ObjectivesTo date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease.MethodsIn this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG4-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68Ga-FAP inhibitor (FAPI)-04), 18F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, 18F-FDG and 68Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data.ResultsUsing combination of 68Ga-FAPI-04 and 18F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG4+ cells in histology, while 68Ga-FAPI-04 PET positive lesions showed abundant activated fibroblasts expressing FAP according to results from RNA-sequencing of activated fibroblasts. The responsiveness of fibrotic lesions to anti-inflammatory treatment was far less pronounced than that of inflammatory lesions.ConclusionFAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG4-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG4-related disease, as subtypes dominated by fibrosis may require different approaches to control disease progression, for example, specific antifibrotic agents rather than broad spectrum anti-inflammatory treatments such as glucocorticoids.
Low temperature fuel cells are clean, effective alternative fuel conversion technology. Oxygen reduction reaction (ORR) at the fuel cell cathode has required Pt as the electrocatalyst for high activity and selectivity of the four-electron reaction pathway. Targeting a less expensive, earth abundant alternative, we have developed the synthesis of cobalt phosphide (Co2P) nanorods for ORR. Characterization techniques that include total X-ray scattering and extended X-ray absorption fine structure revealed a deviation of the nanorods from bulk crystal structure with a contraction along the b orthorhombic lattice parameter. The carbon supported nanorods have comparable activity but are remarkably more stable than conventional Pt catalysts for the oxygen reduction reaction in alkaline environments.
The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.
Structural defects and their dynamics play an important role in controlling the behavior of phase-change materials (PCM) used in low-power nonvolatile memory devices. However, not much is known about the influence of disorder on the electronic properties of crystalline PCM prior to a structural phase-change. Here, we show that the application of voltage pulses to single-crystalline GeTe nanowire memory devices introduces structural disorder in the form of dislocations and antiphase boundaries (APB). The dynamic evolution and pile-up of APBs increases disorder at a local region of the nanowire, which electronically transforms it from a metal to a dirty metal to an insulator, while still retaining single-crystalline long-range order. We also observe that close to this metal-insulator transition, precise control over the applied voltage is required to create an insulating state; otherwise the system ends up in a more disordered amorphous phase suggesting the role of electronic instabilities during the structural phase-change.
We demonstrate the utility of optical second harmonic generation (SHG) polarimetry to perform structural characterization of noncentrosymmetric, single-crystalline II-VI semiconducting nanowires, nanobelts, and nanoflakes. By analyzing anisotropic SHG polarimetric patterns, we distinguish between wurtzite and zincblende II-VI semiconducting crystal structures and determine their growth orientation. The crystallography of these nanostructures was then confirmed via transmission electron microscopy measurements performed on the same system. In addition, we show that some intrinsic material properties such as nonlinear coefficients and geometry-dependent optical in-coupling coefficients can also be determined from the SHG experiments in WZ nanobelts. The ability to perform SHG-based structural characterization and crystallographic study of II-VI semiconducting single-crystalline nanomaterials will be useful to correlate structure-property relationships of nanodevices on which transmission electron microscopy measurements cannot be typically performed.
Oxygen vacancy formation, migration, and subsequent agglomeration into conductive filaments in transition metal oxides under applied electric field is widely believed to be responsible for electroforming in resistive memory devices, although direct evidence of such a pathway is lacking. Here, by utilizing strong metal-support interaction (SMSI) between Pt and TiO2, we observe via transmission electron microscopy the electroforming event in lateral Pt/TiO2/Pt devices where the atomic Pt from the electrode itself acts as a tracer for the propagating oxygen vacancy front. SMSI, which originates from the d-orbital overlap between Pt atom and the reduced cation of the insulating oxide in the vicinity of oxygen vacancies, was optimized by fabricating nanoscale devices causing Pt atom migration tracking the moving oxygen vacancy front from the anode to cathode during electroforming. Experiments performed in different oxidizing and reducing conditions, which tune SMSI in the Pt-TiO2 system, further confirmed the role of oxygen vacancies during electroforming. These observations also demonstrate that the noble metal electrode may not be as inert as previously assumed.
BackgroundHead preservation is the mainstay of management in younger patients with neglected or ununited intracapsular fracture neck of femur. Very few reports have dealt with the results of valgus intertrochanteric osteotomy and fixation with dynamic hip screw in such cases. In this prospective study, we have tried to evaluate the role of valgus osteotomy and fixation with dynamic hip screw and 120° double angle barrel plate in neglected or ununited intracapsular fracture neck of femur in patients below 60 years of age and whose time since injury is equal to or more than 3 weeks.Materials and methodsWe treated 16 such cases with valgus intertrochanteric osteotomy and fixation achieved with dynamic hip screw and 120° double angle barrel plate, with mean age of 36.4 years. The cases were evaluated radiologically and clinically at a mean of 19 months.ResultsIn 14 of the 16 patients, the fracture went on to satisfactory union after an average of 14.7 weeks (10–26.7 weeks). The average Harris hip score increased from 66.6 points (range 55–75 points) before surgery to 88 points (range 75–95 points). All the patients with united fractures were able to sit cross-legged, squat and do one-leg stance. Pain and limitation of motion improved remarkably. Two patients had unfavourable outcome; both had cut-through of the implant, out of the head.ConclusionsValgus intertrochanteric osteotomy is a very cheap and effective procedure to achieve union in neglected and ununited fracture neck femur in young patients. We propose fixation with dynamic hip screw and 120° double angle barrel plate as it provides additional compression and, with valgus osteotomy, improved stability of internal fixation, with few complications.
By integrating silicon nanowires (∼150 nm diameter, 20 μm length) with an Ω-shaped plasmonic nanocavity, we are able to generate broadband visible luminescence, which is induced by high order hybrid nanocavity-surface plasmon modes. The nature of this super bandgap emission is explored via photoluminescence spectroscopy studies performed with variable laser excitation energies (1.959 to 2.708 eV) and finite difference time domain simulations. Furthermore, temperature-dependent photoluminescence spectroscopy shows that the observed emission corresponds to radiative recombination of unthermalized (hot) carriers as opposed to a resonant Raman process.
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