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AbstractTo determine the role of familial factors in head and neck cancer, we analysed data from a hospital‐based case‐control study of squamous cell carcinoma of the head and neck in Brazil. There were 754 cases of squamous cell carcinoma of the head and neck (SCCHN) and 1,507 age‐ and gender‐matched hospital‐based controls with non‐malignant diseases. Subjects provided information on the occurrence of cancer in first‐degree relatives, as well as about other risk factors, including tobacco and alcohol consumption. Relative risks (RRs) were estimated for developing mouth, pharynx and larynx cancer when cancers in relatives were observed. RRs were adjusted for age, sex, city of admission and alcohol and tobacco consumption. The RR for developing SCCHN if a first‐degree relative had cancer at any site was significantly elevated at 1.97. The RR was 3.65 (95% Cl: 1.97–6.76) if the relative had head and neck cancer. Significantly elevated risks for developing head and neck cancer were associated with siblings with head and neck cancer (RR = 8.57) and, to a lesser extent, with fathers with head and neck cancer (RR = 2.49). There was no significantly increased risk associated with mothers with head and neck cancer, but these tumours were rare among mothers. Our data show that familial, possibly genetic, factors are important in the aetiology of head and neck cancer. © 1995 Wiley‐Liss, Inc.

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts. ispartof: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE vol:270 issue:7 pages:921-932 ispartof: location:Germany status: published

In this paper, the mechanical properties of plasma-sprayed coatings are evaluated using the technology of nanoindentation. According to the indentation curve (load versus indenter’s displacement), which is recorded in an indentation experiment, the mechanical behaviour of the plasma-sprayed coating is investigated via inverse analysis using numerical optimization algorithms. The tip rounding of imperfect indenter is investigated in parameter identification. Subsequently, the hardness on the top surface and on the vertical cross section of the plasma-sprayed coating are investigated. The results show that the hardness on the top surface of the coating depends on the indentation depth. Moreover, the results show that the hardness on the cross section of the coating is significantly affected by the substrate if the indentation impression is too close to the coating-substrate interface.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background: Protein kinase Cβ (PKCβ) is critical for B-cell signaling and survival and overexpression of PKCβ in DLBCL is associated with inferior survival. ENZA, an oral serine/threonine kinase inhibitor, targets PKCβ. Here we report immunohistochemical (IHC) and fluorescence in-situ hybridization (FISH) correlative analyses. Methods: PRELUDE ([NCT00332202][1]) was a phase III, double-blind maintenance study of 758 pts with DLBCL who were randomized 2:1 to ENZA 500 mg daily (1125-mg loading dose) (n = 504) or PBO (n = 254), respectively, following CR to induction therapy with R-CHOP. The primary endpoint was disease-free survival (DFS). Overall survival (OS) and assessment of biomarkers specific to ENZA and DLBCL were secondary endpoints. Pre-treatment formalin-fixed, paraffin-embedded samples were assessed via IHC staining in a blinded manner (Eric Hsi) for cell of origin (COO) using Hans’ algorithm. In addition, IHC was performed for c-MYC, BCL2, BCL6, FOXP1, and MUM1 (10% increments/% tumor cells stained), markers relevant to ENZA, including PKCβ2. FISH was performed to identify translocations involving c-MYC, BCL2, and BCL6. Cox regression was used to determine statistical associations between efficacy outcomes and dichotomized markers, adjusting for treatment and additional baseline covariates. All tests of association were conducted at a 2-sided α = 0.05. Results: There was no difference in 4-year DFS (70% vs 71%) or OS (81% vs 82%) between ENZA and PBO arms, respectively. A total of 243 (32%) pts had ≥1 evaluable sample available for IHC and FISH. There was no difference in outcome for pts based on COO (GCB vs non-GCB). Independent of treatment, significant associations were observed for BCL2 (pre-specified cutpoint 20%) and MUM1 (cutpoint 30%) with OS, and FOXP1 (cutpoint 80%) by IHC with DFS (HR [95% CI]: 2.19 [1.01-4.73]), p = 0.031; 1.97 [1.04-3.71], p = 0.032; 1.74 [1.04-2.90], p = 0.032, respectively). Associations were not significant for other IHC markers, including c-MYC and BCL6. Low PKCβ2 (<50% expression) had numerically better (but not significant) DFS/OS vs high PKCβ2. Dual translocation lymphoma by FISH was identified in two pts (1.2%) each for c-MYC/BCL2 and c-MYC/BCL6, and one pt (0.6%) had a triple hit involving c-MYC/BCL2/BCL6. Conclusions: No difference in outcomes between treatment arms was observed for the trial. Independent of treatment, COO was not prognostic of outcomes. Pts with low PKCβ2 expression had numerically better DFS/OS compared with high PKCβ2 expression. Significant treatment-independent associations were observed for BCL2 and MUM1 with OS and for FOXP1 with DFS (low IHC expression corresponded to better outcomes). The small number of double hit and triple hit lymphomas seen in the study may reflect the enrollment of CR patients with more favorable biology. Citation Format: Eric D. Hsi, Kerry J. Savage, Sonali M. Smith, Fritz Offner, Scott P. Myrand, Thomas M. Habermann, Donald E. Thornton, Boris K. Lin, Tuan S. Nguyen, Oday Hamid, Michael Crump. Correlative results from PRELUDE, a phase III study of enzastaurin (ENZA) vs placebo (PBO) in patients (pts) with high-risk diffuse large B-cell lymphoma (DLBCL) following a response to R-CHOP therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5303. doi:10.1158/1538-7445.AM2015-5303 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00332202&atom=%2Fcanres%2F75%2F15_Supplement%2F5303.atom

This work presents records of two endobenthic species of sea cucumber (Holothuroidea: Echinodermata) not previously reported in Canadian waters. Thyone inermis (Dendrochirotida) and Labidoplax buskii (Apodida) were collected south-west of Nova Scotia (eastern Canada) in 2009 in Georges and Crowell Basins in the upper 2 cm of muddy seafloor at upper bathyal depths (240–370 m). Both species are of small size, 3.7–8 mm and 5–8 mm long, respectively.

We present a measurement of the density of GeV muons in near-vertical air showers using three years of data recorded by the IceTop array at the South Pole. Depending on the shower size, the muon densities have been measured at lateral distances between 200 and 1000 m. From these lateral distributions, we derive the muon densities as functions of energy at reference distances of 600 and 800 m for primary energies between 2.5 and 40 PeV and between 9 and 120 PeV, respectively. The muon densities are determined using, as a baseline, the hadronic interaction model Sibyll 2.1 together with various composition models. The measurements are consistent with the predicted muon densities within these baseline interaction and composition models. The measured muon densities have also been compared to simulations using the post-LHC models EPOS-LHC and QGSJet-II.04. The result of this comparison is that the post-LHC models together with any given composition model yield higher muon densities than observed. This is in contrast to the observations above 1 EeV where all model simulations yield for any mass composition lower muon densities than the measured ones. The post-LHC models in general feature higher muon densities so that the agreement with experimental data at the highest energies is improved but the muon densities are not correct in the energy range between 2.5 and about 100 PeV. Physical review / D 106(3), 032010 (2022). doi:10.1103/PhysRevD.106.032010 Published by Inst., Melville, NY