Real-life use of delamanid: results from the European post-authorisation safety study.

BACKGROUND: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). METHODS: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. RESULTS: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. CONCLUSION: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.

CONTEXTE: Une étude de sécurité post-autorisation (PASS) sur le délamanide (DLM) a été menée dans le cadre d'un engagement post-approbation auprès de l'Agence européenne des médicaments. L'objectif de cette étude était d'évaluer l'utilisation du DLM dans un contexte réel, son innocuité et les résultats du traitement chez les patients atteints de TB multirésistante (MDR-TB). MÉTHODES: Il s'agissait d'une étude prospective, multicentrique et non interventionnelle menée dans l'Union européenne. La sélection du schéma thérapeutique de la MDR-TB et le suivi des patients ont été effectués conformément aux pratiques médicales existantes. Les données sur l'utilisation du DLM, les effets indésirables connexes et les résultats du traitement ont été recueillies jusqu'à 30 mois après la première dose de DLM. Des statistiques sommaires descriptives ont été utilisées pour les variables continues et catégorielles. RÉSULTATS: Sur 86 patients, un avait une TB extrapulmonaire. Les deux tiers des patients ont été traités avec du DLM pendant plus de 24 semaines. L'effet indésirable le plus fréquent du DLM était l'allongement de l'intervalle QT. Une résistance au DLM a été détectée chez un patient pendant le traitement. Le taux de réussite du traitement était de 77%. CONCLUSION: Aucun nouveau problème de sécurité n'a été révélé, y compris chez les patients traités par le DLM pendant plus de 24 semaines. Les allongements de l'intervalle QT ont été bien gérés et n'ont pas entraîné d'effets cardiaques cliniquement significatifs. Les résultats du traitement étaient conformes à l'objectif de l'OMS pour l'Europe.

Relative rates of cancers and deaths in Australian communities with PFAS environmental contamination associated with firefighting foams: A cohort study using linked data.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that are potentially harmful to health. We examined if rates of selected cancers and causes of deaths were elevated in three Australian communities with local environmental contamination caused by firefighting foams containing PFAS. The affected Australian communities were Katherine in Northern Territory, Oakey in Queensland and Williamtown in New South Wales. METHODS: All residents identified in the Medicare Enrolment File (1983-2019)-a consumer directory for Australia's universal healthcare-who ever lived in an exposure area (Katherine, Oakey and Williamtown), and a sample of those who ever lived in selected comparison areas, were linked to the Australian Cancer Database (1982-2017) and National Death Index (1980-2019). We estimated standardised incidence ratios (SIRs) for 23 cancer outcomes, four causes of death and three control outcomes, adjusting for sex, age and calendar time of diagnosis. FINDINGS: We observed higher rates of prostate cancer (SIR=1·76, 95 % confidence interval (CI) 1·36-2·24) in Katherine; laryngeal cancer (SIR=2·71, 95 % CI 1·30-4·98), kidney cancer (SIR=1·82, 95 % CI 1·04-2·96) and coronary heart disease (CHD) mortality (SIR=1·81, 95 % CI 1·46-2·33) in Oakey; and lung cancer (SIR=1·83, 95 % CI 1·39-2·38) and CHD mortality (SIR=1·22, 95 % CI 1·01-1·47) in Williamtown. We also saw elevated SIRs for control outcomes. SIRs for all other outcomes and overall cancer were similar across exposure and comparison areas. INTERPRETATION: There was limited evidence to support an association between living in a PFAS exposure area and risks of cancers or cause-specific deaths.

Fluctuations and pairing in Fe-based superconductors: light scattering experiments.

Inelastic scattering of visible light (Raman effect) offers a window into properties of correlated metals such as spin, electron and lattice dynamics as well as their mutual interactions. In this review we focus on electronic and spin excitations in Fe-based pnictides and chalcogenides, in particular but not exclusively superconductors. After a general introduction to the basic theory including the selection rules for the various scattering processes we provide an overview over the major experimental results. In the superconducting state below the transition temperature T c the pair-breaking effect can be observed, and the gap energies may be derived and associated with the gaps on the electron and hole bands. In spite of the similarities of the overall band structures the results are strongly dependent on the family and may even change qualitatively within one family. In some of the compounds strong collective modes appear below T c. In Ba1-x K x Fe2As2, which has the most isotropic gap of all Fe-based superconductors, there are indications that these modes are exciton-like states appearing in the presence of a hierarchy of pairing tendencies. The strong in-gap modes observed in Co-doped NaFeAs are interpreted in terms of quadrupolar orbital excitations which become undamped in the superconducting state. The doping dependence of the scattering intensity in Ba[Formula: see text] is associated with a nematic resonance above a quantum critical point and interpreted in terms of a critical enhancement at the maximal T c. In the normal state the response from particle-hole excitations reflects the resistivity. In addition, there are strongly temperature-dependent contributions from presumably critical fluctuations in the energy range of k B T which can be compared to the elastic properties. Currently it is not settled whether the fluctuations observed by light scattering are related to spin or charge. Another controversy relates to putative two-magnon excitations, typically in the energy range below 0.5 eV. Whereas this response presumably originates from charge excitations in most of the Fe-based compounds theory and experiment suggest that the excitations in the 60 meV range in FeSe stem from localized spins in a nearly frustrated system.

Influence of chemical fixation process on primary mesenchymal stem cells evidenced by Raman spectroscopy.

In investigation of (patho)physiological processes, cells represent frequently used analyte as an exceptional source of information. However, spectroscopic analysis of live cells is still very seldom in clinics, as well as in research studies. Among others, the reasons are long acquisition time during which autolysis process is activated, necessity of specified technical equipment, and inability to perform analysis in a moment of sample preparation. Hence, an optimal method of preserving cells in the existing state is of extreme importance, having in mind that selection of fixative is cell lineage dependent. In this study, two commonly used chemical fixatives, formaldehyde and methanol, are used for preserving primary mesenchymal stem cells extracted from periodontal ligament, which are valuable cell source for reconstructive dentistry. By means of Raman spectroscopy, cell samples were probed and the impact of these fixatives on their Raman response was analyzed and compared. Different chemical mechanisms are the core processes of formaldehyde and methanol fixation and certain Raman bands are shifted and/or of changed intensity when Raman spectra of cells fixed in that manner are compared. In order to get clearer picture, comprehensive statistical analysis was performed.

Probing primary mesenchymal stem cells differentiation status by micro-Raman spectroscopy.

We have employed micro-Raman spectroscopy to get insight into intrinsic biomolecular profile of individual mesenchymal stem cell isolated from periodontal ligament. Furthermore, these cells were stimulated towards adipogenic, chondrogenic, and osteogenic lineages and their status of differentiation was assessed using micro-Raman spectroscopy. In both cases, glass coverslips were used as substrates, due to their wide availability and cost effectiveness. In all sample groups, the same type of behavior was observed, manifested as changes in Raman spectra: the increase of relative intensity of protein/lipid bands and decrease of nucleic acid bands. Comprehensive statistical analysis in the form of principal component analysis was performed, which revealed noticeable grouping of cells with the similar features. Despite the inhomogeneity of primary stem cells and their differentiated lineages, we demonstrated that micro-Raman spectroscopy is sufficient for distinguishing cells' status, which can be valuable for medical and clinical application.

Raman spectroscopy of K x Co2-y Se2 single crystals near the ferromagnet-paramagnet transition.

Polarized Raman scattering spectra of the K x Co2-y Se2 single crystals reveal the presence of two phonon modes, assigned as of the A 1g and B 1g symmetry. The absence of additional modes excludes the possibility of vacancy ordering, unlike in K x Fe2-y Se2. The ferromagnetic (FM) phase transition at [Formula: see text] K leaves a clear fingerprint on the temperature dependence of the Raman mode energy and linewidth. For [Formula: see text] the temperature dependence looks conventional, driven by the thermal expansion and anharmonicity. The Raman modes are rather broad due to the electron-phonon coupling increased by the disorder and spin fluctuation effects. In the FM phase the phonon frequency of both modes increases, while an opposite trend is seen in their linewidth: the A 1g mode narrows in the FM phase, whereas the B 1g mode broadens. We argue that the large asymmetry and anomalous frequency shift of the B 1g mode is due to the coupling of spin fluctuations and vibration. Our density functional theory (DFT) calculations for the phonon frequencies agree rather well with the Raman measurements, with some discrepancy being expected since the DFT calculations neglect the spin fluctuations.

Evidence of superconductivity-induced phonon spectra renormalization in alkali-doped iron selenides.

Polarized Raman scattering spectra of superconducting K(x)Fe(2-y)Se2 and non-superconducting K0.8Fe1.8Co0.2Se2 single crystals were measured in the temperature range from 10 K up to 300 K. Two Raman active modes from the I4/mmm phase and seven from the I4/m phase are observed in the frequency range from 150 to 325 cm(-1) in both compounds, suggesting that the K0.8Fe1.8Co0.2Se2 single crystal also has a two-phase nature. The temperature dependence of the Raman mode energy is analyzed in terms of lattice thermal expansion and phonon-phonon interaction. The temperature dependence of the Raman mode linewidth is dominated by temperature-induced anharmonic effects. It is shown that the change in Raman mode energy with temperature is dominantly driven by thermal expansion of the crystal lattice. An abrupt change of the A1g mode energy near T(C) was observed in K(x)Fe(2-y) Se2, whereas it is absent in non-superconducting K0.8Fe1.8Co0.2Se2. Phonon energy hardening at low temperatures in the superconducting sample is a consequence of superconductivity-induced redistribution of the electronic states below the critical temperature.

Intermolecular and low-frequency intramolecular Raman scattering study of racemic ibuprofen.

We report the low-temperature Raman scattering study of racemic ibuprofen. Detailed analysis of the racemic ibuprofen crystal symmetry, related to the vibrational properties of the system, has been presented. The first principle calculations of a single ibuprofen molecule dynamical properties are compered with experimental data. Nineteen, out of 26 modes expected for the spectral region below 200cm(-1), have been observed.

Lattice dynamics of FeSb2.

The lattice dynamics of FeSb(2) is investigated by first-principles density functional theory calculations and Raman spectroscopy. All Raman- and infrared-active phonon modes are properly assigned. The calculated and measured phonon energies are in good agreement. We have observed strong mixing of the A(g) symmetry modes, with the intensity exchange in the temperature range 210 and 260 K. The A(g) mode repulsion increases by doping FeSb(2) with Co, with no signatures of the electron-phonon interaction for these modes.

Phonon properties of CoSb2 single crystals.

The phonon properties of CoSb(2) have been investigated by Raman scattering spectroscopy and lattice dynamics calculations. Sixteen out of eighteen Raman active modes predicted by factor-group analysis are experimentally observed and assigned. The calculated and measured phonon energies at the Γ point are in very good agreement. The temperature dependence of the A(g) symmetry modes is well represented by phonon-phonon interactions without contribution from any other phonon or electron related interactions.

Studies on the hematologic effects of long-term, low-dose microwave exposure.

Hematologic and morphologic investigations were carried out in order to discover changes during and after prolonged exposure to microwave radiation. A 12-cm wavelength CW microwave generator was used as a source of radiation and the mean power density was 5 mW/cm2. The rats were exposed to microwaves for a period of 90 d for 1 h/d. Before, during, and after the irradiation period, hematologic examinations were carried out. The histological examinations of various organs and tissues of irradiated rats were carried out after the experimental period. No significant difference in any of the observed biological parameters was detected in experimental animals in comparison with control. It was concluded that these results indicate that it is unlikely that prolonged microwave exposure to low-intensity (around 5 mW/cm2) will cause marked changes in the peripheral blood counts of the irradiated organism.