bluuebunny/crossref_metadata_2025_split huggingface dataset:
Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to treatment and correlation with NAb
Authors: Barbero P , Bergui M , Versino E , Ricci A , Zhong J J , Ferrero B , Clerico M , Pipieri A , Verdun E , Giordano L , Durelli L ,   INCOMIN Trial Study Group
Published: December 2005

Background In RRMS, clinical exacerbations are usually associated with different types of active lesions at MRI, including: hyperintense lesions on T1-weighted post-gadolinium sequences; new hyperintense lesions or enlarging old lesions on PD/T2-weighted scans; or new hypointense lesions on T1-weighted pre-Gd sequences. Objective/methods Primary outcome was the occurrence of patients with at least one active MRI lesion of the different types indicated above during treatment with 250 mg every other day (EOD) interferon beta (IFNβ)-1b or 30 mg once weekly (OW) IFNβ-1a in outpatients with RRMS (INCOMIN Trial). Results The number of patients with at least one ‘active’ lesion, evaluated over the two-year follow-up, was significantly (P=0.014) lower in the EOD IFNβ-1b arm (13/76, 17%) then in the OW IFNβ-1a arm (25/73, 34%). NAb frequency over two-year follow-up was 22/65 (33.8%) in the EOD IFNβ-1b arm and 4/62 (6.5%) in the OW IFNβ-1a arm, significantly greater in the EOD IFNβ-1b arm. Conclusions The development of MRI active lesions is strongly reduced by EOD-IFNβ-1b compared with OW-IFNβ-1a, indicating that EOD-IFNβ-1b is more effective than OW-IFNβ-1a in reducing ongoing inflammation and demyelination in MS. Logistic regression showed that NAb status did not affect the risk of MRI activity.
Partial Surgical Removal of Growth Hormone-Secreting Pituitary Tumors Enhances the Response to Somatostatin Analogs in Acromegaly
Authors: Colao Annamaria , Attanasio Roberto , Pivonello Rosario , Cappabianca Paolo , Cavallo Luigi M. , Lasio Giovanni , Lodrini Alessandro , Lombardi Gaetano , Cozzi Renato 
Published: January 2006

Abstract
Context: Surgery is a cornerstone in the treatment of acromegaly, but its efficacy in large, invasive tumors is scant.
Objective: The objective of this study was to investigate whether partial surgical removal of GH-secreting pituitary tumors enhances the response rate to somatostatin analogs (SSA; sc octreotide, slow-release octreotide, and lanreotide).
Design: This was a multicenter, open, retrospective study.
Setting: The study was performed at university hospitals.
Subjects and Methods: Eighty-six patients (42 women and 44 men; age, 42 ± 14 yr) with acromegaly were studied.
Interventions: Patients underwent two courses of octreotide, lanreotide, or slow-release octreotide treatments before and after surgery of at least 6 months.
Main Outcome Measure: The main outcome measure was normal IGF-I levels for age.
Results: Presurgical SSA treatment significantly decreased GH and IGF-I levels in all patients. GH levels were less than 2.5 μg/liter in 12 patients (14%); IGF-I levels normalized in nine (10%). After surgery, GH and IGF-I levels further decreased in all patients; tumor removal was greater than 75% in 50 (58%), 50.1–75% in 21 (24%), 25.1–50% in 10 (12%), and less than 25% in five patients (6%). Preoperatively, pituitary function was impaired in 12 patients (14%). Postsurgical SSA treatment lowered GH levels to less than 2.5 μg/liter in 49 (56%) and normalized IGF-I levels in 48 patients (55%). The success rate was significantly increased compared with that before surgery (P &lt; 0.0001). GH (r = −0.48; P &lt; 0.0001) and IGF-I levels (r = −0.38; P = 0.0003) after postsurgery SSA treatment correlated with the amount of tumor surgically removed. After surgery, pituitary function was impaired in 28 patients (32.6%) and was improved in 12 patients (13.9%). The cumulative prevalence of pituitary deficiency did not change during the study (normal function from 40 to 42%; deficiency from 60 to 58%).
Conclusions: Surgical tumor removal (&gt;75%) enhances the response to SSAs without impairing pituitary function. Our data indicate that surgical debulking has a significant place in the treatment algorithm of acromegaly.
Thyrotropin Suppression by Metformin
Authors: Vigersky Robert A. , Filmore-Nassar Amy , Glass Allan R. 
Published: January 2006

AbstractContext: Drug-drug interactions are common but often are discovered only long after initial drug release. Metformin has been available in the United States for 9 yr and elsewhere for many years, but as of yet there are no reports that the drug modifies thyroid hormone economy.Objective: The objective of the study was to describe the clinical and biochemical findings of four patients with chronic hypothyroidism, previously euthyroid on fixed doses of l-T4 for several years, in whom the metformin was initiated.Design: This was a retrospective review.Setting: The study was conducted at a tertiary care military hospital providing care to active-duty soldiers, sailors, and marines, retirees of the armed forces, and their eligible dependents.Participants: Four patients with chronic hypothyroidism who were placed on metformin participated in the study.Intervention, Main Outcome Measure: Serum TSH, free T4, and free T3 levels were measured during metformin treatment.Results: Initiation of treatment with metformin (three for diabetes mellitus and one for nonalcoholic steatohepatitis) caused suppression of TSH to subnormal levels without clinical symptoms of hyperthyroidism in any patients. There was no change in free T4 or free T3 in patient 1.Conclusions: No other potential causes of TSH suppression, including medication changes or interference in the TSH assay, could be identified. The mechanism of the fall in serum TSH in these four patients is unclear at this time. Should these findings be confirmed in larger prospective studies, metformin’s ability to suppress TSH without causing clinical or chemical hyperthyroidism might render this drug a useful adjunct to the treatment of patients with thyroid cancer.
The crisis in sexual health and developing genitourinary medicine services: lessons from a primary care trust
Authors: Laverty Susan , Pugh R Nicholas , Joseph A T 
Published: December 2005

The House of Commons Health Select Committee recently described a national crisis in sexual health. Alarmed by dramatic increases in the rates of sexually transmitted infections (STIs) and appalled by over-stretched, under-resourced genitourinary (GU) medicine services, the committee has called for urgent action. The increasing rates of STIs locally, a significant cluster of syphilis cases, and an over-burdened GU medicine service prompted Walsall primary care trust to undertake an evaluation of local service provision. The results were used to inform the development of GU medicine services locally and Walsall's sexual health strategy. This paper reports the results of the evaluation and the implications for service development. The Walsall GU medicine service was evaluated using three approaches, based on standards for GU medicine service provision identified from the literature. Routine data were used to analyse trends in STIs and service activity, including access times. These data further informed the evaluation process. Local stakeholder views on GU medicine service provision were sought using semi-structured interviews. Most standards relating to the provision of core services, including those for the management of patients with HIV infection, were met. High levels of patient satisfaction were reported. However, under-staffing, inadequate clinic facilities, and limited joint working with other agencies were highlighted as key concerns. Tackling sexual health inequalities and improving the sexual health of the population requires investment in resources and manpower, improved partnership working, and configuring services around the needs of patients. In addition, and perhaps most importantly, it will require a shift in how both health professionals and the public perceive and utilize sexual health services.
The efficacy of combining several risk factors as a screening test
Authors: Wald Nicholas J , Morris Joan K , Rish Simon 
Published: December 2005

Objective: To determine the quantitative effect on overall screening performance (detection rate for a given false-positive rate) of using several moderately strong, independent risk factors in combination as screening markers. Setting: Theoretical statistical analysis. Methods: For the purposes of this analysis, it was assumed that all risk factors were independent, had Gaussian distributions with the same standard deviation in affected and unaffected individuals and had the same screening performance. We determined the overall screening performance associated with using an increasing number of risk factors together, with each risk factor having a detection rate of 10%, 15% or 20% for a 5% false-positive rate. The overall screening performance was estimated as the detection rate for a 5% false-positive rate. Results: Combining the risk factors increased the screening performance, but the gain in detection at a constant false-positive rate was relatively modest and diminished with the addition of each risk factor. Combining three risk factors, each with a 15% detection rate for a 5% false-positive rate, yields a 28% detection rate. Combining five risk factors increases the detection rate to 39%. If the individual risk factors have a detection rate of 10% for a 5% false-positive rate, it would require combining about 15 such risk factors to achieve a comparable overall detection rate (41%). Conclusion: It is intuitively thought that combining moderately strong risk factors can substantially improve screening performance. For example, most cardiovascular risk factors that may be used in screening for ischaemic heart disease events, such as serum cholesterol and blood pressure, have a relatively modest screening performance (about 15% detection rate for a 5% false-positive rate). It would require the combination of about 15 or 20 such risk factors to achieve detection rates of about 80% for a 5% false-positive rate. This is impractical, given the risk factors so far discovered, because there are too few risk factors and their associations with disease are too weak.
The West Midlands breast cancer screening status algorithm – methodology and use as an audit tool
Authors: Lawrence Gill , Kearins Olive , O'Sullivan Emma , Tappenden Nancy , Wallis Matthew , Walton Jackie 
Published: December 2005

Objectives: To illustrate the ability of the West Midlands breast screening status algorithm to assign a screening status to women with malignant breast cancer, and its uses as a quality assurance and audit tool. Methods: Breast cancers diagnosed between the introduction of the National Health Service [NHS] Breast Screening Programme and 31 March 2001 were obtained from the West Midlands Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via breast screening units, and the remaining cancers were assigned to one of eight screening status categories. Multiple primaries and recurrences were excluded. Results: A screening status was assigned to 14,680 women (96% of the cohort examined), 110 cancers were not registered at the WMCIU and the cohort included 120 screen-detected recurrences. Conclusions: The West Midlands breast screening status algorithm is a robust simple tool which can be used to derive data to evaluate the efficacy and impact of the NHS Breast Screening Programme.
Estimating mean sojourn time and screening test sensitivity in breast cancer mammography screening: new results
Authors: Weedon-Fekjær Harald , Vatten Lars J , Aalen Odd O , Lindqvist Bo , Tretli Steinar 
Published: December 2005

Objective: To assess if new screening techniques, increased use of hormone replacement therapy, or the transition from breast cancer screening trials to large scale screening programmes may influence the average time in preclinical screening detectable phase (mean sojourn time [MST]) or screening test sensitivity (STS). Setting: Screening and interval data for 395,188 women participating in the Norwegian Breast Cancer Screening Programme (NBCSP). Methods: Weighted non-linear least-square regression estimates using a tree step Markov chain model, and a sensitivity analysis of the possible impact by opportunistic screening between ordinary breast cancer screening rounds. Results: MST was estimated to 6.1 (95% confidence interval [CI] 5.1–7.0) years for women aged 50–59 years, and 7.9 (95% CI 6.0–7.9) years for those aged 60–69 years. Correspondingly, STS was estimated to 58% (95% CI 52–64 %) and 73 % (67–78 %), respectively. Simulations revealed that opportunistic screening may give a moderate estimation bias towards higher MST and lower STS. Assuming a probable 21% higher background incidence, due to increased hormone replacement therapy use, MST estimates decreased to 3.9 and 5.0 years for the two age groups, and STS increased to 75 and 85%. Conclusions: The new estimates indicate that screening detectable phase is longer than that found in previous mammography trials/programmes, but also that the sensitivity of the screening test is lower. Overall, the NBCSP detects more cancer cases than most previous trials/programmes.
Development of Sound Absorbers for Large Spaces
Authors: Kobayashi Yoshihito , Kitamura Toshiya , Yamada Shinji 
Published: December 2005

Moulded chairs have been developed, in which sound absorption at low frequency bands is increased by using the seat section and/or the back section as a resonator. In addition, a translucent sound absorption panel has been developed for application in large spaces. In the case of the chairs the resonance frequency, determined by the position, number, and depth of the holes, was examined. Prototypes were constructed, and the equivalent absorption area was measured in a reverberation room. The resonators of the chairs achieved an equivalent absorption area of 0.15 m2/seat, in the 125 Hz band. For the case of the translucent material, sound absorption was measured and compared with conventional sound absorption materials. The panels were designed in order to control sound fields in large spaces. The panels achieved a sound absorption coefficient of 0.6 to 1.0 at middle and high frequency bands.
Measurements of Acoustical Properties in Cistercian Abbeys
Authors: Magrini Ugo , Magrini Anna 
Published: December 2005

The work reports the results of measurements of acoustical parameters obtained in six abbeys of the Cistercian order (XIIth century). Three of them, Silvacane, Senanque and Le Thoronet, are in the South of France. They have the original layout both outside and inside the building, and are finished in local stone. The values of the reverberation time RT, measured in these abbeys, are higher than in other religious buildings of almost the same volume. The other three abbeys, at Tiglieto, Morimondo and Chiaravalle, in Northern Italy, have similar characteristics as regards the plan and the simplicity of the interiors, but their inner surfaces are of bricks and stones, in different proportions. The measured RT values are lower than those of the French abbeys. In the abbey at Le Thoronet, the RT values are higher at low and middle frequencies, which corresponds to the range of liturgical and mainly Gregorian choral music, played in Cistercian abbeys without musical instruments. This effect could have been the aim of the Cistercian architects, experienced in architectural acoustics, or is the consequence of the use of a special kind of stone, that has lower absorbing properties than the materials used in the other churches.
Audit Committees, Boards, and the Quality of Reported Earnings*
Authors: Vafeas Nikos 
Published: January 2006

AbstractI use data on 252 U.S. firms between 1994 and 2000 to study the relationship between audit committees and boards of directors with financial reporting quality. I initially document several changes in committee and board profile during the sample period. Results from logistic regressions suggest that measures of audit committee and board structure are related to earnings quality in a manner that is generally consistent with the predictions of agency theory. This study contributes to extant knowledge by employing different earnings quality measures from prior studies, and by expanding the range of audit committee attributes deemed important in determining audit committee performance.
Evidence of Choice Avoidance in Capital‐Investment Judgements*
Authors: Sawers Kimberly M. 
Published: January 2006

AbstractEvaluating capital‐investment decisions is an important function of managerial accountants. There is anecdotal evidence, however, that managers avoid making decisions or delay decisions, which is costly in terms of time, effort, and lost opportunities. Prior research has shown that choice avoidance among nonprofessionals making personal decisions is associated with having to choose between alternatives with very different features or that require trade‐offs of very important goals (choice difficulty). It is unclear, however, whether experienced managers, using the analytical decision tools at their disposal, respond in the same way as nonprofessionals when making accounting decisions. Hence, this study examines whether increased choice difficulty increases negative affect in the capital‐investment decision‐making process and, as a result, the tendency of managers to avoid choice even when analytical decision tools are used. In an experiment with 120 executives, participants facing more difficult decisions reported they felt more worried, nervous, uneasy, and anxious and had a greater desire to postpone making the decision than participants in a control group. Participants provided with a decision aid designed to help them focus their cognitive effort reported a lower desire to postpone making the decision than participants in the choice‐difficulty conditions without the decision aid. I conclude by discussing the result's implications for managers and accountants.
Determinants of Managerial Earnings Guidance Prior to Regulation Fair Disclosure and Bias in Analysts' Earnings Forecasts*
Authors: Hutton Amy P. 
Published: January 2006

AbstractPrior to Regulation Fair Disclosure (“Reg FD”), some management privately guided analyst earnings estimates, often through detailed reviews of analysts' earnings models. In this paper I use proprietary survey data from the National Investor Relations Institute to identify firms that reviewed analysts' earnings models prior to Reg FD and those that did not. Under the maintained assumption that firms conducting reviews guided analysts' earnings forecasts, I document firm characteristics associated with the decision to provide private earnings guidance. Then I document the characteristics of “guided” versus “unguided” analyst earnings forecasts. Findings demonstrate an association between several firm characteristics and guidance practices: managers are more likely to review analyst earnings models when the firm's stock is highly followed by analysts and largely held by institutions, when the firm's market‐to‐book ratio is high, and its earnings are important to valuation but hard to predict because its business is complex. A comparison of guided and unguided quarterly forecasts indicates that guided analyst estimates are more accurate, but also more frequently pessimistic. An examination of analysts' annual earnings forecasts over the fiscal year does not distinguish between guidance and no‐guidance firms; both experience a “walk‐down” in annual estimates. To distinguish between guidance and no‐guidance firms, one must examine quarterly earnings news: unguided analysts walk down their annual estimates when the majority of the quarterly earnings news is negative; guided analysts walk down their annual estimates even though the majority of the quarterly earnings news is positive.
The Link between Earnings Conservatism and the Price‐to‐Book Ratio*
Authors: PAE JINHAN , THORNTON DANIEL B. , WELKER MICHAEL 
Published: January 2006

AbstractWe hypothesize and find that (1) earnings conservatism, the tendency of firms to recognize bad news in earnings on a more timely basis than good news, is substantially greater in portfolios of firms with lower price‐to‐book ratios than in portfolios of firms with higher price‐to‐book ratios; and (2) the negative association between earnings conservatism and the price‐to‐book ratio stems primarily from the accrual component of earnings, not the operating cash flow component of earnings. Our results suggest that studies using earnings‐returns associations to investigate cross‐sectional or time‐series differences in earnings conservatism risk drawing erroneous inferences unless the research designs control for cross‐sectional or time‐series variation in price‐to‐book ratios.
Aggregation, Dividend Irrelevancy, and Earnings‐Value Relations*
Authors: YEE KENTON K. 
Published: January 2006

AbstractIn this paper I show that the aggregation of operating and financial income imposes three conditions on earnings‐based value functions. These three conditions provide a shortcut way to identify dividend irrelevant value functions. For example, consider any value function Vt of book value bt, earnings xt, and dividends dt. The aggregation conditions imply that Vt must be of the form Vt = (1 − k)bt + k [f xt − dt]. f is the permanent earnings capitalization factor and undetermined weight k may be any function of Δt ≡[φxt − dt] − bt. The Ohlson 1995 model is the special case when k is constant. But generally k does not have to be constant to maintain dividend irrelevancy. Whenk varies with Δt, Vt is nonlinear in earnings. Hence, this result specifies how Vt may be nonlinear in earnings in settings with limited liability or production or abandonment options and still be dividend‐irrelevant.An even more remarkable feature of this result is that it holds whether accounting is clean surplus or not. One must conclude that accounting‐based valuation properly builds from accounting aggregation and Δt, and not from the clean surplus relation and abnormal earnings as many now believe.
Conditional Coalescent Trees With Two Mutation Rates and Their Application to Genomic Instability
Authors: Emily Mathieu , François Olivier 
Published: December 2005

Abstract
Humans have invested several genes in DNA repair and fidelity replication. To account for the disparity between the rarity of mutations in normal cells and the large number of mutations present in cancer, an hypothesis is that cancer cells must exhibit a mutator phenotype (genomic instability) during tumor progression, with the initiation of abnormal mutation rates caused by the loss of mismatch repair. In this study we introduce a stochastic model of mutation in tumor cells with the aim of estimating the amount of genomic instability due to the alteration of DNA repair genes. Our approach took into account the difficulties generated by sampling within tumoral clones and the fact that these clones must be difficult to isolate. We provide corrections to two classical statistics to obtain unbiased estimators of the raised mutation rate, and we show that large statistical errors may be associated with such estimators. The power of these new statistics to reject genomic instability is assessed and proved to increase with the intensity of mutation rates. In addition, we show that genomic instability cannot be detected unless the raised mutation rates exceed the normal rates by a factor of at least 1000.