Management of endocrine resistant breast cancer

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.

Role of electromechanical wave propagation in power systems

In a large interconnected power system, disturbances initiated by a fault or other events cause acceleration in the generator rotors with respect to their synchronous reference frame. This acceleration of rotors can be described by two different dynamic phenomena, as shown in existing literature. One of the phenomena is simultaneous acceleration and the other is electromechanical wave propagation, which is characterized by travelling waves in terms of a wave equation. This paper demonstrates that depending on the structure of the system, the exhibited dynamic response will be dominated by one phenomenon or the other or a mixture of both. Two system structures of choice are examined, with each structure exemplifying each phenomenon present to different degrees in their dynamic responses. Prediction of dominance of either dynamic phenomenon in a particular system can be determined by taking into account the relative sizes of the values of its reduced admittance matrix.

Predicting voltage unbalance impacts of plug-in electric vehicles penetration in residential low-voltage distribution networks

Plug-in electric vehicles will soon be connected to residential distribution networks in high quantities and will add to already overburdened residential feeders. However, as battery technology improves, plug-in electric vehicles will also be able to support networks as small distributed generation units by transferring the energy stored in their battery into the grid. Even though the increase in the plug-in electric vehicle connection is gradual, their connection points and charging/discharging levels are random. Therefore, such single-phase bidirectional power flows can have an adverse effect on the voltage unbalance of a three-phase distribution network. In this article, a voltage unbalance sensitivity analysis based on charging/discharging levels and the connection point of plug-in electric vehicles in a residential low-voltage distribution network is presented. Due to the many uncertainties in plug-in electric vehicle ratings and connection points and the network load, a Monte Carlo-based stochastic analysis is developed to predict voltage unbalance in the network in the presence of plug-in electric vehicles. A failure index is introduced to demonstrate the probability of non-standard voltage unbalance in the network due to plug-in electric vehicles.

Analysis of traffic injury severity in Dhaka, Bangladesh

This research identifies roadway, traffic, and environmental factors that influence the injury severity of road traffic crashes in Dhaka. Dhaka provides a rather unusual driving risk environment to study, since virtually anyone can obtain a drivers’ license and very little traffic enforcement and fines are given when drivers violate traffic rules. To examine this city with presumed heightened crash severity risk, police reported crash data from 2007 to 2011 containing about 2714 road traffic crashes were collected. The injury severity of traffic crashes—recorded as either fatal, serious injury, or property damage only—were modeled using an ordered Probit model. Significant factors increasing the probability of fatal injuries include crashes along highways (65%), absence of a road divider (80%), crashes during night time (54%), and vehicle-pedestrian collisions (367%); whereas two-way traffic configuration (21%), and traffic police controlled schemes (41%) decrease the probability of fatalities. Both similarities and differences of the findings between crash risk in Dhaka and developed countries are discussed in policy relevant terms.

Demand-side response model to avoid spike of electricity price

The aim of this work is to develop a demand-side-response model, which assists electricity consumers exposed to the market price to independently and proactively manage air-conditioning peak electricity demand. The main contribution of this research is to show how consumers can optimize the energy cost caused by the air conditioning load considering to several cases e.g. normal price, spike price, and the probability of a price spike case. This model also investigated how air-conditioning applies a pre-cooling method when there is a substantial risk of a price spike. The results indicate the potential of the scheme to achieve financial benefits for consumers and target the best economic performance for electrical generation distribution and transmission. The model was tested with Queensland electricity market data from the Australian Energy Market Operator and Brisbane temperature data from the Bureau of Statistics regarding hot days from 2011 to 2012.

End-of-life care in the intensive care unit : a systematic review of qualitative studies investigating the experiences and perceptions of the patient's family

Review question/objective The review objective is to synthesise the best available evidence on experiences and perceptions of family members of intensive care unit patients on the adequacy of end-of-life care, where life-support modalities have been withheld or withdrawn. Inclusion criteria Types of participants This review will consider studies that report on the experiences and perceptions of patients’ families on EOLC in the ICU, where life-support modalities have been withheld or withdrawn. The family is defined as “those who are closest to the patient... the family may include the biological family, family by acquisition, and the family of choice and friends”. Phenomena of interest The phenomena of interest for this review are the patients’ families experiences, perceptions or views on the adequacy of EOLC delivered in the ICU, where life-support modalities were withheld or withdrawn. These experiences may refer to the following views on domains of care considered important at the end-of-life in the ICU, which have been described already in the existing literature: timely, consistent, and compassionate communication, clinician availability, clinical decision making based on patients’ preferences, goals and values, physical care implemented to maintain patient comfort, holistic interdisciplinary care and bereavement care for families of patients who died.

A Satellite Selection Algorithm for Achieving High Reliability of Ambiguity Resolution with GPS and Beidou Constellations

Reliability of carrier phase ambiguity resolution (AR) of an integer least-squares (ILS) problem depends on ambiguity success rate (ASR), which in practice can be well approximated by the success probability of integer bootstrapping solutions. With the current GPS constellation, sufficiently high ASR of geometry-based model can only be achievable at certain percentage of time. As a result, high reliability of AR cannot be assured by the single constellation. In the event of dual constellations system (DCS), for example, GPS and Beidou, which provide more satellites in view, users can expect significant performance benefits such as AR reliability and high precision positioning solutions. Simply using all the satellites in view for AR and positioning is a straightforward solution, but does not necessarily lead to high reliability as it is hoped. The paper presents an alternative approach that selects a subset of the visible satellites to achieve a higher reliability performance of the AR solutions in a multi-GNSS environment, instead of using all the satellites. Traditionally, satellite selection algorithms are mostly based on the position dilution of precision (PDOP) in order to meet accuracy requirements. In this contribution, some reliability criteria are introduced for GNSS satellite selection, and a novel satellite selection algorithm for reliable ambiguity resolution (SARA) is developed. The SARA algorithm allows receivers to select a subset of satellites for achieving high ASR such as above 0.99. Numerical results from a simulated dual constellation cases show that with the SARA procedure, the percentages of ASR values in excess of 0.99 and the percentages of ratio-test values passing the threshold 3 are both higher than those directly using all satellites in view, particularly in the case of dual-constellation, the percentages of ASRs (>0.99) and ratio-test values (>3) could be as high as 98.0 and 98.5 % respectively, compared to 18.1 and 25.0 % without satellite selection process. It is also worth noting that the implementation of SARA is simple and the computation time is low, which can be applied in most real-time data processing applications.

Developing the quantum probability ranking principle

In this work, we summarise the development of a ranking principle based on quantum probability theory, called the Quantum Probability Ranking Principle (QPRP), and we also provide an overview of the initial experiments performed employing the QPRP. The main difference between the QPRP and the classic Probability Ranking Principle, is that the QPRP implicitly captures the dependencies between documents by means of quantum interference". Subsequently, the optimal ranking of documents is not based solely on documents' probability of relevance but also on the interference with the previously ranked documents. Our research shows that the application of quantum theory to problems within information retrieval can lead to consistently better retrieval effectiveness, while still being simple, elegant and tractable.

The resistance of PRESENT-80 against related-key differential attacks

We examine the security of the 64-bit lightweight block cipher PRESENT-80 against related-key differential attacks. With a computer search we are able to prove that for any related-key differential characteristic on full-round PRESENT-80, the probability of the characteristic only in the 64-bit state is not higher than 2−64. To overcome the exponential (in the state and key sizes) computational complexity of the search we use truncated differences, however as the key schedule is not nibble oriented, we switch to actual differences and apply early abort techniques to prune the tree-based search. With a new method called extended split approach we are able to make the whole search feasible and we implement and run it in real time. Our approach targets the PRESENT-80 cipher however,with small modifications can be reused for other lightweight ciphers as well.

Safety climate and injury occurrence of repair, maintenance, minor alteration and addition works : a comparison of workers, supervisors and managers

Purpose The repair, maintenance, minor alteration and addition (RMAA) sector has been expanding in many developed cities. Safety problems of the RMAA sector have attracted the attention of many governments. This study has the objectives of comparing the level of safety climate of workers, supervisors and managers in the RMAA sector; and explaining/ predicting the impact of safety climate on injury occurrence of workers, supervisors and managers. Design/methodology/approach A questionnaire survey was administered to RMAA contracting companies in Hong Kong. Findings When comparing the safety climate perception of workers, supervisors and managers in the RMAA sector, the supervisors group had the lowest mean safety climate score. Results showed that a positive workforce safety attitude and acceptance of safety rules and regulations reduced the workers’ likelihood of having injuries. A reasonable production schedule led to a lower probability of supervisors being injured. Management commitment and effective safety management reduced the probability of managers being injured. Originality/value This study revealed variations of safety climate at the different levels in the organizational hierarchy and their varying influence on safety performance of the RMAA sector. Safety of RMAA works could be improved by promulgating specific safety measures at the different hierarchy levels.

Insider comes out : an artist's inquiry and narrative about the relationship of art and mental health

Background Through an account of prevailing experiences of art and mental illness, this paper aims to raise awareness, open dialogue and create agency about art created by people with experience of mental illness. Methods This paper draws on personal narrative and inquiry by an artist with mental illness and data collected as part of a larger participatory action research project that investigated understandings of identity, art and mental illness. Result An inquiry through art raised awareness and attentiveness to the importance of choice in identity construction and exposed frequent dichotomies in art and mental illness that were negotiated to eschew prescribed social stratification. As an artist, the first author challenged values present in one idea and absent in the other, and the options and concessions available to authorise her own dialogue and agency of being an artist. Conclusion Constructing an identity is an important part of being human, the labels that we choose or are chosen for us attribute to our identity. Reflections and recommendations are offered to consider expanded ways of thinking about art and mental illness and the functions that art play in identity construction.

Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

Towards a multi-element simulation of heavily over-consolidated bagasse using a material subroutine

A better understanding of the behaviour of prepared cane and bagasse, and the ability to model the mechanical behaviour of bagasse as it is squeezed in a milling unit to extract juice, would help identify how to improve the current process. There are opportunities to decrease bagasse moisture from a milling unit. The behaviour of bagasse in chutes is poorly understood. Previous investigations have shown that juice flow through bagasse obeys Darcy’s permeability law, that the grip of the rough surface of the grooves on the bagasse can be represented by the Mohr-Coulomb failure criterion for soils, and that the internal mechanical behaviour of the bagasse is critical state behaviour similar to that for sand and clay. Progress has been made in the last 11 years towards implementing a mechanical model for bagasse in finite element software. The objective is to be able to correctly simulate various simple mechanical loading conditions measured in the laboratory. Combining these behaviours together is thought to have a high probability of reproducing the complicated stress conditions in a milling unit. This paper reports on progress made towards modelling the fifth and final (and most challenging) of the simple loading conditions: the shearing of heavily over-consolidated bagasse, using a specific model for bagasse in a multi-element simulation.

Interrupting malaria transmission: quantifying the impact of interventions in regions of low to moderate transmission

Malaria has been eliminated from over 40 countries with an additional 39 currently planning for, or committed to, elimination. Information on the likely impact of available interventions, and the required time, is urgently needed to help plan resource allocation. Mathematical modelling has been used to investigate the impact of various interventions; the strength of the conclusions is boosted when several models with differing formulation produce similar data. Here we predict by using an individual-based stochastic simulation model of seasonal Plasmodium falciparum transmission that transmission can be interrupted and parasite reintroductions controlled in villages of 1,000 individuals where the entomological inoculation rate is <7 infectious bites per person per year using chemotherapy and bed net strategies. Above this transmission intensity bed nets and symptomatic treatment alone were not sufficient to interrupt transmission and control the importation of malaria for at least 150 days. Our model results suggest that 1) stochastic events impact the likelihood of successfully interrupting transmission with large variability in the times required, 2) the relative reduction in morbidity caused by the interventions were age-group specific, changing over time, and 3) the post-intervention changes in morbidity were larger than the corresponding impact on transmission. These results generally agree with the conclusions from previously published models. However the model also predicted changes in parasite population structure as a result of improved treatment of symptomatic individuals; the survival probability of introduced parasites reduced leading to an increase in the prevalence of sub-patent infections in semi-immune individuals. This novel finding requires further investigation in the field because, if confirmed, such a change would have a negative impact on attempts to eliminate the disease from areas of moderate transmission.

Photophysical characterization of light-emitting poly(indenofluorene)s

Time-resolved photoluminescence spectroscopy experiments of three poly(2,8-indenofluorene) derivatives bearing different pendant groups are presented. A comparison of the photophysical properties of dilute solutions and thin films provides information on the chemical purity of the materials. The photophysical properties of poly(2,8-indenofluorene)s are correlated with the morphological characteristics of their corresponding films. Wide-angle X-ray scattering experiments reveal the order in these materials at the molecular level. The spectroscopic results confirm the positive impact of a new synthetic approach on the spectral purity of the poly(indenofluorene)s. It is concluded that complete side-chain substitution of the bridgehead carbon atoms C-6 and C-12 in the indenofluorene unit, prior to indenofluorene ring formation, reduces the probability of keto formation. Due to the intrinsic chemical purity of the arylated derivative, identification of a long-delayed spectral feature, other than the known keto band, is possible in the case of thin films. Controlled doping experiments on the arylated derivative with trace amounts of an indenofluorene-monoketone provide quantitative information on the rates of two major photophysical processes, namely, singlet photoluminescence emission and singlet photoluminescence quenching. These results allow the determination of the minimum keto concentration that can affect the intrinsic photophysical properties of this polymer. The data suggest that photoluminescence quenching operates in the doped films according to the Stern-Volmer formalism.