The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis

AbstractThe exact incidence of extra-cardiac complications (ECC) in patients with infective endocarditis (IE) is unknown but presumed to be high. These patients, although mostly asymptomatic, may require a more aggressive therapeutic approach. 18fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) is used for the diagnosis of infections, but its role in the early diagnosis of IE complications is still unclear. This study aimed to evaluate the role of FDG-PET/CT in the early diagnosis of ECC in IE and its implications for medical management. We prospectively studied 40 consecutive patients with a confirmed diagnosis of IE (according to the modified Duke criteria) who underwent a whole body FDG-PET/CT study within 14 days from diagnosis. The FDG-PET/CT demonstrated ECC in 17 (42.5%) patients, while 8 (38.1%) of them were asymptomatic. The most frequent embolic sites were musculoskeletal and splenic. Owing to the FDG-PET/CT findings, treatment planning was modified in 14 (35%) patients. This included antibiotic treatment prolongation (27.5%), referral to surgical procedures (15%) and, most substantially, prevention of unnecessary device extraction (17.7%). According to our experiences, FDG-PET/CT imaging was useful in the detection of embolic and metastatic infections in IE. This clinical information had a significant diagnostic and therapeutic impact in managing IE disease

Local Charge of the nu=5/2 Fractional Quantum Hall State

Electrons in two dimensions and strong magnetic fields effectively lose their kinetic energy and display exotic behavior dominated by Coulomb forces. When the ratio of electrons to magnetic flux quanta in the system is near 5/2, the unique correlated phase that emerges is predicted to be gapped with fractionally charged quasiparticles and a ground state degeneracy that grows exponentially as these quasiparticles are introduced. Interestingly, the only way to transform between the many ground states would be to braid the fractional excitations around each other, a property with applications in quantum information processing. Here we present the first observation of localized quasiparticles at nu=5/2, confined to puddles by disorder. Using a local electrometer to compare how quasiparticles at nu=5/2 and nu=7/3 charge these puddles, we are able to extract the ratio of local charges for these states. Averaged over several disorder configurations and samples, we find the ratio to be 4/3, suggesting that the local charges are e/3 at seven thirds and e/4 at five halves, in agreement with theoretical predictions. This confirmation of localized e/4 quasiparticles is necessary for proposed interferometry experiments to test statistics and computational ability of the state at nu=5/2.Comment: 6 pages, 4 figures corrected titl

Quasi-Particle Tunneling in Anti-Pfaffian Quantum Hall State

We study tunneling phenomena at the edge of the anti-Pfaffian quantum Hall state at the filling factor $\nu=5/2$. The edge current in a single point-contact is considered. We focus on nonlinear behavior of two-terminal conductance with the increase in negative split-gate voltage. Expecting the appearance of the intermediate conductance plateau we calculate the value of its conductance by using the renormalization group (RG) analysis. Further, we show that non-perturbative quasi-particle tunneling is effectively described as perturbative electron tunneling by the instanton method. The two-terminals conductance is written as a function of the gate voltage. The obtained results enable us to distinguish the anti-Pfaffian state from the Pfaffian state experimentally.Comment: 5 pages, 4 figure

Skeletal growth in class II malocclusion from childhood to adolescence: does the profile straighten?

BACKGROUND There is relatively little appreciation of the changes in maxillary-mandibular relationships occurring during adolescence among subjects with normal and increased overjet. The aim of this study was to assess differences in changes in maxillo-mandibular relationships during the adolescent growth period based on the presence of a normal ( 4 mm) overjet in childhood. Our hypothesis was that there is no difference in the change of the A point, nasion, B point (ANB) angle during growth between these two overjet groups. Lateral cephalograms were obtained from 65 subjects taken from the American Association of Orthodontists Foundation (AAOF) Craniofacial Growth Legacy Collections Project. Cephalograms were obtained at ages 7-10 (T0) and 14-17 (T1) with allocation into two groups based on baseline overjet (> 4 mm: group 1, 2-4 mm: group 2). Random effects linear regression was used to account for multiple within -patient measurements with dependent variables including antero-posterior skeletal pattern (based on sella, nasion, A point (SNA); sella, nasion, B point (SNB); and ANB angles). RESULTS We included a similar number of males (n = 34; 52.3%) and females (n = 31; 47.7%). The mean ANB was higher at baseline in group 1 (5.42, SD 2.16°) than in group 2 (3.08, SD 1.91°). The hypothesis was rejected as the ANB angle reduced by 1.92° more in the larger overjet group with the association being statistically significant after accounting for age and gender (P  4 mm overjet group compared to the 2-4 mm group (0.857°, P = 0.271; 95% CI - 0.669 to 2.383). The SNB angle increased by 1.15° more in the higher overjet group but there was only weak evidence of an association (P = 0.086; 95% CI - 2.464 to 0.164). CONCLUSIONS A slight straightening of the facial profile was observed in both groups with a statistically significant greater reduction in ANB arising in the group with larger baseline overjet. This translated into a marginal reduction in the overjet in this group

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

Effect and Safety of Meropenem\u2013Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial

Introduction: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem\u2013vaborbactam monotherapy versus best available therapy (BAT) for CRE. Methods: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem\u2013vaborbactam (2 g/2 g over 3 h, q8h for 7\u201314 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings. Results: Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, 12 44.7% to 9.3%) for meropenem\u2013vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem\u2013vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk\u2013benefit analyses of composite clinical failure or nephrotoxicity favored meropenem\u2013vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, 12 74.6% to 12 22.9%; P < 0.001). Conclusions: Monotherapy with meropenem\u2013vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT. Clinical Trials Registration: NCT02168946. Funding: The Medicines Company

Hasbara 2.0: Israel’s Public Diplomacy in the Digital Age

The Internet has been a counter-public space for Palestinian liberation politics for over a decade, and digital technologies have become an increasingly important tool for solidarity groups across the world. However, the Israeli state and Zionist supporters worldwide are harnessing the same technologies and platforms to mobilize technology primarily to increase pro-Israel sentiments. The aims of this article are to examine hasbara [Israeli public diplomacy] through an exploration of similar diplomacy programmes; to illustrate how social media have affected the basic algorithms of hasbara; and to probe the assertions of hasbara in the light of pro-Palestinian solidarity. Through a study of public diplomacy, this article critically analyzes hasbara as a site of contestation and a method that is hampered by contradictions. On the one hand, there has been a massive growth in hasbara in recent years—indicated by the increase in funding for it and by its professionalized and centralized character; and on the other hand, hasbara has attracted sharp critiques in Israel for its reputed failures. To understand this contradiction, hasbara must be placed within the context of Israel’s settler-colonialism, which sets the state apart from other ‘post-conflict’ states. This article reviews the methods utilized in hasbara, as well as their readjustment in the context of recent wars. Events in 2014 illustrate that hasbara actually destabilizes Israel’s diplomacy. Online journalism and the suppression of solidarity for Palestine together stimulate more criticism and, in turn, help to shift public opinion. Paradoxically, therefore, adjustments (‘hasbara 2.0’) have underlined the image of Israel as a colonial power engaged in violent occupation