Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking

Pain management

Regardless of the setting in which they work, nurses are responsible for the assessment and management of clients with pain. Pain is a key consideration in all patient care, and nurses play a critical role in pain management. Indeed, throughout history nurses have made important contributions to our understanding and management of pain through research and clinical practice. This chapter aims to provide an introduction to some key concepts in pain management and to encourage you to reflect on some of your own assumptions about pain.

Slide attacks on the Sfinks stream cipher

Sfinks is a shift register based stream cipher designed for hardware implementation and submitted to the eSTREAM project. In this paper, we analyse the initialisation process of Sfinks. We demonstrate a slid property of the loaded state of the Sfinks cipher, where multiple key-IV pairs may produce phase shifted keystream sequences. The state update functions of both the initialisation process and keystream generation and also the pattern of the padding affect generation of the slid pairs.

State convergence in bit-based stream ciphers

Well-designed initialisation and keystream generation processes for stream ciphers should ensure that each key-IV pair generates a distinct keystream. In this paper, we analyse some ciphers where this does not happen due to state convergence occurring either during initialisation, keystream generation or both. We show how state convergence occurs in each case and identify two mechanisms which can cause state convergence.

Slid pairs in the initialisation of the A5/1 stream cipher

A5/1 is a shift register based stream cipher which uses a majority clocking rule to update its registers. It is designed to provide privacy for the GSM system. In this paper, we analyse the initialisation process of A5/1. We demonstrate a sliding property of the A5/1 cipher, where every valid internal state is also a legitimate loaded state and multiple key-IV pairs produce phase shifted keystream sequences. We describe a possible ciphertext only attack based on this property.

Tenofovir-associated proteinuria

Proteinuria was observed in 27% of 153 patients taking tenofovir for more than 1 year. Concomitant protease inhibitor therapy and cumulative tenofovir exposure were independently associated with proteinuria in this cohort. Proteinuria was reversible in 11 of 12 patients who ceased tenofovir because of proteinuria without altering other medications. Clinicians should be aware that tenofovir can cause reversible proteinuria in patients with HIV.

Algebraic analysis of Trivium-like ciphers

Trivium is a bit-based stream cipher in the final portfolio of the eSTREAM project. In this paper, we apply the approach of Berbain et al. to Trivium-like ciphers and perform new algebraic analyses on them, namely Trivium and its reduced versions: Trivium-N, Bivium-A and Bivium-B. In doing so, we answer an open question in the literature. We demonstrate a new algebraic attack on Bivium-A. This attack requires less time and memory than previous techniques which use the F4 algorithm to recover Bivium-A's initial state. Though our attacks on Bivium-B, Trivium and Trivium-N are worse than exhaustive keysearch, the systems of equations which are constructed are smaller and less complex compared to previous algebraic analysis. Factors which can affect the complexity of our attack on Trivium-like ciphers are discussed in detail.

Weak key-IV pairs in the A5/1 stream cipher

A5/1 is a shift register based stream cipher which provides privacy for the GSM system. In this paper, we analyse the loading of the secret key and IV during the initialisation process of A5/1. We demonstrate the existence of weak key-IV pairs in the A5/1 cipher due to this loading process; these weak key-IV pairs may generate one, two or three registers containing all-zero values, which may lead in turn to weak keystream sequences. In the case where two or three registers contain only zeros, we describe a distinguisher which leads to a complete decryption of the affected messages.

Indirect message injection for MAC generation

This paper presents a model for the generation of a MAC tag using a stream cipher. The input message is used indirectly to control segments of the keystream that form the MAC tag. Several recent proposals can be considered as instances of this general model, as they all perform message accumulation in this way. However, they use slightly different processes in the message preparation and finalisation phases. We examine the security of this model for different options and against different types of attack, and conclude that the indirect injection model can be used to generate MAC tags securely for certain combinations of options. Careful consideration is required at the design stage to avoid combinations of options that result in susceptibility to forgery attacks. Additionally, some implementations may be vulnerable to side-channel attacks if used in Authenticated Encryption (AE) algorithms. We give design recommendations to provide resistance to these attacks for proposals following this model.

Security analysis of linearly filtered NLFSRs

Non-linear feedback shift register (NLFSR) ciphers are cryptographic tools of choice of the industry especially for mobile communication. Their attractive feature is a high efficiency when implemented in hardware or software. However, the main problem of NLFSR ciphers is that their security is still not well investigated. The paper makes a progress in the study of the security of NLFSR ciphers. In particular, we show a distinguishing attack on linearly filtered NLFSR (or LF-NLFSR) ciphers. We extend the attack to a linear combination of LF-NLFSRs. We investigate the security of a modified version of the Grain stream cipher and show its vulnerability to both key recovery and distinguishing attacks.

Algebraic analysis of Trivium-like ciphers

Trivium is a bit-based stream cipher in the final portfolio of the eSTREAM project. In this paper, we apply the algebraic attack approach of Berbain et al. to Trivium-like ciphers and perform new analyses on them. We demonstrate a new algebraic attack on Bivium-A. This attack requires less time and memory than previous techniques to recover Bivium-A's initial state. Though our attacks on Bivium-B, Trivium and Trivium-N are worse than exhaustive keysearch, the systems of equations which are constructed are smaller and less complex compared to previous algebraic analyses. We also answer an open question posed by Berbain et al. on the feasibility of applying their technique on Trivium-like ciphers. Factors which can affect the complexity of our attack on Trivium-like ciphers are discussed in detail. Analysis of Bivium-B and Trivium-N are omitted from this manuscript. The full paper is available on the IACR ePrint Archive.

An examination of the legislative framework governing commuter safety in the Queensland Mining Industry

Commuting in the mining industry -Background -The problem -Journey management -The structure of the legislative framework Legislation and Regulation -Workplace safety in Queensland mining -Risk management -Mining legislation and journey management -Commuting and employee responsibilities -Queensland Workers’ Compensation Scheme Industry standards -Industry standards and journey management Regulated and organisational policy documents -Policy documents and journey management Observations & Conclusions

Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial

INTRODUCTION In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts. © 2013 by the International Association for the Study of Lung Cancer.