Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution

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Detecting a stochastic background of gravitational radiation: Signal processing strategies and sensitivities

We analyze the signal processing required for the optimal detection of a stochastic background of gravitational radiation using laser interferometric detectors. Starting with basic assumptions about the statistical properties of a stochastic gravity-wave background, we derive expressions for the optimal filter function and signal-to-noise ratio for the cross-correlation of the outputs of two gravity-wave detectors. Sensitivity levels required for detection are then calculated. Issues related to: (i) calculating the signal-to-noise ratio for arbitrarily large stochastic backgrounds, (ii) performing the data analysis in the presence of nonstationary detector noise, (iii) combining data from multiple detector pairs to increase the sensitivity of a stochastic background search, (iv) correlating the outputs of 4 or more detectors, and (v) allowing for the possibility of correlated noise in the outputs of two detectors are discussed. We briefly describe a computer simulation which mimics the generation and detection of a simulated stochastic gravity-wave signal in the presence of simulated detector noise. Numerous graphs and tables of numerical data for the five major interferometers (LIGO-WA, LIGO-LA, VIRGO, GEO-600, and TAMA-300) are also given. The treatment given in this paper should be accessible to both theorists involved in data analysis and experimentalists involved in detector design and data acquisition.Comment: 81 pages, 30 postscript figures, REVTE

Белково-энергетическая недостаточность как предиктор ранних повторных ревизий после санирующих операций у пациентов с трудноизлечимой перипротезной инфекцией

Background. Protein-energy malnutrition (PEM) is an established risk factor of postoperative complications in orthopedic disorders, including arthroplasty of the large joints. The study aimed to evaluate PEM prevalence and its association with the early postoperative revision in patients with the difficult-to-treat (DTT) prosthetic joint infection (PJI) of the hip. Methods. The retrospective study included 132 patients with chronic DTT PJI of the hip. The patients underwent orthopedic implant removal, radical debridement of the infected tissues, and resection arthroplasty with non-free transplantation of an axial vastus lateralis muscle flap (n = 57) or installation of an antimicrobial spacer (n = 75). DTT PJI was defined as an infection caused by rifampicin-resistant staphylococcal strains, ciprofloxacin-resistant gram-negative bacteria, fungi of the genus Candida, and their associations. The assessment of the patients protein-energy status included the evaluation of reference laboratory parameters, such as levels of hemoglobin, total protein, and albumin and number of lymphocytes. The degree of PEM was determined by the number of laboratory markers below the threshold values. The statistical comparison was performed using Fishers test. The odds ratio (OR, 95% confidence interval [CI]) was calculated to assess the risk of PJI recurrence. Differences were considered significant at p0.05. Results. More than 70% of patients with chronic DTT PJI included in the study were diagnosed with preoperative PEM of varying degrees of severity. Hypoalbuminemia and decreased hemoglobin levels were diagnosed more often: 64.3% and 57.1% in the muscle flap plasty and 57.3% and 31.1% in the antimicrobial spacer group, respectively. In muscle plasty and antimicrobial spacer groups, a decrease in the values of three or more reference PEM markers was detected in 28.5% and 16.0% of patients, and this advanced impairment of the nutritional status increased the risk of early revision intervention by two (OR 2.0; CI 95% 0.478.56; p = 0.35) and six times (OR 6.11; 95% CI 1.0635.35; p0.04), respectively. Conclusion. In general, the analysis of publications and results of our study show that PEM is associated with the development of surgical site infection and recurrence of PJI after revision surgery. A decrease in the values of three or more reference PEM markers is a significant predictor of repeated revisions after debridement surgery with the installation of an antimicrobial spacer. PEM complicates the postoperative course in patients with resection arthroplasty. Given the high incidence of PEM in patients with DTT PJI of the hip joint, further research is needed to develop methods for nutritional status correction and assessment of their effect on the outcomes of debridement surgery.Введение. Белково-энергетическая недостаточность (БЭН) является доказанным фактором риска развития послеоперационных осложнений у ортопедических больных, в том числе и после эндопротезирования крупных суставов. Целью исследования была оценка частоты встречаемости БЭН и ее влияния на необходимость выполнения ревизионного вмешательства в раннем послеоперационном периоде у пациентов с трудноизлечимой (ТИ) перипротезной инфекцией (ППИ) тазобедренного сустава. Материал и методы. В ретроспективное исследование включено 132 пациента с хронической ТИ ППИ тазобедренного сустава, которым были выполнены удаление ортопедического имплантата, радикальная хирургическая обработка очага инфекции и резекционная артропластика с несвободной пересадкой осевого мышечного лоскута из m. vastus lateralis (n = 57) или установка антимикробного спейсера (n = 75). К ТИ ППИ относили инфекцию, обусловленную рифампицин-резистентными штаммами стафилококков, ципрофлоксацин-резистентными штаммами грамотрицательных бактерий, грибами рода Candida, а также их ассоциациями. Оценка белково-энергетического статуса пациента включала определение опорных лабораторных показателей: уровней гемоглобина, общего белка, альбумина и количество лимфоцитов. Степень БЭН определяли по количеству лабораторных маркеров ниже пороговых значений. Сопоставление относительных показателей сравнения выполняли с применением критерия Фишера. Для оценки влияния БЭН на развитие рецидива рассчитывали отношение шансов (ОШ, 95% ДИ). Различия принимали за достоверные при p0,05. Результаты. Более чем у 70٪ больных с хронической ТИ ППИ, включенных в исследование, до операции была диагностирована БЭН различной степени тяжести. Чаще диагностировали гипоальбуминемию и снижение уровня гемоглобина: соответственно 64,3% и 57,1% в группе мышечной пластики и 57,3% и 31,1% в группе антимикробного спейсера. В группах мышечной пластики и антимикробного спейсера дефицит трех и более опорных показателей БЭН был выявлен соответственно у 28,5% и 16,0% пациентов, при этом наличие таких выраженных нарушений нутриционного статуса увеличивало риск раннего ревизионного вмешательства в 2 раза (ОШ = 2,0; ДИ 95% 0,478,56; p = 0,35) и в 6 раз (ОШ = 6,11; ДИ 95% 1,06-35,35; p0,04). Заключение. Анализ научных публикаций и результаты нашего исследования показывают, что БЭН связана с развитием ИОХВ и рецидивом ППИ после ревизионных операций. Снижение трех и более опорных показателей БЭН является значимым предиктором повторных ревизий после санирующих операций с установкой антимикробного спейсера, а также ухудшает течение раннего послеоперационного периода у пациентов с резекционной артропластикой. С учетом высокой частоты встречаемости БЭН различной степени тяжести у пациентов с ТИ ППИ тазобедренного сустава необходимы дальнейшие исследования по разработке методов коррекции нутриционного статуса и оценке их влияния на исходы санирующих операций

Effects of inhomogeneities on apparent cosmological observables: "fake" evolving dark energy

Using the exact Lemaitre-Bondi-Tolman solution with a non-vanishing cosmological constant $\Lambda$, we investigate how the presence of a local spherically-symmetric inhomogeneity can affect apparent cosmological observables, such as the deceleration parameter or the effective equation of state of dark energy (DE), derived from the luminosity distance under the assumption that the real space-time is exactly homogeneous and isotropic. The presence of a local underdensity is found to produce apparent phantom behavior of DE, while a locally overdense region leads to apparent quintessence behavior. We consider relatively small large scale inhomogeneities which today are not linear and could be seeded by primordial curvature perturbations compatible with CMB bounds. Our study shows how observations in an inhomogeneous $\Lambda$CDM universe with initial conditions compatible with the inflationary beginning, if interpreted under the wrong assumption of homogeneity, can lead to the wrong conclusion about the presence of "fake" evolving dark energy instead of $\Lambda$.Comment: 22 pages, 19 figures,Final version to appear in European Physical Journal

Spin-orbit effects on two-electron states in nanowhisker double quantum dots

We investigate theoretically the combined effects of the electron-electron and the Rashba spin-orbit interactions on two electrons confined in quasi-one-dimensional AlInSb-based double quantum dots. We calculate the two-electron wave functions and explore the interplay between these two interactions on the energy levels and the spin of the states. The energy spectrum as a function of an applied magnetic field shows crossings and anticrossings between triplet and singlet states, associated with level mixing induced by the spin-orbit coupling. We find that the fields at which these crossings occur can be naturally controlled by the interdot barrier width, which controls the exchange integral in the structure.Comment: 5 pages, 6 figure

A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC

Testing the Void against Cosmological data: fitting CMB, BAO, SN and H0

In this paper, instead of invoking Dark Energy, we try and fit various cosmological observations with a large Gpc scale under-dense region (Void) which is modeled by a Lemaitre-Tolman-Bondi metric that at large distances becomes a homogeneous FLRW metric. We improve on previous analyses by allowing for nonzero overall curvature, accurately computing the distance to the last-scattering surface and the observed scale of the Baryon Acoustic peaks, and investigating important effects that could arise from having nontrivial Void density profiles. We mainly focus on the WMAP 7-yr data (TT and TE), Supernova data (SDSS SN), Hubble constant measurements (HST) and Baryon Acoustic Oscillation data (SDSS and LRG). We find that the inclusion of a nonzero overall curvature drastically improves the goodness of fit of the Void model, bringing it very close to that of a homogeneous universe containing Dark Energy, while by varying the profile one can increase the value of the local Hubble parameter which has been a challenge for these models. We also try to gauge how well our model can fit the large-scale-structure data, but a comprehensive analysis will require the knowledge of perturbations on LTB metrics. The model is consistent with the CMB dipole if the observer is about 15 Mpc off the centre of the Void. Remarkably, such an off-center position may be able to account for the recent anomalous measurements of a large bulk flow from kSZ data. Finally we provide several analytical approximations in different regimes for the LTB metric, and a numerical module for CosmoMC, thus allowing for a MCMC exploration of the full parameter space.Comment: 70 pages, 12 figures, matches version accepted for publication in JCAP. References added, numerical values in tables changed due to minor bug, conclusions unaltered. Numerical module available at http://web.physik.rwth-aachen.de/download/valkenburg

Does cemented or cementless single-stage exchange arthroplasty of chronic periprosthetic hip infections provide similar infection rates to a two-stage? A systematic review

Background: The best surgical modality for treating chronic periprosthetic hip infections remains controversial, with a lack of randomised controlled studies. The aim of this systematic review is to compare the infection recurrence rate after a single-stage versus a two-stage exchange arthroplasty, and the rate of cemented versus cementless single-stage exchange arthroplasty for chronic periprosthetic hip infections. Methods: We searched for eligible studies published up to December 2015. Full text or abstract in English were reviewed. We included studies reporting the infection recurrence rate as the outcome of interest following single- or two-stage exchange arthroplasty, or both, with a minimum follow-up of 12 months. Two reviewers independently abstracted data and appraised quality assessment. Results: After study selection, 90 observational studies were included. The majority of studies were focused on a two-stage hip exchange arthroplasty (65 %), 18 % on a single-stage exchange, and only a 17 % were comparative studies. There was no statistically significant difference between a single-stage versus a two-stage exchange in terms of recurrence of infection in controlled studies (pooled odds ratio of 1.37 [95 % CI = 0.68-2.74, I2 = 45.5 %]). Similarly, the recurrence infection rate in cementless versus cemented single-stage hip exchanges failed to demonstrate a significant difference, due to the substantial heterogeneity among the studies. Conclusion: Despite the methodological limitations and the heterogeneity between single cohorts studies, if we considered only the available controlled studies no superiority was demonstrated between a single- and two-stage exchange at a minimum of 12 months follow-up. The overalapping of confidence intervals related to single-stage cementless and cemented hip exchanges, showed no superiority of either technique

How close can an Inhomogeneous Universe mimic the Concordance Model?

Recently, spatially inhomogeneous cosmological models have been proposed as an alternative to the LCDM model, with the aim of reproducing the late time dynamics of the Universe without introducing a cosmological constant or dark energy. This paper investigates the possibility of distinguishing such models from the standard LCDM using background or large scale structure data. It also illustrates and emphasizes the necessity of testing the Copernican principle in order to confront the tests of general relativity with the large scale structure.Comment: 15 pages, 7 figure

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Background:Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection.Methods:Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles.Results:Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease.Conclusions:The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis