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End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs. The aims of this systematic review were (1) to evaluate the incidence of ESRD due to all causes and due to diabetic nephropathy in the diabetic population and differences between incidences of ESRD with respect to sex, ethnicity, age and regions, (2) to compare incidence rates in the diabetic and non-diabetic population, and (3) to investigate time trends. The systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in the biomedical databases until January 3rd 2015; thirty-two studies were included. Among patients with incident type 1 diabetes the 30-year cumulative incidence ranged from 3.3% to 7.8%. Among patients with prevalent diabetes, incidence rates of ESRD due to all causes ranged from 132.0 to 167.0 per 100,000 person-years, whereas incidence rates of ESRD due to diabetic nephropathy varied from 38.4 to 804.0 per 100,000 person-years. The incidence of ESRD in the diabetic population was higher compared to the non-diabetic population, and relative risks varied from 6.2 in the white population to 62.0 among Native Americans. The results regarding time trends were inconsistent. The review conducted demonstrates the considerable variation of incidences of ESRD among the diabetic population. Consistent findings included an excess risk when comparing the diabetic to the non-diabetic population and ethnic differences. We recommend that newly designed studies should use standardized methods for the determination of ESRD and population at risk.

Bacillus thuringiensis (Bt) microbial pesticides have a 50-year history of safety in agriculture. Cry proteins are among the active insecticidal ingredients in these pesticides, and genes coding for Cry proteins have been introduced into agricultural crops using modern biotechnology. The Cry gene sequences are often modified to enable effective expression in planta and several Cry proteins have been modified to increase biological activity against the target pest(s). Additionally, the domains of different but structurally conserved Cry proteins can be combined to produce chimeric proteins with enhanced insecticidal properties. Environmental studies are performed and include invertebrates, mammals, and avian species. Mammalian studies used to support the food and feed safety assessment are also used to support the wild mammal assessment. In addition to the NTO assessment, the environmental assessment includes a comparative assessment between the Bt crop and the appropriate conventional control that is genetically similar but lacks the introduced trait to address unintended effects. Specific phenotypic, agronomic, and ecological characteristics are measured in the Bt crop and the conventional control to evaluate whether the introduction of the insect resistance has resulted in any changes that might cause ecological harm in terms of altered weed characteristics, susceptibility to pests, or adverse environmental impact. Additionally, environmental interaction data are collected in field experiments for Bt crop to evaluate potential adverse effects. Further to the agronomic and phenotypic evaluation, potential movement of transgenes from a genetically modified crop plants into wild relatives is assessed for a new pest resistance gene in a new crop. This review summarizes the evidence for safety of crops containing Cry proteins for humans, livestock, and other non-target organisms.

Do women’s political gains in office translate into substantive differences in foreign policy outcomes? Previous research shows that men and women hold different national security policy preferences and that greater representation by women in the legislature reduces conflict behavior. But are these relationships an artifact of confounding variables? To answer this question, we analyze the defense spending and conflict behavior of 22 established democracies between 1970 and 2000. We argue that the ability of female officeholders to represent women’s interests is context dependent—varying with the level of party control over legislators and the gender stereotypes that officeholders confront. Consistent with the literature on stereotypes, we find that increases in women’s legislative representation decreases conflict behavior and defense spending, while the presence of women executives increases both. However, these effects are conditioned by the gendered balance of power in the legislature and the degree of party control in the political system.

The coherent control of a two-level system is among the most essential challenges in modern quantum optics. Understanding its fundamental limitations is crucial, also for the realization of next generation quantum devices. The quantum coherence of a two-level system is fragile in particular, when the two levels are connected via an optical transition, which, at the same time, enables the manipulation of the system. When such quantum emitters are located in solids the coherence suffers from the interaction of the optical transition with the solid state environment, which requires the sample to be cooled to temperatures of a few Kelvin or below. Here, we use a mechanically isolated quantum emitter in hexagonal boron nitride to explore the individual mechanisms which affect the coherence of an optical transition under resonant drive. We operate the system at the threshold where the mechanical isolation collapses in order to study the onset and temperature-dependence of dephasing and independently of spectral diffusion. The insights on the underlying physical decoherence mechanisms reveal a limit in temperature until which coherent driving of the system is possible. This study enables to increase the operation temperature of hBN-based quantum devices, therefore reducing the need for cryogenic cooling.The coherent control of a two-level system is at the core of quantum devices and understanding decoherence mechanisms is crucial for increasing their operating temperatures. Here, a mechanically isolated quantum emitter in hexagonal boron nitride is used to explore the individual mechanisms affecting the coherence of an optical transition under resonant drive.

War heightens public interest in politics, especially when human lives are lost. We examine whether, and how, combat casualties affect the decision to vote in established democracies. Drawing from social psychology research on mortality salience, we expect increasing casualties to increase the salience of death, information that moves people to defend their worldview, especially nationalistic and ideological values. By heightening the importance of values, we propose that combat casualties increase the benefits of voting. In particular, we expect the effect of combat casualties to be pronounced among the least politically engaged. Using both cross-national data of elections in 23 democracies over a 50-year period and survey data from the United States and United Kingdom during the Iraq and Afghanistan wars, we found that mounting casualties increase turnout. Furthermore, as expected, we found the effect of casualties to be most pronounced among those least interested in politics.

How does the domestic political climate within democratic states affect the duration of their foreign military engagements? To answer this question we combine a rationalist model of war termination with a theory about how partisan politics affects the policy preferences of national leaders to predict the duration of democratic military interventions. Specifically, we examine how changes in a chief executive’s public approval ratings interact with partisanship to affect decisions about the timing of conflict termination. We test our expectations on a set of 47 British, French, and American cases from a new dataset of military interventions by powerful states. Our results suggest that partisanship mediates the effect of public approval on the duration of military operations initiated by powerful democratic countries. As executive approval declines, governments on the right of the political spectrum are inclined to continue to fight, while left-leaning executives become more likely to bring the troops home.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by an impaired epidermal barrier and immunological alterations. The activity of the cytoprotective NRF2 transcription factor is reduced in the epidermis of AD patients. To determine the functional relevance of this deficiency, we used mice lacking fibroblast growth factor receptors 1 and 2 in keratinocytes (K5-R1/R2 mice), which exhibit several AD-like symptoms. Proteomics analysis of their epidermis revealed reduced Nrf2 activity. This was accompanied by an increase in DNA damage and in the number of senescent cells. Genetic deletion of Nrf2 in keratinocytes of these mice further promoted DNA damage and senescence, but time-limited pharmacological activation of Nrf2 in the skin had a mild protective effect. Surprisingly, long-term genetic activation of Nrf2 in keratinocytes of K5-R1/R2 mice caused strong hyperkeratosis, keratinocyte hyperproliferation, epidermal thickening, increased keratinocyte apoptosis and DNA damage, and altered immune cell composition. These results reveal a complex role of Nrf2 in the epidermis and show the necessity to optimize the duration and intensity of NRF2 activation for the treatment of epidermal alterations in patients with AD.

Background Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days. Results We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures. Conclusion Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.

The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and is involved in inflammatory and immune responses. Most importantly, RAGE is considered a receptor for HMGB1 and several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that the Ager gene coding for RAGE first appeared in mammals, and is closely related to other genes coding for cell adhesion molecules (CAMs) such as ALCAM, BCAM and MCAM that appeared earlier during metazoan evolution. RAGE is expressed at very low levels in most cells, but when expressed at high levels, it mediates cell adhesion to extracellular matrix components and to other cells through homophilic interactions. Our results suggest that RAGE evolved from a family of CAMs, and might still act as an adhesion molecule, in particular in the lung where it is highly expressed or under pathological conditions characterized by an increase of its protein levels.

Background MUC13 is overexpressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown. Methods Stable cell lines with either overexpressed or suppressed MUC13 levels were analyzed to determine cell growth, colony formation, cell migration, and cell invasion assays. The molecular mechanisms involved in MUC13 regulation were elucidated via chromatin immunoprecipitation (ChIP) and analysis of interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon cancer cells. Results Overexpression of MUC13 increased cell growth, colony formation, cell migration, and invasion. In concordance, MUC13 silencing decreased these tumorigenic features. Overexpression of MUC13 also modulated various cancer-associated proteins, including telomerase reverse transcriptase, sonic hedgehog, B cell lymphoma murine like site 1, and GATA like transcription factor 1. Additionally, MUC13-overexpressing cells showed increased HER2 and P-ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13 promoter. IL6 treatment of colon cancer cells increased the expression of MUC13 via activation of the JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5 signaling by chemical inhibitors abolished IL6-induced MUC13 expression. IHC analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as compared to adjacent normal tissue. Conclusions The results of this study, for the first time, suggest functional roles of MUC13 in colon cancer progression and provide information regarding the regulation of MUC13 expression via JAK2/STAT5 which may reveal promising therapeutic approaches for colon cancer treatment.