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To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.
The mass balance of Glacier de Sarennes, French Alps, has been measured since 1949, using the glaciological method based on core and ablation stake data, and area extrapolations, to find the overall glacier balance. The cumulative balance obtained in this way is very dependent on systematic errors that can increase linearly with the number, N, of measurement years, whereas random errors rise with . The volumetric-balance method based on aerial photogrammetry provides results whose errors do not depend on the number of years. This method was used to test field measurements for the period 1952–2003 and gives a mass balance of −32.30 ± 1.04 m w.e. compared to −34.89 ± 1.15 m w.e. based on field data. The discrepancy between the two methods is discussed on the basis of a careful error analysis. Moreover, the possibility of using the volumetric method to detect biases in field measurements is evaluated in terms of two types of errors. The number and locations of measurement sites required to account for all the spatial and temporal variabilities of the mass balance is discussed by variance analysis. Methodological implications and recommendations are presented to provide mass-balance measurements of the best possible accuracy.
Temporal trends related to recent climatic fluctuations are extracted from the longest glacier-wide winter and summer mass-balance series recorded in the Alps, at Glacier de Sarennes, France. For this, all point balances measured at the glacier surface are used, and different statistical models are developed and tested. First, Lliboutry’s linear variance analysis model is extended to the two seasonal components of the balance. The explicit modelling of variability sources and correlations is proved useful for appropriately quantifying uncertainties in the different components of the balance and estimating missing data. Next, a non-exchangeable structure is added to model the winter and summer balance time series. Two change points separating different underlying trends are thus detected. The first change was in 1976, with a shift of +23% in the winter balance. The second was in 1982 for the summer balance series. These systematic changes explain 20–30% of the variability of the different components of the balance, the rest being made up of random interannual fluctuations. Simplified and/or less physically based models are less efficient in capturing data variability. As a result, the cumulative glacier-wide balance shows systematic parabolic trends, which result in an accelerated mass loss for Glacier de Sarennes over the last 25 years.
Observations show that glaciers around the world are in retreat and losing mass. Internationally coordinated for over a century, glacier monitoring activities provide an unprecedented dataset of glacier observations from ground, air and space. Glacier studies generally select specific parts of these datasets to obtain optimal assessments of the mass-balance data relating to the impact that glaciers exercise on global sea-level fluctuations or on regional runoff. In this study we provide an overview and analysis of the main observational datasets compiled by the World Glacier Monitoring Service (WGMS). The dataset on glacier front variations (∼42 000 since 1600) delivers clear evidence that centennial glacier retreat is a global phenomenon. Intermittent readvance periods at regional and decadal scale are normally restricted to a subsample of glaciers and have not come close to achieving the maximum positions of the Little Ice Age (or Holocene). Glaciological and geodetic observations (∼5200 since 1850) show that the rates of early 21st-century mass loss are without precedent on a global scale, at least for the time period observed and probably also for recorded history, as indicated also in reconstructions from written and illustrated documents. This strong imbalance implies that glaciers in many regions will very likely suffer further ice loss, even if climate remains stable.
The majority of improvements to LIB technology have come through the development of new novel cathode materials. One promising cathode material is Li2FeSiO4 (LFS), desirable for its low cost and high theoretical capacity. However, the ionic conduction and transport mechanisms within this material are still not well understood, and require further investigation to improve upon cycling rate performance. To this end combined measurements of XRD & XANES have been performed in operando on LFS during electrochemical cycling, i.e. at selected electrochemical states of charge during the formation cycle the crystalline structure and the transition metal oxidation state as well as the site symmetry were characterized via the two aforementioned techniques. These in operando measurements expose once more a charging rate-dependent phase evolution during the formation cycle, which can be well characterized using a simplified equivalent circuit analogue.
This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (−165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (−270 g/day). Low responses were observed on growth rate (−12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; −2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (−0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (−10% after five generations of selection) and activity (−21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.
This book addresses the question of whether there are continuities in Latin spanning the period from the early Republic through to the Romance languages. It is often maintained that various usages admitted by early comedy were rejected later by the literary language but continued in speech, to resurface centuries later in the written record (and in Romance). Are certain similarities between early and late Latin all that they seem, or might they be superficial, reflecting different phenomena at different periods? Most of the chapters, on numerous syntactic and other topics and using different methodologies, have a long chronological range. All attempt to identify patterns of change that might undermine any theory of submerged continuity. The patterns found are summarised in a concluding chapter. The volume addresses classicists with an interest in any of the different periods of Latin, and Romance linguists.
To study the association between gastrointestinal colonization of carbapenemase-producing Enterobacteriaceae (CPE) and proton pump inhibitors (PPIs).
We analyzed 31,526 patients with prospective collection of fecal specimens for CPE screening: upon admission (targeted screening) and during hospitalization (opportunistic screening, safety net screening, and extensive contact tracing), in our healthcare network with 3,200 beds from July 1, 2011, through December 31, 2015. Specimens were collected at least once weekly during hospitalization for CPE carriers and subjected to broth enrichment culture and multiplex polymerase chain reaction.
Of 66,672 fecal specimens collected, 345 specimens (0.5%) from 100 patients (0.3%) had CPE. The number and prevalence (per 100,000 patient-days) of CPE increased from 2 (0.3) in 2012 to 63 (8.0) in 2015 (P<.001). Male sex (odds ratio, 1.91 [95% CI, 1.15–3.18], P=.013), presence of wound or drain (3.12 [1.70–5.71], P<.001), and use of cephalosporins (3.06 [1.42–6.59], P=.004), carbapenems (2.21 [1.10–4.48], P=.027), and PPIs (2.84 [1.72–4.71], P<.001) in the preceding 6 months were significant risk factors by multivariable analysis. Of 79 patients with serial fecal specimens, spontaneous clearance of CPE was noted in 57 (72.2%), with a median (range) of 30 (3–411) days. Comparing patients without use of antibiotics and PPIs, consumption of both antibiotics and PPIs after CPE identification was associated with later clearance of CPE (hazard ratio, 0.35 [95% CI, 0.17–0.73], P=.005).
Concomitant use of antibiotics and PPIs prolonged duration of gastrointestinal colonization by CPE.
The second generation instrument of the VLTI, GRAVITY, is expected to reach an astrometric accuracy of about 10 μas. It will thus possible to probe the spacetime close to the compact source Sagittarius A* (Sgr A*) at the Galactic Center by using accurate astrometric observations of the second closest star to the Galactic Center, S2. In particular, we show that combining GRAVITY and spectrograph instruments will allow us to detect several relativistic effects such as pericenter advance or the Lense-Thirring effect.
A layered description of the structure of turbulent flame brushes is provided for situations featuring large but finite values of the Damköhler number, which correspond to the wrinkled flame regime of turbulent premixed combustion. One special focus of this study is placed on the description of the leading edge of the turbulent flame brush, the role of which is known to be essential with respect to propagation, transport and stabilization issues. On the basis of rather simple and well-identified working hypotheses, the influence of slight increases in the Karlovitz number values is revealed. The phenomenology and associated statistics are also investigated analytically, which leads to a mathematical description of the leading edge internal structure. With respect to the progress variable statistics, i.e. probability density function, this leading edge can indeed be thought of as the inner part of a boundary layer where the influence of the finite thickness of laminar flamelets can no longer be neglected. From the proposed description, standard fast-chemistry closures, which are currently used to perform the numerical simulation of turbulent combustion, may easily be generalized to account for the finite-rate chemistry effects occurring in this sublayer, thus emphasizing the interest of the present analysis for turbulent combustion theory and modelling.
Waterborne disease outbreaks (WBDO) of acute gastrointestinal illness (AGI) are a public health concern in France. Their occurrence is probably underestimated due to the lack of a specific surveillance system. The French health insurance database provides an interesting opportunity to improve the detection of these events. A specific algorithm to identify AGI cases from drug payment reimbursement data in the health insurance database has been previously developed. The purpose of our comparative study was to retrospectively assess the ability of the health insurance data to describe WBDO. Data from the health insurance database was compared with the data from cohort studies conducted in two WBDO in 2010 and 2012. The temporal distribution of cases, the day of the peak and the duration of the epidemic, as measured using the health insurance data, were similar to the data from one of the two cohort studies. However, health insurance data accounted for 54 cases compared to the estimated 252 cases accounted for in the cohort study. The accuracy of using health insurance data to describe WBDO depends on the medical consultation rate in the impacted population. As this is never the case, data analysis underestimates the total number of AGI cases. However this data source can be considered for the development of a detection system of a WBDO in France, given its ability to describe an epidemic signal.