Germline breast cancer susceptibility genes, tumor characteristics, and survival.

BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Abstract: Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia

Research Article Investigation of Effects of Different Synthesis Unit to the Quality of Malay Synthetic Speech

Abstract: Synthesis unit of a speech synthesizer directly affects the computational load and output speech quality. Generally, phoneme is the best choice to synthesize high quality speech. But it requires the knowledge of language to precisely draw the segmentation of words into phonemes. And it is expensive to compose an accurate phoneme dictionary. In this study, another type of synthesis unit is introduced which is letter. In Malay language, the unit size of letter is smaller than phoneme. And using letter as the synthesis unit could ease a lot of efforts because the context label can be created in fully automatic manner without the knowledge of the language. Four systems have been created and an investigation was done to find out how synthesis unit could affect the quality of synthetic speech. Forty eight listeners were hired to rate the output speech individually and result showed that no obvious difference between the output speech synthesized using different synthesis units. Listening test showed satisfactory result in terms of similarity, naturalness and intelligibility. Synthetic speech with polyphonic label showed increment in intelligibility compared to synthetic speech without polyphonic label. Using letter as the synthesis unit is recommended because it excludes the dependency of linguist and expands the idea of language independent front end text processing

Milk-run kanban system for raw printed circuit board withdrawal to surface-mounted equipment

Purpose: The paper aims to present a case study and later simulation analysis on a kanban system that incorporating milk-run operation to draw in raw material to the process. Design/methodology/approach: Data collection at the case study company for ten weeks followed by a process study called value stream mapping. The proposed kanban model is simulated to test its various performances including total output, average flow time, average work-in-process, SME utilization, and average waiting time. Response surface methodology is adopted to generate suitable representative regression models. Findings: For all performance measures, simulation results showed that the proposed system consistently outperforms the push system currently practiced. Second, the system indicates the advantages of leveling, particularly in the event of machine failure and blockage. Third, operator in the proposed kanban system has a lower utilization, even with the additional material handling task. Research limitations/implications: This study only begins to reveal the implication of leveling for production control on multi-machine scenario. The simulation of the system is solely based only the case study. The control parameters critical to the case study, were naturally used. The furtherance of the research should include generalizing the system and devising the respective methodology to facilitate wider applications. Practical implications: Originality/value: The kanban system is proposed in the light of conflicting interests in handling the surface mounting and the related upstream processes. Such aspect is common to electronics assembly industry

An Attempt to Maximize the Use of Used Cooking Oil and Fly Ash in the Production of Green Roofing Tile

This study introduces a novel attempt of utilizing used cooking oil (UCO) and fly ash in the production of green roofing tile, namely UCO-GRT. UCO was utilized as an alternative binder to fully replace the cement and clay, while fly ash was used as a fine aggregate instead of virgin sand. This can maximize the percentage of waste substitution in the manufacturing process, consequently reducing the waste disposal issues encountered in Malaysia. The optimization process was carried out to investigate the optimal manufacturing parameters, by considering the curing duration, the composition of UCO and fly ash, and the composition of catalyst incorporated. The mechanical properties of UCO-GRT produced, including density, dry and wet transverse strength, percentage of water absorption, and permeability have been investigated. Findings reveal that the utilization of catalysed UCO and fly ash solely in the production of roofing tiles is feasible. The optimized UCO-GRT fulfilled the basic requirements of a high-profile roofing tile as per ASTM standards. The embodied carbon and embodied energy of the novel roofing tile were also studied and compared with the cementitious and clay roofing tiles