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PubMed2004

The costs and benefits of library site licenses to academic journals.

Scientific publishing is rapidly shifting from a paper-based system to one of predominantly electronic distribution, in which universities purchase site licenses for online access to journal contents. Will these changes necessarily benefit the scientific community? By using basic microeconomics and elementary statistical theory, we address this question and find a surprising answer. If a journal is priced to maximize the publisher's profits, scholars on average are likely to be worse off when universities purchase site licenses than they would be if access were by individual subscriptions only. However, site licenses are not always disadvantageous. Journals issued by professional societies and university presses are often priced so as to maximize subscriptions while recovering average costs. When such journals are sustained by institutional site licenses, the net benefits to the scientific community are larger than if these journals are sold only by individual subscriptions.

Cost-Benefit Analysis↗

PubMed2006

Androgen receptor as a licensing factor for DNA replication in androgen-sensitive prostate cancer cells.

Androgen receptor (AR) protein expression and function are critical for survival and proliferation of androgen-sensitive (AS) prostate cancer cells. Besides its ability to function as a transcription factor, experimental observations suggest that AR becomes a licensing factor for DNA replication in AS prostate cancer cells and thus must be degraded during each cell cycle in these cells to allow reinitiation of DNA replication in the next cell cycle. This possibility was tested by using the AS human prostate cancer cell lines, LNCaP, CWR22Rv1, and LAPC-4. These studies demonstrated that AR levels fluctuate both within and between various phases of the cell cycle in each of these AS lines. Consistent with its licensing ability, AR is degraded during mitosis via a proteasome-dependent pathway in these AS prostate cancer cells. In contrast, proteasome-dependent degradation of AR during mitosis is not observed in AR-expressing but androgen-insensitive human prostate stromal cells, in which AR does not function as a licensing factor for DNA replication. To evaluate mitotic degradation of AR in vivo, the same series of human AS prostate cancers growing as xenografts in nude mice and malignant tissues obtained directly from prostate cancer patients were evaluated by dual Ki-67 and AR immunohistochemistry for AR expression in mitosis. These results document that AR is also down-regulated during mitosis in vivo. Thus, AS prostate cancer cells do not express AR protein during mitosis, either in vitro or in vivo, consistent with AR functioning as a licensing factor for DNA replication in AS prostate cancer cells.

Androgen Receptor Antagonists↗

PubMed2001

The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase.

S-phase onset is controlled, so that it occurs only once every cell cycle. DNA is licensed for replication after mitosis in G(1), and passage through S-phase removes the license to replicate. In fission yeast, Cdc6/18 and Cdt1, two factors required for licensing, are central to ensuring that replication occurs once per cell cycle. We show that the human Cdt1 homologue (hCdt1), a nuclear protein, is present only during G(1). After S-phase onset, hCdt1 levels decrease, and it is hardly detected in cells in early S-phase or G(2). hCdt1 can associate with the DNA replication inhibitor Geminin, however these two proteins are mostly expressed at different cell cycle stages. hCdt1 mRNA, in contrast to hCdt1 protein, is expressed in S-phase-arrested cells, and its levels do not change dramatically during a cell cycle, suggesting that proteolytic rather than transcriptional controls ensure the timely accumulation of hCdt1. Consistent with this view, proteasome inhibitors stabilize hCdt1 in S-phase. In contrast, hCdc6/18 levels are constant through most of the cell cycle and are only low for a brief period at the end of mitosis. These results suggest that the presence of active hCdt1 may be crucial for determining when licensing is legitimate in human cells.

Animals↗

PubMed2002

Prevalence of responsible hospitality policies in licensed premises that are associated with alcohol-related harm.

This study aimed to determine the prevalence of responsible hospitality policies in a group of licensed premises associated with alcohol-related harm. During March 1999, 108 licensed premises with one or more police-identified alcohol-related incidents in the previous 3 months received a visit from a police officer. A 30-item audit checklist was used to determine the responsible hospitality policies being undertaken by each premises within eight policy domains: display required signage (three items); responsible host practices to prevent intoxication and under-age drinking (five items); written policies and guidelines for responsible service (three items); discouraging inappropriate promotions (three items); safe transport (two items); responsible management issues (seven items); physical environment (three items) and entry conditions (four items). No premises were undertaking all 30 items. Eighty per cent of the premises were undertaking 20 of the 30 items. All premises were undertaking at least 17 of the items. The proportion of premises undertaking individual items ranged from 16% to 100%. Premises were less likely to report having and providing written responsible hospitality documentation to staff, using door charges and having entry/re-entry rules. Significant differences between rural and urban premises were evident for four policies. Clubs were significantly more likely than hotels to have a written responsible service of alcohol policy and to clearly display codes of dress and conditions of entry. This study provides an indication of the extent and nature of responsible hospitality policies in a sample of licensed premises that are associated with a broad range of alcohol related harms. The finding that a large majority of such premises appear to adopt responsible hospitality policies suggests a need to assess the validity and reliability of tools used in the routine assessment of such policies, and of the potential for harm from licensed premises.

Alcohol Drinking↗

PubMed1991

The measurement of harmful outcomes following drinking on licensed premises.

The relationships between five potential indicators of alcohol-related harm following drinking on licensed premises in Perth were explored. These were annual purchases made by individual licensees of 'high' (>=3.8%) and 'low' (<3.8%) alcohol content drinks, the number of times a particular licensed establishment is cited by drivers as the last place of drinking prior to failing a roadside breath-test (including after accidents) and the annual number of assaults occurring either on or in the vicinity of particular licensed premises. The study area selected was a central part of the Perth metropolitan area with 367 licensed premises serving a residential population of 400 000. Highly significant correlations were found between each of the five variables. The correlations involving purchases of low alcohol drinks, however, were small. When purchases of alcohol were controlled, significant, though lower, correlations, were still evident between the other three variables. This suggests that there are risk factors other than extent of alcohol sales which further research will need to identify, and that these indicators of harm can be of value in monitoring the impact of future intervention strategies.

Journal Article↗

PubMed2004

The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.

Before S phase, cells license replication origins for initiation by loading them with Mcm2-7 heterohexamers. This process is dependent on Cdc6, which is recruited to unlicensed origins. Using Xenopus egg extracts we show that although each origin can load many Mcm2-7 hexamers, the affinity of Cdc6 for each origins drops once it has been licensed by loading the first hexamers. This encourages the distribution of at least one Mcm2-7 hexamer to each origin, and thereby helps to ensure that all origins are licensed. Although Cdc6 is not essential for DNA replication once licensing is complete, Cdc6 regains a high affinity for origins once replication forks are initiated and Mcm2-7 has been displaced from the origin DNA. We show that the presence of Cdc6 during S phase is essential for the checkpoint kinase Chk1 to become activated in response to replication inhibition. These results show that Cdc6 plays multiple roles in ensuring precise chromosome duplication.

Animals↗

PubMedDate not supplied

Training for child day care staff and for licensing and regulatory personnel in the prevention of infectious disease transmission.

Recognition of the importance of preventing disease transmission in day care facilities has increased as more mothers of infants join the work force and as evidence of the spread of disease in day care mounts; the effectiveness of licensing agencies has eroded with the shrinking of resources, and limited compliance with current standards exists. Both the staff of child day care facilities and the personnel who are responsible for licensing and regulating such facilities require ongoing training in issues of health promotion and disease prevention. The curriculum of all training programs should include, in addition to child development, topics of general health and safety, such as safety hazards and the risk of infection, knowledge of the infectious diseases likely to be encountered in day care, the use of routine screening tests, the principles of good nutrition, the components of routine health assessment, and the special concerns of disabled, abused, and neglected children. Health professionals in the community and licensing personnel should function as channels for the dissemination of new information as it becomes available; inspection of facilities for the purpose of licensing provides an excellent opportunity for training staff. Monitoring has been found to heighten awareness and improve performance. Employees' compliance with regulations has been shown to increase when staff members are trained as advocates of health.

Child Day Care Centers↗

PubMed2006

Impact of the United States Medical Licensing Examination Step 2 Clinical Skills exam on medical school clinical skills assessment.

BACKGROUND: Medical schools face a new responsibility to prepare students for the United States Medical Licensing Exam Step 2 Clinical Skills (CS) exam. METHOD: We conducted semistructured interviews with 25 leaders of medical school clinical skills assessments to explore purposes of in-house assessment and the impact of the Step 2 CS exam. Interviews were coded to identify major themes. RESULTS: Competency assessment, student and curricular feedback, and preparation for the licensing exam emerged as major purposes of in-house exams. Participants asserted that in-house exams assessed faculty-identified competencies, although not all schools had defined competencies. Limited resources made balancing formative and summative assessment goals problematic for some schools. Curricular feedback was general but valued. All schools, even those that disagreed with aspects of the licensing exam, acknowledged their roles in preparing students for the Step 2 CS. CONCLUSION: An external licensing requirement engenders debate and motivates changes in clinical skills assessment and, in some cases, curricula.

Clinical Competence↗

PubMed2004

Illegal alcohol sales to obviously intoxicated patrons at licensed establishments.

BACKGROUND: Early studies assessing propensity of alcohol sales to underage youth found that, before intervention, likelihood of licensed alcohol establishments selling alcohol to underage youth was 50% or higher across many communities. Community-wide interventions successfully lowered underage alcohol sales rates in several communities. Across studies assessing propensity for alcohol sales to obviously intoxicated patrons, sales rate estimates ranged from 58% to 85% for on-premise establishments (e.g., bars). No previous studies have assessed likelihood of alcohol sales to obviously intoxicated patrons in off-premise establishments (e.g., liquor stores). One goal of this study was to assess propensity for illegal alcohol sales to obviously intoxicated patrons at on- and off-premise establishments. Another goal was to assess whether server and/or establishment characteristics were related to the likelihood of illegal sales. Results may inform future interventions to reduce illegal alcohol sales at licensed alcohol establishments. METHODS: Trained actors attempted to purchase alcohol while acting out signs of obvious intoxication at a census of on- and off-premise alcohol establishments (n = 372) in 11 communities. The outcome variable was whether an establishment sold alcohol to a buyer. Independent variables included age and gender of server/clerk, type of establishment, area, exterior maintenance, type of license, and time of purchase attempt. Bivariate and multivariate analyses were conducted. RESULTS: Seventy-nine percent of the establishments sold alcohol to a buyer (83% and 76% at off- and on-premise establishments, respectively). Servers/clerks who appeared younger than age 31 and off-premise establishments were significantly more likely than older appearing servers and on-premise establishments to sell alcohol to buyers. CONCLUSIONS: The likelihood of alcohol sales to obviously intoxicated patrons in licensed alcohol establishments is very high. Interventions to reduce illegal alcohol sales to intoxicated patrons are needed.

Adult↗

PubMed2004

DNA replication licensing affects cell proliferation or endoreplication in a cell type-specific manner.

In eukaryotic cells, the function of DNA replication licensing components (Cdc6 and Cdt1, among others) is crucial for cell proliferation and genome stability. However, little is known about their role in whole organisms and whether licensing control interfaces with differentiation and developmental programs. Here, we study Arabidopsis thaliana CDT1, its regulation, and the consequences of overriding licensing control. The availability of AtCDT1 is strictly regulated at two levels: (1) at the transcription level, by E2F and growth-arresting signals, and (2) posttranscriptionally, by CDK phosphorylation, a step that is required for its proteasome-mediated degradation. We also show that CDC6 and CDT1 are key targets for the coordination of cell proliferation, differentiation, and development. Indeed, altered CDT1 or CDC6 levels have cell type-specific effects in developing Arabidopsis plants: in leaf cells competent to divide, cell proliferation is stimulated, whereas in cells programmed to undergo differentiation-associated endoreplication rounds, extra endocycles are triggered. Thus, we propose that DNA replication licensing control is critical for the proper maintenance of proliferative potential, developmental programs, and morphogenetic patterns.

Arabidopsis↗

PubMed2000

Prevalence and acceptability of public health initiatives in licensed premises.

OBJECTIVES: To determine the prevalence and acceptability of public health initiatives in licensed premises. METHODS: Licensees/managers of all 333 licensed premises in the Hunter Region of NSW were interviewed to assess the practice of, and interest in undertaking public health initiatives relating to: responsible service of alcohol; environmental tobacco smoke; healthy-food choices; skin, breast and cervical cancer prevention; and the prevention of HIV/AIDS. RESULTS: Ninety eight percent of contacted premises participated in the study. Approximately two-thirds of premises reported having a responsible service of alcohol policy and training their staff in responsible service. One third of premises reported the provision of healthy food choices and smoke-free areas. Initiatives concerned with the prevention of cancer and HIV/AIDS were practised by less than 25% of premises. Between 41% and 85% of premises expressed an interest in undertaking all but two initiatives. Almost all interested premises accepted the offer of resources to facilitate adoption of public health initiatives. CONCLUSIONS: The study suggests that licensed premises are already involved in a number of public health initiatives, and that they appear willing to consider the introduction of a wide range of such initiatives. IMPLICATIONS: The prevalence of public health initiatives in licensed premises, and the extent of interest expressed by licensees/managers in undertaking such initiatives suggests that both a need and an opportunity exist for public health and other agencies to be more actively involved in disseminating appropriate services in this setting.

Alcohol Drinking↗

PubMed2003

Community attitudes towards environmental tobacco smoke in licensed premises: follow-up study after the Sharp case.

OBJECTIVE: To examine community attitudes towards environmental tobacco smoke in licensed premises after the Sharp case decision. METHOD: 723 randomly selected New South Wales residents aged 18 years and over completed a telephone survey in November 2001. RESULTS: The vast majority supported some form of smoking restriction in licensed clubs (92.1%) and hotels (90.0%). Compared with a 2000 survey, respondents in the 2001 survey were significantly more likely to support a total smoking ban in licensed clubs and hotels. When support was assessed using a ban-only question, 66.8% supported banning smoking in pubs/clubs. Approximately half reported being less likely to visit non-eating areas of licensed clubs (51.2%) and hotels (49.8%) if smoking were permitted and these proportions were significantly higher than in the 2000 survey. A majority (83.1%) thought bar workers' health should be a major consideration when deciding how to handle smoking in pubs/clubs. More than half (56.8%) believed pubs/clubs would experience significant financial problems if smoking bans were introduced. CONCLUSIONS AND IMPLICATIONS: In New South Wales, majority support exists for banning smoking in pubs and clubs. Legislation banning smoking in all indoor drinking and gaming areas should be introduced immediately.

Adolescent↗

PubMed1993

Alcoholic beverage licensing practices in California: a study of a regulatory agency.

A mail survey sent to all 25 State of California Alcoholic Beverage Control (ABC) offices and distributed to all 167 investigators assessed investigators' decisions to recommend issuance or denial of alcoholic beverage license applications. Investigators responded to three hypothetical vignettes that involved applications for liquor licenses. Findings show that although ABC investigators are influenced by public protests, illegal applications, and an applicant's moral character, they consistently favor licensing the applicant. The two formal rules that were designed specifically to respond to the community's welfare do not present serious barriers to obtaining an alcohol license. As a state regulatory organization, ABC is influenced greatly by the industry that it is supposed to regulate.

Alcohol Drinking↗

PubMed1993

The risks of licensing persons with diabetes to drive trucks.

The 1990 Americans with Disabilities Act forbids employers to bar disabled persons from jobs unless employers can show the disabled person cannot perform the tasks. The Federal Highway Administration will not license persons with diabetes mellitus to drive commercial motor vehicles in interstate commerce. These individuals may experience severe hypoglycemia, greatly increasing their risk of losing control of the truck. This prohibition is currently being reexamined. We describe the disease process leading to severe hypoglycemia and its physical manifestations. To quantify the risks of licensing persons with diabetes to use insulin, we first estimate the number of potential insulin-using drivers. We estimate that 1420 insulin-using persons would seek licenses in the United States if they were permitted to do so (920 noninsulin dependent and 500 insulin dependent). Next, we estimate the annual incidence of mild and severe hypoglycemia in these populations. The third step is to estimate the number of hypoglycemic episodes while driving. Estimating the likelihood of a crash due to a mild or severe hypoglycemic episode is the fourth step. We estimate that an additional 42 crashes each year would occur if insulin using persons were licensed to drive commercial motor vehicles in interstate commerce (20 from insulin dependent and 22 from non-insulin dependent drivers).

Accidents, Traffic↗

PubMed2006

Licensing of natural killer cells by self-major histocompatibility complex class I.

Natural killer (NK) cells have potent capacities to immediately kill cellular targets and produce cytokines that may potentially damage normal self-tissues unless they are kept in check. Such tolerance mechanisms are incompletely understood. Here we discuss recent studies suggesting that NK cells undergo a host major histocompatibility complex (MHC) class I-dependent functional maturation process, termed 'licensing'. Ironically, licensing directly involves inhibitory receptors that recognize target cell MHC class I molecules and block activation of NK cells in effector responses. This process results in two types of tolerant NK cells: functionally competent (licensed) NK cells, whose effector responses are inhibited by self-MHC class I molecules through the same receptors that conferred licensing, and functionally incompetent (unlicensed) NK cells.

Animals↗

PubMed2006

Pediatric licensing status and the availability of suitable formulations for new medical entities approved in the United States between 1998 and 2002.

The availability of new medical entities for children in the United States was examined at the time of marketing approval and 3 years later. New medical entities approved in the United States in each of the years 1998 to 2002 were identified using the Center for Drug Evaluation and Research Web site. Each Physicians' Desk Reference published in the years 1998 to 2005 was examined to determine formulations and licensing information. For the 133 new medical entities licensed to be marketed in the period 1998 to 2002, the number licensed for children increased from 5 (4%) to 39 (29%) in the 3 years after registration. After 3 years' marketing, 79 (59%) drugs were in formulations suitable for children, and 27 (20%) of the new medical entities were licensed and had a suitable formulation for children. Incentives to improve access for children to medicines should focus more on demonstration of improved access.

Adolescent↗

PubMed2006

The effects of business practices, licensing, and intellectual property on development and dissemination of the polymerase chain reaction: case study.

INTRODUCTION: Polymerase chain reaction (PCR) was a seminal genomic technology discovered, developed, and patented in an industry setting. Since the first of its core patents expired in March, 2005, we are in a position to view the entire lifespan of the patent, examining how the intellectual property rights have impacted its use in the biomedical community. Given its essential role in the world of molecular biology and its commercial success, the technology can serve as a case study for evaluating the effects of patenting biological research tools on biomedical research. CASE DESCRIPTION: Following its discovery, the technique was subjected to two years of in-house development, during which issues of inventorship and publishing/patenting strategies caused friction between members of the development team. Some have feared that this delay impeded subsequent research and may have been due to trade secrecy or the desire for obtaining lucrative intellectual property rights. However, our analysis of the history indicates that the main reasons for the delay were benign and were primarily due to difficulties in perfecting the PCR technique. Following this initial development period, the technology was made widely available, but was subject to strict licensing terms and patent protection, leading to an extensive litigation history. DISCUSSION AND EVALUATION: PCR has earned approximately $2 billion in royalties for the various rights-holders while also becoming an essential research tool. However, using citation trend analysis, we are able to see that PCR's patented status did not preclude it from being adopted in a similar manner as other non-patented genomic research tools (specifically, pBR322 cloning vector and Maxam-Gilbert sequencing). CONCLUSION: Despite the heavy patent protection and rigid licensing schemes, PCR seems to have disseminated so widely because of the practices of the corporate entities which have controlled these patents, namely through the use of business partnerships and broad corporate licensing, adaptive licensing strategies, and a "rational forbearance" from suing researchers for patent infringement. While far from definitive, our analysis seems to suggest that, at least in the case of PCR, patenting of genomic research tools need not impede their dissemination, if the technology is made available through appropriate business practices.

Journal Article↗

PubMedDate not supplied

Teaching cognitive rehearsal as a shield for lateral violence: an intervention for newly licensed nurses.

BACKGROUND: Recent literature defines lateral violence as nurses covertly or overtly directing their dissatisfaction inward toward each other, toward themselves, and toward those less powerful than themselves. Newly licensed nurses are an identified group that is vulnerable to lateral violence during their socialization to nursing practice. The use of cognitive rehearsal, an applied cognitive-behavioral technique, was used as an intervention and the theoretical underpinning for this study. METHOD: Twenty-six newly licensed nurses hired by a large acute care tertiary hospital in Boston, Massachusetts, participated in an exploratory descriptive study. They were taught about lateral violence in nursing practice and the use of cognitive rehearsal techniques as a shield from the negative effects of lateral violence on learning and socialization. Small laminated cueing cards with written visual cues for the appropriate responses to the most common forms of lateral violence were provided. One year later, videotaped focus groups designed to collect qualitative data about the applied intervention were conducted. RESULTS: Twenty-six newly licensed nurses in three different focus groups were videotaped responding to six open-ended questions designed to elicit information on their experience with lateral violence, use of cognitive rehearsal as an intervention, and the overall socialization process. CONCLUSIONS: Knowledge of lateral violence in nursing appeared to allow newly licensed nurses to depersonalize it, thus allowing them to ask questions and continue to learn. The learned cognitive responses helped them confront the lateral violence offender. Confrontation was described as difficult but resulted in the resolution of the lateral violence behavior. Overall, the retention rate in this study population was positively affected.

Attitude of Health Personnel↗