Devices of Responsibility: Over a Decade of Responsible Research and Innovation Initiatives for Nanotechnologies.

Responsible research and innovation (RRI) has come to represent a change in the relationship between science, technology and society. With origins in the democratisation of science, and the inclusion of ethical and societal aspects in research and development activities, RRI offers a means of integrating society and the research and innovation communities. In this article, we frame RRI activities through the lens of layers of science and technology governance as a means of characterising the context in which the RRI activity is positioned and the goal of those actors promoting the RRI activities in shaping overall governance patterns. RRI began to emerge during a time of considerable deliberation about the societal and governance challenges around nanotechnology, in which stakeholders were looking for new ways of integrating notions of responsibility in nanotechnology research and development. For this reason, this article focuses on nanotechnology as the site for exploring the evolution and growth of RRI.

Workshops of the Sixth International Brain-Computer Interface Meeting: brain-computer interfaces past, present, and future.

The Sixth International Brain-Computer Interface (BCI) Meeting was held 30 May-3 June 2016 at the Asilomar Conference Grounds, Pacific Grove, California, USA. The conference included 28 workshops covering topics in BCI and brain-machine interface research. Topics included BCI for specific populations or applications, advancing BCI research through use of specific signals or technological advances, and translational and commercial issues to bring both implanted and non-invasive BCIs to market. BCI research is growing and expanding in the breadth of its applications, the depth of knowledge it can produce, and the practical benefit it can provide both for those with physical impairments and the general public. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and highlighting important issues and calls for action to support future research and development.

Nano-enabled drug delivery: a research profile.

Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology application. Understanding the status and developmental prospects of this area around the world is important to determine research priorities, and to evaluate and direct progress. Global research publication and patent databases provide a reservoir of information that can be tapped to provide intelligence for such needs. Here, we present a process to allow for extraction of NEDD-related information from these databases by involving topical experts. This process incorporates in-depth analysis of NEDD literature review papers to identify key subsystems and major topics. We then use these to structure global analysis of NEDD research topical trends and collaborative patterns, inform future innovation directions. FROM THE CLINICAL EDITOR: This paper describes the process of how to derive nano-enabled drug delivery-related information from global research and patent databases in an effort to perform comprehensive global analysis of research trends and directions, along with collaborative patterns.

Detecting deterioration in patients with chronic disease using telemonitoring: navigating the 'trough of disillusionment'.

OBJECTIVES: To examine the evidence base for telemonitoring designed for patients who have chronic obstructive pulmonary disease and heart failure, and to assess whether telemonitoring fulfils the principles of monitoring and is ready for implementation into routine settings. DESIGN: Qualitative data collection using interviews and participation in a multi-path mapping process. PARTICIPANTS: Twenty-six purposively selected informants completed semi-structured interviews and 24 individuals with expertise in the relevant clinical and informatics domains from academia, industry, policy and provider organizations and participated in a multi-path mapping workshop. RESULTS: The evidence base for the effectiveness of telemonitoring is weak and inconsistent, with insufficient cost-effectiveness studies. When considered against an accepted definition of monitoring, telemonitoring is found wanting. Telemonitoring has not been able so far to ensure that the technologies fit into the life world of the patient and into the clinical and organizational milieu of health service delivery systems. CONCLUSIONS: To develop effective telemonitoring for patients with chronic disease, more attention needs to be given to agreeing the central aim of early detection and, to ensure potential implementation, engaging a wide range of stakeholders in the design process, especially patients and clinicians.

Identification of members of the Wnt signaling pathway in the embryonic pituitary gland.

Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pituitary transcription factors remain largely unknown. We have generated a partial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild-type embryonic pituitary gland primordia. Numerous classes of genes including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4% represent novel sequences. Pituitary gland expression of a number of clones was verified using in situ hybridization. Several members of the Wnt signaling pathway were identified in the developing pituitary gland. The frizzled2 receptor, Apc, beta-catenin, groucho, and a novel isoform of TCF4 (officially named Tcf7l2) were identified in developing pituitary libraries. Three N-terminal alternatively spliced Tcf7l2 isoforms are reported here, each of which lacks a DNA-binding domain. Functional studies indicate that these isoforms can act as endogenous inhibitors of Wnt signaling in some contexts. This is the first report of Tcf7l2 and Fzd2 expression in the developing pituitary. These molecules may be important in mediating Wnt signaling during pituitary ontogeny. We expect other transcripts from these libraries to be involved in pituitary gland development.

Partial transcriptome of the developing pituitary gland.

The anterior lobe of the pituitary gland is composed of five hormone-producing cell types and develops from Rathke's pouch, an invagination of oral ectoderm. In mice, rapid cell proliferation occurs in the pouch from embryonic day 12.5 (e12.5) to e14.5, preceding the appearance of most hormone transcripts. Cell-type-specific commitment probably occurs prior to e14.5, but cell differentiation can be demonstrated only by detection of hormone transcripts. Although several transcription factors critical for pouch expansion are known, few of their target genes have been identified. To identify putative transcription factor target genes and cell-type-specific markers, we used differential display PCR analysis of RNA prepared from e12.5 and e14.5 Rathke's pouches. We present an expression profile of the developing pituitary gland including 83 transcripts, 40% of which are novel. The tissue distribution, cell specificity, and developmental regulation were determined for a subset of the transcripts.

Conservative surgery and radiotherapy for early-stage breast cancer using a lung density correction: the University of Michigan experience.

PURPOSE: Although an abundance of reports detail the successful use of definitive radiotherapy of the breast in the treatment in Stage I or II breast cancer, little data have been published concerning the use of lung density correction and its effect upon long-term outcome. As it has been the practice at the University of Michigan to routinely use lung density correction in the dose calculations to the breast, we retrospectively analyzed our results for local control, relapse-free, and overall survival. METHODS AND MATERIALS: Clinical records were reviewed of 429 women with Stage I or II breast cancer treated with lumpectomy, axillary dissection, and breast irradiation with or without systemic chemo/hormonal therapy. Tangential radiotherapy fields delivering 45 to 50 Gy were used to treat the entire breast. A boost was delivered in 95% of cases for a total tumor bed dose of 60 to 66 Gy. All treatment plans were calculated using a lung density correction. RESULTS: With a median follow up of 4.4 years, the 5-year actuarial rate of local control with local failure as the only site of first failure was 96% (95% CI 94-98%). Univariate analysis for local failure as only first failure found the following factors to statistically predict for increased risk of breast recurrence: young age (< or =35 years old), premenopausal status, tumor size >2 cm, positive family history, and positive microscopic margins. Multivariate analysis revealed young age and margin status to be the only factors remaining significant for local failure. The 5-year actuarial relapse-free survival was 85% (95% CI 81-89%); overall survival at 5 years was 90% (95% CI 87-94%). CONCLUSIONS: Lung density correction results in rates of local control, disease-free, and overall survival at 5 years that compare favorably with series using noncorrected unit density calculations. While we will continue to update our results with increasing follow-up, our 5-year data indicate that the use of lung-density correction for dosimetric accuracy does not compromise local control.

Construction of a 3-Mb contig and partial transcript map of the central region of mouse chromosome 11.

We report the establishment of a high-resolution genetic map, a physical map, and a partial transcript map of the Ames dwarf critical region on mouse chromosome 11. A contig of 24 YACs and 13 P1 clones has been assembled and spans approximately 3 Mb from Flt4 to Tcf7. A library of approximately 1000 putative transcript clones from the region was prepared using exon amplification and pituitary cDNA selection. Ten novel transcripts were partially characterized, including a member of the olfactory receptor family, an alpha-tubulin-related sequence, and a novel member of the cdc2/CDC28-like kinase family, Clk4. The location of Prop1, the gene responsible for Ames dwarfism, has been localized within the contig. This contig spans a region of mouse chromosome 11 that exhibits linkage conservation with human chromosome 5q23-q35. The strength of the genetic map and genomic resources for this region suggest that comparative DNA sequencing of this region could reveal the genes responsible for other mouse mutants and human genetic diseases.