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Summary Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa ( n = 5) and non-inflamed mucosa ( n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles ( n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles ( P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium. [ABSTRACT FROM AUTHOR]

Summary: Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect. [ABSTRACT FROM AUTHOR]

Abstract: The durability of thermal barrier coatings (TBCs) employed in most turbine engines is limited by delamination, both within the coating and at the coating–substrate interface. A test used for evaluating the mixed-mode toughness pertinent to such delaminations has been fully-analyzed by determining the steady-state energy release rate, the mode mixity and the critical length for buckling. An analytic solution based on beam theory establishes basic estimates and scaling relationships. Selected finite-element calculations have been used to affirm the fidelity of the results. The energy release rate attains steady-state, but the phase angle changes throughout because of a small (but significant) bending moment induced at the supports. The coating buckles at a critical delamination length, whereupon the energy release rate increases rapidly and violates steady state. The solutions are used to re-interpret measurements reported in the literature for an electron beam physically deposited TBC. [Copyright &y& Elsevier]

Abstract: Possibility of an interferometric method was examined for evaluating local light scattering behaviors in light transmitting materials. Phase profiles of wavefronts through a continuous SiO2 glass fiber–PMMA composite was measured by detecting transmitted light though the composite using the interferometric system with a pair of interferometers. Wavefront though the composite shows an anisotropic phase profile, and the phase delay originates from local light scattering due to refractive index difference at an interface between SiO2 fiber and PMMA matrix. Measured wavefronts demonstrated that the interferometric method is effective tool for an evaluation of local light scattering. [Copyright &y& Elsevier]

Abstract: The thermal radiation energy of reflection and transmission properties of all-oxide layered thermal energy window coatings at temperatures up to 1273 K has been studied and four-layered Al2O3–ZrO2 and two-layered Al2O3–TiO2 coated sapphire substrates fabricated. The thicknesses of individual layers were in the range of 300–600 nm, where the interference effect was determined to appear. Light reflection spectrum at the wavelength region from 2.2 to 10 μm was measured from room temperature to 1273 K. The oscillation behavior of light reflection, which originates from the interference effect of the layered structure, appeared in the reflection spectra. This behavior in both coating systems is maintained up to 1273 K and the reflectance values remain nearly the same as those measured at room temperature. Retention of the oscillation behavior up to 1273 K indicates the possibility of controlling the thermal radiation energy in a high temperature environment using the oxide-layered coating. [Copyright &y& Elsevier]

The effect of particle size on light transmittance of optically transparent nano-meter order particle-dispersed composites is studied on SiO2 particle-dispersed epoxy matrix optical composites. The light transmittance of the composites is measured in wavelength range from 300 to 800 nm. The relationship between light transmittance and particle size parameter, x=πdpnm/λa, is discussed. It is found that the light transmittance has a minimum at the particle size parameter ∼4–6. The addition of nano-meter order particle is effective to obtain high light transmittance composite. In the case of the size parameter less than 20, the smaller size parameter is recommended to achieve high light transmittance. [Copyright &y& Elsevier]

The prognostic role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. Patients with CLM without extrahepatic disease from the GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number, and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex polymerase chain reaction-next-generation sequencing (mPCR-NGS) assay. ctDNA-based MRD status was evaluated 2-10 weeks after curative surgery, before the start of ACT. Among 6061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 months (1-48 months). ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT [33.3% versus not reached, adjusted hazard ratio (HR): 0.07, P < 0.0001]; whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% versus 62.2%, adjusted HR: 0.68, P = 0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P = 0.031) was prognostic of DFS in the MRD-positive group. In the MRD-negative group, however, none of the clinicopathological factors were prognostic of DFS. Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk stratification could be potentially incorporated in future clinical trials for CLM. • Association between ACT benefit and MRD status was assessed in patients with surgically resected colorectal liver metastases. • In the MRD-positive group, the benefit of ACT in improving disease-free survival (DFS) was observed in multivariate analysis. • On the other hand, the benefit of ACT was limited in the MRD-negative group. [ABSTRACT FROM AUTHOR]

Highlights • The sensitivity of PCR-based clonality analysis of IGH gene rearrangements in canine cutaneous plasmacytoma was determined. • Plasmacytomas, diffuse large B cell lymphomas (DLBCLs) and non-lymphoma lymph nodes (LNs) were studied. • IGH clonality was detected in 0–34.5% of plasmacytomas and 17.4–78.3% of DLBCLs. • IGH clonality was detected in only one LN without lymphoma with two out of the seven oligonucleotide primers. • The low frequency of detection of IGH clonality in canine plasmacytomas may reflect variable region somatic hypermutation. Abstract Plasmacytomas are discrete, B cell-derived, round cell tumours that sometimes are difficult to distinguish from canine cutaneous histiocytomas or T cell lymphosarcomas (lymphomas). Diagnosis of plasmacytomas relies on morphological observations and immunohistochemistry for multiple myeloma oncogene-1 (MUM-1) and cluster of differentiation 3 (CD3). Clonality testing often is used as an adjunct diagnostic tool to examine lymphoproliferative diseases. In this study, the sensitivity of PCR-based clonality analysis of antigen receptor gene rearrangements in canine cutaneous plasmacytomas was determined. Formalin-fixed paraffin-embedded sections of 29 canine plasmacytomas, 23 diffuse large B cell lymphomas (DLBCLs) and 23 lymph nodes without lymphoma were used for clonality analysis. New oligonucleotide primers for the framework (FR)2 and FR3 regions of the immunoglobulin heavy chain (IGH) V gene subgroup 3 were designed and used with previously reported FR3 primers. Although plasma cells are of B cell lineage, the detected frequency of IGH clonality in plasmacytoma was 0–34.5% with the seven primers used, whereas in DLBCLs it was 8.7–78.3%. In 23 lymph nodes without lymphoma, IGH clonality was detected in only one case with two out of the seven primers used. Sequence analysis of PCR products from plasmacytomas revealed mismatches in the annealing region of the FR3 primers. The sensitivity of detecting IGH clonality in canine plasmacytomas was lower than in DLBCLs. The low detection rate of IGH clonality in canine plasmacytoma may be due to somatic hypermutation of the variable region. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the type and frequency of c-KIT exon 11 mutations in canine gastrointestinal stromal tumours (GISTs) and investigate the association between the c-KIT mutation status and KIT immunohistochemical staining pattern. Mutations in exon 11 of c-KIT were examined in 46 formalin-fixed paraffin-embedded canine GISTs using PCR of genomic DNA and reverse transcription-PCR (RT-PCR) of cDNA. Exon 11  c-KIT mutations were detected in 15/46 (32.6%) cases by conventional PCR and 34/46 (73.9%) cases by RT-PCR; the mutation detection rate was significantly higher for RT-PCR ( P  = 0.004, Fisher's exact test). Ten different mutations, including deletion, internal tandem duplication and point mutations, were identified by RT-PCR. Immunohistochemistry was performed using an anti-KIT antibody; diffuse KIT staining was detected in the tumour cell cytoplasm in 32/46 (69.6%) cases and partial or stippled cytoplasmic staining of KIT was observed in 14/46 (30.4%) cases. Neither pattern was significantly associated with c-KIT exon 11 mutation status ( P  = 1.000, chi-square test). These data indicate that c-KIT exon 11 mutations occur frequently in canine GISTs, similar to human GISTs; however, there is no association between c-KIT mutations and the KIT expression pattern in canine GISTs. This study suggests that RT-PCR is more sensitive than conventional PCR for the detection of c-KIT mutations in canine GISTs. [ABSTRACT FROM AUTHOR]

Local stress distribution in a thermally-grown-oxide (TGO) layer of a thermal barrier coating system after thermal exposure was measured using a near-field optical microscope with a resolution of 400 nm. Non-uniform stress distribution in TGO layer was found and interpreted based on stress analysis and Cr3+ content effects. [Copyright &y& Elsevier]

The decohesion of high purity Cu–sapphire interfaces has been studied by using double cleavage drilled compressive (DCDC) specimens, accompanied by in situ optical observations of the crack extension mechanisms. The Cu layer thickness was varied between 10 and 100 μm. Decohesion occurred along the interface subject to a resistance, ΓR(Δa), that rises with crack extension. The magnitude of the resistance was determined to be much larger (by a factor 4) for specimens with the thicker (100 μm) Cu layer. The observations revealed that the rupture occurred by a ductile mechanism involving void formation at the interface, followed by plastic void growth in the Cu, and subsequent coalescence by the separation of the interface between voids. Aspects of the failure sequence change with the Cu layer thickness. These changes, as well as the difference in the toughness, are attributable to a transition in constraint between the thin and thick layers. Namely, the thin layer develops high constraint (relative to the thicker layer) that elevates the mean stress ahead of the crack and causes the failure process to progress to a location further from the crack front. The measured trends in ΓR(Δa) for the two different layer thickness are shown consistent with models of the constraint transition for interface failure by ductile mechanisms. [Copyright &y& Elsevier]

The stress distributions in thermally grown oxide (TGO) layer of electron beam enhanced physical vapor deposited thermal barrier coating (EB-PVD TBC) before and after thermal exposure are measured by photo-stimulated luminescence spectrum. It is found that the stress in the TGO layer in original state is an order of ~3 GPa. It increases from 3.0–3.9 GPa with the increase of heat exposure time from 0–100 h. The stress distribution in the direction of thickness in the TGO layer is not uniform. The stress near ceramic top coat is smaller than that close to metal bond coat. The stress at thickness imperfections in the TGO near the bond coat is smaller than that in the regular TGO. [Copyright &y& Elsevier]

Background The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. Patients and methods Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. Results One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P  =   0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39–0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61–1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17–0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. Conclusions The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence. [ABSTRACT FROM AUTHOR]