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The ultra-bright femtosecond X-ray pulses provided by X-ray Free Electron Lasers (XFELs) open capabilities for studying the structure and dynamics of a wide variety of biological and inorganic systems beyond what is possible at synchrotron sources. Although the structure and chemistry at the catalytic sites have been studied intensively in both biological and inorganic systems, a full understanding of the atomic-scale chemistry requires new approaches beyond the steady state X-ray crystallography and X-ray spectroscopy at cryogenic temperatures. Following the dynamic changes in the geometric and electronic structure at ambient conditions, while overcoming X-ray damage to the redox active catalytic center, is key for deriving reaction mechanisms. Such studies become possible by using the intense and ultra-short femtosecond X-ray pulses from an XFEL, where sample is probed before it is damaged. We have developed methodology for simultaneously collecting X-ray diffraction data and X-ray emission spectra, using an energy dispersive spectrometer, at ambient conditions, and used this approach to study the room temperature structure and intermediate states of the photosynthetic water oxidizing metallo-protein, photosystem II. Moreover, we have also used this setup to simultaneously collect the X-ray emission spectra from multiple metals to follow the ultrafast dynamics of light-induced charge transfer between multiple metal sites. A Mn–Ti containing system was studied at an XFEL to demonstrate the efficacy and potential of this method. [ABSTRACT FROM AUTHOR]

Background:Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT.Methods:Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment.Results:Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%.Conclusions:Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging. [ABSTRACT FROM AUTHOR]

Objective: The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates.Design: Randomized controlled trial.Methods: Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18).Results: There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups.Conclusions: Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN. [ABSTRACT FROM AUTHOR]

Parents of preterm, very low birthweight (VLBW <1,500 grams) babies are often uncertain about the relative merits (versus risks) of preschool experience for their infant. To examine this issue, the academic and social functioning at age seven, of 74 VLBW infants who had attended an informal preschool setting was compared to that of 42 VLBW nonattenders of equivalent neonatal medical severity and family milieu, as well as to that of 154 normal birthweight children (NBW >2,500 grams) of similar background. VLBW attenders scored significantly higher than VLBW nonattenders on the cognitive measures of Mean School Performance, Works Hard, and Learns a Lot (Teacher Report Form—Achenbach, 1991), and also on Cognitive Competence (Teacher's Rating Scale—Harter & Pike, 1984). In the case of girls, but not boys, attenders also had lower social nonparticipation scores than nonattenders on the Selective Classmate Evaluation Procedure (Hoy, Sykes, Bill, Halliday, McClure, & McReid, 1992) completed by classmates. While attenders still scored less optimally than the NBW group, their better scores suggest the need to examine prospectively whether exposing VLBW toddlers to child-paced preschool experience prior to more formal teaching may encourage their openness to new experience and learning. © 2000 Michigan Association for Infant Mental Health. [ABSTRACT FROM AUTHOR]

The school-based behavioural adjustment at 7-8 years of a cohort of 243 prematurely born. very low birthweight (< 1501 g) children and their normal birthweight controls is reported, The findings indicate that the children born preterit) (both male and female) were rated by their teachers as expressing more behaviour problems than their controls, and were less well adjusted to the school environment. The deficits noted in the preterms applied across the social classes, with no amelioration noted in preterms of higher social class, It is speculated that the problem behaviours reflect a failure in self-regulatory functions. [ABSTRACT FROM AUTHOR]

Aims: To compare the effect of concentration of a mixed lipid emulsion (50:50 medium chain triglyceride/long chain triglyceride) (MCT/LCT) on lipid tolerance in neonates.Methods: A prospective randomised controlled trial of 75 neonates requiring prolonged parenteral nutrition was conducted in the neonatal intensive care units of the Royal Maternity Hospital, Belfast, and the Waveney Hospital, Ballymena. Thirty eight infants received 10% and 37 20% lipid emulsion. Infants were randomly assigned to groups at the start of parenteral nutrition and studied if they required seven or more days of this. Lipid tolerance was assessed by twice weekly measurements of plasma triglyceride and cholesterol concentrations and weekly measurement of non-esterified fatty acids and beta hydroxy butyrate. Anthropometry was carried out weekly.Results: The mean cholesterol in the 10% group was significantly higher within the first seven days of the study compared with the 20% group (3.5 vs 2.87 mmol/l), and continued to rise over the study period in contrast to the 20% group. A similar pattern was observed with the triglyceride concentrations. There was no significant difference in non-esterified fatty acids, beta hydroxy butyrate, or growth between the two groups.Conclusion: Sick neonates show better biochemical tolerance to 20% MCT/LCT emulsion than to 10% emulsion. [ABSTRACT FROM AUTHOR]