Studies of uncontrolled air traffic patterns, phase 1

The general aviation air traffic flow patterns at uncontrolled airports are investigated and analyzed and traffic pattern concepts are developed to minimize the midair collision hazard in uncontrolled airspace. An analytical approach to evaluate midair collision hazard probability as a function of traffic densities is established which is basically independent of path structure. Two methods of generating space-time interrelationships between terminal area aircraft are presented; one is a deterministic model to generate pseudorandom aircraft tracks, the other is a statistical model in preliminary form. Some hazard measures are presented for selected traffic densities. It is concluded that the probability of encountering a hazard should be minimized independently of any other considerations and that the number of encounters involving visible-avoidable aircraft should be maximized at the expense of encounters in other categories

Entanglement distribution and quantum discord

Establishing entanglement between distant parties is one of the most important problems of quantum technology, since long-distance entanglement is an essential part of such fundamental tasks as quantum cryptography or quantum teleportation. In this lecture we review basic properties of entanglement and quantum discord, and discuss recent results on entanglement distribution and the role of quantum discord therein. We also review entanglement distribution with separable states, and discuss important problems which still remain open. One such open problem is a possible advantage of indirect entanglement distribution, when compared to direct distribution protocols.Comment: 7 pages, 2 figures, contribution to "Lectures on general quantum correlations and their applications", edited by Felipe Fanchini, Diogo Soares-Pinto, and Gerardo Adess

Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-adrenal axis function in humans : a systematic review

BACKGROUND: Synthetic glucocorticoids are commonly used in reproductive medicine. Fetal organ systems are highly sensitive to changes in the intrauterine environment, including overexposure to glucocorticoids. Structural and functional alterations resulting from such changes may persist throughout life and have been associated with diverse diseases. One system that could be particularly sensitive to fetal glucocorticoid overexposure is the hypothalamic-pituitary-adrenal (hpa) axis. Many human studies have investigated this possibility, but a systematic review to identify consistent, emergent findings is lacking. METHODS: We systematically review 49 human studies, assessing the effects of intrauterine exposure to synthetic glucocorticoids on fetal, neonate, and infant hpa function. RESULTS: Study quality varied considerably, but the main findings held true after restricting the analyses to higher-quality studies: intrauterine exposure to synthetic glucocorticoids reduces offspring hpa activity under unstimulated conditions after pain but not pharmacological challenge. Although reduced unstimulated hpa function appears to recover within the first 2 wk postpartum, blunted hpa reactivity to pain is likely to persist throughout the first 4 months of life. There is some evidence that the magnitude of the effects is correlated with the total amount of glucocorticoids administered and varies with the time interval between glucocorticoid exposure and hpa assessment. CONCLUSIONS: This systematic review has allowed the demonstration of the way in which intrauterine exposure to various regimens of synthetic glucocorticoids affects various forms of hpa function. As such, it guides future studies in terms of which variables need to be focused on in order to further strengthen the understanding of such therapy, whilst continuing to profit from its clinical benefits

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

The flying buttress construct for posterior spinopelvic fixation: a technical note

<p>Abstract</p> <p>Background</p> <p>Posterior fusion of the spine to the pelvis in paediatric and adult spinal deformity is still challenging. Especially assembling of the posterior rod construct to the iliac screw is considered technically difficult. A variety of spinopelvic fixation techniques have been developed. However, extreme bending of the longitudinal rods or the use of 90-degree lateral offset connectors proved to be difficult, because the angle between the rod and the iliac screw varies from patient to patient.</p> <p>Methods</p> <p>We adopted a new spinopelvic fixation system, in which iliac screws are side-to-side connected to the posterior thoracolumbar rod construct, independent of the angle between the rod and the iliac screw. Open angled parallel connectors are used to connect short iliac rods from the posterior rod construct to the iliac screws at both sides. The construct resembles in form and function an architectural Flying Buttress, or lateral support arches, used in Gothic cathedrals.</p> <p>Results and discussion</p> <p>Three different cases that illustrate the Flying Buttress construct for spinopelvic fixation are reported here with the clinical details, radiographic findings and surgical technique used.</p> <p>Conclusion</p> <p>The Flying Buttress construct may offer an alternative surgical option for spinopelvic fixation in circumstances wherein coronal or sagittal balance cannot be achieved, for example in cases with significant residual pelvic obliquity, or in revision spinal surgery for failed lumbosacral fusion.</p

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Differential wedging of vertebral body and intervertebral disc in thoracic and lumbar spine in adolescent idiopathic scoliosis – A cross sectional study in 150 patients

<p>Abstract</p> <p>Background</p> <p>Hueter-Volkmann's law regarding growth modulation suggests that increased pressure on the end plate of bone retards the growth (Hueter) and conversely, reduced pressure accelerates the growth (Volkmann). Literature described the same principle in Rat-tail model. Human spine and its deformity i.e. scoliosis has also same kind of pattern during the growth period which causes wedging in disc or vertebral body.</p> <p>Methods</p> <p>This cross sectional study in 150 patients of adolescent idiopathic scoliosis was done to evaluate vertebral body and disc wedging in scoliosis and to compare the extent of differential wedging of body and disc, in thoracic and lumbar area. We measured wedging of vertebral bodies and discs, along with two adjacent vertebrae and disc, above and below the apex and evaluated them according to severity of curve (curve < 30° and curve > 30°) to find the relationship of vertebral body or disc wedging with scoliosis in thoracic and lumbar spine. We also compared the wedging and rotations of vertebrae.</p> <p>Results</p> <p>In both thoracic and lumbar curves, we found that greater the degree of scoliosis, greater the wedging in both disc and body and the degree of wedging was more at apex supporting the theory of growth retardation in stress concentration area. However, the degree of wedging in vertebral body is more than the disc in thoracic spine while the wedging was more in disc than body in lumbar spine. On comparing the wedging with the rotation, we did not find any significant relationship suggesting that it has no relation with rotation.</p> <p>Conclusion</p> <p>From our study, we can conclude that wedging in disc and body are increasing with progression on scoliosis and maximum at apex; however there is differential wedging of body and disc, in thoracic and lumbar area, that is vertebral body wedging is more profound in thoracic area while disc wedging is more profound in lumbar area which possibly form 'vicious cycle' by asymmetric loading to spine for the progression of curve.</p