Temporary Traffic Control and Enforcement of Traffic Laws in Closed Road Sections, June 2007

Public travel by motor vehicles is often necessary in road and street sections that have been officially closed for construction, repair, and/or other reasons. This authorization is permitted in order to provide access to homes and businesses located beyond the point of closure. The MUTCD does address appropriate use of specific regulatory signs at the entrance to closed sections; however, direct guidance for temporary traffic control measures within these areas is not included but may be needed. Interpretation and enforcement of common practices may vary among transportation agencies. For example, some law enforcement officers in Iowa have indicated a concern regarding enforcement and jurisdiction of traffic laws in these areas because the Code of Iowa only appears to address violations on roadways open to “public travel.” Enforcement of traffic laws in closed road sections is desirable to maintain safety for workers and for specifically authorized road users. In addition, occasional unauthorized entry by motor vehicles is experienced in closed road areas causing property damage. Citations beyond simple trespass may be advisable to provide better security for construction sites, reduce economic losses from damage to completed work, and create safer work zones.

Family history of cancer and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).

Current status of a model system: the gene Gp-9 and its association with social organization in fire ants.

The Gp-9 gene in fire ants represents an important model system for studying the evolution of social organization in insects as well as a rich source of information relevant to other major evolutionary topics. An important feature of this system is that polymorphism in social organization is completely associated with allelic variation at Gp-9, such that single-queen colonies (monogyne form) include only inhabitants bearing B-like alleles while multiple-queen colonies (polygyne form) additionally include inhabitants bearing b-like alleles. A recent study of this system by Leal and Ishida (2008) made two major claims, the validity and significance of which we examine here. After reviewing existing literature, analyzing the methods and results of Leal and Ishida (2008), and generating new data from one of their study sites, we conclude that their claim that polygyny can occur in Solenopsis invicta in the U.S.A. in the absence of expression of the b-like allele Gp-9(b) is unfounded. Moreover, we argue that available information on insect OBPs (the family of proteins to which GP-9 belongs), on the evolutionary/population genetics of Gp-9, and on pheromonal/behavioral control of fire ant colony queen number fails to support their view that GP-9 plays no role in the chemosensory-mediated communication that underpins regulation of social organization. Our analyses lead us to conclude that there are no new reasons to question the existing consensus view of the Gp-9 system outlined in Gotzek and Ross (2007).

A Confluence of Risks: Control and Compliance in the World of Unstructured Data, Big Data and the Cloud

The emergence of powerful new technologies, the existence of large quantities of data, and increasing demands for the extraction of added value from these technologies and data have created a number of significant challenges for those charged with both corporate and information technology management. The possibilities are great, the expectations high, and the risks significant. Organisations seeking to employ cloud technologies and exploit the value of the data to which they have access, be this in the form of "Big Data" available from different external sources or data held within the organisation, in structured or unstructured formats, need to understand the risks involved in such activities. Data owners have responsibilities towards the subjects of the data and must also, frequently, demonstrate that they are in compliance with current standards, laws and regulations. This thesis sets out to explore the nature of the technologies that organisations might utilise, identify the most pertinent constraints and risks, and propose a framework for the management of data from discovery to external hosting that will allow the most significant risks to be managed through the definition, implementation, and performance of appropriate internal control activities.

Testosterone and doping control.

BACKGROUND AND OBJECTIVES: Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone. METHODS: Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids. RESULTS: Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone. CONCLUSIONS: Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.

Accurate and efficient simulation of multiphase flow in a heterogeneous reservoir by using error estimate and control in the multiscale finite-volume framework

The multiscale finite-volume (MSFV) method is designed to reduce the computational cost of elliptic and parabolic problems with highly heterogeneous anisotropic coefficients. The reduction is achieved by splitting the original global problem into a set of local problems (with approximate local boundary conditions) coupled by a coarse global problem. It has been shown recently that the numerical errors in MSFV results can be reduced systematically with an iterative procedure that provides a conservative velocity field after any iteration step. The iterative MSFV (i-MSFV) method can be obtained with an improved (smoothed) multiscale solution to enhance the localization conditions, with a Krylov subspace method [e.g., the generalized-minimal-residual (GMRES) algorithm] preconditioned by the MSFV system, or with a combination of both. In a multiphase-flow system, a balance between accuracy and computational efficiency should be achieved by finding a minimum number of i-MSFV iterations (on pressure), which is necessary to achieve the desired accuracy in the saturation solution. In this work, we extend the i-MSFV method to sequential implicit simulation of time-dependent problems. To control the error of the coupled saturation/pressure system, we analyze the transport error caused by an approximate velocity field. We then propose an error-control strategy on the basis of the residual of the pressure equation. At the beginning of simulation, the pressure solution is iterated until a specified accuracy is achieved. To minimize the number of iterations in a multiphase-flow problem, the solution at the previous timestep is used to improve the localization assumption at the current timestep. Additional iterations are used only when the residual becomes larger than a specified threshold value. Numerical results show that only a few iterations on average are necessary to improve the MSFV results significantly, even for very challenging problems. Therefore, the proposed adaptive strategy yields efficient and accurate simulation of multiphase flow in heterogeneous porous media.

Sleep function: current questions and new approaches.

The mammalian brain oscillates through three distinct global activity states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. The regulation and function of these 'vigilance' or 'behavioural' states can be investigated over a broad range of temporal and spatial scales and at different levels of functional organization, i.e. from gene expression to memory, in single neurons, cortical columns or the whole brain and organism. We summarize some basic questions that have arisen from recent approaches in the quest for the functions of sleep. Whereas traditionally sleep was viewed to be regulated through top-down control mechanisms, recent approaches have emphasized that sleep is emerging locally and regulated in a use-dependent (homeostatic) manner. Traditional markers of sleep homeostasis, such as the electroencephalogram slow-wave activity, have been linked to changes in connectivity and plasticity in local neuronal networks. Thus waking experience-induced local network changes may be sensed by the sleep homeostatic process and used to mediate sleep-dependent events, benefiting network stabilization and memory consolidation. Although many questions remain unanswered, the available data suggest that sleep function will best be understood by an analysis which integrates sleep's many functional levels with its local homeostatic regulation.

Pre-hospital tracheal intubation in patients with traumatic brain injury: systematic review of current evidence.

BACKGROUND: We reviewed the current evidence on the benefit and harm of pre-hospital tracheal intubation and mechanical ventilation after traumatic brain injury (TBI). METHODS: We conducted a systematic literature search up to December 2007 without language restriction to identify interventional and observational studies comparing pre-hospital intubation with other airway management (e.g. bag-valve-mask or oxygen administration) in patients with TBI. Information on study design, population, interventions, and outcomes was abstracted by two investigators and cross-checked by two others. Seventeen studies were included with data for 15,335 patients collected from 1985 to 2004. There were 12 retrospective analyses of trauma registries or hospital databases, three cohort studies, one case-control study, and one controlled trial. Using Brain Trauma Foundation classification of evidence, there were 14 class 3 studies, three class 2 studies, and no class 1 study. Six studies were of adults, five of children, and three of both; age groups were unclear in three studies. Maximum follow-up was up to 6 months or hospital discharge. RESULTS: In 13 studies, the unadjusted odds ratios (ORs) for an effect of pre-hospital intubation on in-hospital mortality ranged from 0.17 (favouring control interventions) to 2.43 (favouring pre-hospital intubation); adjusted ORs ranged from 0.24 to 1.42. Estimates for functional outcomes after TBI were equivocal. Three studies indicated higher risk of pneumonia associated with pre-hospital (when compared with in-hospital) intubation. CONCLUSIONS: Overall, the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI. Additional arguments need to be taken into account, including medical and procedural aspects.

Circadian control of tissue homeostasis and adult stem cells.

The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases.

Precision of tibial tunnel placement under arthroscopic control alone in posterior cruciate ligament reconstruction: A radiological study

Introduction: Accurate and reproducible tibial tunnel placement minimizing the risk of neurovascular damage is a crucial condition for successful arthroscopic reconstruction of the posterior cruciate ligament (PCL). This step is commonly performed under fluoroscopic control. Hypothesis: Performing the tibial tunnel under exclusive arthroscopic control allows accurate and reliable tunnel placement according to recommendations in the literature. Materials and Methods: Between February 2007 and December 2009, 108 arthroscopic single bundle PCL reconstructions in tibial tunnel technique were performed. The routine postoperative radiographs were screened according to previously defined quality criterions. After critical analysis, the radiographs of 48 patients (48 knees) were enrolled in the study. 10 patients had simultaneous ACL reconstruction and 7 had PCL revision surgery. The tibial tunnel was placed under direct arthroscopic control through a posteromedial portal using a standard tibial aming device. Key anatomical landmarks were the exposed tibial insertion of the PCL and the posterior horn of the medial meniscus. First, the centre of the posterior tibial tunnel outlet on the a-p view was determined by digital analysis of the postoperative radiographes. Its distance to the medial tibial spine was measured parallel to the tibia plateau. The mediolateral position was expressed by the ratio between the distance of the tunnel outlet to the medial border and the total width of the tibial plateau. On the lateral view the vertical tunnel position was measured perpendicularly to a tangent of the medial tibial plateau. All measurement were repeated at least twice and carried out by two examiners. Results: The mean mediolateral tunnel position was 49.3 ± 4.6% (ratio), 6.7 ± 3.6 mm lateral to the medial tibial spine. On the lateral view the tunnel centre was 10.1 ± 4.5 mm distal to the bony surface of the medial tibial plateau. Neurovascular damage was observed in none of our patients. Conclusion: The results of this radiological study confirm that exclusive arthroscopic control for tibial tunnel placement in PCL reconstruction yields reproducible and accurate results according to the literature. Our technique avoids radiation, facilitates the operation room setting and enables the surgeon to visualize the anatomic key landmarks for tibial tunnel placement.

Advanced geostatistical and machine-learning models for spatial data analysis of radioactively contaminated regions

Radioactive soil-contamination mapping and risk assessment is a vital issue for decision makers. Traditional approaches for mapping the spatial concentration of radionuclides employ various regression-based models, which usually provide a single-value prediction realization accompanied (in some cases) by estimation error. Such approaches do not provide the capability for rigorous uncertainty quantification or probabilistic mapping. Machine learning is a recent and fast-developing approach based on learning patterns and information from data. Artificial neural networks for prediction mapping have been especially powerful in combination with spatial statistics. A data-driven approach provides the opportunity to integrate additional relevant information about spatial phenomena into a prediction model for more accurate spatial estimates and associated uncertainty. Machine-learning algorithms can also be used for a wider spectrum of problems than before: classification, probability density estimation, and so forth. Stochastic simulations are used to model spatial variability and uncertainty. Unlike regression models, they provide multiple realizations of a particular spatial pattern that allow uncertainty and risk quantification. This paper reviews the most recent methods of spatial data analysis, prediction, and risk mapping, based on machine learning and stochastic simulations in comparison with more traditional regression models. The radioactive fallout from the Chernobyl Nuclear Power Plant accident is used to illustrate the application of the models for prediction and classification problems. This fallout is a unique case study that provides the challenging task of analyzing huge amounts of data ('hard' direct measurements, as well as supplementary information and expert estimates) and solving particular decision-oriented problems.

Direct Effect of Birth Weight on Childhood Blood Pressure: a Causal Mediation Analysis

Background: Numerous studies have shown a negative association between birth weight (BW) and blood pressure (BP) later in life. To estimate the direct effect of BW on BP, it is conventional to condition on current weight (CW). However, such conditioning can induce collider stratification bias in the estimate of the direct effect. Objective: To bound the potential bias due to U, an unmeasured common cause of CW and BP, on the estimate of the (controlled) direct effect of BW on BP. Methods: Data from a school based study in Switzerland were used (N = 4,005; 2,010 B/1,995 G; mean age: 12.3 yr [range: 10.1-14.9]). Measured common causes of BW-BP (SES, smoking, body weight, and hypertension status of the mother) and CW-BP (breastfeeding and child's physical activity and diet) were identified with DAGs. Linear regression models were fitted to estimate the association between BW and BP. Sensitivity analyses were conducted to assess the potential effect of U on the association between BW and BP. U was assumed 1) to be a binary variable that affected BP by the same magnitude in low BWand in normal BW children and 2) to have a different prevalence in low BW children and in normal BW children for a given CW. Results: A small negative association was observed between BW and BP [beta: -0.3 mmHg/kg (95% CI: -0.9 to 0.3)]. The association was strengthened upon conditioning for CW [beta: -1.5 mmHg/kg (95% CI: -2.1 to -0.9)]. Upon further conditioning on common causes of BW-BP and CW-BP, the association did not change substantially [beta: -1.4 mmHg/kg (95% CI: -2.0 to -0.8)]. The negative association could be explained by U only if U was strongly associated with BP and if there was a large difference in the prevalence of U between low BWand normal BW children. Conclusion: The observed negative association between BW and BP upon adjustment for CW was not easily explained by an unmeasured common cause of CWand BP.

CT-guided cervical foraminal injection: Is a direct foraminal approach still necessary?

Purpose: Cervical foraminal injection performed with a direct foraminal approach may induce serious neurologic complications. We describe a technique of CT-guided cervical facet joint (CFJ) injection as an indirect foraminal injection, including feasibility and diffusion pathways of the contrast agent. Methods and materials: Retrospective study included 84 punctures in 65 consecutive patients presenting neck pain and/or radiculopathy related to osteoarthritis or soft disc herniation. CT images were obtained from C2 to T1 in supine position, with a metallic landmark on the skin. CFJ punctures were performed by MSK senior radiologists with a lateral approach. CT control of the CFJ opacification was performed after injections of contrast agent (1 ml), followed by slow-acting corticosteroid (25 mg). CFJ opacification was considered as successful when joint space and/or capsular recess opacification occurred. The diffusion of contrast agent in foraminal and epidural spaces was recorded. We assessed the epidural diffusion both on axial and sagittal images, with a classification in two groups (small diffusion or large diffusion). Results: CFJ opacification was successful in 82% (69/84). An epidural and/or foraminal opacification was obtained in 74% (51/69). A foraminal opacification occurred in 92% (47/51) and an epidural opacification in 63% (32/51), with small diffusion in 47% (15/32) and large diffusion in 53% (17/32). No complication occurred. Conclusion: CT- guided CFJ injection is easy to perform and safe. It is most often successful, with a frequent epidural and/or foraminal diffusion of the contrast agent. This technique could be an interesting and safe alternative to foraminal cervical injection.

Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation.

The role of Notch signaling in growth/differentiation control of mammalian epithelial cells is still poorly defined. We show that keratinocyte-specific deletion of the Notch1 gene results in marked epidermal hyperplasia and deregulated expression of multiple differentiation markers. In differentiating primary keratinocytes in vitro endogenous Notch1 is required for induction of p21WAF1/Cip1 expression, and activated Notch1 causes growth suppression by inducing p21WAF1/Cip1 expression. Activated Notch1 also induces expression of 'early' differentiation markers, while suppressing the late markers. Induction of p21WAF1/Cip1 expression and early differentiation markers occur through two different mechanisms. The RBP-Jkappa protein binds directly to the endogenous p21 promoter and p21 expression is induced specifically by activated Notch1 through RBP-Jkappa-dependent transcription. Expression of early differentiation markers is RBP-Jkappa-independent and can be induced by both activated Notch1 and Notch2, as well as the highly conserved ankyrin repeat domain of the Notch1 cytoplasmic region. Thus, Notch signaling triggers two distinct pathways leading to keratinocyte growth arrest and differentiation.

Transscleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels.

The major problems associated with the use of corticosteroids for the treatment of ocular diseases are their poor intraocular penetration to the posterior segment when administered locally and their secondary side effects when given systemically. To circumvent these problems more efficient methods and techniques of local delivery are being developed. The purposes of this study were: (1) to investigate the pharmacokinetics of intraocular penetration of hemisuccinate methyl prednisolone (HMP) after its delivery using the transscleral Coulomb controlled iontophoresis (CCI) system applied to the eye or after intravenous (i.v.) injection in the rabbit, (2) to test the safety of the CCI system for the treated eyes and (3) to compare the pharmacokinetic profiles of HMP intraocular distribution after CCI delivery to i.v. injection. For each parameter evaluated, six rabbit eyes were used. For the CCI system, two concentrations of HMP (62.5 and 150mg ml(-1)), various intensities of current and duration of treatment were analyzed. In rabbits serving as controls the HMP was infused in the CCI device but without applied electric current. For the i.v. delivery, HMP at 10mg kg(-1)as a 62.5mg ml(-1)solution was used. The rabbits were observed clinically for evidence of ocular toxicity. At various time points after the administration of drug, rabbits were killed and intraocular fluids and tissues were sampled for methylprednisolone (MP) concentrations by high pressure liquid chromatography (HPLC). Histology examinations were performed on six eyes of each group. Among groups that received CCI, the concentrations of MP increased in all ocular tissues and fluids in relation to the intensities of current used (0.4, 1.0 and 2.0mA/0.5cm(2)) and its duration (4 and 10min). Sustained and highest levels of MP were achieved in the choroid and the retina of rabbit eyes treated with the highest current and 10min duration of CCI. No clinical toxicity or histological lesions were observed following CCI. Negligible amounts of MP were found in ocular tissues in the CCI control group without application of current. Compared to i.v. administration, CCI achieved higher and more sustained tissue concentrations with negligible systemic absorption. These data demonstrate that high levels of MP can be safely achieved in intraocular tissues and fluids of the rabbit eye, using CCI. With this system, intraocular tissues levels of MP are higher than those achieved after i.v. injection. Furthermore, if needed, the drug levels achieved with CCI can be modulated as a function of current intensity and duration of treatment. CCI could therefore be used as an alternative method for the delivery of high levels of MP to the intraocular tissues of both the anterior and posterior segments.