Safety and efficacy of the combination of trastuzumab with docetaxel for HER2-positive women with advanced breast cancer : a review of the existing clinical trials and results of the expanded access programme in the UK

Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. © 2004 Blackwell Publishing Ltd.

Facebook, telecollaboration, and international access to technology in the classroom

This study uses the well-known social networking site, Facebook (FB), for a study of differences in perceptions on the use of technologies in the classroom around the world. This study is part of a larger project exploring telecollaboration and the use of online discussions between graduate students in an online masters program based in Australia and students in the graduate education program at a regional university in Greece. Postings reveal more similarities between the situations and perceptions of the participants from the different countries than differences. Most participants indicated that while they and their students had access in general to computers and the internet, they did not necessarily have this access in the classroom. Even when technologies were available in schools, participants identified a critical need for professional development to increase teachers’ use of ICT. These findings are relevant to educators and policy development in terms of implementation of ICT or social networking in the language classroom.

Order tracking for discrete-random separation in variable speed conditions

The transmission path from the excitation to the measured vibration on the surface of a mechanical system introduces a distortion both in amplitude and in phase. Moreover, in variable speed conditions, the amplification/attenuation and the phase shift, due to the transfer function of the mechanical system, varies in time. This phenomenon reduces the effectiveness of the traditionally tachometer based order tracking, compromising the results of a discrete-random separation performed by a synchronous averaging. In this paper, for the first time, the extent of the distortion is identified both in the time domain and in the order spectrum of the signal, highlighting the consequences for the diagnostics of rotating machinery. A particular focus is given to gears, providing some indications on how to take advantage of the quantification of the disturbance to better tune the techniques developed for the compensation of the distortion. The full theoretical analysis is presented and the results are applied to an experimental case.

Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures

Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury whilst recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, whilst maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size and permeability decreased, whilst computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (~45% to ~86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment.

Access to commercial destinations within the neighbourhood and walking among Australian older adults

BACKGROUND: Physical activity, particularly walking, is greatly beneficial to health; yet a sizeable proportion of older adults are insufficiently active. The importance of built environment attributes for walking is known, but few studies of older adults have examined neighbourhood destinations and none have investigated access to specific, objectively-measured commercial destinations and walking. METHODS: We undertook a secondary analysis of data from the Western Australian state government's health surveillance survey for those aged 65--84 years and living in the Perth metropolitan region from 2003--2009 (n = 2,918). Individual-level road network service areas were generated at 400 m and 800 m distances, and the presence or absence of six commercial destination types within the neighbourhood service areas identified (food retail, general retail, medical care services, financial services, general services, and social infrastructure). Adjusted logistic regression models examined access to and mix of commercial destination types within neighbourhoods for associations with self-reported walking behaviour. RESULTS: On average, the sample was aged 72.9 years (SD = 5.4), and was predominantly female (55.9%) and married (62.0%). Overall, 66.2% reported some weekly walking and 30.8% reported sufficient walking (>=150 min/week). Older adults with access to general services within 400 m (OR = 1.33, 95% CI = 1.07-1.66) and 800 m (OR = 1.20, 95% CI = 1.02-1.42), and social infrastructure within 800 m (OR = 1.19, 95% CI = 1.01-1.40) were more likely to engage in some weekly walking. Access to medical care services within 400 m (OR = 0.77, 95% CI = 0.63-0.93) and 800 m (OR = 0.83, 95% CI = 0.70-0.99) reduced the odds of sufficient walking. Access to food retail, general retail, financial services, and the mix of commercial destination types within the neighbourhood were all unrelated to walking. CONCLUSIONS: The types of neighbourhood commercial destinations that encourage older adults to walk appear to differ slightly from those reported for adult samples. Destinations that facilitate more social interaction, for example eating at a restaurant or church involvement, or provide opportunities for some incidental social contact, for example visiting the pharmacy or hairdresser, were the strongest predictors for walking among seniors in this study. This underscores the importance of planning neighbourhoods with proximate access to social infrastructure, and highlights the need to create residential environments that support activity across the life course.

The impact of the built environment on health across the life course : design of a cross-sectional data linkage study

Introduction: The built environment is increasingly recognised as being associated with health outcomes. Relationships between the built environment and health differ among age groups, especially between children and adults, but also between younger, mid-age and older adults. Yet few address differences across life stage groups within a single population study. Moreover, existing research mostly focuses on physical activity behaviours, with few studying objective clinical and mental health outcomes. The Life Course Built Environment and Health (LCBEH) project explores the impact of the built environment on self-reported and objectively measured health outcomes in a random sample of people across the life course. Methods and analysis: This cross-sectional data linkage study involves 15 954 children (0–15 years), young adults (16–24 years), adults (25–64 years) and older adults (65+years) from the Perth metropolitan region who completed the Health and Wellbeing Surveillance System survey administered by the Department of Health of Western Australia from 2003 to 2009. Survey data were linked to Western Australia's (WA) Hospital Morbidity Database System (hospital admission) and Mental Health Information System (mental health system outpatient) data. Participants’ residential address was geocoded and features of their ‘neighbourhood’ were measured using Geographic Information Systems software. Associations between the built environment and self-reported and clinical health outcomes will be explored across varying geographic scales and life stages. Ethics and dissemination: The University of Western Australia's Human Research Ethics Committee and the Department of Health of Western Australia approved the study protocol (#2010/1). Findings will be published in peer-reviewed journals and presented at local, national and international conferences, thus contributing to the evidence base informing the design of healthy neighbourhoods for all residents.

Hebbian reverberations in emotional memory micro circuits

The study of memory in most behavioral paradigms, including emotional memory paradigms, has focused on the feed forward components that underlie Hebb’s first postulate, associative synaptic plasticity. Hebb’s second postulate argues that activated ensembles of neurons reverberate in order to provide temporal coordination of different neural signals, and thereby facilitate coincidence detection. Recent evidence from our groups has suggested that the lateral amygdala (LA) contains recurrent microcircuits and that these may reverberate. Additionally this reverberant activity is precisely timed with latencies that would facilitate coincidence detection between cortical and sub cortical afferents to the LA.Thus, recent data at the microcircuit level in the amygdala provide some physiological evidence in support of the second Hebbian postulate.

Knowledge unlatched : encouraging innovation in academic publishing through collective action and Open Access licensing

This case study examines the way in which Knowledge Unlatched is combining collective action and open access licenses to encourage innovation in markets for specialist academic books. Knowledge Unlatched is a not for profit organisation that has been established to help a global community of libraries coordinate their book purchasing activities more effectively and, in so doing, to ensure that books librarians select for their own collections become available for free for anyone in the world to read. The Knowledge Unlatched model is an attempt to re-coordinate a market in order to facilitate a transition to digitally appropriate publishing models that include open access. It offers librarians an opportunity to facilitate the open access publication of books that their own readers would value access to. It provides publishers with a stable income stream on titles selected by libraries, as well as an ability to continue selling books to a wider market on their own terms. Knowledge Unlatched provides a rich case study for researchers and practitioners interested in understanding how innovations in procurement practices can be used to stimulate more effective, equitable markets for socially valuable products.

Knowledge unlatched : enabling open access for scholarly books

Although digital technology has made it possible for many more people to access content at no extra cost, fewer people than ever before are able to read the books written by university-based researchers. This workshop explores the role that open access licenses and collective action might play in reviving the scholarly monograph: a specialised area of academic publishing that has seen sales decline by more than 90 per cent over the past three decades. It also introduces Knowledge Unlatched an ambitious attempt to create an internationally coordinated, sustainable route to open access for scholarly books. Knowledge Unlatched is now in its pilot phase.

Open access and scholarly books : Australian perspectives

This three-hour workshop tackles the crucial question of whether globally coordinated, market based approaches to funding open access monographs can support the unique needs of Australian research communities. The workshop takes place in the context of the release in August 2013 of the Book Industry Collaborative Council (BICC) report and especially the recommendations included in the chapter on scholarly book publishing in the humanities and social sciences. This workshop, with expert speakers from the BICC Committee and from across the scholarly publishing industry, will discuss the policy issues most likely to ensure that Australian scholarly communities and audiences are best served in an era of digital technology and globalisation. Australia must think globally and support developments that enhance the accessibility of publicly-funded research. Speakers will outline recent developments in scholarly monograph publishing including new Open Access initiatives and developments. Knowledge Unlatched, is one example of an attempt to create an internationally coordinated, market-based route to open access for Humanities, Arts and Social Sciences (HASS) monographs. Knowledge Unlatched, a not-for-profit London-based company is piloting a global library consortium approach to funding open access monographs and released its pilot program in early October with 28 titles from 13 publishers. The workshop invites discussion and debate from librarians, publishers, researchers and research funders on the role of international coordination and markets in securing a more open future for Australian HASS scholarship.

Knowledge unlatched : open access and scholarly books - workshop report

On 19 June 2013 Knowledge Unlatched and the Berkman Center for Internet and Society at Harvard Law School jointly convened a one-day workshop titled Open Access and Scholarly Books in Cambridge, MA. The workshop brought together a group of 21 invited publishers, librarians, academics and Open Access innovators to discuss the challenge of making scholarly books Open Access. This report captures discussions that took place on the day.

Intraurban rail access : policy implications of five revealed perspectives from a Q-sorting exercise in three Australian cities

This project advances the current understanding of intraurban rail passengers and their travel experiences to help rail industry leaders tailor policy approaches to fit specific, relevant segments of their target population. Using a Q-sorting technique and cluster analysis, preliminary research identified five perspectives occurring in a small sample of rail passengers who varied in their frequency and location of rail travel as well as certain sociodemographic characteristics. Revealed perspectives (named to capture the gist of their content) included "Rail travel is about the destination, not the journey"; "Despite challenges, public transport is still the best option"; "Rail travel is fine"; "Rail travel? So far, so good"; and "Bad taste for rail travel." This paper discusses each of the perspectives in detail and considers them in relation to tailored policy implications. An overarching finding from this study is that improving railway travel access requires attention to physical, psychological, financial, and social facets of accessibility. For example, designing waiting areas to be more socially functional and comfortable has the potential to increase ridership by addressing social forms of access, decreasing perceived wait times, and making time at the station feel like time well spent. Even at this preliminary stage, the Q-sorting technique promises to provide a valuable, holistic, albeit fine-grained, analysis of passenger attitudes and experiences that will assist industry efforts in increasing ridership.

Data innovation and open access [Blog]

After nearly fifteen years of the open access (OA) movement and its hard-fought struggle for a more open scholarly communication system, publishers are realizing that business models can be both open and profitable. Making journal articles available on an OA license is becoming an accepted strategy for maximizing the value of content to both research communities and the businesses that serve them. The first blog in this two-part series celebrating Data Innovation Day looks at the role that data-innovation is playing in the shift to open access for journal articles.