Patient centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children

Whilst non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared to appendicectomy, children allocated to non-operative treatment reported higher short term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT

Competitive formation of spiro and ansa derivatives in the reactions of tetrafluorobutane-1,4-diol with hexachlorocyclotriphosphazene: a comparison with butane-1,4-diol

Reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), in two stoichiometries (1:1.2 and 1:3) with the sodium derivative of the fluorinated diol, 2,2,3,3-tetrafluorobutane-1,4-diol, (2), in THF solution at room temperature afforded six products, whose structures have been characterized by X-ray crystallography and 1H, 19F and 31P NMR spectroscopy: the mono-spiro compound, N3P3Cl4(OCH2CF2CF2CH2O), (3), its ansa isomer, (4), a di-spiro derivative N3P3Cl2(OCH2CF2CF2CH2O)2, (5), its spiro-ansa (6) and non-gem cis bis-ansa (7) isomers and a tri-spiro compound N3P3(OCH2CF2CF2CH2O)3, (8). The tri-spiro derivative (8) was also formed in the reaction of the ansa compound (4) with diol (2) in a 1:3 ratio in THF at room temperature. The reactions of (1) with step-wise additions of (2) were also investigated at low temperature (-780C) to give the same range of products as at room temperature. The results of all reactions are compared with previous work on the reactions of (1) with butane-1,4-diol/pyridine mixtures and with the reaction of hexafluorocyclotriphosphazene, N3P3F6 (9), with the silyl derivative of the diol (2), (Me3SiOCH2CF2)2, in a 1:0.4 mole ratio in the same solvent, THF

Stereoisomerism in pentaerythritol-bridged cyclotriphosphazene tri-spiranes: spiro and ansa 1,3-propanediyldioxy disubstituted derivatives

Four isomeric products were isolated and purified from the reaction of 1,3-propanediol with the tetra-spirane cyclophosphazene-organophosphate compound (1): viz. the di-monospiro (2a), di-monoansa (2b) and two monospiro-monoansa derivatives (2c) and (2d). It is shown by 31P NMR spectroscopy on addition of a chiral solvating agent (CSA) that both the di-monospiro (2a) and di-monoansa (2b) derivatives are racemates, as expected, whereas no splitting of NMR signals occurred on addition of CSA to solutions of (2c) and (2d). It is found by X-ray crystallography that the two monospiro-monoansa spirane derivatives, (2c) and (2d), are meso diastereoisomers, which represent a new case of the stereochemistry of bis di-substituted cyclophosphazene derivatives of (1). It is also observed from the 31P NMR spectrum of the reaction mixture, supported by the yields of pure compounds, that formation of a spiro group is about 4.5 times more likely than that of an ansa moiety under the conditions of the reaction

Migratory behaviour and spatial dynamics of large sharks and their conservation implications

Content from four of the chapters have been published in the following journal articles: Lea, J.S.E., Humphries, N.E., von Brandis, R., Clarke, C.R., Sims, D.W. 2016. Acoustic telemetry and network analysis reveal space-use of multiple reef predators and enhance MPA design. Proceedings of the Royal Society B, 283 ISSN 1471-2954 DOI: 10.1098/rspb.2016.0717 http://rspb.royalsocietypublishing.org/content/283/1834/20160717 Lea, J.S.E., Humphries, N.E., Clarke, C.R., Sims, D.W. 2015. To Madagascar and back: Long-distance, return migration across open ocean by a pregnant female bull shark Carcharhinus leucas. Journal of Fish Biology, 87, 1313–1321 ISSN: 1095-8649 DOI: 10.1111/jfb.12805 http://onlinelibrary.wiley.com/doi/10.1111/jfb.12805/abstract Lea, J.S.E., Wetherbee, B.M., Queiroz, N., Burnie, N., Aming, C., Sousa, L.L., Mucientes, G.R., Humphries, N.E., Harvey, G.M., Sims, D.W., Shivji, M.S. 2015. Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems. Scientific Reports, 5 ISSN 2045-2322 DOI:10.1038/srep11202 http://www.nature.com/articles/srep11202Edited version embargoed until 28.01.2018 Full version: Access restricted permanently due to 3rd party copyright restrictions. Restriction set on 31.01.2017 by SC, Graduate schoolDetermining the dynamic nature of animal movement has been an important component in a wider understanding of animal population ecology. Generally, this is because temporal change in the density of a population at a specific geographic location is not only a function of births and deaths but also of movements, including migration. The increased availability of remote telemetry and biologging systems in recent years has enabled many studies tracking marine predators, such as turtles, seabirds and marine mammals, but a general understanding of spatial dynamics in large sharks remains less well developed. This is in part due to few studies having achieved sufficiently long-term, multi-year tracks to detect changes in movement behaviour over time. Determining the timing, repeatability and potential motivations for movements of large sharks is necessary to understand the ecological and evolutionary role of such behaviour more generally in marine predators. Furthermore, given global concerns of declining shark populations, a detailed appreciation of shark movements can reveal the extent 6 of overlap with area-focused human activities (e.g. fishing), as well as inform assessments of population trends and spatial management options. In order to demonstrate how shark migratory behaviour and spatial dynamics can vary dramatically depending on the species and location, with subsequent contrasting conservation implications, the present work used longterm, remote telemetry to reveal detailed patterns in shark movement behaviour at two very different geographical scales: broad-scale movements of larger species that encompass ocean basins, versus fine-scale movements of reef-associated species at a remote atoll. First, using satellite telemetry, it was revealed for the tiger shark Galeocerdo cuvier, that adult males undertake annually repeated, roundtrip migrations of over 7,500 km in the northwest Atlantic. Second, acoustic telemetry was used to determine the fine-scale spatial dynamics of a multispecies shark assemblage at a small, remote atoll in the Seychelles, Indian Ocean, where a number of species displayed perennial residency. While the fine-scale movements of reef sharks in the Seychelles suggest an MPA of moderate size may be an effective management option, the long-distance migrations of the tiger sharks in the Atlantic reveal that conservation efforts targeting them must account for dynamic fisheries interactions over large geographical scales, potentially requiring time-area closures to be effective. Examining the long-term movement behaviour of different shark species over contrasting geographical scales has emphasised the importance of understanding spatial dynamics when informing management decisions, and has contributed to a wider understanding of the population ecology of these species

Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders

High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders

Impact of ART on the fertility of HIV-positive women in sub-Saharan Africa.

OBJECTIVE: Understanding the fertility of HIV-positive women is critical to estimating HIV epidemic trends from surveillance data and to planning resource needs and coverage of prevention of mother-to-child transmission services in sub-Saharan Africa. In the light of the considerable scale-up in antiretroviral therapy (ART) coverage over the last decade, we conducted a systematic review of the impact of ART on the fertility outcomes of HIV-positive women. METHODS: We searched Medline, Embase, Popline, PubMed and African Index Medicus. Studies were included if they were conducted in sub-Saharan Africa and provided estimates of fertility outcomes (live births or pregnancies) among women on ART relative to a comparison group. RESULTS: Of 2070 unique references, 18 published papers met all eligibility criteria. Comparisons fell into four categories: fertility of HIV-positive women relative to HIV-negative women; fertility of HIV-positive women on ART compared to those not yet on ART; fertility differences by duration on ART; and temporal trends in fertility among HIV-positive women. Evidence indicates that fertility increases after approximately the first year on ART and that while the fertility deficit of HIV-positive women is shrinking, their fertility remains below that of HIV-negative women. These findings, however, were based on limited data mostly during the period 2005-2010 when ART scaled up. CONCLUSIONS: Existing data are insufficient to characterise how ART has affected the fertility of HIV-positive women in sub-Saharan Africa. Improving evidence about fertility among women on ART is an urgent priority for planning HIV resource needs and understanding HIV epidemic trends. Alternative data sources such as antenatal clinic data, general population cohorts and population-based surveys can be harnessed to understand the issue

Differential rates of perinatal maturation of human primary and nonprimary auditory cortex

Abstract Primary and nonprimary cerebral cortex mature along different timescales; however, the differences between the rates of maturation of primary and nonprimary cortex are unclear. Cortical maturation can be measured through changes in tissue microstructure detectable by diffusion magnetic resonance imaging (MRI). In this study, diffusion tensor imaging (DTI) was used to characterize the maturation of Heschl’s gyrus (HG), which contains both primary auditory cortex (pAC) and nonprimary auditory cortex (nAC), in 90 preterm infants between 26 and 42 weeks postmenstrual age (PMA). The preterm infants were in different acoustical environments during their hospitalization: 46 in open ward beds and 44 in single rooms. A control group consisted of 15 term-born infants. Diffusion parameters revealed that (1) changes in cortical microstructure that accompany cortical maturation had largely already occurred in pAC by 28 weeks PMA, and (2) rapid changes were taking place in nAC between 26 and 42 weeks PMA. At term equivalent PMA, diffusion parameters for auditory cortex were different between preterm infants and term control infants, reflecting either delayed maturation or injury. No effect of room type was observed. For the preterm group, disturbed maturation of nonprimary (but not primary) auditory cortex was associated with poorer language performance at age two years

Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells

Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid pharmacokinetics in pre-clinical neuroblastoma models. Here we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance retinoic acid action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signaling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans

Practical considerations for plant phylogenomics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143756/1/aps31038_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143756/2/aps31038.pd