AI for the Public Sector: Opportunities and challenges of cross-sector collaboration

Public sector organisations are increasingly interested in using data science and artificial intelligence capabilities to deliver policy and generate efficiencies in high uncertainty environments. The long-term success of data science and AI in the public sector relies on effectively embedding it into delivery solutions for policy implementation. However, governments cannot do this integration of AI into public service delivery on their own. The UK Government Industrial Strategy is clear that delivering on the AI grand challenge requires collaboration between universities and public and private sectors. This cross-sectoral collaborative approach is the norm in applied AI centres of excellence around the world. Despite their popularity, cross-sector collaborations entail serious management challenges that hinder their success. In this article we discuss the opportunities and challenges from AI for public sector. Finally, we propose a series of strategies to successfully manage these cross-sectoral collaborations

Experiences of wearing support garments by people living with a urostomy

BACKGROUND:support garments are commonly worn by people with a urostomy but there are no published data about their experiences of doing so. AIMS:to identify the views of people living with a urostomy on the role of support garments. METHODS:a cross-sectional survey of the stoma population's experiences of support garments was conducted in 2018. Recruitment was by social media. The free-text responses provided by a sub-sample of 58 people out of 103 respondents with a urostomy, were analysed. FINDINGS:thematic analysis revealed four themes: physical self-management; psychosocial self-management; lifestyle; and healthcare advice and support. There were mixed feelings about the value of support garments. Many cited a sense of reassurance and confidence and being able to be more sociable and active; others reported discomfort and uncertainty about their value. CONCLUSION:these findings add new understanding of experiences of support garments and provide novel theoretical insights about life with a urostomy

A stable explant culture of HER2/neu invasive carcinoma supported by alpha-Smooth Muscle Actin expressing stromal cells to evaluate therapeutic agents

<p>Abstract</p> <p>Background</p> <p>To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA) expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1) maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro.</p> <p>Methods</p> <p>We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed flow cytometric assays to evaluate the relative responses of the tumor and stroma to the tyrosine kinase inhibitor, Iressa.</p> <p>Results</p> <p>The MAM-1 gene expression profile contains clusters that represent the ErbB-2 breast cancer signature and stroma-specific clusters associated with invasive breast cancers. The stability of this model and the ability to antigenically label the tumor and stromal fractions allowed us to determine the specificity of Iressa, a receptor tyrosine kinase inhibitor, for targeting the tumor cell population. Treatment resulted in a selective dose-dependent reduction in phospho-pMEK1/2 and pp44/42MAPK in tumor cells. Within 24 h the tumor cell fraction was reduced 1.9-fold while the stromal cell fraction increased >3-fold, consistent with specific reductions in phospho-pp44/42 MAPK, MEK1/2 and PCNA in tumor cells and reciprocal increases in the stromal cells. Erosion of the tumor cell nests and augmented growth of the stromal cells resembled a fibrotic response.</p> <p>Conclusion</p> <p>This model demonstrates the specificity of Iressa for HER2/neu expressing tumor cells versus the tumor associated myofibroblasts and is appropriate for delineating effects of therapy on signal transduction in the breast tumor microenvironment and improving strategies that can dually or differentially target the tumor and stromal elements in the microenvironment.</p

Causes and importance of new particle formation in the present-day and pre-industrial atmospheres

New particle formation has been estimated to produce around half of cloud-forming particles in the present-day atmosphere, via gas-to-particle conversion. Here we assess the importance of new particle formation (NPF) for both the present-day and the pre-industrial atmospheres. We use a global aerosol model with parametrisations of NPF from previously published CLOUD chamber experiments involving sulphuric acid, ammonia, organic molecules and ions. We find that NPF produces around 67% of cloud condensation nuclei at 0.2% supersaturation (CCN0.2%) at the level of low clouds in the pre-industrial atmosphere (estimated uncertainty range 45-84%) and 54% in the present day (estimated uncertainty range 38-66%). Concerning causes, we find that the importance of biogenic volatile organic compounds (BVOCs) in NPF and CCN formation is greater than previously thought. Removing BVOCs and hence all secondary organic aerosol from our model reduces low-cloud-level CCN concentrations at 0.2% supersaturation by 26% in the present-day atmosphere and 41% in the pre-industrial. Around three-quarters of this reduction is due to the tiny fraction of the oxidation products of BVOCs that have sufficiently low volatility to be involved in NPF and early growth. Furthermore, we estimate that 40% of pre-industrial CCN0.2% are formed via ion-induced NPF, compared with 27% in the present-day, although we caution that the ion-induced fraction of NPF involving BVOCs is poorly measured at present. Our model suggests that the effect of changes in cosmic ray intensity on CCN is small and unlikely to be comparable to the effect of large variations in natural primary aerosol emissions

The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells

<p>Abstract</p> <p>Background</p> <p>Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells.</p> <p>Results</p> <p>We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV) or the gibbon ape leukemia virus (GALV) envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells.</p> <p>Conclusions</p> <p>A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.</p

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

<p>Abstract</p> <p>Background -</p> <p>Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.</p> <p>Methods -</p> <p>We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.</p> <p>Results -</p> <p>During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ²= 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.</p> <p>Conclusion -</p> <p>In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.</p

Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Myelodysplastic syndrome (MDS) may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (<it>EPO</it>) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS.</p> <p>Methods</p> <p>We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls.</p> <p>Results</p> <p>The G/G genotype was significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95; 6.3%) or in patients with other leukemias (101/813; 12.4%) (all <it>P </it>< 0.001). Individuals with the G/G genotype were more likely than those with other genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and follow up data were available for 112 MDS patients and 186 AML patients. There was no correlation between EPO promoter genotype and response to therapy or overall survival in MDS or AML. In the MDS group, the GG genotype was significantly associated with shorter complete remission duration, as compared with the TT genotype (<it>P </it>= 0.03). Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (<it>P </it>= 0.02).</p> <p>Conclusions</p> <p>These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.</p

Design Principles for Ligand-Sensing, Conformation-Switching Ribozymes

Nucleic acid sensor elements are proving increasingly useful in biotechnology and biomedical applications. A number of ligand-sensing, conformational-switching ribozymes (also known as allosteric ribozymes or aptazymes) have been generated by some combination of directed evolution or rational design. Such sensor elements typically fuse a molecular recognition domain (aptamer) with a catalytic signal generator (ribozyme). Although the rational design of aptazymes has begun to be explored, the relationships between the thermodynamics of aptazyme conformational changes and aptazyme performance in vitro and in vivo have not been examined in a quantitative framework. We have therefore developed a quantitative and predictive model for aptazymes as biosensors in vitro and as riboswitches in vivo. In the process, we have identified key relationships (or dimensionless parameters) that dictate aptazyme performance, and in consequence, established equations for precisely engineering aptazyme function. In particular, our analysis quantifies the intrinsic trade-off between ligand sensitivity and the dynamic range of activity. We were also able to determine how in vivo parameters, such as mRNA degradation rates, impact the design and function of aptazymes when used as riboswitches. Using this theoretical framework we were able to achieve quantitative agreement between our models and published data. In consequence, we are able to suggest experimental guidelines for quantitatively predicting the performance of aptazyme-based riboswitches. By identifying factors that limit the performance of previously published systems we were able to generate immediately testable hypotheses for their improvement. The robust theoretical framework and identified optimization parameters should now enable the precision design of aptazymes for biotechnological and clinical applications

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

Pancreatic cancer is characterised by a hallmark desmoplastic response that includes upregulated expression of the extracellular matrix, and type I collagen in particular. Recent studies indicate that pancreatic cancer cells stimulate type I collagen synthesis in adjacent stellate cells, and that this upregulated type I collagen expression promotes the malignant phenotype in tumour cells as defined by increased proliferation, resistance to chemically induced apoptosis, and increased tumorigenesis. The integrin specificity of this interaction between type I collagen and tumour cells was not identified, however. In the present study, we examined eight pancreatic cancer cell lines for adhesion, proliferation, and migration, on types I and IV collagen, fibronectin, laminin, and vitronectin, as well as integrin expression. Our results indicate, for the overwhelming majority of cell lines, that type I collagen promotes the strongest adhesion, proliferation, and migration relative to the other substrates tested. Utilising function-blocking monoclonal antibodies directed against particular integrin subunits in cell adhesion and migration inhibition assays, we demonstrate further that the malignant phenotype on type I collagen is mediated specifically by the α2β1 integrin. These results identify α2β1 integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer

Lifestyle behaviours of young adult survivors of childhood cancer

This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18–30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001)