Antibiotic prescriptions in Italian hospitalised children after serial point prevalence surveys (or pointless prevalence surveys): has anything actually changed over the years?

BACKGROUND: Point prevalence surveys have been used in several studies to provide immediate and easily comparable information about antibiotic use and showed that about one third of hospitalised children had on ongoing antimicrobial prescription during their hospital admission. The aim of this study, as part of the Global Antimicrobial Resistance, Prescribing and Efficacy in Neonates and Children project, is to describe antimicrobial prescriptions among hospitalised children in four tertiary care hospitals in Italy to show if something has changed over the years. METHODS: Four tertiary care Italian's hospitals joined three Point Prevalence Surveys (PPSs) in three different period of the year. All children under 18 years of age with an ongoing antimicrobial prescription, admitted on the participating wards at 8 o'clock in the morning of the selecting day were enrolled. RESULTS: A total of 1412 patients (475 neonates and 937 children) were admitted in the days of three PPSs. Overall, among the total admitted patients, 565 patients (40%) had an ongoing antimicrobial prescription in the days of the survey A total of 718 antibiotics were administered in the 485 admitted children and 133 in neonates. The most common indications for antibiotic therapy in children was Lower respiratory tract infections (244/718, 34%), while in neonates were prophylaxis for medical problems (35/133, 26.3%), newborn prophylaxis for newborn risk factors (29/133, 21.8%) and prophylaxis for surgical disease (15/133, 11.3%). CONCLUSIONS: Based on our results, it appears that nothing has changed since the last PPS and that the quality improved targets, underlyined in previous studies, are always the same. Serial PPSs can be part of AMS strategies but they are not sufficient alone to produce changes in clinical practice

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit

Dynamical tunneling in molecules: Quantum routes to energy flow

Dynamical tunneling, introduced in the molecular context, is more than two decades old and refers to phenomena that are classically forbidden but allowed by quantum mechanics. On the other hand the phenomenon of intramolecular vibrational energy redistribution (IVR) has occupied a central place in the field of chemical physics for a much longer period of time. Although the two phenomena seem to be unrelated several studies indicate that dynamical tunneling, in terms of its mechanism and timescales, can have important implications for IVR. Examples include the observation of local mode doublets, clustering of rotational energy levels, and extremely narrow vibrational features in high resolution molecular spectra. Both the phenomena are strongly influenced by the nature of the underlying classical phase space. This work reviews the current state of understanding of dynamical tunneling from the phase space perspective and the consequences for intramolecular vibrational energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem. (Review to appear in Oct. 2007

CD93 A POTENTIAL PLAYER IN CYTOTROPHOBLAST AND ENDOTHELIAL CELL MIGRATION

CD93, also known as complement component C1q receptor, is expressed on the surface of diferent cellular types such as monocytes, neutrophils, platelets, microglia, and endothelial cells, and it plays a pivotal role in cell proliferation, cell migration, and formation of capillary-like structures. These processes are strictly regulated, and many fetal and maternal players are involved during placental development. At present, there are no studies in literature regarding CD93 in placental development, so we investigated CD93 expression in frst and third trimester and PE placentas by immunohistochemistry and western blotting analysis. In addition, we performed in vitro experiments under oxidative stress conditions to demonstrate how oxidative stress acts on CD93 protein expression. Our data showed that CD93 was expressed in villous cytotrophoblast cells, in some fetal vessels of frst and third trimester and PE placentas and in the extravillous cytotrophoblast of cell columns in the frst trimester placentas. Moreover, we detected a signifcant decrease of CD93 expression in third trimester and PE placentas compared to frst trimester placentas, while no diferences were detected between third and PE placentas. No diferences of CD93 expression were detected in oxidative stress conditions. We suggest that CD93 can guide extravillous cytotrophoblast migration through β1-integrin in uterine spiral arteries during placentation in the frst trimester of pregnancy and that the decrease of CD93 expression in third trimester and PE placentas could be linked to the poor extravillous cytotrophoblast cells migration. So, it might be interesting to understand the role of CD93 in the frst phases of PE onset

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes.

In recent years, an aberrant gastrointestinal colonization has been found to be associated with an higher risk for postnatal sepsis, necrotizing enterocolitis (NEC) and growth impairment in preterm infants. As a consequence, the reasons of intestinal dysbiosis in this population of newborns have increasingly become an object of interest. The presence of a link between the gut and lung microbiome's development (gut-lung axis) is emerging, and more data show as a gut-brain cross talking mediated by an inflammatory milieu, may affect the immunity system and influence neonatal outcomes. A revision of the studies which examined gut and lung microbiota in preterm infants and a qualitative analysis of data about characteristic patterns and related outcomes in terms of risk of growing impairment, Necrotizing Enterocolitis (NEC), Bronchopulmonary Dysplasia (BPD), and sepsis have been performed. Microbiota take part in the establishment of the gut barrier and many data suggest its immune-modulator role. Furthermore, the development of the gut and lung microbiome (gut-lung axis) appear to be connected and able to lead to abnormal inflammatory responses which have a key role in the pathogenesis of BPD. Dysbiosis and the gut predominance of facultative anaerobes appear to be crucial to the pathogenesis and subsequently to the prevention of such diseases

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit

Microcanonical rates, gap times, and phase space dividing surfaces

The general approach to classical unimolecular reaction rates due to Thiele is revisited in light of recent advances in the phase space formulation of transition state theory for multidimensional systems. We analyze in detail the gap time distribution and associated reactant lifetime distribution for the isomerization reaction HCN $\rightleftharpoons$ CNH. Both algebraic (power law) and exponential decay regimes have been identified. Statistical estimates of the isomerization rate are compared with the numerically determined decay rate. Examination of the decay properties of subsensembles of trajectories that exit the HCN well through either of 2 available symmetry related product channels shows that the complete trajectory ensemble effectively attains the full symmetry of the system phase space on a short timescale $t \lesssim 0.5$ ps, after which the product branching ratio is 1:1, the "statistical" value. At intermediate times, this statistical product ratio is accompanied by nonexponential (nonstatistical) decay. We point out close parallels between the dynamical behavior inferred from the gap time distribution for HCN and nonstatistical behavior recently identified in reactions of some organic molecules.Comment: 44 pages, 9 figure

RECURRENT PREGNANCY LOSS IS ASSSOCIATED TO LEAKY GUT: A NOVEL PATHOGENIC MODEL OF ENDOMETRIUM INFLAMMATION ?

Background: Recurrent pregnancy loss (RPL) occurs in 3\u20135% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1\u3b2 and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1\u3b2 was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome

Correction to: Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation?

Background: Recurrent pregnancy loss (RPL) occurs in 3–5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1β and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1β was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome