Abstract In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria ...are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.
Objective: Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS).
Participants: Participants were 32 invited leaders in the field.
...Evidence: Evidence was obtained by extensive literature review and from clinical experience.
Consensus: Participants reviewed discussion summaries, voted, and reached a majority decision on each document section.
Conclusions: ISS is defined auxologically by a height below −2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 μg/kg·d) for children shorter than −2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3–0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4–7 yr) is 3.5–7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.
Short-range correlated (SRC) nucleon pairs are a vital part of the nucleus, accounting for almost all nucleons with momentum greater than the Fermi momentum (k_{F}). A fundamental characteristic of ...SRC pairs is having large relative momenta as compared to k_{F}, and smaller center of mass (c.m.) which indicates a small separation distance between the nucleons in the pair. Determining the c.m. momentum distribution of SRC pairs is essential for understanding their formation process. We report here on the extraction of the c.m. motion of proton-proton (pp) SRC pairs in carbon and, for the first time in heavier and ansymetric nuclei: aluminum, iron, and lead, from measurements of the A(e,e^{'}pp) reaction. We find that the pair c.m. motion for these nuclei can be described by a three-dimensional Gaussian with a narrow width ranging from 140 to 170 MeV/c, approximately consistent with the sum of two mean-field nucleon momenta. Comparison with calculations appears to show that the SRC pairs are formed from mean-field nucleons in specific quantum states.
Summary
Circulating microRNAs (miRNA) have been intensely investigated as biomarkers in disease and therapy. Several studies have identified miR‐122 as an important regulator of HCV replication. The ...effect of new therapies that directly target the HCV replication life cycle on circulating microRNA levels has not been elucidated. We performed expression profiling of circulating miRNA in serum in subjects treated with HCV direct‐acting antiviral agents (DAAs). Serum miRNA levels were evaluated from two studies in HCV GT1‐infected treatment‐naïve subjects and prior nonresponders to pegylated interferon (pegIFN) and ribavirin (RBV) who received paritaprevir/ritonavir + dasabuvir + RBV for 12 weeks, and in treatment‐naïve genotype (GT)1‐3‐infected subjects who received paritaprevir/ritonavir + ombitasvir ± RBV for 12 weeks. Over 100 different miRNA species were detected in serum. Of these, levels of miR‐122 showed the most consistent change in response to treatment across all HCV genotypes. In all subjects, miR‐122 showed an average four‐fold reduction between baseline and week 2, and remained below baseline through post‐treatment week 12 in subjects who achieved sustained virological response. In contrast, in subjects who did not achieve SVR, miR‐122 levels began to return to baseline levels after the second week of treatment. The change in miR‐122 levels was similar across genotypes, and was comparable with or without RBV. This is the first report comparing expression levels of circulating miRNA in HCV GT1‐3 subjects treated with IFN‐free combinations of DAAs. The results suggest that serum levels of miR‐122 are reduced following treatment in subjects who achieve SVR, and correlate with HCV RNA levels across genotypes.
We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. ...Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity.
Stages III–IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy.
A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027).
IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.
Abstract
In this contribution we report on further investigations of the recently-evaluated Constant-Fraction Time-over-Threshold (CF-ToT) method for neutron/gamma-ray Pulse Shape Discrimination ...(PSD). The superiority of the CF-ToT PSD method over the constant-threshold (CT-ToT) method was previously demonstrated, down to low neutron energy thresholds of 100 keVee. Here, we report on a quantitative comparison between the traditionally used Charge Comparison (CC) method and the CF-ToT method using a stilbene scintillator coupled to a silicon photomultiplier, implementing an offline analysis of recorded fast-neutron and gamma-ray waveforms. An optimization of the constant fraction value indicates that a 20%-fraction yields the optimum figure-of-merit (FOM) and gamma-ray peak-to-valley (P/V) ratio. The results obtained for a particle energy threshold of 100 keVee (kilo electron Volt electron equivalent) show that the FOM and P/V values achieved with the CF-ToT method are superior to those obtained using the standard CC method. In addition, a first electronic implementation of the CF-ToT method was performed using simple circuitry suitable for multichannel architecture. Initial results obtained with this circuit prototype are presented.
Implementing a 3D histogram version of the Energy-Test in ROOT Cohen, E.O.; Reid, I.D.; Piasetzky, E.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2016, Letnik:
828
Journal Article
Recenzirano
Odprti dostop
Comparing simulation and data histograms is of interest in nuclear and particle physics experiments; however, the leading three-dimensional histogram comparison tool available in ROOT, the 3D ...Kolmogorov–Smirnov test, exhibits shortcomings. Throughout the following, we present and discuss the implementation of an alternative comparison test for three-dimensional histograms, based on the Energy-Test by Aslan and Zech. The software package can be found at http://www-nuclear.tau.ac.il/ecohen/.
Abstract Background Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged ...administration. Objectives and Methods The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. Results Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to > 2× upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. Conclusions Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.
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