bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced fatalities related to rear seat shoulder belts
Authors: Robertson Leon S 
Published: December 2008

Objective—To determine the effect on fatality rates in crashes of installation of shoulder belts in automobile back seats.Methods—During 1988–96, fatalities to rear outboard seat occupants of passenger cars, classified by age of occupant and vehicle curb weight were matched to data on model year in which shoulder belts became standard equipment. The same data were obtained from the same years on back seat occupants in crashes from the Crashworthiness Data System. Weighted regression was performed on death rates per occupants in crashes by belt equipment, occupant age, and vehicle weight for all occupants and occupants who claimed to be restrained.Results—The risk of death is significantly lower in vehicles equipped with shoulder belts, midsized to larger cars, and among children. Claimed child restraint use is higher in cars with shoulder belts and claimed use of shoulder belts is higher among adolescents and young adults but lower among those 35 and older. However, older occupants have lower death rates in shoulder belt equipped cars.Conclusions—Shoulder belts substantially reduce risk of death relative to lap belts at prevalent use rates in each age group. Belt effectiveness when used cannot be estimated precisely because of invalid claimed use, but the lowered rates among vehicles with shoulder belts indicates that effectiveness given prevalent use is far more efficacious than lap belts without shoulder belts.
Achieving compliance with pool fencing legislation in New Zealand: a survey of regulatory authorities
Authors: Morrison Luke , Chalmers David J , Langley John D , Alsop Jonathan C , McBean Catriona 
Published: December 2008

Objectives—To identify the status of compliance and enforcement of New Zealand's Fencing of Swimming Pools Act (FOSP Act), 10 years after its introduction, and to identify methods for improving both compliance with the act and the process of enforcement.Methods—A postal questionnaire was sent to all 74 authorities in New Zealand in which they were asked questions about their enforcement of the FOSP Act. Semistructured telephone interviews were conducted with 12 authorities to supplement the data obtained in the postal survey.Results—Based on responses to the survey, it was estimated that there are over 59 000 domestic swimming pools in New Zealand, giving rates of 46 pools/1000 dwellings and 16 pools/1000 persons. The authorities reported that 44% of pools complied with the act, and a further 4% had been granted exemptions. Nineteen per cent of pools were reported to not comply with the act, and the compliance status of a further 33% was not known, or not stated by the authority. Only 9% of authorities had procedures for locating and inspecting pools, while 28% had a programme of reinspection to ensure that pools continued to comply. Pool owner resistance was considered to be the main difficulty with enforcing the act, and nearly half of the authorities believed publicity or education was needed to overcome these barriers. Fifty two per cent of authorities had publicised the act during the 12 months preceding the survey.Conclusions—Due to ambiguities within the legislation, and differing levels of commitment by authorities to locate pools and monitor compliance, compliance with the FOSP Act is not consistent nationally. If the act were less ambiguous, there would be greater consistency and more enforcement.
Unintentional childhood injury mortality in Europe 1984–93: a report from the EURORISC Working Group
Authors: Morrison Anita , Stone David H 
Published: December 2008

Objective—To examine recent trends in unintentional childhood injury mortality in Europe, and to identify the contribution of specific causes.Setting—The 15 current member countries of the European Union.Methods—Analysis of mortality data (1984–93) obtained from the World Health Organisation and national government agencies.Results—Injuries continue to be the leading cause of childhood death in all study countries, with more than 4500 fatalities annually, accounting for over 30% of all child mortality. The major causes of death in all countries were injuries due to motor vehicle traffic accidents, drownings, fire and flames, and falls. Portugal experienced mortality rates double those of most other countries, with the differentials particularly stark early in the study period. Although a decrease in age standardised mortality rates was observed in all countries over the decade, the extent of the decrease varied widely, from −47% in the UK to −11% in Finland.Conclusion—The pattern of childhood injury in Europe is similar to that observed elsewhere in the world. None the less, differences in rates of childhood injury mortality persist between countries. Identifying the reasons for these variations between countries may hold the key to the reduction injury rates in Europe as a whole.
Urban and rural patterns of bicycle helmet use: factors predicting usage
Authors: Harlos Sande , Warda Lynne , Buchan Norma , Klassen Terry P , Koop Virginia L , Moffatt Michael E K 
Published: December 2008

Objectives—To document current bicycle helmet use in Winnipeg, Manitoba and nearby rural communities, and to identify target groups for a helmet promotion campaign.Methods—Cyclist helmet use was observed between 28 May and 20 August 1996 at a sample of urban and rural locations. Age, gender, helmet use, riding companion(s), location type, correct helmet use, and use of headphones were recorded. Univariate and multivariate analyses were performed. Adjusted odds ratios with 95% confidence intervals were calculated from the final models.Results—Altogether 2629 cyclists (70% male, 30% female) were observed: 2316 at 183 urban locations and 313 at 25 rural locations, with nearly equal numbers of children and adults observed. Overall helmet use was 21.3%, with lower use in males (18.9%) than females (26.3%), despite gender only being a significant variable on multivariate analysis for children under 8 years and adults. Urban helmet use was considerably higher (22.9%) than rural use (8.9%). Helmet use increased linearly as mean neighbourhood income increased, with a nearly fourfold difference in use between the highest and lowest income neighbourhoods. Children less than 8 years old and adults had the highest, and teenagers the lowest, use. Significant predictive variables were identified separately by age category to inform targeted programming.Conclusions—We documented low helmet use in our region, emphasizing the need for a regional helmet promotion campaign as well as future helmet legislation. A marked urban-rural difference in helmet use that has not been previously reported was also identified. Target groups for a future campaign include adolescents, males, rural cyclists, and those in lower income neighbourhoods.
Coding the circumstances of injury: ICD-10 a step forward or backwards?
Authors: Langley John D , Chalmers David J 
Published: December 2008

TheInternational Classification of Diseases(ICD) E codes are the most widely used coding frame for categorising the circumstances of injury and poisoning. In 1992 major revisions to the E codes were released. The aim of this paper was to consider whether the changes made are a step forward or backwards in terms of facilitating injury prevention.The approach taken was to reflect on some former injury prevention research needs and the challenges they presented using data coded according to ICD-9, and then to consider how, if at all, ICD-10 has addressed these difficulties.As with ICD-9, there are essentially two axes associated with each cause: intent and mechanism of injury, and these are captured by one code. This approach can have the unintended effect of hiding the significance of some mechanisms of injury. While there have been significant improvements in some areas, such as falls, in others, such as injuries due to firearms, ICD-10 has taken a step backward. In addition the failure to produce mutually exclusive codes presents problems for determining the incidence of downing events.A welcome addition are “optional” activity codes which enable the identification of work related and sport related injury for the first time. Nevertheless, the limited range of codes and absence of coding guides limits their utility. The revised place of occurrence codes do not represent a significant improvement on ICD-9 in that they are limited to 10, they are not mutually exclusive, and they do not adequately cover a range of specific places of occurrence.In summary, relative to its predecessor, ICD-10 represents a significant improvement in many areas. Unfortunately, it still falls far short of the mark for many injury prevention needs.
Child death reviews: a gold mine for injury prevention and control
Authors: Onwuachi-Saunders Chukwudi , Forjuoh Samuel N , West Patricia , Brooks Cimon 
Published: December 2008

Objectives—The purpose of this study was to demonstrate how child death review teams can be used to prevent future deaths through retrospective, multiagency case analysis and recommendations for educational programs and policy change.Methods—A listing of all deaths to persons ages 21 years and younger in Philadelphia that occurred in 1995 was compiled by the Philadelphia Interdisciplinary Youth Fatality Review Team (PIYFRT), a multiagency, multidisciplinary, community based group created in 1993 with the mission to prevent future deaths through review, analysis, and initiation of corrective actions. Data were collected on demographic variables, as well as the circumstantial variables on injuries such as weapon type, alcohol and drug use, and contact with the criminal justice system, among others. Each case was reviewed thoroughly to determine whether or not the death was preventable. Selected injury related death cases were analyzed further by demographic and circumstantial variables.Results—In 1995, 607 children ages 21 years and younger died in Philadelphia from natural causes (61.6%), unintentional injuries (16.3%), homicide (18.6%), suicide (2.3%), and undetermined causes (1.2%). More than a third (37.2%) of all deaths were considered preventable. Of the injury deaths (n=224), 95% were judged to be preventable. Preventable fire/burn injury deaths (n=29) were associated with lack of a smoke detector, non-supervision of children, and faulty home appliances. Violent deaths were associated with substance abuse, gang involvement, chronic truancy, academic failure, and access to weapons.Conclusions—Relevant policies for these preventable or intervenable deaths are discussed such as use of non-battery powered smoke detectors.
USING SCATTERED MOBILE AGENTS TO LOCATE A BLACK HOLE IN AN UN-ORIENTED RING WITH TOKENS
Authors: DOBREV STEFAN , SANTORO NICOLA , SHI WEI 
Published: January 2009

A black hole in a network is a highly harmful host that disposes of any incoming agents upon their arrival. Determining the location of a black hole in a ring network has been studied when each node is equipped with a whiteboard. Recently, the Black Hole Search problem was solved in a less demanding and less expensive token model with co-located agents. Whether the problem can be solved with scattered agents in a token model remains an open problem.In this paper, we show not only that a black hole can be located in a ring using tokens with scattered agents, but also that the problem is solvable even if the ring is un-oriented. More precisely, first we prove that the black hole search problem can be solved using only three scattered agents. We then show that, with K (K ⩾ 4) scattered agents, the black hole can be located in O(kn + n log n) moves. Moreover, when K (K ⩾ K) is a constant number, the move cost can be reduced to O(n log n), which is optimal. These results hold even if both agents and nodes are anonymous.
Impaired Bub1 Function In vivo Compromises Tension-Dependent Checkpoint Function Leading to Aneuploidy and Tumorigenesis
Authors: Schliekelman Mark , Cowley Dale O. , O'Quinn Ryan , Oliver Trudy G. , Lu Lucy , Salmon E.D. , Van Dyke Terry 
Published: December 2008

Abstract
Bub1 is a serine/threonine kinase originally described as a core component of the spindle assembly checkpoint (SAC) mechanism in yeast. Bub1 binding at kinetochores has been reported to be required for SAC function and localization of other SAC components. A proper SAC is believed to be essential for murine embryonic development, as all previously described null mutations in SAC components in mice cause embryonic lethality. We produced mice harboring a Bub1 mutant allele lacking exons 2 and 3, resulting in a hypomorphic mutant expressed at &lt;5% of wild-type levels. Despite this significant reduction, homozygous mutant animals are viable on a mixed 129P2/B6 or FVB background but display increased tumorigenesis with aging, whereas mice with a C57Bl/6J background die perinatally. Bub1 mutant murine embryonic fibroblasts (MEFs) display defects in chromosome congression to the metaphase plate, severe chromosome missegregation, and aneuploidy accompanied by high levels of premature senescence. Mutant MEFs have a robust SAC in response to nocodazole treatment but an impaired response to Taxol. Mutant MEFs also show reduced kinetochore localization of BubR1, but not of Mad2. The significant reduction in SAC response to Taxol, but not nocodazole, coupled with the reduced binding of BubR1, but not Mad2, indicates that Bub1 is particularly critical for the SAC response to a lack of tension on kinetochores. Thus, Bub1 is essential for proper chromosome segregation, a defect that can lead to severe phenotypes, including perinatal lethality and a predisposition to cancer. [Cancer Res 2009;69(1):45–54]
Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance
Authors: Ihle Nathan T. , Lemos Robert , Wipf Peter , Yacoub Adly , Mitchell Clint , Siwak Doris , Mills Gordon B. , Dent Paul , Kirkpatrick D. Lynn , Powis Garth 
Published: December 2008

AbstractThe novel phosphatidylinositol-3-kinase (PI3K) inhibitor PX-866 was tested against 13 experimental human tumor xenografts derived from cell lines of various tissue origins. Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient, but not necessary, as predictors of sensitivity to the antitumor activity of the PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic Ras was a dominant determinant of resistance, even in tumors with coexisting mutations in PIK3CA. The level of activation of PI3K signaling measured by tumor phosphorylated Ser473-Akt was insufficient to predict in vivo antitumor response to PX-866. Reverse-phase protein array revealed that the Ras-dependent downstream targets c-Myc and cyclin B were elevated in cell lines resistant to PX-866 in vivo. Studies using an H-Ras construct to constitutively and preferentially activate the three best-defined downstream targets of Ras, i.e., Raf, RalGDS, and PI3K, showed that mutant Ras mediates resistance through its ability to use multiple pathways for tumorigenesis. The identification of Ras and downstream signaling pathways driving resistance to PI3K inhibition might serve as an important guide for patient selection as inhibitors enter clinical trials and for the development of rational combinations with other molecularly targeted agents. [Cancer Res 2009;69(1):143–50]
Human Multidrug Resistance Protein 7 (ABCC10) Is a Resistance Factor for Nucleoside Analogues and Epothilone B
Authors: Hopper-Borge Elizabeth , Xu Xiu , Shen Tong , Shi Zhi , Chen Zhe-Sheng , Kruh Gary D. 
Published: December 2008

Abstract
Multidrug resistance protein 7 (MRP7; ABCC10) is an ATP-binding cassette transporter which is able to transport amphipathic anions and confer resistance to docetaxel and, to a lesser extent, vincristine and paclitaxel. Whereas some detail on the resistance profile of MRP7 is known, the activities of the pump have not been completely determined. Here, it is shown by the analysis of MRP7-transfected HEK293 cells that, in addition to natural product agents, MRP7 is also able to confer resistance to nucleoside-based agents, such as the anticancer agents cytarabine (Ara-C) and gemcitabine, and the antiviral agents 2′,3′-dideoxycytidine and PMEA. Consistent with the operation of an efflux pump, expression of MRP7 reduced the accumulation of Ara-C and PMEA. In addition, MRP7 is also able to confer resistance to the microtubule-stabilizing agent epothilone B. Ectopic expression of MRP7 in mouse embryo fibroblasts deficient in P-glycoprotein and Mrp1 revealed that MRP7 has a broad resistance profile for natural product agents. In this drug-sensitive cellular background, MRP7 conferred high levels of resistance to docetaxel (46-fold), paclitaxel (116-fold), SN-38 (65-fold), daunorubicin (7.5-fold), etoposide (11-fold), and vincristine (56-fold). Buthionine sulfoximine did not attenuate MRP7-conferred resistance to docetaxel or Ara-C. These experiments indicate that the resistance capabilities of MRP7 include nucleoside-based agents and a range of natural product anticancer agents that includes nontaxane antimicrotubule agents that are not susceptible to P-glycoprotein–mediated transport and that, unlike MRP1 and MRP2, MRP7-mediated drug transport does not involve glutathione. [Cancer Res 2009;69(1):178–84]
Vascular Endothelial Growth Factor-C and C-C Chemokine Receptor 7 in Tumor Cell–Lymphatic Cross-talk Promote Invasive Phenotype
Authors: Issa Amine , Le Thomas X. , Shoushtari Alexander N. , Shields Jacqueline D. , Swartz Melody A. 
Published: December 2008

Abstract
Most carcinomas spread to distant sites through lymphatic vessels. Several preclinical and clinical studies have shown a positive correlation between the incidence of lymph node metastasis and secretion of the lymphatic growth factor vascular endothelial growth factor-C (VEGF-C) by tumor cells, suggesting tumor lymphangiogenesis as an escape mechanism. However, recent evidence has shown VEGF receptor-3 (VEGFR-3) expression on tumor cells and autocrine signaling, which increase metastatic potential. Furthermore, there is growing evidence implicating lymphatic-homing chemokine receptors, particularly C-C chemokine receptor 7 (CCR7), in lymph node metastasis. We report here that expressions of VEGF-C and CCR7 by tumor cells act synergistically to promote their invasion toward lymphatics. First, VEGF-C acts to increase lymphatic secretion of CCL21, which in turn drives CCR7-dependent tumor chemoinvasion toward lymphatics. Second, VEGF-C acts in an autocrine fashion to increase tumor invasiveness by increasing the proteolytic activity and motility of tumor cells in a three-dimensional matrix. Both of these effects are VEGFR-3 dependent and evident only in three-dimensional environments. We further verified that VEGF-C induces lymphatic CCL21 up-regulation in vivo by direct injection of VEGF-C protein intradermally in the mouse. Taken together, these results bridge the prometastatic functions of CCR7 and VEGF-C in tumors and show that, beyond lymphangiogenesis, VEGF-C promotes tumor invasion toward lymphatics by both autocrine and CCR7-dependent paracrine signaling mechanisms, which may be a significant cause of lymph node metastasis. [Cancer Res 2009;69(1):349–57]
Identification of Novel Alternative Splice Isoforms of Circulating Proteins in a Mouse Model of Human Pancreatic Cancer
Authors: Menon Rajasree , Zhang Qing , Zhang Yan , Fermin Damian , Bardeesy Nabeel , DePinho Ronald A. , Lu Chunxia , Hanash Samir M. , Omenn Gilbert S. , States David J. 
Published: December 2008

Abstract
To assess the potential of tumor-associated, alternatively spliced gene products as a source of biomarkers in biological fluids, we have analyzed a large data set of mass spectra derived from the plasma proteome of a mouse model of human pancreatic ductal adenocarcinoma. MS/MS spectra were interrogated for novel splice isoforms using a nonredundant database containing an exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene. This integrated analysis identified 420 distinct splice isoforms, of which 92 did not match any previously annotated mouse protein sequence. We chose seven of those novel variants for validation by reverse transcription–PCR. The results were concordant with the proteomic analysis. All seven novel peptides were successfully amplified in pancreas specimens from both wild-type and mutant mice. Isotopic labeling of cysteine-containing peptides from tumor-bearing mice and wild-type controls enabled relative quantification of the proteins. Differential expression between tumor-bearing and control mice was notable for peptides from novel variants of muscle pyruvate kinase, malate dehydrogenase 1, glyceraldehyde-3-phosphate dehydrogenase, proteoglycan 4, minichromosome maintenance, complex component 9, high mobility group box 2, and hepatocyte growth factor activator. Our results show that, in a mouse model for human pancreatic cancer, novel and differentially expressed alternative splice isoforms are detectable in plasma and may be a source of candidate biomarkers. [Cancer Res 2009;69(1):300–9]
Tumor Protein 53–Induced Nuclear Protein 1 Is a Major Mediator of p53 Antioxidant Function
Authors: Cano Carla E. , Gommeaux Julien , Pietri Sylvia , Culcasi Marcel , Garcia Stéphane , Seux Mylène , Barelier Sarah , Vasseur Sophie , Spoto Rose P. , Pébusque Marie-Josèphe , Dusetti Nelson J. , Iovanna Juan L. , Carrier Alice 
Published: December 2008

Abstract
p53 exerts its tumor suppressor function mainly through transcriptional induction of target genes involved in several processes, including cell cycle checkpoints, apoptosis, and regulation of cell redox status. p53 antioxidant function is dependent on its transcriptional activity and proceeds by sequential induction of antioxidant and proapoptotic targets. However, none of the thus far renowned p53 targets have proved able to abolish on their own the intracellular reactive oxygen species (ROS) accumulation caused by p53 deficiency, therefore pointing to the existence of other prominent and yet unknown p53 antioxidant targets. Here, we show that TP53INP1 represents such a target. Indeed, TP53INP1 transcript induction on oxidative stress is strictly dependent on p53. Mouse embryonic fibroblasts (MEF) and splenocytes derived from TP53INP1-deficient (inp1−/−) mice accumulate intracellular ROS, whereas overexpression of TP53INP1 in p53-deficient MEFs rescues ROS levels to those of p53-proficient cells, indicating that TP53INP1 antioxidant function is p53 independent. Furthermore, accumulation of ROS in inp1−/− cells on oxidant challenge is associated with decreased expression of p53 targets p21/Cdkn1a, Sesn2, TAp73, Puma, and Bax. Mutation of p53 Ser58 (equivalent to human p53 Ser46) abrogates transcription of these genes, indicating that TP53INP1-mediated p53 Ser58 phosphorylation is implicated in this process. In addition, TP53INP1 deficiency results in an antioxidant (N-acetylcysteine)-sensitive acceleration of cell proliferation. Finally, TP53INP1 deficiency increases oxidative stress–related lymphoma incidence and decreases survival of p53+/− mice. In conclusion, our data show that TP53INP1 is a major actor of p53-driven oxidative stress response that possesses both a p53-independent intracellular ROS regulatory function and a p53-dependent transcription regulatory function. [Cancer Res 2009;69(1):219–26]