Risks and benefits of oxygen therapy

Mootha and Chinnery review the risks and benefits of oxygen administration in mitochondrial disease. They highlight probable harm from hyperoxia and possible benefit from hypoxia. At first sight this is counter-intuitive. It seems improbable that reducing the availability of a substrate that enables high-energy phosphate production via oxidative phosphorylation would be of benefit. But recent clinical data beyond the field of inherited metabolic disease support this approach

Expanding the role of the oncology nurse

Oncology nursing continues to evolve in response to advances in cancer treatment, information and biotechnology. As new scientific and technological discoveries are integrated into cancer care, oncology nurses need to play a key role in the management of this patient population. The role of the oncology nurse has expanded significantly and can differ greatly across cultures. Sophisticated treatments and the growth of targeted therapies will create the challenge of ensuring that all nurses working in this arena are well-educated, independent thinkers. Thus the future success of oncology nurses will focus on enhancement of nursing practice through advanced education. The increased globalisation of healthcare offers exciting opportunities to accomplish this goal by allowing for collaborative relationships among oncology nurses across the globe

Long-term drought sensitivity of trees in second-growth forests in a humid region

Classical field methods of reconstructing drought using tree rings in humid, temperate regions typically target old trees from drought-prone sites. This approach limits investigators to a handful of species and excludes large amounts of data that might be useful, especially for coverage gaps in large-scale networks. By sampling in more “typical” forests, network density and species diversity would increase in ways that could potentially improve reconstructions. Ten nonclassical tree-ring chronologies derived from randomly selected trees, trees from logged forests, or both were compared to more classical chronologies and an independent regional drought reconstruction to determine their usefulness for dendrohydroclimatic research. We find that nonclassical chronologies are significantly correlated to classical chronologies and reconstructed drought over the last 2–3 centuries. While nonclassical chronologies have spectral properties similar to those from classical dendroclimatic collections, they do lack spectral power at lower frequencies that are present in the drought reconstruction. Importantly, our results show that tree growth is strongly dependent on moisture availability, even for small, randomly selected trees in cut forests. These results indicate that there could be more data available in areas with few current tree-ring collections for studying climate history and that drought plays an important role in humid forests

Prospective review of radiotherapy trials through implementation of standardised multi-centre workflow and IT infrastructure

Objective: We sought to develop a process that would allow us to perform a prospective review of outlining in trials using expert reviewers based in multiple centres. Methods: We implemented a specific information technology infrastructure and workflow that could serve all organizations involved in the radiotherapy quality assurance (RTQA) process. Results: Data were processed and packaged in the computational environment for radiotherapy research (CERR) binary format and securely transmitted to the expert reviewer at the designated remote organization. It was opened and reviewed using the distributed CERR-compiled application, and a standardized report was sent to the respective centre. Centres were expected to correct any unacceptable deviations and resubmit outlining for approval prior to commencing treatment. 75% of reviews were completed and fed back to centres within 3 working days. There were no delays in treatment start date. Conclusion: Our distributed RTQA review approach provides a method of prospective outlining review at multiple centres, without compromising the quality, delaying the start of treatment or the need for significant additional infrastructure resources. Future progress in the area of prospective individual case review will need to be supported by additional resources for clinician time to undertake the reviews. Advances in knowledge: Trial groups around the world have formulated different approaches to address the need for the prospective review of radiotherapy (RT) data with clinical trials, in line with available resources. We report a UK solution that has allowed the workload for outlining review to be distributed across a wider group of volunteer reviewers without the need for any additional infrastructure costs and has already been adopted within the UK RT trials community

Treatment of necrotizing enterocolitis by conditioned medium derived from human amniotic fluid stem cells

PURPOSE: Necrotizing enterocolitis (NEC) is one of the most distressing gastrointestinal emergencies affecting neonates. Amniotic fluid stem cells (AFSC) improve intestinal injury and survival in experimental NEC but are difficult to administer. In this study, we evaluated whether conditioned medium (CM) derived from human AFSC have protective effects. METHODS: Three groups of C57BL/6 mice were studied: (i) breast-fed mice as control; (ii) experimental NEC mice receiving PBS; and (iii) experimental NEC mice receiving CM. NEC was induced between post-natal days P5 through P9 via: (A) gavage feeding of hyperosmolar formula four-time a day; (B) 10 minutes hypoxia prior to feeds; and (C) lipopolysaccharide administration on P6 and P7. Intra-peritoneal injections of either PBS or CM were given on P6 and P7. All mice were sacrificed on P9 and terminal ileum were harvested for analyses. RESULTS: CM treatment increased survival and reduced intestinal damage, decreased mucosal inflammation (IL-6; TNF-α), neutrophil infiltration (MPO), and apoptosis (CC3), and also restored angiogenesis (VEGF) in the ileum. Additionally, CM treated mice had increased levels of epithelial proliferation (Ki67) and stem cell activity (Olfm4; Lgr5) compared to NEC+PBS mice, showing restored intestinal regeneration and recovery during NEC induction. CM proteomic analysis of CM content identified peptides that regulated immune and stem cell activity. CONCLUSIONS: CM derived from human AFSC administered in experimental NEC exhibited various benefits including reduced intestinal injury and inflammation, increased enterocyte proliferation, and restored intestinal stem cell activity. This study provides the scientific basis for the use of CM derived from AFSC in neonates with NEC

The dynamics of genome replication using deep sequencing

Peer reviewedPublisher PD

Growth and structural transformation

Structural transformation refers to the reallocation of economic activity across the broad sectors agriculture, manufacturing, and services. This review article synthesizes and evaluates recent advances in the research on structural transformation. We begin by presenting the stylized facts of structural transformation across time and space. We then develop a multi-sector extension of the one-sector growth model that encompasses the main existing theories of structural transformation. We argue that this multi-sector model serves as a natural benchmark to study structural transformation and that it is able to account for many salient features of structural transformation. We also argue that this multi-sector model delivers new and sharper insights for understanding economic development, regional income convergence, aggregate productivity trends, hours worked, business cycles, wage inequality, and greenhouse gas emissions. We conclude by suggesting several directions for future research on structural transformation.For financial support, Herrendorf thanks the Spanish Ministry of Education (Grants ECO2009-11165 and ECO2012-31358); Rogerson thanks both the NSF and the Korea Science Foundation (WCU-R33-10005); and Valentinyi thanks the Hungarian Scientific Research Fund (OTKA) (Project K-105660-ny

Monolayer doping of silicon-germanium alloys: a balancing act between phosphorus incorporation and strain relaxation

This paper presents the application of monolayer doping (MLD) to silicon-germanium (SiGe). This study was carried out for phosphorus dopants on wafers of epitaxially grown thin films of strained SiGe on silicon with varying concentrations of Ge (18%, 30%, and 60%). The challenge presented here is achieving dopant incorporation while minimizing strain relaxation. The impact of high temperature annealing on the formation of defects due to strain relaxation of these layers was qualitatively monitored by cross-sectional transmission electron microscopy and atomic force microscopy prior to choosing an anneal temperature for the MLD drive-in. Though the bulk SiGe wafers provided are stated to have 18%, 30%, and 60% Ge in the epitaxial SiGe layers, it does not necessarily mean that the surface stoichiometry is the same, and this may impact the reaction conditions. X-ray photoelectron spectroscopy (XPS) and angle-resolved XPS were carried out to compare the bulk and surface stoichiometry of SiGe to allow tailoring of the reaction conditions for chemical functionalization. Finally, dopant profiling was carried out by secondary ion mass spectrometry to determine the impurity concentrations achieved by MLD. It is evident from the results that phosphorus incorporation decreases for increasing mole fraction of Ge, when the rapid thermal annealing temperature is a fixed amount below the melting temperature of each alloy

Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial

BACKGROUND: Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO_{2}) targets for critically ill children. The harm of interventions to raise SpO_{2} to > 94% may exceed their benefits. METHODS: We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and  94%) or a conservative oxygenation group (SpO_{2} = 88–92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO_{2} and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. RESULTS: A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children’s parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO_{2} was 94.9% (92.6–97.1) in the conservative oxygenation group and 97.5% (96.2–98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3–4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO_{2} was 0.28 (0.24–0.37) in the conservative group and 0.37 (0.30–0.42) in the liberal group (difference 0.08, 95% CI 0.03–0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. CONCLUSION: A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children