EXTUBATE: A randomised controlled trial of nasal biphasic positive airway pressure vs. nasal continuous positive airway pressure following extubation in infants less than 30 weeks' gestation: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Respiratory distress syndrome remains a significant problem among premature infants. Mechanical ventilation through an endotracheal tube remains the mainstay of respiratory support but may be associated with lung injury and the development of chronic lung disease of prematurity. Efforts are needed to reduce the duration of mechanical ventilation in favour of less invasive forms of respiratory support and to improve rates of successful extubation.</p> <p>Non-invasive respiratory support has been demonstrated to be less injurious to the premature lung. Standard practice is to use nasal continuous positive airway pressure (n-CPAP) following extubation to support the baby's breathing. Many clinicians also use nasal biphasic positive airway pressure (n-BiPAP) in efforts to improve rates of successful extubation. However, there is currently no evidence that this confers any advantage over conventional nasal continuous positive airway pressure.</p> <p>Methods</p> <p>We propose an unblinded multi-centre randomised trial comparing n-CPAP with n-BiPAP in babies born before 30 weeks' gestation and less than two weeks old. Babies with congenital abnormalities and severe intra-ventricular haemorrhage will be excluded. 540 babies admitted to neonatal centres in England will be randomised at the time of first extubation attempt. The primary aim of this study is to compare the rate of extubation failure within 48 hours following the first attempt at extubation. The secondary aims are to compare the effect of n-BiPAP and n-CPAP on the following outcomes:</p> <p>1. Maintenance of successful extubation for 7 days post extubation</p> <p>2. Oxygen requirement at 28 days of age and at 36 weeks' corrected gestational age</p> <p>3. Total days on ventilator, n-CPAP/n-BiPAP</p> <p>4. Number of ventilator days following first extubation attempt</p> <p>5. pH and partial pressure of carbon dioxide in the first post extubation blood gas</p> <p>6. Duration of hospital stay</p> <p>7. Rate of abdominal distension requiring cessation of feeds</p> <p>8. Rate of apnoea and bradycardia</p> <p>9. The age at transfer back to referral centre in days</p> <p>The trial will determine whether n-BiPAP is safe and superior to n-CPAP in preventing extubation failure in babies born before 30 weeks' gestation and less than two weeks old.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN18921778">ISRCTN18921778</a></p

Review of multi-scale electromagnetic modeling

This paper reviews various methods to solve multiscale problems ranging from low-frequency methods to very high-frequency methods. ©2010 IEEE.published_or_final_versionThe 2010 International Conference on Electromagnetics in Advanced Applications (ICEAA), Sydney, N.S.W., 20-24 September 2010. In Proceedings of ICEAA'10, 2010, p. 641-64

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Field trial of an automated batch chlorinator system at shared water points in an urban community of Dhaka, Bangladesh

Point-of-use water treatment with chlorine is underutilized in low-income households. The Zimba, an automated batch chlorinator, requires no electricity or moving parts, and can be installed at shared water points with intermittent flow. We conducted a small-scale trial to assess the acceptability and quality of Zimba-treated municipal water. Fieldworkers collected stored drinking water over a 10-week period from control (n = 24 households) and treatment (n = 30 households) compounds to assess levels of free chlorine and E. coli contamination. Overall, 80% of stored drinking water samples had a safe chlorine residual among treatment households, compared to 29% among control households (P &amp;lt; 0.001). Concentrations of E. coli were lower (mean difference = 0.4 log colony-forming units/100 mL, P = 0.004) in treatment compared to control households. Fifty-three percent of mothers (n = 17), thought the Zimba was easy to use and 76% were satisfied with the taste. The majority of mothers mentioned that collecting water from the Zimba took more time and created a long queue at the handpump. The Zimba successfully chlorinated household stored drinking water; however, further technology development is required to address user preferences. The Zimba may be a good option for point-of-collection water treatment in areas where queuing for water is uncommon.</jats:p

The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela(−/−) mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration

A 13C NMR study of decomposing logging residues in an Australian hoop pine plantation

Purpose Residue retention is important for nutrient and water economy in subtropical plantation forests. We examined decomposing hoop pine (Araucaria cunninghamii Ait. Ex D. Don) residues-foliage, branches, and stem wood-to determine the changes in structural chemistry that occur during decomposition. Materials and methods Residues were incubated in situ using 0.05 m2 microplots. We used solid-state 13C nuclear magnetic resonance (NMR) spectroscopy to determine the structural composition of harvest residues in the first 24 months of decomposition. Results and discussion The spectral data for branch and stem residues were generally similar to one another and showed few changes during decomposition. The lignin content of branch and foliage residues decreased during decomposition. When residues were mixed together during decomposition, the O-alkyl fraction of foliage decreased initially then increased up to 24 months, while the alkyl carbon (C) fraction exhibited the opposite pattern. The decomposition of woody hoop pine residues (branch and stem wood) is surprisingly uniform across the major C forms elucidated with 13C NMR, with little evidence of preferential decomposition. When mixed with branch and stem materials, foliage residues showed significant short- and long-term compositional changes. This synergistic effect may be due to the C/N ratio of the treatments and the structure of the microbial decomposer community. Conclusions Twenty-four months of decomposition of hoop pine residues did not result in substantial accumulation of recalcitrant C forms, suggesting that they may not contribute to long-term C sequestration.No Full Tex

Phosphorylation of p65(RelA) on Ser547 by ATM Represses NF-κB-Dependent Transcription of Specific Genes after Genotoxic Stress

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review