Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

Permafrost degradation and nitrogen cycling in Arctic rivers: Insights from stable nitrogen isotope studies

Abstract. Across the Arctic, vast areas of permafrost are being degraded by climate change, which has the potential to release substantial quantities of nutrients, including nitrogen into large Arctic rivers. These rivers heavily influence the biogeochemistry of the Arctic Ocean, so it is important to understand the potential changes to rivers from permafrost degradation. This study utilized dissolved nitrogen species (nitrate and dissolved organic nitrogen (DON)) along with nitrogen isotope values (δ15N-NO3- and δ15N-DON) of samples collected from permafrost sites in the Kolyma River and the six largest Arctic rivers. Large inputs of DON and nitrate with a unique isotopically heavy δ15N signature were documented in the Kolyma, suggesting the occurrence of denitrification and highly invigorated nitrogen cycling in the Yedoma permafrost thaw zones along the Kolyma. We show evidence for permafrost-derived DON being recycled to nitrate as it passes through the river, transferring the high 15N signature to nitrate. However, the potential to observe these thaw signals at the mouths of rivers depends on the spatial scale of thaw sites, permafrost degradation, and recycling mechanisms. In contrast with the Kolyma, with near 100 % continuous permafrost extent, the Ob River, draining large areas of discontinuous and sporadic permafrost, shows large seasonal changes in both nitrate and DON isotopic signatures. During winter months, water percolating through peat soils records isotopically heavy denitrification signals in contrast with the lighter summer values when surface flow dominates. This early year denitrification signal was present to a degree in the Kolyma, but the ability to relate seasonal nitrogen signals across Arctic Rivers to permafrost degradation could not be shown with this study. Other large rivers in the Arctic show different seasonal nitrogen trends. Based on nitrogen isotope values, the vast majority of nitrogen fluxes in the Arctic rivers is from fresh DON sourced from surface runoff through organic-rich topsoil and not from permafrost degradation. However, with future permafrost thaw, other Arctic rivers may begin to show nitrogen trends similar to the Ob. Our study demonstrates that nitrogen inputs from permafrost thaw can be identified through nitrogen isotopes, but only on small spatial scales. Overall, nitrogen isotopes show potential for revealing integrated catchment wide nitrogen cycling processes. </jats:p

Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial

Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3'-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to transdysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important to be able to objectively quantify treatment efficacy at the level of molecular biomarkers. We show how previously described candidate mRNA biomarkers can be used to model an effective reduction in CTG length, using modern high-dimensional statistics (machine learning), and a blood and muscle mRNA microarray dataset. We show how this model could be used to detect treatment effects in the context of a clinical trial

Generalized isothermic lattices

We study multidimensional quadrilateral lattices satisfying simultaneously two integrable constraints: a quadratic constraint and the projective Moutard constraint. When the lattice is two dimensional and the quadric under consideration is the Moebius sphere one obtains, after the stereographic projection, the discrete isothermic surfaces defined by Bobenko and Pinkall by an algebraic constraint imposed on the (complex) cross-ratio of the circular lattice. We derive the analogous condition for our generalized isthermic lattices using Steiner's projective structure of conics and we present basic geometric constructions which encode integrability of the lattice. In particular, we introduce the Darboux transformation of the generalized isothermic lattice and we derive the corresponding Bianchi permutability principle. Finally, we study two dimensional generalized isothermic lattices, in particular geometry of their initial boundary value problem.Comment: 19 pages, 11 figures; v2. some typos corrected; v3. new references added, higlighted similarities and differences with recent papers on the subjec

Understanding the diffusion of public bikesharing systems: evidence from Europe and North America

Since the mid-2000s, public bikesharing (also known as “bike hire”) has developed and spread into a new form of mobility in cities across the globe. This paper presents an analysis of the recent increase in the number of public bikesharing systems. Bikesharing is the shared use of a bicycle fleet, which is accessible to the public and serves as a form of public transportation. The initial system designs were pioneered in Europe and, after a series of technological innovations, appear to have matured into a system experiencing widespread adoption. There are also signs that the policy of public bikesharing systems is transferable and is being adopted in other contexts outside Europe. In public policy, the technologies that are transferred can be policies, technologies, ideals or systems. This paper seeks to describe the nature of these systems, how they have spread in time and space, how they have matured in different contexts, and why they have been adopted. Researchers provide an analysis from Europe and North America. The analysis draws on published data sources, a survey of 19 systems, and interviews with 12 decision-makers in Europe and 14 decision-makers in North America. The data are examined through the lens of diffusion theory, which allows for comparison of the adoption process in different contexts. A mixture of quantitative and qualitative analyses is used to explore the reasons for adoption decisions in different cities. The paper concludes that Europe is still in a major adoption process with new systems emerging and growth in some existing systems, although some geographic areas have adopted alternative solutions. Private sector operators have also been important entrepreneurs in a European context, which has accelerated the uptake of these systems. In North America, the adoption process is at an earlier stage and is gaining momentum, but signs also suggest the growing importance of entrepreneurs in North America with respect to technology and business models. There is evidence to suggest that the policy adoption processes have been inspired by successful systems in Paris, Lyon, Montreal, and Washington, DC, for instance, and that diffusion theory could be useful in understanding public bikesharing policy adoption in a global context

Preorganized tridentate analogues of mixed hydroxyoxime/carboxylate nickel extractants

Simple tridentate ligands can operate as Ni-extractants in the pH-dependent process: 2LHorg + NiSO4 ⇌ [(L)2Ni]org + H2SO4.</p