Channeling diverse innovation pressures to support European sustainability transitions

Innovation patterns and processes must be aligned, and harnessed and accelerated across multiple domains to address our climate objectives and wider sustainability challenges. In this Perspective, we draw from original case studies on specific technologies and their related innovation systems in agriculture, buildings, electricity, ICT, industry, and transport across Germany, Italy, Poland, and the United Kingdom. Across these innovation systems, the Research Note discusses the technologies, infrastructure, actors, policies and institutions that may lead to, or prevent, successful and unsuccessful technology transitions. We synthesize this diverse evidence to offer five key findings on technology costs and configurations, diversity and multiplicity of actors, diversity of value systems, and countervailing pressures. These insights support the design of effective innovation and decarbonization policies to promote low-carbon transitions

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Selecting cash management models from a multiobjective perspective

[EN] This paper addresses the problem of selecting cash management models under different operating conditions from a multiobjective perspective considering not only cost but also risk. A number of models have been proposed to optimize corporate cash management policies. The impact on model performance of different operating conditions becomes an important issue. Here, we provide a range of visual and quantitative tools imported from Receiver Operating Characteristic (ROC) analysis. More precisely, we show the utility of ROC analysis from a triple perspective as a tool for: (1) showing model performance; (2) choosingmodels; and (3) assessing the impact of operating conditions on model performance. We illustrate the selection of cash management models by means of a numerical example.Work partially funded by projects Collectiveware TIN2015-66863-C2-1-R (MINECO/FEDER) and 2014 SGR 118.Salas-Molina, F.; Rodríguez-Aguilar, JA.; Díaz-García, P. (2018). Selecting cash management models from a multiobjective perspective. Annals of Operations Research. 261(1-2):275-288. https://doi.org/10.1007/s10479-017-2634-9S2752882611-2Ballestero, E. (2007). Compromise programming: A utility-based linear-quadratic composite metric from the trade-off between achievement and balanced (non-corner) solutions. European Journal of Operational Research, 182(3), 1369–1382.Ballestero, E., & Romero, C. (1998). Multiple criteria decision making and its applications to economic problems. Berlin: Springer.Bi, J., & Bennett, K. P. (2003). Regression error characteristic curves. In Proceedings of the 20th international conference on machine learning (ICML-03), pp. 43–50.Bradley, A. P. (1997). The use of the area under the roc curve in the evaluation of machine learning algorithms. Pattern Recognition, 30(7), 1145–1159.da Costa Moraes, M. B., Nagano, M. S., & Sobreiro, V. A. (2015). Stochastic cash flow management models: A literature review since the 1980s. In Decision models in engineering and management (pp. 11–28). New York: Springer.Doumpos, M., & Zopounidis, C. (2007). Model combination for credit risk assessment: A stacked generalization approach. Annals of Operations Research, 151(1), 289–306.Drummond, C., & Holte, R. C. (2000). Explicitly representing expected cost: An alternative to roc representation. In Proceedings of the sixth ACM SIGKDD international conference on Knowledge discovery and data mining (pp. 98–207). New York: ACM.Drummond, C., & Holte, R. C. (2006). Cost curves: An improved method for visualizing classifier performance. Machine Learning, 65(1), 95–130.Elkan, C. (2001). The foundations of cost-sensitive learning. In International joint conference on artificial intelligence (Vol. 17, pp. 973–978). Lawrence Erlbaum associates Ltd.Fawcett, T. (2006). An introduction to roc analysis. Pattern Recognition Letters, 27(8), 861–874.Flach, P. A. (2003). The geometry of roc space: understanding machine learning metrics through roc isometrics. In Proceedings of the 20th international conference on machine learning (ICML-03), pp. 194–201.Garcia-Bernabeu, A., Benito, A., Bravo, M., & Pla-Santamaria, D. (2016). Photovoltaic power plants: a multicriteria approach to investment decisions and a case study in western spain. Annals of Operations Research, 245(1–2), 163–175.Glasserman, P. (2003). Monte Carlo methods in financial engineering (Vol. 53). New York: Springer.Gregory, G. (1976). Cash flow models: a review. Omega, 4(6), 643–656.Hernández-Orallo, J. (2013). Roc curves for regression. Pattern Recognition, 46(12), 3395–3411.Hernández-Orallo, J., Flach, P., & Ferri, C. (2013). Roc curves in cost space. Machine Learning, 93(1), 71–91.Hernández-Orallo, J., Lachiche, N., & Martınez-Usó, A. (2014). Predictive models for multidimensional data when the resolution context changes. In Workshop on learning over multiple contexts at ECML, volume 2014.Metz, C. E. (1978). Basic principles of roc analysis. In Seminars in nuclear medicine (Vol. 8, pp. 283–298). Amsterdam: Elsevier.Miettinen, K. (2012). Nonlinear multiobjective optimization (Vol. 12). Berlin: Springer.Ringuest, J. L. (2012). Multiobjective optimization: Behavioral and computational considerations. Berlin: Springer.Ross, S. A., Westerfield, R., & Jordan, B. D. (2002). Fundamentals of corporate finance (sixth ed.). New York: McGraw-Hill.Salas-Molina, F., Pla-Santamaria, D., & Rodriguez-Aguilar, J. A. (2016). A multi-objective approach to the cash management problem. Annals of Operations Research, pp. 1–15.Srinivasan, V., & Kim, Y. H. (1986). Deterministic cash flow management: State of the art and research directions. Omega, 14(2), 145–166.Steuer, R. E., Qi, Y., & Hirschberger, M. (2007). Suitable-portfolio investors, nondominated frontier sensitivity, and the effect of multiple objectives on standard portfolio selection. Annals of Operations Research, 152(1), 297–317.Stone, B. K. (1972). The use of forecasts and smoothing in control limit models for cash management. Financial Management, 1(1), 72.Torgo, L. (2005). Regression error characteristic surfaces. In Proceedings of the eleventh ACM SIGKDD international conference on Knowledge discovery in data mining (pp. 697–702). ACM.Yu, P.-L. (1985). Multiple criteria decision making: concepts, techniques and extensions. New York: Plenum Press.Zeleny, M. (1982). Multiple criteria decision making. New York: McGraw-Hill

Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus

The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other via unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in KIF4A that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an in vitro assay. These data implicate missense variations in KIF4A in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes

Clinical decision-making to facilitate appropriate patient management in chiropractic practice: 'the 3-questions model'

Background A definitive diagnosis in chiropractic clinical practice is frequently elusive, yet decisions around management are still necessary. Often, a clinical impression is made after the exclusion of serious illness or injury, and care provided within the context of diagnostic uncertainty. Rather than focussing on labelling the condition, the clinician may choose to develop a defendable management plan since the response to treatment often clarifies the diagnosis. Discussion This paper explores the concept and elements of defensive problem-solving practice, with a view to developing a model of agile, pragmatic decision-making amenable to real-world application. A theoretical framework that reflects the elements of this approach will be offered in order to validate the potential of a so called '3-Questions Model'; Summary Clinical decision-making is considered to be a key characteristic of any modern healthcare practitioner. It is, thus, prudent for chiropractors to re-visit the concept of defensible practice with a view to facilitate capable clinical decision-making and competent patient examination skills. In turn, the perception of competence and trustworthiness of chiropractors within the wider healthcare community helps integration of chiropractic services into broader healthcare settings

Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids

Inflammation plays a prominent role in tumor growth. Anti-inflammatory drugs have therefore been proposed as anti-cancer therapeutics. In this study, we determined the anti-angiogenic activity of a single dose of liposomal prednisolone phosphate (PLP-L), by monitoring tumor vascular function and viability over a period of one week. C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells. Six animals were PLP-L-treated and six served as control. Tumor tissue and vascular function were probed using MRI before and at three timepoints after treatment. DCE-MRI was used to determine Ktrans, ve, time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T2 and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in Ktrans 48 h post-treatment, which was maintained until one week after drug administration. However, this effect was not sufficient to significantly distinguish treated from non-treated animals. The therapy did not affect tumor tissue viability but did prevent the ADC decrease observed in the control group. No evidence for PLP-L-induced tumor vessel normalization was found on histology. Treatment with PLP-L altered tumor vascular function. This effect did not fully explain the tumor growth inhibition, suggesting a broader spectrum of PLP-L activities

Double-blind, 12 month follow-up, placebo-controlled trial of mifepristone on cognition in alcoholics: the MIFCOG trial protocol

Background: Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol. Methods/Design: The study is a Phase 4 therapeutic use, “Proof of Concept” trial. The trial is a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo. The trial aims to recruit 120 participants referred for an inpatient alcohol detoxification from community alcohol teams, who meet the inclusion criteria; 1) Male, 2) Aged 18–60 inclusive, 3) alcohol dependent for 5 or more years. A screening appointment will take place prior to admission to inpatient alcohol treatment units to ensure that the individual is suitable for inclusion in the trial in accordance with the inclusion and exclusion criteria. On admission participants are randomised to receive 600 mg a day of mifepristone (200 mg morning, afternoon and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Participants will remain in the trial for 4 weeks (at least 2 weeks as an inpatient) and will be followed up at 3, 6 and 12 months post randomisation. Primary outcome measures are cognitive function at week 3 and 4 after cessation of drinking and symptoms of depression over the 4 weeks after cession of drinking, measured using the Cambridge Neuropsychological Test Automated battery and Beck Depression Inventory, respectively. Secondary outcome measures are severity of the acute phase of alcohol withdrawal, alcohol craving, symptoms of protracted withdrawal and maintenance of abstinence and levels of relapse drinking at follow-up. Discussion: The current trial will provide evidence concerning the role of glucocorticoid Type II receptor activation in cognitive function and depression during acute alcohol withdrawal and the efficacy of treatment with mifepristone

Fluorosis risk from early exposure to fluoride toothpaste

Swallowed fluoride toothpaste in the early years of life has been postulated to be a risk factor for fluorosis, but the epidemiological evidence is weakened by the fact that most of the relevant studies were done in developed countries where an individual is exposed to multiple sources of fluoride. Objectives: To quantify the risk of fluorosis from fluoride toothpaste in a population whose only potential source of fluoride was fluoride toothpaste. Methods: Case-control analyses were conducted to test the hypothesis that fluoride toothpaste use before the age of 6 years increased an individual's risk of fluorosis. Data came from a cross-sectional clinical dental examination of schoolchildren and a self-administered questionnaire to their parents. The study was conducted in Goa, India. The study group consisted of 1189 seventh grade children with a mean age of 12.2 years. Results: The prevalence of fluorosis was 12.9% using the TF index. Results of the crude, stratified, and logistic regression analyses showed that use of fluoride toothpaste before the age of 6 years was a risk indicator for fluorosis (OR 1.83, 95% CI 1.05–3.15). Among children with fluorosis, beginning brushing before the age of 2 years increased the severity of fluorosis significantly ( P < 0.001). Other factors associated with the use of fluoride toothpaste, such as eating or swallowing fluoride toothpaste and higher frequency of use, did not show a statistically significant increased risk for prevalence or severity of fluorosis. Conclusions: Fluoride toothpaste use before the age of 6 years is a risk indicator for fluorosis in this study population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75437/1/j.1600-0528.1998.tb01957.x.pd