie Endothelin‐Rezeptor‐Antagonisten empfohlen. Doppelblindstudien fehlen. Die Prognose ist relativ gut. Unter den Todesursachen dominieren pulmonale Hypertonie, respiratorische und Herzinsuffizienz sowie Infektionen.
A Review of the Risk Factors for, Consequences, Diagnosis, and Management ofHelicobacter pyloriin Adults with Intellectual Disabilities
Authors: Wallace R. A. , Schluter P. J. , Duff M. , Ouellette‐Kuntz H. , Webb P. M. , Scheepers M.
Published: February 2005

Abstract This paper reviews the epidemiology ofHelicobacter pylori(H. Pylori) in adults with intellectual disability (ID) including clinical presentation, risk factors for infection and diseases, and assesses the best options for testing and treatment. It was observed that particular groups of adults with ID have significantly higher rates ofH. pyloriinfection, and possibly disease consequences including peptic ulcer disease and gastric cancer, when compared to the general population, although the presentation with typical dyspepsia in people with ID is rare. Identified independent risk factors for infection include a history of institutionalization, lower ability, higher levels of behavior problems, and living with flatmates with oral hypersalivation or fecal incontinence. The presence of ID and the associated biopsychosocial factors necessitate development of adaptations to the usual testing and treatment methods as part of a preventive health strategy in order to relieve occult symptoms, and prevent disease development. Among the available tests, the fecal antigen or serology tests are equally acceptable to adults with ID regardless of their level of disability or behaviors, although only those who function more normally can perform the urea breath test. TheH. pylorieradication rate is lower, with treatment side‐effect and recurrence rates higher, compared to the general population; but, given the evidence that patients with ID carry the infection and associated pathology for long periods, testing and treating those with at‐risk is recommended. While not recommending screening all adults with ID forH. pyloriinfection, the authors provide an overall evidence‐based position statement on whom to test and treat, and how to diagnose and manage this infection, an important cause of preventable disease.
Neurosteroid administration and withdrawal alter GABAA receptor kinetics in CA1 hippocampus of female rats
Authors: Smith Sheryl S. , Gong Qi Hua
Published: February 2005

Withdrawal from the GABA‐modulatory steroid 3α‐OH‐5α‐pregnan‐20‐one (3α,5α‐THP) following exposure of female rats to the parent compound progesterone (P) produces a syndrome characterized by behavioural excitability in association with up‐regulation of the α4 subunit of the GABAA receptor (GABAR) in the hippocampus. Similar changes are seen after 48 h exposure to its stereoisomer, 3α,5β‐THP. Here, we further characterize the effects of P withdrawal on GABAR kinetics, using brief (1 ms) application of 5–10 mm GABA to outside‐out patches from acutely isolated CA1 hippocampal pyramidal cells. Under control conditions, GABA‐gated current deactivated biexponentially, with τfast= 12–19 ms (45–60% of the current), and τslow= 80–140 ms. P withdrawal resulted in marked acceleration of deactivation (τfast= 3–7 ms and τslow= 30–100 ms), as did 48 h exposure to 3α,5β‐THP (τfast= 5–8 ms; τslow= 40–120 ms). When recombinant receptors were tested in HEK‐293 cells, a similar acceleration in τfast was observed for α4β2δ and α4β2γ2 GABARs, compared to α1β2γ2 and α5β2γ2 receptors. In addition, τslow was also accelerated for α4β2δ receptors, which are increased following steroid withdrawal. As predicted by the Jones‐Westbrook model, this change was accompanied by reduced receptor desensitization as well as an acceleration of the rate of recovery from rapid desensitization. A theoretical analysis of the data suggested that steroid treatment leads to receptors with a greater stability of the bound, activatable state. This was achieved by altering multiple parameters, including desensitization and gating rates, within the model. These results suggest that fluctuations in endogenous steroids result in altered GABAR kinetics which may regulate neuronal excitability.
Extracellular potassium effects are conserved within the rat erg K+ channel family
Authors: Sturm Patrick , Wimmers Sönke , Schwarz Jürgen R. , Bauer Christiane K.
Published: February 2005

The biophysical properties of native cardiac erg1 and recombinant HERG1 channels have been shown to be influenced by the extracellular K+ concentration ([K+]o). The erg1 conductance, for example, increases dramatically with a rise in [K+]o. In the brain, where local [K+]o can change considerably with the extent of physiological and pathophysiological neuronal activity, all three erg channel subunits are expressed. We have now investigated and compared the effects of an increase in [K+]o from 2 to 10 mm on the three rat erg channels heterologously expressed in CHO cells. Upon increasing [K+]o, the voltage dependence of activation was shifted to more negative potentials for erg1 (ΔV0.5=−4.0 ± 1.1 mV, n= 28) and erg3 (ΔV0.5=−8.4 ± 1.2 mV, n= 25), and was almost unchanged for erg2 (ΔV0.5=−2.0 ± 1.3 mV, n= 6). For all three erg channels, activation kinetics were independent of [K+]o, but the slowing of inactivation by increased [K+]o was even more pronounced for erg2 and erg3 than for erg1. In addition, with increased [K+]o, all three erg channels exhibited significantly slower time courses of recovery from inactivation and of deactivation. Whole‐cell erg‐mediated conductance was determined at the end of 4 s depolarizing pulses as well as with 1 s voltage ramps starting from the fully activated state. The rise in [K+]o resulted in increased conductance values for all three erg channels which were more pronounced for erg2 (factor 3–4) than for erg1 (factor 2.5–3) and erg3 (factor 2–2.5). The data demonstrate that most [K+]o‐dependent changes in the biophysical properties are well conserved within the erg K+ channel family, despite gradual differences in the magnitude of the effects.
Early origins of obesity: programming the appetite regulatory system
Authors: McMillen I. Caroline , Adam Clare L. , Mühlhäusler Beverly S.
Published: February 2005

There is evidence that changes in perinatal nutrition programme the development of relative fat mass and the regulation of appetite in adult life. These studies have been primarily in the rodent utilizing maternal overnutrition or undernutrition imposed at different stages of pregnancy and beyond, mapping of neuropeptide localization and activity and appropriate null mutant models. Whilst the rodent offers significant advantages in terms of a short gestation and the availability of useful transgenic and null mutant models, there are also advantages to using an animal model more akin to the human, in which all components of the ‘fat–brain axis’ are present before birth, such as the sheep. This review summarizes recent work on the expression and localization of the ‘appetite regulatory’ peptides in the fetal rodent and sheep hypothalamus and their potential role in the early programming of postnatal appetite and obesity.
Exercise in the fasted state facilitates fibre type‐specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans
Authors: De Bock K. , Richter E. A. , Russell A. P. , Eijnde B. O. , Derave W. , Ramaekers M. , Koninckx E. , Léger B. , Verhaeghe J. , Hespel P.
Published: February 2005

The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant‐load bicycle exercise (∼75%), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before (∼150 g) and during (1 g (kg bw)−1 h−1) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type‐specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 ± 2% to 6 ± 2% (P= 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 ± 2% to 10 ± 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise‐induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 ± 7.8 mmol kg−1 h−1), mean rate of postexercise muscle glycogen resynthesis was 3‐fold greater in F (32.9 ± 2.7 mmol kg−1 h−1, P= 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 μU ml−1) than in CHO (+14.63 μU ml−1, P= 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO‐fed state. Furthermore, facilitated glucose‐induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state.
Parametric Analysis of Existing Gas Turbines With Inlet Evaporative and Overspray Fogging
Authors: Bhargava R. , Meher-Homji C. B.
Published: February 2005

With deregulation in the power generation market and a need for flexibility in terms of power augmentation during the periods of high electricity demand, power plant operators all over the world are exploring means to augment power from both the existing and new gas turbines. An approach becoming increasingly popular is that of the high pressure inlet fogging. In this paper, the results of a comprehensive parametric analysis on the effects of inlet fogging on a wide range of existing gas turbines are presented. Both evaporative and overspray fogging conditions have been analyzed. The results show that the performance parameters indicative of inlet fogging effects have a definitive correlation with the key gas turbine design parameters. In addition, this study indicates that the aeroderivative gas turbines, in comparison to the heavy-duty industrial machines, have higher performance improvement due to inlet fogging effects. Plausible reasons for the observed trends are discussed. This paper represents the first systematic study on the effects of inlet fogging for a large number (a total of 67) of gas turbines available from the major gas turbine manufacturers.
A Comparative Study of Two Transition Zone Models in Heat Transfer Predictions
Authors: Byvaltsev P. M. , Kawaike K.
Published: February 2005

A comparative study of two transition zone models was carried out to assess their ability to simulate boundary layer laminar-turbulent transition. Transition modeling is based on the use of an algebraic equation for the intermittency distribution. The crucial difference between the models lies in the nondimensional breakdown rate formulation. A two-dimensional marching code was used to combine these models with the modified Johnson and King turbulence model and the algebraic “nonturbulence” model developed earlier. Flat plate and various turbine blade heat transfer measurements were used in the comparison. One model gave reasonably accurate results for most of the test cases considered.
Cooling Tower Performance Evaluation: Merkel, Poppe, and e-NTU Methods of Analysis
Authors: Kloppers Johannes C. , Kro¨ger Detlev G.
Published: February 2005

The heat rejected and water evaporated in mechanical and natural draft cooling towers are critically evaluated by employing the Merkel, Poppe, and e–number-of-transfer-units e-NTU methods of analysis, respectively, at different operating and ambient conditions. The importance of using a particular method of analysis when evaluating the performance characteristics of a certain fill material and subsequently employing the same analytical approach to predict cooling tower performance is stressed. The effect of ambient humidity and temperature on the performance of cooling towers employing the Merkel, e-NTU, and Poppe methods of analysis are evaluated.
Using Hydrogen as Gas Turbine Fuel
Authors: Chiesa Paolo , Lozza Giovanni , Mazzocchi Luigi
Published: February 2005

This paper addresses the possibility to burn hydrogen in a large size, heavy-duty gas turbine designed to run on natural gas as a possible short-term measure to reduce greenhouse emissions of the power industry. The process used to produce hydrogen is not discussed here: we mainly focus on the behavior of the gas turbine by analyzing the main operational aspects related to switching from natural gas to hydrogen. We will consider the effects of variations of volume flow rate and of thermophysical properties on the matching between turbine and compressor and on the blade cooling of the hot rows of the gas turbine. In the analysis we will take into account that those effects are largely emphasized by the abundant dilution of the fuel by inert gases (steam or nitrogen), necessary to control the NOx emissions. Three strategies will be considered to adapt the original machine, designed to run on natural gas, to operate properly with diluted hydrogen: variable guide vane (VGV) operations, increased pressure ratio, re-engineered machine. The performance analysis, carried out by a calculation method including a detailed model of the cooled gas turbine expansion, shows that moderate efficiency decays can be predicted with elevated dilution rates (nitrogen is preferable to steam under this point of view). The combined cycle power output substantially increases if not controlled by VGV operations. It represents an opportunity if some moderate re-design is accepted (turbine blade height modifications or high-pressure compressor stages addition).
Comparison of Linear and Nonlinear Gas Turbine Performance Diagnostics
Authors: Kamboukos Ph. , Mathioudakis K.
Published: February 2005

The features of linear performance diagnostic methods are discussed, in comparison to methods based on full nonlinear calculation of performance deviations, for the purpose of condition monitoring and diagnostics. First, the theoretical background of linear methods is reviewed to establish a relationship to the principles used by nonlinear methods. Then computational procedures are discussed and compared. The effectiveness of determining component performance deviations by the two types of approaches is examined, on different types of diagnostic situations. A way of establishing criteria to define whether nonlinear methods have to be employed is presented. An overall assessment of merits or weaknesses of the two types of methods is attempted, based on the results presented in the paper.