Skin-stringer separation in post-buckling of butt-joint stiffened thermoplastic composite panels

Two aeronautical thermoplastic composite stiffened panels are analysed and tested to investigate the buckling behaviour, the skin-stringer separation and the final failure mode. The panels are made of fast crystallising polyetherketoneketone carbon composite, have three stringers with an angled cap on one side, and are joined to the skin by a short-fibre reinforced butt-joint. The panels contain an initial damage in the middle skin-stringer interface representing barely visible impact damage. Finite element analysis using the virtual crack closure technique are conducted before the test to predict the structural behaviour. During the tests, the deformation of the panels is measured by digital image correlation, the damage propagation is recorded by GoPro cameras and the final failure is captured by high speed cameras. The panels show an initial three half-wave buckling shape in each bay, with damage propagation starting shortly after buckling. A combination of relatively stable and unstable damage propagation is observed until final failure, when the middle stringer separates completely and the panels fail in an unstable manner. The test results are compared to the numerical prediction, which shows great agreement for both the buckling and failure behaviour

Experimental and numerical evaluation of conduction welded thermoplastic composite joints

The capability of joining two thermoplastic composite parts by welding is a key technology to reduce the weight and cost of assembled parts and enables high volume manufacturing of future aeronautical structures made of thermoplastic composite materials. However, there is not much experimental understanding of the mechanisms involving welded joint failure, and the computational tools available for the simulation of thermoset composites have not yet been completely assessed for thermoplastic materials. In this work, a numerical and experimental evaluation is performed to investigate the strength and failure behavior of conduction welded thermoplastic composite joints. A welded single lap shear joint is designed, manufactured, tested and analyzed proposing two distinct modeling approaches. A simplified modeling strategy which only accounts for damage at the weld is compared to a high-fidelity model which can take into account the physical failure mechanisms at the lamina level. The high-fidelity modeling methodology is able to predict the experimental failure mode of the investigated welded joints with high accuracy and is used to gain new insights into the key-variables that influence the strength of thermoplastic welded joints. It is also found that the joint strength is highly influenced by the failure mechanisms not only of the welded interface but also of the surrounding plies

Biological Signature of Scotian Shelf Water Crossovers on Georges Bank During Spring 1997

Episodic crossovers of cold low salinity Scotian Shelf Water (SSW) onto the Northeast Peak of Georges Bank are a potentially important mechanism transporting plankton species, including the copepod Calanus finmarchicus and its prey and predators, onto the Bank each spring. We provide the first detailed investigation of horizontal and vertical zooplankton distributions in SSW crossovers compared to other onbank locations from three GLOBEC cruises during spring 1997. SSW crossovers are physically and biologically distinct from other Bank locations. In late spring, chlorophyll concentrations and in vivo fluorescence are elevated and light transmission is reduced in SSW, while during early spring, these parameters are more variable. SSW communities do not contain a unique zooplankton assemblage or indicator species but instead show differences in abundance and life history parameters for various taxa compared to other Bank locations. SSW has high abundances of young C. finmarchicus life history stages, almost no diel vertical migration of zooplankton, low abundances of invertebrate predators, and low fish egg abundance. Population development of C. finmarchicus in SSW lags that in adjacent water. The potential biological impact of SSW crossovers on Georges Bank varies seasonally. In April, density inversions and interleaving of SSW and non‐SSW suggest active mixing, resulting in similar community composition of SSW and adjacent non‐SSW. SSW crossovers are probably an important source to Georges Bank of young stages of C. finmarchicus in early spring. In May, after stratification strengthens, the greater differentiation between SSW plankton and elsewhere indicates that mixing between communities is more limited

The role of dose-dense (DD) adjuvant chemotherapy (CT) in HER2-positive (HER2+) early breast cancer (BC) patients (pts) before and after the introduction of trastuzumab (T): Exploratory analysis of the GIM2 trial

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Accuracy and reproducibility of contrast-enhanced mammography in the assessment of response to neoadjuvant chemotherapy in breast cancer patients with calcifications in the tumor bed

This study aimed to evaluate contrast-enhanced mammography (CEM) accuracy and reproducibility in the detection and measurement of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with calcifications, using surgical specimen pathology as the reference. Pre-and post-NAC CEM images of 36 consecutive BC patients receiving NAC in 2012–2020, with calcifications in the tumor bed at diagnosis, were retrospectively reviewed by two radiologists; described were absence/presence and size of residual disease based on contrast enhancement (CE) only and CE plus calcifications. Twenty-eight patients (77.8%) had invasive and 5 (13.9%) in situ-only residual disease at surgical specimen pathology. Considering CE plus calcifications instead of CE only, CEM sensitivity for invasive residual tumor increased from 85.7% (95% CI = 67.3–96%) to 96.4% (95% CI = 81.7–99.9% ) and specificity decreased from 5/8 (62.5%; 95% CI = 24.5–91.5%) to 1/8 (14.3%; 95% CI = 0.4–57.9%). For in situ-only residual disease, false negatives decreased from 3 to 0 and false positives increased from 1 to 2. CEM pathology concordance in residual disease measurement increased (R squared from 0.38 to 0.45); inter-reader concordance decreased (R squared from 0.79 to 0.66). Considering CE plus calcifications to evaluate NAC response in BC patients increases sensitivity in detection and accuracy in measurement of residual disease but increases false positives

Biomarkers changes after neoadjuvant chemotherapy in breast cancer: A seven-year single institution experience

The adoption of neoadjuvant chemotherapy (NACT) for breast cancer (BC) is increasing. The need to repeat the biomarkers on a residual tumor after NACT is still a matter of debate. We verified estrogen receptors (ER), progesterone receptors (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) status changes impact in a retrospective monocentric series of 265 BCs undergoing NACT. All biomarkers changed with an overall tendency toward a reduced expression. Changes in PR and Ki67 were statistically significant (p = 0.001). Ki67 changed in 114/265 (43.0%) cases, PR in 44/265 (16.6%), ER in 31/265 (11.7%) and HER2 in 26/265 (9.8%). Overall, intrinsic subtype changed in 72/265 (27.2%) cases after NACT, and 10/265 (3.8%) cases switched to a different adjuvant therapy accordingly. Luminal subtypes changed most frequently (66/175; 31.7%) but with less impact on therapy (5/175; 2.8%). Only 3 of 58 triple-negative BCs (5.2%) changed their intrinsic subtype, but all of them switched treatment. No correlation was found between intrinsic subtype changes and clinicopathological features. To conclude, biomarkers changes with prognostic implications occurred in all BC intrinsic subtypes, albeit they impacted therapy mostly in HER2 negative and/or hormone receptors negative BCs. Biomarkers retesting after NACT is important to improve both tailored adjuvant therapies and prognostication of patients

Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial.

Background In HR+/HER2- early BC, high tumour infiltrating lymphocytes (TIL) levels predict higher pathological complete response to neoadjuvant chemotherapy, but are associated with shorter overall survival (Denkert, Lancet Oncol 2018). HR+/HER2- BC is a biologically heterogeneous disease, encompassing all BC molecular intrinsic subtypes, with different clinical behaviour (Cejalvo, CTR 2018). Little is known concerning the distribution of TIL levels and immune infiltrate composition across intrinsic subtypes in HR+/HER2- BC. Methods Gene-expression data (Affymetrix platform) from pre-treatment frozen core-biopsies was available from 66 postmenopausal patients with HR+/HER2- early BC from the LETLOB trial (neoadjuvant letrozole+/-lapatinib) (Guarneri, JCO 2014). Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. Relative leukocyte fractions were calculated using CIBERSORT (Newman, Nature Methods 2015), a deconvolution method based on RNA gene-expression signatures. Pre-treatment stromal TILs were assessed on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015). Results Intrinsic subtype distribution was as follows: basal 18% (N = 12), HER2-enriched 8% (N = 5), Luminal A 39% (N = 25), Luminal B 36% (N = 24). Non-luminal subtypes (HER2-enriched and Basal) had significantly higher baseline TIL levels than luminal subtypes (median (range): 7 (0-100) and 2 (0-35), respectively; p = 0.038). Non-luminal subtypes also presented higher fractions of CD4 memory activated T-cells (p = 0.018), γδ T-cells (p = 0.010) and M1 macrophages (p = 0.001) and lower fractions of T-regulatory cells (p = 0.002) than luminal subtypes. Conclusions In HR+/HER2- early BC, non-luminal subtypes show higher TIL levels and a more pro-inflammatory anti-tumour immune infiltrate composition. This immune heterogeneity across intrinsic subtypes should be considered when analysing the complex prognostic role of TILs in HR+/HER2- early BC

tumor infiltrating lymphocytes tils as an independent prognostic factor for early her2 breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shorther trial

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Cutaneous Involvement in Diseases with Plasma Cell Differentiation: Diagnostic Approach

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient’s work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed

Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.

BACKGROUND: There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. PATIENTS AND METHODS: Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs\u2009 6520% and TILs\u2009<20%. Median follow-up was 6.1\u2009years. RESULTS: Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P\u2009=\u20090.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs\u2009<20% and 95.7% for patients with TILs\u2009 6520% (P\u2009=\u20090.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9\u2009weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1\u2009year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P\u2009=\u20090.088). For patients with TILs\u2009<20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs\u2009 6520% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P\u2009=\u20090.064), resulting in a significant interaction (P\u2009=\u20090.015). CONCLUSIONS: TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy