Report on short-term side effects of treatments with 177Lu- octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

Purpose: Treatment with the radiolabelled somatostatin analogue177Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to177Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Methods: Seven patients were treated with 7.4 GBq177Lu-octreotate and capecitabine (1650 mg/m2per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. Results: None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Conclusions: Treatment with the combination of177Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with177Lu-octreotate as single agent with regard to anti-tumour effects and side effects

Using Design Thinking for Co-Creating an Integrated Care Pathway Including Hospital at Home for Older Adults with an Acute Moderate-Severe Respiratory Infection in the Netherlands

Introduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated care is associated with unnecessary hospital referral and admission with potential iatrogenic harm. Therefore, we aimed to co-create a regional integrated care pathway (ICP), including a hospital at home journey. Developing the ICP: Tasked with using design thinking methodology, stakeholders from regional healthcare facilities, together with patient representatives, were assigned to different focus groups based on their expertise. The focus of each session was to co-create ideal patient journeys suitable for embedding in the ICP. Results: Based on these sessions, a regional cross-domain ICP was developed that comprises three patient journeys. The first journey included a hospital at home track, the second a tailored visit, with priority assessment, to regional emergency departments, and the third concerned referral to readily available nursing home ‘recovery-beds’ under the supervision of an elderly care medicine specialist. Conclusion: Using design thinking and involving end-users during the whole process, we created an ICP for community-dwelling frail older people with moderate-severe acute respiratory infections. This resulted in three realistic patient journeys, including a hospital at home track, which will be implemented and evaluated in the near future

Silver nanowires with optimized silica coating as versatile plasmonic resonators

Metal nanoparticles are the most frequently used nanostructures in plasmonics. However, besides nanoparticles, metal nanowires feature several advantages for applications. Their elongation offers a larger interaction volume, their resonances can reach higher quality factors, and their mode structure provides better coupling into integrated hybrid dielectric plasmonic circuits. It is crucial though, to control the distance of the wire to a supporting substrate, to another metal layer or to active materials with sub nanometer precision. A dielectric coating can be utilized for distance control, but it must not degrade the plasmonic properties. In this paper, we introduce a controlled synthesis and coating approach for silver nanowires to fulfill these demands. We synthesize and characterize silver nanowires of around 70 amp; 8201;nm in diameter. These nanowires are coated with nm sized silica shells using a modified Stöber method to achieve a homogeneous and smooth surface quality. We use transmission electron microscopy, dark field microscopy and electron energy loss spectroscopy to study morphology and plasmonic resonances of individual nanowires and quantify the influence of the silica coating. Thorough numerical simulations support the experimental findings showing that the coating does not deteriorate the plasmonic properties and thus introduce silver nanowires as usable building blocks for integrated hybrid plasmonic system

A self-interaction corrected pseudopotential scheme for magnetic and strongly-correlated systems

Local-spin-density functional calculations may be affected by severe errors when applied to the study of magnetic and strongly-correlated materials. Some of these faults can be traced back to the presence of the spurious self-interaction in the density functional. Since the application of a fully self-consistent self-interaction correction is highly demanding even for moderately large systems, we pursue a strategy of approximating the self-interaction corrected potential with a non-local, pseudopotential-like projector, first generated within the isolated atom and then updated during the self-consistent cycle in the crystal. This scheme, whose implementation is totally uncomplicated and particularly suited for the pseudopotental formalism, dramatically improves the LSDA results for a variety of compounds with a minimal increase of computing cost.Comment: 18 pages, 14 figure

Strong-correlation effects in Born effective charges

Large values of Born effective charges are generally considered as reliable indicators of the genuine tendency of an insulator towards ferroelectric instability. However, these quantities can be very much influenced by strong electron correlation and metallic behavior, which are not exclusive properties of ferroelectric materials. In this paper we compare the Born effective charges of some prototypical ferroelectrics with those of magnetic, non-ferroelectric compounds using a novel, self-interaction free methodology that improves on the local-density approximation description of the electronic properties. We show that the inclusion of strong-correlation effects systermatically reduces the size of the Born effective charges and the electron localization lengths. Furthermore we give an interpretation of the Born effective charges in terms of band energy structure and orbital occupations which can be used as a guideline to rationalize their values in the general case.Comment: 10 pages, 4 postscript figure

Emergent and robust ferromagnetic-insulating state in highly strained ferroelastic LaCoO3 thin films

Transition metal oxides are promising candidates for the next generation of spintronic devices due to their fascinating properties that can be effectively engineered by strain, defects, and microstructure. An excellent example can be found in ferroelastic LaCoO3 with paramagnetism in bulk. In contrast, unexpected ferromagnetism is observed in tensile-strained LaCoO3 films, however, its origin remains controversial. Here we simultaneously reveal the formation of ordered oxygen vacancies and previously unreported long-range suppression of CoO6 octahedral rotations throughout LaCoO3 films. Supported by density functional theory calculations, we find that the strong modification of Co 3d-O 2p hybridization associated with the increase of both Co-O-Co bond angle and Co-O bond length weakens the crystal-field splitting and facilitates an ordered high-spin state of Co ions, inducing an emergent ferromagnetic-insulating state. Our work provides unique insights into underlying mechanisms driving the ferromagnetic-insulating state in tensile-strained ferroelastic LaCoO3 films while suggesting potential applications toward low-power spintronic devices