Local uterine Ang-(1-7) infusion augments the expression of cannabinoid receptors and differentially alters endocannabinoid metabolizing enzymes in the decidualized uterus of pseudopregnant rats

Background Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1–7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation. We determined the effects of intra-uterine angiotensin-(1–7) [Ang-(1–7)] (24 microg/kg/h) or vehicle given into the left uterine horn on the ECs in the decidualized uterus. Methods Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment and decidualization was induced by a bolus of oil injected into the left horn; the right horn served as a control. Results Decidualization increased endometrial permeability (3.1+/−0.2 vs. 7.1+/−0.5 uterus/muscle of cpm of (125)I-BSA, p \u3c 0.0001). VEGF mRNA was increased by the decidualization (1.4-fold, p \u3c 0.05) and by Ang-(1–7) (2.0-fold, p \u3c 0.001). CB1R mRNA was reduced by decidualization (2.7-fold, p \u3c 0.001), but increased by Ang-(1–7) (1.9-fold, p \u3c 0.05). CB2R mRNA was increased by decidualization (4-fold, p \u3c 0.05) and by Ang-(1–7) (2.4-fold, p \u3c 0.001). The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (7.8 fold, p \u3c 0.001) and unchanged by Ang-(1–7) (p \u3e 0.05), whereas the enzyme metabolizing 2-arachidonoylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (p \u3e 0.05) and increased by Ang-(1–7) (1.7 fold, p \u3c 0.001). Conclusions These findings report for the first time that Ang-(1–7) augments the expression of CB1R, CB2R and MAGL in the decidualized uterus and thus may interfere with the early events of decidualization

Reorientation Transition in Single-Domain (Ga,Mn)As

We demonstrate that the interplay of in-plane biaxial and uniaxial anisotropy fields in (Ga,Mn)As results in a magnetization reorientation transition and an anisotropic AC susceptibility which is fully consistent with a simple single domain model. The uniaxial and biaxial anisotropy constants vary respectively as the square and fourth power of the spontaneous magnetization across the whole temperature range up to T_C. The weakening of the anisotropy at the transition may be of technological importance for applications involving thermally-assisted magnetization switching.Comment: 4 pages, 4 figure

Mn Interstitial Diffusion in (Ga,Mn)As

We present a combined theoretical and experimental study of the ferromagnetic semiconductor (Ga,Mn)As which explains the remarkably large changes observed on low temperature annealing. Careful control of the annealing conditions allows us to obtain samples with ferromagnetic transition temperatures up to 159 K. Ab initio calculations, and resistivity measurements during annealing, show that the observed changes are due to out-diffusion of Mn interstitials towards the surface, governed by an energy barrier of about 0.7-0.8 eV. The Mn interstitial is a double donor resulting in compensation of charge carriers and suppression of ferromagnetism. Electric fields induced by high concentrations of substitutional Mn acceptors have a significant effect on the diffusion.Comment: 5 pages, 4 figures, submitted to Physical Review Letter

Universal time-evolution of a Rydberg lattice gas with perfect blockade

We investigate the dynamics of a strongly interacting spin system that is motivated by current experimental realizations of strongly interacting Rydberg gases in lattices. In particular we are interested in the temporal evolution of quantities such as the density of Rydberg atoms and density-density correlations when the system is initialized in a fully polarized state without Rydberg excitations. We show that in the thermodynamic limit the expectation values of these observables converge at least logarithmically to universal functions and outline a method to obtain these functions. We prove that a finite one-dimensional system follows this universal behavior up to a given time. The length of this universal time period depends on the actual system size. This shows that already the study of small systems allows to make precise predictions about the thermodynamic limit provided that the observation time is sufficiently short. We discuss this for various observables and for systems with different dimensions, interaction ranges and boundary conditions.Comment: 16 pages, 3 figure

Search For Hole Mediated Ferromagnetism In Cubic (Ga,Mn)N

Results of magnetisation measurements on p-type zincblende-(Ga,Mn)N are reported. In addition to a small high temperature ferromagnetic signal, we detect ferromagnetic correlation among the remaining Mn ions, which we assign to the onset of hole-mediated ferromagnetism in (Ga,Mn)N.Comment: 2 pages, 1 figure, proc. ICPS 27, Flagstaff '0

Control of Coercivities in (Ga,Mn)As Thin Films by Small Concentrations of MnAs Nanoclusters

We demonstrate that low concentrations of a secondary magnetic phase in (Ga,Mn)As thin films can enhance the coercivity by factors up to ~100 without significantly degrading the Curie temperature or saturation magnetisation. Magnetic measurements indicate that the secondary phase consists of MnAs nanoclusters, of average size ~7nm. This approach to controlling the coercivity while maintaining high Curie temperature, may be important for realizing ferromagnetic semiconductor based devices.Comment: 8 pages,4 figures. accepted for publication in Appl. Phys. Let

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology