Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

The Mouse Gastrointestinal Bacteria Catalogue enables translation between the mouse and human gut microbiotas via functional mapping.

Funder: Royal SocietyHuman health and disease have increasingly been shown to be impacted by the gut microbiota, and mouse models are essential for investigating these effects. However, the compositions of human and mouse gut microbiotas are distinct, limiting translation of microbiota research between these hosts. To address this, we constructed the Mouse Gastrointestinal Bacteria Catalogue (MGBC), a repository of 26,640 high-quality mouse microbiota-derived bacterial genomes. This catalog enables species-level analyses for mapping functions of interest and identifying functionally equivalent taxa between the microbiotas of humans and mice. We have complemented this with a publicly deposited collection of 223 bacterial isolates, including 62 previously uncultured species, to facilitate experimental investigation of individual commensal bacteria functions in vitro and in vivo. Together, these resources provide the ability to identify and test functionally equivalent members of the host-specific gut microbiotas of humans and mice and support the informed use of mouse models in human microbiota research.Sir Henry Dale Fellowship jointly funded by Wellcome Trust and Royal Society [206245/Z/17/Z]. Rosetrees Trust [A2194]. Wellcome Trust [098051]

Irish research response to dairy quality in an era of change

peer-reviewedThe Irish dairy sector is recognised for its very significant contribution to the national economic status; it is now worth ∼€5 billion annually and represents the largest food and drink export category, which, in turn, represents one of the four largest manufacturing industries in the country. Given anticipated further growth in global demand for dairy products and the positive attributes and capabilities that Ireland has to meet that demand, in terms of pasture-based production and cost competitiveness, it is incumbent for the sector to attain the highest quality milk and dairy products. The combined collaborative approach between research and industry has ensured significant progress and enabled Ireland to remain at the forefront globally in terms of production of quality milk and dairy products. This paper highlights some specific scientific platforms and technologies currently shaping the industry in this regard and discusses current research activity as well as anticipating key requirements for future progress. While research, and farm and processing plant management have accomplished very significant advances in milk and dairy product quality, some overarching emerging challenges include product substitution and sustainability. Some key pillars for the future have been identified on which a strong, efficient dairy sector can be maintained and progressed. Specifically, the use of evidence-based information and real-time measures in prediction and decision-making will be a crucial pillar for the dairy sector of the future. This can promote an approach of proactive maintenance and optimisation of production through improved predictability and control of manufacturing processes

Information gaps for patients requiring craniotomy for benign brain lesion: a qualitative study

Doctor–patient communication in the setting of a life-threatening illness poses considerable challenges. This study aimed to determine the information needs of a subset of neurosurgical patients. Qualitative case study methodology was used. Twenty-five semi-structured interviews were conducted with ambulatory adult patients who had undergone surgery for a benign brain tumor, arteriovenous malformation, or unruptured aneurysm. Interviews were digitally audio recorded and transcribed, and the data subjected to thematic analysis. Six overarching themes emerged from the data: (1) the amount of information patients want varies; (2) the type of information needed is not limited to information about treatment options and risks; (3) patients engage in independent information seeking for a variety of reasons; (4) patients consider compassion from their surgeon as important; (5) direct communication with the surgeon post-operatively is very important; and (6) patients’ information needs are greatest post-operatively. Many patients felt that the amount and quality of information they received was not sufficient, particularly regarding post-operative recovery and long-term life issues, leading many to do their own research. The findings from this study emphasize the need for improved communication with patients so they can participate meaningfully in choices about their treatment, give a truly informed consent, and effectively participate in their own recovery

A phenomic perspective on factors influencing breast cancer treatment: integrating aging and lifestyle in blood and tissue biomarker profiling

Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management

Virtual Machine Support for Many-Core Architectures: Decoupling Abstract from Concrete Concurrency Models

The upcoming many-core architectures require software developers to exploit concurrency to utilize available computational power. Today's high-level language virtual machines (VMs), which are a cornerstone of software development, do not provide sufficient abstraction for concurrency concepts. We analyze concrete and abstract concurrency models and identify the challenges they impose for VMs. To provide sufficient concurrency support in VMs, we propose to integrate concurrency operations into VM instruction sets. Since there will always be VMs optimized for special purposes, our goal is to develop a methodology to design instruction sets with concurrency support. Therefore, we also propose a list of trade-offs that have to be investigated to advise the design of such instruction sets. As a first experiment, we implemented one instruction set extension for shared memory and one for non-shared memory concurrency. From our experimental results, we derived a list of requirements for a full-grown experimental environment for further research

A Conceptual Framework for Social, Behavioral, and Environmental Change through Stakeholder Engagement in Water Resource Management

Incorporating stakeholder engagement into environmental management may help in the pursuit of novel approaches for addressing complex water resource problems. However, evidence about how and under what circumstances stakeholder engagement enables desirable changes remains elusive. In this paper, we develop a conceptual framework for studying social and environmental changes possible through stakeholder engagement in water resource management, from inception to outcomes. We synthesize concepts from multiple literatures to provide a framework for tracing linkages from contextual conditions, through engagement process design features, to social learning, community capacity building, and behavioral change at individual, group, and group network levels, and ultimately to environmental change. We discuss opportunities to enhance the framework including through empirical applications to delineate scalar and temporal dimensions of social, behavioral, and environmental changes resulting from stakeholder engagement, and the potential for negative outcomes thus far glossed over in research on change through engagement

Inter-cultivar variation in soil-to-plant transfer of radiocaesium and radiostrontium in Brassica oleracea

Radiocaesium and radiostrontium enter the human food chain primarily via soil-plant transfer. However, uptake of these radionuclides can differ significantly within species (between cultivars). The aim of this study was to assess inter-cultivar variation in soil-to-plant transfer of radiocaesium and radiostrontium in a leafy crop species, Brassica oleracea. This study comprised four independent experiments: two pot experiments in a controlled environment artificially contaminated with radiocaesium, and two field experiments in an area contaminated with radiocaesium and radiostrontium in the Chernobyl Exclusion Zone. Radiocaesium concentration ratios varied 35-fold among 27 cultivars grown in pots in a controlled environment. These 27 cultivars were then grown with a further 44 and 43 other cultivars in the Chernobyl Exclusion Zone in 2003 and 2004, respectively. In the field-grown cultivars radiocaesium concentration ratios varied by up to 35-fold and radiostrontium concentration ratios varied by up to 23-fold.In three of these experiments (one pot experiment, two field experiments) one out of the 27 cultivars was found to have a consistently lower radiocaesium concentration ratio than the other cultivars. The two field experiments showed that, five out of the 66 cultivars common to both experiments had consistently lower radiocaesium concentration ratios, and two cultivars had consistently lower radiostrontium concentration ratios. One cultivar had consistently lower radiocaesium and radiostrontium concentration ratios.The identification of cultivars that have consistently lower radiocaesium and/or radiostrontium concentration ratios suggests that cultivar selection or substitution may be an effective remediation strategy in radiologically contaminated areas. Future research should focus on plant species that are known to be the largest contributors to human dose

Intergenerational family support for ‘Generation Rent’:The family home for socially disengaged young people

This paper critically discusses the concept of intergenerational family support in housing for young people. Recognizing increased difficulties faced by the younger generation in the housing market, this paper highlights that support from older family members is increasingly important. Nonetheless, it is critiqued that the role of the family home has been largely ignored in the current ‘generation rent’ discourse. By drawing on recent youth studies debates, this paper argues living in the family home could be an important form of support in housing, especially for marginalized youth. This paper presents insights from qualitative studies in Hong Kong and Scotland and analyses interview accounts of socially disengaged young people. It reflects how remaining at the family home could be interpreted as intergenerational support, and further elicits complexities in expectations, negotiations and emotions involved. This analysis offers new evidence and a more nuanced perspective of intergenerational family support in housing research