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Supplementary Figure 1. Construction of two conventional WT1 DNA vaccines and generation of WT1-expressing AB1 malignant mesothelioma cell line. Supplementary Figure 2. Construction of HIV-1 GAG-expressing AB1 malignant mesothelioma cell line. Supplementary Figure 3. Importance of inducing p24-specific cellular responses for AB1-GAG tumor rejection. Supplementary Figure 4. Anti-tumor effect from CD8+ T cells was cross-confirmed in a B16F10 melanoma mouse model. Supplementary Figure 5. Secreted cytokines from CD8+ T cells significantly arrested AB1-GAG tumor cells at G1 phase. Supplementary Figure 6. Gating strategies for flow cytometric scatter plots. Supplementary Figure 7. Analysis of CD8+ T cell subsets in spleen and tumor. Supplementary Figure 8. Analysis of Th2 and exhaustion markers on CD8+ T cells in spleen and tumor. Supplementary Figure 9. Rapid increase of tumor-induced PD-1+CD8+ T, Tim-3+CD8+ T, MDSCs and CD4+ Treg cells. Supplementary Figure 10. Splenic and tumor-infiltrating CD8+ T cells exhibit distinct phenotypic and functional characteristics. Supplementary Figure 11. Correlation analyses of vaccine-elicited CD8+ T cells in therapeutic exp. Supplementary Figure 12. Correlation analyses in adoptive transfer experiments for inhibitory CD8+ T cells and their cytokine function. eriments.

More detailed description of materials and methods.

The file contains Figure Legends for Supplemental Figures. 12 figure legends are numbered and placed in order.

Introduction The risk of breast cancer increases with age and our global population is ageing. By 2040 the number of breast cancer cases diagnosed per year worldwide will double and over 40% of these will be in patients aged 70 or over. Despite this, there are few treatment guidelines specific to breast cancer in older women and none which consider the unique biological differences of this cohort. Method Surgical and core needle biopsy (CNB) specimens were obtained from an existing series of 1,785 women over the age of 70 with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and 693 CNB specimens. Immunohistochemical staining for 32 biomarkers has been performed in all of the available TMAs. Association between histological score for each biomarker and tumour size, grade, recurrence rate, breast cancer specific and overall survival is currently being investigated in the whole cohort. Results Results to date have revealed a unique biological cluster in older women with primary breast cancer that is not seen in a comparative younger cohort. In the future, bioinformatics analysis will determine which biomarkers and in what combination, can predict chance of recurrence/overall survival in this cohort. Conclusions This information will be used to create a prognostic tool specific to assist older women with decision making regarding primary treatment of breast cancer.

This abstract was withdrawn by the authors. Citation Format: Athanasiou I, Reed MW, Shrestha A, Cheung K-L, Audisio R, Collins K, Wyld L. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-06.

Background: Capivasertib (AZD5363), an AKT1,2,3 inhibitor, significantly improved progression-free and overall survival when added to paclitaxel in triple negative breast cancer (BC) patients (Schmid et al. ASCO 2018). We have previously reported in STAKT, robust target inhibition at 480mg BD versus placebo, including significant decreases in the primary biomarkers (PBs) - Ki67, pPRAS40 & pGSK3β - in primary BCs (Robertson et al. SABCS 2017). We now report the dose- and exposure-response relationship of capivasertib and the correlation between primary and secondary (pAKT, pS6, nuclear FOXO3a) tumor biomarkers. Design: STAKT was a two-stage, double blind, randomized, placebo controlled 'window-of-opportunity' trial in newly diagnosed ER+ BC patients. Stage 1 assessed capivasertib at a dose of 480mg BD p.o. versus placebo. Stage 2 assessed capivasertib at two lower doses 360mg and 240mg BD. Tumor biopsies were taken prior to 1st dose and after 4.5 days of dosing. Evaluable patients (who required pre-defined minimum baseline PD values for PBs) included placebo (n=11), capivasertib at 480mg (n=17), 360mg (n=5) and 240mg (n=6). Blood samples for pharmacokinetic (PK) studies were scheduled at pre-dose; 2, 4, optional 6 & 8 hrs post first dose on Day 1; ˜2-4 h post last dose on Day 5 (before biopsy). The % change from baseline for PBs were evaluated against the following exposure variables (placebo=0): i) Dose, ii) Observed Cmax Day 1 (˜2h post-dose), iii) Observed plasma concentration on Day 5, iv) Model-predicted plasma concentration Day 5 at time of biopsy, and v) Model-predicted AUC on Day 5. Spearman correlation coefficient measured the strength and direction of association between biomarkers. Results: · Significant mean reductions in % change from baseline were observed for the PBs pGSK3β (-39%; p · Dose-response relationships for individual % change from baseline could be described by an Emax model for all PBs. Overall, the correlation to PK exposure (observed or predicted) was similar to the correlation to dose. · Correlation coefficient analyses between biomarkers at capivasertib 480mg BD identified- i) Positive correlations for pGSK3β with Ki67 (ρ = 0.52, p-value < 0.05) & with pS6 (ρ = 0.54, p-value Conclusions · Capivasertib caused dose- and concentration- dependent effects on biomarkers after only 4.5 days. · Significant changes in the PBs were demonstrated at 480 mg BD. Biomarker changes was observed at 360mg and 240mg BD, but statistical analysis was limited by the small sample size at lower doses. · Correlation between a number of tumor biomarkers (relative changes) were identified for capivasertib 480mg BD. Citation Format: Gee J, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Horgan K, Rauchhaus P, Littleford R, Finlay P, Cheung A, Cullberg M, de Bruin E, Foxley A, Koulai L, Pass M, Schiavon G, Rugman P, Deb R, Robertson JFR. Dose- and exposure-response relationship and biomarker correlation analysis in breast tumors from patients treated with capivasertib, an AKT inhibitor, in the STAKT randomized, placebo controlled pre-surgical study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-12-01.

Cyclists form the most vulnerable road user group in terms of injury from traffic accidents, as well as exposure to traffic-related air pollution. Ironically, commuter cyclists are often motivated by improvement in health and fitness. Cycleways away from traffic with lower concentrations of pollutants from motorised vehicles sometimes result in longer distances and hence require longer travel times, while alternative routes sharing the road with other traffic, sometimes with buses, might result in exposure to higher pollutant concentrations. To help commuter cyclists achieve their objectives of getting to work in the shortest possible time and maximising their health benefits, we propose a bi-objective route choice model, with the minimisation of travel time and pollutant dose as the two objectives. A transport network information database is first constructed with comprehensive information on link type, lane width, gradient, link average speed, traffic volume, etc. such that both the travel time and the pollutant dose can be estimated at a reasonable level of accuracy. In particular, the pollutant dose will be dependent on the exercise level as well as the concentration of pollutants. Given an origin and a destination, to be provided by a cyclist, we apply a bi-objective shortest-path algorithm to determine an efficient set of routes such that neither the total travel time nor the total pollutant dose can be reduced without worsening the other. Profiles of this route choice set in terms of other useful information, such as elevation, and pollutant concentrations along the route can also be provided. With our model, cyclists can more easily trade off between commute time and pollutant dose. In cities with hilly terrain, such as in Auckland, New Zealand, such information can be expected to be extremely valuable for current and potential cyclists.

Photovoltaic (PV) is one of the promising solar energy applications. Measured data can give the realistic performance of PV systems under actual operating environments for product selection and system design. This paper studies a grid-connected PV system installed in an institutional building. Technical data including available solar radiation and output energy generated were systematically recorded and analyzed. The performance of the PV system is elaborated in terms of energy, environmental and financial aspects. Feed-in-tariff (FIT) schemes with high electricity selling price can encourage the deployment of PV system. The monetary payback period (MPBP) for the PV system was computed to be 72.4 years when the electricity buying price is equal to the electricity selling price. If carbon trading was considered, the payback was shortened to 61.4 years. The embodied energy payback period (EEPBP) was estimated to be 8.9 years. The findings would be useful for planning grid-connected PV installations and applicable to other spaces with similar architectural layouts.

This paper studies the classification of the International Commission on Illumination (CIE) Standard General Skies using vertical sky component ( VSC ) defined as the procedures for identifying the Standard General Skies are proposed. The performance of the recommended sky classification process was evaluated against measured data in terms of percentage error (PE) and root-mean-square error (RMSE). The results revealed that the method produced the RMSE of not more than 20% for most of classified Standard General Skies. The proposed approach provides an alternative for defining CIE Standard General Skies when the measured vertical and horizontal daylight illuminance data are available.

Climatic variables are frequently used as weighting factors to indicate the degree of clearness for interpreting sky patterns. However, such important parameters are not always widely available and their criteria to define a sky condition are not clear-cut. In addition, certain variables may be more effective than the others in terms of sky identification. This paper studies the capability of various daylight parameters, namely zenith luminance, global, direct-beam and sky-diffuse illuminance, and solar altitude for categorizing the 15 International Commission on Illumination (CIE) standard skies. A new form of artificial neural networks called probabilistic neural network (PNN) which is a powerful technique for pattern recognition was used for the analysis. The findings suggested that the PNN is an appropriate tool when a number of climatic parameters of various criteria for differentiating sky standards are employed, and the ratio of zenith luminance to diffuse illuminance (Lz/Dv) and solar altitude (αs) are respectively the most and the least significant input parameters for discriminating between the 15 CIE skies.

Daylighting is an effective sustainable development strategy to alleviating the problems in energy and the environment, and improving the qualities for visual comfort and health. In Hong Kong, many buildings are high-rise blocks constructed close to each other resulting in severe sky obstructions. Recently, a great deal of attention has been paid to the development of natural daylight exploitation products. One invention is the light-pipe system that transports natural light efficiently from outdoor into rear part of a room. However, this innovative daylighting device is not popular in subtropical Hong Kong. The main reason for such unenthusiastic responses is the lack of local data to indicate the visual performance, energy savings and design implications. A research project was initiated to evaluate these issues. The study includes field measurements of daylight illuminance in a corridor installed a number of light pipes. The results demonstrate that the light-pipe system can provide sufficient illuminance, improve the daylight uniformity and have a high potential to reduce the electric lighting energy consumption.

Background: AKT is an important intracellular control point through which Type 1 growth factors and IGFR signal. Mutations in PIK3CA, AKT and PTEN are prevalent in estrogen receptor positive (ER+) breast cancer (BC) and have been implicated in resistance to endocrine therapies. AZD5363 is an inhibitor of AKT 1, 2 and 3 currently in Phase 2 trials for BC and other solid cancers. Design: The study examined whether AZD5363 impacts on key biomarkers within the AKT pathway and their subsequent effects on Ki67, a marker of tumor proliferation. STAKT is a multi-center, two-stage, double blind, randomized, placebo controlled, biomarker 'window-of-opportunity' trial in women with newly diagnosed, previously untreated ER+ BC who were deemed would require chemotherapy as part of their primary treatment regimen. Stage 1 assessed AZD5363 at a dose of 480mg bd p.o. versus matching placebo. Up to 30 patients per arm were permitted, to allow 12 subjects per arm with evaluable paired biopsies - obtained at baseline, and after 4.5 days of AZD5363 / placebo. Primary endpoint markers were pPRAS40, pGSK3β and Ki67 assessed by immunohistochemistry. pPRAS40 and pGSK3β were assessed by H-scores and measured separately for cytoplasmic (cyto), nuclear (nuc) and total (cyto+nuc) staining. Ki67 was assessed as % positive staining of 500 tumor nuclei. Laboratory staff were blinded to treatment arm and whether the biopsies were taken before or after AZD5363/placebo. Changes in marker expression (both absolute and %) between biopsies were calculated, and compared between the two groups. An ANOVA test was applied for normally distributed data and Wilcoxon Mann-Whitney used if not normally distributed. Results: 28/36 patients were evaluable with patient & tumor characteristics as follows: 17 received AZD5363 and 11 placebo; the median ages were 48 & 49 years respectively. 27 patients were Caucasian and 1 African-American. Tumors were all ER+. For HER2 status 8 were positive & 9 negative in the AZD5363 treated group compared to 2 & 9 respectively in the placebo group. For pPRAS40 and pGSK3β cyto was the predominant staining while for Ki67 staining was nuclear. Changes in each marker with associated p-values are shown in the table. MarkerType of change vs baselineDegree of change in AZD5363 arm (n=17)p-value versus placebo arm (n=11)pPRAS40 (H-score)TotalAbsolute-83.8 Conclusions• AZD5363 for 4.5 days caused highly significant falls in pGSK3β and pPRAS40, key markers of AKT pathway activation • AZD53643 also caused a significant decline in Ki67 even after only 4.5 days of drug. This is one of the shortest 'window'-studies to report such an early effect on proliferation. • Placebo controlled 'window' studies of this short duration can provide important evidence of the therapeutic potential early in a drug's development. Citation Format: Robertson JFR, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Kelly S, Horgan K, Rauchhaus P, Littleford R, Foxley A, Lindemann JPO, Pass M, Rugman P, Deb R, Finlay P, Gee JMW. AZD5363, an AKT inhibitor, significantly inhibits key biomarkers of the AKT pathway and Ki67, in a randomized, placebo, controlled study (STAKT) in human breast cancers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-06.

Electric lighting is one of the major energy consuming items in many non-domestic buildings. Using appropriate energy-efficient light fittings with dimming controls and proper daylighting schemes can help reduce the electrical demand and contribute to visual comfort and green building development. This paper presents a study on the energy and lighting performances for energy-efficient fluorescent lamps associated with electronic ballasts and high frequency photoelectric dimming controls installed in a school building. Electricity expenditures and indoor illuminance levels for a workshop and a classroom employing high frequency dimming controls were analyzed. Simple prediction methods were used to illustrate the lighting savings. The findings provide the operational and performance information, which would be applicable to other spaces with similar building layouts and lighting schemes.

In a dense urban region in which high-rise buildings are packed inside limited land areas, the daylight components reflected from ground and surrounding buildings play significant roles in daylighting design. The natural light available in an interior strongly depends on the amount of daylight reaching the window facades. Lately we proposed a calculation procedure, presented in form of simple mathematical expressions and diagrams, to determine the daylight illuminance on a vertical plane under overcast skies. This paper extends the study to non-overcast sky conditions. The performance of the proposed method was evaluated by comparison with the daylight illuminance simulated by a lighting software, namely RADIANCE, and with measurements under real skies. It was found that the data estimated by the proposed method were in good agreement both with the values simulated by RADIANCE and with the measured results. The paper offers to architects and building engineers a useful tool for estimating the daylight illuminance and in particular for determining and assessing various daylighting schemes and concepts during design and construction stages.

Sustainability is the trend of the modern building designs, in which solar energy conversion systems and daylighting schemes are widely considered as the important building energy strategies to reduce the peak cooling and electrical demands, generate clean energy and save the building electricity expenditures. A semi-transparent photovoltaic (PV) is a renewable energy product producing electricity via solar cells and allowing natural light entering into the interior spaces for daylighting designs. The PV modules are effective in reducing the cooling demand, especially for the skylight atrium that often receives large solar heat gains. This paper studies the thermal and visual properties, energy performance, environmental and financial issues of such semi-transparent PV skylights. Field measurements including solar irradiance, daylight illuminance and electricity generated were carried out. Case studies based on a circulating atrium were conducted to evaluate the energy use, cooling requirements and monetary implications when the PV skylights together with the daylight-linked lighting controls were applied. The results indicated that such an integrated system could save the overall electricity expenditures and benefit to the environmental and financial aspects.

Hong Kong is one of the most densely populated cities in the world. Its buildings are largely high-rise blocks constructed close to each other and, hence outdoor obstructions play significant roles in daylighting designs. The light reflected from the ground and surrounding buildings can be important sources of interior lighting and detailed computations are required. We currently propose a calculation procedure in terms of a number of regression equations to determine the daylight illuminance on vertical surfaces. This paper presents the work to assess this approach via full-scale measurements under real sky conditions. The mean surface reflectance for external obstructions was estimated using lighting simulation techniques. It was shown that daylight illuminance obtained by the proposed method were in reasonably good agreement with measured readings. The simple nature of the proposed approach offers building professionals and students a reliable and convenient alternative to predict daylight illuminance particularly when different daylighting schemes and concepts are being considered.

Principal component analysis of dry-bulb temperature, wet-bulb temperature, global solar radiation, clearness index and wind speed was conducted, and a two-component solution obtained which could explain 80% of the variance in the original weather data. Clustering analysis of these two principal components resulted in a total of 18 typical day types being identified. A year long monitoring of the daily chiller plant electricity consumption in a fully air-conditioned office building was conducted. It was found that the typical day types exhibited daily and seasonal variations similar to the daily and monthly electricity consumption recorded. Three regression models were developed to correlate the daily chiller plant electricity consumption and the corresponding day types. The coefficient of determination (R2) was 0.86–0.99 showing strong correlation. It is proposed that the day type approach can be used as a tool for weather normalisation and inter-year comparisons in the analysis of energy savings due to building retrofits. It was also found that the typical day types identified appeared to show a slight increasing trend during the 28-year period (1979–2006) indicating a subtle, but gradual change of climatic conditions that might affect chiller plant electricity consumption in future years.

Daylighting has long been recognized as an important issue in architecture. In Hong Kong many buildings are constructed close to each other and hence the external environment plays a significant role in building designs. Recently, vertical daylight factor (VDF) has been used as a criterion to justify the provision of natural lighting in buildings. This paper studies the calculation approach of VDF in a heavily obstructed environment. The techniques for determining the sky component and the reflected daylight from surrounding buildings and ground surfaces are described. Calculation tools in the form of simple equations and diagrams through computer-simulation analysis were established. The performance of the proposed method was evaluated against the daylight illuminance obtained by other independent computer simulations. It was found that predictions from the proposed approach were in good agreements with those produced by simulated results. The findings provide architects and building designers with a simple method for estimating the daylight illuminance at early design and planning stage.

This short technical note presents an attempt to develop a new climatic variable Z for assessing climate change (global warming) with respect to the built environment. Principal component analysis of long-term (30-year) dry-bulb temperature (DBT), wet-bulb temperature and global solar radiation data was conducted in the 5 major climate zones in China. It was found that while the long-term trend was increasing for the DBT in all 5 major climates, hot summer and warm winter climate zone showed a decreasing trend (though slightly) in the annual and seasonal average Z values. This suggests that climate change might not necessarily result in higher cooling loads in buildings.

Two-parameter regression models were used to predict global solar radiation (GSR) for the nine major thermal zones and sub-zones – severe cold (I, II and III), cold (I, II and III), hot summer and cold winter, mild, and hot summer and warm winter – across China. The impact of using modelled GSR on building energy simulation was investigated. A total of nine cities were selected, one for each thermal zone. Generic office buildings were developed for each of the nine cities according the local design/energy codes. Two sets of energy simulation were conducted for each city, one with the measured GSR and the other the modelled data. The computed results were analysed in four aspects – solar heat through the windows, building heating loads, building cooling loads and the corresponding building energy consumption. It was found that simulated annual heating/cooling loads could differ by 0.1–6.2% and total building energy consumption 0.1–1.2%. These differences were also compared with the mean bias error and root-mean-squared error of the modelled GSR.

Designing a building to integrate daylight requires an accurate estimation of the amount of available outdoor illuminance. The common method for predicting daylight has been the derivation of illuminance from the more widely measured solar irradiance using the luminous efficacy approach. Recently, the International Commission on Illumination (CIE) has adopted a range of 15 standard skies which cover the whole probable spectrum of skies in the world. This paper presents the work to model the luminous efficacy of diffuse component under the 15 CIE standard skies. Sky luminance distributions measured between 1999 and 2005 were used for the standard sky classifications. An approach to develop luminous efficacy for inclined surfaces was proposed. The predicted vertical outdoor illuminance data for the four cardinal planes (i.e., N, E, S and W) using the proposed luminous efficacy were evaluated against data measured in 2004. Statistical analysis indicated that the estimated daylight illuminance data give acceptable agreements with measured data for all vertical planes.

Sensitivity analysis is performed to observe the response of the system when a given design parameter is changed. It is important to know the relationships between the input parameters and output results such that appropriate design variables can be selected to achieve the optimum building energy performance. This paper studies the sensitivity of energy performance and establishes regression models for office buildings with daylighting designs in Hong Kong. The building energy simulation computer program, namely EnergyPlus, was used to generate data for the analysis. The important input design parameters affecting the daylighting schemes were identified and analysed in terms of annual building electricity expenditures and peak electrical demands. Four building envelope design parameters, namely, window-to-wall ratio, light transmittance of windows, projection ratio of overhang, and projection ratio of side-fins were found to correlate well with the predicted incremental electricity use (IEU) and incremental peak electricity use (IPEU). Both linear and non-linear multiple regression techniques were used to develop regression models and energy equations for the predictions of IEU and IPEU. Statistical results show that such models and equations can be used to evaluate the energy performance of various building envelope design schemes for building with daylighting controls during the early design stage.

An accurate estimation of the amount of daylight entering a building is the key step in evaluating daylighting designs. The concept of the daylight coefficient (DC), which considers changes in the luminance of the sky elements, offers an effective way of computing indoor daylight illuminances under various sky conditions and solar positions. We currently propose a numerical procedure in the form of nomograph to compute the interior daylight illuminance using the DC concept. This paper presents the work to validate this method via scale model measurements under different actual sky patterns. It was shown that daylight illuminances calculated by the proposed method were in reasonably good agreement with measured results. The findings will hopefully provide building professionals and students with a reliable and simple alternative to current practices that incorporate sky luminance variations to predict the indoor daylight illuminance and assess visual performance under various real sky conditions.

Disease-free interval differs amongst invasive breast cancer patients, who had not received any prior adjuvant systemic therapy, with oestrogen receptor (ER) positive cancers treated by endocrine therapy at the time of relapse. This suggests the presence of biological factors inherent in tumours which affect responsiveness to subsequent endocrine therapy. ER splice variants result from exon deletions and can repress wild-type receptors and modulate anti-oestrogen activity. We hypothesise ER splice variants contribute to the differences seen with therapeutic response in these patients. We have characterised variant ER expression in primary invasive breast cancer patients that either responded or not responded to endocrine therapy at the time of relapse. Breast tumour cells were isolated from formalin-fixed archival tumour sections using laser microdissection. Total RNA was extracted and expression of ER�, ER�R2-3, ER�R3, ER�R5, ER�1, ER�2 was quantified using real-time PCR. Gene expression was normalised against 18s expression. Expression of ER� wildtype and variants were detected in most breast tumours although levels differed. ER�1 was highly expressed in tumours with low ER� expression. ER�2 was less commonly expressed. An association between disease-free interval and ER variant expression remains to be elucidated although there was a tendency for tumours expressing ER� also expressed ER�R3.

There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of human epidermal growth factor receptor-2 (HER2) overexpressing tumours in older women. Currently, research involving trastuzumab at large focuses on the younger population. This study aimed to analyse their biological characteristics and to compare them with their younger counterparts from a single centre with a long-term clinical follow-up.Over 37 years (1973-2010), 1758 older (≥70 years) women with early operable (5 cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these, 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray analysis using indirect immunohistochemistry. Comparison was made with data from a well-characterised younger (70 years) series (N = 1711) treated between 1986 and 1998 (before adjuvant trastuzumab became standard) in our institution. Forty five (7.6%) and 140 (8.2%) patients from the older and younger series, respectively, had HER2-positive tumours.HER2 overexpression was seen in 45 (7.6%) older women and 140 (8.2%) in younger patients (P = 0.56). HER2 overexpressing tumours in older women when compared with that in their younger counterparts were associated with low Ki67 and high bcl2 expression (P0.05). Only 26% of the younger patients and none of the older patients received adjuvant chemotherapy, and no patients at the time received trastuzumab. However, there was no significant difference in the outcome of the two age groups (5-year breast cancer-specific survival rate:70 years = 65% versus70 years = 70%, P = 0.51).HER2 overexpressing tumours in older women showed relatively a less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy when compared with the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated.

We describe an exposure of varicella zoster virus in our neonatal intensive-care unit and the emergency procedures instituted to prevent an outbreak. Fifty-seven infants and 129 staff members were exposed but none developed chickenpox. The measures included rapid identification of varicella antibody status in all neonates and those staff members with uncertain history of varicella infection; cohorting of exposed infants according to immune status; and prompt administration of varicella zoster immunoglobulin to susceptible patients. The recommendation of the American Academy of Pediatrics did not accurately predict the immune status of preterm infants, as only one of the eight susceptible infants would have qualified for immunoglobulin prophylaxis if their guidelines had been followed. Mass screening of all exposed infants using the varicella zoster enzyme linked immunosorbent assay (ELISA) test was the only reliable means of determining the immune status. Of the four risk factors evaluated for the prediction of antibody status: gestational age, postnatal age, birthweight and episodes of blood transfusion, only postnatal age was found to independently predict the immune status of our patients. Because varicella zoster susceptible staff members are difficult to identify on the basis of history, we suggest that prospective screening of staff in high-risk units be undertaken and vaccination with live varicella vaccine be offered to susceptibles.

A novel distributed test architecture of transmitting IEEE 1149.1 boundary scan (a.k.a JTAG) test access port (TAP) signals over a serial channel is presented in this paper. It is developed to facilitate the system testing and remote field update of distributed base stations (DBS) in a wireless network. The state-of-the-art DBS does not only improve the overall quality of wireless network services via its ability and ease to provide wider coverage in various environments, but also lowers the installation and operation costs as well as reduces the space requirements. However, the DBS poses great challenges for system testing and field update operation due to its distributed architecture. The proposed distributed test architecture enables the system testing as if the distributed units are on a backplane within the same chassis. In addition, the embedded boundary scan test software, that is running on the microprocessor of the controller board, takes advantage of the proposed distributed test architecture to update the configuration programmable ROMs (PROMs) of the distributed units remotely without on-site visits. A novel slow-fast programming algorithm is also proposed for efficient remote field update in DBS to overcome significant fiber propagation delay. It reduces the time for PROM update from over an hour to less than 19 minutes over a 12 km fiber.

Track 1 Solid Tumours in the Elderly Breast cancer in eldery patients P001 Decision making in older women with primary operable breast cancer R.M. Parks*, P. Howard, L. Hall, S.-W. Tang, R. Lakshmanan, L. Winterbottom, D. Morgan, D. Porock, K. Cox, K.-L. Cheung. Division of Breast Surgery, Nottingham University Hospitals; School of Nursing, University of Nottingham; NottinghamBreast Institute, Nottingham University Hospitals, Nottingham, UK; Department of Oncology, Nottingham University Hospitals, Nottingham, UK; School of Nursing, University of Buffalo, New York, USA

A pair of preterm twins developed fatal necrotizing enterocolitis (NEC) in association with Staphylococcus epidermidis septicaemia after receiving contaminated expressed breast milk (EBM). S. epidermidis NEC can be associated with severe bowel inflammation, high morbidity and mortality. Breast milk is the most suitable nutrient for preterm infants but EBM should undergo regular screening for bacterial overgrowth. We urge caution before administering EBM found to be heavily contaminated with S. epidermidis to preterm infants.

patients aged ≥70 years. Methods: Between October 2011 and April 2012, 403 patients were included: 171 and 232 patients in the retrospective and the prospective study, respectively. Elderly patients (≥70 years) were analysed separately and their characteristics were compared to the youngest patients (b70 years old). Results: In the retrospective study, 55 elderly patients were analysed. Median age was 78 years [70–94]. Thirty-six (65%) and 8 (15%) patients had hormone-sensitive and HER2-positive tumours, respectively. Seven (7) and 24 patients had exclusive bone and visceral metastases, respectively. Twenty-four (24) patients received oral Navelbine as first line therapy, 27 as second line and 4 beyond second line. The median duration of treatment was 6 months regardless the line of treatment. Oral Navelbine was prescribed as single-agent therapy in 36 patients. In case of combination regimen, oral Navelbine was combined with chemotherapy in 13 patients (capecitabine in 12 patients (22%)) or with a targeted therapy in 6 (mainly trastuzumab). In the prospective study, 84 elderly patients were analysed. Median age was 75 years [70–89]. PS was 0 or 1 in 50 patients, and 65 had at least one comorbidity. Sixty-two (74%) and 79 (94%) patients had hormone-sensitive and HER2-positive tumours, respectively. Exclusive bone metastases were found in 25 patients. The median starting dose of oral Navelbine was 59 mg/m. Singleagent therapy was given in 70 patients (31 patients (37%) and 32 patients (38%) in first and second lines, respectively) whereas 14 patients received a combination regimen, of whom 11 patients (79%) received capecitabine. The monitoring showed that the time to the next scheduled visit was less than 30 days in only 63% of the patients. Conclusion: The results of both retrospective and prospective studies show similar profiles of elderly MBC patients treated by oral Navelbine. In this population, oral Navelbine is often prescribed as single-agent, for the first or the second line and for the same duration regardless of the line. In case of combination, oral Navelbine is most often combined with capecitabine or trastuzumab (in HER2positive patients). Interestingly, the prospective study shows that the follow-up of patients needs to be optimized, a particularly important issue in the setting of an oral chemotherapy schedule in the elderly.

O1 Biological characteristics of triple negative early operable primary breast cancer in older women in comparison with their younger counterparts B.M. Syed, A.R. Green, D.A.L. Morgan, I.O. Ellis, K.L. Cheung*. Division of Breast Surgery, University of Nottingham, Nottingham, UK, Divisions of Pathology, University of Nottingham, Nottingham, UK, Department of Oncology, NottinghamUniversity Hospitals, Nottingham, UK