The expression of PD-L1 in salivary gland carcinomas

Objective was to analyze the role of PD-L1 and its relation to demographic, patho-clinical and outcome parameters in salivary gland carcinoma (SGC) patients. Patients treated for salivary gland carcinomas between 1994 and 2010 were included. A retrospective chart review for baseline characteristics, pathohistological, clinical and outcome data was performed. Immunohistochemistry for PD-L1 was performed using tissue microarrays. PD-L1 expression was assessed in tumor cells and tumor-infiltrating immune cells (TIIC) and statistical analysis with regard to baseline and outcome data was performed. Expression of PD-L1 (by means ≥1% of the cells with PD-L1 positivity) was present in the salivary gland carcinoma cells of 17%, in the TIIC of 20% and in both tumor cells and TIIC of 10% the patients. PD-L1 expression in tumor cells and both tumor cells and TIIC was related to tumor grading (p = 0.035 and p = 0.031, respectively). A trend towards higher grading was also seen for PD-L1 expression in TIICs (p = 0.058). Patients with salivary duct carcinomas and PD-L1 expressing TIICs showed a significantly worse DFS and OS (p = 0.022 and p = 0.003, respectively), those with both tumor cells and TIIC expressing PD-L1 a significantly worse DFS (p = 0.030). PD-L1 expression is present in 17% and 20% of salivary gland carcinoma cells and TIIC. Ten percent of the patient showed a PD-L1 positivity in both tumor cells and TIIC. This is related to high tumor grading and therefore might be a negative prognostic factor

Osteopathology induced by bisphosphonates and dental implants: clinical observations

Objectives: Although there are many reports about risk factors for the development of BP-associated osteonecrosis of the jaws, the role of dental implants as a local risk factor is still discussed, especially in patients with oral BP treatment. Until now, a few case reports and surveys display a possible minor risk in patients with oral BP therapy, whereas the avoidance of implant placement is generally accepted in patients with intravenous BP therapy. Patient and methods: In this study, the cases of 14 patients with osteonecrosis of the jaws in association with BP therapy and dental implant placement were analyzed carefully with a detailed literature review. Results: Of 14 patients, nine had underlying malignant disease and five patients had osteoporosis. In ten patients, implants were placed either in the posterior mandible or maxilla; the mean interval between implant insertion and disease onset was 20.9 months. Pain (n12) and signs of infection (n10) were the most common symptoms. Histologically, signs of infection were found in nine of 11 analyzed patients with presence of Actinomyces in six patients. Two patients turned out to have infiltration of underlying malignant disease. Conclusions: Posteriorly placed implants seem to be of higher risk of development of osteonecrosis of the jaws. Not only the implant placement but also the inserted implant itself seems to be a continuous risk factor. Clinical relevance: The herein elaborated risk factors help dentists plan dental rehabilitation with implants in this high-risk group of patients and indicate careful and regular dental recal

Disentangling nucleation and domain growth during a laser-induced phase transition

We use ultrafast x-ray diffraction and the time-resolved polar magneto-optical Kerr effect to study the laser-induced metamagnetic phase transition in two FeRh films with thicknesses below and above the optical penetration depth. In the thin film, we identify an intrinsic 8 ps timescale for the lightinduced nucleation of ferromagnetic domains in the antiferromagnetic material that is substantially slower than the speed of sound. For the inhomogeneously excited thicker film, we additionally identify kinetics of out-of-plane domain growth mediated by near-equilibrium heat transport, which we experimentally verify by comparing Kerr effect experiments in front- and backside excitation geometry

A Time-Domain Perspective on the Structural and Electronic Response in Epitaxial Ferroelectric Thin Films on Silicon

This operando study of epitaxial ferroelectric Pb(Zr0.48Ti0.52)O3 capacitors on silicon substrates studies their structural response via synchrotron-based time-resolved X-ray diffraction during hysteresis-loop measurements in the 2–200 kHz range. At high frequencies, the polarization hysteresis loop is rounded and the classical butterfly-like strain hysteresis acquires a flat dumbbell shape. We explain these observations from a time-domain perspective: The polarization and structural motion within the unit cell are coupled to the strain by the piezoelectric effect and limited by domain wall velocity. The solution of this coupled oscillator system is derived experimentally from the simultaneously measured electronic and structural data. The driving stress σFE(t) is calculated as the product of the measured voltage U(t) and polarization P(t). Unlike the electrical variables, σFE(t) and η(t) of the ferroelectric oscillate at twice the frequency of the applied electrical field. We model the measured frequency-dependent phase shift between η(t) and σFE(t)

Accelerating the laser-induced phase transition in nanostructured FeRh via plasmonic absorption

By ultrafast x-ray diffraction we show that the laser-induced magnetostructural phase transition in FeRh nanoislands proceeds faster and more complete than in continuous films. We observe an intrinsic 8 ps timescale for nucleation of ferromagnetic (FM) domains in both types of samples. For the continuous film, the substrate-near regions, which are not directly exposed to light, are only slowly transformed to the FM state by domain wall motion following heat transport. In contrast, numerical modeling of the plasmonic absorption in the investigated nanostructure reveals a strong contribution near the FeRh/MgO interface. On average, the absorption is larger and more homogeneous in the nanoislands, enabling the phase transition throughout the entire volume at the intrinsic nucleation timescale

Influence of La and Mn vacancies on the electronic and magnetic properties of LaMnO₃ thin films grown by pulsed laser deposition

With pulsed laser deposition, we have grown c axis oriented thin films of the nominal composition LaMnO3 (LMO) on LSAT(001) substrates. We find that, depending on the oxygen background pressure during growth, the LMO films contain sizeable amounts of La and/or Mn vacancies that strongly influence their electronic and magnetic properties. Specifically, we show that the Mn/La ratio can be systematically varied from 0.92 at 0.11 mbar to 1.09 at 0.30 mbar of oxygen. The cationic vacancies have markedly different effects that become most pronounced once the samples are fully oxygenated and thus strongly hole doped. All as-grown and thus slightly oxygen-deficient LMO films are ferromagnetic insulators with saturation moments in excess of 2.5 μB per Mn ion, their transport and optical properties can be understood in terms of trapped ferromagnetic polarons. Upon oxygen annealing, the most La-deficient films develop a metallic response with an even larger ferromagnetic saturation moment of 3.8 μB per Mn ion. In contrast, in the oxygenated Mn-deficient films, the ferromagnetic order is strongly suppressed to less than 0.5 μB per Mn ion, and the transport remains insulatorlike. We compare our results with the ones that were previously obtained on bulk samples and present an interpretation in terms of the much stronger disruption of the electronic and magnetic structure by the Mn vacancies as compared to the La vacancies. We also discuss the implications for the growth of LMO thin films with well-defined physical properties that are a prerequisite for the study of interface effects in multilayers

Complex domain wall dynamics in compressively strained GaMnAs epilayers

The domain wall induced reversal dynamics in compressively strained GaMnAs was studied employing the magneto-optical Kerr effect and Kerr microscopy. Due to the influence of an uniaxial part in the in-plane magnetic anisotropy (90+/-Delta) domain walls with considerably different dynamic behavior are observed. While the (90+Delta) reversal is identified to be propagation dominated with a small number of domain walls, the case of (90-Delta) reversal includes the nucleation of many domain walls. The domain wall nucleation/propagation energy for both transitions are estimated using model calculations from which we conclude that single domain devices can be achievable using the (90+Delta) mode.Comment: 4 figure

Osteopathology induced by bisphosphonates and dental implants: clinical observations

OBJECTIVES: Although there are many reports about risk factors for the development of BP-associated osteonecrosis of the jaws, the role of dental implants as a local risk factor is still discussed, especially in patients with oral BP treatment. Until now, a few case reports and surveys display a possible minor risk in patients with oral BP therapy, whereas the avoidance of implant placement is generally accepted in patients with intravenous BP therapy. PATIENT AND METHODS: In this study, the cases of 14 patients with osteonecrosis of the jaws in association with BP therapy and dental implant placement were analyzed carefully with a detailed literature review. RESULTS: Of 14 patients, nine had underlying malignant disease and five patients had osteoporosis. In ten patients, implants were placed either in the posterior mandible or maxilla; the mean interval between implant insertion and disease onset was 20.9 months. Pain (n12) and signs of infection (n10) were the most common symptoms. Histologically, signs of infection were found in nine of 11 analyzed patients with presence of Actinomyces in six patients. Two patients turned out to have infiltration of underlying malignant disease. CONCLUSIONS: Posteriorly placed implants seem to be of higher risk of development of osteonecrosis of the jaws. Not only the implant placement but also the inserted implant itself seems to be a continuous risk factor. CLINICAL RELEVANCE: The herein elaborated risk factors help dentists plan dental rehabilitation with implants in this high-risk group of patients and indicate careful and regular dental recall

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery

A thorough epidemiological and microbiological investigation of this prolonged outbreak involving 6 open-chest heart surgery patients provided evidence for the airborne transmission of Mycobacterium chimaera, a slow-growing nontuberculous mycobacteria, from contaminated heater-cooler unit water tank

Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAF V600E mutations in colorectal carcinoma

The activating BRAF V600 mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAF V600E mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAF V600E mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAF V600E mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7%) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5%) and 15 IHC-positive cases (15/39; 38.5%) showed a BRAF wild-type by SaS. UDS detected a BRAF V600E mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100% and 63% and specificities of 95 and 100% for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-BRAFV600E (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAF V600E mutations in colorectal carcinom