A double stranded DNA fragment shows a significant decrease in double-helix stability after binding of monofunctional platinum amine compounds

Metals in Catalysis, Biomimetics & Inorganic Material

Frame dragging, vorticity and electromagnetic fields in axially symmetric stationary spacetimes

We present a general study about the relation between the vorticity tensor and the Poynting vector of the electromagnetic field for axially symmetric stationary electrovacuum metrics. The obtained expressions allow to understand the role of the Poynting vector in the dragging of inertial frames. The particular case of the rotating massive charged magnetic dipole is analyzed in detail. In addition, the electric and magnetic parts of the Weyl tensor are calculated and the link between the later and the vorticity is established. Then we show that, in the vacuum case, the necessary and sufficient condition for the vanishing of the magnetic part is that the spacetime be static.Comment: 16 pages Latex. Some minor changes in the text and typos correcte

Isotropic singularity in inhomogeneous brane cosmological models

We discuss the asymptotic dynamical evolution of spatially inhomogeneous brane-world cosmological models close to the initial singularity. By introducing suitable scale-invariant dependent variables and a suitable gauge, we write the evolution equations of the spatially inhomogeneous $G_{2}$ brane cosmological models with one spatial degree of freedom as a system of autonomous first-order partial differential equations. We study the system numerically, and we find that there always exists an initial singularity, which is characterized by the fact that spatial derivatives are dynamically negligible. More importantly, from the numerical analysis we conclude that there is an initial isotropic singularity in all of these spatially inhomogeneous brane cosmologies for a range of parameter values which include the physically important cases of radiation and a scalar field source. The numerical results are supported by a qualitative dynamical analysis and a calculation of the past asymptotic decay rates. Although the analysis is local in nature, the numerics indicates that the singularity is isotropic for all relevant initial conditions. Therefore this analysis, and a preliminary investigation of general inhomogeneous ($G_0$) models, indicates that it is plausible that the initial singularity is isotropic in spatially inhomogeneous brane-world cosmological models and consequently that brane cosmology naturally gives rise to a set of initial data that provide the conditions for inflation to subsequently take place.Comment: 32 pages with 8 pictures. submitted to Class. Quant. Gra

Pharmacological Modulation of Dopamine Receptor D2-Mediated Transmission Alters the Metabolic Phenotype of Diet Induced Obese and Diet Resistant C57Bl6 Mice

High fat feeding induces a variety of obese and lean phenotypes in inbred rodents. Compared to Diet Resistant (DR) rodents, Diet Induced Obese (DIO) rodents are insulin resistant and have a reduced dopamine receptor D2 (DRD2) mediated tone. We hypothesized that this differing dopaminergic tone contributes to the distinct metabolic profiles of these animals. C57Bl6 mice were classified as DIO or DR based on their weight gain during 10 weeks of high fat feeding. Subsequently DIO mice were treated with the DRD2 agonist bromocriptine and DR mice with the DRD2 antagonist haloperidol for 2 weeks. Compared to DR mice, the bodyweight of DIO mice was higher and their insulin sensitivity decreased. Haloperidol treatment reduced the voluntary activity and energy expenditure of DR mice and induced insulin resistance in these mice. Conversely, bromocriptine treatment tended to reduce bodyweight and voluntary activity, and reinforce insulin action in DIO mice. These results show that DRD2 activation partly redirects high fat diet induced metabolic anomalies in obesity-prone mice. Conversely, blocking DRD2 induces an adverse metabolic profile in mice that are inherently resistant to the deleterious effects of high fat food. This suggests that dopaminergic neurotransmission is involved in the control of metabolic phenotype

Shear free solutions in General Relativity Theory

The Goldberg-Sachs theorem is an exact result on shear-free null geodesics in a vacuum spacetime. It is compared and contrasted with an exact result for pressure-free matter: shear-free flows cannot both expand and rotate. In both cases, the shear-free condition restricts the way distant matter can influence the local gravitational field. This leads to intriguing discontinuities in the relation of the General Relativity solutions to Newtonian solutions in the timelike case, and of the full theory to the linearised theory in the null case. It is a pleasure to dedicate this paper to Josh Goldberg.Comment: 17 pages, no figures. For GRG special issue in honor of Josh Goldber

Older patients' experiences with and attitudes towards an oncogeriatric pathway: A qualitative study

INTRODUCTION: To tailor treatment for older patients with cancer, an oncogeriatric care pathway has been developed in the Leiden University Medical Center. In this care pathway a geriatric assessment is performed and preferences concerning cancer treatment options are discussed. This study aimed to explore patient experiences with and attitudes towards this pathway.MATERIALS AND METHODS: A qualitative study was performed using an exploratory descriptive approach. Individual face-to-face semi-structured interviews were conducted with older patients (≥70 years) who had followed the oncogeriatric care pathway in the six months prior to the interview. The interviews were audio-recorded and transcribed verbatim. The transcripts were analyzed inductively using thematic analysis.RESULTS: After interviews with 14 patients with a median age of 80 years, three main themes were identified. (1) Patients' positive experiences with the oncogeriatric pathway: Patients appreciated the attitudes of the healthcare professionals and felt heard and understood. (2) Unmet information needs about the oncogeriatric care pathway: Patients experienced a lack of information about the aim and process. (3) Incomplete information for decision-making: Most patients were satisfied with decision-making process. However, treatment decisions had often been made before oncogeriatric consultation. No explicit naming and explaining of different available treatment options had been provided, nor had risk of physical or cognitive decline during and after treatment been addressed.DISCUSSION: Older patients had predominately positive attitudes towards the oncogeriatric care pathway. Most patients were satisfied with the treatment decision. Providing information on the aim and process of the care pathway, available treatment options, and treatment-related risks of cognitive and physical decline may further improve the oncogeriatric care pathway and the decision-making process.</p

Older patients' experiences with and attitudes towards an oncogeriatric pathway: A qualitative study

INTRODUCTION: To tailor treatment for older patients with cancer, an oncogeriatric care pathway has been developed in the Leiden University Medical Center. In this care pathway a geriatric assessment is performed and preferences concerning cancer treatment options are discussed. This study aimed to explore patient experiences with and attitudes towards this pathway.MATERIALS AND METHODS: A qualitative study was performed using an exploratory descriptive approach. Individual face-to-face semi-structured interviews were conducted with older patients (≥70 years) who had followed the oncogeriatric care pathway in the six months prior to the interview. The interviews were audio-recorded and transcribed verbatim. The transcripts were analyzed inductively using thematic analysis.RESULTS: After interviews with 14 patients with a median age of 80 years, three main themes were identified. (1) Patients' positive experiences with the oncogeriatric pathway: Patients appreciated the attitudes of the healthcare professionals and felt heard and understood. (2) Unmet information needs about the oncogeriatric care pathway: Patients experienced a lack of information about the aim and process. (3) Incomplete information for decision-making: Most patients were satisfied with decision-making process. However, treatment decisions had often been made before oncogeriatric consultation. No explicit naming and explaining of different available treatment options had been provided, nor had risk of physical or cognitive decline during and after treatment been addressed.DISCUSSION: Older patients had predominately positive attitudes towards the oncogeriatric care pathway. Most patients were satisfied with the treatment decision. Providing information on the aim and process of the care pathway, available treatment options, and treatment-related risks of cognitive and physical decline may further improve the oncogeriatric care pathway and the decision-making process.</p

Combined osimertinib, dabrafenib and trametinib treatment for advanced non-small-cell lung cancer patients with an osimertinib-induced BRAF V600E mutation

INTRODUCTION: Previous studies have reported an acquiredBRAF V600E mutation as a potential resistance mechanism to osimertinib treatment in advanced NSCLC patients with an activating mutation in EGFR. However, the therapeutic effect of combining dabrafenib and trametinib with osimertinib remains unclear. Here we report treatment efficacy in two cases with acquired BRAF V600E mutations. METHODS: Two patients with anEGFR exon 19 deletion and a T790 M mutation, both treated with osimertinib, acquired a BRAF V600E mutation at disease progression. Following the recommendation of the molecular tumor board, a concurrent combination of dabrafenib and trametinib plus osimertinib was administered. RESULTS: Because of toxicity, one patient ultimately received a reduced dose of dabrafenib and trametinib combined with a normal dose of osimertinib. Clinical response in this patient lasted for 13.4 months. Re-biopsy upon tumor progression revealed loss ofBRAF V600E and emergence of EGFR C797S. The other patient, treated with full doses of the combined therapy, had progression with metastases in lung and brain one month after starting therapy. CONCLUSION: BRAF V600E may be a resistance mechanism induced by osimertinib in EGFR-mutated advanced NSCLC. Combined treatment using dabrafenib/trametinib concurrently with osimertinib needs to be explored for osimertinib-induced BRAF V600E mutation

Actionability of on-target ALK Resistance Mutations in Patients With Non-Small Cell Lung Cancer:Local Experience and Review of the Literature

Introduction Non-small cell lung cancer (NSCLC) patients with Anaplastic Lymphoma Kinase (ALK) gene fusions respond well to ALK inhibitors but commonly develop on-target resistance mutations. The objective of this study is to collect clinical evidence for subsequent treatment with ALK inhibitors. Patients and methods Local experience with on-target ALK resistance mutations and review of the literature identified 387 patients with ALK inhibitor resistance mutations. Clinical benefit of mutation-inhibitor combinations was assessed based on reported response, progression-free survival and duration of treatment. Furthermore, this clinical evidence was compared to previously reported in vitro sensitivity of mutations to the inhibitors. Results Of the pooled population of 387 patients in this analysis, 239 (62%) received at least one additional line of ALK inhibition after developing on-target resistance to ALK inhibitor therapy. Clinical benefit was reported for 177 (68%) patients, but differed for each mutation-inhibitor combination. Agreement between in vitro predicted sensitivity of six published models and observed clinical benefit ranged from 64 to 87%. The observed clinical evidence for highest probability of response in the context of specific on-target ALK inhibitor resistance mutations is presented. Conclusion Molecular diagnostics performed on tissue samples that are refractive to ALK inhibitor therapy can reveal new options for targeted therapy for NSCLC patients. Our comprehensive overview of clinical evidence of drug actionability of ALK on-target resistance mechanisms may serve as a practical guide to select the most optimal drug for individual patients

Energetics of the Einstein-Rosen spacetime

A study covering some aspects of the Einstein--Rosen metric is presented. The electric and magnetic parts of the Weyl tensor are calculated. It is shown that there are no purely magnetic E--R spacetimes, and also that a purely electric E--R spacetime is necessarily static. The geodesics equations are found and circular ones are analyzed in detail. The super--Poynting and the ``Lagrangian'' Poynting vectors are calculated and their expressions are found for two specific examples. It is shown that for a pulse--type solution, both expressions describe an inward radially directed flow of energy, far behind the wave front. The physical significance of such an effect is discussed.Comment: 19 pages Latex.References added and updated.To appear in Int.J.Theor.Phy