Predicting invasive breast cancer versus DCIS in different age groups.

BackgroundIncreasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age.MethodsWe analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women ≥ 65 (older group), women 50-64 (middle age group), and women < 50 (younger group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC).ResultsThe models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer.ConclusionsClinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age

TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy

Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide

Connectivity mode management for user devices in heterogeneous D2D networks

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Device-to-Device (D2D) paradigm is one of the key enablers for boosting the energy efficiency (EE) of networks. For the actualization of EE in multi-mode heterogeneous D2D networks, resource allocation should be executed accordingly. In that regard, we study resource allocation management in heterogeneous D2D networks where there is a LEO satellite and a cellular base station (BS) with multi-mode user devices (satellite, BS and D2D connectivity modes) dispersed in the terrestrial cell. We formulate the EE optimization of mode selection constrained by a designated total network service capacity threshold. We also implement a sub-optimal pattern search algorithm (PSA) with the aim of enhancing EE while keeping total system service capacity at an acceptable level and compare it to alternative resource management schemes. Based on our simulation results, PSA achieves the most beneficial EE value in contrast to other schemes while still managing to meet the goodput threshold. Additionally, we discuss the multi-mode nature of our heterogeneous network from EE and goodput perspectives

Qualitative characterization of healthcare wastes

The biological hazard inherent in the clinical wastes should be considered during the management and treatment process as well as the disposal into the environment. In this chapter, the risks associated with the clinical wastes as well as the management of these wastes are discussed. The chapter focused on reviewing the types of healthcare wastes generated from hospitals and clinics as well as the regulations and management practices used for these wastes. Moreover, the health risk associated with the infectious agents which have the potential to be transmitted into the environment. It has appeared that the clinical wastes represent real hazards for the human health and the environment if they were not managed properly

Matrix density effect on morphology of germanium nanocrystals embedded in silicon dioxide thin films

Flash type electronic memories are the preferred format in code storage at complex programs running on fast processors and larger media files in portable electronics due to fast write/read operations, long rewrite life, high density and low cost of fabrication. Scaling limitations of top-down fabrication approaches can be overcome in next generation flash memories by replacing continuous floating gate with array of nanocrystals. Germanium (Ge) is a good candidate for nanocrystal based flash memories due its small band gap. In this work, we present effect of silicon dioxide (SiO 2) host matrix density on Ge nanocrystals morphology. Low density Ge+SiO 2 layers are deposited between high density SiO 2 layers by using off-angle magnetron sputter deposition. After high temperature post-annealing, faceted and elongated Ge nanocrystals formation is observed in low density layers. Effects of Ge concentration and annealing temperature on nanocrystal morphology and mean size were investigated by using transmission electron microscopy. Positive correlation between stress development and nanocrystal size is observed at Raman spectroscopy measurements. We concluded that non-uniform stress distribution on nanocrystals during growth is responsible from faceted and elongated nanocrystal morphology. © 2011 Materials Research Society

Testbeam and Laboratory Characterization of CMS 3D Pixel Sensors

The pixel detector is the innermost tracking device in CMS, reconstructing interaction vertices and charged particle trajectories. The sensors located in the innermost layers of the pixel detector must be upgraded for the ten-fold increase in luminosity expected with the High- Luminosity LHC (HL-LHC) phase. As a possible replacement for planar sensors, 3D silicon technology is under consideration due to its good performance after high radiation fluence. In this paper, we report on pre- and post- irradiation measurements for CMS 3D pixel sensors with different electrode configurations. The effects of irradiation on electrical properties, charge collection efficiency, and position resolution of 3D sensors are discussed. Measurements of various test structures for monitoring the fabrication process and studying the bulk and surface properties, such as MOS capacitors, planar and gate-controlled diodes are also presented.Comment: 14 page

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE