Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials

Background: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. Aim: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. Study Design: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. Results (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). Conclusion: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Fluctuation Methods To Study Protein Aggregation in Live Cells: Concanavalin A Oligomers Formation

Prefibrillar oligomers of proteins are suspected to be the primary pathogenic agents in several neurodegenerative diseases. A key approach for elucidating the pathogenic mechanisms is to probe the existence of oligomers directly in living cells. In this work, we were able to monitor the process of aggregation of Concanavalin A in live cells. We used number and brightness analysis, two-color cross number and brightness analysis, and Raster image correlation spectroscopy to obtain the number of molecules, aggregation state, and diffusion coefficient as a function of time and cell location. We observed that binding of Concanavalin A to the membrane and the formation of small aggregates paralleled cell morphology changes, indicating progressive cell compaction and death. Upon protein aggregation, we observed increased membrane water penetration as reported by Laurdan generalized polarization imaging

Determinants of hospitalization in a cohort of chronic dialysis patients in central Italy

Background: Few studies linking hospital discharge records with the population register of chronic dialysis (CD) patients are available. This study aimed to evaluate the frequency and the determinants of hospitalization, taking into account the demographic, clinical and biochemical data. Methods: We conducted a retrospective cohort study in 3411 patients starting dialysis from 1996-2000, reported to the Lazio Dialysis Registry (RDL) (Italy). These patients were linked with the hospital information system from 1996-2002. Hospital admission probability was calculated using the Kaplan-Meier method. To evaluate the determinants of hospitalization risk we used Cox's proportional hazards for the first admission and a marginal model considering competitive effect of mortality, the Wei-Lin-Weissfeld model, for any admission. Results: We found 7530 hospital admissions, referring to 1711 patients (50.7%), with a rate of 63/100 person-years. The most prevalent diagnoses were "diseases of the genitourinary system", (37.4%), and "diseases of the circulatory system", among secondary diagnoses (46.6%). Hospitalization probability was 34.4% at 1 yr after starting dialysis. The risk of first and any hospital admission was higher (p<0.05) for patients having more than one comorbid disease, hematocrit (Hct) level <30%, serum albumin level <3.5 g/dL, and a low degree of self-sufficiency. Conclusions: Hospitalization frequency, mainly during the first months of dialysis, suggests the need to improve the early management of chronic renal failure and indicates the importance of preventing complications and maximizing functional status among the dialysis population

Ion cyclotron resonance heating for tungsten control in various JET H-mode scenarios

Ion cyclotron resonance heating (ICRH) in the hydrogen minority scheme provides central ion heating and acts favorably on the core tungsten transport. Full wave modeling shows that, at medium power level (4 MW), after collisional redistribution, the ratio of power transferred to the ions and the electrons vary little with the minority (hydrogen) concentration n H/n e but the high-Z impurity screening provided by the fast ions temperature increases with the concentration. The power radiated by tungsten in the core of the JET discharges has been analyzed on a large database covering the 2013-2014 campaign. In the baseline scenario with moderate plasma current (I p = 2.5 MA) ICRH modifies efficiently tungsten transport to avoid its accumulation in the plasma centre and, when the ICRH power is increased, the tungsten radiation peaking evolves as predicted by the neo-classical theory. At higher current (3-4 MA), tungsten accumulation can be only avoided with 5 MW of ICRH power with high gas injection rate. For discharges in the hybrid scenario, the strong initial peaking of the density leads to strong tungsten accumulation. When this initial density peaking is slightly reduced, with an ICRH power in excess of 4 MW,very low tungsten concentration in the core (∼10-5) is maintained for 3 s. MHD activity plays a key role in tungsten transport and modulation of the tungsten radiation during a sawtooth cycle is correlated to the fishbone activity triggered by the fast ion pressure gradient

Sawtooth pacing with on-axis ICRH modulation in JET-ILW

A novel technique for sawteeth control in tokamak plasmas using ion-cyclotron resonance heating (ICRH) has been developed in the JET-ILW tokamak. Unlike previous ICRH methods, that explored the destabilization of the internal kink mode when the radio-frequency (RF) wave absorption was placed near the q = 1 surface, the technique presented here consists of stabilizing the sawteeth as fast as possible by applying the ICRH power centrally and subsequently induce a sawtooth crash by switching it off at the appropriate instant. The validation of this method in JET-ILW L-mode discharges, including preliminary tests in H-mode plasmas, is presented

Hybrid cancellation of ripple disturbances arising in AC/DC converters

In AC/DC converters, a peculiar periodic nonsmooth waveform arises, the so-called ripple. In this paper we propose a novel model that captures this nonsmoothness by means of a hybrid dynamical system performing state jumps at certain switching instants, and we illustrate its properties with reference to a three phase diode bridge rectifier. As the ripple corrupts an underlying desirable signal, we propound two observer schemes ensuring asymptotic estimation of the ripple, the first with and the second without knowledge of the switching instants. Our theoretical developments are well placed in the context of recent techniques for hybrid regulation and constitute a contribution especially for our second observer, where the switching instants are estimated. Once asymptotic estimation of the ripple is achieved, the ripple can be conveniently canceled from the desirable signal, and thanks to the inherent robustness properties of the proposed hybrid formulation, the two observer schemes require only that the desirable signal is slowly time varying compared to the ripple. Exploiting this fact, we illustrate the effectiveness of our second hybrid observation law on experimental data collected from the Joint European Torus tokamak