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PubMed1990

Safety effects of relaxing California's clean-record requirement for driver license renewal by mail.

A pilot program was established in California in 1982 authorizing mail renewal of driver licenses for persons under age 70 lacking clean (accident- and conviction-free) 4-year driving records, but showing clean 2-year records at selection. Such drivers constitute about 14% of California's renewal population, or about 500,000 renewees per year. Eligible drivers whose licenses expired in 1983 were subjects of the present study. Half of them were randomly assigned to a group whose members were sent offers of renewal by mail and the other half were sent standard renewal notices requiring appearance in a field office and successful completion of vision and traffic law tests. Traffic accidents and convictions following the mailout of these documents were tracked for both groups; results presented here cover a 4-year period subsequent to mailout. During this period (a normal license term in California), no significant overall difference was shown between the groups with respect to subsequent convictions or accidents. However, significant detrimental effects on accidents were noted for a subgroup of drivers who had experienced recent traffic violations or accidents which were not on their records at selection. Implications of these results are discussed.

Accidents, Traffic↗
PubMed1992

The effects of age and experience on accidents with injuries: should the licensing age be raised?

In Canadian Provinces and in several states of the United States the minimal legal age to drive a motor vehicle is 16 years old and in some, it is 15. The excess mortality and morbidity registered by 15 to 24-year-old drivers is well known. Several studies have reported that accident rates decrease with experience, but the effect of the age of new drivers has not been well documented. The objective is to study injury accident rates in terms of the age and experience factors. The data sources are computer files of the Government Insurance Corporation (Société de l'assurance automobile du Québec), which covers all Quebec drivers. For each driver, the file contains birth date, sex, year and month of first license, involvement in accidents, and other parameters. The yearly rates (1970-1984) of new permits per age last birthday and sex show an increase over time, particularly for 16-year-old men. For the period 1979-1984, injury accident involvement rates were computed for all Quebec drivers by age, sex, and driving experience. An experienced driver has been defined as a person who has been licensed for at least one year. The results show, for experienced as well as inexperienced young men (16-18), a high injury accident rate that decreases with age. For women, the rates are much lower and decrease more gradually than for men. This study does not take into account the kilometers driven. Since young drivers (16-18) have the highest accident rates, the question of regulating access to first licensing for such drivers must be examined as a possible strategy for injury prevention.

Accident Prevention↗
PubMed1995

Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor.

Replication licensing factor is thought to be involved in the strict control of the initiation of DNA replication in eukaryotes. We identified a 100 kDa protein as a candidate for the licensing factor in Xenopus egg extracts. This protein was required for replication; it bound to sperm DNA before the formation of nuclei and apparently dissociated from the nuclear DNA during the progression of replication without being transported into the nuclei. An immunologically homologous protein in HeLa cells behaved similarly to the Xenopus protein during the cell cycle. Cloning and sequencing of the cDNAs encoding the Xenopus and human proteins revealed that they are homologs of yeast Mcm3, a putative yeast DNA replication licensing factor.

Amino Acid Sequence↗
PubMed1994

The MCM2-3-5 proteins: are they replication licensing factors?

DNA replication occurs only once in each normal mitotic cell cycle. To explain this strict control, a 'licensing factor' was proposed to enter the nucleus periodically as the nuclear envelope disintegrates and reassembles at the end of mitosis. Inactivation of licensing factor immediately following initiation of DNA synthesis would prevent reinitiation until after the next mitosis. The MCM2-3-5 proteins of Saccharomyces cerevisiae may be yeast's equivalent of licensing factor: they are present in the nucleus only between M and S phase, bind to chromatin and are important for the initiation of DNA replication.

Journal Article↗
PubMed2007

The acceptability to older drivers of different types of licensing restriction.

The primary objective of this study was to determine the acceptability of various driving restrictions to older drivers. Licensed drivers aged 65 years or more living in the community in the Ottawa, Ontario area were recruited by means of posters and advertisements in regional and local newspapers. We recruited 86 subjects, 56 men and 30 women with a mean age of 75 years (50 urban and 36 rural residents). The subjects completed a one-hour interview with one of two trained study nurses during which their driving restriction preferences (utilities) were determined using a modified standard gamble technique. Highly endorsed restrictions included regular assessment by the Ministry of Transportation (mean utility 0.94), driving with vehicle adaptations (0.94) and daytime driving only (0.93). Less acceptable restrictions included avoidance of roads with a speed limit greater than 60 km/h (0.50), limitation of destinations (0.45), driving only within a 10-km radius of home (0.45) and requirement of another licensed driver in the vehicle (0.42). Our subjects' preferences appeared to be inversely related to the impact on autonomy and the ability to access the community. These findings may be useful to motor transport administrators in designing effective restricted licensing programs that are acceptable to older drivers.

Age Factors↗
PubMed2004

Graduated driver licensing restrictions: awareness, compliance, and enforcement in North Carolina.

PROBLEM: This study examined the extent to which critical restrictions in North Carolina's graduated driver licensing (GDL) system are known, adhered to, and enforced. METHOD: Teenagers and their parents were recruited as they applied for either an intermediate or full license at 1 of 23 licensing offices. Telephone interviews were conducted with 900 teenagers and their parents. RESULTS: Awareness of North Carolina's night and passenger restrictions was very high among both parents and teenagers. Ten percent of teenagers reported violating the night restriction without their parents' knowledge, and 15% had done so with their parents' approval. Only 4% of parents reported allowing their teenagers to drive with more than one teenage passenger, but 19% of teenagers reported that they were allowed to do this. Violations of the passenger restriction without parental knowledge were more common than violations of the night restriction (22% vs. 10%, respectively). Among teenagers who violated restrictions without their parents' knowledge, most reported doing so only once or a few times. Teenagers expressed little concern about detection, although a majority reported driving more carefully to avoid police notice. Neither parents nor teenagers knew much about police enforcement of GDL restrictions. To obtain a sense of the views of law enforcement officers, informal interviews were conducted with 20 officers from five diverse communities and the state highway patrol. These officers were highly supportive of GDL but unfamiliar with many of the specific provisions. Moreover, enforcement of GDL restrictions did not appear to be a high priority. IMPACT ON INDUSTRY: There is a need to increase the belief among teens (and parents) that police are enforcing GDL restrictions in their community; law enforcement participation in well-publicized traffic safety enforcement efforts would likely produce this result.

Adolescent↗
PubMed2006

Gender differences in the Swedish driving-license test.

INTRODUCTION: Male drivers between 18-24 years are involved in many more motor-vehicle accidents than female drivers in Sweden. Is there also a gender difference in test performance in the Swedish driving-license tests? Is it a real difference or do any of the items display differential item functioning (DIF) with respect to gender or educational background? METHOD: Two random samples of test-takers' performance on the Swedish theory driving-license test were examined with descriptive and inference statistics. RESULTS: Female test-takers performed better than male test-takers on the theory test, which is a real difference since no items displayed DIF with respect to gender. There was no gender difference in the practical test. The gender difference in the theory test could not be fully explained by differences in educational background. CONCLUSIONS: Although everyone who passes the driving-license test has fulfilled the goals stated in the curriculum, it is possible that the gender differences in the theory test are consistent over time, and therefore might be one factor that explains why male drivers are over-represented in traffic accidents. IMPACT ON INDUSTRY: Gender differences appear persistent over time. Therefore, by improving male test takers' result on the test may lead to positive effects on the male test takers future driving career.

Accidents, Traffic↗
PubMed2006

Deregulated replication licensing causes DNA fragmentation consistent with head-to-tail fork collision.

Correct regulation of the replication licensing system ensures that no DNA is rereplicated in a single cell cycle. When the licensing protein Cdt1 is overexpressed in G2 phase of the cell cycle, replication origins are relicensed and the DNA is rereplicated. At the same time, checkpoint pathways are activated that block further cell cycle progression. We have studied the consequence of deregulating the licensing system by adding recombinant Cdt1 to Xenopus egg extracts. We show that Cdt1 induces checkpoint activation and the appearance of small fragments of double-stranded DNA. DNA fragmentation and strong checkpoint activation are dependent on uncontrolled rereplication and do not occur after a single coordinated round of rereplication. The DNA fragments are composed exclusively of rereplicated DNA. The unusual characteristics of these fragments suggest that they result from head-to-tail collision (rear ending) of replication forks chasing one another along the same DNA template.

Animals↗
PubMed1998

Assessing medically impaired older drivers in a licensing agency setting.

An exploratory study is being conducted jointly by the California Department of Motor Vehicles and the National Highway Traffic Safety Administration to develop a licensing agency assessment battery for elderly drivers with dementia or other aging-related medical conditions. A preliminary battery of nondriving tests and road tests is described; test results for a small pilot sample are presented, and the tests are evaluated in terms of their utility for detecting functional impairment and predicting driving performance. Some considerations that shape construction of a test battery for licensing agency use are discussed in relation to these goals and the givens of a driver licensing environment.

Aged↗
PubMed2004

Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1.

Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1, leads to overreplication and chromosomal instability (CIN) in lower eukaryotes and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung carcinomas, and investigated for putative relations with G(1)/S phase regulators, tumor kinetics, and ploidy. This is the first study of these fundamental licensing elements in primary human lung carcinomas. We herein demonstrate elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of neoplasms, respectively, whereas aberrant expression of hGeminin was observed in 49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048, respectively). Supportive of the observed link between E2F-1 and hCdt1, we provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian cells. Interestingly, hGeminin overexpression was statistically related to increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The significance of these results was underscored by the fact that the latter parameters were independent of p53 within the hCdt1-hCdc6 normally expressing cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6 overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung carcinomas.

Aged↗
PubMed2003

Other high-risk factors for young drivers--how graduated licensing does, doesn't, or could address them.

PROBLEM: Young drivers, particularly those who are newly licensed, have a very high crash risk. This paper examines the risk factors underlying their high crash rates and assesses the extent to which existing graduated licensing programs address these risks and whether improvements to these programs should be considered. METHOD: Review and synthesis of the literature. RESULTS: The elevated risk among young drivers of being in an injury crash is the result of a number of factors found alone or in combination, such as risky driving, alcohol use, seat belt nonuse, driver distraction, fatigue, and vehicle choice. Nighttime and passenger restrictions, adopted widely in the United States, work by keeping drivers out of hazardous situations rather than by addressing risk factors directly. However, the risk factors remain in play in driving situations not specifically restricted by law. Although other graduated licensing components adopted around the world-more stringent exit tests (i.e., you need to pass a test to move to the next stage), hazard perception tests, and restrictions on speed, vehicle power, and roadway access-make sense based on the identified risk factors, they are not yet supported by research. Should research findings warrant it, consideration should be given to providing guidance to parents about how to keep their beginning drivers safe, including information on vehicle choice. IMPACT ON RESEARCH, PRACTICE, AND POLICY: Researchers should continue to monitor and to evaluate innovative approaches to reduce the crash risk of young drivers. The effectiveness of new approaches should be established before adoption on a wider scale takes place.

Accidents, Traffic↗
PubMed2003

Graduated driver licensing and safer driving.

Graduated Driver Licensing (GDL) inserts between the leaner permit and full licensure an intermediate or "provisional" license that allows novices to drive unsupervised but subject to provisions intended to reduce the risks that accompany entry into highway traffic. Introduction of GDL has been followed by lowered accident rates, resulting from both limiting exposure of novices to unsafe situations and by helping them to deal with them more safely. Sources of safer driving include extended learning, early intervention, contingent advancement, and multistage instruction. To extend the learning process, most GDL systems lengthen the duration of the learner phase and require a specified level of adult-supervised driving. Results indicate that extended learning can reduce accidents substantially if well structured and highly controlled. Early intervention with novice traffic violators have shown both a general deterrent effect upon novice violators facing suspension and a specific effect upon those who have experienced it. Making advancement to full licensure contingent upon a violation-free record when driving on the provisional license has also evidenced a reduction in accidents and violations during that phase of licensure. Multistage instruction attempts development of advanced skills only after novices have had a chance to master more basic skills. Although this element of GDL has yet to be evaluated, research indicates crash reduction is possible in situations where it does not increase exposure to risk. While the various elements of GDL have demonstrated potential benefit in enhancing the safety of novice drivers, considerable improvement in the nature and enforcement of GDL requirements is needed to realize that potential.

Accidents, Traffic↗
PubMed2003

The influenza vaccine licensing process.

Influenza vaccines are unique because they require a licensing process which includes a procedure for rapid annual updates to vaccine strains. The licensing procedures in the European Union and the USA are described as examples. In the event of an influenza pandemic, vaccines will be required urgently and licensing process should reflect such needs.

Drug Approval↗
PubMed2002

Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae.

Faithful duplication of the genetic material requires that replication origins fire only once per cell cycle. Central to this control is the tightly regulated formation of prereplicative complexes (preRCs) at future origins of DNA replication. In all eukaryotes studied, this entails loading by Cdc6 of the Mcm2-7 helicase next to the origin recognition complex (ORC). More recently, another factor, named Cdt1, was shown to be essential for Mcm loading in fission yeast and Xenopus as well as for DNA replication in Drosophila and humans. Surprisingly, no Cdt1 homolog was found in budding yeast, despite the conserved nature of origin licensing. Here we identify Tah11/Sid2, previously isolated through interactions with topoisomerase and Cdk inhibitor mutants, as an ortholog of Cdt1. We show that sid2 mutants lose minichromosomes in an ARS number-dependent manner, consistent with ScCdt1/Sid2 being involved in origin licensing. Accordingly, cells partially depleted of Cdt1 replicate DNA from fewer origins, whereas fully depleted cells fail to load Mcm2 on chromatin and fail to initiate but not elongate DNA synthesis. We conclude that origin licensing depends in S. cerevisiae as in other eukaryotes on both Cdc6 and Cdt1.

Amino Acid Sequence↗
PubMed1999

The RLF-B component of the replication licensing system is distinct from Cdc6 and functions after Cdc6 binds to chromatin.

Replication licensing factor (RLF) is an essential initiation factor that can prevent re-replication of DNA in a single cell cycle [1] [2]. It is required for the initiation of DNA replication, binds to chromatin early in the cell cycle, is removed from chromatin as DNA replicates and is unable to re-bind replicated chromatin until the following mitosis. Chromatography of RLF from Xenopus extracts has shown that it consists of two components termed RLF-B and RLF-M [3]. The RLF-M component consists of complexes of all six Xenopus minichromosome maintenance (MCM/P1) proteins (XMcm2-7), which bind to chromatin in late mitosis and are removed as replication occurs [3] [4] [5] [6] [7]. The identity of RLF-B is currently unknown. At least two factors must be present on chromatin before licensing can occur: the Xenopus origin recognition complex (XORC) [8] [9] and Xenopus Cdc6 (XCdc6) [10]. XORC saturates Xenopus sperm chromatin at approximately one copy per replication origin whereas XCdc6 binds to chromatin only if XORC is bound first [9] [10] [11]. Although XORC has been shown to be a distinct activity from RLF-B [9], the relationship between XCdc6 and RLF-B is currently unclear. Here, we show that active XCdc6 is loaded onto chromatin in extracts with defective RLF, and that both RLF-M and RLF-B are still required for the licensing of XCdc6-containing chromatin. Furthermore, RLF-B can be separated from XCdc6 by immunoprecipitation and standard chromatography. These experiments demonstrate that RLF-B is both functionally and physically distinct from XCdc6, and that XCdc6 is loaded onto chromatin before RLF-B function is executed.

Animals↗
PubMed2001

Driver's license and voter registration lists as population-based sampling frames for rural African Americans.

PURPOSE: To compare coverage of a state driver's license list and county voter registration lists as frames for sampling rural African Americans. METHODS: Name, birth date, sex, and county were extracted from records for all 18--59 year-old African Americans residing in eight rural North Carolina counties and listed in the North Carolina Driver license file [obtained as a SAS dataset from the University of North Carolina (UNC) Highway Safety Research Center] and in machine-readable text files of registered voters (obtained from county boards of elections). Files were edited, merged, and matched by last name and date of birth to produce three files for each five-year age group, sex, and county: 1) persons listed only in the driver's file; 2) persons listed only in the voter's file; and 3) persons listed in both. RESULTS: The median percentages of unique persons found only on the driver's list, only on the voter's list, and on both lists were 54%, 17%, and 30% men, and 35%, 25%, and 41% women, respectively. CONCLUSIONS: The driver's list provided better coverage than did voter registration lists. Federal legislation that prohibits states from releasing driver's license lists for use in surveys removes a valuable resource for population-based research.

Adult↗
PubMed2000

The Cdt1 protein is required to license DNA for replication in fission yeast.

To maintain genome stability in eukaryotic cells, DNA is licensed for replication only after the cell has completed mitosis, ensuring that DNA synthesis (S phase) occurs once every cell cycle. This licensing control is thought to require the protein Cdc6 (Cdc18 in fission yeast) as a mediator for association of minichromosome maintenance (MCM) proteins with chromatin. The control is overridden in fission yeast by overexpressing Cdc18 (ref. 11) which leads to continued DNA synthesis in the absence of mitosis. Other factors acting in this control have been postulated and we have used a re-replication assay to identify Cdt1 (ref. 14) as one such factor. Cdt1 cooperates with Cdc18 to promote DNA replication, interacts with Cdc18, is located in the nucleus, and its concentration peaks as cells finish mitosis and proceed to S phase. Both Cdc18 and Cdt1 are required to load the MCM protein Cdc21 onto chromatin at the end of mitosis and this is necessary to initiate DNA replication. Genes related to Cdt1 have been found in Metazoa and plants (A. Whitaker, I. Roysman and T. Orr-Weaver, personal communication), suggesting that the cooperation of Cdc6/Cdc18 with Cdt1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.

Cell Cycle↗
PubMed2004

Structural basis for inhibition of the replication licensing factor Cdt1 by geminin.

To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.

Animals↗