The Challenges for Smart Cities in the UK

The rising interest in smart cities in the UK and Europe is in danger of sliding into a public/private debate. While the literature on smart cities is extensive, it is also confusing and often contradictory. Moreover, the technology advances that enable smart cities to develop advance far more quickly than does the academic analysis that follows. In this article we briefly summarize the literature in order to create a progress report for smart cities in the UK. We begin with a short review of the Smart Cities concept. Our main finding is that the implementation of smart city concepts across the UK is patchy, partly because in the UK cities control only about 18% of their budgets and their ability to act locally is constrained. As a result, smart city initiatives and investments leave much to be desired in terms of function and impact. We conclude that in the UK, the challenges to meeting the smart city ideal are many and profound, but not insuperable. The results can be summarized in four main issues that cities face in becoming smarter: 1. Critical political challenges--as opposed to technological—require involvement of highly placed political leaders, 2. Marketplace forces need to be shaped for the broader community to benefit, 3. Smart cities cannot be either bottom up or top down, they have to be both, 4. Concerns about privacy, engagement, and appropriate use of all aspects of smart city interfaces need to be better understood

[Access to early breast cancer diagnosis in the Brazilian Unified National Health System: an analysis of data from the Health Information System].

The recent reduction in breast cancer mortality in high-income countries resulted from improvements in early detection and treatment. Breast cancer is the most common cancer in Brazilian women. Since 2004, the government has recommended annual clinical breast examination for women aged ≥ 40 years and biannual mammograms for those aged 50-69. This article investigates the degree of implementation of these guidelines using data from the Brazilian Unified National Health System for 2010 according to major geographic region and age group. The findings showed low national mammogram coverage in the target population (32% in the 50-59-year group; 25% from 60 to 69 years). The percentage of women with abnormal radiological findings who underwent biopsy was also low (27% for 50-59 years; 63% for 60-69 years). The number of breast cancer surgeries exceeded the number of cases detected by mammography but was well below the estimated number of incident breast cancer cases in 2010. There are striking regional inequalities in access to early detection and surgery, being the lowest access in the North Region and the highest in the South Region

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001–14: a case only analysis

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18–89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001–14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001–14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53–1·70; fully adjusted OR 1·45, 95% CI 1·38–1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22–1·30; fully adjusted OR 1·18, 1·14–1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2–49·5) and lowest for women who were white with university education (29·4%, 28·2–30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%–17·2% in 1970–74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50–69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001–14: a case only analysis

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18–89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001–14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001–14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53–1·70; fully adjusted OR 1·45, 95% CI 1·38–1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22–1·30; fully adjusted OR 1·18, 1·14–1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2–49·5) and lowest for women who were white with university education (29·4%, 28·2–30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%–17·2% in 1970–74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50–69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa

Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells

Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB-MNCs) of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses.info:eu-repo/semantics/publishedVersio

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia

Variations in Healthcare Access and Utilization Among Mexican Immigrants: The Role of Documentation Status

The objective of this study is to identify differences in healthcare access and utilization among Mexican immigrants by documentation status. Cross-sectional survey data are analyzed to identify differences in healthcare access and utilization across Mexican immigrant categories. Multivariable logistic regression and the Blinder-Oaxaca decomposition are used to parse out differences into observed and unobserved components. Mexican immigrants ages 18 and above who are immigrants of California households and responded to the 2007 California Health Interview Survey (2,600 documented and 1,038 undocumented immigrants). Undocumented immigrants from Mexico are 27% less likely to have a doctor visit in the previous year and 35% less likely to have a usual source of care compared to documented Mexican immigrants after controlling for confounding variables. Approximately 88% of these disparities can be attributed to predisposing, enabling and need determinants in our model. The remaining disparities are attributed to unobserved heterogeneity. This study shows that undocumented immigrants from Mexico are much less likely to have a physician visit in the previous year and a usual source of care compared to documented immigrants from Mexico. The recently approved Patient Protection and Affordable Care Act will not reduce these disparities unless undocumented immigrants are granted some form of legal status

SUSY Renormalization Group Effects in Ultra High Energy Neutrinos

We have explored the question of whether the renormalization group running of the neutrino mixing parameters in the Minimal Supersymmetric Standard Model is detectable with ultra-high energy neutrinos from active galactic nuclei (AGN). We use as observables the ratios of neutrino fluxes produced at the AGN, focusing on four different neutrino production models: $(\Phi_{\nu_e+\bar{\nu}_e}^0 : \Phi_{\nu_\mu+\bar{\nu}_\mu}^0 : \Phi_{\nu_\tau+\bar{\nu}_\tau}^0)$ = (1:2:0), (0:1:0), (1:0:0), and (1:1:0). The prospects for observing deviations experimentally are taken into consideration, and we find out that it is necessary to impose a cut-off on the transferred momentum of $Q^2 \geq 10^7$ GeV$^2$. However, this condition, together with the expected low value of the diffuse AGN neutrino flux, yields a negligible event rate at a km-scale Cherenkov detector such as IceCube.Comment: 26 pages, 9 figures. Version accepted for publication in JHE

In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease