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PubMed2004

A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.

Viral vaccines could be considered among the most important medical achievements of the 20th century. They have prevented much suffering and saved many lives. Although some curative antiviral drugs exist, we desperately depend on efforts by academic, governmental and industrial scientists in the advancement of viral vaccines in the prevention and control of infectious diseases. In the next decade, we hope to see advancement in the development of current and investigational viral vaccines against childhood and adult infections. In this article, we will review the licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.

Adolescent↗
PubMed2004

Graduated driver licensing research in 2003 and beyond.

This paper updates the comprehensive summary of graduated driver licensing (GDL) published in the January 2003 special issue of the Journal of Safety Research. It summarizes recent research not included in the special issue as well as research in progress or planned research. The most active research areas are risk factors for beginning teen drivers and evaluations of GDL programs. Results in each area strengthen the case for GDL. Additional research is producing valuable information about specific GDL implementation issues and the roles of parents and driver education in helping teenagers learn to drive safely.

Accidents, Traffic↗
PubMed2004

Michigan's graduated driver licensing program: evaluation of the first four years.

INTRODUCTION: To evaluate the four-year outcome of Michigan's graduated driver licensing (GDL) program, motor-vehicle crash data for 16-year-old drivers in 1996 (pre-GDL), and 1998-2001 (post-GDL) were analyzed. METHOD: Relative risks and 95% confidence intervals for several crash types were computed, and pre-post-GDL population-based crash rates were compared. Reductions in crash risks among 16-year-olds previously found in 1998 and 1999 were generally maintained in 2000 and 2001. RESULTS: Reductions in crash risk among 16-year-olds from 1996 to 2001 were 29% for all, 44% for fatal, 38% each for nonfatal-injury and fatal-plus-nonfatal-injury, 32% for day, 31% for evening, 59% for night, 32% for single-vehicle, and 28% for multi-vehicle crashes. Even after adjusting for more general population-wide changes among drivers 25 years and older that might have contributed to changes in 16-year-old crash risk, reductions remained impressive (19% for all crashes in 2001). IMPACT ON INDUSTRY: As one approach to reducing teenage motor-vehicle morbidity and mortality, GDL remains promising.

Accidents, Traffic↗
PubMed2004

Evaluation of California's graduated driver licensing program.

PROBLEM: California's graduated driver licensing (GDL) program was implemented to reduce the high crash risk of teenage drivers. The program enhancements made in 1998 were evaluated in this study using methods that rule out the noticeable downward trend in California teen's fatal/injury crash rates as a possible explanation for any observed crash reductions that could otherwise be mistaken for program effects. METHOD: Monthly per capita fatal/injury crash rates for 15-to-17-year-olds and proportional representations of 16-17-year-olds' nighttime and passenger crashes were analyzed using intervention time series analysis. RESULTS: After removing trend, seasonality, and transition effects in the data, no overall reductions in fatal/injury crashes for 15-17-year-olds or 16-year-olds (separately) were found to be associated with the 1998 program enhancements, suggesting no overall exposure reduction effect of the longer instruction permit period nor increased competency associated with the higher number of required practice hours. However, the 12-month nighttime and 6-month passenger restrictions were found to be associated with annual savings of 55 and 816 fatal/injury crashes, respectively. DISCUSSION: Finding no overall impact of the 1998 GDL enhancements was not surprising given findings of an earlier survey suggesting that California teens and parents were largely already practicing program requirements prior to implementation and were not fully complying with the program requirements afterwards. Though the observed crash savings associated with the restrictions were of modest size, this is the first study to evidence a direct positive impact of the passenger restriction component of GDL programs. Larger reductions could be realized if the nighttime restriction started earlier and parents/law enforcement could be motivated to better enforce these restrictions. IMPACT ON INDUSTRY: The findings provide support for passenger and nighttime restriction components of GDL programs.

Accidents, Traffic↗
PubMed2006

Encouraging compliance with graduated driver licensing restrictions.

PROBLEM: Although graduated driver licensing (GDL) programs have reduced the high crash rates for 16-and 17-year-old drivers, research suggests that some teenagers fail to comply with restrictions on nighttime driving and carrying passengers. METHOD: A program to encourage compliance with GDL restrictions and seat belt requirements was implemented in Guilford County, North Carolina. The program combined increased enforcement with a multi-faceted publicity campaign drawing attention to the enforcement activity. A comparison community was studied to assess whether changes over time could be reasonably attributed to the program. RESULTS: Several measures indicate that greater enforcement did occur in the intervention community and that teenagers perceived the increase. However, self-reported data and direct observations of young drivers in the intervention and comparison communities showed the program resulted in only modest changes in compliance with GDL restrictions. DISCUSSION: The program put in place the mechanisms known to produce changes in driver behavior, but these may have been insufficient to alter the behavior of the minority of teenagers (and parents) who were not already complying with restrictions. However, the modest changes in young driver behavior plus the clear changes in both actual and perceived enforcement suggest that high visibility enforcement programs merit further use and evaluation in other communities, particularly those where compliance with GDL provisions is lower than in Guilford County.

Accidents, Traffic↗
PubMed2004

Comparison of preschool vision screening tests as administered by licensed eye care professionals in the Vision In Preschoolers Study.

PURPOSE: To compare 11 preschool vision screening tests administered by licensed eye care professionals (LEPs; optometrists and pediatric ophthalmologists). DESIGN: Multicenter, cross-sectional study. PARTICIPANTS: A sample (N = 2588) of 3- to 5-year-old children enrolled in Head Start was selected to over-represent children with vision problems. METHODS: Certified LEPs administered 11 commonly used or commercially available screening tests. Results from a standardized comprehensive eye examination were used to classify children with respect to 4 targeted conditions: amblyopia, strabismus, significant refractive error, and unexplained reduced visual acuity (VA). MAIN OUTCOME MEASURES: Sensitivity for detecting children with > or =1 targeted conditions at selected levels of specificity was the primary outcome measure. Sensitivity also was calculated for detecting conditions grouped into 3 levels of importance. RESULTS: At 90% specificity, sensitivities of noncycloplegic retinoscopy (NCR) (64%), the Retinomax Autorefractor (63%), SureSight Vision Screener (63%), and Lea Symbols test (61%) were similar. Sensitivities of the Power Refractor II (54%) and HOTV VA test (54%) were similar to each other. Sensitivities of the Random Dot E stereoacuity (42%) and Stereo Smile II (44%) tests were similar to each other and lower (P<0.0001) than the sensitivities of NCR, the 2 autorefractors, and the Lea Symbols test. The cover-uncover test had very low sensitivity (16%) but very high specificity (98%). Sensitivity for conditions considered the most important to detect was 80% to 90% for the 2 autorefractors and NCR. Central interpretations for the MTI and iScreen photoscreeners each yielded 94% specificity and 37% sensitivity. At 94% specificity, the sensitivities were significantly better for NCR, the 2 autorefractors, and the Lea Symbols VA test than for the 2 photoscreeners for detecting > or =1 targeted conditions and for detecting the most important conditions. CONCLUSIONS: Screening tests administered by LEPs vary widely in performance. With 90% specificity, the best tests detected only two thirds of children having > or =1 targeted conditions, but nearly 90% of children with the most important conditions. The 2 tests that use static photorefractive technology were less accurate than 3 tests that assess refractive error in other ways. These results have important implications for screening preschool-aged children.

Amblyopia↗
PubMed2006

A biochemical comparison of a pharmaceutically licensed coagulation active plasma (Octaplas) with a universally applicable development product (Uniplas) and single-donor FFPs subjected to methylene-blue dye and white-light treatment.

The strive for more standardised and highly efficacious products is one of the important mainstays in modern haemotherapy. Coagulation active plasma for transfusion is the product of choice when treating hereditary or acquired isolated or complex coagulopathies, when no specific concentrate is available. The aim of this study was to perform an extensive biochemical comparison of the pharmaceutically licensed coagulation active plasma named Octaplas with an identical, but universally applicable, development product (Uniplas, working title) and single-donor fresh-frozen plasma (FFP) units subjected to a medical device treatment using a combination of methylene-blue dye and subsequent white-light exposure (MB plasma). Our study showed that there are differences in the biochemical characteristics between Octaplas and MB plasma, while Uniplas revealed the same quality as Octaplas. The variability of selected plasma proteins in the 20 individual MB plasma units tested was high compared to Octaplas/Uniplas. Beyond the reported decreased levels of protein S and plasmin inhibitor found in Octaplas/Uniplas, and the significant loss of fully functional fibrinogen in MB plasma and its impact on selected global coagulation parameters, the latter product additionally revealed several coagulation factor activities outside the ranges given for normal single-donor FFP. It is important for plasma prescribers to be aware of the major inherent differences between Octaplas and MB plasma.

Blood Coagulation↗
PubMed1997

The impact of mail contact strategy on the effectiveness of driver license withdrawal.

The California Department of Motor Vehicles currently uses first-class mail to notify drivers of a suspension or revocation of their driving privilege. The served drivers are instructed to sign and return the order and any driver's license to the department, thereby establishing proof of the driver's knowledge of the order. The establishment of proof is considered essential in the prosecution of drivers cited for operating a motor vehicle while under a suspension or revocation (California Vehicle Code Section 14601). However, past research indicates that a majority of drivers fail to comply with the order. In an attempt to increase proof rates, the present study developed and evaluated a number of mailing strategies for various categories of suspensions and revocations. Among the mailing factors evaluated were (1) use of certified mail, (2) use of a follow-up contact, (3) use of a postage paid return envelope and (4) masking the Department of Motor Vehicles return address of the certified mail action notice. The results indicate that there are significant differences between the type of mail contact employed as well as between the different categories of suspension or revocation reason. The most effective strategies (certified mail, return receipt requested) resulted in proof rates of approximately 60-70% compared to approximately 25% for the current first-class mailing procedure. An analysis of subsequent driving records indicated that certified mail also increased the percentage of convictions which were prosecuted as 14601 violations, while decreasing the total number of entries (convictions and accidents) accumulated during suspension or revocation.

Automobile Driving↗
PubMed1997

Evaluation of a method for reducing unlicensed driving: the Washington and Oregon license plate sticker laws.

This report covers an evaluation of programs designed to reduce unlawful driving in the states of Washington and Oregon by providing for the marking of the license plate of a vehicle when its operator was apprehended driving while suspended. In both states, the records of 101,000 drivers convicted of a drunk-driving offense who were potentially at risk for this sanction were analyzed using time series analysis to determine the general deterrent effect of the law. In addition, the specific deterrent effect of having one's vehicle marked was studied in Oregon using analysis of covariance. Results of these analyses indicated that the law had both a general and specific deterrence effect in Oregon but no measurable effect in Washington.

Accidents, Traffic↗
PubMed1999

An evaluation of the general effect of the New Zealand graduated driver licensing system on motorcycle traffic crash hospitalisations.

In 1987, New Zealand introduced a comprehensive Graduated Driver Licensing System (GDLS) which was designed to allow new drivers to gain driving experience while being excluded from high risk situations. This study sought to evaluate the impact of the GDLS on motorcycle traffic crashes that resulted in serious injury. Injury crash data were obtained from the New Zealand Health Information Services national public hospital inpatient data files for the years 1978-1994, inclusive. Cases were disaggregated into three age groups, 15-19 years, 20-24 years, and 25 years or older, for which injury trends were obtained. In order to determine whether trends in motorcycle traffic crashes simply followed national trends in other injury events, two non-traffic comparison groups for the main target group (15-19 years) were included. Using time series analyses, the introduction of the GDLS was found to be closely followed by a significant reduction (22%) in motorcycle traffic crash hospitalizations for the 15-19 year age group. An examination of vehicle registration and driver licensure data suggests that the reduction in injury crashes may, largely, be attributable to an overall reduction in exposure to motorcycle riding.

Accidents, Traffic↗
PubMed2000

The knowledge, attitudes, and practices of dietitians licensed in Oregon regarding functional foods, nutrient supplements, and herbs as complementary medicine.

OBJECTIVE: To examine the perceived knowledge and attitudes of dietitians licensed in Oregon (LDs) regarding the effectiveness and safety of functional foods, nutrient supplements, and herbs as complementary medicine as well as their personal use, recommendations for the use of others, and training needs. DESIGN: A mailed survey was used to gather data. The questionnaire was developed and face-validated after a focus group discussion. SUBJECTS/SETTING: A geographically stratified, random sample of 202 Oregon LDs was surveyed; usable data were collected from 162 LDs (80%). STATISTICAL ANALYSES: Descriptive statistics and chi 2 tests were used to analyze data. The data were weighted to take account of the sampling method and yield population estimates. RESULTS: LDs considered themselves to be knowledgeable of functional foods and nutrient supplements. More than 80% were confident of the effectiveness of functional foods and nutrient supplements for prevention of illness and treatment of chronic illness, and at least 89% were confident of their safety for these uses. Fewer than 75% considered herbs to be safe and only about 50% were confident of the effectiveness of herbs. Only 10% or fewer LDs considered themselves to be knowledgeable about herbs for prevention and treatment of illness. Interest in training about each of these less-traditional nutrition therapies was high. APPLICATIONS/CONCLUSIONS: Oregon LDs consider themselves to be actively practicing in the area of complementary medicine and have a strong desire for further training. The dietetics profession can capitalize on this interest by taking the lead in training dietitians about the role of functional foods, nutrient supplements, and herbs in health.

Complementary Therapies↗
PubMed1999

Designing a license plate.

The majority of license plates in Saudi Arabia contain a 7-digit code to represent the registration number of vehicles. This information can be difficult to read, memorize, and reproduce in a short period of time, such as in the case of recall of hit-and-run accidents. The study reported proposes a registration code composed of 3 letters and 3 digits. This alphanumeric code can be converted into a numerical value which would give close to 20 million possible permutations, which would cover the projected number of vehicles to the year 2012. The original and proposed designs would give, in addition to two other alphanumeric codes, were tested on 60 participants using computer animations at three exposure times (1, 2, and 3 s). The results of the ANOVA on the errors committed and Sheffe tests reveal a significant difference (alpha = 0.01) between the 7-digit design and the other designs at all time intervals. Validation of the laboratory experiments were conducted on 15 different participants in the field, with similar findings.

Analysis of Variance↗
PubMed2000

The MAT1 cyclin-dependent kinase-activating kinase (CAK) assembly/targeting factor interacts physically with the MCM7 DNA licensing factor.

MAT1 (ménage à trois1) functions as an assembly/targeting factor of CAK (cyclin-dependent kinase-activating kinase). In a search for MAT1-interacting proteins using yeast two-hybrid system, MCM7 (minichromosome maintenance 7), a member of a family of DNA licensing factors, was identified. The physical interaction between MAT1 and MCM7 was confirmed in vivo in yeast cells and verified with in vitro protein binding assays. Further studies showed the RING-finger motif of MAT1 is not required for the interaction with MCM7, while the C-terminal domain of MAT1 is indispensable. Immunoprecipitation of MCM7 in human osteosarcoma MG63 cells demonstrated that MCM7 associates with the CAK complex in vivo.

Amino Acid Motifs↗
PubMed2003

Mitochondria-assisted cell suicide: a license to kill.

Although the mechanisms that underlie cardiac cell death remain cryptic, there is emerging evidence that mitochondria may play a pivotal role in this process. The mitochondrion initially deemed the "power house " is now considered to be a central integration site for biological signals that promote cell life or cell death. Since mitochondria contain the necessary apoptotic machinery to activate the cell-death pathway, it is now appreciated that mitochondria play a key decision-making role in whether a cell will live or die following a noxious signal-literally a "license to kill ". Permeability changes to the outer mitochondrial membrane, collapse of membrane potential, permeability pore complex assembly, release of cytotoxic proteins and caspase activation are associated with the mitochondrial-death pathway. Members of the Bcl-2 gene family can promote or suppress cell death by modulating mitochondrial function. Activation of the mitochondrial-death pathway has been reported in several cardiac pathologies and believed to account for the reported apoptosis observed in these disease entities. Given the meager and limited ability of cardiac muscle for repair or self-renewal after injury, the inordinate loss of cardiac cells is considered to be a key underlying factor in ventricular remodeling and decline in ventricular performance in patients with ischemic heart disease or post-myocardial infarction. This review will provide mechanistic insight into the involvement and contribution of the mitochondrion as a regulator of cell death in health and disease with particular focus on the heart.

Animals↗
PubMed2003

Enhancing the effectiveness of graduated driver licensing legislation.

PROBLEM: Many states have enacted graduated driver licensing (GDL) systems in an effort to reduce the very high crash rates of young beginning drivers. This article addresses how to achieve the maximum benefit from GDL by ensuring compliance with protective restrictions. ENHANCING GDL THROUGH SYSTEM STRUCTURE: The major crash reductions due to GDL systems result from the protective restrictions during the initial two levels, which isolate novice drivers from the highest risk driving situations. Accordingly, GDL systems should include protective restrictions that adequately control the greatest dangers facing young drivers: multiple teen passengers and night driving before midnight. ENCOURAGING COMPLIANCE THROUGH SYSTEM STRUCTURE: Including protective restrictions that are supported by parents and teens will encourage compliance. Furthermore, linking a teen's advancement through GDL to demonstrated responsible driving will likely encourage compliance more than threatening punishment for violations. ENCOURAGING COMPLIANCE THROUGH ENFORCEMENT: Parents are in a prime position to enforce most GDL restrictions, but there is some evidence they do not enforce those restrictions that they consider too extreme. Little is currently known about the involvement of law enforcement in GDL systems, but there is potential for high visibility law enforcement activities to encourage compliance with restrictions. IMPACT ON RESEARCH, PRACTICE, AND POLICY: There is a need for better designed GDL systems in many states; more research is needed to examine compliance with restrictions and to evaluate enforcement efforts by parents and law enforcement.

Accidents, Traffic↗
PubMed2003

Relationship between pathology curricular approaches and performance in the United States medical licensing examination (USMLE), step 1: a national cross-sectional study.

A collaborative multi-institutional study was conducted to study the relationship between characteristics of pathology instruction and student performance in the United States Medical Licensing Examination (USMLE), Step 1. Detailed descriptions of pathology instruction, such as curriculum format, style of instruction, and design of instruction of various areas of pathology for the 1996-1997 academic year were matched with Step 1 total scores and pathology subscores for 10,159 students from 88 schools who took the June 1997 examination. Hierarchical linear modeling was used for analysis while controlling for students' MCAT-bpv scores (Medical College Admission Test scores, average of biological and physical sciences and verbal reasoning). The Step 1 total scores correlate with Step 1 pathology subscores, and both correlate with students' MCAT-bpv scores. The MCAT-bpv scores account for most of the variation in Step 1 scores. Of all of the curricular variables analyzed, 2 possible factors that significantly influence the impact of MCAT-bpv scores on Step 1 scores are (1) multidisciplinary format of instruction and (2) discipline-based general pathology instruction in year 2. Overall, the multidisciplinary format reduced the impact of MCAT-bpv scores on both the Step 1 total score and the pathology subscore by 1 point per MCAT-bpv. Overall, the general pathology instruction in year-2 increased that impact on Step 1 total score by 1 point per MCAT-bpv. The slope became less steep with multidisciplinary format and more steep with year-2 general pathology instruction. As a result, students with higher MCAT-bpv scores tend to benefit from year-2 general pathology instruction, whereas those with lower MCAT-bpv scores appear to benefit from a multidisciplinary format. These differences become more apparent as the MCAT-bpv scores move away from the mean in either direction, indicating that scores of most students are not affected by curricular variables. Overall, there is no significant difference in the school means of Step 1 total scores and pathology subscores of schools with different curricular approaches. This is most likely due to the finding that the students' MCAT-bpv scores, and not curricular variables, are the major predictors of Step 1 scores, and all schools have a mix of students with various MCAT-bpv scores.

Analysis of Variance↗
PubMed1996

Interaction between the origin recognition complex and the replication licensing system in Xenopus.

The origin recognition complex (ORC) binds to origins of replication in budding yeast. We have cloned a Xenopus homolog of the largest ORC polypeptide (XORC1). Immunodepletion of XOrc1 from Xenopus egg extracts blocks the initiation of DNA replication. We have purified Xenopus ORC, consisting of a protein complex similar to yeast ORC. In Xenopus egg extracts, ORC associates with chromatin throughout G1 and S phases. RLF-M, a component of the replication licensing system, also associates with chromatin early in the cell cycle but dissociates during S phase. We show that the assembly of RLF-M onto chromatin is dependent on the presence of chromatin-bound ORC, leading to sequential assembly of initiation proteins onto replication origins during the cell cycle.

Amino Acid Sequence↗
PubMed1995

Commercialization of gene therapy--the evolution of licensing and rights issues.

The scientific community and the general public are intrigued by the potential use of gene therapy to tackle disease at its origin, and the resulting benefits to the quality of lif. At the same time, pharmaceutical researchers are beginning to appreciate how an understanding of the genetic basis of disease, and its associated technologies may revolutionize the discovery process for new drugs. Therefore, companies must understand and anticipate how licensing and rights issues are likely to evolve with the science.

Biological Products↗