Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

The Genetics and Genomics of Virus Resistance in Maize

Viruses cause significant diseases on maize worldwide. Intensive agronomic practices, changes in vector distribution, and the introduction of vectors and viruses into new areas can result in emerging disease problems. Because deployment of resistant hybrids and cultivars is considered to be both economically viable and environmentally sustainable, genes and quantitative trait loci for most economically important virus diseases have been identified. Examination of multiple studies indicates the importance of regions of maize chromosomes 2, 3, 6, and 10 in virus resistance. An understanding of the molecular basis of virus resistance in maize is beginning to emerge, and two genes conferring resistance to sugarcane mosaic virus, Scmv1 and Scmv2, have been cloned and characterized. Recent studies provide hints of other pathways and genes critical to virus resistance in maize, but further work is required to determine the roles of these in virus susceptibility and resistance. This research will be facilitated by rapidly advancing technologies for functional analysis of genes in maize

A Large Maize (Zea mays L.) SNP Genotyping Array: Development and Germplasm Genotyping, and Genetic Mapping to Compare with the B73 Reference Genome

SNP genotyping arrays have been useful for many applications that require a large number of molecular markers such as high-density genetic mapping, genome-wide association studies (GWAS), and genomic selection. We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. The markers, taken from more than 800,000 SNPs, were selected to be preferentially located in genes and evenly distributed across the genome. The array was tested with a set of maize germplasm including North American and European inbred lines, parent/F1 combinations, and distantly related teosinte material. A total of 49,585 markers, including 33,417 within 17,520 different genes and 16,168 outside genes, were of good quality for genotyping, with an average failure rate of 4% and rates up to 8% in specific germplasm. To demonstrate this array's use in genetic mapping and for the independent validation of the B73 sequence assembly, two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped to establish two high density linkage maps with 20,913 and 14,524 markers respectively. 172 mapped markers were absent in the current B73 assembly and their placement can be used for future improvements of the B73 reference sequence. Colinearity of the genetic and physical maps was mostly conserved with some exceptions that suggest errors in the B73 assembly. Five major regions containing non-colinearities were identified on chromosomes 2, 3, 6, 7 and 9, and are supported by both independent genetic maps. Four additional non-colinear regions were found on the LHRF map only; they may be due to a lower density of IBM markers in those regions or to true structural rearrangements between lines. Given the array's high quality, it will be a valuable resource for maize genetics and many aspects of maize breeding

Institutional entrepreneurship, governance, and poverty: Insights from emergency medical response servicesin India

We present an in-depth case study of GVK Emergency Management and Research Institute, an Indian public–private partnership (PPP), which successfully brought emergency medical response to remote and urban settings. Drawing insights from the case, we investigate how the organization established itself through institutional entrepreneurship using a process conceptualized as opportunity framing, entrenchment, and propagation. The case and context highlight the need for innovation in organizational design and governance modes to create a new opportunity that connects state actors, private healthcare providers, and the public at large. We consider the role of open innovation and novel business models in creating these service platforms. The implications of our findings for the literature on PPPs, institutional entrepreneurship, inclusive and open innovation, and organizational design in base of the pyramid contexts are discussed

Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?

Tyrosine kinases are important cellular signaling proteins that have a variety of biological activities including cell proliferation and migration. Multiple kinases are involved in angiogenesis, including receptor tyrosine kinases such as the vascular endothelial growth factor receptor. Inhibition of angiogenic tyrosine kinases has been developed as a systemic treatment strategy for cancer. Three anti-angiogenic tyrosine kinase inhibitors (TKIs), sunitinib, sorafenib and pazopanib, with differential binding capacities to angiogenic kinases were recently approved for treatment of patients with advanced cancer (renal cell cancer, gastro-intestinal stromal tumors, and hepatocellular cancer). Many other anti-angiogenic TKIs are being studied in phase I-III clinical trials. In addition to their beneficial anti-tumor activity, clinical resistance and toxicities have also been observed with these agents. In this manuscript, we will give an overview of the design and development of anti-angiogenic TKIs. We describe their molecular structure and classification, their mechanism of action, and their inhibitory activity against specific kinase signaling pathways. In addition, we provide insight into what extent selective targeting of angiogenic kinases by TKIs may contribute to the clinically observed anti-tumor activity, resistance, and toxicity. We feel that it is of crucial importance to increase our understanding of the clinical mechanism of action of anti-angiogenic TKIs in order to further optimize their clinical efficacy

Anthropogenic noise is associated with changes in acoustic but not visual signals in red-winged blackbirds

Some birds in noisy areas produce songs with higher frequency and/or amplitude and altered timing compared to individuals in quiet areas. These changes may function to increase the efficacy of acoustic signals by reducing masking by noise. We collected audio recordings of red-winged blackbirds and measured noise levels. We found that males in noisier places produced songs with fewer syllables and slower repeat rate of elements in some components (rattles). Birds may also improve the efficacy of communication in noise by increasing usage of other signaling modalities. Red-winged blackbirds also perform a visual display in different intensities while singing. We also tested whether this species performs the visual display in different intensities according to current noise levels, and predicted that if the efficacy of songs is impaired in noisy places, males would compensate by performing a more intense visual display. For this, we also collected visual recordings from the same males from which we obtained acoustic recordings. We found no association between acoustic noise and the intensity of the visual display; thus, our results do not support the idea that males are using the visual display as a backup signal to communicate under acoustic noise. We discuss some possible explanations of this negative finding and for the observed noise-related changes in song length and rattle rate in the context of communication under noise