The trade-off between taxi time and fuel consumption in airport ground movement

Environmental impact is a very important agenda item in many sectors nowadays, which the air transportation sector is also trying to reduce as much as possible. One area which has remained relatively unexplored in this context is the ground movement problem for aircraft on the airport’s surface. Aircraft have to be routed from a gate to a runway and vice versa and it is still unknown whether fuel burn and environmental impact reductions will best result from purely minimising the taxi times or whether it is also important to avoid multiple acceleration phases. This paper presents a newly developed multi-objective approach for analysing the trade-off between taxi time and fuel consumption during taxiing. The approach consists of a combination of a graph-based routing algorithm and a population adaptive immune algorithm to discover different speed profiles of aircraft. Analysis with data from a European hub airport has highlighted the impressive performance of the new approach. Furthermore, it is shown that the trade-off between taxi time and fuel consumption is very sensitive to the fuel-related objective function which is used

Genes That Influence Swarming Motility and Biofilm Formation in Variovorax paradoxus EPS

Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces.We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR.The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant.The data presented here point to complex regulation of these surface behaviors

'Issues of equity are also issues of rights': Lessons from experiences in Southern Africa

BACKGROUND: Human rights approaches to health have been criticized as antithetical to equity, principally because they are seen to prioritise rights of individuals at the expense of the interests of groups, a core tenet of public health. The objective of this study was to identify how human rights approaches can promote health equity. METHODS: The Network on Equity in Health in Southern Africa undertook an exploration of three regional case studies – antiretroviral access, patient rights charters and civic organization for health. A combination of archival reviews and stakeholder interviews were complemented with a literature review to provide a theoretical framework for the empirical evidence. RESULTS: Critical success factors for equity are the importance of rights approaches addressing the full spectrum from civil and political, through to socio-economic rights, as well as the need to locate rights in a group context. Human rights approaches succeed in achieving health equity when coupled with community engagement in ways that reinforce community capacity, particularly when strengthening the collective agency of its most vulnerable groups. Additionally, human rights approaches provide opportunities for mobilising resources outside the health sector, and must aim to address the public-private divide at local, national and international levels. CONCLUSION: Where it is clear that rights approaches are predicated upon understanding the need to prioritize vulnerable groups and where the way rights are operationalised recognizes the role of agency on the part of those most affected in realising their socio-economic rights, human rights approaches appear to offer powerful tools to support social justice and health equity

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Public policy, health system, and community actions against illness as platforms for response to NCDs in Tanzania: a narrative review

This review was supported by grants from the Netherlands Organization for International Co-operation in Higher Education and the Ifakara Health Institute, Tanzania

Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3</jats:p

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

none204Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.noneLagou V.; Magi R.; Hottenga J.-J.; Grallert H.; Perry J.R.B.; Bouatia-Naji N.; Marullo L.; Rybin D.; Jansen R.; Min J.L.; Dimas A.S.; Ulrich A.; Zudina L.; Gadin J.R.; Jiang L.; Faggian A.; Bonnefond A.; Fadista J.; Stathopoulou M.G.; Isaacs A.; Willems S.M.; Navarro P.; Tanaka T.; Jackson A.U.; Montasser M.E.; O'Connell J.R.; Bielak L.F.; Webster R.J.; Saxena R.; Stafford J.M.; Pourcain B.S.; Timpson N.J.; Salo P.; Shin S.-Y.; Amin N.; Smith A.V.; Li G.; Verweij N.; Goel A.; Ford I.; Johnson P.C.D.; Johnson T.; Kapur K.; Thorleifsson G.; Strawbridge R.J.; Rasmussen-Torvik L.J.; Esko T.; Mihailov E.; Fall T.; Fraser R.M.; Mahajan A.; Kanoni S.; Giedraitis V.; Kleber M.E.; Silbernagel G.; Meyer J.; Muller-Nurasyid M.; Ganna A.; Sarin A.-P.; Yengo L.; Shungin D.; Luan J.; Horikoshi M.; An P.; Sanna S.; Boettcher Y.; Rayner N.W.; Nolte I.M.; Zemunik T.; Iperen E.; Kovacs P.; Hastie N.D.; Wild S.H.; McLachlan S.; Campbell S.; Polasek O.; Carlson O.; Egan J.; Kiess W.; Willemsen G.; Kuusisto J.; Laakso M.; Dimitriou M.; Hicks A.A.; Rauramaa R.; Bandinelli S.; Thorand B.; Liu Y.; Miljkovic I.; Lind L.; Doney A.; Perola M.; Hingorani A.; Kivimaki M.; Kumari M.; Bennett A.J.; Groves C.J.; Herder C.; Koistinen H.A.; Kinnunen L.; Faire U.; Bakker S.J.L.; Uusitupa M.; Palmer C.N.A.; Jukema J.W.; Sattar N.; Pouta A.; Snieder H.; Boerwinkle E.; Pankow J.S.; Magnusson P.K.; Krus U.; Scapoli C.; de Geus E.J.C.N.; Bluher M.; Wolffenbuttel B.H.R.; Province M.A.; Abecasis G.R.; Meigs J.B.; Hovingh G.K.; Lindstrom J.; Wilson J.F.; Wright A.F.; Dedoussis G.V.; Bornstein S.R.; Schwarz P.E.H.; Tonjes A.; Winkelmann B.R.; Boehm B.O.; Marz W.; Metspalu A.; Price J.F.; Deloukas P.; Korner A.; Lakka T.A.; Keinanen-Kiukaanniemi S.M.; Saaristo T.E.; Bergman R.N.; Tuomilehto J.; Wareham N.J.; Langenberg C.; Mannisto S.; Franks P.W.; Hayward C.; Vitart V.; Kaprio J.; Visvikis-Siest S.; Balkau B.; Altshuler D.; Rudan I.; Stumvoll M.; Campbell H.; van Duijn C.M.; Gieger C.; Illig T.; Ferrucci L.; Pedersen N.L.; Pramstaller P.P.; Boehnke M.; Frayling T.M.; Shuldiner A.R.; Peyser P.A.; Kardia S.L.R.; Palmer L.J.; Penninx B.W.; Meneton P.; Harris T.B.; Navis G.; Harst P.; Smith G.D.; Forouhi N.G.; Loos R.J.F.; Salomaa V.; Soranzo N.; Boomsma D.I.; Groop L.; Tuomi T.; Hofman A.; Munroe P.B.; Gudnason V.; Siscovick D.S.; Watkins H.; Lecoeur C.; Vollenweider P.; Franco-Cereceda A.; Eriksson P.; Jarvelin M.-R.; Stefansson K.; Hamsten A.; Nicholson G.; Karpe F.; Dermitzakis E.T.; Lindgren C.M.; McCarthy M.I.; Froguel P.; Kaakinen M.A.; Lyssenko V.; Watanabe R.M.; Ingelsson E.; Florez J.C.; Dupuis J.; Barroso I.; Morris A.P.; Prokopenko I.Lagou, V.; Magi, R.; Hottenga, J. -J.; Grallert, H.; Perry, J. R. B.; Bouatia-Naji, N.; Marullo, L.; Rybin, D.; Jansen, R.; Min, J. L.; Dimas, A. S.; Ulrich, A.; Zudina, L.; Gadin, J. R.; Jiang, L.; Faggian, A.; Bonnefond, A.; Fadista, J.; Stathopoulou, M. G.; Isaacs, A.; Willems, S. M.; Navarro, P.; Tanaka, T.; Jackson, A. U.; Montasser, M. E.; O'Connell, J. R.; Bielak, L. F.; Webster, R. J.; Saxena, R.; Stafford, J. M.; Pourcain, B. S.; Timpson, N. J.; Salo, P.; Shin, S. -Y.; Amin, N.; Smith, A. V.; Li, G.; Verweij, N.; Goel, A.; Ford, I.; Johnson, P. C. D.; Johnson, T.; Kapur, K.; Thorleifsson, G.; Strawbridge, R. J.; Rasmussen-Torvik, L. J.; Esko, T.; Mihailov, E.; Fall, T.; Fraser, R. M.; Mahajan, A.; Kanoni, S.; Giedraitis, V.; Kleber, M. E.; Silbernagel, G.; Meyer, J.; Muller-Nurasyid, M.; Ganna, A.; Sarin, A. -P.; Yengo, L.; Shungin, D.; Luan, J.; Horikoshi, M.; An, P.; Sanna, S.; Boettcher, Y.; Rayner, N. W.; Nolte, I. M.; Zemunik, T.; Iperen, E.; Kovacs, P.; Hastie, N. D.; Wild, S. H.; Mclachlan, S.; Campbell, S.; Polasek, O.; Carlson, O.; Egan, J.; Kiess, W.; Willemsen, G.; Kuusisto, J.; Laakso, M.; Dimitriou, M.; Hicks, A. A.; Rauramaa, R.; Bandinelli, S.; Thorand, B.; Liu, Y.; Miljkovic, I.; Lind, L.; Doney, A.; Perola, M.; Hingorani, A.; Kivimaki, M.; Kumari, M.; Bennett, A. J.; Groves, C. J.; Herder, C.; Koistinen, H. A.; Kinnunen, L.; Faire, U.; Bakker, S. J. L.; Uusitupa, M.; Palmer, C. N. A.; Jukema, J. W.; Sattar, N.; Pouta, A.; Snieder, H.; Boerwinkle, E.; Pankow, J. S.; Magnusson, P. K.; Krus, U.; Scapoli, C.; de Geus, E. J. C. N.; Bluher, M.; Wolffenbuttel, B. H. R.; Province, M. A.; Abecasis, G. R.; Meigs, J. B.; Hovingh, G. K.; Lindstrom, J.; Wilson, J. F.; Wright, A. F.; Dedoussis, G. V.; Bornstein, S. R.; Schwarz, P. E. H.; Tonjes, A.; Winkelmann, B. R.; Boehm, B. O.; Marz, W.; Metspalu, A.; Price, J. F.; Deloukas, P.; Korner, A.; Lakka, T. A.; Keinanen-Kiukaanniemi, S. M.; Saaristo, T. E.; Bergman, R. N.; Tuomilehto, J.; Wareham, N. J.; Langenberg, C.; Mannisto, S.; Franks, P. W.; Hayward, C.; Vitart, V.; Kaprio, J.; Visvikis-Siest, S.; Balkau, B.; Altshuler, D.; Rudan, I.; Stumvoll, M.; Campbell, H.; van Duijn, C. M.; Gieger, C.; Illig, T.; Ferrucci, L.; Pedersen, N. L.; Pramstaller, P. P.; Boehnke, M.; Frayling, T. M.; Shuldiner, A. R.; Peyser, P. A.; Kardia, S. L. R.; Palmer, L. J.; Penninx, B. W.; Meneton, P.; Harris, T. B.; Navis, G.; Harst, P.; Smith, G. D.; Forouhi, N. G.; Loos, R. J. F.; Salomaa, V.; Soranzo, N.; Boomsma, D. I.; Groop, L.; Tuomi, T.; Hofman, A.; Munroe, P. B.; Gudnason, V.; Siscovick, D. S.; Watkins, H.; Lecoeur, C.; Vollenweider, P.; Franco-Cereceda, A.; Eriksson, P.; Jarvelin, M. -R.; Stefansson, K.; Hamsten, A.; Nicholson, G.; Karpe, F.; Dermitzakis, E. T.; Lindgren, C. M.; Mccarthy, M. I.; Froguel, P.; Kaakinen, M. A.; Lyssenko, V.; Watanabe, R. M.; Ingelsson, E.; Florez, J. C.; Dupuis, J.; Barroso, I.; Morris, A. P.; Prokopenko, I

Genetic insights into biological mechanisms governing human ovarian ageing.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.Cambridge: Claudia Langenberg and Nicholas J Wareham are funded by the Medical Research Council (MC_UU_12015/1 and MC_UU_00006/1). Nicholas J Wareham is a NIHR Senior Investigator. Ken Ong, John Perry, Stasa Stankovic and Felix Day are supported by the Medical Research Council (Unit programmes: MC_UU_12015/2 and MC_UU_00006/2)