bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomical measurements of the cochlear aqueduct, round window membrane, round window niche, and facial recess.
Authors: Su Wen‐Yang , Marion Mitchell S. , Hinojosa Raul , Matz Gregory J.
Published: October 2006

The otologic surgeon must continue to familiarize himself with the anatomy of the temporal bone. For this purpose, we made precise histologic measurements of the cochlear aqueduct, round window membrane, round window niche, and facial recess. Measurements were taken from a large series of sectioned temporal bones and analyzed according to age. Our results demonstrated a high degree of individual variability in each area measured.
Homograft ossicles in tympanoplasty
Authors: Wehrs Roger E.
Published: October 2006

Homograft ossicles have been utilized in reconstructive middle ear surgery since 1964. In the first few years, simple repositioning of the incus was the method used. Due to the shortcomings of this procedure, a sculptured ossicle, the notched incus, was introduced in 1970 and this has gradually evolved into two standardized and reliable prostheses.

In 1973 hearing results were published on the first 122 cases. An expanded study in 1977 reported in detail on 361 ears. The current study reports the results of 326 patients operated upon during the 5 year period of 1976 through 1980 and compares them with the previous studies. The overall hearing results are very similar for both series with little change being noted in the failure rate. However, in the successful categories, progress seems to have been made in that a greater percentage of the fair to good results has been shifted to the excellent category.

A new concept of ossicular reconstruction is demonstrated with the introduction of the notched incus with high and low profile, to compensate for differences in the stapedial mallear relationship.
Fiber orientation of the facial nerve: An experimental study in the cat
Authors: Gacek Richard R. , Radpour Shokri
Published: October 2006

The Marchi technique and an osmium stain were used to demonstrate the distribution of degenerated motor fibers in the facial nerve and 3 peripheral branches after complete and partial transection of the nerve at the internal auditory meatus. The results in 16 specimens from 10 cats revealed that fibers to all 3 peripheral branches were injured regardless of the section of the facial nerve that was cut. Therefore the motor axons to the peripheral branches are diffusely located throughout the temporal course of the facial nerve.
Malignant histiocytosis showing facial involvement
Authors: Aozasa Katsuyuki , Tokuno Nagao , Ikuno Hiromichi , Mishima Yasuhiko
Published: October 2006

In general, malignant histiocytosis (MH) presents with fever, lymphadenopathy, general fatigue and malaise. Although facial involvement with MH has been mentioned previously, the present report emphasizes the significance and frequency of facial involvement in MH. The patient was a 51‐year‐old woman who presented with fever, general fatigue, diplopia, and numbness on the right side of the face. A roentgenogram of the face showed parasinusitis. Histologic findings of the biopsy from the sinuses showed infiltration by atypical histiocytes. She died two months after onset of symptoms. Autopsy revealed a systemic neoplastic proliferation of atypical histiocytes diagnostic of MH. Facial involvement in MH is discussed with a review of reported cases and our own cases with MH.
Autoimmune hypothesis of acquired subglottic stenosis in premature infants
Authors: Stolovitzky J. Pablo , Todd N. Wendell
Published: October 2006

Acquired subglottic stenosis is a devastating additional burden for nearly 4% of premature infants receiving neonatal intensive care. The duration of endotracheal intubation is considered the most important etiologic factor. Surprisingly, most premature infants do not acquire subglottic stenosis. Infants with similar clinical characteristics and care have varying laryngeal outcomes. We hypothesized an autoimmune mechanism to type‐II collagen to explain the varying laryngeal outcomes of these infants.

A retrospective study of premature infants of comparable birth weight, gestational age, and duration of endotracheal intubation was conducted. The eight control children, who did not manifest symptoms of airway obstruction, had longer durations of intubation than did the infants who developed subglottic stenosis. Three of five affected infants had serum antibodies to type‐II collagen, in contrast to none of the control infants (P = .035). This finding warrants additional study, and might lead to new diagnostic and therapeutic measures for these patients.
Head and neck sequelae of cardiac transplantation
Authors: Teixido Michael , Kron Thomas K. , Plainse Michael
Published: October 2006

Cardiac transplantation has become the treatment of choice for end‐stage cardiomyopathies. In 1987, nearly 2000 cardiac transplants were performed in the United States. Otolaryngologists will be asked with increasing frequency to evaluate and treat these patients. The otolaryngology service at Loyola University Medical Center has been involved in the follow‐up and treatment of head and neck complications in 100 transplant patients. Sixty percent of these patients manifest head and neck sequelae. The results of this review are presented.

The otolaryngologist should be aware of the special features of this patient population that require modification of the treatment approach, such as 1. the need to avoid the drugs erythromycin, trimethoprim/sulfamethoxazole, and ketoconazole, 2. the need to preserve the right internal jugular vein, and 3. the high risk of silent myocardial infarction. A discussion of these treatment modifications is provided. All patients should be treated in close communication with the medical transplant treatment team.
Asbestos and cancer of the larynx: Is there a relationship?
Authors: Parnes Steven M.
Published: October 2006

A head and neck examination was conducted on 322 personnel in a plant that manufactures brake linings and disks where asbestos is a major component. The personnel were categorized according to occupational risk, duration of employment, and smoking and alcohol habits. Thirty‐nine percent had abnormalities, the most common being laryngitis (15%), deviated nasal septum (13%), and neck mass (5.3%). Six members required a biopsy, but no cancer was discovered. Of 47 personnel with laryngitis, 46 were smokers (P<.01). In regard to asbestos exposure, 20% of the high‐risk group had laryngitis, compared to 11% in the low‐risk group (P<.05). The data were compared to a previously prepared longitudinal study of plant personnel (2057 individuals and 37,361.5 person years), where three cases of laryngeal cancer had been observed (0.77 expected). As these cases involved smokers with limited asbestos exposure, neither the longitudinal or cross‐sectional data could support asbestos as an etiologic factor for laryngeal cancer, but it may act as an irritant.
Age‐related changes in the neuromuscular junctions in the human posterior cricoarytenoid muscles: A quantitative study
Authors: Gambino Dean R. , Malmgren Leslie T. , Gacek Richard R.
Published: October 2006

The posterior cricoarytenoid muscle is unique histo‐chemically, ultrastructurally, and functionally. It has been suggested that the posterior cricoarytenoid muscle undergoes early aging. Aging in peripheral nerves has been reported to resemble a “dying back” neuropathy in that the most severe and earliest age‐related changes occur at the most distal levels of the nerve fibers. The lengths and terminal axonal branching of neuromuscular junctions in 17 human posterior cricoarytenoid muscles aged 4 days to 95 years were determined. Both neuromuscular junction lengths and the numbers of axonal terminal branches in the very young group differed significantly from values in two older groups. In contrast to results reported for some other muscles, there was no significant age‐related change in these parameters in the posterior cricoarytenoid muscle during adult life. This difference may be related to the repetitive contraction of the posterior cricoarytenoid muscle.
Production rate and composition of cerumen: Influence of sex and season
Authors: Cipriani C. , Taborelli G. , Gaddia G. , Melagrana A. , Rebora A.
Published: October 2006

The production rate and composition of cerumen have been studied in 11 participants (5 men and 6 women), 25 to 42 years old. The cerumen was obtained in January, May, July, and November to investigate the possible influence of the season. Only the triglyceride content decreased from November to July. Sex was not a factor, which supported the hypothesis that sex hormones play a minor role in the production rate of the lipid component of cerumen.
Interface Direct Shear Testing of Unsaturated Soil
Authors: Miller GA , Hamid TB
Published: October 2006

A commercially available direct shear apparatus was modified for testing unsaturated soil and interfaces between unsaturated soil and stainless steel. Major modifications include the addition of apparatus for suction-controlled testing using the axis translation method, and construction of shear boxes for testing unsaturated soil and interfaces. The major features of the device are described and results of performance tests are presented in this paper. In addition, typical results of tests on unsaturated clayey silt and interfaces are presented for drained tests conducted under different matric suction and net normal stress conditions. The Extended Mohr-Coulomb Failure Envelope for the soil is compared to that obtained for the rough interface. The soil/interface test results demonstrate the successful implementation of the device.
Comparison of Glargine Insulin Versus Rosiglitazone Addition in Poorly Controlled Type 2 Diabetic Patients on Metformin Plus Sulfonylurea
Authors: Triplitt Curtis , Glass Leonard , Miyazaki Yoshiniro , Wajcberg Estela , Gastaldelli Amalia , De Filippis Elena , Cersosimo Eugenio , DeFronzo Ralph A.
Published: October 2006

OBJECTIVE—We sought to examine the mechanisms by which the addition of glargine insulin or rosiglitazone improves glycemic control in type 2 diabetic subjects poorly controlled on maximally effective doses of metformin plus sulfonylurea.

RESEARCH DESIGN AND METHODS—Subjects (aged 47 ± 11 years, BMI 31 ± 5 kg/m2, HbA1c [A1C] 9.4 ± 1.3%) received bedtime glargine insulin (titrated based on the fasting plasma glucose [FPG], n = 10) or rosiglitazone (4 mg twice daily, n = 10). At baseline and after 4 months, A1C was measured and an oral glucose tolerance test and a 3-h euglycemic insulin (80 mU/m2 per min) clamp with [3-3H]glucose were performed.

RESULTS—A1C and FPG decreased similarly in the glargine insulin (9.1 ± 0.4 to 7.6 ± 0.3% and 212 ± 14 to 139 ± 5 mg/dl, respectively, both P < 0.0001) and rosiglitazone (9.4 ± 0.3 to 7.6 ± 0.4% and 223 ± 14 to 160 ± 19 mg/dl, respectively, both P < 0.005) groups. After 4 months, endogenous glucose production (EGP) declined similarly with glargine insulin (2.27 ± 0.10 to 1.73 ± 0.12 mg · kg−1 · min−1, P < 0.0001) and rosiglitazone (2.21 ± 0.12 to 1.88 ± 0.12 mg · kg−1 · min−1, P = 0.01). The hepatic insulin resistance index declined in the rosiglitazone group (32 ± 3 to 21 ± 1 mg · kg−1 · min−1 × μU/ml, P = 0.03 vs. baseline and P < 0.05 vs. glargine insulin) and did not change in the glargine group (22 ± 5 to 20 ± 3 mg · kg−1 · min−1 × μU/ml, P = NS). At 4 months, glargine insulin (3.6 ± 0.5 to 4.2 ± 0.4 mg · kg−1 · min−1, P < 0.01) and rosiglitazone (2.7 ± 0.3 to 3.8 ± 0.3 mg · kg−1 · min−1, P < 0.0005) increased Rd, but the increment was greater in the rosiglitazone group (P < 0.05). Diastolic blood pressure was reduced only by rosiglitazone (P < 0.01).

CONCLUSIONS—Triple therapy with glargine insulin or rosiglitazone similarly reduced A1C, primarily by suppressing basal EGP (hepatic). Glargine insulin reduced basal EGP by increasing plasma insulin levels, while rosiglitazone decreased basal hepatic glucose production by improving hepatic insulin sensitivity.
Long-Term Efficacy of Metformin Therapy in Nonobese Individuals With Type 2 Diabetes
Authors: Ong Cynthia R. , Molyneaux Lynda M. , Constantino Maria I. , Twigg Stephen M. , Yue Dennis K.
Published: October 2006

OBJECTIVE—The U.K. Prospective Diabetes Study (UKPDS) has demonstrated that metformin is as effective as sulfonylureas in obese subjects and is associated with less weight gain, fewer hypoglycemic episodes, and better cardiovascular outcomes. It is hence the pharmacological therapy of choice in this subgroup. However, a gap in our present knowledge is the long-term response to metformin in nonobese individuals. In this study, we compared metformin therapy in normal, overweight, and obese individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A database of patients treated at a referral center in Sydney, Australia, were analyzed. Patients with type 2 diabetes and complete HbA1c (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644). Analysis by BMI and the type of oral agent was performed. Individuals were categorized as normal, overweight, or obese (BMI <25, 25–29.9, and ≥30 kg/m2, respectively).

RESULTS—There were no differences between the initial, follow-up, and last A1C between the three metformin-treated groups. The duration of successful glycemic control with metformin monotherapy in the normal and overweight individuals and their incidences of diabetes-related complications for the entire duration of follow-up were not inferior to those of the obese individuals. The nonobese patients performed better regardless of the type of oral hypoglycemic agent used.

CONCLUSIONS—We conclude that metformin is at least as efficacious in normal and overweight individuals as it is in those who are obese. Our study provides evidence-based data to support metformin use in nonobese individuals with type 2 diabetes.
Combination of Multiple Genetic Risk Factors Is Synergistically Associated With Carotid Atherosclerosis in Japanese Subjects With Type 2 Diabetes
Authors: Yamasaki Yoshimitsu , Katakami Naoto , Sakamoto Ken’ya , Kaneto Hideaki , Matsuhisa Munehide , Sato Hiroshi , Hori Masatsugu , Haneda Masakazu , Kashiwagi Atsunori , Tanaka Yasushi , Kawamori Ryuzo , Kuno Shin-ichi
Published: October 2006

OBJECTIVE— Several genetic risk factors, such as single nucleotide polymorphisms (SNPs), in candidate genes have been reported to be responsible for intima-media thickness (IMT), which is one of the surrogate end points of cardiovascular events. However, the synergistic effects of SNPs have not been evaluated in detail.

RESEARCH DESIGN AND METHODS— We measured the average IMT of the common and internal carotid artery in Japanese type 2 diabetic patients (n = 690) (>50 years old) using ultrasonography. We also determined their genotypes regarding 106 SNPs in candidate genes responsible for cardiovascular diseases. Among the 106 SNPs, we selected 40 common (frequency of minor allele ≥10%) SNPs. We compared the average IMT of subjects with and without any pairs of four genotypes selected from the 40 common SNPs.

RESULTS— The combination of methylen-tetrahydrofolate reductase 677 TT genotype and lymphotoxin-α (LTA) 252 GG genotype and that of ACE DD genotype and LTA 252 GG genotype were evaluated as responsible for a statistically significant (P = 2.7 × 10−9 and 3.5 × 10−6, respectively) increase in average IMT (mean [±SD] 1.54 ± 0.60 and 1.43 ± 0.58 mm, respectively) compared with those of the subjects without these combinations (1.04 ± 0.34 and 1.04 ± 0.34 mm, respectively). No single genotype was shown to be responsible for the statistically significant difference in average IMT after Bonferroni’s multiple comparison procedure.

CONCLUSIONS— The present analysis demonstrates an approach to evaluate combinations of multiple genetic risk factors that are synergistically associated with carotid atherosclerosis.
Effects of Different Modes of Exercise Training on Glucose Control and Risk Factors for Complications in Type 2 Diabetic Patients
Authors: Snowling Neil J. , Hopkins Will G.
Published: October 2006

OBJECTIVE—We sought to meta-analyze the effects of different modes of exercise training on measures of glucose control and other risk factors for complications of diabetes.

RESEARCH DESIGN AND METHODS—The 27 qualifying studies were controlled trials providing, for each measure, 4–18 estimates for the effect of aerobic training, 2–7 for resistance training, and 1–5 for combined training, with 1,003 type 2 diabetic patients (age 55 ± 7 years [mean ± between-study SD]) over 5–104 weeks. The meta-analytic mixed model included main-effect covariates to control for between-study differences in disease severity, sex, total training time, training intensity, and dietary cointervention (13 studies). To interpret magnitudes, effects were standardized after meta-analysis using composite baseline between-subject SD.

RESULTS—Differences among the effects of aerobic, resistance, and combined training on HbA1c (A1C) were trivial; for training lasting ≥12 weeks, the overall effect was a small beneficial reduction (A1C 0.8 ± 0.3% [mean ± 90% confidence limit]). There were generally small to moderate benefits for other measures of glucose control. For other risk factors, there were either small benefits or effects were trivial or unclear, although combined training was generally superior to aerobic and resistance training. Effects of covariates were generally trivial or unclear, but there were small additional benefits of exercise on glucose control with increased disease severity.

CONCLUSIONS—All forms of exercise training produce small benefits in the main measure of glucose control: A1C. The effects are similar to those of dietary, drug, and insulin treatments. The clinical importance of combining these treatments needs further research.
Age and Sex May Significantly Interact With Diabetes on the Risks of Lower-Extremity Amputation and Peripheral Revascularization Procedures
Authors: Chen Hua-Fen , Ho Ching-An , Li Chung-Yi
Published: October 2006

OBJECTIVE—Using the National Health Insurance claim data, we prospectively investigated the age- and sex-specific incidence density and relative hazards of nontraumatic lower-extremity amputation (LEA) and peripheral revascularization procedure (PRP) of the diabetic population in Taiwan.

RESEARCH DESIGN AND METHODS—A total of 500,868 diabetic patients and 500,248 age- and sex-matched control subjects, selected from the ambulatory care claim (1997) and the registry for beneficiaries, respectively, were linked to inpatient claims (1997–2002) to identify hospitalizations due to nontraumatic LEA and PRP. Incidence density was calculated under the Poisson assumption, and the Kaplan-Meier analysis was used to assess the cumulative event rates over a 6-year follow-up period. We also evaluated the age- and sex-specific relative hazards of nontraumatic LEA and PRP in relation to diabetes with Cox proportional hazard regression model adjusted for demographics and regional areas.

RESULTS—The estimated incidence density of nontraumatic LEA and PRP for diabetic men was 410.3 and 317.0 per 100,000 patient-years, respectively. The corresponding data for diabetic women were relatively low at 115.2 and 86.0 per 100,000 patient-years. Compared with control subjects with the same age and sex, diabetic patients consistently suffered from significantly elevated relative hazards of nontraumatic LEA. Young and female patients were especially vulnerable to experience increased risks of nontraumatic LEA, but such effect modification by age and sex was less apparent for PRP.

CONCLUSIONS—Multidisciplinary diabetes foot care systems, including the provision of revascularization procedures, should be further enforced to reduce subsequent risks of nontraumatic LEA, especially in young and female diabetic patients.
Screening for Coronary Disease in Diabetes: When and How
Authors: Ali Yasmine S. , Maron David J.
Published: October 2006

IN BRIEF

Coronary atherosclerosis and silent ischemia are highly prevalent in patients with diabetes. Identification of subclinical atherosclerosis and ischemia in asymptomatic patients with diabetes is valuable for risk stratification and for guiding therapy. This article reviews methods of screening and proposes how to implement them in practice.
Sample Size Calculation for Comparing Proportions
Authors: Wang Hansheng , Chow Shein‐Chung
Published: October 2006

In practice, the objective of sample size calculation is to select the minimum sample size in such a way that the desired power can be obtained for detection of a clinically meaningful difference at the prespecified significance level. Therefore, the selection of the sample size depends on the magnitude of the clinically meaningful difference, the desired power, the prespecified significance level, and the hypotheses of interest under the study of choice (e.g., a parallel design or a crossover design).
Protocol Violators
Authors: McMahon Alex D.
Published: October 2006

This article reviews the distinctions between protocol deviations and protocol deviators. A seriousness scale is introduced to assess the importance different types of deviations to the protocols.
True Positives, True Negatives, False Positives, False Negatives
Authors: Schwenke Carsten , Schering AG
Published: October 2006

In the clinical development of diagnostic procedures, studies are performed to measure the efficacy of the new method in the target population. Those new methods could be new laboratory tests, which measure some tumor marker to evaluate the disease status of a patient. Other examples are imaging methods like ultrasound, where several raters are asked to assess the images.
Generalized Linear Models
Authors: Kauermann Göran , Norrie John
Published: October 2006

Generalized linear models (GLMs) provide a flexible and commonly used tool for modeling data in a regression context. The approach has had a major impact on statistical modeling technology with research on a wide range of extensions continuing today.
Interval Censored
Authors: Gerds Thomas A , Meier‐Hirmer Carolina
Published: October 2006

In survival or time‐to‐event analysis, interval censoring occurs if the time of an event is theendpointof interest that cannot be observed exactly for each patient but occurred chronologically between two follow‐ups. Information of the event status is typically collected by periodically performing clinical examinations or laboratory tests. Events of interest can be the onset of a disease, infection, the recurrence of a tumor, and other changes in the course of a disease. For example, in aclinical trial/study, the progression of a tumor can only be assessed at periodic examination times, e.g., every 6 months. The true time‐to‐progression is hidden somewhere between two adjacent examination times, e.g., between 12 and 18 months. Another typical example is the infection time, e.g., of HIV, when for the diagnosis the result oflaboratory testsis needed. The time‐to‐infection is included in an interval defined by the dates of acquisition. Two sources of censoring can be allocated. External censoring is due to the study design, which prohibits instantaneous access of the event of interest because the patient is not all the time medically supervised. An example for externally introduced censoring is the arrangement of yearly instead of monthly or daily examinations. On the other hand, the censoring can be due to the natural limits of the experiment. For instance, if the event of interest is the onset of a tumor, or anadverse drug reactionbecoming visible only after a certain limit of toxication is exceeded.
Propensity Score
Authors: Rosenbaum Paul R.
Published: October 2006

The propensity score is the conditional probability of exposure to treatment rather than control given observed covariates, or more generally, the conditional probability of selection into a group given observed covariates. It is used in an effort to adjust for nonrandom treatment assignment or nonrandom selection. Propensity scores were proposed by Rosenbaum and Rubin (1).
Using Internet in Community Intervention StudiesThe preparation of this manuscript was supported by grants from the National Cancer Institute (CA78206; CA81864; CA86199).
Authors: Buller David B.
Published: October 2006

The Internet has several characteristics that make it an attractive medium for delivering health care and prevention services. It offers a dynamic, engaging, multimedia environment in which health care and prevention services can be delivered immediately, on demand, 24 hours per day 7 days a week, and for a lower per unit cost than by other delivery systems (e.g., human contact, U.S. mail). Web‐based interventions may reduce demands on other hospital services, such as general inquiries, routine examinations (asthma), or outpatient visits. It can span barriers created by distance, disability, and stigma.
Cluster Randomization
Authors: Klar Neil , Donner Allan
Published: October 2006

The purpose of this article is to present a systematic and unified treatment of comparative trials that randomize intact social units, or clusters of individuals, to different intervention groups. Such trials have become particularly widespread in the evaluation of nontherapeutic interventions, including lifestyle modification, educational programs, and innovations in the provision of health care. Their increasing popularity over the last two decades has led to an extensive body of methodology and a growing, but somewhat scattered, literature that cuts across several disciplines in the statistical, social, and medical sciences.
The Carotene and Retinol Efficacy Trial (Caret)
Authors: Thornquist Mark D.
Published: October 2006

The Carotene and Retinol Efficacy Trial (CARET) is a phase III chemoprevention trial sponsored by the U.S. National Cancer Institute (NCI). The primary hypothesis tested in CARET was whether the daily combination of 30 mg beta‐carotene plus 25,000 International Units (IU) retinyl palmitate (an ester of retinol, also known as Vitamin A) would lower the incidence of lung cancer in individuals at high risk for the disease. Secondary hypotheses tested the effect of the study vitamins on the incidence of other cancers (with particular interest in prostate cancer), overall and cause‐specific mortality (with particular interest in mortality from cardiovascular disease), and symptoms, signs, and laboratory values potentially attributable to the study vitamins.
The Community Intervention Trial for Smoking Cessation (COMMIT)
Authors: Green Sylvan B.
Published: October 2006

The Community Intervention Trial for Smoking Cessation (COMMIT), funded by the U.S. National Cancer Institute (NCI), was a large‐scale study involving 11 pairs of communities in North America, matched on geographic location (state or province), size, and sociodemographic factors. Communities were randomized within pairs to active community‐based intervention versus comparison. Thus, COMMIT is an example of a group randomization design (also called a cluster randomization design), in which intact groups (clusters), rather than individuals, are randomly allocated to intervention condition. Randomization of communities was used in COMMIT to obtain an unbiased assessment of the intervention effect; randomization also provided the basis for the statistical analysis.
Assessment Bias
Authors: Gøtzsche Peter C.
Published: October 2006

Assessment bias in a clinical trial occurs if bias in the assessment of the outcome exists. It is also called ascertainment bias, diagnostic bias, or detection bias. A major cause of assessment bias is lack of blinding. Other problems relate to differential identification of harmless or false‐positive cases of disease, bias in assessment of disease‐specific mortality, the use of composite outcomes, competing risks, timing of the assessments, and bias in assessment of harms.
The Cochrane Collaboration
Authors: Clarke Mike
Published: October 2006

For all but the last 100 years, decisions on how to treat patients were almost always based on personal experience, anecdotal case histories, and comparisons of a group of patients who received one treatment with an entirely separate group who did not. These processes, although subject to many biases, are still in use today, but ways to minimize these biases are now available, accepted, and more easily adopted. Among these methods is the use of the randomized trial as a means of providing more reliable estimates of the relative effects of interventions, as the only difference between the patients in the groups being compared in a randomized trial will be that of most interest: namely, the interventions under investigation. The Cochrane Collaboration, which is the subject of this article, was formed to research and assemble a database of relevant trials to fill this void.
Monotherapy
Authors: Darbyshire Janet
Published: October 2006

A trial that evaluates a monotherapy would most often test a single drug, but the definition could be extended to include other interventions such as immunotherapy or even a different modality such as radiotherapy that contain a single element. The issues around trial design are essentially the same and, therefore, this section focuses on monotherapy trials that evaluate a drug.
Double‐Dummy
Authors: Schulz Kenneth F.
Published: October 2006

Blinding embodies a rich history spanning several centuries. Double‐blinding usually reduces differential assessment of outcomes (information bias), but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment (sometimes called co‐intervention). With an active treatment control group, different options to double‐blinding present production obstacles, compliance impediments, and unblinding opportunities. To double‐blind in this situation, double‐dummy blinding nearly always becomes indispensable.
Update in Hyperlipidemia Clinical Trials
Authors: Chien Kuo‐Liong
Published: October 2006

Current large‐scale clinical trial evidence clearly demonstrates that statins can reduce cardiovascular mortality and morbidity in hyperlipidemic patients. These clinical trial results clearly indicate that cholesterol reduction can reduce cardiovascular risks significantly. However, several issues are still under debate, such as subgroup benefits, lipid subtypes, and new outcome measures. Progress on study design, surrogate endpoints, outcomes measures, and new drugs improve the knowledge of hyperlipidemia treatment. In this review, the recent advances on clinical trials of hyperlipidemia will be discussed and some hints on recent updated information will be provided.
Stability Analysis
Authors: Tsong Yi , Chen Wen Jen
Published: October 2006

Shelf life of a drug product is defined as the length of time under the specific conditions of storage that the product will remain within acceptance criteria established to ensure its identity, strength, quality, and purity. Regulatory agencies request that an adequate stability study be performed by an applicant to collect the chemical data of the batch at a prespecified time point in order to provide supporting evidence of product stability and establish a proposed shelf life (1–7).
Assessment of Health‐Related Quality of Life
Authors: Weng C. S. Wayne
Published: October 2006

This article is intended to provide an overview of assessment of HRQOL in clinical trials. For more specific details on a particular topic mentioned in this article, the readers should consult the cited references. The development of a new HRQOL questionnaire and its translation into various languages are separate topics and are not covered in this article.
Clinical Data Coordination
Authors: Kious Cheryl
Published: October 2006

This article provides an overview of the role of the Lead Data Manager, including best practices and considerations in the clinical data management process. The clinical data management process is responsible for taking the raw data provided by investigative sites and converting it into a high‐quality database “…enabling the data to be efficiently analysed and displayed.” The processes outlined are assumed for a regulatory study, and they are divided into the phases of study initiation, study conduct, and study closure.
Multiple Endpoints
Authors: Bretz Frank , Branson Michael
Published: October 2006

The analysis of multiple endpoints is common practice in pharmaceutical research. A vast amount of literature exists on the design and the analysis of clinical trials with multiple endpoints. Related statistical approaches can roughly be classified into endpoint‐specific multiple testing methods and multivariate global tests. This article briefly summarizes the main approaches, describes their advantages and disadvantages, and provides some recommendations on practical issues.
An optimized anti‐lock braking system in the presence of multiple road surface types
Authors: Rattasiri W. , Wickramarachchi N. , K. Halgamuge S.
Published: October 2006

In this paper, the use of adaptive anti‐lock braking system (A‐ABS) comprising of a road surface identification (RSID) system and road surface information modules is presented. The proposed ABS system is capable of identifying and differentiating different types of road surfaces, and applying an amount of brake force appropriate to the road surface type being encountered in order to prevent wheel lockup as well as to minimize the braking distance. A discriminative hierarchical evolutionary fuzzy system learns and identifies on‐the‐fly the road surface characteristics, from a set of built‐in road surface information modules, in a closed‐loop adaptive configuration. The closed‐loop nature of RSID allows the system to adapt and respond very fast to a sudden change in surface condition. In order to verify the performance of the proposal, simulation results obtained from cars equipped with A‐ABS, a reference ABS, and a non‐ABS are provided and discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Multiscale planning and scheduling in the secondary pharmaceutical industry
Authors: Stefansson Hlynur , Shah Nilay , Jensson Pall
Published: October 2006

Most sophisticated planning and scheduling approaches for the process industry consider a fixed time horizon and assume that all data is given at the time of application. Planning and scheduling approach for a continuous and dynamic decision process where decisions have to be made before all data are available is proposed. As an inspiration we have a real world problem originating from a complex pharmaceutical enterprise. The approach is based on a hierarchically structured moving horizon framework. On each level optimization models are proposed to provide support for the relevant decisions. The levels differ regarding the time scope, aggregation, update rate and availability of data at the time applied. The framework receives input data piece by piece and has to make decisions with only a partial knowledge of the required input. Solution procedures have been developed and the optimization models have been validated and tested with data from the real world problem. The solution procedures were able to obtain good solutions within acceptable computational times. It is believed that multiscale dynamic online procedures are more suitable than traditional offline procedures for many specific types of planning and scheduling problems found in the process industry and should be explored further. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Genetics of Parkinson's disease and parkinsonism
Authors: Hardy John , Cai Huaiban , Cookson Mark R. , Gwinn‐Hardy Katrina , Singleton Andrew
Published: October 2006

Until 10 years ago, conventional wisdom held that Parkinson's disease was not a genetic disorder. Since that time, there have been a plethora of genetic findings, culminating in the cloning of several genes that derive from the loci given the nomenclature PARK1‐PARK12 (OMIM 168600). Recently, these research findings have begun to impact clinical practice, and this impact is likely to increase. The primary purpose of this article is to outline these genetic advances, discuss their importance for current practice in clinical and related settings, and outline briefly how they are influencing research into the causes of and possible future treatments for this prevalent disorder. Ann Neurol 2006;60:389–398
Humidity sensing and electrical properties of polyaniline/cobalt oxide composites
Authors: Parvatikar Narsimha , Jain Shilpa , Kanamadi C. M. , Chougule B. K. , Bhoraskar S. V. , Prasad M. V. N. Ambika
Published: October 2006

Polyaniline/cobalt oxide composites were synthesized by an in situ chemical polymerization method with ammonium persulfate as an oxidizing agent. This was a single‐step polymerization process for the direct synthesis of the emeraldine salt phase of the polymer. The polymers were characterized with X‐ray diffraction, scanning electron microscopy, and Fourier transform infrared spectral analysis. The formation of mixed phases of the polymer together with the conducting emeraldine salt phase was confirmed by spectroscopic techniques. High‐temperature conductivity measurements showed thermally activated behavior. A change in the resistance was observed with respect to the relative humidity when the pellets were exposed to a wide humidity range of 10–95%. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 653–658, 2007
Easy preparation of crosslinked polymer films from polyoxyalkylene diamine and poly(styrene–maleic anhydride) for electrostatic dissipation
Authors: Wei Kuan‐Liang , Wu Jeng‐Yue , Chen Yu‐Min , Hsu Yen‐Chi , Lin Jiang‐Jen
Published: October 2006

The curing reaction of polyoxyalkylene diamine and poly(styrene–maleic anhydride) was able to produce polymer films that were hygroscopic in nature. The process involved the formation of an imine intermediate by dissolving the diamine monomers in a ketone solvent, followed by instant casting into films before the solution self‐cured into a gel product. Hydrophilic films were formed by the fast reaction of amine with anhydride while evaporating the solvent under vacuum. The resulting films exhibited dissipation of electrostatic charges over a wide range, from 109.4 to 104.1 Ω/sq surface resistivity. The low resistivity was attributed to the functionality of hydrophilic polyoxyethylene (POE), which was able to adsorb moisture and optionally to the added metal ion salts. Furthermore, the slightly crosslinked network prevented POE from having crystallinity and rendered the films solvent resistant, thermally stable, and suitable for applications as antistatic and polymeric electrolytes. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 716–723, 2007
Radical polymerization of methyl methacrylate in the presence of N,N‐dimethyl‐N‐(methylferrocenyl)amine
Authors: Monakov Y. B. , Puzin Y. I. , Zaikina A. V. , Yarmukhamedova E. I. , Fatykhov A. A. , Zaikov G. E.
Published: October 2006

The specific features of free‐radical polymerization of methyl methacrylate in the presence of a new initiating system, benzoyl peroxide‐N,N‐dimethyl‐N‐(methylferrocenyl)amine, are studied. Mutual influence of ferrocenyl‐ and amine groups on kinetic parameters of polymerization and on the microstructure of the resulting polymers is found. It is shown that the polymer obtained in the presence of this initiating system has predominantly syndiotactic structure. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 724–727, 2007
Strategy for kinetic parameter estimation—Thermal degradation of polyurethane elastomers
Authors: Agić Ante , Bajsić Emi Govorĉin
Published: October 2006

The kinetics of the thermal degradation of polyurethane (PU) elastomers based on poly(ether polyol) soft segments and an aromatic type of diisocyanate were investigated by thermogravimetric analysis (TGA) under a nitrogen atmosphere employing four heating rates. The corresponding kinetic parameters of the two degradation stages were estimated by minimizing the output error functional and by the Kissinger method. In evaluating the kinetic parameters of the two‐step PU thermal decomposition, a differential thermogravimetry curve was applied as an objective functional in a regression procedure. Parameter estimation was obtained by minimizing the weighted quadratic output error functional with the modified Nelder–Mead simplex search algorithm. The confidence regions in the preexponential factor‐activation energy space were established for both the first and second stages of degradation. The effect of the molecular weight of the soft segment and the content of the hard segment on the activation energy of the degradation process was constructed by response surface methodology. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 764–772, 2007
Electrochemical behaviors of poly(ferrocenylsilane) solutions
Authors: Wang Xue‐Jie , Wang Li , Wang Jian‐Jun , Chen Tao
Published: October 2006

The electrochemical behaviors of two kinds of poly(ferrocenylsilanes) (PFS) with different substituent groups in CH2Cl2 solutions were investigated by means of cyclic voltammetry (CV) and electrochemical quartz crystal microbalance. The results demonstrated that the CV processes of the PFS on the glass carbon electrode surface in CH2Cl2 solutions are the diffusion‐controlled reversible processes. The oxidative state of PFS forms an adsorption layer on the electrode surface during the oxidation process. The interaction of active ferrocene centers along the main chain induces the stepwise redox process, and makes the CV waves of the PFS solutions present two couples of peaks. The diffusion coefficients of PFS in CH2Cl2 solution are much larger than those of PFS in films. The different electrochemical behaviors of the two PFS solutions indicated that the molecular structure of polymer has influence on the electrochemical properties of the PFS. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 789–794, 2007
Truncated midkine correlates with sensitivity to anticancer drugs and malignancy in human tumor cell line
Authors: Akuzawa Natsuyo , Nobata Shigenori , Shinozawa Takao
Published: October 2006

Midkine (MK) is a heparin binding growth factor having functions of neurite‐outgrowth, mitogenesis and tissue repair. This molecule is involved in tumor growth and metastasis. The MK molecule consists of five exons, but there is a truncated isoform, lacking exon 3. We established SW13 cells transfected with the human truncated MK cDNA. These cells were induced to undergo apoptosis by anticancer agents, cisplatin, etoposide (ETP), mitomycin C (MMC) and paclitaxel (PAX). Truncated midkine (tMK) suppressed cell death and helped the cells to be viable. When the cells were cultured on dishes coated with extracellular matrix molecules, spontaneous detachment occurred in the tMK expressing cells. Also tMK enhanced cell invasion. These results suggest that expression of tMK has cell‐protective functions and plays important roles in carcinogenesis and malignancy. Furthermore, it is suggested that tMK has a greater ability of malignant transformation than full‐length MK. Whether tMK is expressed or not will be useful information for improving cancer chemotherapy. Copyright © 2006 John Wiley & Sons, Ltd.
Fluorescent Perylene Diimide Rotaxanes: Spectroscopic Signatures of Wheel–Chromophore Interactions
Authors: Baggerman Jacob , Jagesar Dhiredj C. , Vallée Renaud A. L. , Hofkens Johan , De Schryver Frans C. , Schelhase Frauke , Vögtle Fritz , Brouwer Albert M.
Published: October 2006

[2]‐ and [3]‐rotaxanes with a tetraphenoxy perylene diimide core were synthesized. Hydrogen bonding between the wheel and the imide changes the optical properties of the perylene chromophore: the absorption and fluorescence spectra are red‐shifted. The decay times of the rotaxanes are shorter in comparison with that of the axle. Single molecule fluorescence measurements reveal relatively narrow distributions of emission maxima and decay times. The averages are in agreement with ensemble measurements. The observed red shifts make the perylene diimide a suitable chromophore for sensing the position of the wheel on the axle.
Performance evaluation of non‐Gaussian channel estimation techniques on ultrawideband impulse radio channels
Authors: Barton Richard J. , Daniel Manoj
Published: October 2006

We study the problem of adaptive channel estimation for a multipath channel on an ultrawideband (UWB) impulse radio (IR) system. The purpose of the work is to demonstrate that the statistical characteristics of the UWB‐IR environment are strongly non‐Gaussian and that as a result, non‐Gaussian signal processing techniques are both efficient and powerful in a UWB‐IR environment. The multipath channel estimation problem has been chosen as an illustrative example because UWB‐IR systems often operate in complex multipath environments. We study both blind and training‐based estimation techniques and demonstrate that even simple non‐Gaussian strategies can achieve significant performance improvement when compared to more common second‐order estimation techniques. Copyright © 2006 John Wiley & Sons, Ltd.
Cycloaddition approach to the curing of polyimides via precursor containing thiophene‐S,S‐dioxide
Authors: Magyarosy Andrew , Mohareb Rafat M. , Ho Jonathan Z.
Published: October 2006

A new method for linear polymerization of maleimides via the Diels–Alder reaction has been developed. This method involves use of a new cross‐linking agent, benzene‐3,4‐dimethylenesuccinimide, which can be generated in situ from its thiophene precursor, benzene‐2,5‐dihydrothiophene‐3,4‐dicarboximide‐S,S‐dioxide. This new cross‐linking agent is reasonably reactive, readily prepared, and stable at room temperature. A controlled molecular weight oligomer has been synthesized and applied to the polymerization to yield a highly thermal stable polyimide. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:648–652, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20249
Molecular effects of sodium hyaluronate on the healing of avian supracoracoid tendon tear: According to in situ hybridization and real‐time polymerase chain reaction
Authors: Shimpuku Eiji , Hamada Kazutoshi , Handa Akiyoshi , Kobayashi Kunihiko , Nakajima Tomotaka , Yamazaki Hitoshi , Nakamura Masato , Fukuda Hiroaki , Mochida Joji
Published: October 2006

Hyluronic acid (HA) on tissue healing has been controversial. We examined the molecular pharmacology of HA injection at the suture site in an acute model of supracoracoid tendon laceration using chickens, an injury of a nonweight‐bearing joint considered similar to the human shoulder. Expression of mRNAs encoding α I (I) and αI (III) procollagens was localized using in situ hybridization (ISH). Intensities of mRNA expression for α I (I) and α I (III) procollagens, transforming growth factor‐β1 (TGF‐ β1), basic fibroblast growth factor (bFGF), and insulin‐like growth factor (IGF) were determined by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). Histologically, chickens with HA injection (HA group) showed early restoration of continuity at the laceration site than saline‐injection controls (saline‐injection group). By ISH, the expression rate of cells at the lesion site that contained α I (I) and α I (III) procollagen mRNAs were somewhat higher in the HA group than in the saline‐injection group. By RT‐PCR, the HA‐ and saline‐injection groups showed no significant difference in expression of α I (I) and α I (III) procollagen mRNA between weeks 1 and 6. The saline ‐injection group exhibited significant decrease in TGF‐β1 expression between weeks 1 and 3, and in bFGF expression between weeks 1 and 2; however, the HA group showed no such decrease. As for IGF, no difference was appreciable in both groups between weeks 1 and 6. A single injection of HA could cause earlier restoration of continuity at the lacerated site of the supracoracoid tendon. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:173–184, 2007