The Use of Minipigs for Testing the Local Intranasal Toxicity of Fentanyl

The local intranasal toxicity of a nasal formulation of the opioid analgesic fentanyl was investigated in this  study. Minipigs were used as the experimental model. Fentanyl was administered using the formulation and  the device intended for human use. Doses of 400 μg fentanyl were administered 5 times daily to the minipigs  for 4 weeks. In addition, the spreading pattern of the formulation in the minipig nasal cavity was investigated  by applying a formulation containing methylene blue at necropsy. Results: The methylene blue spread to the middle parts of the endoturbinates. The No-Observed-Adverse-  Effect-Level (NOAEL) of intranasally administered fentanyl in minipigs was documented to be above 5 x  400 μg/day. After necropsy, no relevant treatment related macroscopic or microscopic findings were  observed, but minimal focal deciliation/degradation of the respiratory epithelium was seen in one animal.  In conclusion, intranasal administration of 400 μg fentanyl 5 times daily for a period of 4 weeks did not  cause any treatment related changes in the nasal cavity of the minipig.

Transition to adult care in Finnish adolescents with juvenile idiopathic arthritis

Objective The symptoms of juvenile idiopathic arthritis (JIA) and the necessity for continuous treatment may persist in adulthood. Therefore, patients with JIA need to be appropriately transferred to adult care. We aimed to analyse the timing of the patients' transition to adult care, and patients' self-management skills with the process and the quality of the transition. Method This study included 161 Finnish participants of the population-based Nordic JIA cohort who attended a 17 year follow-up appointment. Special attention was paid to the three groups: those referred by the paediatric rheumatology outpatient clinic to primary healthcare (PHC), those who were directly transferred to adult rheumatology care, and those who were later referred. Results A total of 136 patients (84%) were eligible to participate in the study, and 40% of them were directly transferred to an adult rheumatology clinic. Of the patients, 72% eventually ended up being referred to an adult rheumatology outpatient clinic. However, 16% of the patients in the PHC group had active disease during the study appointment and were referred to adult services after the study visit. Conclusion This study reveals the need to improve the transition process from paediatric care to adult care and to find the variables that can indicate the need for immediate transition. Although challenging, it is important to avoid treatment delay in adult patients with JIA who may have active disease but who do not have appropriate access to an adult rheumatological outpatient clinic.Peer reviewe

A retrospective observational study to determine baseline characteristics and early prescribing patterns for patients receiving Alirocumab in UK clinical practice

Background Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) and has been previously shown, in the phase III ODYSSEY clinical trial program, to provide significant lowering of lowdensity lipoprotein cholesterol (LDL-C) and reduction in risk of major adverse cardiovascular events. However, real-world evidence to date is limited. Objective The primary objective was to describe baseline characteristics, clinical history, and prior lipid-lowering therapy (LLT) use of patients initiated on alirocumab in UK clinical practice following publication of health technology appraisal (HTA) body recommendations. Secondary objectives included description of alirocumab use and lipid parameter outcomes over a 4-month follow-up period. Methods In this retrospective, single-arm, observational, multicenter study, data were collected for 150 patients initiated on alirocumab. Results Mean (standard deviation; SD) age of patients was 61.4 (10.5) years and baseline median (interquartile range; IQR) LDL-C level was 4.8 (4.2–5.8) mmol/l. Alirocumab use occurred predominantly in patients with heterozygous familial hypercholesterolemia (HeFH) (n = 100/150, 66%) and those with statin intolerance (n = 123/150, 82%). Most patients started on alirocumab 75 mg (n = 108/150 [72%]) and 35 (23.3%) were up-titrated to 150 mg. Clinically significant reductions in atherogenic lipid parameters were observed with alirocumab, including LDL-C (median [IQR] change from baseline, − 53.6% [− 62.9 to − 34.9], P < 0.001). Conclusion This study highlights the unmet need for additional LLT in patients with uncontrolled hyperlipidemia and demonstrates the clinical utility of alirocumab in early real-world practice, where dosing flexibility is an important attribute of this therapeutic option

High field level crossing studies on spin dimers in the low dimensional quantum spin system Na2_2T2_2(C2_2O4_4)3_3(H2_2O)2_2 with T=Ni,Co,Fe,Mn

In this paper we demonstrate the application of high magnetic fields to study the magnetic properties of low dimensional spin systems. We present a case study on the series of 2-leg spin-ladder compounds Na$_2$T$_2$(C$_2$O$_4$)$_3$(H$_2$O)$_2$ with T = Ni, Co, Fe and Mn. In all compounds the transition metal is in the $T^{2+}$ high spin configuation. The localized spin varies from S=1 to 3/2, 2 and 5/2 within this series. The magnetic properties were examined experimentally by magnetic susceptibility, pulsed high field magnetization and specific heat measurements. The data are analysed using a spin hamiltonian description. Although the transition metal ions form structurally a 2-leg ladder, an isolated dimer model consistently describes the observations very well. This behaviour can be understood in terms of the different coordination and superexchange angles of the oxalate ligands along the rungs and legs of the 2-leg spin ladder. All compounds exhibit magnetic field driven ground state changes which at very low temperatures lead to a multistep behaviour in the magnetization curves. In the Co and Fe compounds a strong axial anisotropy induced by the orbital magnetism leads to a nearly degenerate ground state and a strongly reduced critical field. We find a monotonous decrease of the intradimer magnetic exchange if the spin quantum number is increased

BN domains included into carbon nanotubes: role of interface

We present a density functional theory study on the shape and arrangement of small BN domains embedded into single-walled carbon nanotubes. We show a strong tendency for the BN hexagons formation at the simultaneous inclusion of B and N atoms within the walls of carbon nanotubes. The work emphasizes the importance of a correct description of the BN-C frontier. We suggest that BN-C interface will be formed preferentially with the participation of N-C bonds. Thus, we propose a new way of stabilizing the small BN inclusions through the formation of nitrogen terminated borders. The comparison between the obtained results and the available experimental data on formation of BN plackets within the single walled carbon nanotubes is presented. The mirror situation of inclusion of carbon plackets within single walled BN nanotubes is considered within the proposed formalism. Finally, we show that the inclusion of small BN plackets inside the CNTs strongly affects the electronic character of the initial systems, opening a band gap. The nitrogen excess in the BN plackets introduces donor states in the band gap and it might thus result in a promising way for n-doping single walled carbon nanotubes

Atomic Configuration of Nitrogen Doped Single-Walled Carbon Nanotubes

Having access to the chemical environment at the atomic level of a dopant in a nanostructure is crucial for the understanding of its properties. We have performed atomically-resolved electron energy-loss spectroscopy to detect individual nitrogen dopants in single-walled carbon nanotubes and compared with first principles calculations. We demonstrate that nitrogen doping occurs as single atoms in different bonding configurations: graphitic-like and pyrrolic-like substitutional nitrogen neighbouring local lattice distortion such as Stone-Thrower-Wales defects. The stability under the electron beam of these nanotubes has been studied in two extreme cases of nitrogen incorporation content and configuration. These findings provide key information for the applications of these nanostructures.Comment: 25 pages, 13 figure

Nitrogen doping of metallic single-walled carbon nanotubes: n-type conduction and dipole scattering

The charge transport properties of individual, metallic nitrogen doped, single-walled carbon nanotubes are investigated. It is demonstrated that n-type conduction can be achieved by nitrogen doping. Evidence was obtained by appealing to electric-field effect measurements at ambient condition. The observed temperature dependencies of the zero-bias conductance indicate a disordered electron system with electric-dipole scattering, caused mainly by the pyridine-type nitrogen atoms in the honeycomb lattice. These results illustrate the possibility of creating all-metallic molecular devices, in which the charge carrier type can be controlled.Comment: 16 page

Lattice dynamical study of optical modes in Tl2Mn2O7 and In2Mn2O7 pyrochlores

The Raman, IR and force field have been investigated for A2Mn2O7 (A= Tl, In) by means of a short-range force constant model which includes four stretching and four bending force constants. Unusual spectral and force field changes are observed and analyzed. The stretching force constant Mn-O and A-O, are found to be relatively higher than those of other pyrochlore oxides of the A2Mn2O7 family, while the remaining force constant values are significantly smaller, especially for Tl2Mn2O7. This trend may be due to strong hybridization of the Tl (6s) orbital with O (2p) and Mn (3d). The assignment of all the modes has been proposed and potential energy distribution is also reported. The evaluated frequencies are close to the available observed infrared and Raman frequencies, giving further support to the present assignments.Comment: To be published in PRB, 17 page

The effect of compressive strain on the Raman modes of the dry and hydrated BaCe0.8Y0.2O3 proton conductor

The BaCe0.8Y0.2O3-{\delta} proton conductor under hydration and under compressive strain has been analyzed with high pressure Raman spectroscopy and high pressure x-ray diffraction. The pressure dependent variation of the Ag and B2g bending modes from the O-Ce-O unit is suppressed when the proton conductor is hydrated, affecting directly the proton transfer by locally changing the electron density of the oxygen ions. Compressive strain causes a hardening of the Ce-O stretching bond. The activation barrier for proton conductivity is raised, in line with recent findings using high pressure and high temperature impedance spectroscopy. The increasing Raman frequency of the B1g and B3g modes thus implies that the phonons become hardened and increase the vibration energy in the a-c crystal plane upon compressive strain, whereas phonons are relaxed in the b-axis, and thus reveal softening of the Ag and B2g modes. Lattice toughening in the a-c crystal plane raises therefore a higher activation barrier for proton transfer and thus anisotropic conductivity. The experimental findings of the interaction of protons with the ceramic host lattice under external strain may provide a general guideline for yet to develop epitaxial strained proton conducting thin film systems with high proton mobility and low activation energy