Spin injection between epitaxial Co2.4Mn1.6Ga and an InGaAs quantum well

Electrical spin injection in a narrow [100] In0.2Ga0.8As quantum well in a GaAs p-i-n optical device is reported. The quantum well is located 300 nm from an AlGaAs Schottky barrier and this system is used to compare the efficiencies and temperature dependences of spin injection from Fe and the Heusler alloy Co2.4Mn1.6Ga grown by molecular-beam epitaxy. At 5 K, the injected electron spin polarizations for Fe and Co2.4Mn1.6Ga injectors are 31% and 13%, respectively. Optical detection is carried out in the oblique Hanle geometry. A dynamic nuclear polarization effect below 10 K enhances the magnetic field seen by the injected spins in both devices. The Co2.4Mn1.6Ga thin films are found to have a transport spin polarization of similar to 50% by point contact Andreev reflection conductivity measurements. (c) 2005 American Institute of Physics

A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable tumours (MSS). The primary tumours also had MSI in the residual tumours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest that tumour MSI changes during CDDP-based chemotherapy, and that the loss of hMLH1 expression is one of the factors that has the greatest effect on this transformation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Stakeholder involvement in systematic reviews:a scoping review

Abstract Background There is increasing recognition that it is good practice to involve stakeholders (meaning patients, the public, health professionals and others) in systematic reviews, but limited evidence about how best to do this. We aimed to document the evidence-base relating to stakeholder involvement in systematic reviews and to use this evidence to describe how stakeholders have been involved in systematic reviews. Methods We carried out a scoping review, following a published protocol. We searched multiple electronic databases (2010–2016), using a stepwise searching approach, supplemented with hand searching. Two authors independently screened and discussed the first 500 abstracts and, after clarifying selection criteria, screened a further 500. Agreement on screening decisions was 97%, so screening was done by one reviewer only. Pre-planned data extraction was completed, and the comprehensiveness of the description of methods of involvement judged. Additional data extraction was completed for papers judged to have most comprehensive descriptions. Three stakeholder representatives were co-authors for this systematic review. Results We included 291 papers in which stakeholders were involved in a systematic review. Thirty percent involved patients and/or carers. Thirty-two percent were from the USA, 26% from the UK and 10% from Canada. Ten percent (32 reviews) were judged to provide a comprehensive description of methods of involving stakeholders. Sixty-nine percent (22/32) personally invited people to be involved; 22% (7/32) advertised opportunities to the general population. Eighty-one percent (26/32) had between 1 and 20 face-to-face meetings, with 83% of these holding ≤ 4 meetings. Meetings lasted 1 h to ½ day. Nineteen percent (6/32) used a Delphi method, most often involving three electronic rounds. Details of ethical approval were reported by 10/32. Expenses were reported to be paid to people involved in 8/32 systematic reviews. Discussion/conclusion We identified a relatively large number (291) of papers reporting stakeholder involvement in systematic reviews, but the quality of reporting was generally very poor. Information from a subset of papers judged to provide the best descriptions of stakeholder involvement in systematic reviews provide examples of different ways in which stakeholders have been involved in systematic reviews. These examples arguably currently provide the best available information to inform and guide decisions around the planning of stakeholder involvement within future systematic reviews. This evidence has been used to develop online learning resources. Systematic review registration The protocol for this systematic review was published on 21 April 2017. Publication reference: Pollock A, Campbell P, Struthers C, Synnot A, Nunn J, Hill S, Goodare H, Watts C, Morley R: Stakeholder involvement in systematic reviews: a protocol for a systematic review of methods, outcomes and effects. Research Involvement and Engagement 2017, 3:9. https://doi.org/10.1186/s40900-017-0060-4

Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: Study protocol for a randomised controlled trial

© The Author(s). 2017. Background: Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE. Methods/design: This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up. Discussion: This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting

Coastal Upwelling Supplies Oxygen-Depleted Water to the Columbia River Estuary

Low dissolved oxygen (DO) is a common feature of many estuarine and shallow-water environments, and is often attributed to anthropogenic nutrient enrichment from terrestrial-fluvial pathways. However, recent events in the U.S. Pacific Northwest have highlighted that wind-forced upwelling can cause naturally occurring low DO water to move onto the continental shelf, leading to mortalities of benthic fish and invertebrates. Coastal estuaries in the Pacific Northwest are strongly linked to ocean forcings, and here we report observations on the spatial and temporal patterns of oxygen concentration in the Columbia River estuary. Hydrographic measurements were made from transect (spatial survey) or anchor station (temporal survey) deployments over a variety of wind stresses and tidal states during the upwelling seasons of 2006 through 2008. During this period, biologically stressful levels of dissolved oxygen were observed to enter the Columbia River estuary from oceanic sources, with minimum values close to the hypoxic threshold of 2.0 mg L−1. Riverine water was consistently normoxic. Upwelling wind stress controlled the timing and magnitude of low DO events, while tidal-modulated estuarine circulation patterns influenced the spatial extent and duration of exposure to low DO water. Strong upwelling during neap tides produced the largest impact on the estuary. The observed oxygen concentrations likely had deleterious behavioral and physiological consequences for migrating juvenile salmon and benthic crabs. Based on a wind-forced supply mechanism, low DO events are probably common to the Columbia River and other regional estuaries and if conditions on the shelf deteriorate further, as observations and models predict, Pacific Northwest estuarine habitats could experience a decrease in environmental quality

Substitutions in the Amino-Terminal Tail of Neurospora Histone H3 Have Varied Effects on DNA Methylation

Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin, respectively. In Neurospora crassa, heterochromatin formation requires methylation of histone H3 at lysine 9 (H3K9) by the SET domain protein DIM-5. Heterochromatin protein 1 (HP1) reads this mark and directly recruits the DNA methyltransferase, DIM-2. An ectopic H3 gene carrying a substitution at K9 (hH3K9L or hH3K9R) causes global loss of DNA methylation in the presence of wild-type hH3 (hH3WT). We investigated whether other residues in the N-terminal tail of H3 are important for methylation of DNA and of H3K9. Mutations in the N-terminal tail of H3 were generated and tested for effects in vitro and in vivo, in the presence or absence of the wild-type allele. Substitutions at K4, K9, T11, G12, G13, K14, K27, S28, and K36 were lethal in the absence of a wild-type allele. In contrast, mutants bearing substitutions of R2, A7, R8, S10, A15, P16, R17, K18, and K23 were viable. The effect of substitutions on DNA methylation were variable; some were recessive and others caused a semi-dominant loss of DNA methylation. Substitutions of R2, A7, R8, S10, T11, G12, G13, K14, and P16 caused partial or complete loss of DNA methylation in vivo. Only residues R8-G12 were required for DIM-5 activity in vitro. DIM-5 activity was inhibited by dimethylation of H3K4 and by phosphorylation of H3S10, but not by acetylation of H3K14. We conclude that the H3 tail acts as an integrating platform for signals that influence DNA methylation, in part through methylation of H3K9

The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants

BACKGROUND: Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function. METHODS/DESIGN: This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age. DISCUSSION: Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ--German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957