Rationale and design of XAMOS: noninterventional study of rivaroxaban for prophylaxis of venous thromboembolism after major hip and knee surgery

Venous thromboembolism is a frequent and potentially life-threatening complication of orthopedic surgery. Rivaroxaban is an oral direct factor Xa inhibitor, which was shown to be effective for the prevention of venous thromboembolism after elective hip and knee arthroplasty in the RECORD study program. Rivaroxaban has the potential to overcome the limitations of the current standards of care in the prevention of venous thromboembolism. XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopedic surgery of hip or knee) is an international, noninterventional, parallel-group study to gain insight into the safety (major bleeding, side effects) and effectiveness (prevention of symptomatic thromboembolic events) of rivaroxaban in daily clinical practice. XAMOS will follow 15,000 patients after major orthopedic surgery in approximately 200 centers worldwide, with about 7500 patients receiving rivaroxaban and about 7500 standard of care. XAMOS will supplement the clinical data obtained in the Phase III RECORD 1, 2, 3, and 4 trials in which rivaroxaban was shown to be superior for the primary efficacy endpoints, and with a safety profile similar to that of enoxaparin after hip or knee replacement surgery. XAMOS was started in 2009 and will complete recruitment and follow-up in 2011

Increased homozygosity in the first Hispanic patient with plantar lipomatosis, unusual facies, and developmental delay (Pierpont syndrome): a case report

BACKGROUND: Pierpont syndrome was first described in 1998 with key characteristics including developmental delay, dysmorphic facial features, fat pads on hands and feet, and feeding difficulties. To date the mechanism of inheritance is unknown. Nine out of ten previously described patients with Pierpont syndrome were boys. This is the first report of a case of a non-white patient with Pierpont syndrome and she is the second female patient to be described as having Pierpont syndrome. CASE PRESENTATION: Our patient is a 16-month-old Hispanic girl with extreme developmental delay, microcephaly, large ears, short and thick upper lip, broad philtrum, widely spaced teeth, constipation, dysphagia, fat pads on feet and hands, autistic behavior and seizure-like episodes. She had a normal karyotype (46,XX), and array testing showed greater than 8 % homozygosity with otherwise normal results. Genes within these areas of homozygosity may provide clues to an etiology and suggest autosomal recessive inheritance. This case report highlights the possibility of ethnic variations in this syndrome’s presentation, which may have ramifications in uncovering the pathogenesis as well as expanding the phenotype. CONCLUSION: Pierpont syndrome should be considered in the evaluation of children with the described features, regardless of their gender and ethnicity

Carrier-envelope phase effects on the strong-field photoemission of electrons from metallic nanostructures

Sharp metallic nanotapers irradiated with few-cycle laser pulses are emerging as a source of highly confined coherent electron wavepackets with attosecond duration and strong directivity. The possibility to steer, control or switch such electron wavepackets by light is expected to pave the way towards direct visualization of nanoplasmonic field dynamics and real-time probing of electron motion in solid state nanostructures. Such pulses can be generated by strong-field induced tunneling and acceleration of electrons in the near-field of sharp gold tapers within one half-cycle of the driving laser field. Here, we show the effect of the carrier-envelope phase of the laser field on the generation and motion of strong-field emitted electrons from such tips. This is a step forward towards controlling the coherent electron motion in and around metallic nanostructures on ultrashort length and time scales

Differential postural effects of plantar-flexor muscles fatigue under normal, altered and improved vestibular and neck somatosensory conditions

The aim of the present study was to assess the effects of plantar-flexor muscles fatigue on postural control during quiet standing under normal, altered and improved vestibular and neck somatosensory conditions. To address this objective, young male university students were asked to stand upright as still as possible with their eyes closed in two conditions of No Fatigue and Fatigue of the plantar-flexor muscles. In Experiment 1 (n=15), the postural task was executed in two Neutral head and Head tilted backward postures, recognized to degrade vestibular and neck somatosensory information. In Experiment 2 (n=15), the postural task was executed in two conditions of No tactile and Tactile stimulation of the neck provided by the application of strips of adhesive bandage to the skin over and around the neck. Centre of foot pressure displacements were recorded using a force platform. Results showed that (1) the Fatigue condition yielded increased CoP displacements relative to the No Fatigue condition (Experiment 1 and Experiment 2), (2) this destabilizing effect was more accentuated in the Head tilted backward posture than Neutral head posture (Experiment 1) and (3) this destabilizing effect was less accentuated in the condition of Tactile stimulation than that of No tactile stimulation of the neck (Experiment 2). In the context of the multisensory control of balance, these results suggest an increased reliance on vestibular and neck somatosensory information for controlling posture during quiet standing in condition of altered ankle neuromuscular function

A precision study of the fine tuning in the DiracNMSSM

Recently the DiracNMSSM has been proposed as a possible solution to reduce the fine tuning in supersymmetry. We determine the degree of fine tuning needed in the DiracNMSSM with and without non-universal gaugino masses and compare it with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed parameter regions we perform a precise calculation of the Higgs mass. In addition, we include the limits from direct SUSY searches and dark matter abundance. We find that both models are comparable in terms of fine tuning, with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure

The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

ADARRI:a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit

We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson’s and Clifford’s method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson’s method and 55%, 98%, 96%, 27.5, 0.460 for Clifford’s method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement

The generalised NMSSM at one loop: fine tuning and phenomenology

We determine the degree of fine tuning needed in a generalised version of the NMSSM that follows from an underlying Z4 or Z8 R symmetry. We find that it is significantly less than is found in the MSSM or NMSSM and extends the range of Higgs mass that have acceptable fine tuning up to Higgs masses of mh ~ 130 GeV. For universal boundary conditions analogous to the CMSSM the phenomenology is rather MSSM like with the singlet states typically rather heavy. For more general boundary conditions the singlet states can be light, leading to interesting signatures at the LHC and direct detection experiments.Comment: 20 pages, 9 figures, matches published versio

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

Dynamical R-parity Breaking at the LHC

In a class of extensions of the minimal supersymmetric standard model with (B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity symmetry is an essential and dynamical requirement for successful gauge symmetry breaking. Two consequences of these models are: (i) a new kind of R-parity breaking interaction that protects proton stability but adds new contributions to neutrinoless double beta decay and (ii) an upper bound on the extra gauge and parity symmetry breaking scale which is within the large hadron collider (LHC) energy range. We point out that an important prediction of such theories is a potentially large mixing between the right-handed charged lepton ($e^c$) and the superpartner of the right-handed gauge boson ($\widetilde W_R^+$), which leads to a brand new class of R-parity violating interactions of type $\widetilde{\mu^c}^\dagger\nu_\mu^c e^c$ and \widetilde{d^c}^\dagger\u^c e^c. We analyze the relevant constraints on the sparticle mass spectrum and the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note the "smoking gun" signals for such models to be lepton flavor/number violating processes: $pp\to \mu^\pm\mu^\pm e^+e^-jj$ (or $\tau^\pm\tau^\pm e^+e^-jj$) and $pp\to\mu^\pm e^\pm b \bar{b} jj$ (or $\tau^\pm e^\pm b \bar{b} jj$) without significant missing energy. The predicted multi-lepton final states and the flavor structure make the model be distinguishable even in the early running of the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde