The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.

Export of Abscisic Acid, 1-Aminocyclopropane-1-Carboxylic Acid, Phosphate, and Nitrate from Roots to Shoots of Flooded Tomato Plants (Accounting for Effects of Xylem Sap Flow Rate on Concentration and Delivery).

We determined whether root stress alters the output of physiologically active messages passing from roots to shoots in the transpiration stream. Concentrations were not good measures of output. This was because changes in volume flow of xylem sap caused either by sampling procedures or by effects of root stress on rates of whole-plant transpiration modified concentrations simply by dilution. Thus, delivery rate (concentration x sap flow rate) was preferred to concentration as a measure of solute output from roots. To demonstrate these points, 1-aminocyclopropane-1-carboxylic acid (ACC), abscisic acid, phosphate, nitrate, and pH were measured in xylem sap of flooded and well-drained tomato (Lycopersicon esculentum Mill., cv Ailsa Craig) plants expressed at various rates from pressurized detopped roots. Concentrations decreased as sap flow rates were increased. However, dilution of solutes was often less than proportional to flow, especially in flooded plants. Thus, sap flowing through detopped roots at whole-plant transpiration rates was used to estimate solute delivery rates in intact plants. On this basis, delivery of ACC from roots to shoots was 3.1-fold greater in plants flooded for 24 h than in well-drained plants, and delivery of phosphate was 2.3-fold greater. Delivery rates of abscisic acid and nitrate in flooded plants were only 11 and 7%, respectively, of those in well-drained plants.

Previous exposure to amphetamine increases incentive to obtain the drug: long-lasting effects revealed by the progressive ratio schedule.

The present experiment tested whether previous exposure to amphetamine would enhance rats' predisposition to self-administer a high dose of the drug under fixed (FR) and progressive ratio (PR) schedules of reinforcement. Rats in different groups were given five injections of either amphetamine (1.5 mg/kg, i.p.) or saline (1.0 ml/kg, i.p.), one injection administered every third day and, starting 10 days later, given the opportunity to lever press for amphetamine (200 microg/kg/infusion, i.v.) on each of several 4 h sessions. When allowed to self-administer up to 10 infusions under first an FR-1 and then an FR-2 schedule, amphetamine and saline pre-exposed rats were indistinguishable and readily acquired the lever press response. However, when tested under the PR schedule of reinforcement, rats previously exposed to amphetamine achieved higher break points than saline pre-exposed rats across six consecutive PR sessions. This difference between groups was long lasting and durable. When compared to saline pre-exposed rats on three separate tests conducted 10, 14 and 21 days following the last PR session, rats pre-exposed to amphetamine also showed (i) greater nucleus accumbens dopamine reactivity to amphetamine (1.0 mg/kg, i.p.), (ii) higher break points when retested on the PR schedule, and (iii) a greater locomotor response to amphetamine (1.0 mg/kg, i.p.). On the last test, both groups showed higher levels of locomotion than no drug control animals that received amphetamine for the first time on this test. These findings suggest that previous exposure to amphetamine produces a long lasting enhancement in the incentive motivation animals will exhibit in their effort to obtain the drug. This enhancement appears to parallel sensitization of the drug's locomotor and nucleus accumbens dopamine activating effects. It may very well be exacerbated by continued exposure to self-administered amphetamine.

Spatial and temporal aspects of the genetic structure of Juniperus communis populations.

Juniperus communis is a dioecious, wind pollinated shrub or small tree that produces 'berries' (female cones) containing a small number of seeds that are thought to be dispersed by birds. The expectation, therefore, would be that populations of Juniper are genetically diverse with little structuring between them. In Britain, the species has two main centres of distribution: a highland zone in the north and west, in which populations are still large and sexually reproducing, and a southern zone on chalk downlands in which populations are small and fragmented and individuals suffer from a decline in fertility. Thus, one would expect the large sexually viable populations in the north to exhibit high levels of within-population genetic variation, while the declining southern populations would be genetically depauperate. The analysis of amplified fragment length polymorphisms (AFLPs) was used to test this hypothesis. Surprisingly, all populations studied showed high levels of genetic variation although there was clear structuring between populations. On the basis of the geographical structuring of the populations it was hypothesized that J. communis colonized Britain via three separate routes.

Isolation and characterization of polymorphic microsatellites in Cocos nucifera L.

Microsatellites or simple sequence repeats (SSRs) were isolated from coconut (Cocos nucifera) and tested for polymorphism on restricted germplasm. Sequencing of 197 clones from a cv. Tagnanan Tall-enriched genomic library showed that 75% contained a microsatellite, of which 64% were dinucleotide (GA/CT, CA/GT and GC/CG), 6% were trinucleotide, and 30% were compound repeats. Of 41 primer pairs tested on Tagnanan Tall genomic DNA, 38 gave the expected size product, two amplified two loci, and another gave a multilocus pattern. On 20 coconut samples, the 38 SSRs detected 198 alleles (average: 5.2 alleles per microsatellite). Genetic diversity (D = 1 - sigma pi2) values ranged from 0.141 to 0.809. Heterozygotes were present at high frequencies among some dwarf samples. Analysis of similarity matrices based either on shared alleles at each locus (simple matching coefficient) or on allele bands across all loci (Jaccard coefficient) showed similar results. Dwarfs grouped separately from talls and showed less genetic diversity. In a wider test on 40 samples, 8 SSRs detected 64 alleles (average: eight alleles per microsatellite). These results indicate the high potential of microsatellites to detect genetic diversity in coconut germplasm.

Characterisation of genetic diversity in potential biomass willows (Salix spp.) by RAPD and AFLP analyses.

The genus Salix (willow) contains a number of species which have great potential value as biomass crops in short rotation coppice (SRC). Efforts to improve biomass willows by breeding are currently hampered by the limited information available on genetic diversity and on genetic relationships within and among species, clones, and hybrids in the gene pool. Hybridisation occurs commonly in nature and the relatedness of many clones is unclear. Molecular markers were used to assess genetic diversity in a reference set of willows maintained within the U.K. National Collection and 16 elite clones currently being evaluated in field trials at several European sites. The two marker systems tested, RAPDs and AFLPs, were equally informative for revealing relationships within the reference set of clones. No differences were observed when alternative similarity coefficients were compared or when analysis was restricted to the use of polymorphic bands only. Good agreement with available knowledge of the clonal origins was obtained and one instance of duplicate clones was identified. AFLPs revealed more genetic diversity and discriminated between closely related clones. A difference in the relationships revealed was observed with one AFLP primer combination. RAPDs were more problematic, both in terms of reproducibility and scorability.

Microsatellite analysis of the inbreeding grass weed Barren Brome (Anisantha sterilis) reveals genetic diversity at the within- and between-farm scales.

Nine microsatellites were used to screen 131 samples of Barren Brome (Anisantha sterilis: synonym Bromus sterilis) collected from within the fields of three English farms [from Oxfordshire (Oxon), Leicestershire (Leics) and Wiltshire (Wilts)] and eight seeds taken from samples of each of 10 farms across England, UK. Most individuals (approximately 97%) were homozygous. Polymorphism occurred at all nine loci in all three farms sampled at the field scale, and at most loci for nine of the other 10 farm samples. Between three and 11 alleles were found per locus. Gene diversity (D = 1 - summation operator p(i)2) ranged from 0.088 to 0.760. Polymorphism occurred among individuals within and among fields, and farms. Some alleles were found in only one farm. On the basis of the alleles at all nine loci in the 211 sampled plants, a total of 92 (44%) different genotypes was identified. Clustering analysis using the unweighted pair group method with arithmetic averages (UPGMA) for the combined Oxon, Wilts and Leics samples did not cluster them into their respective farms. Similarly, a phenogram of samples from all 10 farms showed considerable mixing of individuals with respect to farm origins. Identification of genotypes on field plans showed evidence of both spatial localization and mixing. Previous reports have suggested that A. sterilis is strictly inbreeding with little intrapopulation variation at the genetic level. Our data reveal that A. sterilis exists as numerous separate and genetically different lines, which are maintained by inbreeding but which very occasionally outcross. Possible explanations for this pattern of high genetic diversity are discussed.

The development of multiplex simple sequence repeat (SSR) markers to complement distinctness, uniformity and stability testing of rape (Brassica napus L.) varieties.

To assess the potential of multiplex SSR markers for testing distinctness, uniformity and stability of rape (Brassica napus L.) varieties, we developed three multiplex SSR sets composed of five markers each. These were used to measure the extent of diversity within and between a set of ten varieties using a fluorescence-based semi-automated detection technology. Also, we evaluated the significance of any correlation between SSRs, pedigree and five of the morphological characters currently used for statutory distinctness, uniformity and stability testing of rape varieties. An assignment test was allowed to identify 99% of the plants examined, with the correct variety based on the analysis of 48 individual plants for each variety. Principal coordinate analysis confirmed that a high degree of separation between varieties could be achieved. Varieties were separated in three groups corresponding to winter, spring and forage types. These results suggested that it should be possible to select a set of markers for obtaining a suitable separation. Diversity within varieties varied considerably, according to the variety and the locus examined. No significant correlation was found between SSR and morphological data. However, genetic distances measured by SSRs were correlated to pedigree. These results suggested that SSRs could be used for pre-screening or grouping of existing and candidate varieties, allowing the number of varieties that need to be grown for comparison to be reduced. Multiplex SSR sets gave high-throughput reproducible results, thus reducing the costs of SSR assessment. Multiplex SSR sets are a promising way forward for complementing the current variety testing system in B. napus.