“I drove after drinking alcohol” and other risky driving behaviours reported by young novice drivers in Queensland, Australia

Background. Volitional risky driving behaviours such as drink- and drug-driving (i.e. substance-impaired driving) and speeding contribute to the overrepresentation of young novice drivers in road crash fatalities, and crash risk is greatest during the first year of independent driving in particular. Aims. To explore the: 1) self-reported compliance of drivers with road rules regarding substance-impaired driving and other risky driving behaviours (e.g., speeding, driving while tired), one year after progression from a Learner to a Provisional (intermediate) licence; and 2) interrelationships between substance-impaired driving and other risky driving behaviours (e.g., crashes, offences, and Police avoidance). Methods. Drivers (n = 1,076; 319 males) aged 18-20 years were surveyed regarding their sociodemographics (age, gender) and self-reported driving behaviours including crashes, offences, Police avoidance, and driving intentions. Results. A relatively small proportion of participants reported driving after taking drugs (6.3% of males, 1.3% of females) and drinking alcohol (18.5% of males, 11.8% of females). In comparison, a considerable proportion of participants reported at least occasionally exceeding speed limits (86.7% of novices), and risky behaviours like driving when tired (83.6% of novices). Substance-impaired driving was associated with avoiding Police, speeding, risky driving intentions, and self-reported crashes and offences. Forty-three percent of respondents who drove after taking drugs also reported alcohol-impaired driving. Discussion and Conclusions. Behaviours of concern include drink driving, speeding, novice driving errors such as misjudging the speed of oncoming vehicles, violations of graduated driver licensing passenger restrictions, driving tired, driving faster if in a bad mood, and active punishment avoidance. Given the interrelationships between the risky driving behaviours, a deeper understanding of influential factors is required to inform targeted and general countermeasure implementation and evaluation during this critical driving period. Notwithstanding this, a combination of enforcement, education, and engineering efforts appear necessary to improve the road safety of the young novice driver, and for the drink-driving young novice driver in particular.

Continuous after-the-fact leakage-resilient key exchange

Security models for two-party authenticated key exchange (AKE) protocols have developed over time to provide security even when the adversary learns certain secret keys. In this work, we advance the modelling of AKE protocols by considering more granular, continuous leakage of long-term secrets of protocol participants: the adversary can adaptively request arbitrary leakage of long-term secrets even after the test session is activated, with limits on the amount of leakage per query but no bounds on the total leakage. We present a security model supporting continuous leakage even when the adversary learns certain ephemeral secrets or session keys, and give a generic construction of a two-pass leakage-resilient key exchange protocol that is secure in the model; our protocol achieves continuous, after-the-fact leakage resilience with not much more cost than a previous protocol with only bounded, non-after-the-fact leakage.

MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells

We have previously reported that human breast carcinoma (HBC) cell lines expressing the mesenchymal intermediate filament protein vimentin (VIM+) are highly invasive in vitro, and highly metastatic in nude mice when compared to their VIM- counterparts. Since only VIM+ cell lines can be induced to activate matrix metalloproteinase-2 (MMP-2) upon stimulation with Concanavalin A (Con A), we have examined here membrane type 1 MMP (MT1-MMP), a cell surface activator of MMP-2. Northern analysis reveals baseline expression of MT1-MMP in five of the six VIM+ cell lines studied (MDA-MB-231, MDA-MB-435, BT-549, Hs578T, MCF-7(ADR)), each of which showed variable activation of exogenous MMP-2 after treatment with Con A. In contrast, the four VIM-, poorly invasive HBC cell lines studied (MCF-7, T47D, MDA-MB 468, ZR-75-1) lacked baseline MT1-MMP mRNA expression, and showed no induction of either MT1-MMP expression or MMP-2-activation with Con A. Such differential MT1-MMP expression was confirmed in vivo using in situ hybridization analysis of nude mouse tumor xenografts of representative cell lines. Western analysis of the MDA-MB-231 cells revealed baseline membrane expression of a 60 kDa species, which was strongly induced by Con A treatment along with a weaker band co-migrating with that from MT1-MMP-transfected COS-1 cells (63 kDa), presumably representing latent MT1-MMP. MT1-MMP immunofluorescence strongly decorated Con A-stimulated MDA-MB-231 cells in a manner consistent with membranous staining, but did not decorate the unstimulated MDA-MB-231 cells or MCF-7 cells under either condition. Collectively, the results suggest the constitutive production of active MT1-MMP which is unavailable for either MMP-2 activation or immuno-decoration until Con A treatment. Since VIM expression arises by virtue of the so-called epithelial to mesenchymal transition (EMT) in invasive embryonic epithelia, we propose that this represents a major metastasis mechanism in breast carcinomas. MT1-MMP on the surface of such 'fibroblastoid' carcinoma cells may mediate a paracrine loop for the utilization of stromally produced MMP-2, and contribute to the poorer survival associated with VIM+ breast carcinomas.

Physical activity levels among children attending after-school programs

Purpose To describe the physical activity (PA) levels of children attending after-school programs, 2) examine PA levels in specific after-school sessions and activity contexts, and 3) evaluate after-school PA differences in groups defined by sex and weight status. Methods One hundred forty-seven students in grades 3-6 (mean age: 10.1 +/- 0.7, 54.4% male, 16.5% overweight (OW), 22.8% at-risk for OW) from seven after-school programs in the midwestern United States wore Actigraph GT1M accelerometers for the duration of their attendance to the program. PA was objectively assessed on six occasions during an academic year (three fall and three spring). Stored activity counts were uploaded to a customized data-reduction program to determine minutes of sedentary (SED), light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) physical activity. Time spent in each intensity category was calculated for the duration of program attendance, as well as specific after-school sessions (e.g., free play, snack time). Results On average, participants exhibited 42.6 min of SED, 40.8 min of LPA, 13.4 min of MPA, and 5.3 min of VPA. The average accumulation of MVPA was 20.3 min. Boys exhibited higher levels of MPA, VPA, and MVPA, and lower levels of SED and LPA, than girls. OW and at-risk-for-OW students exhibited significantly less VPA than nonoverweight students, but similar levels of LPA, MPA, and MVPA. MVPA levels were significantly higher during free-play activity sessions than during organized or structured activity sessions. Conclusion After-school programs seem to be an important contributor to the PA of attending children. Nevertheless, ample room for improvement exists by making better use of existing time devoted to physical activity.

An acute growth factor treatment that preserves function after spinal cord contusion injury

Inflammation of the spinal cord after traumatic spinal cord injury leads to destruction of healthy tissue. This “secondary degeneration” is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study we showed that combined delivery of two growth factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), significantly reduced secondary degeneration after hemi-section injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30d compared to control animals and further reduced the cavity at 90d in treated animals while in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behaviour after spinal contusion injury, a more relevant preclinical model of spinal cord injury. The growth factors were delivered for the first 7d to the injury site via osmotic minipump. Locomotor behaviour was monitored at 1-28d after injury using the BBB score and at 30d using automated gait analysis. Treated animals had BBB scores of 18; Control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.

Management of periprosthetic joint infection after total hip arthroplasty using a Custom Made Articulating Spacer (CUMARS); the exeter experience

Periprosthetic joint infection (PJI) after THA is a major complication with an incidence of 1-3%. We report our experiences with a technique using a custom-made articulating spacer (CUMARS) at the first of two-stage treatment for PJI. This technique uses widely available all-polyethylene acetabular components and the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy-six hips were treated for PJI using this technique. Performed as the first of a two-stage procedure, good functional results were commonly seen, leading to postponing second stage indefinitely with retention of the CUMARS prosthesis in 34 patients. The CUMARS technique presents an alternative to conventional spacers, using readily available components that are well tolerated, allowing weight bearing and mobility, and achieving comparable eradication rates.

A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury

Collagen synthesis inhibition potentially can reduce adhesion formation after tendon injury but also may affect cutaneous wound healing. We hypothesized that a novel orally administered collagen synthesis inhibitor (CPHI-I) would substantially reduce flexor tendon adhesions after injury, without any clinically important effect on cutaneous wound healing. The experiments were performed in a rat model with an in-continuity crush injury model in the rat hindfoot flexor tendon to provoke adhesion formation. Assays of dermal collagen production and the rate of healing of an excised wound were performed to assess cutaneous wound healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and were assessed at either 2 or 6 weeks. The work of flexion in the injured digit was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I did not retard wound healing.

Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine

SPARC (secreted protein acidic and rich in cysteine)/ osteonectin/BM-40 is a matricellular protein implicated in development, cell transformation and tumorigenesis. We have examined the role of SPARC in cell transformation induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA) and 12- tetradecanoylphorbol-13-acetate (TPA) in embryonic fibroblasts and in the skin of mice. Embryonic fibroblasts from SPARCnull mice showed increases in cell proliferation, enhanced sensitivity to DMBA and a higher number of DMBA/TPA-induced transformation foci. The number of DMBA-DNA adducts was 9 times higher in SPARCnull fibroblasts and their stability was lower than wild-type fibroblasts, consistent with a reduction in excision repair cross-complementing 1 the nucleotide excision repair enzyme in these cells. The SPARCnull mice showed an increase in both the speed and number of papillomas forming after topical administration of DMBA/TPA to the skin. These papillomas showed reduced growth and reduced progression to a more malignant phenotype, indicating that the effect of SPARC on tumorigenesis depends upon the transformation stage and/or tissue context. These data reinforce a growing number of observations in which SPARC has shown opposite effects on different tumor types/stages.

Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas

Background: The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)-12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side-effects of IL-12 gene therapy, the objective was to achieve the controlled release of IL-12 after intramuscular gene electrotransfer. Methods: Gene electrotransfer of the plasmid pORF-mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL-12 was monitored in the serum of mice after carrying out two sets of intramuscular IL-12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL-12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X-rays, was evaluated on subcutaneous SA-1 and LPB tumors, as well as on lung metastases. Results: A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL-12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3-fold was determined. The amount of circulating IL-12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid. Conclusions: The present study demonstrates the feasibility of treatment by IL-12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.

Before and after the creative city : the politics of urban cultural policy in Austin, Texas

This article examines the politics and practice of urban cultural policy in Austin, Texas. I demonstrate how aspects of the local context frame how local government and cultural sector interests strive to initiate the direction of policy. While larger trends—such as Richard Florida's creative city thesis—influence cultural policy and planning, specific contextual factors including prior economic development and growth management policy, departmental organization, the forum for interaction between municipal actors and non-governmental coalitions, and the character of the city's cultural economy mediate such trends to produce policy outcomes. As this case shows, contemporary urban cultural policy is not simply due to the rise of the creative city discourse, but is an evolving product of past policy structures and shaped by local institutions and actors.

Angiogenesis in old-aged subjects after ischemic stroke : a cautionary note for investigators

Angiogenesis represents a form of neovascularisation of exceptional importance in numerous pathological conditions including stroke. In this context it is directly related to neuroregeneration which is seen in close proximity. However, numerous experimental data have been drawn from studies that have ignored the age criterion. This is extremely important as angiogenesis is different in young versus old subjects. Extrapolating data obtained from studies performed in young subjects or "in vitro" to old-age patients could lead to inexact conclusions since the dynamics of angiogenesis is age-dependent.The current review covers the key features of brain senescence including morphological and functional changes related to the brain parenchyma, its vascular network and blood flow which could possibly influence the process of angiogenesis. This is followed by a description of post-stroke angiogenesis and its relationship to neuroregeneration and its modulation by vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF 1), the most important factors active in old brain after ischemic injury.